Abstract
San-Huang-Xie-Xin decoction (SHXXD), composed of Rhei Radix et Rhizoma, Coptidis Rhizoma, and Scutellariae Radix, is a representative antipyretic and detoxifying prescription in traditional Chinese medicine. In this study, we investigated the antistress effects and underlying mechanisms of San-Huang-Xie-Xin decoction (SHXXD) on restraint-stressed mice by 1H NMR-based metabolomics combined with biochemistry assay. A total of 48 male mice (5 weeks old, 18-22 g) were divided randomly into 6 groups (n = 8), including the normal group, restraint-stressed group, vitamin C group (positive drug, 17 mg/kg), and 3-dosage groups of SHXXD (200, 400, and 800 mg/kg). The stress model was induced by restraining mice in a polypropylene centrifuge tube for 6 h every day. The rotarod test was performed, and several biochemical indicators were measured. Moreover, other 24 animals were divided into 3 groups (n = 8) including the normal group, restraint-stressed group, and SHXXD group (800 mg/kg) for 1H NMR-based metabolomics analysis. Our results showed that SHXXD significantly increased the rotarod time, thymus index, spleen index, and the levels of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and interleukin- (IL-) 2, but decreased the levels of malondialdehyde (MDA), IL-1β, tumor necrosis factor- (TNF-) α, corticosterone (CORT), and adrenocorticotropic hormone (ACTH) in restraint-stressed mice. Moreover, the contents of eight endogenous metabolites that were changed by restraint stress were significantly reversed by SHXXD. The results of both metabolomics and biochemical analysis indicated that SHXXD (800 mg/kg, p.o.) could improve the biochemical changes and metabolic disorders in restraint-stressed mice by antioxidation and anti-inflammation, enhancing the body's immune function and restoring several disturbed metabolic pathways (i.e., lipid metabolism, glycolysis and gluconeogenesis, inflammatory injury, and energy metabolism). Taken together, these results indicated that SHXXD has a potential antistress effect in restraint-stressed mice and could be considered as a candidate drug for stress-related disorders.
Highlights
Previous reports have indicated that stress could negatively affect physical and mental performances of a human being and result in various stress-related disorders, such as anxiety and insomnia [1, 2]
Aloe-emodin and rhein are mainly from Rhei Radix et Rhizoma; jatrorrhizine, palmatine, and berberine are from Coptidis Rhizoma; and baicalin, wogonoside, baicalein, and wogonin are from Scutellariae Radix
The results indicated that lactate, lowdensity lipoprotein (LDL)/very low-density lipoprotein (VLDL), alanine, lipids, N-acetyl glycoproteins, glycerol, choline, and phosphorylcholine levels were significantly increased, whereas acetoacetate and valine were significantly decreased by the restraint stress procedure
Summary
Previous reports have indicated that stress could negatively affect physical and mental performances of a human being and result in various stress-related disorders, such as anxiety and insomnia [1, 2]. The current available pharmacotherapies to treat these stress-related disorders are limited due to low efficacy and oppressive side effects [5]. Increasing scientific evidences have suggested that traditional Chinese medicines (TCMs), which have been utilized to treat diseases for thousands of years in China, possess promising curative effects for treating some difficult miscellaneous diseases, including some neuropsychiatric disorders such as depression, anxiety, and insomnia [6, 7]. To the best of our knowledge, there is no systemic research regarding the effects of SHXXD against stress-related disorders
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