Xiaoxianxiong Decoction Ameliorates Obesity-induced Type 2 Diabetes by Suppressing the NLRP3 Inflammasome Activation

¹Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

²National Research Institute for Family Planning, Beijing 100081, China

³Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China

*Corresponding author: Zhenhua Zhang, Ph.D, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China, Tel: (86) 10-8280-5570, Fax: (86) 10-8280-1380, E-mail: [email protected]

Received: April 02, 2026

Published: May 28, 2026

ABSTRACT

Obesity leads to chronic and systemic inflammation, resulting in insulin resistance (IR) and type 2 diabetes (T2D). This chronic inflammation has emerged as a key feature of T2D. Xiaoxianxiong decoction (XXXD) is a classic and well-known decoction that has been used to treat patients with severe pneumonia by inhibiting the inflammatory response. However, the pharmacological mechanism underlying XXXD ameliorates obesity-induced T2D is poorly understood. Here, we demonstrated that XXXD alleviated T2D by suppressing the inflammation through the NLRP3-dependent pathway. We found that XXXD-treated mice had significantly lower blood glucose levels and body weights in the HFD + STZ mouse model (Streptozotocin with high-fat diet). XXXD improved insulin resistance (IR) as indicated by the Oral glucose tolerance test (OGTT) and the insulin tolerance test (ITT) analyses. Oil red O staining and hematoxylin and eosin (H&E) staining showed that XXXD protected against the development of hepatic steatosis in the T2D mice model. Mechanistically, XXXD reduced hepatic inflammation through the NLRP3-mediated signaling pathway. In addition, we demonstrated that XXXD inhibited the accumulation of macrophages and their transformation into a pro-inflammatory state in the T2D livers. Through molecular docking simulation and molecular dynamics (MD) simulations, we identified the glucocorticoid receptor (GR) as a potential molecular target of XXXD treatment. Collectively, these findings demonstrated that XXXD reduced adiposity, improved glucose tolerance, and restored insulin sensitivity through the suppression of inflammation in the NLRP3-dependent signaling pathway.

Keywords: Xiaoxianxiong Decoction, Type 2 diabetes, Glucose Tolerance, Inflammation, NLRP3