Global and Targeted Metabolomics Evidence of the Protective Effect of Chinese Patent Medicine Jinkui Shenqi Pill on Adrenal Insufficiency after Acute Glucocorticoid Withdrawal in Rats.
Glucocorticoids are commonly used in anti-inflammatory and immunomodulatory therapies, but glucocorticoid withdrawal can result in life-threatening risk of adrenal insufficiency. Chinese patented pharmaceutical product Jinkui Shenqi pill (JKSQ) has potent efficacy on clinical adrenal insufficiency resulting from glucocorticoid withdrawal. However, the underlying molecular mechanism remains unclear. We used an animal model to study JKSQ-induced metabolic changes under adrenal insufficiency and healthy conditions. Sprague-Dawley rats were treated with hydrocortisone for 7 days with or without 15 days of JKSQ pretreatment. Sera were collected after 72 h hydrocortisone withdrawal and used for global and free fatty acids (FFAs)-targeted metabolomics analyses using gas chromatography/time-of-flight mass spectrometry and ultraperformance liquid chromatography/quadruple time-of-flight mass spectrometry. Rats without hydrocortisone treatment were used as controls. JKSQ pretreatment normalized the significant changes of 13 serum metabolites in hydrocortisone-withdrawal rats, involving carbohydrates, lipids, and amino acids. The most prominent effect of JKSQ was on the changes of FFAs and some [product FFA]/[precursor FFA] ratios, which represent estimated desaturase and elongase activities. The opposite metabolic responses of JKSQ in adrenal insufficiency rats and normal rats highlighted the "Bian Zheng Lun Zhi" (treatment based on ZHENG differentiation) guideline of TCM and suggested that altered fatty acid metabolism was associated with adrenal insufficiency after glucocorticoid withdrawal and the protective effects of JKSQ.
College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science , Shanghai 201620, China.|Metabolomics Shared Resource, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
Linjing
L
Zhao
Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
Aihua
A
Zhao
Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
Tianlu
T
Chen
Metabolomics Shared Resource, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
Wenlian
W
Chen
Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
Jiajian
J
Liu
Metabolomics Shared Resource, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
Runmin
R
Wei
School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, China.
Jing
J
Su
School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, China.
Xuelan
X
Tang
School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, China.
Keyi
K
Liu
School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, China.
Ran
R
Zhang
Metabolomics Shared Resource, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
Guoxiang
G
Xie
Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii at Manoa , Manoa, Hawaii 96813, United States.
Jun
J
Panee
School of Pharmacy, Shanghai Jiao Tong University , Shanghai 200240, China.
Mingfeng
M
Qiu
Metabolomics Shared Resource, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.|Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.
Wei
W
Jia
D000309:Adrenal Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002681:China; D002853:Chromatography, Liquid; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D008401:Gas Chromatography-Mass Spectrometry; D005938:Glucocorticoids / Q000009:adverse effects; D006854:Hydrocortisone; D055432:Metabolomics / Q000379:methods*; D020011:Protective Agents / Q000627:therapeutic use; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D005230:Fatty Acids, Nonesterified; D005938:Glucocorticoids; D020011:Protective Agents; C585913:shenqi; D006854:Hydrocortisone
Jinkui Shenqi pill; TCM; fatty acid metabolism; glucocorticoid withdrawal; glucocorticoid-induced adrenal insufficiency; metabolomics