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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Ethnopharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1426767

Qianggu concentrate: unlocking bone protection power via antioxidative SIRT1/NRF2/HO-1 pathways in type 2 diabetic osteoporosis

Provisionally accepted
Kaili Wang Kaili Wang 1Xiang Dang Xiang Dang 2*Yanyan Wang Yanyan Wang 2*Qing Yang Qing Yang 2*Tingting Zhang Tingting Zhang 1*Peng Yang Peng Yang 1*Ling Yuan Ling Yuan 3Rongming Xu Rongming Xu 3*Yuqi Dang Yuqi Dang 2*Yi Nan Yi Nan 1*
  • 1 College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
  • 2 Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, affiliated with Ningxia Medical University, Yinchuan, China
  • 3 School of Pharmacy, Ningxia Medical University, Yinchuan, China

The final, formatted version of the article will be published soon.

    Background: Qianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce. Objective: to explore QGHJ's osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration. Methods: QGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-PCR and Western blot. BMSCs' responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays. Results: UPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ's key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARĪ³, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs' viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARĪ³ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress. Conclusion: In T2DOP rat and BMSCs oxidative stress models, QGHJ's bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

    Keywords: Traditional Chinese medicine 1, Diabetic 2, Osteoporosis 3, Oxidative stress 4, Osteogenic differentiation 5

    Received: 02 May 2024; Accepted: 26 Jul 2024.

    Copyright: Ā© 2024 Wang, Dang, Wang, Yang, Zhang, Yang, Yuan, Xu, Dang and Nan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Xiang Dang, Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, affiliated with Ningxia Medical University, Yinchuan, China
    Yanyan Wang, Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, affiliated with Ningxia Medical University, Yinchuan, China
    Qing Yang, Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, affiliated with Ningxia Medical University, Yinchuan, China
    Tingting Zhang, College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
    Peng Yang, College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China
    Rongming Xu, School of Pharmacy, Ningxia Medical University, Yinchuan, China
    Yuqi Dang, Department of Endocrinology, Yinchuan Hospital of Traditional Chinese Medicine, affiliated with Ningxia Medical University, Yinchuan, China
    Yi Nan, College of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan, China

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