RESUMEN
Chronic unpredictable stressors can produce a situation similar to clinical depression, and such animal models can be used for the preclinical evaluation of antidepressants. Many findings have shown that the levels of proinflammatory cytokines (e.g., TNF-α) and oxidative stress (increased lipid peroxidation, decreased glutathione levels, and endogenous antioxidant enzyme activities) are increased in patients with depression. Silibinin is the major active constituent of silymarin, a standardized extract of the milk thistle seeds, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silicristin, silidianin and exhibit antioxidant activity. Objectives The present study was designed to investigate the effect of silibinin on unpredictable chronic stressinduce behavioral and biochemical alterations in mice. METHODS: Mice were subjected to different stress paradigms daily for a period of 45 days to induce depressive like behavior such as memory acquisition, and retention. RESULTS: Chronic treatment with silibinin significantly reversed the unpredictable chronic stress-induced behavioral (improve memory function), biochemical changes (decreased glutathione levels, superoxide dismutas), and inflammation surge (serum TNF-α IL 1ß) in stressed mice. CONCLUSION: The study revealed that silibinin exerted effects in behavioral despair paradigm in chronically stressed mice, specifically by modulating central oxidative stress and inflammation.
RESUMEN
BACKGROUND: Soya supplements are used in the treatment of neuropathic pain. Previous reports reveal that consumption of soy diet before nerve injury prevents the development of neuropathic pain in rats. Biochanin-A, a soy isoflavone, has a naturally occurring inhibitor of fatty acid amide hydrolase (FAAH) that metabolized endocannabinoids. OBJECTIVE: The objective was to evaluate efficacy of biochanin-A in streptozotocin (STZ) induced neuropathic pain in rat model. MATERIALS AND METHODS: Diabetes mellitus was induced by an injection of STZ at a dose of 45 mg/kg, i.v. into tail vein of male albino Wistar rats. Biochanin-A was dosed at 0.1, 1 and 5 mg/kg by intraperitoneal (i.p.) administration in diabetic neuropathic rats. Mechanical hyperalgesia and allodynia was measured using Randall-Selitto analgesymeter and manual von Frey filaments of increasing weights respectively. Paw withdrawal threshold (PWT) and percent PWT was determined with respect to both hyperalgesia and allodynia. RESULTS: Treatment of biochanin-A at three different levels of 0.1, 1 and 5 mg/kg had not significantly altered serum glucose levels throughout the treatment period. In hyperalgesia study, acute treatment with higher dose exhibited 51.1% reversal of paw withdrawal threshold (PWT) while with chronic treatment, efficacy declined to 22.5% reversal of PWT. In allodynia study, acute treatment reversed PWT by 79.4% while with chronic treatment, efficacy was raised to 88.2% reversal of PWT. CONCLUSION: Biochanin-A demonstrated better efficacy in reversing mechanical allodynia than mechanical hyperalgesia. Biochanin-A could be a good drug candidate for further studies to establish the mechanism of attenuation of neuropathic pain.