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Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues

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Abstract

Objective

To investigate the effects of Clean-DM1 (C-DM1), a polyherbal formulation of Radix Scrophulariae, Radix Astragali, Rhizoma Atractylodis, and Radix Salviae Miltiorrhizae, on high-fat diet (HFD)-induced diabetes mice.

Methods

The information about active components of C-DM1 extract and molecular mechanism was obtained from network pharmacology analysis. Main compounds of C-DM1 extract by high performance liquid chromatography-mass spectrometry (HPLC-MS) analysis were conducted for quality control. For in vivo study, mice were induced diabetes by HFD for 12 weeks. The mice in the normal group (Nor) were maintained with a regular diet and treated with saline by gavage. The HFD model mice were randomly divided into 3 groups, including a HFD diabetic model group, a C-DM1 extract-administered group (C-DM1, 500 mg/kg), and metformin-administered groups (Met, 500 mg/kg), 8 mice in each group. Food intake, body weight (BW), and fasting blood glucose (FBG) levels were recorded weekly for 4 weeks. After 4 weeks of treatment, alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood glucose, low-density lipoprotein cholesterol (LDL-C) were determined using an automated clinical chemistry analyzer, and homeostatic model for assessing insulin resistance (HOMA-IR) levels and oral glucose tolerance test (OGTT) were detected. The histopathological changes of liver and pancreatic tissues were observed by hematoxylin-eosin staining. Insulin receptor substrate (IRS)/phosphatidylinositol 3 kinase (PI3K)/ protein kinase B (AKT) and adenosine 5′-monophosphate-activated protein kinase (AMPK) expressions in liver and pancreas tissues were detected by Western blot analysis.

Results

HPLC-MS identified dihydroisotanshinone, dihydroisotanshinone I, cryptotanshinone, harpagoside, and atractyloside A in C-DM1 extract. The administration of C-DM1 extract significantly decreased body weight, calorie intake, and the levels of blood glucose and insulin in the diabetic mice (P<0.05 or P<0.01). The C-DM1 extract administration improved the impaired glucose tolerance and insulin resistance in the diabetic mice and significantly decreased the levels of LDL-C, ALT and AST (P<0.01). The C-DM1 extract inhibited the histopathological changes of fatty liver and hyperplasia of pancreatic islets in the diabetic mice. The C-DM1 extract significantly increased the phosphorylation of IRS, AKT, and AMPK and the expression of PI3K in pancreas and liver tissues (P<0.05 or P<0.01), which was consistent with the analysis results of network pharmacology.

Conclusion

C-DM1 extract improved diabetes symptoms in long-term HFD-induced mice by regulation of IRS/PI3K/AKT and AMPK expressions in pancreas and liver tissues, suggesting that C-DM1 formulation may help prevent the progression of T2DM.

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Author information

Authors and Affiliations

  1. Department of Herbology, College of Korean Medicine, Dongguk University, Gyeongju, 38066, Korea

    Piao Wang, Yi Liu, Seok Yong Kang, Chenzi Lyu, Tianjun Ho, Kyung Jae Lee, Yong-Ki Park & Hyo Won Jung

  2. College of Pharmacy & Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 03760, Korea

    Yi Liu

  3. Korean Medicine R&D Center, Dongguk University, Gyeongju, 38066, Korea

    Seok Yong Kang, Yong-Ki Park & Hyo Won Jung

  4. Shanxi Key Laboratory of Traditional Herbal Medicines Processing, Shanxi University of Chinese Medicine, Jinzhong, Shanxi Province, 030619, China

    Chenzi Lyu, Xiang Han & Xianglong Meng

Authors
  1. Piao Wang
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  2. Yi Liu
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  5. Xiang Han
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Contributions

Liu Y and Wang P contributed equally in this manuscript and completed first draft. Jung HW and Park YK as co-correspondences conceptualized the experiments; Liu Y, Wang P, Kang SY, Ho T and Lee KJ performed in vivo experiments and analyzed the data. Meng X, Lyu C and Han X analyzed network pharmacology and performed HPLC analysis. Jung HW, Park YK and Meng X reviewed and edited the manuscript. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Hyo Won Jung.

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The authors declare that there is no conflict of interest.

Additional information

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

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Wang, P., Liu, Y., Kang, S.Y. et al. Clean-DM1, a Korean Polyherbal Formula, Improves High Fat Diet-Induced Diabetic Symptoms in Mice by Regulating IRS/PI3K/AKT and AMPK Expressions in Pancreas and Liver Tissues. Chin. J. Integr. Med. 30, 125–134 (2024). https://doi.org/10.1007/s11655-023-3548-9

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  • DOI: https://doi.org/10.1007/s11655-023-3548-9

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