TY - JOUR
T1 - Zhishi Xiebai Guizhi Decoction modulates hypoxia and lipid toxicity to alleviate pulmonary vascular remodeling of pulmonary hypertension in rats
AU - Fu, Min
AU - Li, Yuan
AU - Liu, Jingjing
AU - Liu, Junjie
AU - Wei, Jiaoxia
AU - Qiao, Yuxin
AU - Zhong, Hanxin
AU - Han, Dongyang
AU - Lu, Haitao
AU - Yao, Li
N1 - Funding Information:
This work was supported by Natural Science Foundation of Heilongjiang Province, (Grant No. LH2021H016), Harbin Medical University Marshal Initiative Funding (Grant No. HMUMIF-21026), the Fundamental Research Funds for the Central Universities (Grant No. 22X010201564), the opening grant provided by Key Laboratory of Systems Biomedicine (Ministry of Education) in Shanghai Jiao Tong University (Grant No. KLSB2022KF-02), Science Foundation for Traditional Chinese Medicine of Administration of Traditional Chinese Medicine of Heilongjiang (Grant No. ZHY2024-135), National Key Research and Development Program of China (Nos. 2017YFC1308600 and 2017YFC1308605) and the key grant provided by National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (Shanghai, China) (Grant No. NRCTM (SH)-2021-07).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Background: Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.Methods: We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this.Results: Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl-l-carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH.Conclusion: Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs.
AB - Background: Pulmonary hypertension (PH) is a severe cardio-pulmonary vascular disease, involves complex molecular mechanism especially during the pathological process of pulmonary vascular remodeling, brings a significant challenge to clinical treatment and thus resulting in high mortality rates. Classic Traditional Chinese medicine formula, Zhishi Xiebai Guizhi Decoction (ZXGD), holds therapeutic potential for PH. In present study, we sought to explore therapeutic potential of ZXGD against PH in rats.Methods: We employed a combination methods of chemical profiling, echocardiographic, morphologic measurements, molecular biology, rats models and cultured pulmonary artery smooth muscle cells (PASMCs) to achieve this.Results: Eighteen compounds were precisely identified in ZXGD using UHPLC-QTOF-MS/MS. Our data demonstrated ZXGD could alleviate PH by reducing pulmonary artery pressure and alleviating pulmonary vascular remodeling in rats. Specifically, ZXGD was found to intervene in abnormal expansion of PASMCs, thereby attenuating pulmonary vascular remodeling. ZXGD was also observed to modulate expressions of HIF-1α, ROS, and Nrf2 to alleviate hypoxia and oxidative stress. Additionally, ZXGD significantly regulated disorders in pro-inflammatory cytokines, thus mitigating inflammation. Furthermore, ZXGD decreased levels of decadienyl-l-carnitine and LDL-C, while elevating HDL-C and lipid droplet counts, thereby reducing cholesterol and lipid toxicity and preserving mitochondrial function. Importantly, inhibition of HIF-1α reversed expression of key pathological triggers for pulmonary vascular remodeling. Neohesperidin and naringin in ZXGD extract were identified as the primary contributors to its pharmacological effects against PH.Conclusion: Altogether, our study empirically explored therapeutic potential and pharmacological mechanisms of ZXGD in treating PH, offering a groundwork for the development of novel anti-PH drugs.
KW - Chemical compounds
KW - HIF-1α
KW - Pulmonary hypertension
KW - Pulmonary vascular remodeling
KW - Zhishi Xiebai Guizhi Decoction
UR - http://www.scopus.com/inward/record.url?scp=85212440835&partnerID=8YFLogxK
U2 - 10.1186/s13020-024-01039-0
DO - 10.1186/s13020-024-01039-0
M3 - Journal article
AN - SCOPUS:85212440835
SN - 1749-8546
VL - 19
JO - Chinese Medicine
JF - Chinese Medicine
IS - 1
M1 - 173
ER -
