| Summary: | 碩士 === 國立中興大學 === 食品暨應用生物科技學系所 === 98 === Type 1 diabetes (T1D) is one of autoimmune diseases. T1D patients having Th1-skewed immune responses result in chronic inflammation. The chronic inflammation may further deteriorate diabetic complications. Berberine is an isoquinoline alkaloid. Recently, berberine is reported to have many pharmacological functions, including hypolipidemic and anti-inflammatory effects. However, the effect of berberine on T1D is still not clear. Therefore, this study first investigated the effects of berberine supplementation in vivo on immunomodulatory functions, especially anti-inflammation, using type 1 non-obese diabetes (NOD) mice. The NOD mice were randomly divided into four groups, including control (CO) group which was intragastric gavage with water, berberine low dose (BL), berberine medium dose (BM) and berberine high dose (BH) groups which were respectively administrated with 50, 150, and 500 mg berberine/kg bw through 14 weeks by consecutive tube feeding. ICR mice were also selected as a species control (SC) group to compare with NOD mice (CO). The results showed that secretion ratios of Th1/Th2 cytokines by splenocytes of NOD mice significantly decreased after berberine supplementation. Secretion ratios of anti-/pro-inflammatory cytokines by splenocytes of NOD mice significantly increased after high-dose berberine supplementation. Furthermore, berberine administration increased ratios of anti-/pro-inflammatory cytokines mRNA expression in the liver but decreased the ratios of pro-/anti-inflammatory cytokines mRNA expression in the kidney of NOD mice. Overall, the results suggest that berberine supplementation may improve T1D symptoms via its potent anti-inflammatory and Th2-inclination activities. We found that berberine supplementation increased islet cell numbers of NOD mice in a dose-dependent manner, possibly via an anti-apoptotic pathway. To unravel the protective mechanism of berberine against apoptosis, we established in vitro experimental models using primary pancreatic islet cells from ICR mice. Results showed that berberine administration before streptozotocin (STZ)-stimulation significantly down-regulated ratios of pro-/anti-apoptotic genes (Bax/Bcl-2) expression (mRNA levels) in islet cells compared to those in STZ-stimulation alone group. We concluded that the protective mechanism of berberine on primary islet cells may be via its anti-apoptotic effect in a preventive manner.
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