Hepatotoxicity or Hepatoprotection? Pattern Recognition for the Paradoxical Effect of the Chinese Herb Rheum palmatum L. in Treating Rat Liver Injury

Abstract

The hepatotoxicity of some Chinese herbs has been a cause for concern in recent years. However, some herbs, such as rhubarb, have been documented as having both therapeutic and toxic effects on the liver, leading to the complex problem of distinguishing the benefits from the risks of using this herb. To comparatively analyze the dose-response relationship between rhubarb and hepatic health, we administrated total rhubarb extract(RE) to normal and carbon tetrachloride(CCl4)-treated rats for 12 weeks at 4 dosage levels(2.00, 5.40, 14.69 and 40.00 g·kg−1, measured as the quantity of crude material), followed by biochemical and histopathological tests of the rats' livers. A composite pattern was extracted by factor analysis, using all the biochemical indices as variables, into a visual representation of two mathematically obtained factors, which could be interpreted as the fibrosis factor and the cellular injury factor, according to the values of the variable loadings. The curative effect of administering the two lowest dosages of RE to CCl4-treated rats was mainly expressed as a decrease in the extent of cellular injury. The hepatoprotective mechanism of RE might be related to its antioxidant effect, the antagonism of the free radical damage to hepatocytes caused by CCl4. By contrast, the RE-induced liver damage was mainly expressed as a significant increase in the amount of fibrosis in both normal rats at all dosage levels and CCl4-treated rats at the two highest dosage levels. Therefore, the hepatotoxic potential of RE could be attributable to the liver cell fibrosis induced by high doses of the herb. This study illustrates the bidirectional potential of rhubarb and demonstrates the feasibility of using factor analysis to study the dose-response relationships between herbal medicines and hepatotoxicity or the healing effects of these herbs by extracting the underlying interrelationships among a number of functional bio-indices in a holistic manner.

Oleanolic acid alters bile acid metabolism and produces cholestatic liver injury in mice

“…However, “hepatoprotective” herbs such as rhubarb, have been documented as having both therapeutic and toxic effects to the liver, leading to a complex situation of distinguishing benefits from risks (Wang et al, 2011). OA and its derivatives have been shown to produce both hepatoprotective and hepatotoxic effects in cultured rat hepatocytes (Kinjo et al, 1999).…”

Enhancement of rhubarb extract solubility and bioactivity by 2-hydroxypropyl-β-cyclodextrin

“…Rhubarb is widely used as a laxative or a liver cleanser in the treatment of indigestion and jaundice (Fang et al, 2011;Fok, 2001;Tsai, Tsai, & Chang, 2004;Wang et al, 2011;Yu et al, 2005). The major components of the ethanolic extract of rhubarb include anthraquinone derivatives such as emodin, chrysophanol, rhein, aloe-emodin, and physicione and are shown in Fig.…”

“…To the best of our knowledge, there is no standard condition for extraction. We used alcohol to extract rhubarb, because alcohol has been reported as the solvent for extraction of rhubarb for bioactivity study (Fang et al, 2011;He, He, Ma, & But, 2009;Ngoc et al, 2008;Tsai et al, 2004;Wang et al, 2011) and is less toxic than other organic solvents.…”

Evaluation of Antioxidant and Hepatoprotective Effects of Dendrophthoe pentranda Leaves on CCl4 -Induced Hepatotoxic Rat

“…Then it is biotransformed to the trichloromethyl free radical (NCCl 3 * ) and further converted to a peroxy radical (CCl 3 O 2 N * ). This conversion takes place in the liver by the help of cytochrome P450 (CYP2E1) of endoplasmic reticulum (Sahil et al, 2013;Wang et al, 2011). These radicals lead to auto-oxidation of cellular lipids and proteins, and thereby induce cellular damage and generate some endogenous toxicants.…”