Rhodiola crenulata extract decreases fatty acid oxidation and autophagy to ameliorate pulmonary arterial hypertension by targeting inhibiton of acylcarnitine in rats  

作　　者：REN Huan-Huan NIU Zheng GUO Rui FU Min LI Hai-Ru ZHANG Xuan-Yu YAO Li 

机构地区：[1]Department of Medicinal Chemistry and Natural Medicine Chemistry,Department of Pharmacognosy,College of Pharmacy,Harbin Medical University,Harbin 150081,China [2]State-Province Key Laboratory of Biomedicine-Pharmaceutics of China,Harbin Medical University,Harbin 150081,China [3]Key Laboratory of Systems Biomedicine(Ministry of Education),Shanghai Center for Systems Biomedicine,Shanghai Jiao Tong University,Shanghai 200240,China [4]Department of Ultrasound,The Second Affiliated Hospital of Harbin Medical University,Harbin 150081,China

出　　处：《Chinese Journal of Natural Medicines》2021年第2期120-133,共14页中国天然药物（英文版）

基　　金：the National Natural Science Foundation of China(No.81302764);the Science and Technology Grant for Excellent Talents of Harbin(No.2017RAXXJ-060).

摘　　要：Pulmonary arterial hypertension(PAH)is a devastating pulmonary circulation disease lacking high-efficiency therapeutics.The present study aims to decipher the therapeutic mechanism of Rhodiola crenulata,a well-known traditional chinese medicine with cardiopulmonary protection capacity,on PAH by exploiting functional lipidomics.The rat model with PAH was successfully established for first,following Rhodiola crenulata water extract(RCE)treatment,then analysis of chemical constituents of RCE was performed,additional morphologic,hemodynamic,echocardiographic measurements were examined,further targeted lipidomics assay was performed to identify differential lipidomes,at last accordingly mechanism assay was done by combining qRT-PCR,Western blot and ELISA.Differential lipidomes were identified and characterized to differentiate the rats with PAH from healthy controls,mostly assigned to acylcarnitines,phosphatidylcholines,sphingomyelin associated with the PAH development.Excitingly,RCE administration reversed high level of decadienyl-L-carnitine by the modulation of metabolic enzyme CPT1A in mRNA and protein level in serum and lung in the rats with PAH.Furthermore,RCE was observed to reduce autophagy,confirmed by significantly inhibited PPARγ,LC3B,ATG7 and upregulated p62,and inactivated LKB1-AMPK signal pathway.Notably,we accurately identified the constituents in RCE,and delineated the therapeutic mechansim that RCE ameliorated PAH through inhibition of fatty acid oxidation and autophagy.Altogether,RCE might be a potential therapeutic medicine with multi-targets characteristics to prevent the progression of PAH.This novel findings pave a critical foundation for the use of RCE in the treatment of PAH.

关 键 词：Pulmonary arterial hypertension Rhodiola crenulata Target lipidomics Fatty acid oxidation AUTOPHAGY 

分 类 号：R965[医药卫生—药理学]