Medicinal Plants as Efficacious Agents for Diabetic Foot Ulcers

A Systematic Review of Clinical Studies

Roohollah Ahmadian, PhD Candidate; Roodabeh Bahramsoltani, PharmD, PhD; André M Marques, Msc, PhD; Roja Rahimi, PharmD, PhD; Mohammad Hosein Farzaei, PharmD, PhD


Wounds. 2021;33(8):207-218. 

In This Article

Abstract and Introduction


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.


Diabetes mellitus (DM) is a substantial health problem worldwide. In 2015, approximately 415 million patients were identified as having DM; this number is estimated to increase to 642 million by 2040.[1,2] This sharp rise in worldwide prevalence of DM will exacerbate the deleterious complications related to chronic hyperglycemia, such as microvascular and macrovascular problems.[3] A diabetic foot ulcer (DFU), which is one of the most disturbing complications of DM, is a common result of diverse etiological pathways such as neuropathy, ischemia, and infection.[1] The prevalence of DFU in the diabetic population is estimated to be 4% to 15%, affecting the elderly in particular.[4,5] The risk of foot ulcer is 25% higher in persons with DM than in persons without DM.[6] According to the World Health Organization, patients with DM are 10 to 20 times more likely than patients without DM to require lower extremity amputation owing to infected, nonhealing foot ulcers.[7] These ulcers may strongly affect health disbursement owing to hospitalization and amputation, which cause an overall reduction in patients' quality of life resulting from high rates of morbidity and mortality.[8–10]

Standard care for DFU includes offloading and debridement. In addition, some adjuvant therapies such as modern dressings, electrophysical therapy, negative pressure wound therapy, biological and hyperbaric oxygen therapies, and some Chinese herbal medications have been shown to have positive effects on healing DFU.[11–15] Of note, this paper identifies herbal treatments as medicinal treatments; while recognized in many parts of the world, these herbal treatments are not classified as such in Western medicine at this time.

Since approximately the year 2000, several studies have shown a 40% to 60% reduction in rates of amputation among adult patients with DM in high-income countries.[7] Ten percent to 15% of these wounds are of the chronic, nonhealing type,[4] and 5% to 24% of patients with DFU undergo limb amputation as a result.[16] As of 2020, reports on the use of hyperbaric oxygen therapy indicate that its treatment effects are not yet conclusive,[17] and this therapy is not recommended as a routine part of DFU management.[18] Similarly, only 3 of 7 high-quality clinical trials support the efficacy of negative pressure wound therapy.[19] Thus, there is an urgent need to find an alternative and efficacious strategy for better management of DFU.

Herbal medicines have been used as reliable treatments for various health problems since ancient times. Currently, many studies indicate that bioactive molecules from medicinal plants have multiple pharmacological properties that can prevent several types of destructive cellular damage, including chronic wounds. For instance, debridement is a primary standard treatment for DFU; sometimes this treatment is performed by enzymatic means, in which proteolytic enzymes such as papain and bromelain are used.[4] Papain and bromelain are natural, plant-derived enzymes obtained from papaya and pineapple, respectively. The selective removal of necrotic tissue without affecting healthy tissue suggests that this method is a valuable treatment for DFU.[4] Medicinal plants are traditionally used as different topical preparations to treat burns, infected wounds, skin irritations, and inflammations.[20–24] The traditional use of plants as wound healing remedies has also been demonstrated by in vitro, in vivo, and clinical studies.[22,25,26]

Use of medicinal plants alone or as an adjuvant therapy along with current therapeutic approaches has been shown to reduce the complications of DFUs in patients with DM.[27–29] The present review provides information on herbal medicinal options for the management of DFUs based on currently available clinical evidence. Outcomes considered for study selection included but were not limited to reduction in wound healing time, wound area, markers of inflammation, and oxidative stress, as well as the number of patients who required amputation.