Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798, Korea.
Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheong-ju si, Chungcheongbuk-do 28116, Korea.
Nutrients. 2020 Mar 14;12(3):773. doi: 10.3390/nu12030773.
The chronic low-grade inflammation in adipose tissue plays a causal role in obesity-induced insulin resistance and its associated pathophysiological consequences. In this study, we investigated the effects of extracts of root bark (PRE) and its bioactive components on inflammation and insulin sensitivity. PRE inhibited TNF-α-induced NF-κB transcriptional activity in the NF-κB luciferase assay and pro-inflammatory genes' expression by blocking phosphorylation of IκB and NF-κB in 3T3-L1 adipocytes, which were mediated by activating AMPK. Ten-week-high fat diet (HFD)-fed C57BL6 male mice treated with PRE had improved glucose intolerance and decreased inflammation in adipose tissue, as indicated by reductions in NF-κB phosphorylation and pro-inflammatory genes' expression. Furthermore, PRE activated AMP-activated protein kinase (AMPK) and reduced lipogenic genes' expression in both adipose tissue and liver. Finally, we identified broussoflavonol B (BF) and kazinol J (KJ) as bioactive constituents to suppress pro-inflammatory responses via activating AMPK in 3T3-L1 adipocytes. Taken together, these results indicate the therapeutic potential of PRE, especially BF or KJ, in metabolic diseases such as obesity and type 2 diabetes.
脂肪组织中慢性低度炎症在肥胖引起的胰岛素抵抗及其相关病理生理后果中起因果作用。在这项研究中，我们研究了根皮提取物（PRE）及其生物活性成分对炎症和胰岛素敏感性的影响。PRE 通过激活 AMPK，在 NF-κB 荧光素酶测定和 3T3-L1 脂肪细胞中促炎基因表达中阻断 IκB 和 NF-κB 的磷酸化，抑制 TNF-α诱导的 NF-κB 转录活性。用 PRE 治疗 10 周高脂饮食（HFD）喂养的 C57BL6 雄性小鼠改善了葡萄糖耐量，并降低了脂肪组织中的炎症，这表明 NF-κB 磷酸化和促炎基因表达减少。此外，PRE 在脂肪组织和肝脏中激活 AMP 激活的蛋白激酶（AMPK）并降低脂肪生成基因的表达。最后，我们鉴定出布氏黄酮 B（BF）和卡齐醇 J（KJ）是生物活性成分，通过在 3T3-L1 脂肪细胞中激活 AMPK 来抑制促炎反应。总之，这些结果表明 PRE，特别是 BF 或 KJ，在肥胖和 2 型糖尿病等代谢疾病中的治疗潜力。
