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Liujunzi decoction ameliorats cisplatin-induced anorexia via adjusting metabolic disorders in rats / 中国药理学与毒理学杂志
Chinese Journal of Pharmacology and Toxicology ; (6): 728-729, 2021.
Article in Chinese | WPRIM | ID: wpr-909570
ABSTRACT
OBJECTIVE Cisplatin is a formidable chemotherapy agent widely applying in antineoplastic treatments, but its side effects often limit the clinical usage. Metabolic disorders are one of the side effects induced by cisplatin, which closely relate to the onset of chemotherapy-induced anorexia (CIA) in cancer patients but lacks effective controls. Liujunzi decoction (LJZD) is a traditional Chinese formula that has a promising effect in treating CIA. However, whether LJZD ameliorates CIA through adjusting cisplatin-induced metabolic disorders remain unknow. The present study evalu?ated the mechanism of cisplatin-induced metabolic disorders, and the effect of LJZD in ameliorating these disturbances. METHODS 42 male Sprague-Dawley (SD) rats (180-220 g) were randomly divided into 3 groupsnormal control group (distilled water+saline), model group (distilled water+cisplatin), LJZD group (4.8 g·kg-1 Liujunzi decoction ingredients+cisplatin). Intragastrical administered each drug twice a day (700-1900) since day 0 for 4 d, animals were intraperito?neal injected with cisplatin 6 mg·kg-11 h after administration while normal control groups were injected with same volume of saline. On day 3, each group was anesthetized with pentobarbital sodium 45 mg · kg-1 (ip), and blood samples were collected from aorta abdominalis. Then the samples were analyzed using an LC-ESI-MS/MS system. Significantly regu?lated metabolites between groups were determined by VIP≥1 and absolute Log2FC (fold change)≥1. Identified metabo?lites were mapped to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Metaboanalyst 5.0 (https//www.metaboanalyst.ca/). RESULTS A total of 133, 77 and 32 differential metabolites were filtrated in control vs model, control vs LJZD and model vs LJZD groups respectively. Comparing to control, the levels of hexadecanoic acid (Log2FC=6.3153), linoleic acid (Log2FC=5.3478), and 8, 11-icosadienoic acid (Log2FC=5.2342) significantly increased, and the levels of N-acetyl-L-tyrosine (Log2FC = -2.6283), cinnamic acid (Log2FC = -2.3381), N-acetylphenylalanine (Log2FC = -2.2501) significantly decreased in model group. The KEGG pathway enrichments of these metabolites indi?cated that, cisplatin-induced metabolic disorders by disturbing metabolism pathways such as linoleic acid metabolism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism, which suggested that the onset of CIA was partly associated with the metabolic disorders of linoleic acid, unsaturated fatty acids, and phenylalanine. Compared to control, treatment of LJZD significantly increased the levels of 4-hydroxytryptamine (Log2FC =12.0186), hexadecanoic acid (Log2FC = 5.7412), linoleic acid (Log2FC = 5.1877) and significantly decreased the levels of N-acetylmethionine (Log2FC=-1.7317), 2-aminoethanesulfinic acid (Log2FC=-1.6578), N-acetyl-L-tyrosine (Log2FC=-1.5355). And com?paring to the model group, 4-hydroxytryptamine (Log2FC = 12.0186), 7, 12-diketocholic acid (Log2FC = 2.0998), N-acetylneuraminic acid (Log2FC = 2.0560) markedly increased, and 3-hydroxy-3-methylpentane-1 (Log2FC = -1.9202), 5-dioic acid (Log2FC = -1.7166), N-isovaleroylglycine, hexanoyl glycine (Log2FC = -1.4958) markedly decreased in LJZD group. It was worth noting that, there were 23 differential metabolites filtrated both in control vs model and model vs LJZD groups, which were the key metabolites of LJZD in treating CIA. Among these 23 common metabolites, there were 16 metabolites excluding the control vs LJZD group, that was, LJZD had no effect in normal rats while being able to ameliorated cisplatin-induced metabolic disorders by regulating these 16 metabolites. Cisplatin-induced downregula?tion of 11 metabolites such as hydrocinnamic acid, (±)12(13)epoxy-9Z-octadecenoic acid, cinnamic acid were upregulated after LJZD treatment, and cisplatin-induced upregulation of imidazoleacetic acid, 2'-deoxycytidine-5'-monophosphate and other 5 metabolites were downregulated by LJZD. The KEGG pathway analysis indicated that the linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism were the most enriched metabolic pathway. Thus, cisplatin-induced metabolic disturbances mainly by disturbing linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism, and LJZD interacted with these metabolic pathways to reduce metabolic disorders and thus ameliorated CIA. CONCLUSION Cisplatin-induced anorexia was closely related to the metabolic disorders of linoleic acid metabo?lism, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. The mechanism of LJZD in ameliorating CIA was in concerned with the metabolic adjustments, relating to the regulation of linoleic acid metabolism, histidine metabolism, and pyrimidine metabolism.

Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Language: Chinese Journal: Chinese Journal of Pharmacology and Toxicology Year: 2021 Type: Article