Medicinal Plants as Efficacious Agents for Diabetic Foot Ulcers: A Systematic Review of Clinical Studies

A diabetic foot ulcer (DFU) is a chronic, nonhealing wound that occurs in approximately 15% to 25% of patients with diabetes, and amputation is necessary in approximately 5% to 24% of these patients. Medicinal plants have demonstrated promising wound healing activities in animal models of DFUs as well as in clinical studies. These plants, which are described as medicinal in different regions of the world, are not considered to be standard medicinal treatments in Western medicine at this time. Some medicinal products, such as bromelain-an herbal protease currently used for enzymatic debridement of wounds-have been obtained from plants, showing the important role of these natural products as sources of wound healing agents. This paper aims to review clinical studies on the effects of medicinal plants in patients with DFUs based on the improvement of local and systemic parameters related to wound healing. Electronic databases including PubMed, Scopus, and Cochrane Library were searched for studies from inception through May 2019 using the keywords "diabetic foot ulcer" and "plant," "phytochemical," "extract," or "herb." Inclusion criteria were controlled or before-after clinical studies with English-language full-text in which topical or systemic herbal preparations for DFUs were evaluated by considering outcomes such as reduction of wound healing time and wound area, markers of inflammation and oxidative stress, and number of cases requiring amputation. Studies on non-herbal materials and human studies other than clinical trials were excluded. Fourteen studies were included in the present review. Herbal medicines were administered as add-on therapy to standard wound care in the form of topical (cream, gel, oil) or systemic (capsule, decoction, injection) preparations. Parameters such as ulcer width and depth, phagocytic function, tumor necrosis factor α level, epithelialization, vascularization, and wound closure were evaluated in clinical trials, several of which were significantly improved in patients compared with their baseline values or control group. Per the studies included in this review, medicinal plants can be recommended as promising adjuvant therapies to conventional wound care to accelerate wound healing in patients with DFUs.