-IBIS-1.7.6-
tx
digestive system
hepatitis
Botanicals
primary herbs
Achillea millefolium: as compress for warm to liver (Husemann, 437)
Berberis spp.: cholagogue, cholecystitis, cholelithiasis, jaundice (British Herbal Pharmacopoeia, 40)
Bryonia alba (toxic): chronic with deep seated soreness and quick, shooting pains especially with some elevation in temperature (Ellingwood, 90)
Chelidonium majus (toxic): chronic (Felter, 556)
Cichorium intybus: jaundice (Anderson Geller)
Chionanthus virginica: chronic (Felter, 556)
Glycyrrhizin (Licorice extract): solid extract 1/2 teaspoon twice daily; individuals with a history of hypertension should take licorice only under the supervision of a physician trained in herbal therapeutics and then in the deglycyrrhinated form.
(Sato H, et al. Antiviral Res 1996 May;30(2-3):171-177; Takahara T, et al. J Hepatol 1994 Oct;21(4):601-609; Arase Y, et al. Cancer 1997 Apr 15;79(8):1494-1500.; van Rossum TG, et al. Aliment Pharmacol Ther 1998 Mar;12(3):199-205; Suzuki H, et al. Asian Med J 26:423-438, 1984; Crance JM, et al. Antiviral Res 1994;23:63-76.)
Lentinus edodes (Shiitake mushrooms) (Harada T, et al. Gastroenterol Intl 1988;1(suppl 1):abstract 719; Hobbs, C. 1995, 96-107.)
Phyllanthus spp. (urinaria and amarus): 200 mg three times daily; research has shown inconsistent benefits for hepatitis B, possibly related to varying origins of plant materials, with the urinaria species showing greater effectiveness than the amarus species.
(Wang M, et al. J Lab Clin Med 1995 Oct;126(4):350-352; Doshi JC, et al. Ind J Gastroenterol 1994;13:7-8; Meixa W, et al. J Lab Clin Med 1995;126:350-352.)
Podophyllum peltatum (toxic): chronic (Felter, 556)
Reishi mushrooms
Silybum marianum (Silymarin): Many studies showing signifcant beneficial responses for a wide range of liver pathologies, including reversals of tissue damage. Standardized extract (70-80%) 400 mg twice daily. (1/4 teaspoon twice daily.). Can also use intravenously (IV form comes form Germany).
(Weiss RF. 79, 82; Bode JC, et al. Med Klin 1977;72:513-518; Salmi HA, Sarna S. Scand J Gastroenterol 1982 Jun;17(4):517-521; Ferenci P, et al. J Hepatol. 1989 Jul;9(1):105-113; Berkson BM. Med Klin. 1999 Oct 15;94 Suppl 3:84-89.)
Taraxacum officinale: jaundice (British Herbal Pharmacopoeia, 208.)
Curcuma longa (Tumeric or Curcumin): Research involving rats has shown hepatoprotective effects against inflammatory conditions of the liver found in toxic exposure to carbontetrachloride and glucosamine. It tends to prevent liver enzymes from reaching excessive levels. It also increases the flow and solubility of bile, so that it may protect against gall bladder stone formation.
(Deshpande UR, et al. Indian J Exp Biol. 1998 Jun;36(6):573-577.)
Veronicastrum virginicum: (Priest and Priest, p. 101; Felter, Lloyd, p. 1129)
nutritive and tonic herbs: (Anderson Geller)
Eleutherococcus senticosus
Medicago sativa
Panax spp.
Rumex officinalis
Taraxacum officinale
Urtica dioica
Green tea: couple cups per day.
Note: see also Chinese Herbs for many herbs now commonly used by American and European medical herbalists.
complementary herbs
Veronicastrum virginicum + Ceanothus americanus + Urtica urens + sunlight + vitamins A, B, C, E (Sherman)
footnotes
Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN. A preliminary open trial on interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure. Indian J Med Res 1993 Apr;98:69-74,
Abstract: The efficacy of the interferon stimulator named Stronger Neo Minophagen-C (SNMC) derived form the plant G. glabra was studied at a dose of 40 or 100 ml daily for 30 days followed by thrice weekly intravenously for 8 wk in 18 patients of subacute hepatic failure due to viral hepatitis. The survival rate amongst these patients was 72.2 per cent, as compared to the earlier reported rate of 31.1 per cent in 98 patients who received supportive therapy (P < 0.01). Death in four of the five patients was due to associated infections leading to hepatorenal failure and terminal coma. Further studies are necessary to standardize the dose and duration of therapy with SNMC in subacute hepatic failure.
Arase Y, Ikeda K, Murashima N, Chayama K, Tsubota A, Koida I, Suzuki Y, Saitoh S, Kobayashi M, Kumada H. The long term efficacy of glycyrrhizin in chronic hepatitis C patients. Cancer 1997 Apr 15;79(8):1494-1500.
Abstract: BACKGROUND: Hepatocellular carcinoma (HCC) occurs in patients with hepatitis C virus-RNA positive chronic liver disease. It is important to prevent HCC with drug administration. METHODS: A retrospective study was undertaken to evaluate the long term preventive effect of Stronger Neo-Minophagen C (SNMC) on HCC development. SNMC is a Japanese medicine that is commonly administered to patients with chronic hepatitis C to improve the serum alanine aminotransferase (ALT) level. Of 453 patients diagnosed with chronic hepatitis C retrospectively in the study hospital between January 1979 and April 1984, 84 patients (Group A) had been treated with SNMC; SNMC was given at a dose of 100 mL daily for 8 weeks, then 2-7 times a week for 2-16 years (median, 10.1 years). Another group of 109 patients (Group B) could not be treated with SNMC or interferon for a long period of time (median, 9.2 years) and were given other herbal medicine (such as vitamin K). The patients were retrospectively monitored, and the cumulative incidence of HCC and risk factors for HCC were examined. RESULTS: The 10th-year rates of cumulative HCC incidence for Groups A and B were 7% and 12%, respectively, and the 15th-year rates were 12% and 25%. By Cox regression analysis, the relative risk of HCC incidence in patients not treated with SNMC (Group B) was 2.49 compared with that of patients treated with SNMC (Group A). CONCLUSIONS: In this study, long term administration of SNMC in the treatment of chronic hepatitis C was effective in preventing liver carcinogenesis.
Barzaghi N, Crema F, Gatti G, Pifferi G, Perucca E. Pharmacokinetic studies on IdB 1016, a silybin- phosphatidylcholine complex, in healthy human subjects. Eur J Drug Metab Pharmacokinet 1990 Oct-Dec;15(4):333-338.
Abstract: IdB 1016 is a complex of silybin (the main active component of silymarin) and phosphatidylcholine, which in animal models shows greater oral bioavailability and therefore greater pharmacological activity compared with pure silybin and silymarin. In order to assess its pharmacokinetic profile in man, plasma silybin levels were determined after administration of single oral doses of IdB 1016 and silymarin (equivalent to 360 mg silybin) to 9 healthy volunteers. Although absorption was rapid with both preparations, the bioavailability of IdB 1016 was much greater than that of silymarin, as indicated by higher plasma silybin levels at all sampling times after intake of the complex. Regardless of the preparation used, the terminal
half-life was relatively short (generally less than 4 h). In a subsequent study, 9 healthy volunteers received IdB 1016 (120 mg twice daily, expressed as silybin equivalents) for 8 consecutive days. The plasma silybin level profiles and kinetic parameters
on day 1 were similar to those determined on day 8. Most of the silybin present in the systemic circulation was in conjugated form. Less than 3% of the administered dose was accounted for by urinary recovery of free plus conjugated silybin, a significant proportion of the dose probably being excreted in the bile. It is concluded that complexation with phosphatidylcholine in IdB 1016 greatly increases the oral bioavailability of silybin, probably by facilitating its passage across the gastrointestinal mucosa.
Berk L, de Man RA, Schalm SW, Labadie RP, Heijtink RA. Beneficial effects of Phyllanthus amarus for chronic hepatitis B, not confirmed. J Hepatol 1991 May;12(3):405-406.
Berkson BM. A conservative triple antioxidant approach to the treatment of hepatitis C. Combination of alpha lipoic acid (thioctic acid), silymarin, and selenium: three case histories. Med Klin. 1999 Oct 15;94 Suppl 3:84-89.
Abstract: BACKGROUND: There has been an increase in the number of adults seeking liver transplantation for hepatitis C in the last few years and the count is going up rapidly. There is no reliable and effective therapy for chronic hepatitis C since interferon and antivirals work no more than 30% of the time, and liver transplant surgery is uncertain and tentative over the long run. This is because, ultimately, residual hepatitis C viremia infects the new liver. Furthermore, liver transplantation can be painful, disabling and extremely costly. TREATMENT PROGRAM: The author describes a low cost and efficacious treatment program in 3 patients with cirrhosis, portal hypertension and esophageal varices secondary to chronic hepatitis C infection. This effective and conservative regimen combines 3 potent antioxidants (alpha-lipoic acid [thioctic acid], silymarin, and selenium) that possess antiviral, free radical quenching and immune boosting qualities. CONCLUSION: There are no remarkably effective treatments for chronic hepatitis C in general use. Interferon and antivirals have less than a 30% response rate and because of the residual viremia, a newly transplanted liver usually becomes infected again. The triple antioxidant combinaton of alpha-lipoic acid, silymarin and selenium was chosen for a conservative treatment of hepatitis C because these substances protect the liver from free radical damage, increase the levels of other fundamental antioxidants, and interfere with viral proliferation. The 3 patients presented in this paper followed the triple antioxidant program and recovered quickly and their laboratory values remarkably improved. Furthermore, liver transplantation was avoided and the patients are back at work, carrying out their normal activities, and feeling healthy. The author offers a more conservative approach to the treatment of hepatitis C, that is exceedingly less expensive. One year of the triple antioxidant therapy described in this paper costs less than $2,000, as compared to more than $300,000 a year for liver transplant surgery. It appears reasonable, that prior to liver transplant surgery evaluation, or during the transplant evaluation process, the conservative triple antioxidant treatment approach should be considered. If these is a significant betterment in the patient's condition, liver transplnat surgery may be avoided.
Blumberg BS, Millman I, Venkateswaran PS, Thyagarajan SP. Hepatitis B virus and primary hepatocellular carcinoma: treatment of HBV carriers with Phyllanthus amarus. Vaccine 1990 Mar;8 Suppl:S86-92.
Abstract: A viricide capable of eliminating hepatitis B virus (HBV) from chronic carriers should, theoretically, decrease the risk of primary hepatocellular carcinoma. Extracts of Phyllanthus amarus have been shown to inhibit the DNA polymerase of HBV and woodchuck hepatitis virus (WHV) in vitro. Three of four recently infected WHV carriers treated i.p. with P. amarus extract lost WHV, animals infected for greater than or equal to 3 months showed a decrease in virus levels. Preliminary results in human carriers treated orally with P. amarus for 1 month indicated that approximately 60% of the carriers lost HBV during the observation period.
Bode JC, Schmidt U, Durr HK. Silymarin for the treatment of acute viral hepatitis? Report of a controlled trial. Med Klin 1977;72:513-518. [Article in German]
British Herbal Medicine Association. British Herbal Pharmacopeia. West Yorks, England: BHMA, 1983.
Buzzelli G, Moscarella S, Giusti A, Duchini A, Marena C, Lampertico M. A Pilot Study on the Liver Protective Effect of Silybinphosphatidylcholine Complex (IdB1016) in Chronic Active Hepatitis. Int J Clin Pharmacol Ther Toxicol. 1993; 31(9):456-460.
Abstract: In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin twice daily (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (±SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (±13.3) to 65.9 (±7.5) u/l, (p <0.01), of alanine aminotransferase (ALT) from 115.9 (±12.9) to 82.5 (±10.6) u/l (p <0.01), of gamma-glutamyltranspeptidase (y-GT) from 51.4 (±9.3) to 41.3 (±4.2) u/1 (p <0.02) and of total bilirubin (TB) from 0.76 (±0.08) to 0.53 (±0.04) mg/dl (p <0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (±6.4) to 137.5 (±7.8) u/1. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.
Crance JM, Leveque F, Biziagos E, et al. Studies on mechanism of action on glycyrrhizin against hepatitis A virus replication in vitro. Antiviral Res 1994;23:63-76.
Deak G, Muzes G, Lang I, Niederland V, Nekam K, Gonzalez-Cabello R, Gergely P, Feher J. [Immunomodulator effect of silymarin therapy in chronic alcoholic liver
diseases]. Orv Hetil 1990 Jun 17;131(24):1291-2, 1295-1296. [Article in Hungarian]
Abstract: The effects of the hepatoprotective, antioxidant drug silymarin (Legalon) on some cellular immune parameters of patients with histologically proven chronic alcoholic liver disease were studied in a six month double blind study. The lectin induced proliferative activity of the lymphocytes got enhanced, the originally low T cell percentage and the originally high CD8+ cell percentage have been normalized, the antibody-dependent and natural cytotoxicity of the lymphocytes decreased during silymarin therapy. All these changes were significant, while in the placebo group no significant changes occurred, except for a moderate elevation of the T cell percentage. Thus, the immunomodulatory activity of silymarin might be involved in the hepatoprotective action of the drug and improves the depressed immunoreactivity of the patients.
Deshpande UR, Gadre SG, Raste AS, Pillai D, Bhide SV, Samuel AM. Protective effect of turmeric (Curcuma longa L.) extract on carbon tetrachloride-induced liver damage in rats. Indian J Exp Biol. 1998 Jun;36(6):573-577.
Abstract: The protective effect of tumeric extract (TE) in diet on CCl4-treated rats was studied. Rats were divided into 5 groups: (1) untreated, (2) CCl4 treated, (3) pre-TE for 2 weeks followed by CCl4, (4) TE + CCl4 given concurrently and (5) 5% TE as positive control. The serum levels of bilirubin, cholesterol, aspartate aminotransferase, (AST), alanine amino transferase (AST), (ALT) and alkaline phosphatase were estimated after 1, 2 and 3 months. CCl4 caused a maximum increase (2-3-fold in all the above parameters. As compared to CCl4 group, a short pre-treatment of TE showed reduction in cholesterol, bilirubin, AST, ALT and alkaline phosphatase activity whereas concurrent treatment of TE + CCl4 reduced to a greater extent the levels of all parameters except ALT. To conclude, concurrent treatment of TE gave significant protection against CCl4 though the values did not reach the normal levels.
Desai IV, Dudhia MV, Gandhi VK. A clinical study of infective hepatitis treated with Liv. 52. Indian Pediatr 1977 Mar;14(3):197-202.
Doshi JC, Vaidya AB, Antarkar DS, et al. A two-stage clinical trial of Phyllanthus amarus in hepatitis B carriers: Failure to eradicate the surface antigen. Ind J Gastroenterol 1994;13:7-8.
Eisenburg J. [Treatment of chronic hepatitis B. Part 2: Effect of glycyrrhizic acid on the course of illness]. Fortschr Med 1992 Jul 30;110(21):395-8 [Article in German]
Abstract: AIMS: Testing of the therapeutic efficacy of Remefa S, a pharmaceutical comprising glycyrrhizinic acid, the major active substance of licorice, on the evolution of the disease in late chronic viral hepatitis B. METHODS: Prospective evaluation of the biochemical, virus-serological and histomorphological data (blind liver aspiration, laparoscopy) during and following 12 months of application (three times a week, short infusions) of Remefa S, and comparison with the course of the disease (12 months) prior to treatment. PATIENTS: Intermediate report on an ongoing multicentre study begun in 1989, with evaluation of 7 subjects receiving the preparation and 3 controls after 12 months of treatment and 10 months of follow-up. RESULTS: During or after treatment, 4 patients experienced a regression of biochemical disease activity. In 2 of the 4 patients, during treatment, an HBe-Ag seroconversion occurred for the first time and has persisted (to date 10 months); in another patient with no detectable HBe-Ag prior to treatment, HBe antibodies were formed under treatment, and have persisted to the present time. In 2 of these responders, histology also revealed an unequivocal reduction in disease activity. In contrast, HBs-Ag seroconversion was observed in none of the patients treated. Since in these three patients the virus genome was already integrated within the chromosome of the host cell (hybridization), this had not been expected from the start. CONCLUSIONS: Intravenous chronic application (12 months) of glycyrrhizinic acid in the form of Remefa S in patients with chronic viral hepatitis B, is capable of exercising a positive effect on the evolution of the disease. On the basis of the results obtained so far (30-40% success rate), a comparison with the results obtained with interferon suggests itself.
Ellingwood F. American Materia Medica, Therapeutics and Pharmacognosy, 11th ed. Sandy, OR: Eclectic Medical Publications, 1919, 1998.
Farese RV Jr, Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R. Licorice-induced hypermineralocorticoidism. N Engl J Med 1991 Oct 24;325(17):1223-1227.
Felter HW, Lloyd JU. Kings American Dispensatory, 18th ed. Sandy, OR: Eclectic Medical Publications, 1898, 1983.
Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol. 1989 Jul;9(1):105-113.
Abstract: Silymarin, the active principle of the milk thistle Silybum marianum, protects experimental animals against various hepatotoxic substances. To determine the effect of silymarin on the outcome of patients with cirrhosis, a double blind, prospective, randomized study was performed in 170 patients with cirrhosis. 87 patients (alcoholic 46, non-alcoholic 41; 61 male, 26 female; Child A, 47; B, 37; C, 3; mean age 57) received 140 mg silymarin three times daily. 83 patients (alcoholic 45, non-alcoholic 38; 62 male, 21 female; Child A, 42; B, 32; C, 9: mean age 58) received a placebo. Non-compliant patients and patients who failed to come to a control were considered as 'drop outs' and were withdrawn from the study. All patients received the same treatment until the last patient entered had finished 2-years of treatment. The mean observation period was 41 months. There were 10 drop outs in the placebo group and 14 in the treatment group. In the placebo group, 37 (+2 drop outs) patients had died, and in 31 of these, death was related to liver disease. In the treatment group, 24 (+4 drop outs) had died, and in 18 of these, death was related to liver disease. The 4-year survival rate was 58 +/- 9% (S.E.) in silymarin-treated patients and 39 +/- 9% in the placebo group (P = 0.036). Analysis of subgroups indicated that treatment was effective in patients with alcoholic cirrhosis (P = 0.01) and in patients initially rated 'Child A' (P = 0.03). No side effects of drug treatment were observed.
Harada T, Kanetaka T, Suzuki H, Suzuki K. Therapeutic effect of LEM (extract of cultured Lentinus edodes mycelia) against HBeAg-positive chronic hepatitis B. Gastroenterol Intl 1988;1(suppl 1):abstract 719.
Hobbs C. Medicinal Mushrooms. Santa Cruz, CA: Botanica Press, 1995, 96-107.
Lee CD, Ott M, Thyagarajan SP, Shafritz DA, Burk RD, Gupta S. Phyllanthus amarus down-regulates hepatitis B virus mRNA transcription and replication. Eur J Clin Invest 1996 Dec;26(12):1069-1076.
Abstract: The Phyllanthus amarus plant shows potential for treating hepatitis B virus. To define the mechanism of action of P. amarus, we used HepG2 2.2.15 cells, which support hepatitis B virus replication. P. amarus inhibited hepatitis B virus polymerase activity, decreased episomal hepatitis B virus DNA content and suppressed virus release into culture medium. To examine transcriptional control mechanisms, we used G26 hepatitis B virus transgenic mice, which produce serum HBsAg but neither HBcAg nor virion particles. When P. amarus was administered to transgenic mice, hepatic HBsAg mRNA levels decreased, indicating transcriptional or post-transcriptional down-regulation of the transgene. Increase in hepatitis B virus mRNA expression after stimulation of the glucocorticoid responsive element was also suppressed by P. amarus, suggesting involvement of the hepatitis B virus enhancer in this response. Disruption by P. amarus of hepatitis B virus polymerase activity, mRNA transcription and replication supports its role as an antiviral agent.
Leelarasamee A, Trakulsomboon S, Maunwongyathi P, Somanabandhu A, Pidetcha P, Matrakool B, Lebnak T, Ridthimat W, Chandanayingyong D. Failure of Phyllanthus amarus to eradicate hepatitis B surface antigen from symptomless carriers. Lancet 1990 Jun 30;335(8705):1600-1601.
Lirussi F, Okolicsanyi L. Cytoprotection in the nineties: Experience with ursodeoxycholic acid and silymarin in chronic liver disease. Acta Physiol Hung 1992;80:363-367.
Magliulo E, Gagliardi B, Fiori GP. [Results of a double blind study on the effect of silymarin in the treatment of acute viral hepatitis, carried out at two medical centres]. Med Klin 1978 Jul 14;73(28-29):1060-5 [Article in German]
Abstract: In a double blind study carried out under standard conditions at two treatment centers silymarin, 2 sugar-coated tablets 70 mg three times daily, showed a definite therapeutic influence on the characteristic increased serum levels of bilirubin, GOT and GPT associated with acute viral hepatitis. The above mentioned values in 28 patients treated with silymarin were compared with those in 29 patients treated with placebo. The laboratory parameters in the silymarin group regressed more than in the placebo group after the 5th day of treatment. The number of patients having attained normal values after 3 weeks' treatment was higher in the silymarin group than in the placebo group. A statistical comparison revealed a difference between bilirubin and GOT values in the placebo and silymarin groups and a definite trend in the regression of GPT values in favour of silymarin. The course of the immune reaction in HBS Ag patients was not influenced by silymarin. As already proved by other investigators, the use of silymarin in acute viral hepatitis can lead to an accelerated regression in pathological values, thus indicating its use in the treatment of this liver disease.
Marena C, Lampertico. Preliminary clinical development of silipide: A new complex of silybin in toxic liver disorders. Planta Medica 57(S2): A124-125, 1991.
Meixa W, Cheng H, Li Y, et al. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: Observations with three preparations from different geographical sites. J Lab Clin Med 1995;126:350-352.
Milne A, Hopkirk N, Lucas CR, Waldon J, Foo Y. Failure of New Zealand hepatitis B carriers to respond to Phyllanthus amarus. N Z Med J 1994 Jun 22;107(980):243.
Mori K, Sakai H, Suzuki S, Akutsu Y, Ishikawa M, Imaizumi M, Tada K, Aihara M, Sawada Y, Yokoyama M, et al. Effects of glycyrrhizin (SNMC: Stronger Neo-Minophagen C) in hemophilia patients with HIV-1 infection. Tohoku J Exp Med 1990 Oct;162(2):183-193.
Abstract: Forty-two hemophiliacs with HIV infection were treated with high-dose glycyrrhizin, Stronger Neo-Minophagen C (SNMC). The dose was 100-200 ml of SNMC in 21 patients and 400-800 ml in the other 21. The patients were divided into an asymptomatic carrier (AC) group and AIDS related-complex (ARC)/AIDS group. SNMC was administered intravenously daily for the first 3 weeks, and every second day for the following 8 weeks to the 42 HIV-infected hemophilia patients, in accordance with the protocol proposed by the Japanese National Research Committee. The CD4/CD8 ratio and CD4 positive lymphocyte counts did not change during the treatment period. However, significant improvement was noted in some cases. A slight increase in mitogenic responsiveness to phytohemagglutinin, Concanavalin A and pokeweed mitogen was noted in most patients of both groups, especially significant improvement was seen in the AC group administered over 400 ml of SNMC. Furthermore, complete improvement was noted in liver dysfunction, which has been thought to be one of the major problems for hemophiliacs treated with blood products. Thus, prophylactic administration of high-dose SNMC to HIV positive hemophiliacs who have impaired immunological ability and liver dysfunction was considered to be effective in preventing the development from AC/ARC to AIDS.
Moscarella S, Giusti A, Marra F, Marena C, Lampertico M, Relli P, Gentilini P, Buzzelli G. Therapeutic and Antilipoperoxidant Effects of Silybin-Phosphatidylcholine Complex in Chronic Liver Disease: Preliminary Results. Curr Ther Res. 1993; 53(1):98-102.
Abstract: Eight patients (two men and six women; mean age, 54.6 + 5 years) with viral chronic active hepatitis were treated with silipide (IdB1016), a new silybin-phosphatidylcholine complex, for 2 months. After treatment with IdB1016, serum malondialdehyde levels decreased by 36%, and the quantitative liver function evaluation, as expressed by galactose elimination capacity, increased by 15%. A statistically significant reduction (P < 0.05) of transaminases was also seen. These results suggest that silipide may be effective in improving the biochemical and quantitative indices of hepatic function in patients with chronic active hepatitis.
Okuno T, Arai K, Shindo M [Efficacy of interferon combined glycyrrhizin therapy in patients with interferon-resistant chronic hepatitis C]. Nippon Rinsho 1995 Sep;53 Suppl:1022-1025. [Article in Japanese]
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 Nov;27(11):908-15
Abstract: The Phyllanthus amarus plant suppresses HBV mRNA transcription in vitro and exhibits therapeutic potential in chronic HBV carriers, although further work is necessary to define its mechanism of action. Analysis in HuH-7 cells with transfected plasmids using a luciferase reporter showed that P. amarus specifically inhibited HBV enhancer I activity. To identify the mechanism of this HBV enhancer I inhibition, liver-enriched cellular transcription factors were co-expressed in HuH-7 cells. The C/EBP alpha and beta, as well as HNF-3 alpha and beta transcription factors, significantly up-regulated the HBV enhancer I activity. In contrast, co-transfection of HNF-I alpha or beta had no effect upon the HBV enhancer I activity. Exposure to P. amarus inhibited C/EBP alpha- and beta-mediated up-regulation of HBV enhancer I activity in a dose-dependent manner, whereas HNF-3 alpha- and beta-mediated up-regulation of HBV enhancer I was unaffected. In vitro gel shifts showed that P. amarus inhibited complexing of C/EBP transcription factors to a consensus oligonucleotide sequence, whereas DNA binding of AP-1 and SP-1 transcription factors was unaffected. As P. amarus down-regulates HBV mRNA transcription by a specific mechanism involving interactions between HBV enhancer I and C/EBP transcription factors, purification and further analysis of the active P. amarus component will advance insights into its antiviral activity.
Parés A, Planas R, Torres M, et al. Effects of silymarin in alcoholic patients with cirrhosis of the liver: Results of a controlled, double-blind, randomized and multicenter trial. J Hepatol 1998;28:615-621.
Salmi HA, Sarna S. Effect of silymarin on chemical, functional, and morphological alterations of the liver. A double-blind controlled study. Scand J Gastroenterol 1982 Jun;17(4):517-521.
Abstract: One hundred and six consecutive patients with liver disease were selected on the basis of elevated serum transaminase levels. The patients were randomly allocated into a group treated with silymarin (treated) and a group receiving placebo (controls). Ninety-seven patients complete the 4-week trial-47 treated and 50 controls. In general, the series represented a relatively slight acute and subacute liver disease, mostly induced by alcohol abuse. There was a statistically highly significantly greater decrease of S-SGPT (S-ALAT) and S-SGOT (S-ASAT) in the treated group than in controls. Serum total and conjugated bilirubin decreased more in the treated than in controls, but the differences were not statistically significant. BSP retention returned to normal significantly more often in the treated group. The mean percentage decrease of BSP was also markedly higher in the treated. Normalization of histological changes occurred significantly more often in the treated than in controls.
Sato H, Goto W, Yamamura J, Kurokawa M, Kageyama S, Takahara T, Watanabe A,
Shiraki K. Therapeutic basis of glycyrrhizin on chronic hepatitis B. Antiviral Res 1996 May;30(2-3):171-177.
Abstract: Glycyrrhizin, a major component of a herb (licorice), has been intravenously used for the treatment of chronic hepatitis B in Japan and improves liver function with occasional complete recovery from hepatitis. This substance modifies the intracellular transport and suppresses sialylation of hepatitis B virus (HBV) surface antigen (HBsAg) in vitro. This study was designed to clarify the pharmacological basis for its effectiveness. The structure-bioactivity relationship of glycyrrhizin, glycyrrhetic acid 3-O-monoglucuronide and glycyrrhetic acid was determined, and glycyrrhetic acid was found to be the most active of them. The amounts of three substances bound to the liver were evaluated in guinea pig after intravenous administration of glycyrrhizin. Glycyrrhizin and glycyrrhetic acid 3-O-monoglucuronide were detected at concentrations of 31.8-1.3 micrograms/g of liver, but glycyrrhetic acid was not detected. When glycyrrhizin attained these concentrations in the cellular fraction of the PLC/PRF/5 cell culture, it suppressed the secretion of HBsAg as reported previously. These results indicated that glycyrrhizin administered intravenously might bind to hepatocytes at the concentration at which glycyrrhizin could modify the expression of HBV-related antigens on the hepatocytes and suppress sialylation of HBsAg.
Schandalik R, Gatti G, Perucca E. Pharmacokinetics of Silybin in Bile Following Administration of Silipide and Silymarin in Cholecystectomy Patients. Arzneim.-Forsch/Drug Res. 1992; 42:964-968.
Abstract: The biliary excretion of silybin, the main active component of silymarin, was evaluated by using a specific HPLC method in 9 cholecystectomy patients with T-tube drainage following single oral doses of silipide (CAS 134499-06-2), a lipophilic silybin-phosphatidylcholine complex (IdB 1016), and of silymarin (120 mg, expressed as silybin equivalents). After intake of silipide, the concentration of silybin in bile reached a peak within 4 h and declined thereafter with a mean time of about 10 h. After administration of silymarin, biliary silybin concentrations were several-fold lower than those observed after intake of silipide. The bile collected after silymarin intake also contained considerable amounts of isosilybin (a silybin isomer) and very low levels of silydianin and silycristin. The amount of silybin recovered in bile in free and conjugated form within 48 h accounted for 11% of the dose after silipide and for 3% of the dose after silymarin. Plasma silybin concentrations, determined in 3 subjects, were several-fold lower than those in bile after intake of silipide and mostly undetectable after intake of silymarin.
Stormer FC, Reistad R, Alexander J. Glycyrrhizic acid in liquorice--evaluation of health hazard. Food Chem Toxicol 1993 Apr;31(4):303-312.
Abstract: Literature on case reports, clinical studies and biochemical mechanisms of the sweet-tasting compound glycyrrhizic acid in liquorice was critically reviewed to provide a safety assessment of its presence in liquorice sweets. A high intake of liquorice can cause hypermineralocorticoidism with sodium retention and potassium loss, oedema, increased blood pressure and depression of the renin-angiotensin-aldosterone system. As a consequence, a number of other clinical symptoms have also been observed. Glycyrrhizic acid is hydrolysed in the intestine to the pharmacologically active compound glycyrrhetic acid, which inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (in the direction of cortisol to cortisone) as well as some other enzymes involved in the metabolism of corticosteroids. Inhibition of 11 beta-hydroxysteroid dehydrogenase leads to increased cortisol levels in the kidneys and in other mineralocorticoid-selective tissues. Since cortisol, which occurs in much larger amounts than aldosterone, binds with the same affinity as aldosterone to the mineralocorticoid receptor, the result is a hypermineralocorticoid effect of cortisol. The inhibitory effect on 11 beta-hydroxysteroid dehydrogenase is reversible; however, the compensatory physiological mechanisms following hypermineralocorticoidism (e.g. depression of the renin-angiotensin system) may last several months. It is not possible, on the basis of existing data, to determine precisely the minimum level of glycyrrhizic acid required to produce the described symptoms. There is apparently a great individual variation in the susceptibility to glycyrrhizic acid. In the most sensitive individuals a regular daily intake of no more than about 100 mg glycyrrhizic acid, which corresponds to 50 g liquorice sweets (assuming a content of 0.2% glycyrrhizic acid), seems to be enough to produce adverse effects. Most individuals who consume 400 mg glycyrrhizic acid daily experience adverse effects. Considering that a regular intake of 100 mg glycyrrhizic acid/day is the lowest-observed-adverse-effect level and using a safety factor of 10, a daily intake of 10 mg glycyrrhizic acid would represent a safe dose for most healthy adults. A daily intake of 1-10 mg glycyrrhizic acid/person has been estimated for several countries. However, an uneven consumption pattern suggests that a considerable number of individuals who consume large amounts of liquorice sweets are exposed to the risk of developing adverse effects.
Suzuki H, et al. Effects of Glycyrrhizin on biochemical teests in patients with chronic hepatitis - Double blind trial. Asian Med J 26:423-438, 1984.
Takahara T, Watanabe A, Shiraki K. Effects of glycyrrhizin on hepatitis B surface antigen: a biochemical and morphological study. J Hepatol 1994 Oct;21(4):601-609.
Abstract: Glycyrrhizin, a major component of a herb (licorice), has been widely used to treat chronic hepatitis B in Japan. This substance improves liver function with occasional complete recovery from hepatitis; its effects on the secretion of hepatitis B surface antigen (HBsAg) were examined in vitro. Glycyrrhizin suppressed the secretion of HBsAg and accumulated it dose-dependently in PLC/PRF/5 cells. Its action was further analyzed and determined in the HBsAg-expression system using the varicella-zoster virus. Glycyrrhizin suppressed the secretion of HBsAg, resulting in its accumulation in the cytoplasmic vacuoles in the Golgi apparatus area. HBsAg labeled with 35S-methionine and cysteine accumulated in the cells and its secretion was suppressed dose-dependently in glycyrrhizin-treated culture. The secreted HBsAg was modified by N-linked and O-linked glycans but its sialylation was inhibited dose-dependently by glycyrrhizin. Thus glycyrrhizin suppressed the intracellular transport of HBsAg at the trans-Golgi area after O-linked glycosylation and before its sialylation. HBsAg particles were mainly observed on the cell surface in the glycyrrhizin-treated culture but not in the untreated culture. This suggests that asialylation of HBsAg particles resulted in the novel surface nature of glycyrrhizin-treated HBsAg particles. We elucidated the unique mechanism of action of glycyrrhizin on HBsAg processing, intracellular transport, and secretion.
Takahashi M, Nakano S, Takeda I, Kumada T, Sugiyama K, Osada T, Kiriyama S, Toyoda H, Shimada S, Samori T. [The pharmacokinetics of the glycyrrhizin and glycyrrhetic acid after intravenous administration of glycyrrhizin for the patients with chronic liver disease caused by type C hepatitis virus]. Nippon Shokakibyo Gakkai Zasshi 1995 Dec;92(12):1929-1936. [Article in Japanese]
Abstract: Glycyrrhizin had been used widely for the patients with chronic liver disease. We examined the pharmacokinetics of the glycyrrhizin and glycyrrhetic acid in the blood stream after intra-venous administration of glycyrrhizin. The stream concentration of glycyrrhizin in the patients of liver cirrhosis tend to be kept higher than that of chronic hepatitis but there were no significant difference between them except for after a half hour from the administration. There was negative correlation between ICG R15 and the speed of excretion of glycyrrhizin from the serum. On the other hand, the concentration of the glycyrrhetic acid was kept higher in the patients with liver cirrhosis than that of chronic hepatitis, but
there were no significant difference between them except for after a half hour from the administration. These findings suggested that the accumulation of glycyrrhizin and glycyrrhetic acid in the patients of liver cirrhosis can be seen by long
term administration.
Thyagarajan SP, Jayaram S, Valliammai T, Madanagopalan N, Pal VG, Jayaraman K. Phyllanthus amarus and hepatitis B. Lancet 1990 Oct 13;336(8720):949-950.
Thyagarajan SP, Subramanian S, Thirunalasundari T, Venkateswaran PS, Blumberg BS. Effect of Phyllanthus amarus on chronic carriers of hepatitis B virus. Lancet 1988 Oct 1;2(8614):764-766.
Abstract: In a preliminary study, carriers of hepatitis B virus were treated with a preparation of the plant Phyllanthus amarus for 30 days. 22 of 37 (59%) treated patients had lost hepatitis B surface antigen when tested 15-20 days after the end of the treatment compared with only 1 of 23 (4%) placebo-treated controls. Some subjects have been followed for up to 9 months. In no case has the surface antigen returned. Clinical observation revealed few or no toxic effects. The encouraging results of this preliminary study recommend continued evaluation of this plant and the active principles isolated from it.
Vailaii A, Aristia I, Sozze E, Milani F, Inglese V, Galenda P, Bossolo PA, Ascari F, Lampertico M, Comis S, Marena C. Randomized open study of the dose-effect, relationship of a short course of IdB 1016 in patients with viral or alcoholic hepatitis. Fitoterapia 1993;64(3):219-228.
Abstract: A phase-II randomized open trial was performed to clinically evaluate the dose-response relationship to a complex of silybin and phosphatidylcholine, in patients with chronic hepatitis of either alcoholic or viral aetiology. Twenty patients received IdB 1016 capsules dosed at 80 mg twice daily, twenty patients received IdB 1016 capsules dosed at 120 mg twice daily, and twenty patients received IdB 1016 at 120 mg t.i.d. (contents expressed as silybin equivalents). The treatment lasted two weeks. The therapy was generally well tolerated. Overall, 6 patients complained of nausea (2), dyspepsia (2), heartburn (1), meteorism (1); in four cases the treatment was suspended. There was no relationship of the adverse events with the daily dose. At all tested doses, silybin-phosphatidycholine complex treatment resulted in a remarkable and statistically significant decrease of mean virum activity of aspartate aminotransferase (P < 0.001) and of total bilirubin (P < 0.050-0.001). When used at the dose of 240 or 360 mg per day, but not at the dose of 160 mg per day, it also resulted in a remarkable and statistically significant decrease of alanine aminotransferase (P < 0.01-0.001), and y-glutamyl transperidase (P < 0.01-0.001). A clinically relevant statistically significant dose-effect relationship was observed on both aminotransferase and y-glutamyl transpeptidase (NS for alanine aminotransferase). The results suggest that treatment with IdB 1016 is of benefit to patients with viral or alcohol-induced hepatitis already at the dose of 160 mg per day, but with significant advantages at the dose of 240 mg per day and still greater benefits with the dose of 360 mg per day.
van Rossum TG, Vulto AG, de Man RA, Brouwer JT, Schalm SW. Review article: glycyrrhizin as a potential treatment for chronic hepatitis C. Aliment Pharmacol Ther 1998 Mar;12(3):199-205.
Abstract: Chronic hepatitis C is a slowly progressive liver disease that may evolve into cirrhosis with its potential complications of liver failure or hepatocellular carcinoma. Current therapy with alpha-interferon is directed at viral clearance, but sustained response is only achieved in 20-40% of patients without cirrhosis, and less than 20% in patients with cirrhosis who have the greatest need for therapy. Treatment for those who do not respond to anti-viral therapy is highly desirable. In Japan glycyrrhizin has been used for more than 20 years as treatment for chronic hepatitis. In randomized controlled trials, glycyrrhizin induced a significant reduction of serum aminotransferases and an improvement in liver histology compared to placebo. Recently, these short-term effects have been amplified by a well-conducted retrospective study suggesting that long-term usage of glycyrrhizin prevents development of hepatocellular carcinoma in chronic hepatitis C. The mechanism by which glycyrrhizin improves liver biochemistry and histology are undefined. Metabolism, pharmacokinetics, side-effects, and anti-viral and hepatoprotective effects of glycyrrhizin are discussed.
Velussi M, Cernigoi AM, Viezzoli L, et al. Silymarin reduces hyperinsulinemia, malondialdehyde levels, and daily insulin need in cirrhotic diabetic patients. Curr Ther Res 1993;53:533-545.
Wang M, Cheng H, Li Y, Meng L, Zhao G, Mai K. Herbs of the genus Phyllanthus in the treatment of chronic hepatitis B: observations with three preparations from different geographic sites. J Lab Clin Med 1995 Oct;126(4):350-352.
Abstract: It has been suggested that herbs of the Phyllanthus family may have antiviral activity. We therefore tested the effects of three different Phyllanthus extracts on the serologic status of 123 patients with chronic hepatitis B. Eleven patients received an extract of Phyllanthus amarus (L) provided by S.P. Thyagarajan, Madras, India. Forty-two patients received Phyllanthus niruri (L), gathered from Hainan Province in China, and 35 patients received an extract of Phyllanthus urinaria (L), which had been gathered in Henan Province. Thirty-five control patients received no herbal therapy. The patients receiving Phyllanthus urinaria (L) were both more likely to lose detectable hepatitis B e-antigen from their serum and more likely to seroconvert hepatitis B e-antibody status from negative to positive than were patients given either of the other two preparations. No patient changed status with respect to hepatitis B s-antigen.
Wang MX, Cheng HW, Li YJ, Meng LM, Mai K. [Efficacy of Phyllanthus spp. in treating patients with chronic hepatitis B]. Chung Kuo Chung Yao Tsa Chih 1994 Dec;1 (12):750-1, 764. [Article in Chinese]
Abstract: The efficacy of Phyllanthus amarus produced in india, P. niruri gathered from hainan province and P. urinaria from Henan province was assessed in a total of 88 cases of chronic hepatitis B with 11.42 and 35 each. It was shown that P. urinaria had the effect of seroconversion on HBeAg from positive to negative as well as on HBeAb from negative to positive, while the other two herbs had not. In addition none of these three herbs had similar effect on HBsAg.
Weiss RF. Herbal Medicine. Gothenhburg, Sweden; Beaconsfield, England: Beaconsfield Publishers, Ltd., 1988.
Yamamura Y, Kotaki H, Tanaka N, Aikawa T, Sawada Y, Iga T. The pharmacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbon-tetrachloride-intoxicated rats. Biopharm Drug Dispos 1997 Nov;18(8):717-725.
Abstract: The relationships between the pharmacokinetic behaviour of glycyrrhizin and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl4-treated rats).mIn patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were 62.2 +/- 7.4 and 64.4 +/- 7.5%, respectively, after daily 80 mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63.1 +/- 19.1 and 68.7 +/- 15.2% after 120 mg doses. The present work suggests that the threshold plasma glycyrrhizin concentration for sufficient effect is near 5 micrograms mL-1. In rats, the total body clearance (Cltot) for glycrrhizin in the CCl4-treated rats after i.v. administration of glycyrrhizin (5 mg kg-1 dose) was three-tenths of that of the control, and the t1/2 for glycyrrhizin was 3.4-fold longer than that of the control. A good correlation was observed between Cltot and AST (r = -0.838) or ALT (r = -0.873) activity in both rats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl4-treated rats showed a greater improvement than for a 10 mg kg-1 dose. Furthermore, the finding on the threshold plasma concentration in patients as above was also supported from the results of the experiments in rats.
Yasuda K, Hino K, Fujioka S, et al. Effects of high dose therapy with Stronger Neo-Minophagen C (SNMC) on hepatic histography in non-A, non-B chronic active hepatitis. In: Viral Hepatitis C, D, E, ed. T Shikata, RH Purcell, T Uchida. Amsterdam: Excerpta Medica, 1991, 205-209.
Yoshikawa M, Matsui Y, Kawamoto H, Umemoto N, Oku K, Koizumi M, Yamao J, Kuriyama S, Nakano H, Hozumi N, Ishizaka S, Fukui H. Effects of glycyrrhizin on immune-mediated cytotoxicity. J Gastroenterol Hepatol 1997 Mar;12(3):243-248.
Abstract: Intravenous administration of glycyrrhizin is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatitis, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumour necrosis factor (TNF)-alpha is considered to play an important pathogenic role. However, the immunological interpretation of the transaminase-lowering action of glycyrrhizin is not known. Studies were performed to elucidate this action immunologically by assessing the effects of glycyrrhizin on immune-mediated cytotoxicity using an antigen-specific murine CD4+ T hybridoma line, which exhibits cytotoxicity against antigen-presenting cells after stimulation with specific antigen, and a murine TNF-alpha-sensitive fibroblast line. Glycyrrhizin inhibited the cytotoxic activity of the T cells against antigen-presenting cells and also suppressed TNF-alpha-induced cytotoxicity in the TNF-alpha-sensitive cell line in vitro. These results suggest that the decrease of elevated transaminase levels by glycyrrhizin in patients with chronic viral hepatitis is mediated in part by inhibition of immune-mediated cytotoxicity against hepatocytes.
Zeuzem S. [Glycyrrhizin for the treatment of allergic diseases and chronic hepatitis]. Dtsch Med Wochenschr 1998 Mar 20;123(12):372. [Article in German]
Zheng MS, Zhang YZ. [Anti-HBsAg herbs employing ELISA technique]. Chung Hsi I Chieh Ho Tsa Chih 1990 Sep;10(9):560-2, 518. [Article in Chinese]
Abstract: With the aid of the ELISA system this schema represented a laboratory approach to the recognition of anti-HBsAg capability of herbs by using 300 herbal extracts. Altogether 10 herbs (3.0%) were identified as effective. When forming a multiplex plan by employing 10 average P/N ratios as exemplified by 5 varying doses of herb (0.3, 0.6, 1.2, 2.5, 5.0 mg/100 microliters), 2 varying concentrations of HBsAg (10.92, 14.26 P/N ratio), and 3 varying contact time periods (immediate, 1h, 2h) for the comprehensive appraisal of herb efficacy index, these 10 effective herbs were listed in the following order: Prunella vulgaris (1.00), Litchi chinensis (1.26), Gossypium herbaceum (1.45), Cudrania cochinochinensis (1.56), Caesalpinia sappan (1.73), Oldenlandia tenelliflora (1.77), Cautis parthenocissus (1.99), Evodia rutaecarpa (2.01), Portulaca grandiflora (2.44), and Anemone hupehensis (2.83).