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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Plantamajoside improves type 2 diabetes mellitus pancreatic β-cell damage by inhibiting endoplasmic reticulum stress through Dnajc1 up-regulation
Duo Wang, Yuan-Song Wang, Hong-Min Zhao, Peng Lu, Meng Li, Wei Li, Huan-Tian Cui, Zhong-Yong Zhang, Shu-Quan Lv
Duo Wang, Yuan-Song Wang, Hong-Min Zhao, Zhong-Yong Zhang, Shu-Quan Lv, Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou 061000, Hebei Province, China
Peng Lu, Department of Endocrinology, Xianxian Hospital of Traditional Chinese Medicine of Hebei, Cangzhou 062250, Hebei Province, China
Meng Li, Graduate School, Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Wei Li, Graduate School, Hebei University of Chinese Medicine, Shijiazhuang 050299, Hebei Province, China
Huan-Tian Cui, The First School of Clinical Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 065000, Yunnan Province, China
Zhong-Yong Zhang, Shu-Quan Lv, Zhong-Yong Zhang and Shu-Quan Lv.
Co-corresponding authors: Zhong-Yong Zhang and Shu-Quan Lv.
Author contributions: Wang D contributed to manuscript drafting, investigation, and funding acquisition; Wang YS contributed to manuscript drafting, investigation, validation, and data curation; Zhao HM contributed to investigation, validation, and data curation; Lu P and Li M contributed to manuscript drafting and formal analysis; Li W contributed to investigation and validation; Cui HT contributed to review and editing of the manuscript drafts, conceptualization; Zhang ZY, Lv SQ contributed to manuscript drafting, investigation, validation, data curation, validation, and conceptualization.
Supported by Yuansong Wang National Famous Traditional Chinese Medicine Expert Heritage Studio, No. 4 (2022).
Institutional review board statement: All experimental procedures received approval from Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province.
Institutional animal care and use committee statement: All experimental procedures followed the Guidelines for Animal Ethics and received approval from Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province (Approval Number: CZX2024-KY-052).
Conflict-of-interest statement: The authors declare no conflict of interests.
Data sharing statement: Data will be made available on reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Shu-Quan Lv, PhD, Doctor, Researcher, Department of Endocrinology, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine of Hebei Province Affiliated to Hebei University of Chinese Medicine, No. 31 West Yellow River Road, Cangzhou 061000, Hebei Province, China.
czlvshuquan@163.com
Received: July 12, 2024
Revised: October 26, 2024
Accepted: November 26, 2024
Published online: February 15, 2025
Processing time: 171 Days and 5.8 Hours
BACKGROUND
Plantamajoside (PMS) has shown potential in mitigating cell damage caused by high glucose (HG) levels. Despite this, the precise therapeutic effects of PMS on type 2 diabetes mellitus (T2DM) and the underlying regulatory mechanisms require further exploration.
AIM
To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.
METHODS
An in vitro damage model of MIN6 cells was established using HG and palmitic acid (PA). PMS's protective effect on cell damage was assessed. Next, transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells. Furthermore, the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated. A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.
RESULTS
PMS intervention ameliorated cell injury in HG + PA-induced MIN6 cell damage. Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS, with significant downregulation of the gene Dnajc1. Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors (Bax, CytC) and endoplasmic reticulum stress (ERS)-related factors [ATF6, XBP1, Ddit3 (CHOP), GRP78], while promoting the expression of Bcl-2 and Dnajc1. Additionally, the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing. Furthermore, in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage, suppressed the expression of apoptosis-related factors (Bax, CytC), and ERS-related factors [ATF6, XBP1, Ddit3 (CHOP), GRP78], while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.
CONCLUSION
PMS intervention could alleviate pancreatic tissue damage effectively. The mechanism of action involves Dnajc1 activation, which subsequently inhibits apoptosis and ERS, ameliorating damage to pancreatic β-cells.
Core Tip: Plantamajoside (PMS) exhibits therapeutic effects in rats with type 2 diabetes mellitus pancreatic β-cell damage. The mechanism of action of PMS appears to involve Dnajc1 activation, which subsequently inhibits apoptosis and endoplasmic reticulum stress, ultimately ameliorating damage to pancreatic β-cells.
