Journal of Korean Medicine for Obesity Research (한방비만학회지)

The Society of Korean Medicine for obesity Research (한방비만학회)
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The Herbal Formula C-DM3 Improves the Changes of Diabetes-Related Biomarkers in High-Fat Diet-Induced Obese Mice through Regulation of the IRS1/PI3K/AKT and AMPK Signaling Pathways in the Liver and Pancreas

고지방식이를 통해 비만이 유발된 마우스에서 C-DM3 복합추출물의 항비만 및 항당뇨 효능 연구

  • Yoon Yong Choi (Department of Herbology, College of Korean Medicine, Dongguk University) ;
  • Chenzi Lyu (Department of Herbology, College of Korean Medicine, Dongguk University) ;
  • Tong Zhang (Department of Herbology, College of Korean Medicine, Dongguk University) ;
  • Haifeng Shao (Department of Herbology, College of Korean Medicine, Dongguk University) ;
  • Xianglong Meng (Shanxi Key Laboratory of Traditional Herbal Medicines Processing, Shanxi University of Chinese Medicine) ;
  • Chu Duc Thanh (Pharmaceutical Analysis Laboratory, College of Pharmacy, Chungnam National University) ;
  • Jong-Seong Kang (Pharmaceutical Analysis Laboratory, College of Pharmacy, Chungnam National University) ;
  • Hyo Won Jung (Department of Herbology, College of Korean Medicine, Dongguk University) ;
  • Yong-Ki Park (Department of Herbology, College of Korean Medicine, Dongguk University)
  • 최윤용 (동국대학교 한의과대학 본초학교실) ;
  • 류천지 (동국대학교 한의과대학 본초학교실) ;
  • 장동 (동국대학교 한의과대학 본초학교실) ;
  • 소해봉 (동국대학교 한의과대학 본초학교실) ;
  • 맹상용 (산시중의약대학교 중의약가공중점연구실) ;
  • 추득탄 (충남대학교 약학대학 약품분석연구실) ;
  • 강종성 (충남대학교 약학대학 약품분석연구실) ;
  • 정효원 (동국대학교 한의과대학 본초학교실) ;
  • 박용기 (동국대학교 한의과대학 본초학교실)
  • Received : 2024.05.09
  • Accepted : 2024.05.27
  • Published : 2024.06.30
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Abstract

Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.

Keywords

Acknowledgement

The Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), Ministry of Health and Welfare, Korea (No. HF20C0121), Shanxi Key Laboratory of Tradition Herbal Medicines Processing (No. 20210901), and Innovation Team of Shanxi University of Chinese Medicine (No. 2022TD1014).

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