Naoxintong accelerates diabetic wound healing by attenuating inflammatory response

Abstract

Context Naoxintong (NXT), a prescribed traditional Chinese medicine, widely used in cerebrovascular and cardiovascular diseases, could be effective in diabetic wounds. Objective This study evaluates the wound healing activity of NXT by employing an excisional wound splinting model. Materials and methods NXT was dissolved in saline and given daily by gavage. Wounds were induced at the dorsum of non-diabetic (db/+) and diabetic (db/db) mice and treated with saline or 700 mg/kg/d NXT for 16 days. Wound closure was measured every four days. Extracellular matrix (ECM) remodelling, collagen deposition, leukocyte infiltration and expression of Col-3, CK14, CXCL1, CXCL2, MPO, Ly6G, CD68, CCR7, CD206, p-JAK1, p-STAT3 and p-STAT6 was analysed. Results NXT significantly accelerated rate of wound closure increased from 70% to 84%, accompanied by up-regulation of collagen deposition and ECM at days 16 post-injury. Moreover, NXT alleviated neutrophil infiltration, accompanied by down-regulation of CXCL1 and CXCL2 mRNA expression. In addition, NXT markedly augmented neutrophil efferocytosis. In diabetic wounds, the levels of M1 marker gene (CCR7) increased, while M2 marker gene (CD206) decreased, demonstrating a pro-inflammatory shift. Application of NXT increased M2 macrophage phenotype in db/db mice. Mechanistically, NXT treatment increased expression level of p-STAT3 and p-STAT6 at days 3 post-injury, indicating NXT mediated macrophages towards M2 phenotype and alleviated inflammation in diabetic wounds by activation of STAT3 and STAT6. Conclusions Our study provides evidence that NXT accelerates diabetic wound healing by attenuating inflammatory response, which provides an important basis for use of NXT in the treatment of chronic diabetic wound healing.

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“…Therefore, the traditional treatment plan still deserves our attention. In its long-term practice, traditional Chinese medicine has accumulated many rich and effective methods to treat chronic wounds ( 32 , 33 ).…”

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“…However, this transition is often stagnant in chronic wounds. [81] In addition, chronic wounds are often accompanied by disorders of inflammation and impaired macrophage invasion, aggregation, movement, and phenotypic transformation, leading to an increase in M1-type macrophages and a sustained release of inflammatory factors, which in turn provokes persistent inflammation, leading to a substan-tial Infiltrative cell infiltration on the wound substrate and delayed healing. [82][83][84] For example, one of the most common complications of diabetes is delayed wound healing, where impaired angiogenesis, neuropathy, and hyperglycemia are important factors in delaying subsequent wound closure.…”