Broad range lipidomics and metabolomics coupled with 16S rRNA sequencing to reveal the mechanisms of Huangkui Capsule against cisplatin-induced nephrotoxicity.

IF 4.8 2区 医学 Q1 CHEMISTRY, MEDICINAL
Jian-Cheng Liao, Jie Xiang, Wan-Yu Gui, Hui-Zhi Luo, Qing You, Qi-Rui He, Ming-Xia Lu, Shu-Yun Yang, Qiong Wang, Jian-Dong Zou, Chang-Yin Li
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引用次数: 0

Abstract

Ethnopharmacological relevance: Huangkui Capsule (HKC) is a traditional Chinese medicinal preparation. Numerous clinical studies have reported that HKC has a good nephroprotection effect. The clinical application of cisplatin is greatly limited by its nephrotoxicity, and HKC shows promise in preventing cisplatin-induced nephrotoxicity (CIN).

Aim of the study: To evaluate the effectiveness of HKC in alleviating CIN and explore its underlying action mechanisms.

Materials and methods: A rat model of CIN was established via single-dose injection of cisplatin. The effectiveness of HKC was evaluated by biochemical indices and pathological sections. Then, serum, kidney, and cecal endogenous metabolic profiles as well as the gut microbiota were characterized using lipidomics, metabolomics, and 16S rRNA high-throughput sequencing technique. Spearman's correlation analysis was carried out between gut microbiota, biomarkers, and biochemical indices. Finally, antibiotic treatment was performed to establish pseudo-sterile rat model and validate the nephroprotection of HKC in a gut microbiota-dependent manner.

Results: HKC could significantly attenuate the abnormal elevation of serum creatinine and urea nitrogen, kidney index, and kidney injury score in CIN rats, remarkably alleviate the disturbance of metabolic profiles of serum, kidney, and cecal contents, corresponding to the endogenous metabolites such as fatty acids, phosphatidylcholines, amino acids, acylcarnitines, and short-chain fatty acids, and enrich the diversity of gut microbiota. Spearman's correlation analysis revealed that Clostridium_sensu_stricto_1 was positively correlated with the altered short-chain fatty acids in serum and negatively correlated with the altered acylcarnitine in the kidney. In the pseudo-sterile rat model, the attenuation effect of HKC on the abnormal elevation of serum creatinine and urea nitrogen, along with the alleviation of metabolic profile disorders, was greatly diminished or even abolished, demonstrating the nephroprotective effect of HKC in a gut microbiota-dependent manner.

Conclusions: HKC exerted the nephroprotective effect on CIN in a gut microbiota-dependent manner, mainly by regulating Clostridium_sensu_stricto_1 mediated metabolisms of phosphatidylcholines, acylcarnitines, fatty acids, tryptophan and short-chain fatty acids, thereby reducing the inflammatory response. The present study could provide reliable scientific evidence for gut microbiota-dependent mechanisms of HKC in the treatment of kidney injury and may widen the clinical application of HKC in cisplatin-containing cancer therapy.

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来源期刊
Journal of ethnopharmacology
Journal of ethnopharmacology 医学-全科医学与补充医学
CiteScore
10.30
自引率
5.60%
发文量
967
审稿时长
77 days
期刊介绍: The Journal of Ethnopharmacology is dedicated to the exchange of information and understandings about people''s use of plants, fungi, animals, microorganisms and minerals and their biological and pharmacological effects based on the principles established through international conventions. Early people confronted with illness and disease, discovered a wealth of useful therapeutic agents in the plant and animal kingdoms. The empirical knowledge of these medicinal substances and their toxic potential was passed on by oral tradition and sometimes recorded in herbals and other texts on materia medica. Many valuable drugs of today (e.g., atropine, ephedrine, tubocurarine, digoxin, reserpine) came into use through the study of indigenous remedies. Chemists continue to use plant-derived drugs (e.g., morphine, taxol, physostigmine, quinidine, emetine) as prototypes in their attempts to develop more effective and less toxic medicinals.
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