title: Forsythoside A exerts antipyretic effect on yeast-induced pyrexia mice via inhibiting transient receptor potential vanilloid 1 function.
abstract: Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel gated by noxious heat, playing major roles in thermoregulation. Forsythoside A (FT-A) is the most abundant phenylethanoid glycosides in Fructus Forsythiae, which has been prescribed as a medicinal herb for treating fever in China for a long history. However, how FT-A affects pyrexia and what is the underlying molecular mechanism remain largely unknown. Here we found that FT-A exerted apparent antipyretic effect through decreasing the levels of prostaglandin E2(PGE2) and interleukin 8 (IL-8) in a dose-dependent fashion on the yeast induced pyrexia mice. Interestingly, FT-A significantly downregulated TRPV1 expression in the hypothalamus and dorsal root ganglion (DRG) of the yeast induced pyrexia mice. Moreover, FT-A inhibited IL-8 and PGE2secretions, and calcium influx in the HEK 293T-TRPV1 cells after stimulated with capsaicin, the specific TRPV1 agonist. Further investigation of the molecular mechanisms revealed that FT-A treatment rapidly inhibited phosphorylation of extracellular signal-regulated kinase (ERK), Jun N-terminal kinase (JNK) and p38 in both yeast induced pyrexia mice and HEK 293T-TRPV1 cells. These results suggest that FT-A may serve as a potential antipyretic agent and the therapeutic action of Fructus Forsythiae on pyretic related disease is, in part, due to the FT-A activities.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Cuiling
authors.initials: C
authors.lastname: Liu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Hongchang
authors.initials: H
authors.lastname: Su
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Hongye
authors.initials: H
authors.lastname: Wan
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Qingxia
authors.initials: Q
authors.lastname: Qin
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Wu
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Xiangying
authors.initials: X
authors.lastname: Kong
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Na
authors.initials: N
authors.lastname: Lin
mesh_terms: D000818:Animals; D058633:Antipyretics / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005334:Fever / Q000188:drug therapy* / Q000378:metabolism* / Q000382:microbiology; D005434:Flow Cytometry; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006027:Glycosides / Q000627:therapeutic use*; D057809:HEK293 Cells; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism; D051379:Mice; D012441:Saccharomyces cerevisiae / Q000472:pathogenicity*; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D058633:Antipyretics; D006027:Glycosides; D016209:Interleukin-8; D050916:TRPV Cation Channels; D015232:Dinoprostone; C058049:forsythiaside
keywords: Fever; Forsythoside A, Mitogen-activated protein kinases.; Transient receptor potential