TY - JOUR
T1 - Zhenwu decoction ameliorates cardiac hypertrophy through activating sGC (soluble guanylate cyclase) - cGMP (cyclic guanosine monophosphate) - PKG (protein kinase G) pathway
AU - Chen, Liqian
AU - Zhou, Xinghong
AU - Deng, Yijian
AU - Yang, Ying
AU - Chen, Xiaohu
AU - Chen, Qinghong
AU - Liu, Yanyan
AU - Fu, Xiuqiong
AU - Kwan, Hiu Yee
AU - You, Yanting
AU - Jin, Wen
AU - Zhao, Xiaoshan
N1 - Funding Information:
This work was supported by the Key Project of National Natural Science Foundation of China (81830117); the National Natural Science Foundation of China (82074424, 81673949); the Natural Science Foundation of Guangdong Province, China (2019A1515010400), the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202001) and open Project of State Key Laboratory of Dampness Syndrome of Chinese Medicine, and the Second Affiliated Hospital of Guangzhou University of Chinese Medicine (SZ2021KF12).
Publisher Copyright:
© 2022 The Authors.
PY - 2023/1/10
Y1 - 2023/1/10
N2 - Ethnopharmacological relevance: Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear.Aim of the study: The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms.Materials and methods: The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies.Results: Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC.Conclusion: ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
AB - Ethnopharmacological relevance: Zhenwu Decoction (ZWD) is a traditional Chinese medicine (TCM) formula which has wide scope of indications related to Yang deficiency and dampness retention in TCM syndrome. Cardiac hypertrophy can induce similar symptoms and signs to the clinical features of Yang deficiency and dampness retention syndrome. ZWD can increase the left ventricular ejection fraction, reduce cardiac hypertrophy of patients with chronic heart failure. However, its underlying pharmacological mechanism remains unclear.Aim of the study: The study aimed to confirm the protective effects of ZWD on cardiac hypertrophy and explore the underlying mechanisms.Materials and methods: The potential targets and pathways of ZWD in cardiac hypertrophy were highlighted by network pharmacology and validated by mechanistic and functional studies.Results: Our network pharmacology analysis suggests that the protective effects of ZWD on cardiac hypertrophy are related to cyclic guanosine monophosphate (cGMP) - protein kinase G (PKG) pathway. Subsequent animal studies showed that ZWD significantly ameliorated cardiac function decline, cardiac hypertrophy, cardiac fibrosis and cardiomyocyte apoptosis. To explore the underlying mechanisms of action, we performed Western blotting, immunohistochemical analysis, and detection of inflammatory response and oxidative stress. Our results showed that ZWD activated the soluble guanylate cyclase (sGC) - cGMP - PKG signaling pathway. The sGC inhibitor ODQ that blocks the sGC-cGMP-PKG signaling pathway in zebrafish abolished the protective effects of ZWD, suggesting sGC-cGMP-PKG is the main signaling pathway mediates the protective effect of ZWD in cardiac hypertrophy. In addition, three major ingredients from ZWD, poricoic acid C, hederagenin and dehydrotumulosic acid, showed a high binding energy with prototype sGC.Conclusion: ZWD reduces oxidative stress and inflammation and exerts cardioprotective effects by activating the sGC-cGMP-PKG signaling pathway.
KW - Cardiac hypertrophy
KW - Cyclic guanosine monophosphate (cGMP)
KW - Protein kinase G (PKG)
KW - Soluble guannylate cyclase(sGC)
KW - Zhenwu decoction
UR - http://www.scopus.com/inward/record.url?scp=85138800011&partnerID=8YFLogxK
U2 - 10.1016/j.jep.2022.115705
DO - 10.1016/j.jep.2022.115705
M3 - Journal article
C2 - 36099983
AN - SCOPUS:85138800011
SN - 0378-8741
VL - 300
JO - Journal of Ethnopharmacology
JF - Journal of Ethnopharmacology
M1 - 115705
ER -
