2. Academic Validation
  3. Serum metabolomics and 16S rRNA amplicon sequencing reveal the role of puerarin in alleviating bone loss aggravated by antidiabetic agent pioglitazone in type 2 diabetic mice

Serum metabolomics and 16S rRNA amplicon sequencing reveal the role of puerarin in alleviating bone loss aggravated by antidiabetic agent pioglitazone in type 2 diabetic mice

  • J Ethnopharmacol. 2025 Jan 31:340:119128. doi: 10.1016/j.jep.2024.119128.
Junzheng Yang 1,  Chuyi Chen 2,  Hua Zhang 2,  Baihao Chen 2,  Ke Xiao 2,  Yiming Tang 2,  Kai Meng 3,  Ling Qin 4,  Peng Chen 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Traditional Chinese Medicine Syndrome, Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Fifth School of Clinical Medicine, Guangzhou University of Chinese Medicine, 12 Jichang Road, Baiyun Area, Guangzhou, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
  • 2 State Key Laboratory of Traditional Chinese Medicine Syndrome, Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; The Laboratory of Orthopaedics and Traumatology of Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou, PR China.
  • 3 Department of Orthopaedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369, Jingshi Road, Lixia Area, Jinan, PR China.
  • 4 Musculoskeletal Research Laboratory and Innovative Orthopaedic Biomaterials and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, PR China. Electronic address: lingqin@cuhk.edu.hk.
  • 5 State Key Laboratory of Traditional Chinese Medicine Syndrome, Department of Orthopaedics, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, PR China; Department of Orthopaedics, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, 16 Jichang Road, Baiyun Area, Guangzhou, PR China. Electronic address: docchen777@gmail.com.
PMID: 39617084 DOI: 10.1016/j.jep.2024.119128
Abstract

Ethnopharmacological relevance: Pioglitazone (PIO) was an anti type 2 diabetes (T2D) agent but caused bone loss and bone marrow fat accumulation. Puerarin (PUE) was a natural component of herbal medicine extracted from Pueraria lobata (Willd.) Ohwi and reduced glycemia and improved bone mass as a supplementary drug. A combination of PIO and PUE might be good for maintaining bone mass and blood glucose.

Aim of the study: We aimed to elucidate the potential correlation and underlying mechanisms of dietary supplement PUE in reducing side effects caused by PIO.

Materials and methods: In vitro, Alkaline Phosphatase (ALP) staining, alizarin S (ARS) staining and qRT-PCR were performed to detect the osteogenesis activity in MC3T3-E1 cells. In vivo, we established the T2D model by treating C57BL6/J mice with high-fat diets and streptozotocin (STZ). Micro-CT, hematoxylin and eosin (H&E) staining and tartrate-resistant Acid Phosphatase (TRAcP) staining were performed to observe the difference in skeletal phenotype. Serum metabolomics and 16S rRNA amplicon Sequencing were applied to analyze the potential effect of the combination of PIO and PUE.

Results: We showed that the PUE could increase ALP activity and mineralization nodes of MC3T3-E1 with PIO. PIO could aggravate bone loss but PUE alleviated the effect caused by PIO in T2D mice. PUE promoted alpha-linolenic acid metabolism and glycerophospholipid metabolism, and affected the alpha diversity of the gut microbiome by regulating the genera of Alloprevotella, Fusobacterium, Rodentibacter, etc. Correlation analysis indicated that sphingosine-1-phosphate, nonadecylic acid, and margaric acid were associated with the effect of PUE.

Conclusions: Taken together, we demonstrated that PIO combined with PUE was able to lower blood sugar levels without causing bone loss. The effect of PUE mainly correlated with the genua of Alloprevotella, Fusobacterium, Rodentibacter, and Alistipes. Also, alpha-linolenic acid metabolism and glycerophospholipid metabolism were major targets of PUE.

Keywords

Gut microbiome; Herbal medicine; Metabolism; Type 2 diabetes.

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