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 herb...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.展开更多
Loss of excessive hair growth causes psychological distress in many people,seriously affecting their social confidence and quality of life.The dermal papilla(DP)plays a pivotal role in regulating hair follicle(HF)morp...Loss of excessive hair growth causes psychological distress in many people,seriously affecting their social confidence and quality of life.The dermal papilla(DP)plays a pivotal role in regulating hair follicle(HF)morphogenesis and hair growth.However,the genes that govern the DP function in HF have not been extensively investigated.Genome-wide association studies have reported that two single-nucleotide polymorphisms(rs929626 and rs1081073)of the transcription factor EBF1(early B-cell factor 1)are associated with male pattern baldness.展开更多
基金supported by the Natural Science Foundation of Guangdong Province(2021A1515010648)the National Natural Science Foundation of China(81903616)+1 种基金The Hong Kong Polytechnic University Start-up Funding(A0038607)The Mainland-Hong Kong Joint Funding Scheme(ITFMOST:MHX/002/20).
文摘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.
基金supported by the National Key Research and Development Program of China(No.2020YFA01130002)the National Natural Science Foundation of China(No.81972563).
文摘Loss of excessive hair growth causes psychological distress in many people,seriously affecting their social confidence and quality of life.The dermal papilla(DP)plays a pivotal role in regulating hair follicle(HF)morphogenesis and hair growth.However,the genes that govern the DP function in HF have not been extensively investigated.Genome-wide association studies have reported that two single-nucleotide polymorphisms(rs929626 and rs1081073)of the transcription factor EBF1(early B-cell factor 1)are associated with male pattern baldness.
