OBJECTIVE:To examine the anti-fatigue function of anwulignan from Schisandra and its underlying mechanism.

METHODS:After an excessive fatigue mouse model was created, anwulignan was administered to the mice, and its effect on exercise tolerance was studied by the weight-bearing swimming test, rotarod test, grip strength test, and tail suspension test. The biochemical indicators closely related to fatigue, including blood urea nitrogen (BUN), lactic acid (LD), lactate dehydrogenase (LDH), and creatine kinase (CK) in the serum; liver glycogen (LG) in the liver tissue; muscle glycogen (MG); inorganic phosphate (Pi) and Annexin V in the gastrocnemius; superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities; malondialdehyde (MDA), catalase (CAT), and thiobarbituric acid reactive substances (TBARS); and the 8-hydroxy-2-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) content in both serum and the gastrocnemius were detected. Morphological changes were also observed. The anti-fatigue-related proteins of the NRF2/ARE, Bcl2, and PGC-1α pathways in the gastrocnemius of the mice were detected by western blot.

RESULTS:Anwulignan significantly increased the exercise tolerance by decreasing BUN, LD, LDH, CK, Pi, MDA, TBARS, 8-OHdG, ROS, and Annexin V levels and increasing LG, MG, SOD, CAT, and GSH-Px levels, significantly upregulated the expression of NRF2 and Bcl2 proteins, which are anti-oxidation and anti-apoptosis regulators, and also activated the p38MAPK-PGC-1α pathway.

CONCLUSION:Anwulignan can increase exercise tolerance and relieve fatigue in an excessive fatigue mouse model. The underlying mechanism may be through its regulatory effect on the NRF2 and PGC-1α signaling pathway. This study will provide scientific data for anwulignan to be developed as a novel and efficient component in anti-oxidant or anti-fatigue health food.

BACKGROUND: The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection. AIMS: To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants. METHODS: Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire. RESULTS: In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted. CONCLUSIONS: These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.

BACKGROUND: The pathogenesis of chronic hepatitis C virus (HCV) infection is associated with a defective host antiviral immune response and intrahepatic oxidative stress. Oxidative stress and lipid peroxidation play major roles in the fatty liver accumulation (steatosis) that leads to necro-inflammation and necrosis of hepatic cells. Previous trials suggested that antioxidative therapy may have a beneficial effect on patients with chronic HCV infection. AIMS: To determine the safety and efficacy of treatment of chronic HCV patients via a combination of antioxidants. METHODS: Fifty chronic HCV patients were treated orally on a daily basis for 20 weeks with seven antioxidative oral preparations (glycyrrhizin, schisandra, silymarin, ascorbic acid, lipoic acid, L-glutathione, and alpha-tocopherol), along with four different intravenous preparations (glycyrrhizin, ascorbic acid, L-glutathione, B-complex) twice weekly for the first 10 weeks, and followed up for an additional 20 weeks. Patients were monitored for HCV-RNA levels, liver enzymes, and liver histology. Assessment of quality of life was performed using the SF-36 questionnaire. RESULTS: In one of the tested parameters (eg, liver enzymes, HCV RNA levels, or liver biopsy score), a combination of antioxidants induced a favorable response in 48% of the patients (24). Normalization of liver enzymes occurred in 44% of patients who had elevated pretreatment ALT levels (15 of 34). ALT levels remained normal throughout follow-up period in 72.7% (8 of 11). A decrease in viral load (one log or more) was observed in 25% of the patients (12). Histologic improvement (2-point reduction in the HAI score) was noted in 36.1% of the patients. The SF-36 score improved in 26 of 45 patients throughout the course of the trial (58% of the patients). Treatment was well tolerated by all patients. No major adverse reactions were noted. CONCLUSIONS: These data suggest that multi antioxidative treatment in chronic HCV patients is well tolerated and may have a beneficial effect on necro-inflammatory variables. A combination of antiviral and antioxidative therapies may enhance the overall response rate of these patients.