Abstract
This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson’s Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells.
Highlights
The liver is the largest internal organ in vertebrates, including humans
Hepatic fibrosis arises from perpetual wound-healing, which results in abnormal production and accumulation of connective tissue and leads to liver cirrhosis [2]
Acute Toxicity Analysis Animals pretreated with 2500 mg/kg ELAP or vehicle were observed for 14 days
Summary
The liver is the largest internal organ in vertebrates, including humans. It is vital to survival, as it is the key organ of metabolism and excretion, and supports every other organ. Hepatic fibrosis arises from perpetual wound-healing, which results in abnormal production and accumulation of connective tissue and leads to liver cirrhosis [2]. The rate of fibrosis progression is reported to depend on the cause of liver disease, host, and environmental factors. Liver cirrhosis has a high global prevalence. It is the end-stage of most liver pathologies and leads to chronic liver dysfunction, altered metabolism, and death [1]. Medicinal plants reported to possess hepatoprotective activity include Vitex negundo [4], Boesenbergia rotunda [5], Phyllanthus niruri [6], Ipomoea aquatic [7], Orthosiphon stamineus [8], Zingiber officinale [9], and Caesalpinia sappan [10]
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