• herbal medicine for liver diseases;
  • Indian systems of medicine;
  • Phyllanthus amarus;
  • Picrorhiza kurroa


  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

Abstract  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.

© 2002 Blackwell Publishing Asia Pty Ltd


  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

The use of herbal medicine can be traced back to 2100 bc in ancient China at the time of Xia dynasty, and in India during the Vedic period. The first written reports are timed to 600 bc with Charaka samhita of India, and in China the same became systematic by 400 bc.1 The basic concept in these medicinal systems is that the disease is a manifestation of a general imbalance of the dichotomous energies that govern life as a whole and human life in particular, and they focus on medicine that can balance these energies and maintain good health. In Ayurvedha of India, the forces are said to be agni (strength, health and innovation) and ama (weakness, disease and intoxication). In India there are also other systems of traditional medicine besides Ayurvedha and these are called Siddha, which originated almost at the same time as Ayurvedha from southern India, and Unani, which entered India during the Mogul dynasty periods. Like Ayurvedha, practitioners of Siddha medicine believe in a perfect balance of three doshas known as vatha (space and air elements), pitta (fire and water elements) and kapha (water and earth elements). All these Indian systems of medicine have primarily claimed a curative potential for their medicinal preparations for all kinds of liver diseases.

In spite of the significant popularity of these medicinal systems, they are still to be recognized as being universally acceptable treatment modalities for chronic liver disease.

The limiting factors that contribute to such an eventuality are (i) lack of standardization of the herbal drugs; (ii) lack of randomized placebo controlled clinical trials; and (iii) lack of traditional toxicologic evaluations.

Herbal preparations used in indian systems of medicine

  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

There are more than 300 preparations in the Indian systems of medicine for the treatment of jaundice and chronic liver diseases (Tables 1–3).

Table 1.  Siddha medicine preparations approved by the Indian Medicinal Practitioner's Co-operative Pharmacy and Stores for the treatment of jaundice and chronic liver diseases 2
SL. no.Preparation
1.Arumuga chendooram.
2.Annabedhi chendooram no. 1 and 2.
3.Ayakantha chendooram.
4.Mandooradi kudineer.
5.Ayabringaraja karpam.
6.Karisalai lehyam.
7.Kantha chendooram and
8.Loha mandooram.
Table 2.  Ayurvedic preparations approved by the Indian Medicinal Practitioner's Co-operative Pharmacy and Stores for the treatment of jaundice and chronic liver diseases 2
SL. no.Preparation
 3.Drakahadi rasayam.
 4.Guduchi satwam.
 5.Jambeeradi panakam.
 6.Panchatiktakwatha churnam.
 7.Dhathri loham.
 8.Tapyadi loham.
 9.Pipilyadi loham.
10.Saptamiruda loham.
Table 3.  Unani preparations approved by the Indian Medicinal Practitioner's Co-operative Pharmacy and Stores for the treatment of jaundice and chronic liver diseases 2
SL. no.Preparation
 2.Jawarish-e-Amila luluvi.

In India more than 87 medicinal plants are used in different combinations as herbal drugs for liver diseases.3–6 However, not all the plants have been evaluated for their pharmacological and antiviral efficacy although several plants were reported as being hepatoprotective (Table 4).7–36

Table 4.  List of the Indian medicinal plants having liver protection properties against chemical-induced liver damage in experimental animals 7–36
SL. no.Preparation
 1.Acacia catechu.
 2.Achillea millfolium.
 3.Azadirachta indica.
 4.Andrographis paniculata.
 5.Boerhaavia diffusa.
 6.Capparis spinosa.
 7.Chelidonium majus.
 8.Cichorium intybus.
 9.Daucus carota.
10.Eclipta alba.
11.Geophila renifbrmis.
12.Glycosmis pentaphylla.
13.Mikania cordata.
14.Moringa oleffera.
15.Ocimum sanctum.
16.Phyllanthus embilica.
17.Phyllanthus debilis.
18.Phyllanthus kozhikodianus.
19.Phyllanthus maderaspatensis.
20.Phyllanthus niruri/amarus.
21.Picrorhiza kurroa.
22.Ricinus communis.
23.Sida cordifolia.
24.Sida rhombifolia.
25.Swertia chirata.
26.Tephrosia purpuria.
27.Trichopus zeylanicus.
28.Verbena officinalis.
29.Wedelia calendulacea.
30.Withania somnifera.

Scientific validation in medicinal plant research in india

  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

There are data available on the following plants: (i) Picrorhiza kurroa; (ii) Phyllanthus amarus (niruri); (iii) Silybum marianum; and (iv) Glycyrrhiza glabra.

Picrorhiza kurroa

  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

Picroside 1 and 2, catapol, kutkoside I and kutkoside have been identified as major bioactive components of P. kurroa.37,38Picrorhiza kurroa, a known hepatoprotective plant, was studied in experimental and clinical situations. Basic research has been carried out on the whole plant, picroside 1 alone, and on picroliv, which contain picroside 1, catapol, kutkoside I and kutkoside.

Dwivedi et al. have shown significant hepato-protective properties of picroliv using models such as monocrotaline- and CCl4-induced liver injury in rats.38–40 Shukla et al. compared picroliv with silymarin in rat and guinea pig models and found potent choleretic and anticholestatic functions.41 Chander et al. also found hepatoprotective properties in picroliv.42 Using in vitro HBsAg binding assay, Mehrotra et al. have shown HBsAg inhibition in picroliv and its major component, catapol.37 Pandey and Das, and Atal Mehrotra et al. have demonstrated anti-inflammatory and immuno-modulating potential in P. kurroa, stimulating both cell-mediated and humoral immunity.43–45

Picrorhiza kurroa has also been found to be helpful in clinical and biochemical recovery in acute hepatitis. 46

Jayaram found P. kurroa to be effective in HBeAg seroconversion in 28.5% of patients compared to 16% seroconversion with placebo.47

The existing literature on P. kurroa suggests that it is a powerful immuno-modulator rather than an antiviral drug in liver diseases.

Phyllanthus amarus

  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

Historical use of Phyllanthus niruri in jaundice

Even though clinical uses of P. niruri and other species, namely P. amarus, have been cited for over a century in the Ayurvedha and Siddha literature, scientific studies were carried out only during the last 50 years.

Studies on Phyllanthus niruri/amarus against hepatitis B virus

Thyagarajan et al. have shown that there exist antiviral properties against HBV for the whole plant extract of P. niruri.48,49 This plant from Tamilnadu, India, has been identified taxonomically as P. amarus. The aqueous extracts of the plant inhibits the viral DNA polymerase (DNAp) of HBV and woodchuck hepatitis virus (WHV) in vitro.50–52

Yanagi et al. have also reported that aqueous extracts of high dilutions of P. amarus collected from South India inhibited HBV DNAp, DNApI, T4-DNAp, the Klenow fragment and reverse transcriptase of avian myeloblastosis virus.52 Shead et al. have shown the aqueous extracts to inhibit the endogenous DNAp of Duck hepatitis virus (DHBV) at high dilutions.53 Niu et al. with suitable controls found that after 10 weeks treatment, there was a transient reduction of duck hepatitis B viral DNA in the serum of congenitally infected ducks, but there was no effect on the level of virus DNA or surface antigen in the liver.54

Jayaram and Thyagarajan reported in vitro inhibition of HBsAg secretion by PLC/PRF/5 (Alexander) cell line for 48 h when the cell line was treated with 1 mg/mL concentration of P. amarus as a single dose.55 Lee et al. found that P. amarus downregulated HBVm transcription and replication in transgenic mice and transgenic cell lines.56Phyllanthus amarus possibly interrupts the interaction between HBV enhancer I and cellular transcription factors.57

Phyllanthus amarus is reported to be safe and non-toxic to mice in a dose of 10 g/kg bodyweight. 58 A 20% aqueous extract of P. niruri is effective as an oral pretreatment at 0.2 mL/100 mg bodyweight against CCl 4 -induced hepatotoxicity in rats. 59 The hexane-extracted compounds, phyllanthin and hypophyllanthin, were found to reduce CCl 4 - or galactosamine-induced cytotoxicity to cultured rat hepatocytes. 60

The aqueous extract of the dried whole plant did not produce any chronic toxicity in mice at 0.2 mg daily dose per animal for 90 days, as determined by physiological, biochemical and histopathological parameters.61 Venkateswaran et al. demonstrated its in vivo safety using woodchucks as animal models,50 while Niu et al. have shown P. amarus to be non-toxic in Pekin ducks chronically infected with duck hepatitis B virus.54 Jayaram et al., studying the effect of P. amarus on β-galactosamine-induced hepatotoxicity on isolated rat hepatocytes, found that P. amarus by itself was not hepatotoxic and at 1 mg/mL concentration it was found to be hepatoprotective.62

In the traditional medicine systems, several formulatory medicines are used for the treatment of jaundice without taking into consideration the etiology. Phyllanthus niruri is one of the constituents of such multiherbal preparations, which contain anywhere up to 12 medicinal herbs. Most of the treatment evaluations were based only on improvement in the clinical condition of the patient.

In a clinical trial in acute viral hepatitis (AVH) patients, Jayanthi et al. used P. niruri and compared it with other herbal medicines.63 A significantly greater decrease in transaminase levels after 2 weeks’ treatment with P. niruri in both HBsAg-positive and -negative groups was observed. In another study, P. amarus treatment improved liver functions significantly faster in both acute hepatitis A and B, with a higher rate of HBsAg clearance.64

In a clinical trial on chronic HBV carriers, HBsAg clearance in the P. amarus-treated group was 59%, versus 4% in the placebo group.65 The second open trial in 1990 showed 20% HBsAg clearance and 63.6% loss of infectivity by HBeAg sero-conversion.66 Additional clinical trials were undertaken in subsequent years (Table 5).69 However, several investigators from other countries including Leelarasamee et al. from Thailand and Wang et al. from China could not reproduce the treatment efficacy.67,68 This could partly be due to the use of the local variety of P. amarus grown in their respective countries.

Table 5.  Clinical trials of Phylllanthus amarus on patients with chronic HBV
Clinical trial no.Study/yearDosage mg/tdsDurationNo. treatedHBsAgHBeAg seroconversion %
  1. ND, not done. In summary, these trials enumerated in Table 5 have shown a mean HBsAg clearance rate of 25.6% and mean HBeAg seroconversion rate of 55.3% with a recommended dose of 500 mg dosage of P. amarus preparation in capsules given orally three times daily for 6 months. P. amarus grown in Tamilnadu; for convenience it is termed as ‘university preparation’.

1Thyagarajan et al. (1988)65, Madras2001 month4038594NDND
2Thyagarajan et al. (1990)66, Madras2503 months20Nil2063.6
3Samuel et al. (1991)69, Vellore2502 months1012208.337.5 0
4Thyagarajan etal (1992)69, Madras2506 months72Nil2554.0
5Thyagarajan etal (1993)69, Madras5003 months 8 825071.416.0
6Walker et al. (1993–1995)69, Glasgow5004–6 months26Nil11.645.4
7Thyagarajan et al. (1996–1997)69,  Madras5006 months37Nil18.960.0

Standardization of phyllanthus amarus

  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

In order to determine the reasons for variation in the in vitro efficacy of different collections of P. amarus made from different parts of India, in vitro analysis for biological properties was done. It revealed that the quantitative HBsAg binding ability and HBV DNA polymerase inhibition ability varied significantly in different plant collections, and some of them did not possess demonstrable anti-hepatitis B properties. When the extracts of these collections were analyzed by HPLC profiles, there were similar variations of diminished elution peaks or even absence of such peaks that could be correlated with the absence of biological properties. These observations were considered along with the report of Mitra and Jain on the botanical survey of India, which stated that the P. niruri is a mixture of three distinct species, namely P. amarus Schum and Thonn, P. fraternus Webster and P. debilis Kleinx Wild.70 From the reports it is now understood that the variety that is predominant in South India is P. amarus only.71

Based on these observations it was necessary to define a multistep standardization procedure for assuring the reproducible, maximized bio-efficacy of P. amarus when used in the treatment of chronic liver disease with special reference to chronic HBV infection. These steps are: (i) taxonomic identification of the specific variety of P. amarus as the source material; (ii) preparation of the soil for the optimum growth of the selected P. amarus variety; (iii) a formulation of the combination of specific extracts that will possess the following six demonstrable in vitro activities: (a) HBsAg binding property, which will facilitate the inactivation of the virus in circulation, ultimately leading to viral clearance; (b) HBV-DNA polymerase enzyme-inhibiting potential, thus acting as an antiviral and preventing the multiplication of HBV; (c) reverse transcriptase enzyme inhibition, also required for the prevention of initiation of HBV replication; (d) inhibition of HBsAg secretion from HBV-transinfected liver cells, thus possessing activity against virus-infected chronic liver disease conditions; (e) hepatoprotective and antihepatotoxic properties against the liver cell toxicity brought about by all hepatitis viruses (A,B,C,D,E) and other hepatotoxic agents; and (f) immunomodulating property to potentiate the immune system of HBV-infected patients towards virus clearance and protective antibody (anti-HBs) responses; and (iv) a ‘chemobiological finger printing methodology’ using the aforementioned six biological tests along with a matching HPLC profile to assess batch-to-batch in vitro reproducibility.

The evaluation of herbal products face several major problems. The first is the use of mixed extracts (concoctions) and variations in methods of harvesting, preparing and extracting the herb, which can result in dramatically different levels of certain alkaloids. The biologically active substances have been structurally defined and standardized for only a few of the herbs. Even then it may not be known whether this is the sole active principal or if efficacy depends on the mixture of compounds.

Second, there is a lack of randomized placebo controlled clinical trials for many of these preparations using end-points of treatment efficacy such as viral clearance, and histological improvement.

Numerous reports on toxic effects contradict the popular view that herbal drugs are natural and are harmless.72–76 A survey by the National Poison Information Service for the years 1991–1995 documented 785 cases of possible or confirmed adverse reactions to herbal drugs, among which hepatotoxicity was the most frequent.73 Hence, safety studies are needed to generate scientifically sufficient data that may serve as a basis for future herbal drug development.

In addition to the well-accepted laboratory parameters as described here using P. amarus as an example, if the aforementioned three aspects viz., herbal drug standardization, randomized controlled clinical trials and well-designed safety studies are incorporated as integral components, then herbal drug development, potent, safe and acceptable herbal drugs can be launched for the treatment of acute and chronic liver diseases. The drug development of P. amarus in India may be an example of such an effort in an international setting.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References

The authors wish to acknowledge the collaboration extended by Late Dr N. Madanagopalan, Professor and Head, Department of Gastroenterology, Madras Medical College and other gastroenterologists of Tamilnadu; Dr Eric Walker, Scottish Center for Infection and Environmental Health, UK; Dr Stephen Locarnini, MacFarlane Center for Virology, Australia; and Dr Sanjeev Gupta, Albert Einstein Center for Liver Diseases, USA. The financial help extended by Indian Council of Medical Research, Council of Industrial and Scientific Research, India and the HEL Programme of British Council Division for the research by the authors on P. amarus is sincerely acknowledged.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Herbal preparations used in indian systems of medicine
  5. Scientific validation in medicinal plant research in india
  6. Picrorhiza kurroa
  7. Phyllanthus amarus
  8. Standardization of phyllanthus amarus
  9. Acknowledgments
  10. References
  • 1
    Schuppan D, Jia J-D, Brinkhaus B, Hahn EG. Herbal products for liver diseases: A therapeutic challenge for the new millennium. Hepatology 1999; 30: 1099104.
  • 2
    Thyagarajan SP. Changing therapy: Treatment of viral hepatitis in modern and alternative medicine systems. IAP J. Pract. Pediatr. 1996; 4: 1617.
  • 3
    Handa SS, Sharma A, Chakraborty KK. Natural products and plants as liver protecting drugs. Fitoterapia 1989; 57: 30751.
  • 4
    Hikino H, Kiso Y. Natural products for liver diseases. In: Economic and Medicinal Plant Research, vol. 2. London: Academic Press, 1988; 3972.
  • 5
    Evans WC. An overview of drugs having antihepatotoxic and oral hypoglycemic activities. In: Trease AK, Evans WC, eds. Pharmacognosy, 14th edn. UK: WD Sanders, 1996.
  • 6
    Sharma A, Shing RT, Sehgal V, Handa SS. Antihepatotoxic activity of some plants used in herbal formulations. Fitoterapia 1991; 62: 1318.
  • 7
    Doreswamy R, Sharma D. Plant drugs for liver disorders management. Indian Drugs 1995; 32: 13944.
  • 8
    Jayasekhar P, Mohanan PV, Rathinum K. Hepatoprotective activity of ethyl acetate extract of Acacia catechu. Indian J. Pharmaocol. 1997; 29: 4268.
  • 9
    Gadgoli C, Mishra SH. Preliminary screening of Achillea millefolium, Cichorium intybus and Capparis spinosa for anti-hepatotoxic activity. Fitoterapia 1995; 66: 31923.
  • 10
    Chattopadhyay RR, Sarkar SK, Ganguly S, Banerjee RN, Basu TK, Mukherjee A. Hepatoprotective activity of Azadiracha indica leaves on paracetamol-induced hepatic damage in rats. Indian J. Pharmacol. 1994; 24: 3540.
  • 11
    Handa SS, Sharma A. Hepatoprotective andrographolide from Andrographis paniculata. Indian J. Med. Res. 1990; 92: 27692.
  • 12
    Rawat AKS, Mehrotra S, Tripathi SC, Shome U. Hepatoprotective activity of Boerhaavia diwffusa L roots, a popular Indian ethnomedicine. J. Ethnopharmacol. 1997; 56: 615.
  • 13
    Cakraborti KK, Handa SS. Antihepatotoxic activity of Boerhaavia diffusa and B. repanda. Indian Drugs 1989; 27: 1924 and 161–6.
  • 14
    Gadgoli C, Mishra SH. Antihepatotoxic activity of Cichorium intybus. J. Ethanopharmacol. 1997; 58: 1314.
  • 15
    Bishayee A, Sarkar A, Chatterjee M. Hepatoprotective activity of carrot (Daucus carota L.) against carbon tetrachloride intoxication in mouse liver. J. Ethanopharmacol. 1995; 7: 6994.
  • 16
    Saxena AK, Singh B, Anand KK. Hepatoprotective effects of Eclipta alba on subcellular levels in rats. J. Ethnopharmacol. 1993; 40: 15561.
  • 17
    Subramoniam A, Rajasekharan S, Vinodkumar TG, Pushpangadan P. Studies on the hepatoprotective activity of Geophila renifbrmis. In: 6th World Congress on Holistic Life and Medicine, 5–7 January, Kozhikode, India (Abstract), 1996.
  • 18
    Mitra S, Sur RK. Hepatoprotection with Glycosmis pentaphylla. Indian J. Exp. Biol. 1997; 35: 13069.
  • 19
    Mandal PK, Bishayee A, Chatterjee M. Stimulation of tissue repair by Mikania cordata extract on CCl4 induced liver injury in mice. Phytother. Res. 1993; 7: 1035.
  • 20
    Ruckmani K, Kavimani S, Anandan R, Jaykar B. Effect of Moringa oleifera Lam on paracetamol-induced hepatotoxicity. Indian J. Pharm. Sci. 1998; 60: 335.
  • 21
    Chattopadhyay RR, Sarkar SK, Ganguly S, Medda C, Basu TK. Hepatoprotective activity of Ocimum sanctum leaf extract against paracetamol induced hepatic damage in rats. Indian J. Pharmacol. 1992; 24: 1635.
  • 22
    Gulati RK, Agarwal SS. Hepatoprotective studies on Phyllanthus emblica Linn. and quercetin. Indian J. Exp. Biol. 1994; 33: 2618.
  • 23
    Sane RT, Kuber VV, Mary SC, Menon S. Hepatoprotection by Phyllanthus amarus and P. debelis in CCl4 induced liver dysfunction. Curr. Sci. 1995; 68: 12426.
  • 24
    Asha VV, Pushpangadan P. Preliminary evaluation of antihepatotoxic activity of Phyllanthus maderaspatensis, P. kozhikodianus and Solanum indicum. Fitoterapia 1998; 69: 2604.
  • 25
    Reddy BP, Murthy VN, Venkateshwarulu V, Kokate CK, Rambhau D. Antihepatotoxic activity of Phyllanthus niruri, Tinospora cordifolia and Ricinus communis. Indian Drugs 1993; 30: 33841.
  • 26
    Ansari RA, Aswal BS, Chander R et al. Hepatoprotective activity of Kutkin, the iridold glycoside mixture of Picrorrhiza kurroa. Indian J. Med. Res. 1998; 87: 4014.
  • 27
    Saraswat B, Visen PKS, Patnaik GK, Dhawan BN. Protective affect of picroliv, active principle of Picrorrhiza kurroa against oxytetracycline-induced hepatic damage. Indian J. Exp. Biol. 1997; 35: 130215.
  • 28
    Dwivedi Y, Rastogi R, Garag NK, Dhawan BN. Prevention of paracetamol-induced hepatic damage in rats by picroliv, the standardized active fraction from Picrorrhiza kurroa. Phytother. Res. 1991; 5: 11519.
  • 29
    Kumar SR, Mishra SH. Isolation and assessment of hepatoprotective activity of fumaric acid obtained for the first time from Sida cordifolia Linn. Indian Drugs 1997; 34: 7026.
  • 30
    Kumar SR, Mishra SH. Antiinflammatory and hepatoprotective activities of Sida rhombifolia. Indian J. Pharmacol. 1997; 29: 11016.
  • 31
    Mukherjee S, Sur A, Maiti BR. Hepatoprotective effects of Swertia chirata on rats. Indian J. Exp. Biol. 1997; 35: 3848.
  • 32
    Ramamurthy SM, Srinivasan M. Hepatoprotective effects of Tephrosia purpurea in experimental animals. Indian J. Pharmacol. 1993; 25: 348.
  • 33
    Subramoniam A, Evans DA, Rajasekharan S, Pushpangadan P. Hepatoprotective activity of Trichopus zeylanicus extract against paracetamol induced hepatic damage in rats. Indian J. Exp. Biol. 1998; 36: 3859.
  • 34
    Singh B, Saxena AK, Chandan BK et al. Hepatoprotective activity of verbenalin on experimental liver damage in rodents. Fitoterapia 1998; 69: 13541.
  • 35
    Sharma AK, Anand KK, Pushpangadan P et al. Hepatoprotective effects of Wedelia calendulacea. J. Ethnopharmacol. 1989; 25: 93102.
  • 36
    Sudhir S, Budhiraja RD. Protective effect of Witthferin against an experimental model of hepatitis. Indian J. Pharmacol. 1991; 23: 1620.
  • 37
    Mehrotra P, Rawat S, Kulshreshtha DK, Patnaik GK, Dhawan BN. Invitro studies on the effect of certain natural products against hepatitis B virus. Indian J. Med. Res. 1990; 92: 1338.
  • 38
    Dwivedi Y, Rastogi R, Sharma SK, Mehrotra R, Garg NK, Dhawan BN. Picroliv protects against monocrotaline-induced hepatic damage in rats. Pharmacol. Res. 1991; 23: 399407.
  • 39
    Dwivedi Y, Rastogi R, Sharma SK, Garg NK, Dhawan BN. Picroliv affords protection against thioacetamide-induced hepatic damage in rats. Plants Med. 1991; 57: 258.
  • 40
    Dwivedi Y, Rastogi R, Chander R. et al. Hepatoprotective activity of picroliv against carbon tetrachloride induced liver damage in rats. Indian J. Med. Res. 1990; 92: 195200.
  • 41
    Shukla B, Visen PK, Patnaik GK, Dhawan BN. Choleretic effect of picroliv, the hepatoprotective principle of Picrorhiza kurroa. Plants Med. 1991; 57: 2933.
  • 42
    Chander R, Dwivedi Y, Rastogi R et al. Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei. Indian J. Med. Res. 1990; 92: 347.
  • 43
    Pandey BL, Das PK. Immunopharmacological studies on Picrorhiza kurroa Royle-Ex-Benth. Part IV. Cellular mechanisms of anti-inflammatory action. Indian J. Physiol. Pharmacol. 1989; 33: 2830.
  • 44
    Pandey BL, Das PK. Immunopharmacological studies on picrorohiza kurroa Royle-Ex-Benth. Part V. Anti-inflammatory action: Relation with cell types involved in inflammation. Indian J. Physiol. Pharmacol. 1988; 32: 28992.
  • 45
    Atal CK, Sharma ML, Kaul A, Khajuria A. Immunomodulating agents of plant origin. I. Preliminary screening. J. Ethnopharmacol. 1986; 18: 13341.
  • 46
    Rajalakshmi S, Sivanandam G, Veluchamy G. Effect of Kadugurohini (Picrorhiza kurroa Royle) in the treatment of Viral Hepatitis: A double blind study with placebo control. J. Res. AyurvedhaSiddha. 1990; 13: 2734.
  • 47
    Jayaram S. Studies on prevention and control of Hepatitis B virus infection. PhD Thesis , University of Madras, India. 1992.
  • 48
    Thyagarajan SP. Studies on Hepatitis B virus infection in Tamilnadu, laying special emphasis on the immunological and biochemical markers with an assessment on the antiviral properties of certain indigenous herbs. PhD Thesis , University of Madras, India. 1979.
  • 49
    Thyagarajan SP, Thiruneelakandan K, Subramanian S, Sundaravelu T. Invitro inactivation of HBsAg by Eclipta alba Hassk and Phyllanthus niruri Linn. Indian J. Med. Res. 1982; 76 (Suppl.): 12430.
  • 50
    Venkateswaran PS, Millman I, Blumberg BS. Effect and an extract from Phyllanthus niruri on hepatitis B and woodchuch hepatitis viruses: Invitro and invivo studies. Proc. Natl Acad. Sci. USA 1987; 84: 2748.
  • 51
    Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Hepatitis B Virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus. Cancer Detect. Prev. 1989; 14: 195202.
  • 52
    Yanagi M, Unoura M, Kobayashi K et al. Inhibitory effect of an extract from Phyllanthus niruri on reaction of endogenous HBV–DNA polymerase and other DNA synthetases. In: Abstracts of Papers Presented at the 1989 Meeting on Hepatitis, B viruses. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory, 1989; 77, 25–8.
  • 53
    Shead A, Vickery K, Medhurst R, Freiman J, Cossart Y. Neutralisation but not cure of duck hepatitis b by Australian Phyllanthus extracts. In: Scientific Program and abstract volume, the 1990 International Symposium on Viral Hepatitis and Liver Disease. Houston, Texas, 1990.
  • 54
    Niu J, Wang Y, Qiau M et al. Effect of Phyllanthus amarus on duck hepatitis B virus replication in vivo. J. Med. Virol. 1990; 32: 21218.
  • 55
    Jayaram S, Thyagarajan SP. Inhibition of HBsAg secretion from Alexander cell line by Phyllanthus amarus. Indian J. Pathol. Microbiol. 1996; 39: 21115.
  • 56
    Lee CD, Ott M, Thyagarajan SP, Sharfritz DA, Burk RD, Gupta S. Phyllanthus amarus down regulates hepatitis B virus mRNA transcription and replication. Eur. J. Clin. Invest. 1996; 4: 1618.
  • 57
    Ott M, Thyagarajan SP, Gupta S. Phyllanthus amarus suppresses hepatitis B virus by interrupting interactions between HBV-enhancer I and cellular transcription factors. Eur. J. Clin. Invest. 1997; 27: 90815.
  • 58
    Mokkhasmit M, Swasdimongkol K, Satrwaha P. Study on toxicity of Thai medicinal plants. Bull. Med. Sci. 1971; 12: 3665 (Abstract).
  • 59
    Rao YS. Experimental production of liver damage and its protection with Phyllanthus niruri and Cappris spinosa (both ingredients of Liv 52) in white albino rats. Probe 1985; 3: 11719.
  • 60
    Syamasundar KV, Singh B, Thakur RS, Hussain A, Kiso H. Antihepatotoxic principles of Phyllanthus niruri herbs. J. Ethanopharmacol. 1985; 14: 414.
  • 61
    Jayaram S, Thyagarajan SP, Panchanadam M, Subramanian S. Anti hepatitis B virus properties of Phyllanthus niruri Linn. and Eclipta alba Hassk: Invitro and Invivo safety studies. Biomedicine 1987; 7: 916.
  • 62
    Jayaram S, Udaya Shankar K, Rajendran P, Thyagarajan SP. Antihepatotoxicity potentials of Phyllanthus amarus: An invitro study using isolated rat hepatocyte cultures. Indian J. Med. Microbiol. 1994; 12: 24851.
  • 63
    Jayanthi V, Madanagopalan N, Thyagarajan SP, Balakumar V, Parimalam S, Malathi S. Value of herbal medicines, Phyllanthus niruri, Eclipta alba, Piper Longus, Thippili (Tamil) and combination of Phyllanthus niruri and Ricinus communis (Icterus-Pharm. products) in acute viral hepatitis. J. Gasteroenterol. Hepatol. 1988; 3: 5334.
  • 64
    Geetha J, Manjula R, Malathi S et al. Efficacy of ‘Essential Phospholipid substance’ of Soya Bean oil and Phyllanthus niruri in acute viral hepatitis. J. Gen. Med. 1992; 4: 538.
  • 65
    Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet 1988; 2: 7646.
  • 66
    Thyagarajan SP, Jayaram S, Valliammai T, Madanagopalan N, Pal VG, Jayaraman K. Phyllanthus amarus and hepatitis B. Lancet 1990; 336: 94950.
  • 67
    Leelarasamee A, Trakulsomboon S, Maunwongyathi P et al. Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Lancet 1990; 1: 16001.
  • 68
    Wang M, Zhou H-B, Zhao G-I, Zhao S, Mai K. Phyllanthus amarus cannot eliminate HBsAg in chronic hepatitis B virus infection. Hepatology 1991; 21: 224.
  • 69
    Thyagarajan SP, Jayaram S, Panneerselvam A et al. Effect of Phyllanthus amarus, an Indian medicinal plant on healthy carriers of hepatitis B virus: Results of six clinical trials, 1990–1996. Indian J. Gastroenterol. 1999; 18 (Suppl. 1): S26.
  • 70
    Mitra RL, Jain SK. Concept of Phyllanthus niruri (Euphorbiaceae) in Indian Floras. Bull. Botan. Surv. India 1985; 27: 16176.
  • 71
    Unander DW, Webster GL, Blumberg BS. Use age and bioassays in Phyllanthus (Euphorbiaceae): A compilation II. The subgenus Phyllanthus. J. Ethanopharmacol. 1991; 34: 97133.
  • 72
    Yogeeswaran G, Sathyakumar J. Convergence of Indian systems and modern medicine: A new promise in health care. LABCON 2002; 2: 18.
  • 73
    Shaw D, Leon C, Koleu S, Murray V. Traditional remedies and food supplements. A five-year toxicological study (1991–1995). Drug Safety 1997; 17: 34256.
  • 74
    Yoshida EM, McLean CA, Chen ES et al. Chinese herbal medicine, fulminant hepatitis and liver transplantation. Am. J. Gastroenterol. 1996; 91: 14368.
  • 75
    Larrey D, Pageaux GP. Hepatotoxicity of herbal remedies and mushrooms. Semin. Liver Dis. 1995; 15: 1838.
  • 76
    Kaplowitz N. Hepatotoxicity of herbal remedies: Insight into the intricacies of plant–animal warfare and cell death. Gastroenterology 1997; 113: 140812.
  • 77
    Thyagarajan SP, Jayaram S. Natural History of Phyllanthus amarus in the treatment of hepatitis B. Indian J. Med. Microbiol. 1992; 10: 6480.