Evaluation of efficacy and safety of Liv.52 DS tablets in acute viral hepatitis:
A prospective, double-blind, randomized, placebo-controlled,
phase III clinical trial
Dr. Rajiv Baijal, M.D., D.N.B.1, Dr. Nikhil Patel, M.D.,2 and Dr. S. A. Kolhapure, M.D.3* 1Gastroenterologist, 2Research Associates, Department of Gastroenterology,
Jagjivanram Western Railway Hospital, Mumbai Central, Mumbai, India. 3Senior Medical Advisor, R&D Center, The Himalaya Drug Company, Bangalore, India
Liv.52 DS tablets in acute viral hepatitis
CONCLUSION
Viral hepatitis (A, B, C, D, E and G) is a global public health problem, which is responsible for a major chunk of morbidity and mortality. Viral hepatitis occurs endemically and sporadically throughout the world, depending on the endemicity of infection. The primary goal in management of acute viral hepatitis is the early renormalizations of hepatic functions with symptomatic and clinical recovery. There are no established drugs for hepatitis A, hepatitis E and hepatitis G; while the available treatment options for hepatitis B, hepatitis C and hepatitis D have various limitations such as dependable clinical efficacy, associated adverse effects and affordability issues. This study was planned to evaluate the efficacy and safety of Liv.52 DS tablets in acute viral hepatitis.
The enrolled patients in this study were suffering from different types of hepatitis (hepatitis A, hepatitis B, hepatitis E and hepatitis non A-E). This study observed a highly significant and rapid symptomatic improvement in the mean scores for loss of appetite, weight loss, fatigue and jaundice in Liv.52 DS group. There was a significant and rapid renormalization in the biochemical parameters of liver functions and the levels of SA, SG, and TP were renormalized. The increased level of ESR and WBC were significantly reduced in Liv.52 DS group. There were no clinically significant changes in the other biochemical parameters such as Hb levels and PC, which indicates excellent short- and long-term safety profile of Liv.52 DS. There were no clinically significant adverse effects, either observed or reported during the entire study period, and the overall compliance to the drug treatment was found to be excellent. Therefore, it may be concluded that, Liv.52 DS tablets are clinically effective and safe in the management of acute viral hepatitis.
References:
1. Krugman S, Ward R, Giles JP. The natural history of infectious hepatitis Am. J. Med. 1962; 32: 717-728
2. Simons JN, Pilot-Matias TJ, Leary TP, et al. Identification of two flavivirus-like genomes in the GB hepatitis agent. Proceedings of the National Academy of Sciences U.S.A. 1995; 92: 3401-3405.
3. Oshiba, Okamoto H, Mishiro S. Detection of the GBV-C hepatitis virus genome in serum from patients with fulminant hepatitis of unknown aetiology. Lancet 1995; 346: 1131-1132.
4. Ikawa T, Sugai Y, Okamoto H. Hepatitis G infection in drug abusers with chronic hepatitis C (letter). New Engl. J. Med. 1996; 334: 195-196.
5. Innen J, Wages J, Jr. Zhang-Keck et al. Molecular cloning and disease association of hepatitis G virus: A transfusion-transmissible agent. Science 1996; 271: 505-508.
6. Asuko K, Mitsui T, Iwano K, et al. Infection with hepatitis GB virus C in patients on maintenance hemodialysis. New Engl. J. Med. 1996; 334: 1485-1490.
7. Khanfar MA, Sabri SS, Zarga MH, Zeller KP. The chemical constituents of Capparis spinosa of Jordanian origin. Nat. Prod. Res. 2003; 17(1): 9-14
8. Gadgoli C, Mishra SH. Antihepatotoxic activity of p-methoxy benzoic acid from Capparis spinosa. J. Ethnopharmacol. 1999; 66(2): 187-192.
9. Al-Said MS, Abdelsattar EA, Khalifa SI, el-Feraly FS. Isolation and identification of an anti-inflammatory principle from Capparis spinosa. Pharmazie. 1988; 43(9): 640-641.
10. Ageel AM, Parmar NS, Mossa JS, Al-Yahya MA, Al-Said MS, Tariq M. Anti-inflammatory activity of some Saudi Arabian medicinal plants. Agents Actions 1986; 17(3-4): 383-384.
11.Bonina F, Puglia C, Ventura D, Aquino R, Tortora S, Sacchi A. et al. In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of Capparis spinosa L. buds. J. Cosmet. Sci. 2002; 53(6): 321-335.
12. Germano MP, De Pasquale R, D'Angelo V, Catania S, Silvari V, Costa C. Evaluation of extracts and isolated fraction from Capparis spinosa L. buds as an antioxidant source. J. Agric. Food Chem. 2002; 50(5): 1168-1171.
13.Mahasneh AM. Screening of some indigenous Qatari medicinal plants for antimicrobial activity. Phytother. Res. 2002; 16(8): 751-753.
14.Ali-Shtayeh MS, Abu Ghdeib SI. Antifungal activity of plant extracts against dermatophytes. Mycoses 1999; 42(11-12): 665-672.
15. He Y, Guo YJ, Gao YY. Studies on chemical constituents of root of Cichorium intybus. Zhongguo. Zhong. Yao. Za. Zhi. 2002; 27(3): 209-210.
16.Du H, Yuan S, Jiang P. Chemical constituents of Cichorium intybus L. Zhongguo. Zhong. Yao. Za. Zhi. 1998; 23(11): 682-683, 704.
17. Aktay G, Deliorman D, Ergun E, Ergun F, Yesilada E, Cevik C. Hepatoprotective effects of Turkish folk remedies on experimental liver injury. J. Ethnopharmacol. 2000; 73(1-2): 121-129.
18. Zafar R, Mujahid Ali S. Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L. J. Ethnopharmacol. 1998; 63(3): 227-231.
19. Ahmed B, Al-Howiriny TA, Siddiqui AB. Antihepatotoxic activity of seeds of Cichorium intybus. J. Ethnopharmacol. 2003; 87(2-3): 237-240.
20. Mun JH, Woo YJ, Jeon WH, An NH, Park JS. Effects of the ethanol extract of Cichorium intybus on the immunotoxicity by ethanol in mice. Int. Immunopharmacol. 2002; 2(6): 733-744.
21. Sultana S, Perwaiz S, Iqbal M, Athar M. Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus inhibit free radical-mediated DNA damage. J. Ethnopharmacol. 1995; 45(3): 189-192.
22. El SN, Karakaya S. Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet. Int. J. Food Sci. Nutr. 2004; 55(1): 67-74.
23. Papetti A, Daglia M, Gazzani G. Anti- and pro-oxidant activity of water soluble compounds in Cichorium intybus var. silvestre (Treviso red chicory). J. Pharm. Biomed. Anal. 2002; 30(4): 939-945.
24. Gurbuz I, Ustun O, Yesilada E, Sezik E, Akyurek N. In vivo gastroprotective effects of five Turkish folk remedies against ethanol-induced lesions. J. Ethnopharmacol. 2002; 83(3): 241-244.
25. Amirghofran Z, Azadbakht M, Karimi MH. Evaluation of the immunomodulatory effects of five herbal plants. J. Ethnopharmacol. 2000; 72(1-2): 167-172.
26. Kim HM, Kim HW, Lyu YS, Won JH, Kim DK, Lee YM. et al. Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus. Pharmacol. Res. 1999; 40(1): 61-65.
27. Ikeda T, Tsumagari H, Nohara T. Steroidal oligoglycosides from Solanum nigrum. Chem. Pharm. Bull. (Tokyo) 2000; 48(7): 1062-1064.
28. Raju K, Anbuganapathi G, Gokulakrishnan V, Rajkapoor B, Jayakar B, Manian S. Effect of dried fruits of Solanum nigrum LINN against CCl4-induced hepatic damage in rats. Biol. Pharm. Bull. 2003; 26(11): 1618- 1619.
29. Moundipa PF, Domngang FM. Effect of the leafy vegetable Solanum nigrum on the activities of some liver drug-metabolising enzymes after aflatoxin B1 treatment in female rats. Br. J. Nutr. 1991; 65(1): 81-91.
30. Son YO, Kim J, Lim JC, Chung Y, Chung GH, Lee JC. Ripe fruit of Solanum nigrum L. inhibits cell growth and induces apoptosis in MCF-7 cells. Food Chem. Toxicol. 2003; 41(10): 1421-1428.
31. Prashanth Kumar V, Shashidhara S, Kumar MM, Sridhara BY. Cytoprotective role of Solanum nigrum against gentamicin-induced kidney cell (Vero cells) damage in vitro. Fitoterapia 2001; 72(5): 481-486.
32. Akhtar MS, Munir M. Evaluation of the gastric antiulcerogenic effects of Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats. J. Ethnopharmacol. 1989; 27(1-2): 163-176.
33. Qureshi S, Rai MK, Agrawal SC. In vitro evaluation of inhibitory nature of extracts of 18-plant species of Chhindwara against 3-keratinophilic fungi. Hindustan Antibiot. Bull. 1997; 39(1-4): 56-60.
34. Upadhyay RK, Pandey MB, Jha RN, Singh VP, Pandey VB. Triterpene glycoside from Terminalia arjuna. J. Asian. Nat. Prod. Res. 2001; 3(3): 207-212.
35. Munasinghe TC, Seneviratne CK, Thabrew MI, Abeysekera AM. Antiradical and antilipoperoxidative effects of some plant extracts used by Sri Lankan traditional medical practitioners for cardioprotection. Phytother. Res. 2001; 15(6): 519-523.
36. Ali A, Kaur G, Hayat K, Ali M, Ather M. A novel naphthanol glycoside from Terminalia arjuna with antioxidant and nitric oxide inhibitory activities. Pharmazie. 2003; 58(12): 932-934.
37. Ali A, Kaur G, Hamid H, Abdullah T, Ali M, Niwa M. et al. Terminoside A, a new triterpene glycoside from the bark of Terminalia arjuna inhibits nitric oxide production in murine macrophages. J. Asian. Nat. Prod. Res. 2003; 5(2): 137-142.
38. Cheng HY, Lin CC, Lin TC. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral. Res. 2002; 55(3): 447-455.
39. Perumal Samy R, Ignacimuthu S., Sen A. Screening of 34 Indian medicinal plants for antibacterial properties. J. Ethnopharmacol. 1998; 62(2): 173-182.
40. Jafri MA, Jalis Subhani M, Javed K, Singh S. Hepatoprotective activity of leaves of Cassia occidentalis against paracetamol and ethyl alcohol intoxication in rats. J. Ethnopharmacol. 1999; 66(3): 355-361.
41. Bin-Hafeez B, Ahmad I, Haque R, Raisuddin S. Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice. J. Ethnopharmacol.
2001; 75(1): 13-18.
42. Samy RP, Ignacimuthu S. Antibacterial activity of some folklore medicinal plants used by tribals in Western Ghats of India. J. Ethnopharmacol. 2000; 69(1): 63-71.
43. Perez C, Anesini C. In vitro antibacterial activity of Argentine folk medicinal plants against Salmonella typhi. J. Ethnopharmacol. 1994; 44(1): 41-46.
44. Tona L, Ngimbi NP, Tsakala M, Mesia K, Cimanga K, Apers S et al. Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa, Congo. J. Ethnopharmacol. 1999; 68(1-3): 193-203.
45. Caceres A, Lopez B, Juarez X, del Aguila J, Garcia S. Evaluation of antifungal activity of seven American plants. J. Ethnopharmacol. 1993; 40(3): 207-213.
46. Graham JG, Zhang H, Pendland SL, Santarsiero BD, Mesecar AD, Cabieses F. et al. Antimycobacterial Naphthopyrones from Senna obliqua. J. Nat. Prod. 2004; 67(2): 225-227.
47. Harnyk TP. The use of preparations of plant origin in treating and rehabilitating elderly patients with chronic hepatitis. Lik. Sprava. 1999; (7-8): 168-170.
48. Krivenko VV, Potebnia GP, Loiko VV. Experience in treating digestive organ diseases with medicinal plants. Vrach. Delo. 1989; (3): 76-78.
49. Lin LT, Liu LT, Chiang LC, Lin CC. In vitro anti-hepatoma activity of fifteen natural medicines from Canada. Phytother. Res. 2002; 16(5): 440-444.
50. Candan F, Unlu M, Tepe B, Daferera D, Polissiou M, Sokmen A. et al. Antioxidant and antimicrobial activity of the essential oil and methanol extracts of Achillea millefolium Subsp. millefolium Afan. (Asteraceae). J. Ethnopharmacol. 2003; 87(2-3): 215-220.
51. Bezic N, Skocibusic M, Dunkic V, Radonic A. Composition and antimicrobial activity of Achillea clavennae L. essential oil. Phytother. Res. 2003; 17(9): 1037-1040.
52. Devarshi P, Kanase A, Kanase R, Mane S, Patil S, Varute AT. Effect of Mandura bhasma on lipolytic activities of liver, kidney and adipose tissue of albino rat during CCl4-induced hepatic injury. J. Biosciences. 1986; 10(2): 227-234.
Viral hepatitis (A, B, C, D, E and G) is a global public health problem, which is responsible for a major chunk of morbidity and mortality. Viral hepatitis occurs endemically and sporadically throughout the world, depending on the endemicity of infection. The primary goal in management of acute viral hepatitis is the early renormalizations of hepatic functions with symptomatic and clinical recovery. There are no established drugs for hepatitis A, hepatitis E and hepatitis G; while the available treatment options for hepatitis B, hepatitis C and hepatitis D have various limitations such as dependable clinical efficacy, associated adverse effects and affordability issues. This study was planned to evaluate the efficacy and safety of Liv.52 DS tablets in acute viral hepatitis.
The enrolled patients in this study were suffering from different types of hepatitis (hepatitis A, hepatitis B, hepatitis E and hepatitis non A-E). This study observed a highly significant and rapid symptomatic improvement in the mean scores for loss of appetite, weight loss, fatigue and jaundice in Liv.52 DS group. There was a significant and rapid renormalization in the biochemical parameters of liver functions and the levels of SA, SG, and TP were renormalized. The increased level of ESR and WBC were significantly reduced in Liv.52 DS group. There were no clinically significant changes in the other biochemical parameters such as Hb levels and PC, which indicates excellent short- and long-term safety profile of Liv.52 DS. There were no clinically significant adverse effects, either observed or reported during the entire study period, and the overall compliance to the drug treatment was found to be excellent. Therefore, it may be concluded that, Liv.52 DS tablets are clinically effective and safe in the management of acute viral hepatitis.
1. Krugman S, Ward R, Giles JP. The natural history of infectious hepatitis Am. J. Med. 1962; 32: 717-728
2. Simons JN, Pilot-Matias TJ, Leary TP, et al. Identification of two flavivirus-like genomes in the GB hepatitis agent. Proceedings of the National Academy of Sciences U.S.A. 1995; 92: 3401-3405.
3. Oshiba, Okamoto H, Mishiro S. Detection of the GBV-C hepatitis virus genome in serum from patients with fulminant hepatitis of unknown aetiology. Lancet 1995; 346: 1131-1132.
4. Ikawa T, Sugai Y, Okamoto H. Hepatitis G infection in drug abusers with chronic hepatitis C (letter). New Engl. J. Med. 1996; 334: 195-196.
5. Innen J, Wages J, Jr. Zhang-Keck et al. Molecular cloning and disease association of hepatitis G virus: A transfusion-transmissible agent. Science 1996; 271: 505-508.
6. Asuko K, Mitsui T, Iwano K, et al. Infection with hepatitis GB virus C in patients on maintenance hemodialysis. New Engl. J. Med. 1996; 334: 1485-1490.
7. Khanfar MA, Sabri SS, Zarga MH, Zeller KP. The chemical constituents of Capparis spinosa of Jordanian origin. Nat. Prod. Res. 2003; 17(1): 9-14
8. Gadgoli C, Mishra SH. Antihepatotoxic activity of p-methoxy benzoic acid from Capparis spinosa. J. Ethnopharmacol. 1999; 66(2): 187-192.
9. Al-Said MS, Abdelsattar EA, Khalifa SI, el-Feraly FS. Isolation and identification of an anti-inflammatory principle from Capparis spinosa. Pharmazie. 1988; 43(9): 640-641.
10. Ageel AM, Parmar NS, Mossa JS, Al-Yahya MA, Al-Said MS, Tariq M. Anti-inflammatory activity of some Saudi Arabian medicinal plants. Agents Actions 1986; 17(3-4): 383-384.
11.Bonina F, Puglia C, Ventura D, Aquino R, Tortora S, Sacchi A. et al. In vitro antioxidant and in vivo photoprotective effects of a lyophilized extract of Capparis spinosa L. buds. J. Cosmet. Sci. 2002; 53(6): 321-335.
12. Germano MP, De Pasquale R, D'Angelo V, Catania S, Silvari V, Costa C. Evaluation of extracts and isolated fraction from Capparis spinosa L. buds as an antioxidant source. J. Agric. Food Chem. 2002; 50(5): 1168-1171.
13.Mahasneh AM. Screening of some indigenous Qatari medicinal plants for antimicrobial activity. Phytother. Res. 2002; 16(8): 751-753.
14.Ali-Shtayeh MS, Abu Ghdeib SI. Antifungal activity of plant extracts against dermatophytes. Mycoses 1999; 42(11-12): 665-672.
15. He Y, Guo YJ, Gao YY. Studies on chemical constituents of root of Cichorium intybus. Zhongguo. Zhong. Yao. Za. Zhi. 2002; 27(3): 209-210.
16.Du H, Yuan S, Jiang P. Chemical constituents of Cichorium intybus L. Zhongguo. Zhong. Yao. Za. Zhi. 1998; 23(11): 682-683, 704.
17. Aktay G, Deliorman D, Ergun E, Ergun F, Yesilada E, Cevik C. Hepatoprotective effects of Turkish folk remedies on experimental liver injury. J. Ethnopharmacol. 2000; 73(1-2): 121-129.
18. Zafar R, Mujahid Ali S. Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L. J. Ethnopharmacol. 1998; 63(3): 227-231.
19. Ahmed B, Al-Howiriny TA, Siddiqui AB. Antihepatotoxic activity of seeds of Cichorium intybus. J. Ethnopharmacol. 2003; 87(2-3): 237-240.
20. Mun JH, Woo YJ, Jeon WH, An NH, Park JS. Effects of the ethanol extract of Cichorium intybus on the immunotoxicity by ethanol in mice. Int. Immunopharmacol. 2002; 2(6): 733-744.
21. Sultana S, Perwaiz S, Iqbal M, Athar M. Crude extracts of hepatoprotective plants, Solanum nigrum and Cichorium intybus inhibit free radical-mediated DNA damage. J. Ethnopharmacol. 1995; 45(3): 189-192.
22. El SN, Karakaya S. Radical scavenging and iron-chelating activities of some greens used as traditional dishes in Mediterranean diet. Int. J. Food Sci. Nutr. 2004; 55(1): 67-74.
23. Papetti A, Daglia M, Gazzani G. Anti- and pro-oxidant activity of water soluble compounds in Cichorium intybus var. silvestre (Treviso red chicory). J. Pharm. Biomed. Anal. 2002; 30(4): 939-945.
24. Gurbuz I, Ustun O, Yesilada E, Sezik E, Akyurek N. In vivo gastroprotective effects of five Turkish folk remedies against ethanol-induced lesions. J. Ethnopharmacol. 2002; 83(3): 241-244.
25. Amirghofran Z, Azadbakht M, Karimi MH. Evaluation of the immunomodulatory effects of five herbal plants. J. Ethnopharmacol. 2000; 72(1-2): 167-172.
26. Kim HM, Kim HW, Lyu YS, Won JH, Kim DK, Lee YM. et al. Inhibitory effect of mast cell-mediated immediate-type allergic reactions by Cichorium intybus. Pharmacol. Res. 1999; 40(1): 61-65.
27. Ikeda T, Tsumagari H, Nohara T. Steroidal oligoglycosides from Solanum nigrum. Chem. Pharm. Bull. (Tokyo) 2000; 48(7): 1062-1064.
29. Moundipa PF, Domngang FM. Effect of the leafy vegetable Solanum nigrum on the activities of some liver drug-metabolising enzymes after aflatoxin B1 treatment in female rats. Br. J. Nutr. 1991; 65(1): 81-91.
30. Son YO, Kim J, Lim JC, Chung Y, Chung GH, Lee JC. Ripe fruit of Solanum nigrum L. inhibits cell growth and induces apoptosis in MCF-7 cells. Food Chem. Toxicol. 2003; 41(10): 1421-1428.
31. Prashanth Kumar V, Shashidhara S, Kumar MM, Sridhara BY. Cytoprotective role of Solanum nigrum against gentamicin-induced kidney cell (Vero cells) damage in vitro. Fitoterapia 2001; 72(5): 481-486.
32. Akhtar MS, Munir M. Evaluation of the gastric antiulcerogenic effects of Solanum nigrum, Brassica oleracea and Ocimum basilicum in rats. J. Ethnopharmacol. 1989; 27(1-2): 163-176.
33. Qureshi S, Rai MK, Agrawal SC. In vitro evaluation of inhibitory nature of extracts of 18-plant species of Chhindwara against 3-keratinophilic fungi. Hindustan Antibiot. Bull. 1997; 39(1-4): 56-60.
34. Upadhyay RK, Pandey MB, Jha RN, Singh VP, Pandey VB. Triterpene glycoside from Terminalia arjuna. J. Asian. Nat. Prod. Res. 2001; 3(3): 207-212.
35. Munasinghe TC, Seneviratne CK, Thabrew MI, Abeysekera AM. Antiradical and antilipoperoxidative effects of some plant extracts used by Sri Lankan traditional medical practitioners for cardioprotection. Phytother. Res. 2001; 15(6): 519-523.
36. Ali A, Kaur G, Hayat K, Ali M, Ather M. A novel naphthanol glycoside from Terminalia arjuna with antioxidant and nitric oxide inhibitory activities. Pharmazie. 2003; 58(12): 932-934.
37. Ali A, Kaur G, Hamid H, Abdullah T, Ali M, Niwa M. et al. Terminoside A, a new triterpene glycoside from the bark of Terminalia arjuna inhibits nitric oxide production in murine macrophages. J. Asian. Nat. Prod. Res. 2003; 5(2): 137-142.
38. Cheng HY, Lin CC, Lin TC. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral. Res. 2002; 55(3): 447-455.
39. Perumal Samy R, Ignacimuthu S., Sen A. Screening of 34 Indian medicinal plants for antibacterial properties. J. Ethnopharmacol. 1998; 62(2): 173-182.
40. Jafri MA, Jalis Subhani M, Javed K, Singh S. Hepatoprotective activity of leaves of Cassia occidentalis against paracetamol and ethyl alcohol intoxication in rats. J. Ethnopharmacol. 1999; 66(3): 355-361.
41. Bin-Hafeez B, Ahmad I, Haque R, Raisuddin S. Protective effect of Cassia occidentalis L. on cyclophosphamide-induced suppression of humoral immunity in mice. J. Ethnopharmacol.
2001; 75(1): 13-18.
42. Samy RP, Ignacimuthu S. Antibacterial activity of some folklore medicinal plants used by tribals in Western Ghats of India. J. Ethnopharmacol. 2000; 69(1): 63-71.
43. Perez C, Anesini C. In vitro antibacterial activity of Argentine folk medicinal plants against Salmonella typhi. J. Ethnopharmacol. 1994; 44(1): 41-46.
44. Tona L, Ngimbi NP, Tsakala M, Mesia K, Cimanga K, Apers S et al. Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa, Congo. J. Ethnopharmacol. 1999; 68(1-3): 193-203.
45. Caceres A, Lopez B, Juarez X, del Aguila J, Garcia S. Evaluation of antifungal activity of seven American plants. J. Ethnopharmacol. 1993; 40(3): 207-213.
46. Graham JG, Zhang H, Pendland SL, Santarsiero BD, Mesecar AD, Cabieses F. et al. Antimycobacterial Naphthopyrones from Senna obliqua. J. Nat. Prod. 2004; 67(2): 225-227.
47. Harnyk TP. The use of preparations of plant origin in treating and rehabilitating elderly patients with chronic hepatitis. Lik. Sprava. 1999; (7-8): 168-170.
48. Krivenko VV, Potebnia GP, Loiko VV. Experience in treating digestive organ diseases with medicinal plants. Vrach. Delo. 1989; (3): 76-78.
49. Lin LT, Liu LT, Chiang LC, Lin CC. In vitro anti-hepatoma activity of fifteen natural medicines from Canada. Phytother. Res. 2002; 16(5): 440-444.
50. Candan F, Unlu M, Tepe B, Daferera D, Polissiou M, Sokmen A. et al. Antioxidant and antimicrobial activity of the essential oil and methanol extracts of Achillea millefolium Subsp. millefolium Afan. (Asteraceae). J. Ethnopharmacol. 2003; 87(2-3): 215-220.
51. Bezic N, Skocibusic M, Dunkic V, Radonic A. Composition and antimicrobial activity of Achillea clavennae L. essential oil. Phytother. Res. 2003; 17(9): 1037-1040.
52. Devarshi P, Kanase A, Kanase R, Mane S, Patil S, Varute AT. Effect of Mandura bhasma on lipolytic activities of liver, kidney and adipose tissue of albino rat during CCl4-induced hepatic injury. J. Biosciences. 1986; 10(2): 227-234.
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