Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy
Aims and backgroundAutophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates in DN injury is not well understood. Our previous studies have shown that Astragalus membranaceus - Cornus officinalis (AM-CO) improves DN lipid metabol...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1505637/full |
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| author | Rui Zhang Rui Zhang Xushan Lan Wenhui Zhu Lifan Wang Peng Liu Peng Liu Ping Li |
| author_facet | Rui Zhang Rui Zhang Xushan Lan Wenhui Zhu Lifan Wang Peng Liu Peng Liu Ping Li |
| author_sort | Rui Zhang |
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| description | Aims and backgroundAutophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates in DN injury is not well understood. Our previous studies have shown that Astragalus membranaceus - Cornus officinalis (AM-CO) improves DN lipid metabolism disorders, however, the exact mechanism of which is also not well defined. The aim of this study was to investigate the therapeutic effects of AM-CO officinalis on DN and the mechanism of action on DN using lipidomic techniques and network pharmacological approaches.Experimental methodsThe in vivo experiments were carried out using the KKAy mice model with the intervention of AM-CO. Analysis of kidney and serum samples from KKAy mice treated with AM-CO using lipidomic technology to obtain biomarkers for the treatment of DN and to identify the main targets associated with DN; Analyse potential signalling pathways for the treatment of DN using network pharmacology methods. In vitro experiments were performed with PA-induced HK-2 cells and results verified by protein blotting and immunofluorescence.ResultsLipidomic analysis revealed 363 differential metabolites in serum and 195 differential metabolites in kidney tissue, which were compared and analysed to find their common differential metabolites belonging to the phosphatidylethanolamine (PE) classes, respectively. In addition, PE plays a vital functiona in the process of autophagy. And the network analysis results speculated that Calycosin (Cal), a major component of AM-CO, could ameliorate DN injury by regulating autophagy through modulating the PI3K-AKT signaling pathway. In vivo experiments showed that AM-CO could induce autophagy, an increase in LC3II expression and a decrease in P62 expression. Meanwhile, in vitro experiments showed that Cal could also increase the expression of LC3II and inhibit the protein expression levels of p62, PI3K, P-AKT and AKT. The addition of a PI3K activator resulted in a reversal of protein expression.ConclusionIn conclusion, Cal can ameliorate the injury in DN by regulating autophagy, and PI3K-AKT is the main pathway for its regulation of autophagy and a key pathway for the action of AM-CO. |
| format | Article |
| id | doaj-art-76de46ce629d4a6e8e5e497dec7727dc |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj-art-76de46ce629d4a6e8e5e497dec7727dc2025-08-20T02:57:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-05-011610.3389/fphar.2025.15056371505637Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathyRui Zhang0Rui Zhang1Xushan Lan2Wenhui Zhu3Lifan Wang4Peng Liu5Peng Liu6Ping Li7Xiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, ChinaRenal Division, Department of Medicine, Heilongjiang Academy of Chinese Medicine Sciences, Harbin, ChinaRenal Division, Department of Medicine, Heilongjiang Academy of Chinese Medicine Sciences, Harbin, ChinaCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, ChinaRenal Division, Department of Medicine, Heilongjiang Academy of Chinese Medicine Sciences, Harbin, ChinaXiyuan Hospital, China Academy of Traditional Chinese Medicine, Beijing, ChinaShunyi Hospital, Beijing Hospital of Traditional Chinese Medicine, Beijing, ChinaBeijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, ChinaAims and backgroundAutophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates in DN injury is not well understood. Our previous studies have shown that Astragalus membranaceus - Cornus officinalis (AM-CO) improves DN lipid metabolism disorders, however, the exact mechanism of which is also not well defined. The aim of this study was to investigate the therapeutic effects of AM-CO officinalis on DN and the mechanism of action on DN using lipidomic techniques and network pharmacological approaches.Experimental methodsThe in vivo experiments were carried out using the KKAy mice model with the intervention of AM-CO. Analysis of kidney and serum samples from KKAy mice treated with AM-CO using lipidomic technology to obtain biomarkers for the treatment of DN and to identify the main targets associated with DN; Analyse potential signalling pathways for the treatment of DN using network pharmacology methods. In vitro experiments were performed with PA-induced HK-2 cells and results verified by protein blotting and immunofluorescence.ResultsLipidomic analysis revealed 363 differential metabolites in serum and 195 differential metabolites in kidney tissue, which were compared and analysed to find their common differential metabolites belonging to the phosphatidylethanolamine (PE) classes, respectively. In addition, PE plays a vital functiona in the process of autophagy. And the network analysis results speculated that Calycosin (Cal), a major component of AM-CO, could ameliorate DN injury by regulating autophagy through modulating the PI3K-AKT signaling pathway. In vivo experiments showed that AM-CO could induce autophagy, an increase in LC3II expression and a decrease in P62 expression. Meanwhile, in vitro experiments showed that Cal could also increase the expression of LC3II and inhibit the protein expression levels of p62, PI3K, P-AKT and AKT. The addition of a PI3K activator resulted in a reversal of protein expression.ConclusionIn conclusion, Cal can ameliorate the injury in DN by regulating autophagy, and PI3K-AKT is the main pathway for its regulation of autophagy and a key pathway for the action of AM-CO.https://www.frontiersin.org/articles/10.3389/fphar.2025.1505637/fulldiabetic nephropathyAstragalus membranaceus -Cornus officinaliscalycosinlipidomic technologynetwork analysis |
| spellingShingle | Rui Zhang Rui Zhang Xushan Lan Wenhui Zhu Lifan Wang Peng Liu Peng Liu Ping Li Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy Frontiers in Pharmacology diabetic nephropathy Astragalus membranaceus -Cornus officinalis calycosin lipidomic technology network analysis |
| title | Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy |
| title_full | Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy |
| title_fullStr | Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy |
| title_full_unstemmed | Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy |
| title_short | Regulation of autophagy by the PI3K-AKT pathway in Astragalus membranaceus -Cornus officinalis to ameliorate diabetic nephropathy |
| title_sort | regulation of autophagy by the pi3k akt pathway in astragalus membranaceus cornus officinalis to ameliorate diabetic nephropathy |
| topic | diabetic nephropathy Astragalus membranaceus -Cornus officinalis calycosin lipidomic technology network analysis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1505637/full |
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