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Clinical Studies

Abstracts are presented below for clinical studies on Andrographis.

  • Botanical Name: Andrographis Paniculata

  • Ayurvedic Name: Bhunimba

  • Common Name: Andrographis

Andrographis Paniculata

Plant Phytonutrient Profile


1: Int Immunopharmacol. 2007 Apr;7(4):515/​23. Epub 2007 Jan 17.

Modulation of immune response in mice immunised with an inactivated Salmonella
vaccine and gavaged with Andrographis paniculata extract or andrographolide.

Xu Y, Chen A, Fry S, Barrow RA, Marshall RL, Mukkur TK.

Department of Biological and Physical Sciences, Faculty of Sciences, University
of Southern Queensland, Toowoomba, Queensland 4350, Australia.

Gavage of mice, immunised with an inactivated S. typhimurium vaccine, with
Andrographis paniculata extract [APE] or andrographolide [AND] resulted in an
enhancement of Salmonella/​specific antibody response and induction of
cell/​mediated response against salmonellosis. Mice were vaccinated with either
one or two doses of killed S. typhimurium vaccine and fed two different
quantities of APE or AND, for 14 days in mice immunised with one dose of the
vaccine, and for 28 days in mice immunised with two doses of vaccine,
respectively. Both APE and AND were found to enhance IgG antibody levels against
S. typhimurium, the enhancement being statistically significant in mice
receiving two doses of the vaccine. Splenocyte cultures, prepared from mice
immunised with the killed Salmonella vaccine and treated with APE or AND, showed
a remarkable increase in the production IFN/​gamma following stimulation with the
bacterial lysate, indicating an induction of Salmonella/​specific cell/​mediated
response/immune response.

PMID: 17321475 [PubMed /​ in process]

2: Asian Pac J Cancer Prev. 2006 Oct/​Dec;7(4):609/​14.

Ameliorating effects of Andrographis paniculata extract against
cyclophosphamide/​induced toxicity in mice.

Sheeja K, Kuttan G.

Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur,
Kerala, India.

Major drawbacks of chemotherapeutic agents are their toxic side effects and lack
of tumor specificity. Immunological and biochemical studies were here carried
out to investigate protective effects of ethanolic extract of Andrographis
paniculata against cyclophosphamide (CTX) induced toxicity in vivo.
Intraperitoneal administration of the extract significantly increased the total
WBC account (3256.5+//​196 cells/cm(2)), bone marrow cellularity
(17.1+//​10.4x10(6) cells/femur) and betaesterase positive cells (849+//​23.2
cells/4000 cells) in CTX treated animals, when compared to CTX alone treated
control mice. Weights of lymphoid organs such as a spleen and thymus, reduced by
CTX administration, were also increased by A paniculata treatment. Reduction of
GSH in liver (4.8+//​0.21nmol/mg protein) and in intestinal mucosa (13+//​0.67
nmol/mg protein) of CTX/​treated controls was significantly reversed by A
paniculata administration (liver: 6.4+//​0.13, intestinal mucosa: 17.11+//​0.06),
with amelioration of changes in serum and liver ALP, GPT, LPO (lipid
peroxidation). Histopathological analysis of small intestine also suggests that
extract could reduce the CTX induced intestinal damage. The level of
proinflammatory cytokine TNF/​alpha, which was elevated during CTX
administration, was significantly reduced by the A paniculata extract
administration. The lowered levels of other cytokines like IFN/​gamma, IL/​2,
GM/​CSF, after CTX treatment were also found to be increased by extract
administration.

PMID: 17250437 [PubMed /​ in process]

3: Phytochemistry. 2007 Jan 17; [Epub ahead of print]

Semisynthesis and in vitro anticancer activities of andrographolide analogues.

Jada SR, Subur GS, Matthews C, Hamzah AS, Lajis NH, Saad MS, Stevens MF,
Stanslas J.

Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400
Serdang, Selangor, Malaysia.

The plant Andrographis paniculata found throughout Southeast Asia contains
Andrographolide 1, a diterpenoid lactone, which has antitumour activities
against in vitro and in vivo breast cancer models. In the present study, we
report on the synthesis of andrographolide derivatives,
3,19/​isopropylideneandrographolide (2),
14/​acetyl/​3,19/​isopropylideneandrographolide (3) and 14/​acetylandrographolide
(4), and their in vitro antitumour activities against a 2/​cell line panel
consisting of MCF/​7 (breast cancer cell line) and HCT/​116 (colon cancer cell
line). Compounds 2 and 4 were also screened at the US National Cancer Institute
(NCI) for their activities against a panel of 60 human cancer cell lines derived
from nine cancer types. Compound 2 was found to be selective towards leukaemia
and colon cancer cells, and compound 4 was selective towards leukaemia, ovarian
and renal cancer cells at all the dose/​response parameters. Compounds 2 and 4
showed non/​specific phase of the cell cycle arrest in MCF/​7 cells treated at
different intervals with different concentrations. NCI's COMPARE and SOM
mechanistic analyses indicated that the anticancer activities of these new class
of compounds were not similar to that of standard anticancer agents, suggesting
novel mechanism(s) of action.

PMID: 17234223 [PubMed /​ as supplied by publisher]

4: Int Immunopharmacol. 2007 Feb;7(2):211/​21. Epub 2006 Nov 2.

Antiangiogenic activity of Andrographis paniculata extract and andrographolide.

Sheeja K, Guruvayoorappan C, Kuttan G.

Department of Immunology, Amala Cancer Research Centre, Amala Nagar, Thrissur,
Kerala, India.

Inhibition of angiogenesis is currently perceived as one of the promising
strategies in the treatment of cancer. In this study we analyzed the
antiangiogenic activity of Andrographis paniculata extract (APE) and its major
component andrographolide (ANDLE) using both in vitro and in vivo models.
Intraperitoneal administration of APE and ANDLE significantly inhibited the
B16F/​10 melanoma cell line induced capillary formation in C57BL/6 mice. Analysis
of serum cytokine profile showed a drastic elevation in the proinflammatory
cytokines such as IL/​1beta, IL/​6, TNF/​alpha and GM/​CSF and the most potent
angiogenic factor VEGF in angiogenesis induced animals. Treatment of APE and
ANDLE significantly reduced this elevated levels. Moreover, VEGF mRNA level in
B16F/​10 cell line showed a reduced level of expression in the presence of APE
and ANDLE. Serum NO level which was increased in B16F/​10 melanoma injected
control animals was also found to be significantly lowered by the administration
of APE and ANDLE. Antiangiogenic factors such as TIMP/​1 and IL/​2 level was
elevated in APE and ANDLE treated angiogenesis induced animals. In the rat
aortic ring assay APE and ANDLE inhibited the microvessel outgrowth at non toxic
concentrations. Taken together our results demonstrate that APE and ANDLE
inhibit the tumor specific angiogenesis by regulating the production of various
pro and antiangiogenic factors such as proinflammatory cytokine, nitric oxide,
VEGF, IL/​2 and TIMP/​1.

PMID: 17178389 [PubMed /​ in process]

5: Zhongguo Zhong Yao Za Zhi. 2006 Oct;31(19):1594/​7.

[Studies on diterpenoids from Andrographis paniculata]

[Article in Chinese]

Chen LX, Qu GX, Qiu F.

Department of Natural Products Chemistry, Shenyang Pharmaceutical University,
Shenyang 110016, China.

OBJECTIVE: To study the diterpenoids in the 85% ethanol extract of the aerial
parts of Andrographis paniculata. METHOD: Fourteen diterpenoids from the 85%
EtOH extract were isolated by the silica gel, Sephadex LH/​20, ODS column
chromatography and HPLC, and their structures were identified by the spectal
analyses and chemical evidences. RESULT: The 14 compounds were obtained and
identified as neoandrographolide (1), 3, 14/​di/​deoxyandrographolide (2),
andrographolide (3), 14/​deoxy/​11, 12/​didehydroandrographolide (4), 19/​hydroxy/​8
(17), 13/​labdadien/​15, 16/​olide (5), 14/​deoxy/​andrographolide (6),
3/​oxo/​14/​deoxy/​andrographolide (7), isoandrographolide, (8), bisandrographolide
(9, 10, 11), deoxyandrographiside (12), 14/​deoxy/​11, 12/​didehydroandrographiside
(13), andrographiside (14), respectively. CONCLUSION: Compound 7 was a new
natural product, and compound 5 was obtained for the first time from the
Andrographis species.

Publication Types:
English Abstract

PMID: 17165582 [PubMed /​ in process]

6: J Chromatogr A. 2007 Jan 26;1140(1/​2):71/​7. Epub 2006 Dec 6.

On/​line coupling of dynamic microwave/​assisted extraction with high/​performance
liquid chromatography for determination of andrographolide and
dehydroandrographolide in Andrographis paniculata Nees.

Chen L, Jin H, Ding L, Zhang H, Wang X, Wang Z, Li J, Qu C, Wang Y, Zhang H.

College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012,
China.

A novel technique based on dynamic microwave/​assisted extraction (DMAE) coupled
on/​line with high/​performance liquid chromatography (HPLC) through a flow
injection interface has been developed for determination of andrographolide and
dehydroandrographolide in Andrographis paniculata Nees. A TM(010) microwave
resonance cavity built in the laboratory was applied to concentrating the
microwave energy. An extraction vessel was placed in microwave irradiation zone.
The extraction was performed in a recirculating system. When a number of
extraction cycles were completed, the fractional extract (20muL) was driven to
the analytical column by 65% aqueous methanol and was measured by diode array
detector (DAD) at 225nm. The optimized extraction conditions are follows:
extraction solvent 60% aqueous methanol; microwave forward power 80W; extraction
time 6min; extraction solvent flow/​rate 1.0mLmin(/​1). The detection and
quantification limits obtained are 0.5 and 1.7microgmL(/​1) for andrographolide
and 0.6 and 1.9microgmL(/​1) for dehydroandrographolide, respectively. The
within/​day and between/​day precision (RSD) are 2.1% and 3.7% for andrographolide
and 1.7% and 4.1% for dehydroandrographolide, respectively. Mean recoveries for
andrographolide and dehydroandrographolide are 97.7% and 98.7%, respectively.
Compared with ultrasonic extraction used in the Chinese pharmacopoeia, the
proposed method was demonstrated to obtain higher extraction yield in a shorter
time. In addition, only small quantities of solvent (5mL) and sample (10mg) were
required.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 17156791 [PubMed /​ in process]

7: J Ethnopharmacol. 2006 Oct 28; [Epub ahead of print]

Protective activity of andrographolide and arabinogalactan proteins from
Andrographis paniculata Nees. against ethanol/​induced toxicity in mice.

Singha PK, Roy S, Dey S.

Microbiology and Immunology Laboratory, Department of Human Physiology with
Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India;
Plant Biotechnology Laboratory, Department of Biotechnology, IIT, Kharagpur 721
302, West Bengal, India.

To find out the active principles against ethanol/​induced toxicity in mice,
Andrographis paniculata Nees. (Ap) was chosen and isolated andrographolide
(ANDRO) and arabinogalactan proteins (AGPs). ANDRO was detected by HPTLC, FTIR
and quantified by HPLC (10mg/g of Ap powder). AGPs was detected by beta/​glucosyl
Yariv staining of SDS/​PAGE gel, FTIR and quantified by single radial gel
diffusion assay with beta/​glucosyl Yariv reagent (0.5mg/g Ap powder). The mice
are pretreated intra/​peritoneally (i.p.) with different doses (62.5, 125, 250,
and 500mg/kg) of body weight of mice] of ANDRO and AGPs for 7 days and then
ethanol (7.5g/kg of body weight) was injected, i.p. Besides, silymarin was used
as standard hepatoprotective agent for comparative study with ANDRO and AGPs.
The ameliorative activity of ANDRO and AGP against hepatic renal alcohol
toxicity was measured by assessing GOT, GPT, ACP, ALP and LP levels in liver and
kidney. It has been observed that pretreatment of mice with ANDRO and AGPs at
500mg/kg of body weight and 125mg/kg of body weight respectively could able to
minimize the toxicity in compare to ethanol treated group as revealed by the
different enzymatic assay in liver and kidney tissues and the results were
comparable with silymarin. Hence, out of several ill/​defined compounds present
in Ap, ANDRO and AGPs are the potential bioactive compounds responsible for
protection against ethanol/​induced toxicity.

PMID: 17127022 [PubMed /​ as supplied by publisher]

8: Mol Cell Biochem. 2006 Nov 16; [Epub ahead of print]

Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E(2)
production in LPS/​stimulated murine macrophage.

Liu J, Wang ZT, Ji LL, Ge BX.

Key Laboratory of Standardization of Chinese Medicines of Ministry of Education,
Institute of Chinese Material Medica, Shanghai University of Traditional Chinese
Medicine, 1200 Cailun Road, Zhangjiang Hi/​Tech Park, Shanghai, 201203, P. R.
China, wangzht@hotmail.com.

Activated macrophages express inducible isoforms of nitric oxide synthase (iNOS)
and cyclooxygenase/​2 (COX/​2), produce excessive amounts of nitric oxide (NO) and
prostaglandin E(2) (PGE(2)), which play key roles in the processes of
inflammation. Andrographis paniculata Nees is a traditional Chinese herb
commonly used for treatment of infection, inflammation, and diarrhea. However,
the mechanism of its therapeutic function is not well known. In the present
study, the effect of neoandrographolide, one of bioactive components in A.
paniculata, on iNOS/​mediated NO production and COX/​2/​mediated PGE(2) in
bacterial lipopolysaccharide (LPS) stimulated/​murine macrophages was
investigated. Neoandrographolide at concentrations (30/​90 muM) significantly (p
< 0.05) inhibited the productions of NO and PGE(2) in LPS stimulated macrophages
without inducing cytotoxicity. The effect of neoandrographolide also has been
investigated on iNOS and COX/​2 expression in activated macrophage by using
RT/​PCR and immunoblotting. The inhibition of NO release by neoandrographolide
can be attributed to the block of iNOS mRNA transcription followed by inhibiting
protein expression. However, neoandrographolide inhibited COX/​2 protein
expression only but without inhibiting COX/​2 mRNA expression, which was involved
in the inhibitory activity against the PGE(2 )overproduction. This suggests that
the effect of neoandrographolide on iNOS expression may occur at the
transcriptional level and the inhibition of COX/​2 expression occurs at the
translational level. Furthermore, we have found that the addition of
neoandrographolide inhibited the activation of p38 mitogen/​activated protein
kinase (MAPKs) instead of JNK, ERK1/2, or NF/​kappaB. These results indicated
that the anti/​inflammatory properties of neoandrographolide might result from
the inhibition of iNOS and COX/​2 expression through inhibiting p38 MAPKs
activation. Therefore, neoandrographolide isolated from A. paniculata could be
offered as a leading compound for anti/​inflammation.

PMID: 17109078 [PubMed /​ as supplied by publisher]

9: Eur J Pharmacol. 2006 Dec 28;553(1/​3):39/​45. Epub 2006 Sep 30.

Inhibitory effect of Andrographis paniculata extract and its active diterpenoids
on platelet aggregation.

Thisoda P, Rangkadilok N, Pholphana N, Worasuttayangkurn L, Ruchirawat S,
Satayavivad J.

Toxicology Graduate Programme, Faculty of Science, Mahidol University, Rama VI
Road, Bangkok 10400, Thailand; Laboratory of Pharmacology, Chulabhorn Research
Institute, Vipavadee/​Rangsit Highway, Laksi, Bangkok 10210, Thailand.

Andrographis paniculata has been widely used for the prevention and treatment of
common cold especially in Asia and Scandinavia. The three active diterpenoids
from this plant, including aqueous plant extracts, were investigated for the
inhibitory effect on platelet aggregation in vitro. The results indicated that
andrographolide (AP(1)) and 14/​deoxy/​11,12/​didehydroandrographolide (AP(3))
significantly inhibited thrombin/​induced platelet aggregation in a
concentration/​(1/​100 microM) and time/​dependent manner while neoandrographolide
(AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity
than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory
mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the
results indicated that the inhibition of extracellular signal/​regulated
kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two
compounds. In addition, standardized aqueous extracts of A. paniculata
containing different amounts of AP(3) inhibited thrombin/​induced aggregation to
different degrees. The extracts significantly decreased platelet aggregation in
a concentration/​(10/​100 microg/ml) and time/​dependent manner. However, the
extract with high level of AP(3) (Extract B) (IC(50) values=50/​75 microg/ml)
showed less inhibitory activity against thrombin than the extract with lower
level of AP(3) (Extract A) (IC(50) values=25/​50 microg/ml). These results
indicate that the standardized A. paniculata extract may contain other
antiplatelet compounds rather than AP(1) and AP(3), which contribute to high
antiplatelet activity. Therefore, the consumption of A. paniculata products may
help to prevent or treat some cardiovascular disorders i.e. thrombosis; however,
it should be used with caution by patients with bleeding disorders.

Publication Types:
In Vitro

PMID: 17081514 [PubMed /​ indexed for MEDLINE]

10: J Food Prot. 2006 Oct;69(10):2336/​41.

Medicinal plant extracts as anti/​Escherichia coli O157:H7 agents and their
effects on bacterial cell aggregation.

Voravuthikunchai SP, Limsuwan S.

Department of Microbiology, Faculty of Science, Prince of Songkla University,
Hatyai, Songkla 90112, Thailand. supayang.v@psu.ac.th

Ethanolic extracts of eight Thai medicinal plants (representing five families)
that are used as traditional remedies for treating diarrhea were examined with a
salt aggregation test for their ability to modulate cell surface hydrophobicity
of enterohemorrhagic Escherichia coli strains, including E. coli O157:H7. Four
of these medicinal plants, Acacia catechu, Peltophorum pterocarpum, Punica
granatum, and Quercus infectoria, have high bacteriostatic and bactericidal
activities. The ethanolic extract of Q. infectoria was the most effective
against all strains of E. coli, with MICs of 0.12 to 0.98 mg/ml and MBCs of 0.98
to 3.91 mg/ml. The ethanolic extract of P. granatum had MICs of 0.49 to 1.95
mg/ml and MBCs of 1.95 to 3.91 mg/ml. Ethanolic extracts of Q. infectoria, P.
pterocarpum, and P. granatum were among the most effective extracts against the
two strains of E. coli O157:H7. The other four plants, Andrographis paniculata,
Pluchia indica, Tamarindus indica, and Walsura robusta, did not have high
bacteriostatic and bactericidal activities but were able to affect
hydrophobicity characteristics on their outermost surface. All plants except Q.
infectoria had some ability to increase cell surface hydrophobicity. There
appears to be no correlation between antibacterial activity and cell aggregative
properties.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 17066910 [PubMed /​ indexed for MEDLINE]

11: Planta Med. 2006 Aug;72(10):954/​6. Epub 2006 Aug 10.

Stability of andrographolide in powdered Andrographis herb under accelerated
conditions.

Plubrukarn A, Pinsuwan S, Ingkatawornwong S, Supavita T.

Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical
Sciences, Prince of Songkla University, Songkhla, Thailand.

The stability of andrographolide in powdered Andrographis Herb/​/​the aerial part
of Andrographis paniculata (Burm. f.) Nees (Acanthaceae)/​/​was determined using a
heat/​accelerated experiment to reveal a second/​order kinetics of degradation.
The fast decomposition was observed regardless of the method of analysis. The
rate constant of the decomposition of andrographolide at 25 degrees C ( K(25)(
degrees C)), predicted from the Arrhenius plot, was 6.58 x 10 (/​6) d (/​1).

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16902869 [PubMed /​ indexed for MEDLINE]

12: J Biol Chem. 2006 Oct 6;281(40):29897/​904. Epub 2006 Aug 9.

Bisandrographolide from Andrographis paniculata activates TRPV4 channels.

Smith PL, Maloney KN, Pothen RG, Clardy J, Clapham DE.

Department of Cardiology, Howard Hughes Medical Institute, Children's Hospital,
Boston, Massachusetts 02115, USA.

Many transient receptor potential (TRP) channels are activated or blocked by
various compounds found in plants; two prominent examples include the activation
of TRPV1 channels by capsaicin and the activation of TRPM8 channels by menthol.
We sought to identify additional plant compounds that are active on other types
of TRP channels. We screened a library of extracts from 50 Chinese herbal plants
using a calcium/​imaging assay to find compounds active on TRPV3 and TRPV4
channels. An extract from the plant Andrographis paniculata potently activated
TRPV4 channels. The extract was fractionated further, and the active compound
was identified as bisandrographolide A (BAA). We used purified compound to
characterize the activity of BAA on certain TRPV channel subtypes. Although BAA
activated TRPV4 channels with an EC(50) of 790/​950 nm, it did not activate or
block activation of TRPV1, TRPV2, or TRPV3 channels. BAA activated a large
TRPV4/​like current in immortalized mouse keratinocytes (308 cells) that have
been shown to express TRPV4 protein endogenously. This compound also activated
TRPV4 currents in cell/​free outside/​out patches from HEK293T cells
overexpressing TRPV4 cDNA, suggesting that BAA can activate the channel in a
membrane/​delimited manner. Another related compound, andrographolide, found in
abundance in the plant Andrographis was unable to activate or block activation
of TRPV4 channels. These experiments show that BAA activates TRPV4 channels, and
we discuss the possibility that activation of TRPV4 by BAA could play a role in
some of the effects of Andrographis extract described in traditional medicine.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, Non/​U.S. Gov't

PMID: 16899456 [PubMed /​ indexed for MEDLINE]

13: Trop Biomed. 2005 Dec;22(2):165/​70.

In vitro screening of five local medicinal plants for antibacterial activity
using disc diffusion method.

Zaidan MR, Noor Rain A, Badrul AR, Adlin A, Norazah A, Zakiah I.

Bioassay Unit, Herbal Medicine Research Centre, Institute for Medical Research,
Kuala Lumpur.

Medicinal plants have many traditional claims including the treatment of
ailments of infectious origin. In the evaluation of traditional claims,
scientific research is important. The objective of the study was to determine
the presence of antibacterial activity in the crude extracts of some of the
commonly used medicinal plants in Malaysia, Andrographis paniculata, Vitex
negundo, Morinda citrifolia, Piper sarmentosum, and Centella asiatica. In this
preliminary investigation, the leaves were used and the crude extracts were
subjected to screening against five strains of bacteria species, Methicillin
Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Klebsiella
pneumoniae, Pseudomonas aeruginosa and Escherichia coli, using standard protocol
of Disc Diffusion Method (DDM). The antibacterial activities were assessed by
the presence or absence of inhibition zones and MIC values. M. citrifolia, P.
sarmentosum and C. asiatica methanol extract and A. paniculata (water extract)
have potential antibacterial activities to both gram positive S. aureus and
Methicillin Resistant S. aureus (MRSA). None of the five plant extracts tested
showed antibacterial activities to gram negative E. coli and K. pneumoniae,
except for A. paniculata and P. sarmentosum which showed activity towards P.
aeruginosa. A. paniculata being the most potent at MIC of 2 g/disc. This finding
forms a basis for further studies on screening of local medicinal plant extracts
for antibacteria properties.

PMID: 16883283 [PubMed /​ in process]

14: Integr Cancer Ther. 2006 Sep;5(3):244/​51.

Protective effect of Andrographis paniculata and andrographolide on
cyclophosphamide/​induced urothelial toxicity.

Sheeja K, Kuttan G.

Amala Cancer Research Centre, Amala Nagar, Thrissur, Kerala, India.

The protective effect of Andrograhis paniculata and andrographolide (ANDLE)
against cyclophosphamide (CTX)/​induced urothelial toxicity was investigated in
this study. Pretreatment of Swiss albino mice with A paniculata extract (10
mg/dose/animal intraperitoneally [ip]) and ANDLE (500 microg/dose/animal ip)
could significantly reduce CTX (1.5 nmol/kg body weight)/​induced urothelial
toxicity. Morphological and histopathological analysis of urinary bladder of
CTX/​treated mice showed severe inflammation and dark coloration, whereas A
paniculata and ANDLE/​treated mice showed almost normal bladder morphology.
Elevation of urinary protein level (7.33 +//​ 0.3 g/L) by CTX administration was
reduced by A paniculata (3.78 +//​ 0.4 g/L) and ANDLE treatment (4.19 +//​ 0.1
g/L). Urinary urea N2 level, which was elevated after 48 hours of CTX
administration (24.25 +//​ 0.2 g/L) was found to be reduced by the treatment with
A paniculata (14.19 +//​ 0.5 g/L) and ANDLE (15.79 +//​ 0.4 g/L). A decreased
level of reduced glutahione (GSH) content in liver (2.81 +//​ 0.1 nmol/mg
protein) and bladder (1.20 +//​ 0.2 nmol/mg protein) after CTX administration was
also increased by the treatment with A paniculata (liver: 5.78 +//​ 0.3 nmol/mg
protein; bladder: 2.96 +//​ 0.2 nmol/mg protein) and ANDLE (liver: 5.14 +//​ 0.3
nmol/mg protein; bladder: 2.84 +//​ 0.2 nmol/mg protein). Production of the
proinflammatory cytokine, tumor necrosis factor/​alpha, which was elevated during
CTX administration, was found to be inhibited by A paniculata and ANDLE
treatment. The lowered level of interleukin/​2 and interferon/​gamma during CTX
treatment was elevated by the administration of A paniculata and ANDLE.

PMID: 16880430 [PubMed /​ indexed for MEDLINE]

15: J Enzyme Inhib Med Chem. 2006 Apr;21(2):145/​55.

Erratum in:
J Enzyme Inhib Med Chem. 2006 Jun;21(3):327.

Semisynthesis and cytotoxic activities of andrographolide analogues.

Jada SR, Hamzah AS, Lajis NH, Saad MS, Stevens MF, Stanslas J.

Clinical Pharmacology Laboratory, Division of Medical Sciences, National Cancer
Centre, 11 Hospital Drive, 169610, Singapore.

Andrographolide 1, a diterpenoid lactone of the plant Andrographis paniculata,
known to possess antitumour activity in in vitro and in vivo breast cancer
models was subjected to semisynthesis leading to the preparation of a number of
novel compounds. These compounds exhibited in vitro antitumour activity with
moderate to excellent growth inhibition against MCF/​7 (breast) and HCT/​116
(colon) cancer cells. Compounds 3,19/​(2/​chlorobenzylidene)andrographolide(5),
3,19/​(3/​chlorobenzylidene)andrographolide(6), 3,19/​(3/​fluorobenzylidene)
andrographolide(7), 3,19/​(4/​fluorobenzylidene)andrographolide(8),
3,19/​(2/​fluorobenzylidene)andrographolide(10),
3,19/​(2/​chloro/​5/​nitrobenzylidene)andrographolide (21),
3,19/​(4/​chlorobenzylidene)andrographolide(30) and
3,19/​(2/​chloro/​4/​fluorobenzylidene) andrographolide(31) were also screened
against 60 NCI (National Cancer Institute, USA) human tumour cell lines derived
from nine cancer cell types.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16789428 [PubMed /​ indexed for MEDLINE]

16: Explore (NY). 2006 Jan;2(1):25/​9.

Andrographis paniculata for the treatment of upper respiratory infection: a
systematic review by the natural standard research collaboration.

Kligler B, Ulbricht C, Basch E, Kirkwood CD, Abrams TR, Miranda M, Singh Khalsa
KP, Giles M, Boon H, Woods J.

Continuum Center for Health and Healing, New York, NY, USA.
bkligler@bethisraelny.org

Publication Types:
Review

PMID: 16781605 [PubMed /​ indexed for MEDLINE]

17: Biochem Pharmacol. 2006 Jul 14;72(2):132/​44. Epub 2006 Apr 29.

Critical role of pro/​apoptotic Bcl/​2 family members in andrographolide/​induced
apoptosis in human cancer cells.

Zhou J, Zhang S, Ong CN, Shen HM.

Department of Community, Occupational and Family Medicine, Yong Loo Lin School
of Medicine, National University of Singapore, 16 Medical Drive, Singapore
117597, Republic of Singapore.

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional
herbal medicine Andrographis paniculata, is known to possess potent
anti/​inflammatory activity. In this study, Andro induced apoptosis in human
cancer cells via activation of caspase 8 in the extrinsic death receptor pathway
and subsequently with the participation of mitochondria. Andro triggered a
caspase 8/​dependent Bid cleavage, followed by a series of sequential events
including Bax conformational change and mitochondrial translocation, cytochrome
c release from mitochondria, and activation of caspase 9 and 3. Inhibition of
caspase 8 blocked Bid cleavage and Bax conformational change. Consistently,
knockdown of Bid protein using small interfering RNA (siRNA) technique
suppressed Andro/​induced Bax conformational change and apoptosis. In conclusion,
the pro/​apoptotic Bcl/​2 family members (Bid and Bax) are the key mediators in
relaying the cell death signaling initiated by Andro from caspase 8 to
mitochondria and then to downstream effector caspases, and eventually leading to
apoptotic cell death.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16740251 [PubMed /​ indexed for MEDLINE]

18: Zhongguo Zhong Yao Za Zhi. 2006 Mar;31(5):391/​5.

[Studies on flavonoids of Andrographis paniculata]

[Article in Chinese]

Chen LX, Qu GX, Qiu F.

Shenyang Pharmaceutical University, China.

OBJECTIVE: To study the flavonoids of the aerial parts of Andrographis
paniculata. METHOD: Twelve flavonoids from the 85% EtOH extract were isolated by
the silica gel column, Sephadex LH/​20 column, ODS column chromatography and
HPLC, and their structures were identified by the spectal analyses and chemical
evidences. RESULT: The 12 compounds were obtained and identified as
7/​O/​methylwogonin (1), 7/​O/​methyldihydrowogonin (2), 5/​hydroxy/​7, 8, 2',
5'/​tetramethoxy/​flavone (3), skullcapflavone/​2'/​methoxylether (4), 5/​hydroxy/​7,
8, 2', 3'/​tetramethoxyflavone (5), 5, 4'/​dihydroxy/​7, 8, 2',
3'/​tetramethoxyflavone (6), dihydroskullcapflavone (7), 5, 7,
8/​trimethoxydihydroflavone (8), 5, 2'/​dihydroxy/​7, 8/​dimethoxyflvone (9),
andrographidine C (10), 5, 7, 4'/​trihydroxyflavone (11), 5, 7, 3',
4'/​tetrahydroxyflavone (12). CONCLUSION: Compound 6 is a new naturally occurring
product isolated from A. paniculata, and compound 8, 11 and 12 are obtained for
the first time from the Andrographis species.

Publication Types:
English Abstract

PMID: 16711423 [PubMed /​ indexed for MEDLINE]

19: Immunopharmacol Immunotoxicol. 2006;28(1):129/​40.

Antioxidant and anti/​inflammatory activities of the plant Andrographis
paniculata Nees.

Sheeja K, Shihab PK, Kuttan G.

Amala Cancer Research Centre, Thrissur, Kerala, India.

In this study, we explored the antioxidant and anti/​inflammatory properties of
the medicinal herb Andrographis paniculata using in vitro as well as in vivo
systems. Methanolic extract of Andrographis paniculata was found to inhibit
formation of oxygen derived free radicals such as superoxide (32%) hydroxyl
radicals (80%) lipid peroxidation (80%) and nitric oxide (42.8%) in in vitro
system. In vivo studies using BALB/c mice models also showed significant
inhibition in PMA induced superoxide (32.4%) and nitric oxide (65.3%) formation.
Interestingly we also found that, administration of Andrographis paniculata
extract produced complete inhibition of carageenan induced inflammation compared
with control models.

PMID: 16684672 [PubMed /​ indexed for MEDLINE]

20: Phytomedicine. 2006 May;13(5):318/​23. Epub 2005 Sep 16.

The effect of Kan Jang extract on the pharmacokinetics and pharmacodynamics of
warfarin in rats.

Hovhannisyan AS, Abrahamyan H, Gabrielyan ES, Panossian AG.

"Exlab" Expert Analytical Laboratory of Drug and Medical Technology Agency of
Ministry of Health, Yerevan, Armenia. arego@sci.am

Significant pharmacokinetic/pharmacodynamic interactions between various herbal
products and warfarin have recently been reported. The aim of this study was to
determine whether concomitant treatment of rats with Kan Jang (a standardized
fixed combination of extracts from Andrographis paniculata and Eleutherococcus
senticosus) and warfarin would lead to an alteration in the pharmacological
effects of warfarin. Each day for 5 days a group of animals was treated orally
with an aqueous solution of Kan Jang at a dose of 17 mg/kg of the active
principle andrographolide (a daily dose some 17/​fold higher than that
recommended for humans): the control group received similar treatment with
appropriate volumes of water only. Sixty minutes after the final daily
administration of Kan Jang or water, an aqueous solution of warfarin (0.2 mg/ml)
was given to each animal at a dose of 2 mg/kg. From each group, 6 animals were
sacrificed at 0, 2, 4, 6, 8, 12, 24, 30 and 48 h after warfarin administration
and blood samples taken. The concentration of warfarin in blood plasma was
measured by capillary electrophoresis using 50 mM borate buffer (pH 9.3) as
mobile phase with simultaneous detection of warfarin at 208.1 and 307.5 nm.
Prothrombin time in blood plasma was measured using thromboplastin reagent. The
concomitant application of Kan Jang and warfarin did not produce significant
effects on the pharmacokinetics of warfarin, and practically no effect on its
pharmacodynamics.

Publication Types:
Comparative Study

PMID: 16635739 [PubMed /​ indexed for MEDLINE]

21: J Ethnopharmacol. 2006 Sep 19;107(2):205/​10. Epub 2006 Mar 17.

The effect of medicinal plants used in Chinese folk medicine on RANTES secretion
by virus/​infected human epithelial cells.

Ko HC, Wei BL, Chiou WF.

Division of Basic Chinese Medical Research, National Research Institute of
Chinese Medicine, Shipai, Taipei, Taiwan, ROC.

The accumulation of inflammatory cells in the infective sites has been reported
to play a crucial role in the progression of chronic inflammation and multiple
sclerosis after viral infection. In the present study, nine ethanol extracts of
Forsythia suspensa Vahl. (Oleaceae), Lonicera japonica Thunb. (Caprifoliaceae),
Isatis indigotica Fort. (Cruciferae), Strobilanthes cusia (Ness.) O. Kuntze
(Acanthaceae), Astragalus membranaceus (Fisch.) Bge. (Leguminosae), Hedysarum
polybotrys Hand./​Mazz. (Leguminosae), Andrographis paniculata (Burm. f.) Ness.
(Acanthaceae), Glycyrrhiza uralensis Fischer. (Leguminosae) and Ligusticum
wallichii Franch. (Umbelliferae), medicinal plants traditionally used in China
for treating conditions likely to be associated with inflammation and viral
infection, were screened for their effect on RANTES secretion by influenza A
virus (H1N1)/​infected human bronchial epithelial cells (A549). With exception of
Lonicera japonica, Isatis indigotica, Astragalus membranaceus and Hedysarum
polybotrys, all plants tested at concentration of 200 microg/ml possessed more
than 50% suppressing effect on RANTES secretion by H1N1/​infected A549 bronchial
epithelial cells. Among the plants tested, Andrographis paniculata showed the
most promising property to inhibit RANTES secretion with an IC(50) of 1.2 +//​
0.4 microg/ml while the next two were Glycyrrhiza uralensis and Forsythia
suspensa (IC(50) ranging from 35 to 48 microg/ml).

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16621378 [PubMed /​ indexed for MEDLINE]

22: J Nat Prod. 2006 Mar;69(3):403/​5.

Andropanolide and isoandrographolide, minor diterpenoids from Andrographis
paniculata: structure and X/​ray crystallographic analysis.

Pramanick S, Banerjee S, Achari B, Das B, Sen AK Sr, Mukhopadhyay S, Neuman A,
Prange T.

Indian Institute of Chemical Biology, Kolkata, India.

Phytochemical investigation of the leaves of Andrographis paniculata has led to
the isolation of a new labdane type diterpenoid, andropanolide (1), along with
seven known diterpenoids including isoandrographolide (2), previously reported
as a rearrangement product of andrographolide. The structures and
stereochemistry of compounds 1 and 2 were established by X/​ray crystallographic
analysis.

PMID: 16562845 [PubMed /​ indexed for MEDLINE]

23: J Nat Prod. 2006 Mar;69(3):319/​22.

ent/​Labdane diterpenoids from Andrographis paniculata.

Shen YH, Li RT, Xiao WL, Xu G, Lin ZW, Zhao QS, Sun HD.

State Key Laboratory of Phytochemistry and Plant Resources in West China,
Kunming Institute of Botany, Chinese Academy of Sciences, People's Republic of
China.

Six new ent/​labdane diterpenoids,
3/​O/​beta/​D/​glucopyranosyl/​14,19/​dideoxyandrographolide (1),
14/​deoxy/​17/​hydroxyandrographolide (2),
19/​O/​[beta/​D/​apiofuranosyl(1/​/​>2)/​beta/​D/​glucopyranoyl]/​3,14/​dideoxyandrographol
ide (3), 3/​O/​beta/​d/​glucopyranosylandrographolide (4),
12S/​hydroxyandrographolide (5), and andrographatoside (6), together with 17
known analogues, were isolated from the aerial parts of Andrographis paniculata.
The structures of 1/​6 were determined by spectroscopic data analysis. All
compounds isolated were evaluated for their inhibitory activity against several
bacterial and fungal strains.

PMID: 16562826 [PubMed /​ indexed for MEDLINE]

24: J Ethnopharmacol. 2006 May 24;105(3):464/​7. Epub 2006 Jan 6.

Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450
enzymes.

Jarukamjorn K, Don/​in K, Makejaruskul C, Laha T, Daodee S, Pearaksa P,
Sripanidkulchai BO.

Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon
Kaen University, Khon Kaen 40002, Thailand. kanok_ja@kku.ac.th

Modulatory influence of Andrographis paniculata crude extract on cytochrome P450
(CYP) enzymes was performed by administration of the crude extract of
Andrographis paniculata to ICR male mice. Total hepatic P450 content was not
significantly modified by either the aqueous or the alcoholic extracts of
Andrographis paniculata. Assessment of hepatic microsomal P450 activities by
alkoxyresorufin O/​dealkylations noted that both the aqueous and alcoholic
extracts of Andrographis paniculata significantly increased ethoxyresorufin
O/​dealkylase and pentoxyresorufin O/​dealkylase activities, while those of
methoxyresorufin O/​dealkylase activities were not elevated. These results
suggested that Andrographis paniculata might effectuate hepatic cytochrome P450
enzymes of which CYP1A1 and CYP2B are the responsive P450 isoforms.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16406417 [PubMed /​ indexed for MEDLINE]

25: Phytother Res. 2006 Jan;20(1):79/​81.

Inhibitory effect of Thai plant extracts on P/​glycoprotein mediated efflux.

Junyaprasert VB, Soonthornchareonnon N, Thongpraditchote S, Murakami T, Takano
M.

Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447
Sri/​Ayutthaya, Rajathavee, Bangkok 10400, Thailand. pyvbp@mahidol.ac.th

Curcuminoids from Curcuma longa L. and extracts of Psidium guajava L.,
Andrographis paniculata (Burm. f.) Nees, Phyllanthus emblica L. and Solanum
trilobatum L. were investigated for their inhibitory effect on P/​glycoprotein
(P/​gp) on the efflux transport of rhodamine 123 (Rho/​123 ) in Caco/​2 cells and
rat ileum. Of the five tested samples, curcuminoids and an extract of P. guajava
showed the highest inhibitory effect on P/​gp mediated efflux of Rho/​123 in
Caco/​2 cells. Additionally, they were found to have equal potential in
inhibiting Rho/​123 efflux transport from serosal to mucosal surfaces of the rat
ileum. Copyright 2006 John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16397849 [PubMed /​ indexed for MEDLINE]

26: Planta Med. 2005 Dec;71(12):1106/​11.

Andrographolide isolated from Andrographis paniculata induces cell cycle arrest
and mitochondrial/​mediated apoptosis in human leukemic HL/​60 cells.

Cheung HY, Cheung SH, Li J, Cheung CS, Lai WP, Fong WF, Leung FM.

Department of Biology and Chemistry, City University of Hong Kong, Hong Kong
SAR, China. bhhonyun@cityu.edu.hk

The in vitro cytotoxicities of the ethanol extract of Andrographis paniculata
(APE) and its main diterpenoid components were evaluated in various cancer
cells. APE was found to be significantly growth inhibitory to human acute
myeloid leukemic HL/​60 cells with an IC (50) value of 14.01 microg/mL after 24 h
of treatment. Among the three main diterpenoids in A. paniculata,
andrographolide exhibited the highest degree of cytotoxicity followed by
deoxyandrographolide while neoandrographolide was the least effective. Laser
confocal microscopy and gel electrophoresis studies revealed chromosomal DNA
fragmentations suggesting the occurrence of apoptosis. An increase of G (0)/G
(1) phase cells from 51.88 % to 78.69 % was noted after andrographolide
treatment for 36 h. The G (0)/G (1) phase arrest and apoptosis were associated
with disappearance of mitochondrial cytochrome c and increased expression of Bax
but decreased expression of Bcl/​2 proteins in the inhibited cells. Although the
order of all these events has not been determined, it is concluded that APE and
andrographolide induce cell cycle arrest and affect an intrinsic
mitochondria/​dependent pathway of apoptosis by regulating the expression of some
pro/​apoptotic markers in HL/​60 cells.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16395645 [PubMed /​ indexed for MEDLINE]

27: Am J Health Syst Pharm. 2006 Jan 1;63(1):33/​9.

Complementary and alternative medicine for upper/​respiratory/​tract infection in
children.

Carr RR, Nahata MC.

College of Pharmacy, The Ohio State University, Columbus, OH 43210/​1291, USA.

PURPOSE: Evidence on the efficacy and safety of complementary and alternative
medicine (CAM) for the prevention and treatment of upper/​respiratory/​tract
infection (URTI) in children is reviewed. SUMMARY: A search of the literature to
June 2005 identified six clinical trials examining the use of herbal medicines
and nine trials of other CAM therapies. All articles were critically evaluated
for adherence to standards of efficacy and safety research. Echinacea did not
reduce the duration and severity of URTI. Andrographis paniculata or echinacea
decreased nasal secretions (p < 0.01) but not URTI symptoms. A combination of
echinacea, propolis, and ascorbic acid decreased the number of URTI episodes,
the duration of symptoms, and the number of days of illness (p < 0.001).
Echinacea was associated with a higher frequency of rash compared with placebo
(p = 0.008). Neither ascorbic acid nor homeopathy was effective. The efficacy of
zinc was not clear, and zinc may be associated with adverse effects in children.
Osteopathic manipulation decreased episodes of acute otitis media (p = 0.04) and
the need for tympanostomy tube insertion (p = 0.03) in children with recurrent
acute otitis media. Stress/​management therapy reduced the duration of URTI
compared with relaxation therapy with guided imagery or standard care (p <
0.05). CONCLUSION: Current data are generally inadequate to support CAM for the
prevention or treatment of URTI in children.

Publication Types:
Review

PMID: 16373463 [PubMed /​ indexed for MEDLINE]

28: Phytother Res. 2005 Dec;19(12):1069/​70.

Antiviral properties of ent/​labdene diterpenes of Andrographis paniculata nees,
inhibitors of herpes simplex virus type 1.

Wiart C, Kumar K, Yusof MY, Hamimah H, Fauzi ZM, Sulaiman M.

Department of Pharmacy, Faculty of Medicine, University of Malaya, Malaysia.
christophe_wiart@yahoo.com

Andrographolide, neoandrographolide and 14/​deoxy/​11,12/​didehydroandrographolide,
ent/​labdene diterpenes isolated from Andrographis paniculata showed viricidal
activity against herpes simplex virus 1 (HSV/​1). None of these compounds
exhibited significant cytotoxicity at viricidal concentrations. Copyright 2005
John Wiley & Sons, Ltd.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16372376 [PubMed /​ indexed for MEDLINE]

29: Se Pu. 2002 Sep;20(5):446/​8.

[Determination of andrographolide and dehydroandrographolide in Andrographis
paniculata nees materials and related patent medicines by reversed/​phase high
performance liquid chromatography]

[Article in Chinese]

Xu XQ, Hu GL, Shen JC, Li Q, Wang XR.

The Key Laboratory of Analytical Sciences of Ministry of Education of China,
College of Chemistry and Chemical Engineering, Xiamen Unitersity, Xiamen 361005,
China.

A simple and accurate method for the determination of andrographolide and
dehydroandrographolide in andrographis paniculata Nees materials and patent
medicines with high performance liquid chromatography (HPLC) has been developed.
The two components were extracted from powdered samples by shaking with
methanol. The resultant extracts were separated within 15 min on a BECKMAN C18
column (4.6 mm i. d. x 250 mm, 5 microm) and with a gradient elution of
acetonitrile/​water at a flow rate of 0.5 mL/min. The detection wavelength was
225 nm and the injection volume was 20 microL. In gradient elution program the
volume fraction of acetonitrile in mobile phase was as follows: 0 min /​ 1 min,
40%; 1 min /​ 5 min, 40% /​ 50%; 5 min /​ 15 min, 50% /​ 70%. Both andrographolide
and dehydroandrographolide have good linearity in the range of 10 mg/L to 100
mg/L with the correlation coefficients of 0.997 6 and 0.998 6 respectively. This
method has been successfully applied for the analysis of andrographis paniculata
Nees materials and related patent medicines.

Publication Types:
English Abstract

PMID: 16358699 [PubMed /​ in process]

30: J Ethnopharmacol. 2006 Apr 21;105(1/​2):196/​200. Epub 2005 Nov 18.

Anti/​diabetic potentials of Momordica charantia and Andrographis paniculata and
their effects on estrous cyclicity of alloxan/​induced diabetic rats.

Reyes BA, Bautista ND, Tanquilut NC, Anunciado RV, Leung AB, Sanchez GC, Magtoto
RL, Castronuevo P, Tsukamura H, Maeda KI.

Thomas Jefferson University, Department of Neurosurgery, Farber Institute for
Neurosciences, Philadelphia, Pennsylvania 19107, USA. bsr103@jefferson.edu

Momordica charantia and Andrographis paniculata are the commonly used herbs by
the diabetic patients in Pampanga, Philippines. While the anti/​diabetic
potential of Momordica charantia is well established in streptozocin/​ or
alloxan/​induced diabetic animals, the anti/​diabetic potential of Andrographis
paniculata in alloxan/​induced diabetic rat is not known. Neither the effects of
these herbs on estrous cyclicity of alloxan/​induced diabetic rats are
elucidated. Thus, in these experiments, Momordica charantia fruit juice or
Andrographis paniculata decoction was orally administered to alloxan/​induced
diabetic rats. Rats that were treated with Momordica charantia and Andrographis
paniculata had higher body weight (BW) compared with diabetic positive control
(P < 0.01) from day 22 to day 27 (D27) but exhibited lower BW than the
non/​diabetic control (P < 0.05). These rats had lower feed (P < 0.05) and liquid
intakes (P < 0.01) compared with diabetic positive control from day 17 to D27,
but similar with the non/​diabetic control. The blood glucose levels in these
groups were significantly reduced from day 12 to D27 compared with diabetic
positive control (P < 0.01), however, comparable with non/​diabetic control. The
diabetic positive control had extended mean estrous cycles (8 days) compared to
Momordica charantia and Andrographis paniculata/​treated diabetic rats (5 days; P
< 0.05). Our results suggest that the anti/​diabetic potentials of Momordica
charantia and Andrographis paniculata could restore impaired estrous cycle in
alloxan/​induced diabetic rats.

PMID: 16298503 [PubMed /​ indexed for MEDLINE]

31: J Ethnopharmacol. 2006 Jan 16;103(2):201/​7. Epub 2005 Sep 15.

Screening of plants acting against Heterometrus laoticus scorpion venom activity
on fibroblast cell lysis.

Uawonggul N, Chaveerach A, Thammasirirak S, Arkaravichien T, Chuachan C, Daduang
S.

Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen
40002, Thailand.

The aqueous extracts of 64 plant species, listed as animal/​ or insect/​bite
antidotes in old Thai drug recipes were screened for their activity against
fibroblast cell lysis after Heterometrus laoticus scorpion venom treatment. The
venom was preincubated with plant extract for 30 min and furthered treated to
confluent fibroblast cells for 30 min. More than 40% efficiency (test/control)
was obtained from cell treatment with venom preincubated with extracts of
Andrographis paniculata Nees (Acanthaceae), Barringtonia acutangula (L.) Gaertn.
(Lecythidaceae), Calamus sp. (Palmae), Clinacanthus nutans Lindau (Acanthaceae),
Euphorbia neriifolia L. (Euphorbiaceae), Ipomoea aquatica Forssk
(Convolvulaceae), Mesua ferrea L. (Guttiferae), Passiflora laurifolia L.
(Passifloraceae), Plectranthus amboinicus (Lour.) Spreng. (Labiatae), Ricinus
communis L. (Euphorbiaceae), Rumex sp. (Polygonaceae) and Sapindus rarak DC.
(Sapindaceae), indicating that they had a tendency to be scorpion venom
antidotes. However, only Andrographis paniculata and Barringtonia acutangula
extracts provided around 50% viable cells from extract treatments without venom
preincubation. These two plant extracts are expected to be scorpion venom
antidotes with low cytotoxicity.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16169172 [PubMed /​ indexed for MEDLINE]

32: Planta Med. 2005 Jul;71(7):604/​8.

14/​deoxyandrographolide as a platelet activating factor antagonist in bovine
neutrophils.

Burgos RA, Hidalgo MA, Monsalve J, LaBranche TP, Eyre P, Hancke JL.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Facultad de
Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile.
rburgos1@uach.cl

14/​Deoxyandrographolide (14/​DAP) is a labdane diterpene isolated from
Andrographis paniculata with previously reported calcium channel blocking
activity. Its potential platelet activating factor (PAF) antagonistic activity
in bovine neutrophils was assessed. 14/​DAP, in concentrations between 10/​100
microM, reduced the extracellular acidification rate and the intracellular
alkalinization in a dose/​dependent manner. In addition, 14/​DAP reduced
PAF/​induced calcium flux in the presence of extracellular calcium, and tyrosine
phosphorylation of a 44 kDa protein corresponding to the MAPK(ERK1). However,
14/​DAP reduced the 3H/​PAF binding with a Ki of 7.8 x 10 (/​ 9)M, and a Hill slope
of 0.63, suggesting that there is more than one binding site for 14/​DAP. We
concluded that 14/​DAP is an effective antagonist of PAF/​mediated processes in
bovine neutrophils, probably by virtue of its calcium channel blocking property.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 16041644 [PubMed /​ indexed for MEDLINE]

33: Phytomedicine. 2005 Jun;12(6/​7):403/​9.

A phase I clinical study of Andrographis paniculata fixed combination Kan Jang
versus ginseng and valerian on the semen quality of healthy male subjects.

Mkrtchyan A, Panosyan V, Panossian A, Wikman G, Wagner H.

Republican Medical Scientific Centre of Dermatology and Diseases Disseminated by
Sexual Contacts, Yerevan, Armenia.

The safety of different doses of Kan Jang/​/​a fixed combination of Andrographis
paniculata special extract (SHA/​10) and Acanthopanax senticosus/​/​compared to two
extensively used medicinal plants, Valeriana officinalis and Panax ginseng in
the form of standardized extracts, has been examined. A phase I clinical study
was designed to evaluate the effect on semen quality of healthy males in terms
of spermatogenesis and quality of semen. The results of the study revealed no
significant negative effect of Kan Jang on male semen quality and fertility, but
rather a positive trend with respect to the number of spermatozoids in the whole
ejaculate, the percentage of active (normokinetic) forms of spermatozoids, and
fertility indexes, together with a decrease in the percentage of inactive
(diskinetic) forms of spermatozoids. In the group receiving ginseng, no
significant negative effects on the fertility parameters were revealed and there
was a clear decrease in the percentage of diskinetic forms of spermatozoids.
Subjects receiving valerian showed a temporary increase in the percentage of
normokinetic spermatozoids and a decrease in diskinetic forms, but these changes
had no effect on fertility indices. The results indicate that Kan Jang, ginseng
and valerian are safe with respect to effects on human male sterility when
administered at dose levels corresponding to approximately 3 times the human
daily dose.

Publication Types:
Clinical Trial
Clinical Trial, Phase I
Randomized Controlled Trial

PMID: 16008115 [PubMed /​ indexed for MEDLINE]

34: J Cell Biochem. 2005 Aug 1;95(5):970/​8.

Andrograpanin, a compound isolated from anti/​inflammatory traditional Chinese
medicine Andrographis paniculata, enhances chemokine SDF/​1alpha/​induced
leukocytes chemotaxis.

Ji LL, Wang Z, Dong F, Zhang WB, Wang ZT.

Department of Pharmacognosy, China Pharmaceutical University, 1 Shen Nong Road,
Nanjing, People's Republic of China.

Andrographis paniculata is a traditional Chinese medicine (TCM) that has been
effectively used for treatment of infection, inflammation, cold, fever, and
diarrhea in China. However, mechanism of its therapeutic function is not well
known. In the current study, we showed one of its components, andrograpanin,
could enhance chemokine stromal cell/​derived factor/​1alpha (SDF/​1alpha) induced
chemotaxis in Jurkat and THP/​1 cells. Further study demonstrated that this kind
of effect was CXC chemokine receptor/​4 (CXCR4) specific, since andrograpanin
could not enhance other chemokines, such as RANTES, monocyte chemotactic
protein/​1 (MCP/​1), etc. induced cell chemotaxis. Mechanisms of andrograpanin
exerting its effect were not directly in the receptor and G protein coupling
level because it had no effect on the binding of SDF/​1 to CXCR4, SDF/​1 induced G
protein activation and adenyly cyclase inhibition. However, receptor
internalization might be involved, since we found it significantly reduced
SDF/​1alpha/​induced CXCR4 internalization. (c) 2005 Wiley/​Liss, Inc.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15937916 [PubMed /​ indexed for MEDLINE]

35: Planta Med. 2005 May;71(5):429/​34.

Andrographolide inhibits IFN/​gamma and IL/​2 cytokine production and protects
against cell apoptosis.

Burgos RA, Seguel K, Perez M, Meneses A, Ortega M, Guarda MI, Loaiza A, Hancke
JL.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Faculty of
Veterinary Science, Universidad Austral de Chile, Valdivia, Chile.
rburgos1@uach.cl

Andrographolide is the main labdane diterpene present in Andrographis
paniculata. Two lines of evidence report immunostimulant and anti/​inflammatory
properties for andrographolide in different models. Using murine T/​cells in
vitro we demonstrated that andrographolide and to a lesser extent,
14/​deoxyandrographolide (14/​DAP), reduced significantly, in a dose/​dependent
manner, the IFN/​gamma production induced by concanavaline A (CON/​A), with an
IC50 of 1.7 +//​ 0.07 microM and 35.8 +//​ 0.50 microM, respectively.
Andrographolide, but not 14/​DAP, inhibited partially the IL/​2 production induced
by CON/​A. Andrographolide at doses of 5 and 10 microM reduced the
extracellular/​signal/​regulated protein kinase (ERK1/2) phosphorylation induced
by CON/​A, whereas 14/​DAP only reduced ERK1 and partially the ERK2
phosphorylation. The inhibition of ERK1/2 phosphorylation was associated to a
decrease in the IFN/​gamma production, due that UO126, a specific ERK1/2
inhibitor, also reduced the IFN/​gamma production in murine T/​cells induced by
CON/​A. Additionally, andrographolide and to a lesser extent 14/​DAP, at doses of
50 microM and 100 microM, respectively, reduced the apoptosis induced by
hydrocortisone and PMA in thymocytes, which was associated to a decrease in
caspase/​3 like activity. We conclude that both diterpenic labdanes isolated from
A. paniculata can exert potent immunosuppressant effects without affecting the
viability of the cells.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15931581 [PubMed /​ indexed for MEDLINE]

36: J Pharm Biomed Anal. 2006 Jan 23;40(1):157/​61.

Simultaneous determination of andrographolide and dehydroandrographolide in
Andrographis paniculata and Chinese medicinal preparations by microemulsion
electrokinetic chromatography.

Yanfang Z, Xingping L, Zongde Z, Liren C, Yongmin L.

Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou
730000, China.

The present paper describes the development of a microemulsion electrokinetic
chromatographic (MEEKC) method for simultaneous determination of andrographolide
and dehydroandrographolide in traditional Chinese medicines and Chinese
medicinal preparations. The MEEKC method involved the use of sodium dodecyl
sulfate (SDS) as surfactant, heptane as organic solvent and butan/​1/​ol as
co/​solvent. The effect of temperature and pH of running buffers on separation
were examined. The optimized conditions (heptane 0.81% (w/w), SDS 3.31% (w/w),
butan/​1/​ol 6.61% (w/w) and 10mM sodium tetraborate buffer, pH 9.2) allowed a
useful and good reproducible separation of the studied analytes to be achieved.

PMID: 15894448 [PubMed /​ indexed for MEDLINE]

37: Nat Prod Res. 2005 Apr;19(3):223/​30.

A new bis/​andrographolide ether from Andrographis paniculata nees and evaluation
of anti/​HIV activity.

Reddy VL, Reddy SM, Ravikanth V, Krishnaiah P, Goud TV, Rao TP, Ram TS, Gonnade
RG, Bhadbhade M, Venkateswarlu Y.

Natural Products Laboratory, Organic Chemistry Division/​I, Indian Institute of
Chemical Technology, Hyderabad/​500 007, India.

Novel bis/​andrographolide ether (1) and six known compounds andrographolide,
14/​deoxy/​11,12/​didehydroandrographolide, andrograpanin, 14/​deoxyandrographolide,
(+//​)/​5/​hydroxy/​7,8/​dimethoxyflavanone, and 5/​hydroxy/​7,8/​dimethoxyflavone have
been isolated from the aerial parts of Andrographis paniculata and their
structures were established by spectral data. All the isolates were tested for
the anti/​HIV and cytotoxic activity.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15702635 [PubMed /​ indexed for MEDLINE]

38: Br J Pharmacol. 2005 Mar;144(5):680/​6.

Andrographolide interferes with binding of nuclear factor/​kappaB to DNA in
HL/​60/​derived neutrophilic cells.

Hidalgo MA, Romero A, Figueroa J, Cortes P, Concha II, Hancke JL, Burgos RA.

Laboratory of Molecular Pharmacology, Institute of Pharmacology, Universidad
Austral de Chile, PO Box 567, Isla Teja s/n, Valdivia, Chile.

1. Andrographolide, the major active component from Andrographis paniculata, has
shown to possess anti/​inflammatory activity. Andrographolide inhibits the
expression of several proinflammatory proteins that exhibit a nuclear factor
kappa B (NF/​kappaB) binding site in their gene. 2. In the present study, we
analyzed the effect of andrographolide on the activation of NF/​kappaB induced by
platelet/​activating factor (PAF) and N/​formyl/​methionyl/​leucyl/​phenylalanine
(fMLP) in HL/​60 cells differentiated to neutrophils. 3. PAF (100 nM) and fMLP
(100 nM) induced activation of NF/​kappaB as determined by degradation of
inhibitory factor B alpha (IkappaB alpha) using Western blotting in cytosolic
extracts and by binding to DNA using electrophoretic mobility shift assay (EMSA)
in nuclear extracts. 4. Andrographolide (5 and 50 microM) inhibited the
NF/​kappaB/​luciferase activity induced by PAF. However, andrographolide did not
reduce phosphorylation of p38 MAPK or ERK1/2 and did not change IkappaB alpha
degradation induced by PAF and fMLP. 5. Andrographolide reduced the DNA binding
of NF/​kappaB in whole cells and in nuclear extracts induced by PAF and fMLP. 6.
Andrographolide reduced cyclooxygenase/​2 (COX/​2) expression induced by PAF and
fMLP in HL/​60/neutrophils. 7. It is concluded that andrographolide exerts its
anti/​inflammatory effects by inhibiting NF/​kappaB binding to DNA, and thus
reducing the expression of proinflammatory proteins, such as COX/​2.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15678086 [PubMed /​ indexed for MEDLINE]

39: Phytochem Anal. 2004 Nov/​Dec;15(6):365/​71.

Determination and variation of three active diterpenoids in Andrographis
paniculata (Burm.f.) Nees.

Pholphana N, Rangkadilok N, Thongnest S, Ruchirawat S, Ruchirawat M, Satayavivad
J.

Laboratory of Pharmacology, Chulabhorn Research Institute, Vibhavadee/​Rangsit
Highway, Laksi, Bangkok 10210, Thailand.

Simple and rapid methods have been developed for the extraction and simultaneous
determination of the three active diterpenoids, andrographolide (AP1),
14/​deoxy/​11,12/​didehydroandrographolide (AP3) and neoandrographolide (AP4), from
various samples of Andrographis paniculata (Burm.f.) Nees. Methanol extracts
from the dried leaves, stems and crude products were analysed by isocratic HPLC
using a methanol and water mobile phase with monitoring at 220 nm. There was a
large variation of the three active diterpenoids in different A. paniculata
products obtained from Thai markets. The results indicated that the amounts of
these active compounds consumed, based on the recommended daily doses, from
materials obtained from the different suppliers will be different. In addition,
the stability of these three active compounds was also examined in dry herbs
stored at room temperature. The results showed that andrographolide was more
stable than the others. In contrast, the content of
14/​deoxy/​11,12/​didehydroandrographolide increased and the neoandrographolide
content fluctuated during storage time. The combination of different levels of
these compounds in the source materials and the changes during storage could
have a significant effect on the efficacy of this traditional herbal medicine in
clinical treatment.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15595451 [PubMed /​ indexed for MEDLINE]

40: Zhong Xi Yi Jie He Xue Bao. 2004 Nov;2(6):456/​8.

[Effect of ultra/​fine powder technique on dissolution rates of andrographolide
and dehydroandrographolide in Andrographis paniculata]

[Article in Chinese]

Qiu RL, Li L, Li X, Zhang HX, Chen JW.

Department of Medicinal Chemistry, School of Pharmacy, Nanjing University of
Traditional Chinese Medicine, Nanjing, Jiangsu Province 210029, China.
rongliq@hotmail.com

OBJECTIVE: To investigate the effects of ultra/​fine powder technique on
dissolution rates of the components in Andrographis paniculata. METHODS: High
performance liquid chromatography was employed to determine the concentration of
andrographolide and dehydroandrographolide in common powdered or ultra/​fine
powdered Andrographis paniculata. RESULTS: The dissolution rates of
andrographolide and dehydroandrographolide in ultra/​fine powdered Andrographis
paniculata were higher than those of the general powder. CONCLUSION: Ultra/​fine
powder technique promotes the dissolution rates of andrographolide and
dehydroandrographolide.

Publication Types:
English Abstract

PMID: 15539030 [PubMed /​ indexed for MEDLINE]

41: Phytochem Anal. 2004 Sep/​Oct;15(5):280/​5.

Chemical fingerprinting of Andrographis paniculata using HPLC, HPTLC and
densitometry.

Srivastava A, Misra H, Verma RK, Gupta MM.

Central Institute of Medicinal and Aromatic Plants, PO CIMAP, Lucknow/​226015,
India.

An attempt has been made to develop a method by which to determine the chemical
fingerprint of Andrographis paniculata (Acanthaceae). High/​performance thin
layer chromatography (HPTLC) was used to analyse hexane, chloroform, methanol
and water extracts of leaves of A. paniculata. A computerised densitometer was
applied to the two/​dimensional spectrographic image analysis of the HPTLC
plates. An HPLC equipped with a photodiode array detector was used for the
analyses of these different extracts. The analyses showed that andrographolide
and neoandrographolide are absent in the hexane extract but are present in
greater amounts in the methanol extract as compared with the other extracts.
These chromatograms may serve as a chemical fingerprint of the drug A.
paniculata for quality control purposes and in the preparation of formulations
based on the drug.

PMID: 15508831 [PubMed /​ indexed for MEDLINE]

42: J Ethnopharmacol. 2004 Dec;95(2/​3):247/​51.

Anti/​malarial activity of some xanthones isolated from the roots of Andrographis
paniculata.

Dua VK, Ojha VP, Roy R, Joshi BC, Valecha N, Devi CU, Bhatnagar MC, Sharma VP,
Subbarao SK.

Malaria Research Centre, Sector III, BHEL, Hardwar 249 403, India.
virendradua@hotmail.com

Four xanthones were isolated from the roots of Andrographis paniculata using a
combination of column and thin/​layer chromatographic methods. They were
characterized as (i) 1,8/​di/​hydroxy/​3,7/​dimethoxy/​xanthone, (ii)
4,8/​dihydroxy/​2,7/​dimethoxy/​xanthone, (iii) 1,2/​dihydroxy/​6,8/​dimethoxy/​xanthone
and (iv) 3,7,8/​trimethoxy/​1/​hydroxy xanthone by IR, MS and NMR spectroscopic
methods. In vitro study revealed that compound
1,2/​dihydroxy/​6,8/​dimethoxy/​xanthone possessed substantial anti/​plasmodial
activity against Plasmodium falciparum with its IC(50) value of 4 microg ml(/​1).
Xanthones bearing hydroxyl group at 2 position demonstrated most potent activity
while xanthones with hydroxyl group at 1,4 or 8 position possessed very low
activity. In vivo anti/​malarial sensitivity test of this compound on Swiss
Albino mice with Plasmodium berghei infection using Peters' 4/​day test gave
substantial reduction (62%) in parasitaemia after treating the mice with 30 mg
kg(/​1) dose. In vitro cytotoxicity against mammalian cells revealed that
1,2/​dihydroxy/​6,8/​dimethoxy/​xanthone is non/​cytotoxic with its IC(50) > 32
microg ml(/​1).

Publication Types:
Comparative Study
Research Support, Non/​U.S. Gov't

PMID: 15507344 [PubMed /​ indexed for MEDLINE]

43: J Ethnopharmacol. 2004 Dec;95(2/​3):205/​8.

Screening for antihyperglycaemic activity in several local herbs of Malaysia.

Husen R, Pihie AH, Nallappan M.

School of Bioscience and Biotechnology, Faculty of Science and Technology,
Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.

Screening of aqueous extract of Phyllantus niruri (PL), Zingiber zerumbet (ZG),
Eurycoma longifolia (TA/​a and TA/​b) and Andrographis paniculata (AP) to
determine their blood glucose lowering effect were conducted in normoglycaemic
and Streptozotocin/​induced hyperglycaemic rats. Significant reduction in blood
glucose level at 52.90% was shown when hyperglycaemic rats were treated with 50
mg/kg body weight (BW) aqueous extract of AP. This effect is enhanced when
freeze/​dried material was used, where 6.25 mg/kg BW gave 61.81% reduction in
blood glucose level. In the administration of TA/​a and TA/​b, positive results in
hyperglyacaemic rats were only obtained when 150 mg/kg BW of the aqueous extract
was used. No significant reduction in blood glucose level were shown in
hyperglycaemic rats treated with PL and ZG at all concentrations used (50, 100
and 150 mg/kg BW). In normoglycaemic rats, no significant reduction was noted
when all the same extracts were used.

Publication Types:
Comparative Study

PMID: 15507337 [PubMed /​ indexed for MEDLINE]

44: Phytochemistry. 2004 Aug;65(16):2317/​21.

Flavonoids and andrographolides from Andrographis paniculata.

Koteswara Rao Y, Vimalamma G, Rao CV, Tzeng YM.

Department of Applied Chemistry, Chaoyang University of Technology, 168 Gifeng
E. Road, Wufeng, Taichung 413, Taiwan.

Two flavonoids, identified as 5,7,2',3'/​tetramethoxyflavanone and
5/​hydroxy/​7,2',3'/​trimethoxyflavone, as well as several other flavonoids,
andrographolide diterpenoids, and polyphenols, were obtained from the
phytochemical investigation of the whole plant of Andrographis paniculata, a
well known medicinal plant. The structures of these compounds were established
with the aid of spectroscopic methods, including analysis by 2D NMR
spectroscopy.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15381002 [PubMed /​ indexed for MEDLINE]

45: J Pharmacol Exp Ther. 2005 Jan;312(1):366/​72. Epub 2004 Aug 26.

Andrographolide interferes with T cell activation and reduces experimental
autoimmune encephalomyelitis in the mouse.

Iruretagoyena MI, Tobar JA, Gonzalez PA, Sepulveda SE, Figueroa CA, Burgos RA,
Hancke JL, Kalergis AM.

Departamento de Genetica Molecular y Microbiologia, Facultad de Ciencias
Biologicas, Pontificia Universidad Catolica de Chile, Alameda 340, Santiago,
Chile.

Andrographolide is a bicyclic diterpenoid lactone derived from extracts of
Andrographis paniculata, a plant indigenous to South Asian countries that shows
anti/​inflammatory properties. The molecular and cellular bases for this
immunomodulatory capacity remain unknown. Here, we show that andrographolide is
able to down/​modulate both humoral and cellular adaptive immune responses. In
vitro, this molecule was able to interfere with T cell proliferation and
cytokine release in response to allogenic stimulation. These results were
consistent with the observation that T cell activation by dendritic cells (DCs)
was completely abolished by exposing DCs to andrographolide during antigen
pulse. This molecule was able to interfere with maturation of DCs and with their
ability to present antigens to T cells. Furthermore, in vivo immune responses
such as antibody response to a thymus/​dependent antigen and delayed/​type
hypersensitivity were drastically diminished in mice by andrographolide
treatment. Finally, the ability of andrographolide to inhibit T cell activation
was applied to interfere with the onset of experimental autoimmune
encephalomyelitis (EAE), an inflammatory demyelinating disease of the central
nervous system that is primarily mediated by CD4(+) T cells and serves as an
animal model for human multiple sclerosis. Treatment with andrographolide was
able to significantly reduce EAE symptoms in mice by inhibiting T cell and
antibody responses directed to myelin antigens. Our data suggest that
andrographolide is able to efficiently block T cell activation in vitro, as well
as in vivo, a feature that could be useful for interfering with detrimental T
cell responses.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15331658 [PubMed /​ indexed for MEDLINE]

46: Bioorg Med Chem Lett. 2004 Sep 20;14(18):4711/​7.

Synthesis and structure/​activity relationships of andrographolide analogues as
novel cytotoxic agents.

Nanduri S, Nyavanandi VK, Thunuguntla SS, Kasu S, Pallerla MK, Ram PS, Rajagopal
S, Kumar RA, Ramanujam R, Babu JM, Vyas K, Devi AS, Reddy GO, Akella V.

Discovery Chemistry, Dr. Reddy's Laboratories Ltd, Discovery Research, Bollaram
Road, Miyapur, Hyderabad 500 049, India. nandurisrinivas@drreddys.com

Andrographolide 1, the cytotoxic agent of the plant Andrographis paniculata was
subjected to semi/​synthetic studies leading to the preparation of a number of
potent and novel analogues. Of the analogues synthesized, while 8,17/​epoxy
andrographolide 6 retained the cytotoxic activity of 1, ester derivatives of 6
exhibited considerable improvement in activity. Lower activity was observed when
the epoxy moiety in the triacetate 9, derived from 6 was modified. Synthesis and
structure/​activity relationships are discussed.

Publication Types:
Comparative Study

PMID: 15324893 [PubMed /​ indexed for MEDLINE]

47: J Ethnopharmacol. 2004 Jun;92(2/​3):291/​5.

Anticancer and immunostimulatory compounds from Andrographis paniculata.

Kumar RA, Sridevi K, Kumar NV, Nanduri S, Rajagopal S.

Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad 500050, India.

Andrographis paniculata extract is traditionally used as a medicine to treat
different diseases in India, China and Southeast Asia. In the present study, we
evaluated the anticancer and immunomodulatory activity of the methanolic extract
of Andrographis paniculata in human cancer and immune cells. The methanolic
extract of Andrographis paniculata was fractionated into dichloromethane,
petroleum ether and aqueous extracts and screened for bioactivity. Our results
indicate that the dichloromethane fraction of the methanolic extract retains the
active compounds contributing for both the anticancer and immunostimulatory
activity. Dichloromethane fraction significantly inhibits the proliferation of
HT/​29 (colon cancer) cells and augments the proliferation human peripheral blood
lymphocytes (HPBLs) at low concentrations. On further fractionation of the
dichloromethane extract we could isolate three diterpene compounds, i.e. [1]
andrographolide, [2] 14/​deoxyandrographolide and [3]
14/​deoxy/​11,12/​didehydroandrographolide. Andrographolide showed anticancer
activity on diverse cancer cells representing different types of human cancers.
Whereas all the three molecules showed enhanced proliferation and interleukin/​2
(IL/​2) induction in HPBLs.

PMID: 15138014 [PubMed /​ indexed for MEDLINE]

48: J Ethnopharmacol. 2004 Jun;92(2/​3):281/​9.

Inhibitory effect of some herbal extracts on adherence of Streptococcus mutans.

Limsong J, Benjavongkulchai E, Kuvatanasuchati J.

Department of Pharmacology, Faculty of Dentistry, Chulalongkorn University,
Henri/​Dunant Road, Bangkok 10330, Thailand.

The objective of this study was to investigate the inhibitory effect of the
crude extracts from some herbs on adherence of Streptococcus mutans (S. mutans)
ATCC 25175 and TPF/​1 in vitro. Six herbs, Andrographis paniculata; Cassia alata;
Chinese black tea (Camellia sinensis); guava (Psidium guajava); Harrisonia
perforata and Streblus asper, were extracted with 50 or 95% ethanol and dried.
Herbal extracted solution at 0.5% concentration (w/v) was initially tested for
bacterial adherence on glass surfaces. In order to identify type and effective
concentration of the extracts, the extracts that showed the inhibition on glass
surfaces were then tested on saliva/​coated hydroxyapatite by the use of
radiolabeled bacteria. To study the mechanism of action, the effect of the
extracts at such concentration on glucosyltransferase and glucan/​binding lectin
activities were examined. It was found that all extracts, but Streblus asper,
showed significant inhibitory effect on bacterial adherence to glass surfaces.
For the saliva/​coated hydroxyapatite adherence assay, Andrographis paniculata,
Cassia alata, Chinese black tea and Harrisonia perforata could inhibit adherence
of S. mutans ATCC 25175. Chinese black tea was the strongest inhibitor followed
by Andrographis paniculata, Cassia alata and Harrisonia perforata, respectively.
For S. mutans TPF/​1, adherence inhibition was observed from Andrographis
paniculata and Cassia alata at similar levels. The lowest concentrations of the
extracts that inhibited the adherence at least 50% were 0.5% of Andrographis
paniculata, 0.5% of Cassia alata, 0.3% of Chinese black tea and 0.5% of
Harrisonia perforata for S. mutans ATCC 25175. For S. mutans TPF/​1, the
effective concentrations were 0.5% of Andrographis paniculata and 0.4% of Cassia
alata. All extracts at such concentrations decreased the activity of
glucosyltransferase from both strains. Only Andrographis paniculata and Cassia
alata eliminated or decreased the activity of glucan/​binding lectin from both
strains. These findings suggested that Andrographis paniculata, Cassia alata,
Chinese black tea and Harrisonia perforata could inhibit adherence of S. mutans
ATCC 25175, while Andrographis paniculata and Cassia alata had an effect on S.
mutans TPF/​1 in vitro at the concentrations employed in this study.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15138013 [PubMed /​ indexed for MEDLINE]

49: Planta Med. 2004 Apr;70(4):293/​8.

Andrographis paniculata in the treatment of upper respiratory tract infections:
a systematic review of safety and efficacy.

Coon JT, Ernst E.

Complementary Medicine, Peninsula Medical School, Universities of Exeter and
Plymouth, Exeter, UK. Jo.Thompson/​Coon@pms.ac.uk

Acute respiratory infections represent a significant cause of over/​prescription
of antibiotics and are one of the major reasons for absence from work. The
leaves of Andrographis paniculata (Burm. f.) Wall ex Nees (Acanthaceae) are used
as a medicinal herb in the treatment of infectious diseases. Systematic
literature searches were conducted in six computerised databases and the
reference lists of all papers located were checked for further relevant
publications. Information was also requested from manufacturers, the spontaneous
reporting schemes of the World Health Organisation and national drug safety
bodies. No language restrictions were imposed. Seven double/​blind, controlled
trials (n = 896) met the inclusion criteria for evaluation of efficacy. All
trials scored at least three, out of a maximum of five, for methodological
quality on the Jadad scale. Collectively, the data suggest that A. paniculata is
superior to placebo in alleviating the subjective symptoms of uncomplicated
upper respiratory tract infection. There is also preliminary evidence of a
preventative effect. Adverse events reported following administration of A.
paniculata were generally mild and infrequent. There were few spontaneous
reports of adverse events. A. paniculata may be a safe and efficacious treatment
for the relief of symptoms of uncomplicated upper respiratory tract infection;
more research is warranted.

Publication Types:
Research Support, Non/​U.S. Gov't
Review

PMID: 15095142 [PubMed /​ indexed for MEDLINE]

50: Biochem Pharmacol. 2004 Apr 1;67(7):1337/​45.

Andrographolide suppresses endothelial cell apoptosis via activation of
phosphatidyl inositol/​3/​kinase/Akt pathway.

Chen JH, Hsiao G, Lee AR, Wu CC, Yen MH.

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei
114, Taiwan, ROC. jhchen@ndmctsgh.edu.tw

Andrographolide (Andro), an active component isolated from the Chinese official
herbal Andrographis paniculata, which has been reported to prevent oxygen
radical production and thus prevent inflammatory diseases. In this study, we
investigated the molecular mechanisms and signaling pathways by which Andro
protects human umbilical vein endothelial cells (HUVECs) from growth factor (GF)
deprivation/​induced apoptosis. Results demonstrated that HUVECs undergo
apoptosis after 18 hr of GF deprivation but that this cell death was suppressed
by the addition of Andro in a concentration/​dependent manner (1/​100 microM).
Andro suppresses the mitochondrial pathway of apoptosis by inhibiting release of
cytochrome c into the cytoplasm and dissipation of mitochondrial potential
(Deltapsi(m)), as a consequence, prevented caspase/​3 and /​9 activation.
Treatment of endothelial cells with Andro/​induced activation of the protein
kinase Akt, an anti/​apoptotic signal, and phosphorylation of BAD, a down/​stream
target of Akt. Suppression of Akt activity by wortmannin, by LY/​294002 and by
using a dominant negative Akt mutant abolished the anti/​apoptotic effect of
Andro. In contrast, the ERK1/2 activities were not affected by Andro. The ERK1/2
inhibitor, PD98059 failed to antagonize the protective effect of Andro. In
conclusion, Andro exerts its anti/​apoptotic potential via activation of the
Akt/​BAD pathway in HUVECs and thus may represent a candidate of therapeutic
agent for atherosclerosis.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 15013849 [PubMed /​ indexed for MEDLINE]

51: Phytother Res. 2004 Jan;18(1):47/​53.

Comparative controlled study of Andrographis paniculata fixed combination, Kan
Jang and an Echinacea preparation as adjuvant, in the treatment of uncomplicated
respiratory disease in children.

Spasov AA, Ostrovskij OV, Chernikov MV, Wikman G.

Research Institute of Pharmacology of Volgograd Medical Academy, Volgograd,
Russia.

A three/​arm study comparing the efficacy of Kan Jang, a fixed herbal combination
containing standardized Andrographis paniculata (N.) SHA/​10 extract, with
Immunal, a preparation containing Echinacea purpurea (L.) extract, in
uncomplicated common colds was carried out in 130 children aged between 4 and 11
years over a period of 10 days. The study was designed as an adjuvant treatment
of Kan Jang and Immunal with a standard treatment. The patients were assigned to
one of the three groups. In control group C; 39 patients received only standard
treatment. Kan Jang and Immunal were used as an adjuvant to this therapy in the
other two groups. Adjuvant group A; 53 patients treated with Kan Jang tablets
concomitant to standard treatment, and adjuvant control group B; 41 patients
treated with concomitant Immunal. It was found that the adjuvant treatment with
Kan Jang, was significantly more effective than Immunal, when started at an
early stage of uncomplicated common colds. The symptoms of the disease were less
severe in the Kan Jang group. The effect of Kan Jang was particularly pronounced
in two objective parameters, amount of nasal secretion g/day and nasal
congestion. Kan Jang also accelerated the recovery time, whereas Immunal did not
show the same efficacy. The use of standard medication was significantly less in
the Kan Jang adjuvant group than in either the Immunal or standard treatment
group. Kan Jang treatment was well tolerated and no side effects or adverse
reactions were reported. Copyright 2004 John Wiley & Sons, Ltd.

Publication Types:
Clinical Trial
Comparative Study
Randomized Controlled Trial

PMID: 14750201 [PubMed /​ indexed for MEDLINE]

52: Planta Med. 2003 Dec;69(12):1075/​9.

Antihyperglycemic effect of andrographolide in streptozotocin/​induced diabetic
rats.

Yu BC, Hung CR, Chen WC, Cheng JT.

Department of Pharmacology, College of Medicine, National Cheng Kung University,
Tainan City, Taiwan.

The antihyperglycemic action of andrographolide, an active principle in the
leaves of Andrographis paniculata (Burm. f.) Nees, was investigated in
streptozotocin/​induced diabetic rats (STZ/​diabetic rats). Oral treatment of
andrographolide decreased the plasma glucose concentrations of STZ/​diabetic rats
in a dose/​dependent manner. Similar treatment with andrographolide also
decreased the plasma glucose in normal rats and the maximal effect was more
marked than that in STZ/​diabetic rats. Andrographolide at the effective dose
(1.5 mg/kg) significantly attenuated the increase of plasma glucose induced by
an intravenous glucose challenge test in normal rats. In the isolated soleus
muscle of STZ/​diabetic rats, andrographolide enhanced the uptake of radioactive
glucose in a concentration/​dependent manner. Moreover, the mRNA and protein
levels of the subtype 4 form of the glucose transporter (GLUT4) in soleus muscle
were increased after repeated intravenous administration of andrographolide in
STZ/​diabetic rats for 3 days. These results suggest that andrographolide can
increase the glucose utilization to lower plasma glucose in diabetic rats
lacking insulin.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 14750020 [PubMed /​ indexed for MEDLINE]

53: J Clin Pharm Ther. 2004 Feb;29(1):37/​45.

Andrographis paniculata in the symptomatic treatment of uncomplicated upper
respiratory tract infection: systematic review of randomized controlled trials.

Poolsup N, Suthisisang C, Prathanturarug S, Asawamekin A, Chanchareon U.

Department of Pharmacy, Faculty of Pharmacy, Silpakorn University,
Nakhon/​Pathom, Thailand. nalinee@email.pharm.su.ac.th

OBJECTIVE: To assess the efficacy of Andrographis paniculata in the symptomatic
treatment of uncomplicated upper respiratory tract infection. METHODS:
Systematic review of the literature and meta/​analysis of randomized controlled
trials. Mean difference in the reduction in symptom severity scores between
treatment and control groups was calculated to obtain an overall estimate of
effect. RESULTS: Four studies met our inclusion criteria and were reviewed. A
total of 433 patients reported in three trials were included in the statistical
analysis. Andrographis paniculata fixed combination with Acanthopanax senticosus
was more effective than placebo. The mean difference was 2.13 points (95% CI
1.00/​3.26 points, P=0.0002) on the symptom severity score. The difference in
effects between A. paniculata and placebo was 10.85 points (95% CI 10.36/​11.34
points, P<0.0001) in favour of A. paniculata. CONCLUSION: Current evidence
suggests that A. paniculata extract alone or in combination with A. senticosus
extract may be more effective than placebo and may be an appropriate alternative
treatment of uncomplicated acute upper respiratory tract infection.

Publication Types:
Comparative Study
Review

PMID: 14748896 [PubMed /​ indexed for MEDLINE]

54: J Exp Ther Oncol. 2003 May/​Jun;3(3):147/​58.

Andrographolide, a potential cancer therapeutic agent isolated from Andrographis
paniculata.

Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R.

Discovery Research, Dr. Reddy's Laboratories, Miyapur, Hyderabad, India/​500050.
sriramrajagopal@drreddys.com

Andrographis paniculata plant extract is known to possess a variety of
pharmacological activities. Andrographolide, the major constituent of the
extract is implicated towards its pharmacological activity. We studied the
cellular processes and targets modulated by andrographolide treatment in human
cancer and immune cells. Andrographolide treatment inhibited the in vitro
proliferation of different tumor cell lines, representing various types of
cancers. The compound exerts direct anticancer activity on cancer cells by
cell/​cycle arrest at G0/G1 phase through induction of cell/​cycle inhibitory
protein p27 and decreased expression of cyclin/​dependent kinase 4 (CDK4).
Immunostimulatory activity of andrographolide is evidenced by increased
proliferation of lymphocytes and production of interleukin/​2. Andrographolide
also enhanced the tumor necrosis factor/​alpha production and CD marker
expression, resulting in increased cytotoxic activity of lymphocytes against
cancer cells, which may contribute for its indirect anticancer activity. The in
vivo anticancer activity of the compound is further substantiated against B16F0
melanoma syngenic and HT/​29 xenograft models. These results suggest that
andrographolide is an interesting pharmacophore with anticancer and
immunomodulatory activities and hence has the potential for being developed as a
cancer therapeutic agent.

Publication Types:
Research Support, Non/​U.S. Gov't

PMID: 14641821 [PubMed /​ indexed for MEDLINE]

55: Fitoterapia. 2003 Dec;74(7/​8):692/​4.

Antimicrobial activity of Andrographis paniculata.

Singha PK, Roy S, Dey S.

Plant Biotechnology Laboratory, Biotechnology Department, Indian Institute of
Technology, Kharagpur 721 302, West Bengal, India.

The antimicrobial activity of aqueous extract, andrographolides and
arabinogalactan proteins from Andrographis paniculata were evaluated. The
aqueous extract showed significant antimicrobial activity, which may be due to
the combined effect of the isolated arabinogalactan proteins and
andrographolides.

PMID: 14630176 [PubMed /​ indexed for MEDLINE]

56: Zhong Yao Cai. 2000 Jun;23(6):366/​8.

[Advances in the study of Andrographis paniculata (Burm.f.) Nees]

[Article in Chinese]

Zhang T.

Institute for Drug Control, Wuzhou City, Guangxi Province, 543000

Publication Types:
Review

PMID: 12934603 [PubMed /​ indexed for MEDLINE]

57: Drug News Perspect. 2001 Aug;14(6):353/​63.

Herbal preparations as a source of hepatoprotective agents.

Ram VJ.

Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.

Mono/​ and polyherbal preparations with potent antihepatotoxic activity in
various liver disorders, made from traditionally used herbs with proven
efficacy, have been described. More than 700 mono/​ and polyherbal preparations
in the form of decoction, tincture, tablets and capsules from more than 100
plants are in clinical use. Some of the herbs/​/​such as Silybum marianum,
Picrorhiza kurroa, Andrographis paniculata and Glycyrrhizae radix/​/​are very
common in most of the polyherbal preparations. This review covers the
preparations of widely used herbs such as S. marianum, Schisandra chinensis,
Phyllanthus amarus, P. kurroa, A. paniculata, G. radix, Lycium chinense and
Cochlospermum tinctorium as hepatoprotectants and includes the mode of action of
these preparations. Some polyherbal preparations such as Livex, HD/​03, Hepatomed
and Hepatoguard with proven efficacy are also described in this review. (c) 2001
Prous Science. All rights reserved.

PMID: 12813598 [PubMed]

58: Phytomedicine. 2003 May;10(4):271/​85.

Double/​blind, placebo/​controlled, randomized, pilot clinical trial of
ImmunoGuard/​/​a standardized fixed combination of Andrographis paniculata Nees,
with Eleutherococcus senticosus Maxim, Schizandra chinensis Bail. and
Glycyrrhiza glabra L. extracts in patients with Familial Mediterranean Fever.

Amaryan G, Astvatsatryan V, Gabrielyan E, Panossian A, Panosyan V, Wikman G.

Republican Children's FMF Center, Yerevan State Medical University, Yerevan,
Armenia.

Double blind, randomized, placebo controlled pilot study of ImmunoGuard/​/​a
standardized fixed combination of Andrographis paniculata Nees., Eleutherococcus
senticosus Maxim., Schizandra chinensis Bail., and Glycyrrhiza glabra L. special
extracts standardized for the content of Andrographolide (4 mg/tablet),
Eleuteroside E, Schisandrins and Glycyrrhizin, was carried out in two parallel
groups of patients. The study was conducted in 24 (3/​15 years of both genders)
patients with Familial Mediterranean Fever (FMF), 14 were treated with tablets
of series A (verum) and 10 patients received series B product (placebo). The
study medication was taken three times of four tablets daily for 1 month. Daily
dose of the andrographolide/​/​48 mg. The primary outcome measures in physician's
evaluation were related to duration, frequency and severity of attacks in FMF
patients (attacks characteristics score). The patient's self/​evaluation was
based mainly on symptoms/​/​abdominal, chest pains, temperature, arthritis,
myalgia, erysipelas/​like erythema. All of 3 features (duration, frequency,
severity of attacks) showed significant improvement in the verum group as
compared with the placebo. In both clinical and self evaluation the severity of
attacks was found to show the most significant improvement in the verum group.
Both the clinical and laboratory results of the present phase II (pilot)
clinical study suggest that ImmunoGuard is a safe and efficacious herbal drug
for the management of patients with FMF.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 12809357 [PubMed /​ indexed for MEDLINE]

59: Phytochemistry. 2003 Apr;62(8):1271/​5.

A flavone and an unusual 23/​carbon terpenoid from Andrographis paniculata.

Reddy MK, Reddy MV, Gunasekar D, Murthy MM, Caux C, Bodo B.

Natural Products Division, Department of Chemistry, Sri Venkateswara University,
Tirupati 517 502, India.

Phytochemical investigation of the roots and aerial parts of Andrographis
paniculata Nees yielded a new flavone, 5/​hydroxy/​7,2',6'/​trimethoxyflavone and
an unusual 23/​carbon terpenoid,
14/​deoxy/​15/​isopropylidene/​11,12/​didehydroandrographolide together with five
known flavonoids and four known diterpenoids. The structures of these compounds
were determined on the basis of spectral and chemical stu