Clinical Studies

Abstracts are presented below for clinical studies on Picrorhiza.

  • Botanical Name: Picrorhiza Kurrooa

  • Ayurvedic Name: Katuka

  • Common Name: Picrorhiza

Picrorhiza Kurrooa

Plant Phytonutrient Profile


1: Planta Med. 2007 Feb 22; [Epub ahead of print]

Picroliv Accelerates Epithelialization and Angiogenesis in Rat Wounds.

Singh AK, Sharma A, Warren J, Madhavan S, Steele K, Rajeshkumar NV, Thangapazham
RL, Sharma SC, Kulshreshtha DK, Gaddipati J, Maheshwari RK.

Center for Combat Casualty and Life Sustainment Research, Department of
Pathology, Uniformed Services University of the Life Sciences, Bethesda,
Maryland, USA.

Tissue repair and wound healing are complex processes that involve inflammation,
granulation and tissue remodeling. Angiogenesis plays a central role in wound
healing. Earlier, we have shown that picroliv, a natural product obtained from
the roots of PICRORHIZA KURROOA, up-regulates the expression of vascular
endothelial growth factor in human umbilical vein endothelial cells and of
insulin-like growth factor in rats during hypoxia. In the present study, we have
investigated the effect of picroliv in an EX VIVO rat aorta ring model of
angiogenesis. Picroliv enhanced the sprouting and migration of endothelial
cells. We also investigated punch wound healing on days 4 and 7 after wounding
by histology, morphometry and collagenization. The data showed improved
re-epithelialization, neovascularization and migration of various cells such as
endothelial, dermal myofibroblasts and fibroblasts into the wound bed after
picroliv treatment. Immunohistochemical localization showed increased VEGF and
alpha smooth muscle actin staining consistent with an increased number of
microvessels in granulation tissue. These findings suggest that picroliv could
be developed as a therapeutic angiogenic agent for the restoration of the blood
supply in diseases involving inadequate blood supply such as limb ischemia,
ischemic myocardium and wound healing.

PMID: 17318779 [PubMed - as supplied by publisher]

2: Chem Biodivers. 2004 Mar;1(3):426-41.

Novel lipid-peroxidation- and cyclooxygenase-inhibitory tannins from Picrorhiza
kurroa seeds.

Zhang Y, DeWitt DL, Murugesan S, Nair MG.

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and
National Food Safety and Toxicology Center, Michigan State University, East
Lansing, Michigan 48824, USA.

From the AcOEt extract of the seeds of Picrorhiza kurroa were isolated
picrorhiza acid (1), picrorhizoside A (2), picrorhizoside B (3), picrorhizoside
C (4), (-)-shikimic acid (5), gallic acid (6), ellagic acid (7), isocorilagin
(8), 1-O-galloyl-beta-D-glucose (9), 1-O,3-O,6-O-trigalloyl-beta-D-glucose (10),
and 1-O,2-O,3-O,4-O,6-O-pentagalloyl-beta-D-glucose (11), and their structures
were established by extensive NMR and chemical studies. Constituents 1-4 are
novel compounds, and the known compounds 5-11 have been isolated for the first
time from the seeds of P. kurroa. Compounds 2 and 3 were hydrolyzed and yielded
12, isochebulic acid. Compounds 1-12 showed 89.6, 77.3, 56.1, 50.5, 11.0, 86.4,
50.5, 29.2, 70.9, 50.5, 56.5, and 86.1% inhibition of lipid peroxidation at 5
microg/ml, respectively. The commercial antioxidants BHA (1.8 microg/ml), BHT
(2.2 microg/ml), and TBHQ (1.66 microg/ml) inhibited lipid peroxidation at 85.6,
87.1, and 81.1%, respectively. The inhibition of cyclooxygenase-1 (COX-1) by
2-5, 7, 8, and 10-12 at 100 microg/ml was 41.9, 28.4, 32.9, 9.3, 70.7, 34.7,
16.0, 89.6, and 53.4%, respectively. Similarly, compounds 1-8 and 11 and 12, at
100 microg/ml, inhibited COX-2 by 12.6, 15.3, 25.1, 5.3, 13.2, 21.7, 2.0, 42.4,
43.4, and 36.9%, respectively.

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

PMID: 17191857 [PubMed - indexed for MEDLINE]

3: Fitoterapia. 2006 Dec;77(7-8):579-84. Epub 2006 Sep 22.

Hypolipemic effect of water extracts of Picrorrhiza kurroa in high fat diet
treated mouse.

Lee HS, Yoo CB, Ku SK.

Department of Herbal Biotechnology, Daegu Haany University, Gyeongsan, 712-715,
Republic of Korea.

A hypolipemic effect of the water extract of Picrorrhiza kurroa (PR) was
observed in a high fat diet feeding hyperlipemic mouse at doses of 50, 100 and
200 mg/kg, orally, once a day for 12 weeks. Liver weight, serum aspartate
transferase (AST), alanine transferase (ALT), low density lipoprotein (LDL),
triglyceride and total cholesterol levels were significantly reduced by the
treatment. On the contrary, serum HDL level seems not affected by P. kurroa
water extract.

PMID: 17056204 [PubMed - indexed for MEDLINE]

4: Int Immunopharmacol. 2006 Oct;6(10):1543-9. Epub 2006 Jun 16.

Immunomodulatory activity of biopolymeric fraction RLJ-NE-205 from Picrorhiza
kurroa.

Gupta A, Khajuria A, Singh J, Bedi KL, Satti NK, Dutt P, Suri KA, Suri OP, Qazi
GN.

Division of Pharmacology, Regional Research Laboratory (CSIR), Jammu-180001,
India.

In the last three decades, numerous biopolymeric fractions have been isolated
from medicinal plants and used as a source of therapeutic agents. The most
promising biopharmacological activities of these biopolymers are their
immunomodulatory effects. The biopolymeric fraction RLJ-NE-205 was isolated and
purified from the rhizomes of Picrorhiza kurroa. We evaluated the effects of
biopolymeric fraction RLJ-NE-205 from P. kurroa on the in vivo immune function
of the mouse. Balb/c mice were treated with the biopolymeric fraction RLJ-NE-205
(12.5, 25 and 50 mg/kg body weight) for 14 days with sheep red blood cells
(SRBC) as an antigen. Haemagglutination antibody (HA) titre, plaque forming cell
(PFC) assay, delayed type hypersensitivity (DTH) reaction, phagocytic index,
proliferation of lymphocytes, analysis of cytokines in serum and CD4/CD8
population in spleen (determined by flowcytometry) were studied. At the dose of
50 mg/kg, significant increases in the proliferation of lymphocytes (p<0.001)
and cytokine levels (IL-4 and IFN-gamma) in serum (p<0.001) were observed. A
dose dependent increase was demonstrated in HA titre (p<0.05), DTH (p<0.01), PFC
(p<0.05), phagocytic index (p<0.05) and CD4/CD8 (p<0.01) population. This
suggests that the biopolymeric fraction RLJ-NE-205 improves the immune system
and might be regarded as a biological response modifier.

PMID: 16919826 [PubMed - indexed for MEDLINE]

5: Vaccine. 2006 Jul 10; [Epub ahead of print]

RLJ-NE-299A: A new plant based vaccine adjuvant.

Khajuria A, Gupta A, Singh S, Malik F, Singh J, Suri KA, Satti NK, Qazi GN,
Srinivas VK, Gopinathan, Ella K.

Division of Pharmacology, Regional Research Laboratory (CSIR), Jammu 180001,
India.

Alum has been in use since long as an adjuvant for vaccines. However, its use as
a vaccine adjuvant offers limitation in supporting cell mediated response.
Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported
for its immunostimulatory activity, has been explored for its potential as an
alternative adjuvant. In order to compare the adjuvant activity with alum,
antigen-specific immune responses were evaluated following immunization with a
formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with
RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably
the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2
cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization
with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1
(Th2) subtypes increased profoundly in blood sera of mice immunized with
HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential
to increase both cell mediated and humoral immune responses and is capable of
sustaining the total antigen-specific antibody response. Besides, the
RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and
CD8 cells populations, which may have important implications for vaccination
against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40mug)
containing vaccine antigen (HBsAg) were well tolerated with optimum T cell
response at 2.5mug/ml. Not only this, the adjuvant was also able to induce
cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines
upregulation, which enabled mice to overcome the unresponsiveness to antigen
HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice
population. The study presents evidence that the HPLC standardized fraction
RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the
improved immune status against HBsAg, and may also prove useful adjuvant
candidate with other vaccine antigens, too.

PMID: 16872726 [PubMed - as supplied by publisher]

6: J Asian Nat Prod Res. 2006 Apr-May;8(3):259-63.

Two new iridoid glucosides from Picrorhiza scrophulariiflora.

Huang SX, Zhou Y, Nie QJ, Ding LS, Peng SL.

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041,
China.

Two new iridoid glucosides with 3,4-dihydrocatalpol skeleton, piscrosides A (1)
and B (2) together with nine known iridoid glucosides and three known
cucurbitacin glucosides, were isolated from the stems of Picrorhiza
scrophulariiflora. Their structures were established by MS, 1H NMR, 13C NMR and
2D NMR methods (including HSQC, HMBC and NOESY experiments).

PMID: 16864432 [PubMed - in process]

7: J Ethnopharmacol. 2006 May 24;105(3):380-6. Epub 2006 Jan 9.

Hypolipemic effect of water extracts of Picrorrhiza rhizoma in PX-407 induced
hyperlipemic ICR mouse model with hepatoprotective effects: a prevention study.

Lee HS, Ahn HC, Ku SK.

Department of Herbal Biotechnology, Daegu Haany University, Gyeongsan 712-715,
Republic of Korea.

The preventive hypolipemic effect of water extract of Picrorrhiza rhizoma (PR)
was observed in Poloxamer (PX)-407 induced hyperlipemic mice with their
hepatoprotective effects. Doses of 50, 100 and 200 mg/kg of PR extracts were
given orally once a day for 12 weeks initiated with intraperitoneal injection of
PX-407 (0.5 g/kg), and changes in body weight and gains, liver weight, serum
aspartate transferase (AST) and alanine transferase (ALT) levels were monitored
with serum low density lipoprotein (LDL), high density lipoprotein (HDL),
triglyceride and total cholesterol levels. The efficacy of PX-407 was compared
to that of 10mg/kg of simvastatin (SIMVA). No meaningful changes in the body
weight were detected in all dosing groups compared to that of vehicle control
group. Dramatic decrease of both absolute and relative liver weight was
dose-dependently observed in all PR extracts dosing groups compared to that of
vehicle control group. The serum AST and ALT levels were significantly and
dose-dependently decreased in PR extracts dosing groups. However, slight
increase of liver weight, serum AST and ALT levels were detected in SIMVA-dosing
groups. The serum LDL, triglyceride and total cholesterol levels were
dose-dependently decreased in PR extracts dosing groups and SIMVA-dosing group
compared to that of vehicle control group, respectively. The serum HDL levels
were slightly but dose-dependently increased in PR extracts dosing groups
compared to that in vehicle control group, respectively. However, the efficacy
on the serum lipid levels of PR extracts was lower than that of SIMVA-about 200
mg/kg of PR extracts which showed similar effect compared to that of SIMVA
10mg/kg. On the basis of these results, it is concluded that water extract of PR
has a relatively good favorable preventive effect on the PX-407 inducing
hyperlipemia with favorable hepatoprotective effect.

PMID: 16406704 [PubMed - indexed for MEDLINE]

8: Life Sci. 2005 Nov 4;77(25):3222-30. Epub 2005 Jun 23.

Cyclooxygenase-2 enzyme inhibitory triterpenoids from Picrorhiza kurroa seeds.

Zhang Y, Dewitt DL, Murugesan S, Nair MG.

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and
National Food Safety and Toxicology Center, Michigan State University, East
Lansing, Michigan 48824, USA.

A bioassay guided phytochemical study of the ethyl acetate extract of the seeds
of Picrorhiza kurroa afforded a new triterpenoid, 2alpha, 3beta, 19beta,
23-tetrahydroxyolean-12-en-28-O-beta-D-glucoside (1), along with five known
triterpenoids, 2alpha, 3beta, 19beta, 23-tetrahydroxyolean-12-en-28-oic acid
(2), 2alpha, 3beta, 23-trihydroxyolean-12-en-28-O-beta-d-glucoside (3), 2alpha,
3beta, 23-trihydroxyolean-12-en-28-oic acid (4), 2alpha, 3beta, 19beta,
trihydroxyolean-12-en-28-oic acid (5), and 2alpha, 3beta, 6beta,
23-tetrahydroxyolean-12-en-28-oic acid (6). Their structures were established by
extensive NMR spectral studies. The acetyl derivatives, compounds 7 and 8, were
prepared from compounds 1 and 2, respectively, to aid in their structure
elucidation. The inhibition of cyclooxygenase-2 (COX-2) enzyme by compounds 1--6
at 100 microg/mL was 38.3%, 39%, 37%, 49.6%, 25%, and 45.0%, respectively.
However, compounds 1--6, at 100 microg/mL, did not inhibit cyclooxygenase-1
(COX-1) enzyme. Compound 1 is a novel triterpenoid and compounds 1--6 are
isolated for the first time from the seeds of P. kurroa.

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

PMID: 15979098 [PubMed - indexed for MEDLINE]

9: Indian J Med Res. 2005 May;121(5):676-82.

Protective activity of picroliv on hepatic amoebiasis associated with carbon
tetrachloride toxicity.

Singh M, Tiwari V, Jain A, Ghoshal S.

Division of Microbiology, Central Drug Research Institute, Lucknow, India.

BACKGROUND AND OBJECTIVE: Picroliv, isolated from the root and rhizome of
Picrorhiza kurroa, is known to have significant hepatoprotective activity. Its
effects against Entamoeba histolytica induced liver damage are not studied. This
study aims to evaluate the hepatoprotective action of picroliv against the
hepatotoxic changes induced by carbon tetrachloride (CCl(4)) and E. histolytica
infection in three animal models. METHODS: Mastomys, gerbils and albino Druckray
rats were used in this study. A total of 30 animals were used for each model and
divided into five groups of six animals each. Group I consisted of normal
animals. The rest received six doses of CCl(4) intraperitoneally. Group II
served as hepatotoxic control. The remaining animals were infected
intraperitoneally with E. histolytica trophozoites, of which group III was the
hepatotoxic plus amoeba infected control. The remaining animals were divided
into two groups, one received hepatoprotective agent picroliv and the other
silymarin. All animals were sacrificed seven days post amoeba infection.
RESULTS: Increase in the enzyme levels induced by CCl(4) was further elevated
after E. histolytica infection. Pinpoint abscesses were found to develop only in
gerbils after E. histolytica infection. Picroliv was found to possess
hepatoprotective activity against amoebic liver abscess. INTERPRETATION AND
CONCLUSION: Significant recovery obtained in serum enzyme levels in all animal
models and against amoebic liver abscess in gerbils on treatment with picroliv
indicated that picroliv possesses therapeutic activity against E. histolytica
induced hepatic damage.

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

PMID: 15937372 [PubMed - indexed for MEDLINE]

10: Acta Pharmacol Sin. 2005 Jun;26(6):729-36.

Inhibitory effect of picroside II on hepatocyte apoptosis.

Gao H, Zhou YW.

College of Chemistry and Molecular Engineering, Peking University, Beijing
100871, China.

AIM: To investigate the influence of picroside II on hepatocyte apoptosis and
its mechanism. METHODS: Morphological changes and quantification of apoptotic
cells were determined under transmission electron microscopy and flow cytometry
respectively. DNA fragmentation was visualized by agarose gel electrophoresis.
Semi-quantitative reverse transcription-PCR (RT-PCR) was used to analyze the
expression of bcl-2 and bax genes. The content of manganese-superoxide dismutase
(SOD) in liver mitochondria was detected by the Marland method. The content of
malonic aldehyde (MDA) and the protein level in liver tissue were determined by
thiobarbituric acid colorimetry and Lowry method. RESULTS: Picroside II
decreased the levels of alanine aminotransferase and aspartate aminotransferase
in the serum resulting from acute-liver injured mice induced with D-GalN and
LPS; it also reduced the content of MDA, and thus, enhanced the activity of SOD.
Picroside II 10 mg/kg was found to protect hepatocytes against apoptosis in a
dose-dependent manner; it up-regulated the expression of bcl-2 genes, thus
increased the bcl-2/bax ratio. CONCLUSION: Picroside II can protect hepatocytes
against injury and prevent hepatocytes from apoptosis. It might by upregulating
the bcl-2 gene expression and antioxidation.

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

PMID: 15916740 [PubMed - indexed for MEDLINE]

11: Acta Trop. 2005 Apr;94(1):41-7.

Efficacy of picroliv in combination with miltefosine, an orally effective
antileishmanial drug against experimental visceral leishmaniasis.

Gupta S, Ramesh SC, Srivastava VM.

Divisions of Parasitology, Central Drug Research Institute, Lucknow 226001,
India. gupta_suman@yahoo.com

Visceral leishmaniasis (VL) or kala-azar continues to persist as one of the
major public health problems in many tropical countries. However, no effective
treatment for radical cure of the disease is yet available. Miltefosine, an
alkyl phospholipid compound, is the first orally effective drug, which has shown
98% cure rate of VL patients during phase III clinical trial in India. Since
this drug requires long course of treatment and has long half-life, there are
fairly good chances of emergence of resistance. Furthermore, this drug has
produced severe side-effects in some of the cases.We therefore examined the
possibility of minimizing these effects by applying miltefosine in lower doses
in combination with picrloviv, an immunomodulator against Leishmania donovani in
hamsters (Mesocricetus auratus). The picroliv per se showed no antileishmanaial
potential. However, when given with suboptimal dose of miltefosine, it enhanced
efficacy of the latter from 45 to 86% on day 7 post treatment and from 32 to 64%
on day 28 post treatment. Interestingly, the efficacy of this combination was as
good as the curative dose of miltefosine alone. Thus, this combination appears
to offer a fruitful strategy for treatment of VL.

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

PMID: 15895483 [PubMed - indexed for MEDLINE]

12: Zhongguo Zhong Yao Za Zhi. 2004 Jun;29(6):531-4.

[Phenylethanoid glycosides from root of Picrorhiza scrophulariiflora]

[Article in Chinese]

Wang H, Ye WC, Xiong F, Zhao SX.

Department of Phytochemistry, China Pharmaceutical University, Nanjing 210009,
China.

OBJECTIVE: To study the phenylethanoid glycosides from root of Picrorhiza
scrophulariiflora. METHOD: Column chromatographic techniques were used for
isolation and purification of chemical constituents of the plant and the
structures were identified by spectroscopic analysis. RESULT: Six phenylethanoid
glycosides were isolated and elucidated as:
2-(3,4-dihydroxyphenyl)-ethyl-O-beta-D-glucopyranoside (1),
2-(3-hydroxy-4-methoxyphenyl)-ethyl-O-beta-D-glucopyranosyl (1-->3)
beta-D-glucopyranoside (2), scroside B (3), hemiphroside A (4), plantainoside D
(5) and scroside A (6), respectively. CONCLUSION: Compounds 1, 2, 4 and 5 were
isolated from this plant for the first time and compound 2 was firstly obtained
from natural source.

Publication Types:
English Abstract

PMID: 15706916 [PubMed - indexed for MEDLINE]

13: Indian J Exp Biol. 2003 Aug;41(8):875-9.

Free radical scavenging potential of Picrorhiza kurrooa Royle ex Benth.

Govindarajan R, Vijayakumar M, Rawat AK, Mehrotra S.

Pharmacognosy and Ethnopharmacology Division, National Botanical Research
Institute, Lucknow 226 001, India.

For assessing free radical scavenging potential of P. kurrooa, the antioxidant
activity of P. kurrooa extract was studied by lipid peroxidation assay using rat
liver homogenate. The extract (1 mg/ml) showed marked protection (up to 66.68%)
against peroxidation of liver phospholipids. Besides, reduced glutathione showed
very encouraging activity. The extract also exhibited significant scavenging
activity. Thus augmenting the wide use of plant in the indigenous system of
medicine, which may partly be due to antioxidant and free radical scavening
activity of the extract.

Publication Types:
In Vitro

PMID: 15248488 [PubMed - indexed for MEDLINE]

14: Free Radic Biol Med. 2004 Jul 15;37(2):156-65.

Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH
oxidase and glutathione redox-dependent mechanisms.

Barbieri SS, Cavalca V, Eligini S, Brambilla M, Caiani A, Tremoli E, Colli S.

E. Grossi Paoletti Center, Department of Pharmacological Sciences, University of
Milan, Italy.

In the present study we report the preventive effect of apocynin, an active
constituent of the Himalayan herb Picrorhiza kurrooa, on cyclooxygenase-2
(Cox-2) synthesis and activity in human adherent monocytes exposed to serum
treated zymosan (STZ) and phorbol myristate acetate (PMA). Apocynin markedly
decreases the intracellular reduced/oxidized glutathione ratio (GSH/GSSG) and
prevents nuclear factor-kappaB (NF-kappaB) activation in stimulated monocytes.
Moreover, it reduces intracellular reactive oxygen species (ROS) generation,
NADPH oxidase activity in monocyte homogenates and translocation of p47phox
subunit in monocyte membranes. p47phox levels are also reduced in lysates of
apocynin-treated monocytes. The inhibition of Cox-2 by apocynin is completely
abrogated by GSH provision. Results from this study indicate that apocynin
inhibits Cox-2 synthesis and activity induced in monocytes by an increased
oxidative tone and provide an explanation for the protective effect exerted by
this compound in numerous cell and animal models of inflammation. Attenuation of
NADPH oxidase derived ROS coupled with GSH/GSSG reduction and suppression of
NF-kappaB activation are highlighted as the molecular mechanisms responsible for
Cox-2 inhibition.

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

PMID: 15203187 [PubMed - indexed for MEDLINE]

15: Chem Pharm Bull (Tokyo). 2004 May;52(5):615-7.

Antioxidative phenylethanoid and phenolic glycosides from Picrorhiza
scrophulariiflora.

Wang H, Sun Y, Ye WC, Xiong F, Wu JJ, Yang CH, Zhao SX.

Department of Phytochemistry, China Pharmaceutical University, Nanjing,
P.R.China.

One new phenylenthanoid glycoside, scroside D (2), was isolated from the roots
of Picrorhiza scrophulariiflora (Scrophulariaceae), together with nine known
phenylethanoid and phenolic glycosides:
2-(3,4-dihydroxyphenyl)-ethyl-O-beta-D-glucopyranoside (1),
2-(3-hydroxy-4-methoxyphenyl)-ethyl-O-beta-D-glucopyranosyl
(1-->3)-beta-D-glucopyranoside (3), scroside B (4), hemiphroside A (5),
plantainoside D (6), scroside A (7), androsin (8), piceoside (9), and
6-O-feruloyl-beta-D-glucopyranoside (10). The structures of these compounds were
elucidated using spectroscopic methods. The antioxidative activities of these
isolated compounds were evaluated based on their scavenging effects on hydroxyl
radicals and superoxide anion radicals, respectively. Compounds 1, 2, and 6
showed potent antioxidative effects as those of ascorbic acid and the
structure-activity relationship is discussed.

PMID: 15133218 [PubMed - indexed for MEDLINE]

16: Planta Med. 2004 Apr;70(4):382-4.

Three new cyclopentanoid monoterpenes from Picrorhiza scrophulariiflora.

Wang H, Ye WC, Jiang RW, Wu JJ, Mak TC, Zhao SX, Yao XS.

Department of Phytochemistry, China Pharmaceutical University, Nanjing, P. R.
China.

Three new cyclopentanoid monoterpenes, named piscrocins A , B and C, were
isolated from the roots of Picrorhiza scrophulariiflora (Scrophulariaceae). The
structures of these new compounds were established by 1D and 2D NMR
spectroscopic techniques ( (1)H- (1)H COSY, HMQC, HMBC, and NOESY) in
combination with X-ray crystallographic analysis.

PMID: 15095161 [PubMed - indexed for MEDLINE]

17: Cryo Letters. 2003 May-Jun;24(3):181-90.

Cryopreservation of shoot tips of Picrorhiza kurroa Royle ex Benth, an
indigenous endangered medicinal plant, through vitrification.

Sharma N, Sharma B.

Tissue Culture and Cryopreservation Unit, National Bureau of Plant Genetic
Resources, Pusa Campus, New Delhi-110012, India. neelam@nbpgr.delhi.nic.in

The cryopreservation of shoot tips of Picrorhiza kurroa Royle ex Benth (IC
266698), an endangered medicinal plant of India was investigated. Shoot tips
(about 1 mm in length) excised from four-week-old proliferating shoot cultures
were precultured on MS medium supplemented with various osmotica before
dehydrating with PVS2 solution at 0 degrees C. The dehydrated shoot tips were
directly immersed in LN2. Following cryopreservation, and after rapid rewarming
at 45 degrees C, shoot tips were quickly washed with 1.2 M sucrose solution and
then plated on solidified shoot culture medium. Shoot tips were successfully
cryopreserved by vitrification, when they were precultured on medium
supplemented with 5% DMSO at 4 degrees C for two days before dehydrating in PVS2
for 10-20 minutes at 0 degrees C. Average survival in terms of normal shoot
formation after 4 wks of plating was about 20% without callus formation. Cold
hardening of shoot cultures for four weeks at 4 degrees C significantly improved
the survival and shoot regeneration of cryopreserved shoot tips to 70% and 35%,
respectively.

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

PMID: 12908028 [PubMed - indexed for MEDLINE]

18: 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]

19: J Asian Nat Prod Res. 2003 Jun;5(2):105-11.

Colorimetric estimation of total iridoid content of Picrorhiza kurrooa.

Narayanan P, Akamanchi KG.

University Department of Chemical Technology, Matunga, Mumbai 400019, India.

A colorimetric method has been developed for the selective analysis of the total
iridoid content of the rhizomes of Picrorhiza kurrooa in terms of catalpol. The
method of analysis is based on the reaction between iridoid compounds and
primary amine. The iridoid glycosides present in P. kurrooa are mainly the
esters of catalpol, and can be easily converted into catalpol by saponification.
Catalpol thus obtained by hydrolysis is treated with glycine in acidic medium to
give a purple color with a maxmimum absorption of 542 nm. The method was
validated as per the ICH guidelines for linearity, accuracy and precision.
Several other rhizome samples of the plant were also assayed using this method.
The method developed is precise, sensitive, reproducible and easy to perform and
can be used for the standardization of crude drug.

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

PMID: 12765194 [PubMed - indexed for MEDLINE]

20: J Gastroenterol Hepatol. 2002 Dec;17 Suppl 3:S370-S376.

Herbal medicines for liver diseases in India.

Thyagarajan S, Jayaram S, Gopalakrishnan V, Hari R, Jeyakumar P, Sripathi M.

The use of natural remedies for the treatment of liver diseases has a long
history, starting with the Ayurvedhic treatment, and extending to the Chinese,
European and other systems of traditional medicines. The 21st century has seen a
paradigm shift towards therapeutic evaluation of herbal products in liver
diseases by carefully synergizing the strengths of the traditional systems of
medicine with that of the modern concept of evidence-based medicinal evaluation,
standardization of herbal products and randomized placebo controlled clinical
trials to support clinical efficacy. The present review provides the status
report on the scientific approaches made to herbal preparations used in Indian
systems of medicine for the treatment of liver diseases. In spite of the
availability of more than 300 preparations for the treatment of jaundice and
chronic liver diseases in Indian systems of medicine using more than 87 Indian
medicinal plants, only four terrestrial plants have been scientifically
elucidated while adhering to the internationally acceptable scientific
protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative,
antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and
liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and
capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be
anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on
Phyllanthus amarus have confirmed this plant preparation as being anti-viral
against hepatitis B and C viruses, hepatoprotective and immunomodulating, as
well as possessing anti-inflammatory properties. For the first time in the
Indian systems of medicine, a chemo-biological fingerprinting methodology for
standardization of P. amarus preparation has been patented. Copyright 2002
Blackwell Publishing Asia Pty Ltd

PMID: 12472966 [PubMed - as supplied by publisher]

21: Zhongguo Zhong Yao Za Zhi. 1999 Feb;24(2):102-3, 126-7.

[Quantitative determination of vanillic acid in rhizoma Picrorhizae by
TLC-scanning]

[Article in Chinese]

Yu J, Song Y, Cheng Y.

Institute of Traditional Chinese Medicine and Materia Medica of Jiangxi
Province, Nanchang 330077.

OBJECTIVE: To establish a method to determine the content of vanillic acid in
Rhizoma Picrorhizae. METHOD: The content was determined by dual wavelength
TLC-scanning. RESULT: The peak area of vanillic acid is reproducible in 4 hours;
recovery 96.5%; RSD-3%; RSD of duplicate experiment-5%. CONCLUSION: A thin-layer
chromatographic scanning method has been developed for determining the content
of vanillic acid. The method is reproducible, workable and reliable.

Publication Types:
English Abstract

PMID: 12242805 [PubMed - indexed for MEDLINE]

22: Cell Mol Life Sci. 1999 Oct 15;56(3-4):348-55.

Picroliv modulates the expression of insulin-like growth factor (IGF)-I, IGF-II
and IGF-I receptor during hypoxia in rats.

Gaddipati JP, Mani H, Banaudha KK, Sharma SK, Kulshreshtha DK, Maheshwari RK.

Center for Combat Casualty Care and Life Sustainment Research, Department of
Pathology, Uniformed Services University of the Health Sciences, Bethesda,
Maryland 20814, USA.

The insulin-like growth factors (IGFs), IGF-I and IGF-II, play important roles
in normal growth and differentiation. In recent studies, IGFs have been
implicated in tissue repair and regeneration after hypoxicischemic injury. The
growth effects of these genes are exerted primarily through IGF-I receptor
(IGF-IR). We have earlier shown that picroliv, obtained from the roots of
Picrorhiza kurrooa, reduces cellular damage caused by hypoxia in vitro. We have
now studied the modulation of IGF-I, IGF-II and IGF-IR in hypoxia and the
ability of picroliv to modify their expression in vivo. Male Sprague-Dawley
rats, placed in 10% oxygen for 4 days, were sacrificed, and the expression of
IGF-I, IGF-II and IGF-IR was determined by immunohistochemistry, in situ
hybridization and reverse transcriptase polymerase chain reaction (RT-PCR) in
brain, liver and lung. One group of animals was pretreated with picroliv and the
other served as control. IGF-I and IGF-IR were expressed in distinct regions of
the brain but not in liver or lung. IGF-I was mainly expressed in the
hippocampus and cerebellum, whereas IGF-IR expression was also observed in the
cortex. A significant reduction in the messenger RNA (mRNA) level of these genes
was observed in response to hypoxia. Pretreatment with picroliv not only
prevented such downregulation but more importantly resulted in increased levels
of IGF-I and IGF-IR. These observations correlated with reduced neuronal cell
death observed in these animals. The mRNA of IGF-II was constitutively expressed
and was not altered by hypoxia. Modulation of IGF-I and IGF-II expression by
picroliv, a novel pharmacological agent, could benefit in similar clinical
settings such as myocardial ischemia and certain cerebral injuries.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 11212361 [PubMed - indexed for MEDLINE]

23: Eur J Pharmacol. 2000 May 3;395(3):229-39.

Picroliv preconditioning protects the rat liver against ischemia-reperfusion
injury.

Singh AK, Mani H, Seth P, Gaddipati JP, Kumari R, Banuadha KK, Sharma SC,
Kulshreshtha DK, Maheshwari RK.

Department of Pathology, Uniformed Services University of the Health Sciences,
Bethesda, MD 20814, USA.

Cell death following ischemia-reperfusion injury is a major concern in clinical
issues such as organ transplantation and trauma. The need to identify agents
with a potential for preventing such damage has assumed great importance. We
have evaluated the efficacy of picroliv, a potent antioxidant derived from the
plant Picrorhiza kurrooa, in protecting against hepatic ischemia-reperfusion
injury in vivo. Picroliv was fed to male Sprague Dawley rats in a dose of 12
mg/kg once daily by oral gavage for 7 days prior to hepatic ischemia. Ischemia
was induced by occluding the hepatic pedicel with a microaneurysm clip for 30
min and reperfusion was allowed thereafter for varying period (15-120 min) by
releasing the microaneurysm clip. Picroliv pretreatment resulted in better
hepatocyte glycogen preservation and reduced apoptosis. Reduction in apoptosis
was associated with decreased mRNA expression of caspase-3 and Fas. Oxidant
induced cellular damage as measured by tissue malondialdehyde (MDA) levels was
significantly less following picroliv pretreatment. Both a reduction in
neutrophil infiltration and an increased level of intracellular antioxidant
enzyme superoxide dismutase possibly contributed to the reduction in tissue
lipid peroxidation. Tissue inflammatory cytokines level of interleukin-1alpha
(IL-1alpha) and interleukin-1beta (IL-1beta) was also lower in picroliv group.
Furthermore, picroliv pretreatment resulted in enhanced proliferating cell
nuclear antigen (PCNA) immunoreactivity. These studies strongly suggest picroliv
to be a promising agent for ameliorating injury following ischemia-reperfusion.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10812054 [PubMed - indexed for MEDLINE]

24: Biochem Pharmacol. 2000 May 15;59(10):1315-22.

Prevention of renal ischemia-reperfusion-induced injury in rats by picroliv.

Seth P, Kumari R, Madhavan S, Singh AK, Mani H, Banaudha KK, Sharma SC,
Kulshreshtha DK, Maheshwari RK.

Center for Combat Casualty Care and Life Sustainment Research, Department of
Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD
20814, USA.

Picroliv is a potent antioxidant extracted from the roots and rhizome of
Picrorhiza kurrooa. It has been shown to impart significant hepatoprotective
activities, partly by modulation of free radical-induced lipid peroxidation.
Lipid peroxidation and reactive oxygen species are associated with tissue injury
in post-ischemic acute renal failure. The efficacy of picroliv was assessed in
an in vivo model of renal ischemia-reperfusion injury (IRI) in rats at a dose of
12 mg/kg orally for 7 days. The animals were killed at various times after
reperfusion. Increased lipid peroxidation and apoptotic cell number reflected
the oxidative damage following renal IRI. Picroliv-pretreated rats exhibited
lower lipid peroxidation, improved antioxidant status, and reduced apoptosis,
indicating better viability of renal cells. Immunohistochemical studies revealed
that picroliv pretreatment attenuated the expression of intercellular adhesion
molecule-1 in the glomerular region. These results suggested that picroliv
pretreatment protects rat kidneys from IRI, perhaps by modulation of free
radical damage and adhesion molecules.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10736432 [PubMed - indexed for MEDLINE]

25: Mol Cell Biochem. 1999 Apr;194(1-2):271-81.

Picroliv -- a natural product protects cells and regulates the gene expression
during hypoxia/reoxygenation.

Gaddipati JP, Madhavan S, Sidhu GS, Singh AK, Seth P, Maheshwari RK.

Center for Combat Casualty and Life Sustainment Research, Department of
Pathology, Uniformed Services University of the Life Sciences, Bethesda,
Maryland 20814, USA.

Cellular adaptation to hypoxia involves regulation of specific genes such as
vascular endothelial growth factor (VEGF), erythropoietin (EPO) and hypoxia
inducible factor (HIF)-1 . In this study, we have evaluated the protective
effect of picroliv (a purified iridoid glycoside fraction from roots of
Picrorhiza kurrooa with hepatoprotective, anti-inflammatory and antioxidant
properties) against hypoxic injury by examining lactate dehydrogenase (LDH)
release in Hep 3B and Glioma cells. The expression of hypoxia regulated genes,
VEGF and HIF-1 was studied in human umbilical vein endothelial cells (HUVEC),
Hep 3B and Glioma cells. Picroliv reduced the cellular damage caused by hypoxia
as revealed by a significant reduction in LDH release compared to untreated
control. The expression of VEGF and HIF-1 subunits (HIF-1alpha and HIF-1beta)
was enhanced by treatment with picroliv during normoxia and hypoxia in HUVEC and
Hep 3B cells and on reoxygenation the expression of these genes was
significantly reduced as revealed by mRNA analysis using RT-PCR. Simultaneous
treatment with picroliv during hypoxia inhibited VEGF and HIF-1 expression in
Glioma cells whereas the expression was not reduced by picroliv treatment during
reoxygenation as evidenced by both RT-PCR and Northern hybridization. VEGF
expression as revealed by immunofluorescence studies correlates well with the
regulations observed in the mRNA expression. We have also examined the kinase
activity of tyrosine phosphorylated proteins and protein kinase C (PKC) in
Glioma cells treated with picroliv during hypoxia/reoxygenation. A selective
inhibition of protein tyrosine kinase activity leading to tyrosine
dephosphorylation of several proteins including 80 kd protein, and a reduction
in PKC was seen in cells treated with picroliv and hypoxia. These findings
suggest that picroliv may act as a protective agent against
hypoxia/reoxygenation induced injuries, and the underlying mechanism may involve
a novel signal transduction pathway.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10391150 [PubMed - indexed for MEDLINE]

26: J Pharmacol Toxicol Methods. 1998 Oct;40(3):173-9.

Curative effect of picroliv on primary cultured rat hepatocytes against
different hepatotoxins: an in vitro study.

Visen PK, Saraswat B, Dhawan BN.

Division of Pharmacology, Central Drug Research Institute, Lucknow, UP, India.

Picroliv, the standardized active principle from the plant Picrorhiza kurrooa
showed significant curative activity in vitro in primary cultured rat
hepatocytes against toxicity induced by thioacetamide (200 microg/mL),
galactosamine (400 microg/mL), and carbon tetrachloride (3 microl/mL). Activity
was assessed by determining the change in hepatocyte viability and rate of
oxygen uptake and other biochemical parameters (GOT, GPT, and AP). The toxic
agents alone produced a 40-62% inhibition of cell viability and a reduction of
biochemical parameters after 24 h of incubation at 37 degrees C which (on
removal of the toxic agents) was reversed after further incubation for 48 h.
Incubation of damaged hepatocytes with picroliv exhibited a concentration-
(1-100 microg/mL) dependent curative effect in restoring altered viability
parameters. The results warrant the use of this in vitro system as an
alternative for in vivo assessment of hepatoprotective activity of new agents.

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

PMID: 10334634 [PubMed - indexed for MEDLINE]

27: Indian J Exp Biol. 1998 Apr;36(4):371-4.

Picroliv prevents oxidation in serum lipoprotein lipids of Mastomys coucha
infected with Plasmodium berghei.

Chander R, Singh K, Visen PK, Kapoor NK, Dhawan BN.

Biochemistry Division, Central Drug Research Institute, Lucknow, India.

Picroliv, an iridoid glycoside mixture from the root and rhizome of Picrorhiza
kurrooa, at the dose of 6 mg/kg p.o. for two weeks provided significant
protection against the generation of lipid peroxidation products in serum
beta-lipoproteins of P. berghei infected M. coucha. Incubation of normal rat
hepatocytes with very low density lipoprotein or low density lipoprotein
isolated from infected animals caused significant generation of lipid peroxides
followed by a decrease in the viability of these cells, however these effects
were partially reversed with the lipoproteins from infected and picroliv treated
groups. High density lipoprotein from infected animals was not toxic to
hepatocytes in vitro.

PMID: 9717447 [PubMed - indexed for MEDLINE]

28: Indian J Exp Biol. 1997 Dec;35(12):1302-5.

Protective effect of picroliv, active constituent of Picrorhiza kurrooa, against
oxytetracycline induced hepatic damage.

Saraswat B, Visen PK, Patnaik GK, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Central Drug Reserach Institute, Lucknow, India.

Picroliv, the active constituent of P. kurrooa, showed a dose dependent (1.5-12
mg/kg, po for 7 days) hepatoprotective activity against oxytetracycline induced
hepatic damage in rat. It increased the number of viable hepatocytes (ex-vivo)
significantly. Increase in bile volume and its contents in conscious rat
suggests potent anticholestatic property. Picroliv also antagonised alterations
in enzyme levels (GOT, GPT, and alkaline phosphatase) in isolated hepatocytes
and serum, induced by oxytetracycline (200 mg/kg, i.p.) feeding. Picroliv was
more potent than silymarin a known hepatoprotective drug.

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

PMID: 9567764 [PubMed - indexed for MEDLINE]

29: Indian J Gastroenterol. 1998 Jan;17(1):6-9.

Prevention of carbon tetrachloride-induced hepatic injury in mice by Picrorhiza
kurrooa.

Santra A, Das S, Maity A, Rao SB, Mazumder DN.

Department of Gastroenterology, Institute of Post Graduate Medical Education and
Research, Calcutta.

OBJECTIVE: Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian
indigenous system of medicine. We undertook this study to determine whether Pk
extract possesses hepatoprotective function and if so to determine its nature
and mechanism. METHODS: Liver injury was induced in 16 mice by thrice-a-week
injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were
given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection.
Control mice (n = 6) were injected with olive oil for the same period. Serum
markers of liver injury and histology of liver tissues were studied. Hepatic
glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD),
catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also
determined. RESULTS: CCl4 treatment resulted in significant elevation of serum
ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein],
-SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control
358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced.
Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole
MDA/mg protein] and histologic changes characteristic of liver injury were also
seen. Feeding of Pk extract in CCl4-treated mice caused significantly less
alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH,
G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi
released/min/mg protein]. Histologic lesions of liver and lipid peroxidation
[1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals.
CONCLUSION: The extract of Pk appears to offer significant protection against
liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor
of lipid peroxidation of liver plasma membrane.

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

PMID: 9465504 [PubMed - indexed for MEDLINE]

30: J Ethnopharmacol. 1997 Sep;58(1):15-20.

Effect of some Indian herbs on macrophage functions in ochratoxin A treated
mice.

Dhuley JN.

Department of Pharmacology and Toxicology, Research Centre, Hindustan
Antibiotics Limited, Pimpri, India.

The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia,
Withania somnifera and Picrorhiza kurrooa on the functions of macrophages
obtained from mice treated with the carcinogen ochratoxin A (OTA) was
investigated. The chemotactic activity of murine macrophages was significantly
decreased by 17 weeks of treatment with OTA compared with controls. Production
of interleukin-1 (IL-1) and tumor necrosis factor (TNF) was also markedly
reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania
somnifera and Picrorhiza kurrooa significantly inhibited OTA-induced suppression
of chemotactic activity and production of IL-1 and TNF-alpha by macropahges.
Moreover, we found that Withania somnifera treated macrophage chemotaxis and
that Asparagus racemosus induced excess production of TNF-alpha when compared
with controls.

Publication Types:
Comparative Study

PMID: 9324000 [PubMed - indexed for MEDLINE]

31: Cancer Lett. 1996 Apr 19;102(1-2):223-6.

Inhibitory effect of iridoids on Epstein-Barr virus activation by a short-term
in vitro assay for anti-tumor promoters.

Kapadia GJ, Sharma SC, Tokuda H, Nishino H, Ueda S.

Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical
Sciences, Howard University, Washington, DC 20059, USA.

The in vitro anti-tumor promoting effect of the methanolic extracts of iridoids
containing three plants and several pure iridoids isolated from other plants,
has been evaluated. The alcoholic extracts of Paederia scandens, P. scandens
var. mairei and the Ayurvedic herbal remedy Picrorhiza kurrooa were tested
against the Epstein-Barr virus. Among the 15 iridoids evaluated, the glycoside,
paederoside, displayed the highest order of anti-tumor promoting activity.

Publication Types:
Research Support, U.S. Gov't, Non-P.H.S.

PMID: 8603374 [PubMed - indexed for MEDLINE]

32: Indian J Exp Biol. 1994 May;32(5):324-7.

Picroliv affects gamma-glutamyl cycle in liver and brain of Mastomys natalensis
infected with Plasmodium berghei.

Chander R, Kapoor NK, Dhawan BN.

Biochemistry Division, Central Drug Research Institute, Lucknow, India.

Picroliv, the standardized preparation of iridoid glycosides from Picrorhiza
kurrooa, at the dose of 6 mg/kg, po for two weeks provided significant
protection against depletion of reduced glutathione levels in liver and brain of
Plasmodium berghei infected Mastomys natalensis. The activation of
gamma-glutamyl transpeptidase enzyme and decreased levels of cysteine,
sulphydryl groups as well as glutathione synthesis in both tissues due to P.
berghei infection were reversed by picroliv. Enzymatic and non enzymatic lipid
peroxidation in microsomes in vitro was significantly reduced by picroliv along
with the recovery of reduced glutathione.

PMID: 7927525 [PubMed - indexed for MEDLINE]

33: Indian J Exp Biol. 1993 Apr;31(4):316-8.

Anticholestatic effect of picroliv, active hepatoprotective principle of
Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis.

Saraswat B, Visen PK, Patnaik GK, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Division of Pharmacology, Lucknow, India.

Picroliv showed a dose (3-12 mg/kg, po for 7 days) dependent choleretic activity
as evidenced by increase in bile flow and its contents (bile salts and bile
acids). Significant anticholestatic activity was also observed against carbon
tetrachloride induced cholestasis in conscious rat, anaesthetized guinea pig and
cat. Picroliv was more active than the known hepatoprotective drug silymarin.

Publication Types:
Comparative Study

PMID: 8359830 [PubMed - indexed for MEDLINE]

34: Planta Med. 1993 Feb;59(1):37-41.

Prevention of galactosamine-induced hepatic damage by picroliv: study on bile
flow and isolated hepatocytes (ex vivo).

Visen PK, Shukla B, Patnaik GK, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Central Drug Research Institute, Lucknow, India.

Picroliv, a standardized extract from the plant Picrorhiza kurrooa containing
active constituents, showed a significant dose dependent (3-12 mg/kg p.o. x 7)
protective activity against galactosamine-induced hepatic damage in rat as
evaluated on the isolated hepatocytes (ex vivo) preparation. It markedly
increased the percentage of viability of hepatocytes. It also restored the
galactosamine-induced changes in the levels of enzymes (GOT, GPT and alkaline
phosphatase) both in isolated hepatic cells as well as in serum. In addition,
picroliv possessed a marked anticholestatic effect. Picroliv was found to be
more potent than silymarin, a standard hepatoprotective agent.

Publication Types:
In Vitro

PMID: 8441780 [PubMed - indexed for MEDLINE]

35: Planta Med. 1992 Dec;58(6):528-32.

Immunostimulant Activity of Picroliv, the Iridoid Glycoside Fraction of
Picrorhiza kurroa, and its Protective Action against Leishmania donovani
Infection in Hamsters1.

Puri A, Saxena RP, Guru PY, Kulshreshtha DK, Saxena KC, Dhawan BN.

ICMR Centre for Advanced Pharmacological Research on Traditional Remedies,
Central Drug Research Institute, Post Box No. 173, Lucknow 226001 (U.P.), India.

Picroliv, a standardised fraction from root and rhizome of PICRORHIZA KURROA,
consisting of iridoid glycosides and shown to be responsible for its
hepatoprotective activity, was studied for immunostimulant activity. Oral
administration of Picroliv (10 mg/kg x 7 days) in mice prior to immunization
with sheep red blood cells (SRBC) resulted in a significant increase in
haemagglutinating antibody (HA) titre, plaque forming cells (PFC), and delayed
hypersensitivity (DTH) response to SRBC. Picroliv enhanced the non-specific
immune response characterized by an increase in macrophage migration index
(MMI), [ (14)C]-glucosamine uptake, phagocytosis of [ (14)C]-leucine labelled
ESCHERICHIA COLI, chemiluminescence of peritoneal macrophages, and higher uptake
of [ (3)H]-thymidine in the lymphocytes of treated mice. It also induced a high
degree of protection in golden hamsters against challenge infection with
LEISHMANIA DONOVANI promastigotes.

PMID: 17226519 [PubMed - in process]

36: Indian J Exp Biol. 1992 Aug;30(8):711-4.

Effect of picroliv on glutathione metabolism in liver and brain of Mastomys
natalensis infected with Plasmodium berghei.

Chander R, Kapoor NK, Dhawan BN.

Biochemistry Division, Central Drug Research Institute, Lucknow, India.

Administration of picroliv, the active principle from Picrorhiza kurrooa, at a
dose of 6 mg/kg, po for two weeks showed significant protection against changes
in liver and brain glutathione metabolism of Plasmodium berghei infected
Mastomys natalensis. The depletion of reduced glutathione level and inhibition
of glutathione-S-transferase, glutathione reductase and glutathione peroxidase
activities due to P. berghei infection were markedly recovered by picroliv. The
increased levels of lipid peroxidation products in damaged tissues were also
reduced along with the recovery of glutathione metabolism.

PMID: 1459651 [PubMed - indexed for MEDLINE]

37: Biochem Pharmacol. 1992 Jul 7;44(1):180-3.

Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of
superoxide anions.

Chander R, Kapoor NK, Dhawan BN.

Biochemistry Division, Central Drug Research Institute, Lucknow, India.

Picroliv, the active principle of Picrorhiza kurrooa, and its main components
which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were
studied in vitro as potential scavengers of oxygen free radicals. The superoxide
(O2-) anions generated in a xanthine-xanthine oxidase system, as measured in
terms of uric acid formed and the reduction of nitroblue tetrazolium were shown
to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as
both glycosides inhibited the non-enzymic generation of O2- anions in a
phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver
microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems
was shown to be inhibited by the Picroliv glycosides. Known antioxidants
tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared
with regard to their antioxidant actions in the above system. It was found that
BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in
microsomes but did not interfere with enzymic or non-enzymic O2- anion
generation; and tocopherol inhibited lipid peroxidation in microsomes by both
prooxidant systems and the generation of O2- anions in the non-enzymic system
but did not interfere with xanthine oxidase activity. The present study shows
that picroliv, picroside-I and kutkoside possess the properties of antioxidants
which appear to be mediated through activity like that of superoxide dismutase,
metal ion chelators and xanthine oxidase inhibitors.

Publication Types:
Comparative Study

PMID: 1321626 [PubMed - indexed for MEDLINE]

38: J Ethnopharmacol. 1991 Aug;34(1):61-8.

Antihepatotoxic properties of picroliv: an active fraction from rhizomes of
Picrorhiza kurrooa.

Ansari RA, Tripathi SC, Patnaik GK, Dhawan BN.

Indian Council of Medical Research Centre for Advanced Pharmacological Research
on Traditional Remedies, Central Drug Research Institute, Lucknow.

The hepatoprotective activity of picroliv, the irridoid glycoside mixture from
Picrorhiza kurrooa, was determined in adult male albino rats. Pretreatment with
picroliv prevented the hepatotoxic effects of paracetamol and galactosamine as
evidenced by various biochemical and histopathological observations. Maximum
hepatoprotective effect was observed with daily oral doses of 6 and 12 mg/kg for
7 or 8 days. The antihepatotoxic action of picroliv seems likely due to an
alteration in the biotransformation of the toxic substances resulting in
decreased formation of reactive metabolites.

PMID: 1753788 [PubMed - indexed for MEDLINE]

39: Planta Med. 1989 Dec;55(6):559-63.

New cucurbitacin glycosides from Picrorhiza kurrooa.

Stuppner H, Wagner H.

From the roots of Picrorhiza kurrooa Royle and Benth., seven cucurbitacin
glycosides have been isolated and structurally elucidated mainly by NMR and mass
spectroscopy. Four of them (4, 5, 6, 7) are new and two, the 2-O-glycoside of
cucurbitacin B (25-acetoxy-2-beta-glucosyloxy-16,20-dihydroxy-9-methyl-19-norl
anosta-5, 23-diene-3,11,22-trione) and the 2-O-glucoside of 23,24
didydrocucurbitacin B
(25-acetoxy-2-beta-glucosyloxy-16,20-dihydroxy-9-methyl-19-norl anost-5-ene-3,
11-22-trione) were so far not reported as constituents of this plant. The four
new cucurbitacins could be identified as
2-beta-glucosyloxy-3,16,20,25-tetrahydroxy-9-methyl-19-norlanos ta-5,
23-diene-22-one, 2-beta-glucosyloxy-3,16,20,25-tetrahydroxy-9-methyl-19-norlanos
t-5-ene-22-one, the 2-O-glucoside of cucurbitacin Q
(25-acetoxy-2-beta-glucosyloxy-3,16,20-trihydroxy-9-methyl-19-n orlanosta-5,
23-diene-11,22-dione), and the 2-O-glucoside of deacetoxycucurbitacin B
(2-beta-glucosyloxy-16,20-dihydroxy-9-methyl-19-norlanosta-5 ,
24-diene-3,11,22-trione).

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

PMID: 2616673 [PubMed - indexed for MEDLINE]

40: Planta Med. 1989 Oct;55(5):467-9.

Minor Iridoid and Phenol Glycosides of Picrorhiza kurrooa.

Stuppner H, Wagner H.

Institut fur Pharmakognosie, Universitat Innsbruck, Innrain 52,
Josef-Moeller-Haus, A-6020 Innsbruck, Austria.

From the roots of PICRORHIZA KURROOA a new iridoid glycoside, 6-feruloylcatalpol
has been isolated, along with veronicoside and minecoside and two phenol
glucosides, picein and androsin.

PMID: 17262460 [PubMed - in process]

41: Planta Med. 1988 Dec;54(6):564.

Immunomodulatory Compounds from Picrorhiza kurroa: Isolation and
Characterization of two Anticomplementary Polymeric Fractions from an Aqueous
Root Extract.

Simons JM, 't Hart LA, van Dijk H, de Silva KT, Labadie RP.

Department of Chemical Pharmacy, Section of Pharmacognosy, Laboratory of
Pharmacy, State University of Utrecht, Catharijnesingel 60, 3511 GH Utrecht, The
Netherlands.

PMID: 17265350 [PubMed - in process]

42: Indian J Med Res. 1988 Apr;87:401-4.

Erratum in:
Indian J Med Res 1988 Dec;88:iv.

Hepatoprotective activity of kutkin--the iridoid glycoside mixture of Picrorhiza
kurrooa.

Ansari RA, Aswal BS, Chander R, Dhawan BN, Garg NK, Kapoor NK, Kulshreshtha DK,
Mehdi H, Mehrotra BN, Patnaik GK, et al.

PMID: 3049327 [PubMed - indexed for MEDLINE]  

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