ABSTRACT
Protective effect of protodioscin or methyl protodioscin against inflammation had been reported in various inflammation diseases. This study aimed to investigate the effect of protodioscin against Complete Freund's adjuvant (CFA)-induced arthritis rats. Rats randomly divided into model groups were injected with CFA, companied with different dose of protodioscin (50, 100, and 200 mg/kg body weight). The histology, changes in biochemical parameters and inflammatory cytokines expression were detected for anti-inflammation effect evaluation of protodioscin. CFA treatment induced arthritic rats with swelling paw, ankle inflammation, and area of lymphocyte infiltration, upregulated inflammatory cytokines (IL-1ß, TNF-α, cyclo-oxygenase 2, and IL-6 as well as prostaglandin E2), articular elastase, myeloperoxidase, lipid peroxidase and nitrite oxide levels, downregulated glutathione, catalase, and superoxide dismutase. In contrast, protodioscin ameliorated all the changes induced by CFA in rats, suggesting the anti-inflammatory effect of protodioscin. We concluded that protodioscin administration into CFA-induced arthritis rats protected against CFA-induced oxidative stress, neutrophil infiltration, and inflammation, suggesting the anti-inflammatory effect and the therapeutic potential of protodioscin for arthritis.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Arthritis, Experimental/drug therapy , Diosgenin/analogs & derivatives , Edema/drug therapy , Gene Expression Regulation/drug effects , Saponins/pharmacology , Animals , Apoptosis/drug effects , Arthritis, Experimental/chemically induced , Arthritis, Experimental/genetics , Arthritis, Experimental/pathology , Catalase/genetics , Catalase/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Dinoprostone/metabolism , Diosgenin/pharmacology , Dose-Response Relationship, Drug , Edema/chemically induced , Edema/genetics , Edema/pathology , Freund's Adjuvant/administration & dosage , Glutathione/metabolism , Hindlimb , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Male , Nitric Oxide/metabolism , Oxidative Stress , Pancreatic Elastase/genetics , Pancreatic Elastase/metabolism , Peroxidase/genetics , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
A new neolignan, (R)-( - )-sassarandainol (1), together with 10 known compounds (2-11), was isolated from the stem of Sassafras randaiense. The structures were determined by spectroscopic techniques. Among these isolates, γ-tocopherol (5), subamolide B (7) and ß-sitosterone (9) exhibited moderate iNOS inhibitory activity on nitrite production induced (%) value of 30.51, 28.68 and 16.96, respectively.
Subject(s)
Anti-Inflammatory Agents/chemistry , Lignans/chemistry , Plant Stems/chemistry , Sassafras/chemistry , 4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/chemistry , 4-Butyrolactone/isolation & purification , Animals , Anti-Inflammatory Agents/isolation & purification , Cell Line , Lignans/isolation & purification , Mice , Molecular Structure , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitrites/metabolism , Sitosterols , gamma-Tocopherol/chemistry , gamma-Tocopherol/isolation & purificationABSTRACT
BACKGROUND: Ginsenosides, the major bioactive compounds in ginseng root, have been found to have antioxidant, immunomodulatory and anti-inflammatory activities. This study investigated the effects of ginsenosides on carbon tetrachloride (CCl4)-induced hepatitis and liver fibrosis in rats. METHODS: Male Sprague-Dawley rats were randomly divided into four groups: control, CCl4, CCl4 + 0.5 g/kg Panax ginseng extract and CCl4 + 0.05 g/kg ginsenoside Rb1 groups. The treated groups were orally given Panax ginseng extract or ginsenoside Rb1 two weeks before the induction of liver injury for successive 9 weeks. Liver injury was induced by intraperitoneally injected with 400 ml/l CCl4 at a dose of 0.75 ml/kg body weight weekly for 7 weeks. The control group was intraperitoneally injected with olive oil. RESULTS: The pathological results showed that ginsenoside Rb1 decreased hepatic fat deposition (2.65 ± 0.82 vs 3.50 ± 0.75, p <0.05) and Panax ginseng extract lowered hepatic reticular fiber accumulation (1.05 ± 0.44 vs 1.60 ± 0.39, p <0.01) increased by CCl4. Plasma alanine aminotransferase and aspartate aminotransferase activities were increased by CCl4 (p <0.01), and aspartate aminotransferase activity was decreased by Panax ginseng extract at week 9 (p <0.05). Exposure to CCl4 for 7 weeks, the levels of plasma and hepatic triglycerides (p <0.01), hepatic cholesterol (p <0.01), interleukin-1ß (p <0.01), prostaglandin E2 (p <0.05), soluble intercellular adhesion molecule-1 (p <0.05), hydroxyproline (p <0.05), matrix metalloproteinase-2 (p <0.05) and tissue inhibitor of metalloproteinase-1 (TIMP-1) (p <0.01) were elevated, however, hepatic interleukin-10 level was lowered (p <0.05). Both Panax ginseng extract and ginsenoside Rb1 decreased plasma and hepatic triglyceride, hepatic prostaglandin E2, hydroxyproline and TIMP-1 levels, and Panax ginseng extract further inhibited interleukin-1ß concentrations (p <0.05). CONCLUSIONS: Panax ginseng extract and ginsenoside Rb1 attenuate plasma aminotransferase activities and liver inflammation to inhibit CCl4-induced liver fibrosis through down-regulation of hepatic prostaglandin E2 and TIMP-1.
