Chronic, non-healing wounds are a significant medical problem that affects patients’ quality of life and poses a burden on healthcare systems worldwide. These wounds, including venous leg ulcers, diabetic foot ulcers, and pressure ulcers, can persist for months or even years, leading to pain, decreased mobility, and increased morbidity for patients. The increasing incidence of diabetes and the aging population contribute to the growing problem of chronic wounds in developed countries.
Currently, there is a lack of effective treatment options for chronic wounds, and traditional medicines containing bioactive small molecules are being explored as potential remedies. These natural remedies have been used by indigenous populations for generations and are believed to have properties that promote wound healing and reduce inflammation. Some of these bioactive small molecules found in plants also possess antibacterial properties, which can help combat infections in wounds.
While there have been numerous studies highlighting the effects of naturally occurring small molecules in wound healing assays in vitro, it is essential to conduct well-designed clinical trials to determine their efficacy and safety. In this review, we examine the clinical trials conducted over the past 20 years on natural remedies for wound healing. We also explore the bioactive small molecules involved and their mechanisms of action, where available.
Diabetic Foot Ulcers
One clinical trial assessed the use of Vasconcellea pubescens, commonly known as Mountain Papaya, for diabetic foot ulcers. The study included 50 participants and compared the treatment outcome of a proteolytic fraction of Vasconcellea pubescens to a control hydrogel. The proteolytic fraction showed enhanced wound repair and a shorter healing time compared to the control.
Another study evaluated the effects of Pycnogenol®, a French maritime pine extract, on diabetic foot ulcers. The study included 30 participants and found that treatment with Pycnogenol® significantly reduced ulcer size within 6 weeks, with the combination of oral and topical application showing the most significant improvement.
Calendula officinalis, commonly known as pot marigold, was studied for its effects on diabetic foot ulcers. A pilot study with 41 patients showed that treatment with Calendula officinalis hydroglycolic extract resulted in a high proportion of complete wound closure within 30 weeks, along with a reduction in bacterial colonization and pain.
Symphytum Herba extract cream, derived from the comfrey plant, was assessed for its effects on pressure ulcers. The study included 151 participants with pressure ulcers, and the cream showed a high rate of successful wound repair, along with minimal incidence of skin sensitivity.
A salve containing Norway spruce resin was evaluated for its effects on pressure ulcers. The salve demonstrated enhanced wound healing compared to a standard wound care treatment, with a higher rate of complete healing and a shorter healing time.
Venous Leg Ulcers
Triticum vulgare, commonly known as wheat plant, was studied for its effects on venous leg ulcers. Different formulations of Triticum vulgare, including cream, impregnated gauzes, foam, hydrogel, and dressing gel, were assessed. All formulations showed a reduction in ulcer size, with cream, gauze, and hydrogel demonstrating the most significant improvement.
Mimosa tenuiflora cortex extract, derived from the bark of the tepescohuite tree, was evaluated for its effects on venous leg ulcers. Clinical trials showed enhanced wound healing and increased re-epithelialization in patients treated with the extract.
A combination cream containing Aloe vera and olive oil was studied for its effects on various chronic wounds, including venous leg ulcers. The combination cream showed an enhanced wound healing response compared to a standard wound care treatment, with improvements in ulcer size, exudate amount, and peripheral tissue edema.
Clinical trials have shown promising results for the use of natural remedies in the treatment of chronic wounds, including diabetic foot ulcers, pressure ulcers, and venous leg ulcers. Bioactive small molecules from natural sources, such as Vasconcellea pubescens, Pycnogenol®, Calendula officinalis, Symphytum Herba, Norway spruce resin, Triticum vulgare, Mimosa tenuiflora cortex extract, and Aloe vera, have demonstrated beneficial effects on wound healing.
Further research and larger clinical trials are needed to confirm the efficacy and safety of these natural remedies. Additionally, the development of standardized formulations and dosage regimens will be essential for their successful translation into clinical practice. Natural remedies, including manuka honey, have the potential to provide alternative and effective treatments for chronic wounds, addressing the unmet medical need and reducing the burden on healthcare systems.
Keywords: manuka honey, surgical wounds, chronic wounds, wound healing, natural remedies, clinical trials.