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 PGE2 secretions, 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.

Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison

“…Pyrexia in mice was induced as described by Liu et al [8] with minor modifications. The initial rectum temperature of each animal was measured using a lubricated digital thermometer.…”

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“…Various studies have used this protocol after the injection of yeast and have induced the antipyretic drugs 21 . It was observed that Bacopa monnieri caused a significant (p<0.05) decrease in the rectal pyrexia which is also similar to the standard drug indomethacin Fig.…”

Forsythoside A and Forsythoside B Contribute to Shuanghuanglian Injection-Induced Pseudoallergic Reactions through the RhoA/ROCK Signaling Pathway

“…In recent years, forsythoside A has been reported to exhibit multiple pharmacological activities, including anti-inflammatory [43][44][45][46][47][48][49], anti-endotoxin [50,51], antivirus [52], and antipyretic [53] effects, as well as preventing hippocampal injury [54]. It is a good candidate agent for treating inflammatory diseases [46], asthma [47], Ti implant-associated infection [48], bronchitis infection [52], pyretic disease [53], and Alzheimer's diseases [54]. In our study, we elucidated that the application of forsythoside A at a high concentration could disturb the function of the endothelial barrier and cause vascular leakiness.…”