beta-hederin and Liver-Diseases

The pharmacological properties of Nigella sativa L. are well attributed to the presence of bioactive compounds, mainly, thymoquinone (TQ), thymol (THY) and α hederin and their antioxidant effects. TQ, THY and alpha-hederin (α-hederin) provide protection to liver from injury via different mechanisms including inhibition of iron-dependent lipid peroxidation, elevation in total thiol content and (GSH) level, radical scavenging, increasing the activity of quinone reductase, catalase, superoxide dismutase (SOD) and glutathione transferase (GST), inhibition of NF-κB activity and inhibition of both (COX) and (LOX) protects liver from injuries. Review and Conclusion: The main aim of this literature review is to reflect the relevant role of ROS in inducing hepatic diseases and also the preventive role of N. sativa L. in hepatic diseases. The present article is directed towards highlighting the beneficial contribution of researchers to explore the pharmacological actions with therapeutic potential of this precious natural herb and its bioactive compounds pertaining to the hepatoprotective effects. We systematically searched for research literature through well-framed review question and presented the data in the tabular forms for the convenience of the readers. Two hundred and forty-one papers were embodied in this review, oxidative effect and the reactive oxygen species (ROS) are known to be the major causes of many diseases such as hepatic cancer. Many drugs and chemicals have shown to incite oxidative damage by generation of ROS in the body. Therefore, this review intends to focus the role of ROS in liver diseases and the mechanisms through which N. sativa prevents hepatic diseases. The mechanisms by which N. sativa impede progression in chronic liver diseases should be used as a preventive medicine in patients with hepatic disorders.

Topics: Animals; Antioxidants; Benzoquinones; Humans; Lipid Peroxidation; Liver Diseases; Nigella sativa; Oleanolic Acid; Plant Extracts; Protective Agents; Reactive Oxygen Species; Saponins; Superoxide Dismutase

This study was designed to determine the protective effects of alpha-hederin on chemical-induced liver injury in CF-1 mice and to evaluate cytochrome P450 suppression by alpha-hederin as a means of protection. alpha-Hederin pretreatment (30 mumol/kg, sc x 3 days) protected mice from acetaminophen-, bromobenzene-, carbon tetrachloride-, furosemide-, and thioacetamide-induced liver injury, without affecting the hepatotoxicity of chloroform and dimethylnitrosamine. To examine the role of P450 in hepatoprotection by alpha-hederin, liver microsomes were prepared 24 hr following the last dose of alpha-hederin treatment (10 and 30 mumol/kg, sc x 3 days). Treatment of mice with alpha-hederin produced a dose-dependent suppression of liver cytochrome P450 (30-50%) and cytochrome b5 (20-30%) levels, as well as NADPH-cytochrome c reductase activity (15-25%). alpha-Hederin treatment also decreased the activities of P450 enzymes, such as 7-ethoxyresorufin O-dealkylation (65%), 7-pentoxyresorufin O-dealkylation (50%), coumarin 7-hydroxylation (40%), 7-ethoxycoumarin O-deethylation (45%), caffeine N3-demethylation (30-50%), chlorzoxazone 6-hydroxylation (35-55%), and the oxidation of testosterone to 2 alpha-, 6 alpha-, 15 alpha-, 15 beta-, 16 alpha-, 16 beta-, and 18/12 alpha-hydroxyltestosterone, androstenedione, and 6-dehydroxytestosterone (25-60%). Consistent with these observations, the levels of CYP1A, CYP2A, and CYP3A enzymes were also suppressed, as determined by immunoblotting with antibodies against rat P450 enzymes. These results demonstrate that treatment of mice with alpha-hederin decreases the levels and activities of several P450 enzymes. The suppression of P450 appears to be one of mechanisms by which alpha-hederin protects mice from the hepatotoxicity of some chemicals.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Antagonism; Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Drugs, Chinese Herbal; Liver Diseases; Male; Methylation; Mice; Microsomes, Liver; Oleanolic Acid; Saponins