Hospital-acquired infections and treatment-related wound complications constitute a tremendous burden for the health care system, particularly given the serious increase in multidrug resistant pathogens. Imagine that a large part of nosocomial infections can be prevented using a simple treatment. In this respect, honey is used mainly in topical cutaneous wound care because of its potent broad-spectrum antibacterial and wound healing activities. However, therapeutic use outside this scope has been limited. The current review provides an in-depth view of studies using honey outside the conventional wound care indications. Non-conventional routes of honey application include subcutaneous, intra-socket, abdominal, and oral administration in novel indications, such as post colon surgery, mucositis, and tooth extraction. Honey consistently demonstrates beneficial therapeutic activities in these novel applications, orchestrating antimicrobial and prophylactic activity, reducing inflammation and wound dehiscence, and inducing healing, epithelialization, and analgesic activity. Several molecular mechanisms are responsible for these beneficial clinical effects of honey during the course of wound healing. Pro-inflammatory effects of honey, such as induction of iNOS, IL-1β, and COX-2, are mediated by TLR4 signaling. In contrast, honey's anti-inflammatory actions and flavonoids induce anti-inflammatory and antioxidant pathways by inducing NRF2 target genes, including HO-1 and PRDX1. The molecular and biochemical pathways activated by honey during the different phases of wound healing are also discussed in more detail in this review. Variation between different honey origins exists, and therefore standardized medical-grade honey may offer an optimized and safe treatment. Honey is a valuable alternative to conventional antimicrobial and anti-inflammatory therapies that can strongly reduce nosocomial infections.

医院获得性感染和治疗相关的伤口并发症构成了医疗保健系统的巨大负担，特别是考虑到多重耐药病原体的严重增加。想象一下，通过简单的治疗可以预防大部分医院感染。在这方面，蜂蜜主要用于局部皮肤伤口护理，因为它具有强大的广谱抗菌和伤口愈合活性。然而，在此范围之外的治疗用途受到限制。目前的审查提供了在常规伤口护理适应症之外使用蜂蜜的研究的深入观点。蜂蜜应用的非常规途径包括在新适应症中的皮下、窝内、腹部和口服给药，例如结肠手术后、粘膜炎和拔牙。蜂蜜在这些新应用中始终表现出有益的治疗活性，协调抗菌和预防活性，减少炎症和伤口裂开，并诱导愈合、上皮化和镇痛活性。在伤口愈合过程中，蜂蜜的这些有益临​​床效果有多种分子机制。蜂蜜的促炎作用，例如诱导 iNOS、IL-1β 和 COX-2，是由 TLR4 信号传导介导的。相比之下，蜂蜜的抗炎作用和类黄酮通过诱导包括 HO-1 和 PRDX1 在内的 NRF2 靶基因来诱导抗炎和抗氧化途径。本综述还更详细地讨论了蜂蜜在伤口愈合的不同阶段激活的分子和生化途径。不同蜂蜜来源之间存在差异，因此标准化的医用级蜂蜜可以提供优化和安全的治疗。蜂蜜是传统抗菌和抗炎疗法的一种有价值的替代品，可以大大减少医院感染。