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Title: | Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment | Authors: | Zhu, YX Tang, ZL Lu, L Qiu, ZC Pan, D Yu, Y Xiao, HH Wong, MS |
Issue Date: | Mar-2024 | Source: | Acupuncture and herbal medicine, Mar. 2024, v. 4, no. 1, p. 102-112 | Abstract: | Objective: Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation. Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance, a folk herbal medicine used to treat bone fractures and joint diseases in China, exerted bone-protective effects, and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1 (TPH-1). However, there is no direct evidence for the action of lignans on TPH-1. This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties. Methods: Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1. The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells. The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined. Result: The lignans showed high binding scores and binding affinities to TPH-1, inhibited the activity and protein expression of TPH-1, suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density. Conclusion: This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases, including osteoporosis. |
Keywords: | Lignan Osteoporosis Sambucus williamsii Hance Serotonin TPH-1 inhibitor |
Publisher: | Wolters Kluwer Health | Journal: | Acupuncture and herbal medicine | ISSN: | 2097-0226 | EISSN: | 2765-8619 | DOI: | 10.1097/HM9.0000000000000095 | Rights: | Copyright © 2024 Tianjin University of Traditional Chinese Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. The following publication Zhu, Yu-Xin1; Tang, Zi-Ling2; Lu, Lu1; Qiu, Zuo-Cheng2; Pan, Dabo3; Yu, Yang3; Xiao, Hui-Hui1,4,5,*; Wong, Man-Sau1,4,5. Exploring a novel class tryptophan hydroxylase 1 inhibitor derived from Sambucus williamsii Hance for the osteoporosis treatment. Acupuncture and Herbal Medicine 4(1):p 102-112, March 2024 is available at https://doi.org/10.1097/HM9.0000000000000095. |
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