Sophorolipid inhibits histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity

Rui-Qi Xu, Ling Ma, Timson Chen, Wei-Xiong Zhang, Kuan Chang, Jing Wang
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引用次数: 1

Abstract

Abstract Biosurfactants are attracting much interest due to their potential application as therapeutic agents in the medical field. Previous studies have demonstrated that biosurfactant such as sophorolipid (SL) exhibits immunomodulatory effects. In this paper, we found the potential of sophorolipid for inhibiting histamine-induced itch and preliminarily explored its molecular basis. First, behavioral tests indicated that SL could remit the histamine-induced scratching behaviors of mice. Second, SL could suppress the the calcium influx induced by histamine, HTMT and VUF8430 in HaCaT cells. RT-PCR analysis showed that the histamine-induced upregulation of mRNA levels of phospholipase Cγ1 (PLCγ1), 1,4,5-trisphosphate receptor (IP3R), and protein kinase Cα (PKCα) could be inhibted by SL, suggesting that SL may impede the PLC-IP3R signaling pathway activated by histamine. In further tests, the capsaicin-induced calcium influx could also be inhibited by SL, and molecular docking analysis indicated the possible binding of SL with transient receptor potential vanilloid-1 (TRPV1). In summary, these results revealed that SL may inhibit histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity. This paper indicates that SL may be a useful treatment medicine for histamine-dependent itch.
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苦参脂通过降低PLC/IP3R信号通路激活和调节TRPV1活性来抑制组胺诱导的瘙痒
摘要生物表面活性剂因其在医学领域的潜在应用前景而备受关注。以往的研究表明,生物表面活性剂如槐油脂(SL)具有免疫调节作用。本文发现了槐磷脂抑制组胺致痒的潜力,并初步探讨了其分子基础。首先,行为学实验表明,SL可以缓解组胺诱导的小鼠抓痕行为。其次,SL可以抑制组胺、HTMT和VUF8430诱导的HaCaT细胞钙内流。RT-PCR分析显示,SL可抑制组胺诱导的磷脂酶Cγ1 (PLCγ1)、1,4,5-三磷酸受体(IP3R)和蛋白激酶Cα (PKCα) mRNA水平上调,提示SL可能阻碍了组胺激活的PLC-IP3R信号通路。在进一步的实验中,SL也可以抑制辣椒素诱导的钙内流,分子对接分析表明SL可能与瞬时受体电位香草素-1 (TRPV1)结合。综上所述,这些结果表明,SL可能通过降低PLC/IP3R信号通路激活和调节TRPV1活性来抑制组胺诱导的瘙痒。提示SL可能是治疗组胺依赖性瘙痒的有效药物。
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