Toxicity mechanism of Rhododendri Mollis Flos: based on serum metabolomics and network toxicology.
10.19540/j.cnki.cjcmm.20211223.702
- Author:
Xiao-Hong GUO
1
;
Meng-Jun HUANG
2
;
Li-Juan WANG
3
;
Qiang RAN
3
;
Sen YANG
4
;
Wen-Hui WU
3
;
Xiao-Qiong ZHANG
3
;
You-Ping LIU
4
Author Information
1. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu 611137, China Chongqing Traditional Chinese Medicine Hospital Chongqing 400021,China.
2. National-Local Joint Engineering Research Center for Innovative Targeted Drugs, College of Pharmaceutical Sciences, Chongqing University of Arts and Sciences Chongqing 402160, China.
3. Chongqing Traditional Chinese Medicine Hospital Chongqing 400021,China.
4. State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine Chengdu 611137, China.
- Publication Type:Journal Article
- Keywords:
Rhododendri Mollis Flos;
biomarkers;
metabolomics;
network toxicology;
target protein;
toxicity
- MeSH:
Animals;
Cardiotoxicity;
Chemical and Drug Induced Liver Injury;
Drugs, Chinese Herbal/toxicity*;
Hormones;
Metabolomics;
Rats
- From:
China Journal of Chinese Materia Medica
2022;47(7):1932-1941
- CountryChina
- Language:Chinese
-
Abstract:
This study aims to explore the toxicity mechanism of Rhododendri Mollis Flos(RMF) based on serum metabolomics and network toxicology. The toxic effect of RMF on normal rats was evaluated according to the symptoms, serum biochemical indexes, and histopathology. Serum metabolomics was combined with multivariate statistical analysis to search endogenous differential metabolites and related metabolic pathways. The toxic components, targets, and signaling pathways of RMF were screened by network toxicology technique, and the component-target-metabolite-metabolic pathway network was established with the help of serum metabolomics. The result suggested the neurotoxicity, hepatotoxicity, and cardiotoxicity of RMF. A total of 31 differential metabolites and 10 main metabolic pathways were identified by serum metabolomics, and 11 toxic components, 332 related target genes and 141 main signaling pathways were screened out by network toxicology. Further analysis yielded 7 key toxic components: grayanotoxin Ⅲ,grayanotoxinⅠ, rhodojaponin Ⅱ, rhodojaponin Ⅴ, rhodojaponin Ⅵ, rhodojaponin Ⅶ, and kalmanol, which acted on the following 12 key targets: androgen receptor(AR), albumin(ALB), estrogen receptor β(ESR2), sex-hormone binding globulin(SHBG), type 11 hydroxysteroid(17-beta) dehydrogenase(HSD17 B11), estrogen receptor α(ESR1), retinoic X receptor-gamma(RXRG), lactate dehydrogenase type C(LDHC), Aldo-keto reductase(AKR) 1 C family member 3(AKR1 C3), ATP binding cassette subfamily B member 1(ABCB1), UDP-glucuronosyltransferase 2 B7(UGT2 B7), and glutamate-ammonia ligase(GLUL). These targets interfered with the metabolism of gamma-aminobutyric acid, estriol, testosterone, retinoic acid, 2-oxobutyric acid, and affected 4 key metabolic pathways of alanine, aspartate and glutamate metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, and retinol metabolism. RMF exerts toxic effect on multiple systems through multiple components, targets, and pathways. Through the analysis of key toxic components, target genes, metabolites, and metabolic pathways, this study unveiled the mechanism of potential neurotoxicity, cardiotoxicity, and hepatotoxicity of RMF, which is expected to provide a clue for the basic research on toxic Chinese medicinals.
