Forsythoside A Exerts Antipyretic Effect on Yeast-induced Pyrexia Mice Via Inhibiting Transient Receptor Potential Vanilloid 1 Function

Overview

Journal Int J Biol Sci

Specialty Biology

Date 2017 Jan 27

PMID 28123347

Citations 14

Authors

Cuiling Liu

Hongchang Su

Hongye Wan

Qingxia Qin

Xuan Wu

Xiangying Kong

Na Lin

Affiliations

Soon will be listed here.

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 E (PGE) 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 PGE 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.

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References

Chen Y, Geis C, Sommer C . Activation of TRPV1 contributes to morphine tolerance: involvement of the mitogen-activated protein kinase signaling pathway. J Neurosci. 2008; 28(22):5836-45. PMC: 6670790. DOI: 10.1523/JNEUROSCI.4170-07.2008. View

Benemei S, Patacchini R, Trevisani M, Geppetti P . TRP channels. Curr Opin Pharmacol. 2015; 22:18-23. DOI: 10.1016/j.coph.2015.02.006. View

Bautista D, Movahed P, Hinman A, Axelsson H, Sterner O, Hogestatt E . Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A. 2005; 102(34):12248-52. PMC: 1189336. DOI: 10.1073/pnas.0505356102. View

Morera E, De Petrocellis L, Morera L, Moriello A, Nalli M, Di Marzo V . Synthesis and biological evaluation of [6]-gingerol analogues as transient receptor potential channel TRPV1 and TRPA1 modulators. Bioorg Med Chem Lett. 2012; 22(4):1674-7. DOI: 10.1016/j.bmcl.2011.12.113. View

Caspani O, Zurborg S, Labuz D, Heppenstall P . The contribution of TRPM8 and TRPA1 channels to cold allodynia and neuropathic pain. PLoS One. 2009; 4(10):e7383. PMC: 2753652. DOI: 10.1371/journal.pone.0007383. View

Jan S, Khan M . Antipyretic, analgesic and anti-inflammatory effects of Kickxia ramosissima. J Ethnopharmacol. 2016; 182:90-100. DOI: 10.1016/j.jep.2016.02.020. View

Bandell M, Story G, Hwang S, Viswanath V, Eid S, Petrus M . Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron. 2004; 41(6):849-57. DOI: 10.1016/s0896-6273(04)00150-3. View

Huang J, Zhang X, McNaughton P . Modulation of temperature-sensitive TRP channels. Semin Cell Dev Biol. 2006; 17(6):638-45. DOI: 10.1016/j.semcdb.2006.11.002. View

Wei N, Lv H, Wu Y, Yang S, Sun X, Lai R . Selective Activation of Nociceptor TRPV1 Channel and Reversal of Inflammatory Pain in Mice by a Novel Coumarin Derivative Muralatin L from Murraya alata. J Biol Chem. 2015; 291(2):640-51. PMC: 4705384. DOI: 10.1074/jbc.M115.654392. View

10.

Straub R . TRPV1, TRPA1, and TRPM8 channels in inflammation, energy redirection, and water retention: role in chronic inflammatory diseases with an evolutionary perspective. J Mol Med (Berl). 2014; 92(9):925-37. DOI: 10.1007/s00109-014-1175-9. View

11.

Bandell M, Dubin A, Petrus M, Orth A, Mathur J, Hwang S . High-throughput random mutagenesis screen reveals TRPM8 residues specifically required for activation by menthol. Nat Neurosci. 2006; 9(4):493-500. DOI: 10.1038/nn1665. View

12.

Gourgou E, Aggeli I, Beis I, Gaitanaki C . Hyperthermia-induced Hsp70 and MT20 transcriptional upregulation are mediated by p38-MAPK and JNKs in Mytilus galloprovincialis (Lamarck); a pro-survival response. J Exp Biol. 2009; 213(2):347-57. DOI: 10.1242/jeb.036277. View

13.

Watanabe T, Terada Y . Food Compounds Activating Thermosensitive TRP Channels in Asian Herbal and Medicinal Foods. J Nutr Sci Vitaminol (Tokyo). 2015; 61 Suppl:S86-8. DOI: 10.3177/jnsv.61.S86. View

14.

Sundivakkam P, Natarajan V, Malik A, Tiruppathi C . Store-operated Ca2+ entry (SOCE) induced by protease-activated receptor-1 mediates STIM1 protein phosphorylation to inhibit SOCE in endothelial cells through AMP-activated protein kinase and p38β mitogen-activated protein kinase. J Biol Chem. 2013; 288(23):17030-17041. PMC: 3675634. DOI: 10.1074/jbc.M112.411272. View

15.

Green D, Ruparel S, Gao X, Ruparel N, Patil M, Akopian A . Central activation of TRPV1 and TRPA1 by novel endogenous agonists contributes to mechanical allodynia and thermal hyperalgesia after burn injury. Mol Pain. 2016; 12. PMC: 4955965. DOI: 10.1177/1744806916661725. View

16.

Sengar N, Joshi A, Prasad S, Hemalatha S . Anti-inflammatory, analgesic and anti-pyretic activities of standardized root extract of Jasminum sambac. J Ethnopharmacol. 2014; 160:140-8. DOI: 10.1016/j.jep.2014.11.039. View

17.

Patapoutian A, Peier A, Story G, Viswanath V . ThermoTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci. 2003; 4(7):529-39. DOI: 10.1038/nrn1141. View

18.

Wang Y, Zhao H, Lin C, Ren J, Zhang S . Forsythiaside A Exhibits Anti-inflammatory Effects in LPS-Stimulated BV2 Microglia Cells Through Activation of Nrf2/HO-1 Signaling Pathway. Neurochem Res. 2015; 41(4):659-65. DOI: 10.1007/s11064-015-1731-x. View

19.

Qu H, Zhang Y, Wang Y, Li B, Sun W . Antioxidant and antibacterial activity of two compounds (forsythiaside and forsythin) isolated from Forsythia suspensa. J Pharm Pharmacol. 2008; 60(2):261-6. DOI: 10.1211/jpp.60.2.0016. View

20.

Szolcsanyi J . Effect of capsaicin on thermoregulation: an update with new aspects. Temperature (Austin). 2016; 2(2):277-96. PMC: 4843897. DOI: 10.1080/23328940.2015.1048928. View