Girish C, Koner B C, Jayanthi S, Rao K R, Rajesh B, Pradhan S C
Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India.
Indian J Med Res. 2009 May;129(5):569-78.
BACKGROUND & OBJECTIVE: Polyherbal formulations available with a wide range of indications like protective to liver, appetite and growth promoters, gastrointestinal and hepatic regulator, as treatment for hepatic dysfunction, for hepatic regeneration as well as liver stimulant and tonic. Despite the widespread use, there is a lack of scientific evidence on their efficacy and safety. This study was undertaken to evaluate the hepatoprotective activity of six commercially available formulations, namely Liv 52, Livergen, Livokin, Octogen, Stimuliv and Tefroliv in acute liver toxicity in mice model induced by paracetamol (PCM).
Swiss albino mice of either sex were used, divided in 28 groups with six in each group. The dose of the polyherbal formulations was calculated from human dose (20 ml/day) using a standard conversion table. They were given as pretreatment (2.60 ml/kg/day) for 7 days by oral route twice a day prior to PCM administration. Hepatotoxicity was induced by administering a single oral dose of PCM (500 mg/kg bw) on day 8. The study parameters were conducted on day 9. The biochemical parameters included liver enzyme levels alanine tranaminases (ALT), aspartate transaminases (AST) and alkaline phosphatase (ALP). The pharmacological and pathological parameters were phenobarbitone sleeping time and macroscopic and microscopic changes of liver tissues respectively.
PCM toxicity significantly increased ALT, AST and ALP (321.00 +/- 87.93, 273.17 +/- 45.68, 257.50 +/- 17.64 IU/l vs normal control, 33.33 +/- 0.61, 89.33 +/- 9.50, 152.17 +/- 11.40 IU/l respectively, P<0.05), prolonged phenobarbitone induced sleeping time (from 277.50 +/- 8.04 min to 335.83 +/- 7.00 min, P<0.05). When PCM higher dose (1g/kg p.o. single dose) was used, the liver tissue, in macroscopic appearance, showed extensive necrosis associated with haemorrhages. Low dose (500 mg/kg p.o. single dose) showed punctate haemorrhagic necrosis of liver tissue. In the microscopic studies, PCM induced toxicity showed haemorrhages, fatty changes and necrosis. The pretreatment in low doses (2.6 ml/kg/day) with liquid formulations of Liv 52 and Livergen reversed the PCM induced liver toxicity. At higher doses (5.2 ml/ kg/day), all the six herbal formulations conclusively showed marked beneficial effects in the studied pharmacological, biochemical and histological parameters.
INTERPRETATION & CONCLUSION: The present findings demonstrated the efficacy of polyherbal liquid formulations at two dose levels in PCM induced hepatotoxicity in mice. However, it suggests that a dose adjustment may be necessary to optimize the effects in clinical settings.
多种草药配方制剂具有广泛的适应证，如肝脏保护、食欲及生长促进、胃肠及肝脏调节、肝功能障碍治疗、肝脏再生以及肝脏刺激与滋补等。尽管其应用广泛，但关于其疗效和安全性缺乏科学证据。本研究旨在评估六种市售制剂，即利维52（Liv 52）、肝生源（Livergen）、利沃金（Livokin）、奥克托金（Octogen）、斯迪姆利夫（Stimuliv）和特弗罗利夫（Tefroliv）对扑热息痛（PCM）诱导的小鼠急性肝毒性的肝保护活性。
采用瑞士白化小鼠，雌雄不限，分为28组，每组6只。根据人体剂量（20 ml/天）使用标准换算表计算草药配方制剂的剂量。在给予PCM前，通过口服途径每天两次给予预处理剂量（2.60 ml/kg/天），持续7天。在第8天通过单次口服给予PCM（500 mg/kg体重）诱导肝毒性。在第9天进行研究参数测定。生化参数包括肝酶水平，即丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和碱性磷酸酶（ALP）。药理和病理参数分别为苯巴比妥睡眠时间以及肝脏组织的大体和显微镜下变化。
PCM毒性显著升高了ALT、AST和ALP水平（分别为321.00±87.93、273.17±45.68、257.50±17.64 IU/l，而正常对照组分别为33.33±0.61、89.33±9.50、152.17±11.40 IU/l，P<0.05），延长了苯巴比妥诱导的睡眠时间（从277.50±8.04分钟延长至335.83±7.00分钟，P<0.05）。当使用PCM高剂量（1 g/kg口服单剂量）时，肝脏组织大体外观显示广泛坏死并伴有出血。低剂量（500 mg/kg口服单剂量）显示肝脏组织点状出血性坏死。在显微镜研究中，PCM诱导的毒性表现为出血、脂肪变性和坏死。用利维52和肝生源的液体制剂进行低剂量（2.6 ml/kg/天）预处理可逆转PCM诱导的肝毒性。在高剂量（5.2 ml/kg/天）时，所有六种草药制剂在研究的药理、生化和组织学参数方面均显示出明显的有益作用。
本研究结果表明，两种剂量水平的草药液体制剂对PCM诱导的小鼠肝毒性具有疗效。然而，这表明在临床环境中可能需要调整剂量以优化效果。
