Hepatoprotective effects of Yulangsan polysaccharide against nimesulide-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Yulangsan polysaccharide (YLSPS) is often used in popular folk medicine in the Guangxi Zhuang Autonomous Region of China as a chief ingredient of Millettia pulchra, which is used as a hepatic protection, anti-aging and memory improving agent. AIM OF THE STUDY: This study was designed to investigate the protective effects of polysaccharides from Millettia pulchra Kurz var.laxior (Dunn) (Yulangsan polysaecharide, YLSPS) against nimesulide-induced hepatotoxicities in mice. MATERIALS AND METHODS: Liver injury was induced in mice by administering nimesulide. Simultaneously, YLSPS was administered 2h prior to the administration of nimesulide. Dimethyl diphenyl bicarboxylate (DDB) was used as a reference drug. RESULTS: Compared with the nimesulide group, YLSPS significantly decreased the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and the content of bilirubin in the serum. The anti-oxidative effect of YLSPS was observed from the increase of the superoxide dismutase (SOD) and catalase and glutathione peroxidase (GSH-Px) activities in the liver, both of which were decreased by nimesulide. Moreover, the content of malondialdehyde (MDA) was reduced, and histological findings also confirmed the anti-hepatotoxic activity. In addition, YLSPS significantly inhibited proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6). Additionally, YLSPS also enhanced the mitochondrial antioxidant and inhibited dead cells by preventing the down-regulation of Bcl-2, up-regulation and release of Bax along with caspase 9 and 3 activity, confirming the involvement of mitochondria in the nimesulide-induced apoptosis. CONCLUSION: The protective effect of YLSPS against nimesulide-induced hepatic injury may rely on its ability to reduce oxidative stress and prevent nimesulide-induced hepatotoxicity by inhibiting critical control points of apoptosis.

Antihepatotoxic effect of tadehaginoside, extracted from Tadehagi triquetrum (L.), against CCl4-lesioned rats through activating the Nrf2 signaling pathway and attenuating the inflammatory response.

Recently, an increasing number of studies suggest that oxidative stress and inflammation are associated with hepatocellular injuries. Thus, we aimed to evaluate the potential hepatoprotective role of tadehaginoside (TA) on liver lesions induced by carbon tetrachloride (CCl4). The results in vitro suggested that TA dose-dependently suppressed the cell proliferation of HepG2 cells, whereas the phosphorylated level of IκBα in cells was effectively inactivated. The study in vivo showed that TA significantly lowered the serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), immunoglobulin E (IgE), and leukotriene (LT) in CCl4-lesioned rats. Pathological examination indicated that CCl4-induced hepatocellular damage was effectively mitigated by TA treatment. Meanwhile, the contents of γ-glutamylcysteine synthetase (γ-GCS), glutathione (GSH), and catalase (CAT) in liver tissue were gradually elevated. In addition, cytochrome c oxidase (COX) mRNA expression in hepatocytes was markedly upregulated, and nuclear factor E2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keapl) levels were progressively increased. Furthermore, the tumor necrosis factor alpha (TNF-α) and nuclear factor-kappa B (NF-κB)-expressed protein were downregulated. These findings demonstrate that tadehaginoside effectively protects against CCl4-induced oxidative injury and inflammatory reaction in hepatocytes, in which the underlying mechanisms are involved in activating the Nrf2 signaling pathway and inhibiting the NF-κB pathway, thereby attenuating oxidative stress and reducing the inflammation in liver cells.

Beneficial effects of asiaticoside on cognitive deficits in senescence-accelerated mice.

The effect of asiaticoside isolated from Hydrocotyle sibthorpioides (AHS) on the promotion of cognition in senescence-accelerated mice (SAMP) was evaluated. Six-month old male SAMP8 mice were orally administered 20, 40 or 80 mg/kg AHS daily for three months. SAMR1 mice were used as a "normal aging" control. The results showed that treatment with AHS significantly improved learning and memory abilities in behavioral tests. AHS-treated mice showed higher antioxidant enzyme activity and lower lipid oxidation in serum compared with untreated SAMP8 mice. Mechanistically, studies showed that AHS markedly reduced the content and deposition of ß-amyloid peptide (Aß) by inhibiting the expression of mRNA for amyloid protein precursor, ß-site amyloid cleaving enzyme-1 and cathepsin B and promoting the expression of mRNA for neprilysin and insulin degrading enzyme. In addition, AHS significantly increased the expression of plasticity-related proteins including postsynaptic density-95, phosphor-N-methyl-D-aspartate receptor 1, phospho-calcium-calmodulin dependent kinase II, phospho-protein kinase A Catalyticß subunit, protein kinase Cγ subunit, phospho-CREB and brain derived neurotrophic factor. Furthermore, AHS increased the levels of acetylcholine (Ach), but decreased cholinesterase (AchE) activity. These results demonstrated that AHS administration may prevent spatial learning and memory decline by scavenging free radicals, up-regulating the activity of antioxidant enzymes, decreasing the level of Aß, ameliorating dysfunction in synaptic plasticity, and reversing abnormal changes in Ach level and AchE activity. Thus, AHS should be developed as a new drug to prevent age-related cognitive deficits.