Antidepressant activities and regulative effects on serotonin transporter of Nardostachys jatamansi DC

• Published in: Journal of ethnopharmacology 2021-03, Vol.268, p.113601, Article 113601
• Main Authors: Li, Ran, Wang, Zhi-Mei, Wang, Yan, Dong, Xueqi, Zhang, Li-Hua, Wang, Tao, Zhu, Yan, Gao, Xiu-Mei, Wu, Hong-Hua, Xu, Yan-Tong
• Format: Article
• Language: English
• Subjects: Animals; Antidepressant; Antidepressive Agents - isolation & purification; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Caprifoliaceae; Depression - drug therapy; Depression - metabolism; Depression - psychology; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - isolation & purification; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Hindlimb Suspension - adverse effects; Hindlimb Suspension - physiology; Hindlimb Suspension - psychology; Locomotion - drug effects; Locomotion - physiology; Male; Mice; Mice, Inbred ICR; Nardostachys; Nardostachys jatamansi; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin transporter
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2020.113601

Nardostachys jatamansi (D.Don) DC. (family Caprifoliaceae, NJ) is well-documented and commonly used in the systems of traditional medicine in China, Tibet, Nepal, Bhutan, India and Japan for curing digestive and neuropsychiatric disorders with a long history of medication. However, the possible action mechanisms of antidepressant effects of NJ remain unraveled. The aim of this study was to systematically investigate chemical substances of NJ and their effects on serotonin transporter (SERT) in antidepressant activity. Antidepressant effects of total methanol extract of NJ were evaluated by tail suspension test (TST) and open field test (OFT). Then the total extract was analyzed by ultra-high-performance liquid chromatography (UHPLC) method, and its effect on SERT activity was evaluated by high content assay (HCA) to determine half maximal effective concentration (EC50). This total extract was subfractioned into twenty subfractions by preparative high-performance liquid chromatography (p-HPLC) method, and ‘subfraction-SERT activity’ relationship curve was fitted with medians of the retention time of those subfractions and their SERT activity values. Then, the fraction NJFr.01 enriched with SERT enhancers was optimized, prepared and analyzed by UHPLC method. Antidepressant effects of the fraction NJFr.01 were evaluated by TST and OFT. Further, major constituents of the total extract and fraction NJFr.01 were isolated by p-HPLC and identified by extensive nuclear magnetic resonance (NMR) analyses and comparisons with those reported data, and their SERT activities were also evaluated. Finally, antagonistic effects of chlorogenic acid and desoxo-narchinol A against fluoxetine on SERT were evaluated. Results of TST and OFT demonstrated antidepressant effects of toatal extract of NJ. The EC50 of total extract on SERT enhancement was 31.63 μg/mL. The fitted ‘subfraction-SERT activity’ relationship curve revealed that fraction NJFr.01 was enriched with SERT enhancing constituents. Both total extract and fraction NJFr.01 significantly enhanced SERT activity, while the rest fraction NJFr.02 didn't show any SERT activity. Then, antidepressant effects of fraction NJFr.01 were demonstrated by TST and OFT. Further, phytochemistry investigation and UHPLC analyses confirmed the identification of fourteen constituents in the total extract of NJ, including 7-oxonardinoperoxide (1), desoxo-narchinol A (2), kanshone B (3), narchinol B (4), nardosinonediol (5), kanshone A (6),