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IMMUNOLOGY / BASIC RESEARCH
Network pharmacology and in vitro experiments reveal the autophagy mechanism of Yanggan-Yishui granules in improving hypertensive renal injury
1
Research Institute of Acupuncture and Meridian, Anhui University of Chinese Medicine, Yaohai District, Hefei, Anhui, China
2
Department of Emergency or ICU, Anhui Provincial Hospital of Integrated Traditional and Western Medicine, Shushan District, Hefei, Anhui, China
3
The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Branch Center of the National Clinical Research Center for Cardiovascular Disease, Cardiovascular Institute of Anhui Academy of Chinese Medicine, Shushan District, Hefei, Anhui, China
Submission date: 2024-04-02
Final revision date: 2024-07-02
Acceptance date: 2024-07-03
Online publication date: 2024-07-28
Corresponding author
Xiaohua Dai
The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine Branch Center of the National Clinical Research Center for Cardiovascular Disease Cardiovascular Institute of Anhui Academy of Chinese Medicine 117 Meishan Road Shushan District Hefei 230031 Anhui, China
The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine Branch Center of the National Clinical Research Center for Cardiovascular Disease Cardiovascular Institute of Anhui Academy of Chinese Medicine 117 Meishan Road Shushan District Hefei 230031 Anhui, China
Jing Wang
Research Institute of Acupuncture and Meridian Anhui University of Chinese Medicine Qianjiang Road Yaohai District Hefei 230012 Anhui, China
Research Institute of Acupuncture and Meridian Anhui University of Chinese Medicine Qianjiang Road Yaohai District Hefei 230012 Anhui, China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
In China, Yanggan-Yishui granules (YGYSG) have been used to treat hypertensive renal damage (HRD) for over 20 years. Network pharmacology was used to determine whether YGYSG affects HRD via the autophagy pathway, which was verified using in vitro experiments.
Material and methods:
Common targets of YGYSG, HRD, and the autophagy pathway were screened using network pharmacology, and effective compounds, core targets, and signaling pathways were identified. The affinity of the compounds for the core targets was evaluated using molecular docking simulations. Angiotensin II (Ang II) was used to generate an in vitro renal podocyte model using MPC-5 cells. Morphological changes in the autophagosomes were observed using transmission electron microscopy (TEM). The expression levels of autophagy-related and pathway proteins were detected using western blotting and reverse transcription quantitative real-time polymerase chain reaction (PCR).
Results:
Network pharmacology and molecular docking analyses identified eight autophagy-related core targets and ten core components in the YGYSG treatment of HRD. These targets are mainly involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related biological processes. In vitro experiments showed that Ang II-stimulated renal podocytes exhibited abnormal autophagy, and YGYSG protected renal podocytes from abnormal autophagy. In addition, YGYSG reversed abnormal autophagy and improved HRD by activating the PI3K/AKT/mTOR signaling pathway.
Conclusions:
YGYSG may regulate abnormal autophagy in renal podocytes by activating the PI3K/AKT/mTOR signaling pathway and may play a role in improving HRD.
In China, Yanggan-Yishui granules (YGYSG) have been used to treat hypertensive renal damage (HRD) for over 20 years. Network pharmacology was used to determine whether YGYSG affects HRD via the autophagy pathway, which was verified using in vitro experiments.
Material and methods:
Common targets of YGYSG, HRD, and the autophagy pathway were screened using network pharmacology, and effective compounds, core targets, and signaling pathways were identified. The affinity of the compounds for the core targets was evaluated using molecular docking simulations. Angiotensin II (Ang II) was used to generate an in vitro renal podocyte model using MPC-5 cells. Morphological changes in the autophagosomes were observed using transmission electron microscopy (TEM). The expression levels of autophagy-related and pathway proteins were detected using western blotting and reverse transcription quantitative real-time polymerase chain reaction (PCR).
Results:
Network pharmacology and molecular docking analyses identified eight autophagy-related core targets and ten core components in the YGYSG treatment of HRD. These targets are mainly involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway and autophagy-related biological processes. In vitro experiments showed that Ang II-stimulated renal podocytes exhibited abnormal autophagy, and YGYSG protected renal podocytes from abnormal autophagy. In addition, YGYSG reversed abnormal autophagy and improved HRD by activating the PI3K/AKT/mTOR signaling pathway.
Conclusions:
YGYSG may regulate abnormal autophagy in renal podocytes by activating the PI3K/AKT/mTOR signaling pathway and may play a role in improving HRD.
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