Baicalin suppresses macrophage JNK-mediated adipose tissue inflammation to mitigate insulin resistance in obesity

Ziyue Zhu; Mei Yu; Mengfan Xu; Xin Ji; Xicui Zong; Zhenwen Zhang; Wenbin Shang; Li Zhang; Penghua Fang

doi:10.1016/j.jep.2024.118355

Baicalin suppresses macrophage JNK-mediated adipose tissue inflammation to mitigate insulin resistance in obesity

J Ethnopharmacol. 2024 May 16:332:118355. doi: 10.1016/j.jep.2024.118355. Online ahead of print.

Authors

Ziyue Zhu¹, Mei Yu¹, Mengfan Xu¹, Xin Ji², Xicui Zong³, Zhenwen Zhang⁴, Wenbin Shang⁵, Li Zhang⁶, Penghua Fang⁷

Affiliations

¹ Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
² Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, China.
³ Hanlin College, Nanjing University of Chinese Medicine, Taizhou, 225300, China.
⁴ Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, 225001, China. Electronic address: zwzhang@yzu.edu.cn.
⁵ Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: wbshang@njucm.edu.cn.
⁶ Hanlin College, Nanjing University of Chinese Medicine, Taizhou, 225300, China. Electronic address: zhangli@njucm.edu.cn.
⁷ Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China. Electronic address: hlcollegesci@sina.cn.

PMID: 38762213
DOI: 10.1016/j.jep.2024.118355

Abstract

Ethnopharmacological relevance: Radix scutellariae (the root of Scutellaria baicalensis Georgi) is a traditional Chinese medicine (TCM) used to treat a wide range of inflammation-related diseases, such as obesity, diabetes, diabetic kidney disease, and COVID-19-associated inflammatory states in the lung and kidney. Baicalin is the major anti-inflammatory component of Radix scutellariae and has shown the potential to inhibit inflammation in metabolic disorders. In this study, we explored the ability and underlying mechanisms of baicalin to modulate the macrophage to mitigate insulin resistance in obesity.

Materials and methods: Obese mice were administered baicalin (50 mg/kg/day) intraperitoneally for 3 weeks. RAW264.7 and BMDM cells were stimulated with LPS and treated with baicalin for 24 h, while 3T3-L1 and primary white adipocytes were treated with the supernatants from baicalin-treated RAW264.7 cells for 24 h.

Results: The results showed that baicalin significantly improved glucose and insulin tolerance as well as decreased fat and adipose tissue macrophage levels in obese mice. Besides, baicalin significantly reduced serum and adipose tissue IL-1β, TNF-α and IL-6 levels in obese mice, as well as suppressed LPS-induced IL-1β, TNF-α and IL-6 expression and release in macrophages. Furthermore, treatment with the supernatant from baicalin-treated RAW264.7 cells increased the levels of PGC-1α, SIRT1, p-IRS-1 and p-AKT in adipocytes. Moreover, baicalin treatment dramatically downregulated macrophage p-p38, p-JNK, and Ac-p65^Lys310 levels while increasing SIRT1 both in vivo and in vitro. Importantly, JNK inhibitor SP600125 blocked most of the effects of baicalin on SIRT1, Ac-p65^Lys310 and pro-inflammatory factors in macrophages.

Conclusion: Therefore, these results demonstrated for the first time that baicalin exerts its anti-inflammatory effects in obese adipose tissue macrophages mainly through suppressing JNK/SIRT1/p65 signaling. These findings amplified the mechanisms of baicalin and its potential to attenuate insulin resistance.

Keywords: Adipose tissue; Baicalin; Inflammation; Insulin resistance; Obesity.