State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Acta Pharmacol Sin. 2012 Sep;33(9):1195-203. doi: 10.1038/aps.2012.87. Epub 2012 Aug 27.
Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a potent and selective inhibitor of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) with the ability to ameliorate metabolic disorders in diet-induced obese mice. In the present study, we investigated the effects of emodin on adipocyte function and the underlying mechanisms in vitro, and its anti-diabetic effects in ob/ob mice.
3T3-L1 adipocytes were used for in vitro studies. 11β-HSD1A activity was evaluated with a scintillation proximity assay. The adipogenesis, glucose uptake, lipolysis and adiponectin secretion were investigated in 3T3-L1 adipocytes treated with emodin in the presence of active (corticosterone) or inactive glucocorticoid (11-dehydrocorticosterone). For in vivo studies, ob/ob mice were administered emodin (25 and 50 mg·kg⁻¹·d⁻¹, ip) for 26 d. On the last day of administration, the serum was collected and the mesenteric and perirenal fat were dissected for analyses.
Emodin inhibited the 11β-HSD1 activity in 3T3-L1 adipocytes in concentration- and time-dependent manners (the IC₅₀ values were 7.237 and 4.204 μmol/L, respectively, after 1 and 24 h treatment. In 3T3-L1 adipocytes, emodin (30 μmol/L) suppressed 11-dehydrocorticosterone-induced adipogenesis without affecting corticosterone-induced adipogenesis; emodin (3 μmol/L) reduced 11-dehydrocorticosterone-stimulated lipolysis, but had no effect on corticosterone-induced lipolysis. Moreover, emodin (3 μmol/L) partly reversed the impaired insulin-stimulated glucose uptake and adiponectin secretion induced by 11-dehydrocorticosterone but not those induced by corticosterone. In ob/ob mice, long-term emodin administration decreased 11β-HSD1 activity in mesenteric adipose tissues, lowered non-fasting and fasting blood glucose levels, and improved glucose tolerance.
Emodin improves the inactive glucocorticoid-induced adipose tissue dysfunction by selective inhibition on 11β-HSD1 in adipocyte in vitro and improves glycemic control in ob/ob mice.
大黄素（1,3,8-三羟基-6-甲基蒽醌）是一种有效的选择性 11β-羟甾醇脱氢酶 1（11β-HSD1）抑制剂，能够改善饮食诱导肥胖小鼠的代谢紊乱。本研究旨在探讨大黄素在体外对脂肪细胞功能的影响及其作用机制，并研究其在 ob/ob 小鼠中的抗糖尿病作用。
采用 3T3-L1 脂肪细胞进行体外研究。采用闪烁接近测定法评估 11β-HSD1A 活性。在大黄素存在下，用活性（皮质酮）或非活性糖皮质激素（11-去氢皮质酮）处理 3T3-L1 脂肪细胞，研究脂肪生成、葡萄糖摄取、脂肪分解和脂联素分泌情况。对于体内研究，给 ob/ob 小鼠腹腔注射大黄素（25 和 50 mg·kg⁻¹·d⁻¹）26 d。在给药的最后一天，收集血清，并分离肠系膜和肾周脂肪进行分析。
大黄素呈浓度和时间依赖性抑制 3T3-L1 脂肪细胞的 11β-HSD1 活性（1 h 和 24 h 处理后的 IC₅₀ 值分别为 7.237 和 4.204 μmol/L）。在 3T3-L1 脂肪细胞中，大黄素（30 μmol/L）抑制 11-去氢皮质酮诱导的脂肪生成，而不影响皮质酮诱导的脂肪生成；大黄素（3 μmol/L）降低 11-去氢皮质酮刺激的脂肪分解，但对皮质酮诱导的脂肪分解没有影响。此外，大黄素（3 μmol/L）部分逆转了 11-去氢皮质酮诱导的胰岛素刺激的葡萄糖摄取和脂联素分泌受损，但对皮质酮诱导的葡萄糖摄取和脂联素分泌无影响。在 ob/ob 小鼠中，长期给予大黄素可降低肠系膜脂肪组织中的 11β-HSD1 活性，降低非禁食和禁食血糖水平，并改善葡萄糖耐量。
大黄素通过选择性抑制脂肪细胞中的 11β-HSD1，改善了体外非活性糖皮质激素诱导的脂肪组织功能障碍，并改善了 ob/ob 小鼠的血糖控制。
