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World J Diabetes. Jun 15, 2026; 17(6): 118650
Published online Jun 15, 2026. doi: 10.4239/wjd.118650
Tangwang formula ameliorates diabetic retinopathy by inhibiting cell apoptosis and regulating the intestinal microbiota and metabolic profiles
He Zhang, Jia-Xin Xing, Yi-Fei Yin, Jun Li, Chen-Xu Jing, Song-Yan Liu, Jin-Zhu Yin, Xiang Gao, Zu-Guo Liang, Tong-Yi Yuan, Hang Su, Ying-Qian Li, Ze-Yu Wang, Hai-Si Dong, Da-Qing Zhao, Da-Shi Ying, Zhen-Wei Zhou, Qing-Xia Huang
He Zhang, Jun Li, Chen-Xu Jing, Jin-Zhu Yin, Qing-Xia Huang, Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, Changchun 130021, Jilin Province, China
Jia-Xin Xing, Yi-Fei Yin, Song-Yan Liu, Xiang Gao, Zu-Guo Liang, Tong-Yi Yuan, College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
Hang Su, Ze-Yu Wang, Hai-Si Dong, Da-Qing Zhao, Zhen-Wei Zhou, Northeast Asia Research Institute of Traditional Chinese Medicine, Jilin Provincial Key Laboratory for Efficacy Research and Utilization of Characteristic Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun 130117, Jilin Province, China
Ying-Qian Li, Department of Quality Certification, Jilin Provincial Product Quality Supervision and Inspection Institute, Changchun 130103, Jilin Province, China
Da-Shi Ying, College of Traditional Chinese Medicine, Jilin Agriculture Science and Technology University, Jilin 132109, Jilin Province, China
Co-first authors: He Zhang and Jia-Xin Xing.
Co-corresponding authors: Zhen-Wei Zhou and Qing-Xia Huang.
Author contributions: Zhang H and Xing JX designed the study, wrote the original draft, and contributed equally to this work as co-first authors; Yin YF was responsible for design research and writing manuscript; Li J, Jing CX, Liu SY, Yin JZ, Su H, and Li YQ carried out the animal experiments; Gao X, Liang ZG, and Yuan TY carried out the cell experiments; Wang ZY, Dong HS, and Zhao DQ contributed to the conceptualization and project administration; Ying DS, Zhou ZW, and Huang QX contributed to the conceptualization and revised the manuscript; Zhou ZW and Huang QX contributed equally to this work as co-corresponding authors; all authors have read and approved the final manuscript.
Supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project, No. 2023ZD0509300; Science and Technology Development Plan Project of Jilin Province, No. 20230402040GH; Jilin Province Undergraduate Innovation Training Program Project, No. 202410199024; and Medical Center Project of Changchun University of Traditional Chinese Medicine Affiliated Hospital, No. DXZX-04-08.
Institutional animal care and use committee statement: The animal study was approved by the Animal Ethics Committee of Changchun University of Chinese Medicine approved the animal experiment, and the animals were treated humanely based on the guidelines outlined in the Institutional Animal Care and Use committee and the ARRIVE guidelines (No. 2024251). The study was conducted in accordance with the local legislation and institutional requirements.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The raw data are available upon reasonable request from the corresponding author.
Corresponding author: Qing-Xia Huang, MD, Research Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese Medicine, No. 1478 Gongnong Road, Chaoyang District, Changchun 130021, Jilin Province, China.
hqx19890928@163.com
Received: January 8, 2026
Revised: March 10, 2026
Accepted: May 13, 2026
Published online: June 15, 2026
Processing time: 155 Days and 5.6 Hours
BACKGROUND
Tangwang formula (TWF), a traditional Chinese medicine, has been shown to delay the progression of diabetic retinopathy (DR) over the past 20 years. However, the potential therapeutic mechanisms and effective components of TWF remain unclear.
AIM
To investigate the effective components of TWF and elucidate the mechanism underlying TWF treatment for DR.
METHODS
The chemical ingredients of TWF were detected using high-pressure liquid chromatography. Network pharmacology and molecular docking were applied to identify the targets and pathways associated with TWF and DR. A DR mouse model was established by streptozotocin to evaluate the therapeutic effect of TWF in vivo. High glucose treatment was used to induce injury in mouse retinal endothelial cells (mRECs) to verify the mechanism of TWF in vitro. The 16S ribosomal RNA sequencing and untargeted metabolomics were performed to detect intestinal bacteria and fecal metabolites in DR mice.
RESULTS
Eight important active constituents were identified by high-pressure liquid chromatography. Network pharmacology results showed that Bcl2 and Casp3 were key targets between TWF and DR. Isorhamnetin-3-O-neohespeidoside, naringenin, ononin, and calycosin-7-O-β-D-glucoside from TWF had strong affinities with Bcl2 and Casp3. TWF significantly reduced random blood glucose, inhibited the levels of proinflammatory factors in DR mice and mRECs, and alleviated retinal damage by downregulating the expressions of vascular endothelial growth factor and receptor advanced glycation end products, and upregulating the expressions of zonula occludens-1 and RBP-3. TWF inhibited the apoptosis in mouse retinal tissues and mRECs. Analysis of intestinal bacteria and metabolites revealed that TWF increased the richness and evenness of intestinal microbiota and improved fecal metabolic profiles in DR mice. Importantly, seven genus bacteria were closely correlated with amino acids, fatty acids, glycerophosphocholine, and bile acid, which could participate in ameliorating retinal injury.
CONCLUSION
These findings suggest that TWF may ameliorate retinal damage in DR mice via anti-inflammatory and anti-apoptotic activities, which may be associated with modulation of the intestinal microbiota and metabolic profiles.
Core Tip: This study identified the main active components of Tangwang formula (TWF) and explored its protective mechanism against diabetic retinopathy mice induced by streptozotocin using network pharmacology, molecular docking, 16S ribosomal RNA sequencing, and metabolomics analysis. Four key active components were identified in TWF that participated in regulating the inflammation and apoptosis. TWF might reduce blood glucose, and alleviate retinal injury by modulating the intestinal microbiota and metabolic homeostasis. These findings provide a theoretical basis for the clinical application of TWF in the treatment of diabetic retinopathy.
