Zhao Ting, Zha Yanmei, Jiang Shangjun, Wang Rong, Song Yanting, Li Lushuang, Lyu Junchen, Hu Wenting, Zhang Daqi, Wu Shuang, Zhang Yingxia
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Collaborative Innovation Center of One Health, Hainan University, Haikou, China.
Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Collaborative Innovation Center of One Health, Hainan University, Haikou, China; College of Life Sciences, Hainan University, Haikou, China.
Int Immunopharmacol. 2025 Jun 5;157:114756. doi: 10.1016/j.intimp.2025.114756. Epub 2025 May 2.
Acne vulgaris is a widespread chronic inflammatory skin disease that is mainly caused by Cutibacterium acnes infection and subsequent inflammation. Temporin-GHaR4G7R (GHaR4G7R) was derived from Temporin-GHa of frog Hylarana guentheri. Its antibacterial performance against C. acnes and potential mechanism against acne vulgaris in vitro and in vivo were evaluated. In vitro tests demonstrated that GHaR4G7R displayed potent bactericidal effects against C. acnes, with both the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 3.1 μM. It exerted antibacterial effect by disrupting the bacterial membranes, accompanied by low propensity for developing drug resistance. GHaR4G7R significantly inhibited the formation of early biofilms and eliminated established biofilms of C. acnes by decreasing exopolysaccharide synthesis. Meanwhile, GHaR4G7R demonstrated an anti-inflammatory effect on HaCaT cells challenged with heat-inactivated C. acnes by significantly down-regulating the expression of TLR2/NF-κB/MAPK pathway-associated proteins by qRT-PCR, immunofluorescence, and Western blot assays. As expected, GHaR4G7R significantly decreased the bacterial colonization in rat ear model induced by C. acnes, and relieved the auricular swelling and inflammatory cell infiltration through inhibiting the TLR2/NF-κB/MAPK signaling pathway, leading to down-regulation of the inflammatory cytokine expression and alleviation of the skin inflammation in vivo. The research indicates that GHaR4G7R might be a potential alternative for developing novel strategies for treating acne vulgaris.
寻常痤疮是一种广泛存在的慢性炎症性皮肤病，主要由痤疮丙酸杆菌感染及随后的炎症引起。天蚕素-GHaR4G7R（GHaR4G7R）源自虎纹蛙的天蚕素-GHa。评估了其对痤疮丙酸杆菌的抗菌性能以及在体外和体内针对寻常痤疮的潜在作用机制。体外试验表明，GHaR4G7R对痤疮丙酸杆菌显示出强大的杀菌作用，最低抑菌浓度（MIC）和最低杀菌浓度（MBC）均为3.1 μM。它通过破坏细菌膜发挥抗菌作用，且产生耐药性的倾向较低。GHaR4G7R通过减少胞外多糖合成，显著抑制痤疮丙酸杆菌早期生物膜的形成并消除已形成的生物膜。同时，通过qRT-PCR、免疫荧光和蛋白质印迹分析，GHaR4G7R对经热灭活的痤疮丙酸杆菌刺激的HaCaT细胞显示出抗炎作用，可显著下调TLR2/NF-κB/MAPK通路相关蛋白的表达。正如预期的那样，GHaR4G7R显著减少了痤疮丙酸杆菌诱导的大鼠耳部模型中的细菌定植，并通过抑制TLR2/NF-κB/MAPK信号通路减轻了耳廓肿胀和炎性细胞浸润，导致体内炎性细胞因子表达下调和皮肤炎症减轻。该研究表明，GHaR4G7R可能是开发治疗寻常痤疮新策略的一种潜在替代物。
