L-Borneol promotes skin flap survival by regulating HIF-1α/NF-κB pathway

A skin flap is a dynamic tissue made up of skin tissue with underlying blood vessels. Skin flaps are used for wound healing when there is a large wound that cannot be covered directly by sutures from the surrounding skin. It is frequently employed for wound repair, limb function restoration, and esthetic enhancement. Skin flaps play a vital role in surgery and are an important part of wound healing by enabling precise reconstruction and promoting optimal healing.

With the development of microsurgery, the types of skin flaps have progressed from random flaps and axial flaps to perforator flaps and branched flaps. However, regardless of the type used, distal necrosis is probably going to happen at the distal end, limiting the development of flap surgery in clinical applications (Lan et al., 2023). Upon the restoration of blood supply, a multitude of intricate mechanisms are initiated, encompassing ischemia-reperfusion injury (IRI) as well as inflammatory responses. The beginning event of necrosis is referred to as IRI (Lan et al., 2023). An inflammatory reaction is the main factor leading to ischemic necrosis of a skin flap during IRI (Elsurer et al., 2020). Therefore, promoting angiogenesis and inhibiting IRI and inflammatory responses are key methods of improving flap survival.

Borneol is an organic molecule characterised by a bicyclic terpene structure, which is obtained through extraction from either Cinnamomum camphora (L.) Presl or Blumea balsamifera (L.) DC. and the initial record of borneol may be traced back to " Ming Yi Bie Lu", a seminal text on Chinese herbal medicine (Mei et al., 2023). Borneol has been used to treat diseases in China for 1500 years (Ma et al., 2023). It exhibits heat-clearing, detoxifying, putridity elimination, and flesh regeneration effects and is commonly used as an excipient in drugs promoting blood circulation and removing blood stasis (Barreto et al., 2016; Xiao et al., 2020; Xie et al., 2022; Zou et al., 2017a).

The Chinese Pharmacopoeia (2020 edition) lists 173 borneol preparations (Mei et al., 2023). Currently, the market offers three variants of borneol: D-borneol, L-borneol, and synthetic borneol (Commission, 2020). It's important to note that the first two variants, D-borneol and L-borneol, are categorized as natural borneol. L-Borneol refers to a crystallized extract derived from the fresh leaves of Blumea balsamifera (L.) DC., also known as Ai-Na-Xiang, belonging to the Asteraceae family (Zhang et al., 2018). In traditional Chinese medicine, it is believed that blood stasis leads to skin flap necrosis, and the primary treatment involves activating blood circulation, removing blood stasis, clearing away heat, and detoxifying (Wang et al., 2022). L-Borneol plays a role in reducing inflammation and alleviating pain, primarily through its involvement in the metabolic route of arachidonic acid (Madhuri and Naik, 2017; Xie et al., 2023; Zhong et al., 2014). Additionally, it has been suggested that L-borneol can mitigate free radical oxidation processes and neurotoxicity by enhancing SOD activity and decreasing malondialdehyde (MDA) concentration (Liu et al., 2021). Furthermore, research has indicated that L-borneol protects human neuroblastoma cells from the detrimental effects caused by amyloid β protein. This protective mechanism is attributed to the antioxidant properties of L-borneol and its ability to impede apoptosis (Hur et al., 2013). Therefore, we investigated the effect and mechanism of L-borneol on the survival rate of skin flaps.

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