Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach

Liang Dai, Jingjuan Xu, Baocheng Liu, Yanqi Dang, Ruirui Wang, Lijie Zhuang, Dong Li, Lulu Jiao, Jianying Wang, Lei Zhang, Linda L. D. Zhong, Wenjun Zhou, Guang Ji*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Lingguizhugan Decoction (LGZG) has been investigated in basic studies, with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease (NAFLD). This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting. A randomized, double-blinded, placebo-controlled trial was performed. A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG (two groups: standard dose and low dose) or placebo for 12 weeks on the basis of lifestyle modifications. The primary efficacy variable was homeostasis model assessment of insulin resistance (HOMA-IR). Analyses were performed in two populations in accordance with body mass index (BMI; overweight/obese, BMI ⩾ 24 kg/m2; lean, BMI < 24 kg/m2). For overweight/obese participants, low-dose LGZG significantly decreased their HOMA-IR level compared with placebo (−0.19 (1.47) versus 0.08 (1.99), P = 0.038). For lean subjects, neither dose of LGZG showed a superior effect compared with placebo. Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A (PPP1R3A) and autophagy related 3 (ATG3) significantly increased after LGZG intervention in overweight/obese population. Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD. The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3. Lean subjects may not be a targeted population for LGZG.

Original languageEnglish
JournalFrontiers of Medicine
DOIs
Publication statusE-pub ahead of print - 26 Apr 2022

Scopus Subject Areas

  • Medicine(all)

User-Defined Keywords

  • Chinese herbal medicine
  • DNA N6-methyladenine modification
  • insulin resistance
  • non-alcoholic fatty liver disease
  • randomized controlled trial

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