Institute of Pharmaceutical Science, China Pharmaceutical University, NO. 24 TongJiaXiang St., Nanjing City, 210009, Jiangsu Province, China.
Department of Endocrinology, Affiliated Hospital of Nanjing University of Chinese Medicine, NO. 155 HanZhong Rd., Nanjing, 210029, Jiangsu Province, China.
J Ethnopharmacol. 2021 Apr 6;269:113684. doi: 10.1016/j.jep.2020.113684. Epub 2020 Dec 9.
Ethnopharmacological relevance Ainsliaea fragrans Champ. (A. fragrans) is used to treat infection of the lower genital tract in gynecology, such as cervicitis and pelvic inflammatory disease. This study analyzed the therapeutic efficiency of A. fragrans on cervicitis and the inhibition mechanism of AF-p2 in MALP-2-stimulated RAW264.7 cells. Materials and methods The anti- Ureaplasma urealyticum (Uu) activity of A. fragrans and AF-p2 were determined by antimicrobial susceptibility testing. The activity of A. fragrans extracts (AFext) was evaluated in female BALB/c mice with cervicitis induced by Uu. Furthermore, the therapeutic mechanism of AFext and AF-p2 on myeloid differentiation factor 88 (MyD88) pathway were studied in macrophage activating lipopeptide-2 (MALP-2) irritated RAW264.7 cells. Results AFext could suppress the proliferation of Uu in vitro, including the azithromycin resistant strains. Meanwhile, AFext prevented cervicitis caused by Uu infection in BALB/c mice. Moreover, both AFext and AF-p2 could significantly suppress the nitric oxide (NO) production as well as other proinflammatory cytokines (IL-1β,IL-6,TNF-α) in MALP-2 stimulated RAW264.7 cells. Moreover, AF-p2 also down-regulated iNOS, p65, Iκ-Bα, MyD88 and cyclooxygenase-2 (COX-2) levels in RAW264.7 cells. Conclusion This study indicated that AFext had a therapeutic effect in cervicitis induced by Uu infection. Furthermore, the lead compound AF-p2 showed an anti-infectious effect in MALP-2 irritated RAW264.7 cells through downregulating MyD88-NF-κB signaling pathway.
阿魏侧耳(A. fragrans)用于治疗妇科下生殖道感染,如宫颈炎和盆腔炎。本研究分析了阿魏侧耳对宫颈炎的治疗效果及其在 MALP-2 刺激 RAW264.7 细胞中 AF-p2 的抑制机制。
通过抗菌药敏试验测定阿魏侧耳和 AF-p2 对解脲支原体(Uu)的抗活性。采用 Uu 诱导的 BALB/c 雌性小鼠宫颈炎模型评价阿魏侧耳提取物(AFext)的活性。此外,还研究了 AFext 和 AF-p2 对脂多糖刺激 RAW264.7 细胞中髓样分化因子 88(MyD88)通路的治疗机制。
结果表明,AFext 可抑制 Uu 在体外的增殖,包括对阿奇霉素耐药株的抑制。同时,AFext 可预防 Uu 感染引起的 BALB/c 小鼠宫颈炎。此外,AFext 和 AF-p2 均可显著抑制 MALP-2 刺激的 RAW264.7 细胞中一氧化氮(NO)的产生以及其他促炎细胞因子(IL-1β、IL-6、TNF-α)的产生。此外,AF-p2 还可下调 RAW264.7 细胞中的 iNOS、p65、Iκ-Bα、MyD88 和环氧化酶-2(COX-2)水平。
综上所述,本研究表明 AFext 对 Uu 感染引起的宫颈炎具有治疗作用。此外,先导化合物 AF-p2 通过下调 MyD88-NF-κB 信号通路,在 MALP-2 刺激的 RAW264.7 细胞中表现出抗感染作用。