Antimicrobial resistance is a dramatic global threat; however, the slow progress of new antibiotic development has impeded the identification of viable alternative strategies. Natural antioxidant-based antibacterial approaches may provide potent therapeutic abilities to effectively block resistance microbes’ pathways. While essential oils (EOs) have been reported as antimicrobial agents, its application is still limited ascribed to its low solubility and stability characters; additionally, the related biomolecular mechanisms are not fully understood. Hence, the study aimed to develop a nano-gel natural preparation with multiple molecular mechanisms that could combat bacterial resistance in an acne vulgaris model. A nano-emulgel of thyme/clove EOs (NEG8) was designed, standardized, and its antimicrobial activity was screened in vitro and in vivo against genetically identified skin bacterial clinical isolates (Pseudomonas stutzeri, Enterococcus faecium and Bacillus thuringiensis). As per our findings, NEG8 exhibited bacteriostatic and potent biofilm inhibition activities. An in vivo model was also established using the commercially available therapeutic, adapalene in contra genetically identified microorganism. Improvement in rat behavior was reported for the first time and NEG8 abated the dermal contents/protein expression of IGF-1, TGF-β/collagen, Wnt/β-catenin, JAK2/STAT-3, NE, 5-HT, and the inflammatory markers; p(Ser536) NF-κBp65, TLR-2, and IL-6. Moreover, the level of dopamine, protective anti-inflammatory cytokine, IL-10 and PPAR-γ protein were enhanced, also the skin histological structures were improved. Thus, NEG8 could be a future potential topical clinical alternate to synthetic agents, with dual merit mechanism as bacteriostatic antibiotic action and non-antibiotic microbial pathway inhibitor.

中文翻译：

---

外用纳米丁香/百里香凝胶对抗基因鉴定的临床皮肤分离物：体内靶向行为改变和 IGF-1/pFOXO-1/PPAR γ 线索

抗微生物药物耐药性是一个巨大的全球威胁；然而，新抗生素开发进展缓慢阻碍了可行替代策略的确定。基于天然抗氧化剂的抗菌方法可能提供有效的治疗能力来有效阻断耐药微生物的途径。虽然精油 (EOs) 已被报道为抗菌剂，但由于其低溶解性和稳定性特性，其应用仍然受到限制；此外，相关的生物分子机制尚未完全了解。因此，该研究旨在开发一种具有多种分子机制的纳米凝胶天然制剂，可以对抗寻常痤疮中的细菌耐药性。模型。设计并标准化了一种百里香/丁香 EOs (NEG8) 纳米乳剂，并针对基因鉴定的皮肤细菌临床分离株（施氏假单胞菌、屎肠球菌和苏云金芽孢杆菌）在体外和体内筛选了其抗菌活性）。根据我们的发现，NEG8 表现出抑菌和有效的生物膜抑制活性。还使用市售的治疗剂阿达帕林在相反遗传鉴定的微生物中建立了体内模型。首次报道了大鼠行为的改善，NEG8 减少了 IGF-1、TGF-β/胶原蛋白、Wnt/β-catenin、JAK2/STAT-3、NE、5-HT 和炎症标志物；p(Ser536) NF-κBp65、TLR-2 和 IL-6。此外，多巴胺、保护性抗炎细胞因子、IL-10和PPAR-γ蛋白的水平增加，皮肤组织结构也得到改善。因此，NEG8 可能是合成药物的未来潜在的局部临床替代品，具有双重优点机制，即抑菌抗生素作用和非抗生素微生物途径抑制剂。