Journal of Traditional Chinese Medicine ›› 2026, Vol. 46 ›› Issue (5): 1206-1217.DOI: 10.19852/j.cnki.jtcm.2026.05.014
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Jiangtang Xiaozhi formula (降糖消脂方) alleviates type 2 diabetes mellitus by improving islet beta-cell dedifferentiation: a network pharmacology-based study
ZHU Meilin1, DU Jianpeng2, LUO Yunpeng3, LIU Yunlu4, NIU Zenghui4, LAN Tian1, YANG Jing4, CHEN Zhuhong1(
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Department of Endocrinology ,Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China
2Cardiovascular Diseases Center ,Xiyuan Hospital, China Academy of Chinese Medical Sciences Beijing 100091, China
3Department of Endocrinology ,Dongzhimen Hospital, Beijing University of Chinese Medicine Beijing 100700, China
4Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases ,Experimental Research Center, China Academy of Chinese Medical Sciences Beijing 100700, China
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Received:2025-04-04Accepted:2026-01-27Online:2026-10-15Published:2026-10-09 -
Contact:CHEN Zhuhong, Department of Endocrinology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. 13264214919@163.com,Telephone: +86-17852938921 -
Supported by:Science and Technology Innovation Project of China Academy of Chinese Medical Sciences: Study on the Mechanism of Jiangtang Xiaozhi Formula in Treating Diabetes by Regulating Pancreatic Beta-cell Dedifferentiation via the Forkhead Box O1-Mediated Insulin-like Growth Factor 1/Phosphatidylinositol 3-Kinase/Protein Kinase B Pathway(Grant Number: CI2021A01618);Special Project for Research And Development And Transformation of Intellectual Property Medical Institution Preparations and New Chinese Medicines of Xiyuan Hospital, China Academy of Chinese Medical Sciences: a Randomized, Double-Blind, Placebo-Controlled Clinical Study of Jiangtang Xiaozhi Granules for the Treatment of Metabolic Dysfunction-Associated Fatty Liver Disease(Grant Number: XYZX0303-01);Youth Quest Project of China Association of Chinese Medicine: a Clinical Study of Jiangtang Xiaozhi Formula for the Treatment of Type 2 Diabetes Mellitus Complicated with Non-Alcoholic Fatty Liver Disease(Grant Number: 2023-QNQS-07);National Natural Science Foundation of China: Molecular Mechanism of Yiqi Huoxue Formula in Delaying Vascular Inflammatory Aging Based on the Angiotensin II/Angiotensin II Type 1 Receptor/Nuclear Factor Kappa B Inflammatory Pathway(Grant Number: 82074260)
Cite this article
ZHU Meilin, DU Jianpeng, LUO Yunpeng, LIU Yunlu, NIU Zenghui, LAN Tian, YANG Jing, CHEN Zhuhong. Jiangtang Xiaozhi formula (降糖消脂方) alleviates type 2 diabetes mellitus by improving islet beta-cell dedifferentiation: a network pharmacology-based study[J]. Journal of Traditional Chinese Medicine, 2026, 46(5): 1206-1217.
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Figure 1 Network pharmacology analysis A: venn diagram of overlapping targets of T2DM, Islet beta-cell dedifferentiation and JTXZF; B: PPI network of 93 overlapping genes of T2DM, Islet beta-cell dedifferentiation and JTXZF; C: regarding the drug-component-target network of JTXZF in relation to T2DM and beta-cell dedifferentiation. T2DM: type 2 diabetes mellitus; PPI: protein-protein interaction; JTXZF: Jiangtang Xiaozhi formula.
Figure 1 Network pharmacology analysis A: venn diagram of overlapping targets of T2DM, Islet beta-cell dedifferentiation and JTXZF; B: PPI network of 93 overlapping genes of T2DM, Islet beta-cell dedifferentiation and JTXZF; C: regarding the drug-component-target network of JTXZF in relation to T2DM and beta-cell dedifferentiation. T2DM: type 2 diabetes mellitus; PPI: protein-protein interaction; JTXZF: Jiangtang Xiaozhi formula.
Figure 2 Inhibition of the PI3K/AKT/FoxO1 signaling pathway mediates PA-induced islet beta-cell dedifferentiation A: Min6 cells were cultured in 3 and 25 mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; B: densitometric quantification of Western blot bands for PDX1, Oct-4 and NEUROG3, normalized to β-Actin; C: densitometric quantification of Western blot bands for p-PI3K/PI3K, p-AKT/AKT and p-FoxO1/FoxO1, normalized to β-Actin; D: PDX1 expression in Min6 cells was detected by immunofluorescence staining; D1, D2, D4, D5: original magnification, × 200; scale bar = 100 μm; D3, D6: original magnification, × 400; scale bar = 50 μm; E: Oct-4 expression in Min6 cells was detected by immunofluorescence staining; E1, E2, E4, E5: original magnification, × 200; scale bar = 100 μm; E3, E6: original magnification, × 400; scale bar = 50 μm; F: NEURGO3 expression in Min6 cells was detected by immunofluorescence staining; F1, F2, F4, F5: original magnification, × 200; scale bar = 100 μm; F3, F6: original magnification, × 400; scale bar = 50 μm; G: fluorescence intensity for PDX1, Oct-4 and NEUROG3; D1, D2, D3, E1, E2, E3, F1, F2, F3: Control group; D4, D5, D6, E4, E5, E6, F4, F5, F6: PA group. Control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h. PA: palmitic acid; PDX1: pancreatic and duodenal homeobox 1; Oct-4: octamer-binding transcription factor 4; NEUROG3: neurogenin 3; p-PI3K/PI3K: phosphorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1. Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control.
Figure 2 Inhibition of the PI3K/AKT/FoxO1 signaling pathway mediates PA-induced islet beta-cell dedifferentiation A: Min6 cells were cultured in 3 and 25 mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; B: densitometric quantification of Western blot bands for PDX1, Oct-4 and NEUROG3, normalized to β-Actin; C: densitometric quantification of Western blot bands for p-PI3K/PI3K, p-AKT/AKT and p-FoxO1/FoxO1, normalized to β-Actin; D: PDX1 expression in Min6 cells was detected by immunofluorescence staining; D1, D2, D4, D5: original magnification, × 200; scale bar = 100 μm; D3, D6: original magnification, × 400; scale bar = 50 μm; E: Oct-4 expression in Min6 cells was detected by immunofluorescence staining; E1, E2, E4, E5: original magnification, × 200; scale bar = 100 μm; E3, E6: original magnification, × 400; scale bar = 50 μm; F: NEURGO3 expression in Min6 cells was detected by immunofluorescence staining; F1, F2, F4, F5: original magnification, × 200; scale bar = 100 μm; F3, F6: original magnification, × 400; scale bar = 50 μm; G: fluorescence intensity for PDX1, Oct-4 and NEUROG3; D1, D2, D3, E1, E2, E3, F1, F2, F3: Control group; D4, D5, D6, E4, E5, E6, F4, F5, F6: PA group. Control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h. PA: palmitic acid; PDX1: pancreatic and duodenal homeobox 1; Oct-4: octamer-binding transcription factor 4; NEUROG3: neurogenin 3; p-PI3K/PI3K: phosphorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1. Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control.
Figure 3 JTXZF alleviates PA-induced dysfunction and dedifferentiation in Min6 cells via the PI3K/Akt/FoxO1 signaling pathway A: Min6 cells were cultured in 3 and 25 mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; B: protein electrophoresis of PDX1, Oct-4, NEUROG3 and PI3K/AKT/FoxO1 signaling molecule; C: densitometric quantification of Western blot bands for p-PI3K/PI3K, normalized to β-Actin; D: densitometric quantification of Western blot bands for p-AKT/AKT, normalized to β-actin. E: densitometric quantification of Western blot bands for p-FoxO1/FoxO1, normalized to β-Actin. control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h; negative control group: PA-treated cells received 20% blank serum for 24 h; JTXZF group: PA-treated cells received 20% JTXZF-containing serum for 24 h; J + L group: Cells were treated with 0.3 mM PA, 20% Jiangtang Xiaozhi formula-containing serum, and 5 μM PI3K inhibitor LY294002 for 24 h; Metformin group: Cells were treated with 0.3 mM PA and 200 μM metformin. PA: palmitic acid; JTXZF: Jiangtang Xiaozhi formula; J + L: JTXZF + PI3K inhibitor LY294002; PDX1: pancreatic and duodenal homeobox 1; Oct-4: octamer-binding transcription factor 4; NEUROG3: neurogenin 3; p-PI3K/PI3K: phosphorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1.Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control; bP < 0.05 vs respective PA.
Figure 3 JTXZF alleviates PA-induced dysfunction and dedifferentiation in Min6 cells via the PI3K/Akt/FoxO1 signaling pathway A: Min6 cells were cultured in 3 and 25 mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; B: protein electrophoresis of PDX1, Oct-4, NEUROG3 and PI3K/AKT/FoxO1 signaling molecule; C: densitometric quantification of Western blot bands for p-PI3K/PI3K, normalized to β-Actin; D: densitometric quantification of Western blot bands for p-AKT/AKT, normalized to β-actin. E: densitometric quantification of Western blot bands for p-FoxO1/FoxO1, normalized to β-Actin. control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h; negative control group: PA-treated cells received 20% blank serum for 24 h; JTXZF group: PA-treated cells received 20% JTXZF-containing serum for 24 h; J + L group: Cells were treated with 0.3 mM PA, 20% Jiangtang Xiaozhi formula-containing serum, and 5 μM PI3K inhibitor LY294002 for 24 h; Metformin group: Cells were treated with 0.3 mM PA and 200 μM metformin. PA: palmitic acid; JTXZF: Jiangtang Xiaozhi formula; J + L: JTXZF + PI3K inhibitor LY294002; PDX1: pancreatic and duodenal homeobox 1; Oct-4: octamer-binding transcription factor 4; NEUROG3: neurogenin 3; p-PI3K/PI3K: phosphorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1.Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control; bP < 0.05 vs respective PA.
Figure 4 JTXZF upregulates IGF-1 to activate the PI3K/Akt/FoxO1 signaling pathway, thereby alleviating PA-induced dysfunction and dedifferentiation in MIN6 cells A: the Min6 cells expression of IGF-1 mRNA quantified by RT-qPCR; B: Min6 cells were cultured in 3 and 25mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; C: fluorescence intensity for IGF-1; D: IGF-1 expression in Min6 cells was detected by immunofluorescence staining; D1, D2, D4, D5, D7, D8, D10, D11: original magnification, ×200; scale bar = 100 μm; D3, D6, D9, D12: original magnification, × 400; scale bar = 50 μm; E: protein electrophoresis of IGF-1, and PI3K/AKT/FoxO1 signaling molecule; F: densitometric quantification of Western blot bands for IGF-1, normalized to β-Actin; G: densitometric quantification of Western blot bands for p-PI3K/PI3K, p-AKT/AKT and p-FoxO1/FoxO1, normalized to β-Actin; D1, D2, D3: Control group; D4, D5, D6: PA group; D7, D8, D9: JTXZF group; D10, D11, D12: J + si-IGF-1 group. Control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h; JTXZF group: PA-treated cells received 20% Jiangtang Xiaozhi formula -containing serum for 24 h; J + si-IGF-1 group: Cells were treated with 0.3 mM PA and 20% JTXZF-containing serum and transfected with small interfering RNA targeting IGF-1 for 24 h. PA: palmitic acid; JTXZF: Jiangtang Xiaozhi formula; J + si-IGF-1: JTXZF + IGF-1 inhibitor group; IGF-1: insulin-like growth factor 1; p-PI3K/PI3K: phos-phorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1; RT-qPCR: real-time quantitative polymerase chain reaction. Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control; bP < 0.05 vs respective PA.
Figure 4 JTXZF upregulates IGF-1 to activate the PI3K/Akt/FoxO1 signaling pathway, thereby alleviating PA-induced dysfunction and dedifferentiation in MIN6 cells A: the Min6 cells expression of IGF-1 mRNA quantified by RT-qPCR; B: Min6 cells were cultured in 3 and 25mM glucose before measuring insulin concentrations of the supernatant using a commercial ELISA kit; C: fluorescence intensity for IGF-1; D: IGF-1 expression in Min6 cells was detected by immunofluorescence staining; D1, D2, D4, D5, D7, D8, D10, D11: original magnification, ×200; scale bar = 100 μm; D3, D6, D9, D12: original magnification, × 400; scale bar = 50 μm; E: protein electrophoresis of IGF-1, and PI3K/AKT/FoxO1 signaling molecule; F: densitometric quantification of Western blot bands for IGF-1, normalized to β-Actin; G: densitometric quantification of Western blot bands for p-PI3K/PI3K, p-AKT/AKT and p-FoxO1/FoxO1, normalized to β-Actin; D1, D2, D3: Control group; D4, D5, D6: PA group; D7, D8, D9: JTXZF group; D10, D11, D12: J + si-IGF-1 group. Control group: normal group; PA group: cells were treated with 0.3 mM palmitic acid for 24 h; JTXZF group: PA-treated cells received 20% Jiangtang Xiaozhi formula -containing serum for 24 h; J + si-IGF-1 group: Cells were treated with 0.3 mM PA and 20% JTXZF-containing serum and transfected with small interfering RNA targeting IGF-1 for 24 h. PA: palmitic acid; JTXZF: Jiangtang Xiaozhi formula; J + si-IGF-1: JTXZF + IGF-1 inhibitor group; IGF-1: insulin-like growth factor 1; p-PI3K/PI3K: phos-phorylated phosphoinositide 3-kinase/total phosphoinositide 3-kinase; p-AKT/AKT: phosphorylated protein kinase B/total protein kinase B; p-FoxO1/FoxO1: phosphorylated forkhead box O1/total forkhead box O1; RT-qPCR: real-time quantitative polymerase chain reaction. Statistical comparisons between two groups were conducted using unpaired t-tests, while multiple group comparisons were performed using one-way analysis of variance, followed by Tukey’s test for pairwise multiple comparisons. All data are expressed as mean ± standard error of the mean (n = 3). aP < 0.05 vs respective Control; bP < 0.05 vs respective PA.
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