Toxicity and Its Mechanism Study of Arecae semen Aqueous Extract in Wistar Rats by UPLC-HDMS-Based Serum Metabolomics

Zhe Jia; Ting Han; Qinghua Lin; Wenjia Qu; Tianying Jia; Mengnan Liu; Haili Wang; Jieping Xin; Xinfang Xu; Xiangri Li

doi:10.1155/2020/2716325

Toxicity and Its Mechanism Study of Arecae semen Aqueous Extract in Wistar Rats by UPLC-HDMS-Based Serum Metabolomics

Evid Based Complement Alternat Med. 2020 Jan 29:2020:2716325. doi: 10.1155/2020/2716325. eCollection 2020.

Authors

Zhe Jia^{1

2}, Ting Han^{1

2}, Qinghua Lin³, Wenjia Qu^{1

2}, Tianying Jia^{1

2}, Mengnan Liu^{1

2}, Haili Wang^{1

2}, Jieping Xin^{1

2}, Xinfang Xu^{1

2}, Xiangri Li^{1

2}

Affiliations

¹ School of Chinese Materia Medica, Beijing University of Chinese Medicine, Higher Education Park, Fangshan District, Beijing 102488, China.
² Beijing Key Laboratory for Quality Evaluation of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China.
³ College of Pharmacy, Guangxi University of Chinese Medicine, Guangxi Province, Nanning, China.

Abstract

Background: Arecae semen (AS) is officially recorded in Chinese Pharmacopoeia and it is known for its multiple functions, including antidepressive, antioxidant, anti-inflammatory, and cholesterol-lowering effects, which have been confirmed by modern pharmacological study. Previous study in our laboratory showed that long-term oral administration of Arecae semen (AS) is officially recorded in Chinese Pharmacopoeia and it is known for its multiple functions, including antidepressive, antioxidant, anti-inflammatory, and cholesterol-lowering effects, which have been confirmed by modern pharmacological study. Previous study in our laboratory showed that long-term oral administration of Hypothesis. The aim of this work was to characterize the metabolome, evaluate the metabolic changes, and study the mechanisms of the toxicity induced by different treatment doses of ASAE via metabolomics.

Methods: Wistar rats were administered orally two different doses of ASAE (1500 and 4500 mg/kg/d) for 30 days. The investigation was carried out to evaluate the safety of ASAE. And, the UPLC-HDMS-based serum metabolomics in conjunction with multivariate statistical techniques was applied to investigate the serum metabolite profile and potential markers of toxicity induced by different doses of ASAE.

Results: Coupled with blood biochemistry and histopathology results, the significant difference in metabolic profiling was observed between 1500 and 4500 mg/kg/d dosages of ASAE-treated rats and normal rats by using pattern recognition analysis, indicating that changes in serum metabolites must have occurred. Some significant changed metabolites such as arachidonic acid, linoleic acid, stearic acid, and LPC (18 : 1) have been found and identified. These biochemical changes in serum metabolites are related to the perturbation of linoleic acid metabolism, arachidonic acid metabolism, glycerophospholipid metabolism, and purine metabolism, which may be helpful to further understand the cardiotoxicity and neurotoxicity of ASAE.

Conclusion: The study shows that the metabolomic method may be a valuable tool for studying the essence of toxicity induced by traditional Chinese medicine.