Center for Traditional Medicine

CTM Curated Research

Traditional Herbal Medicine and Wound Healing: Cellular Mechanisms, Ethnobotany, and Clinical Applications

Traditional herbal medicine systems have long used plants to support wound healing, while recent research continues to examine the cellular, immunological, and microbiome-related mechanisms involved in these practices. Across ethnobotanical traditions and contemporary biomedical studies, medicinal plants are being explored not only as historical remedies but as part of emerging integrative approaches to tissue repair and regenerative care.

White black-veined butterfly feeding on blue comfrey flowers (Symphytum officinale) in a green garden setting.
Comfrey (Symphytum officinale) in bloom alongside a black-veined butterfly. Long used in traditional wound-healing practices, comfrey continues to be studied in ethnobotanical and pharmacological research on tissue repair and regeneration.

Across traditional herbal medicine systems worldwide, plants have long been demonstrated to accelerate wound healing. Scientific investigations substantiate the efficacy of these medicinal plants. From Sri Lankan and South Indian classical traditions to Brazilian folk medicine and Japanese Kampo, plant-based wound-healing represents a vast yet largely undervalued body of therapeutic knowledge. This review examines four recent studies to examine cellular mechanisms, ethnobotanical foundations, nanotechnology-enhanced delivery, and microbiome interactions. The findings across these studies validate the therapeutic foundations of traditional herbal medicine in wound care and signal the need for integrative research frameworks that bridge empirical tradition and clinical evidence.

The first study is an in vitro/ex vivo preclinical study. Researchers used two plants from Sri Lankan traditional medicine, Vernonia zeylanica and Mallotus repandus, to determine whether they facilitate accelerated cellular and molecular processes in wound healing. They used primary fibroblasts (cells that help rebuild the structural integrity of skin) derived from human tissue. They confirmed that the cells were fibroblasts using flow cytometry (which identifies cells based on proteins) and trilineage differentiation (confirming the cells could develop into fat, bone, or cartilage). They compared the plant extract with β-fibroblast growth factor (bFGF, also known as FGF2), a well-known synthetic signaling protein that triggers fibroblast proliferation. Results revealed that these traditional remedies actively upregulated specific gene networks that drive all three phases of healing, outperforming the synthetic growth factor in cell viability and wound closure rate, with no cytotoxicity or DNA damage observed. This indicates that ADVM may play a significant role in the future of cell therapy by enabling the ex vivo cultivation of fibroblasts for applications in skin grafting and regenerative medicine.

The second study is a systematic ethnobotanical review with a focus on Southern Brazil (a region with an exceptionally robust tradition of plant-based medicine and high biodiversity). They surveyed the existing literature across two categories: ethnobotanical studies (documenting the plants local communities have used for traditional wound healing) and pharmacological studies (lab-based research examining the efficacy of the plants, how they work, and why). They found 73 medicinal plants across 39 botanical families, and of those, 15 were cited across surveys, indicating the consensus around use, a factor considered in ethnobotany as reliability. Symphytum officinale L. (comfrey) was most frequently cited, consistent with its well-documented global history of use in wound healing. The active compounds include allantonin (a promoter of cell proliferation) and rosmarinic acid (an anti-inflammatory). The pharmacological aspect examined 44 studies demonstrating wound-healing effects in plants. Limitations include that many traditional plants have not been pharmacologically studied, creating a gap in what communities have used and how they work. The specific compounds (phytochemical profiles) are not well characterized, and the mechanisms underlying their molecular interactions, concentrations, and receptor pathways are largely unexplored. This research offers a comprehensive framework that outlines the areas where scientific inquiry has yielded significant findings and highlights existing gaps in knowledge. The results affirm that Southern Brazil’s ethnobotanical traditions provide a meaningful but non-validated source of wound-healing remedies, with research still needed.

The third study is an in vivo preclinical investigation utilizing the Siddha system, recognized as one of the oldest classical medical traditions globally. Researchers reformulated Paccai eruvai, a traditional remedy for treating ulcers, into a nanogel. The gel-based delivery method increases bioavailability and tissue penetration by using particles reduced to a nanometer scale. Using two standard animal and wound models, they developed an incision model to assess tensile strength (the structural integrity of healed tissue) and an excision model to assess wound contraction and epithelialization (the speed and completeness of healing). Findings showed that the nanogel outperformed both the original formulation and the traditional formulation, as well as the synthetic bacterial treatment. The key findings demonstrated that the nanogel performed significantly better across all three phases of wound healing, with greater wound contraction, higher hydroxyproline content (a direct indicator of collagen synthesis), and greater tensile strength in the healed tissue.

The fourth study utilizes a narrative review to address the persistent challenge of chronic wound healing by examining three interconnected domains: the wound microbiome, immune response regulation, and topical herbal medicine delivery. The authors integrate a biomedical reductionist approach that isolates individual compounds, systematically fragmenting traditional herbal medicine’s mechanisms of action by failing to study whole-herb effects within their full biological context. They review how the skin microbiome contributes to wound healing and how traditional medicines modulate immune signaling, particularly during the transition from the inflammatory to the proliferative phase of healing. They also review how drug delivery technologies (ie, nanoparticles and hydrogels) can be formulated to deliver herbal compounds more effectively to wound sites. The authors assert that advancement of traditional herbal medicine in wound care requires an integrated framework that accounts for microbiome dynamics, immune modulation, and improved delivery responses. Future research should aim to bridge the gap between traditional practice and clinical evidence by adopting holistic, integrative models.

Tags: Ayurveda, collagen synthesis, drug delivery, ethnobotany, ex vivo, fibroblasts, immune modulation, nanogel, phytochemistry, preclinical research, Siddha medicine, skin microbiome, traditional herbal medicine, wound healing, wound microbiome

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Referenced Research Publications

Journal of Ethnopharmacology
2024, April 24

Aqueous distillate of mature leaves of Vernonia zeylanica (L.) Less. and Mallotus repandus (Rottler) Müll. Arg. cued from traditional medicine exhibits rapid wound healing properties

Abstract

Ethnopharmacological relevance

Sri Lankan traditional medicine uses Vernonia zeylanica and Mallotus repandus broadly for the treatment of a multitude of disease conditions, including wound healing.
Aim of the study
We aimed to scientifically validate the safety and efficacy of wound healing of an aqueous distillate of Vernonia zeylanica and Mallotus repandus (ADVM) mature leaves, tested on primary human dermal fibroblasts.

Materials and methods

Human dermal fibroblasts isolated from clinical waste from circumcision surgery were characterized by flowcytometry and trilineage differentiation. The MTT dye reduction assay, and the ex vivo wound healing scratch assay established wound healing properties of ADVM using the primary human dermal fibroblast cell line. Upregulation of genes associated with wound healing (MMP3, COL3A1, TGFB1, FGF2) were confirmed by RT qPCR. GC-MS chromatography evaluated the phytochemical composition of ADVM.

Results

Compared to the synthetic stimulant, β fibroblast growth factor, ADVM at 0.25% concentration on the primary dermal fibroblast cell line exhibited significant ex vivo, (i) 1.7-fold % cell viability (178.7% vs 304.3 %, p < 0.001), (ii) twofold greater % wound closure (%WC) potential (47.74% vs 80.11%, p < 0.001), and (iii) higher rate of % WC (3.251 vs 3.456 % WC/h, p < 0.05), sans cyto-genotoxicity. Up regulated expression of FGF2, TGFB1, COL3A1 and MMP3, genes associated with wound healing, confirmed effective stimulation of pathways of the three overlapping phases of wound healing (P < 0.05). GC-MS profile of ADVM characterized four methyl esters, which may be posited as wound healing phytochemicals.

Conclusions

Exceeding traditional medicine claims, the ex vivo demonstration of rapid skin regeneration, reiterated by upregulated expression of genes related to wound healing pathways, sans cytotoxicity, propounds ADVM, cued from traditional medicine, as a potential safe and effective natural stimulant for rapid wound-healing. Additionally, it may serve as an effective proliferative stimulant of dermal fibroblasts for cell therapy, with potential in reparative and regenerative therapy of skin disorders.

Reference

Ratnayake, P., Samaratunga, U., Perera, I., Seneviratne, J., & Udagama, P. (2024). Aqueous distillate of mature leaves of Vernonia zeylanica (L.) Less. and Mallotus repandus (Rottler) Müll. Arg. cued from traditional medicine exhibits rapid wound healing properties. Journal of ethnopharmacology, 324, 117763. https://doi.org/10.1016/j.jep.2024.117763

Chemistry & Biodiversity
2023, January 26

Traditional Plants Used in Southern Brazil as a Source for Wound Healing Therapies

Abstract

In southern Brazil, the biodiversity is great and the traditional use of medicinal plants for wound healing has been documented in ethnobotanical studies and pharmacological studies have assessed their wound properties and phytochemistry. Therefore, this study evaluated ethnobotanical surveys regarding medicinal plants used in southern Brazil for wound healing and studies about the healing properties of these plants published between 2000 and 2022. To retrieve articles related to the study, Web of Science, PubMed (NLM), Open Access Journals, Scielo, Lilacs, and Google Scholar, with keywords including medicinal plants, wound healing, and South of Brazil, have been used. As a result, 73 medicinal plants belonging to 39 families were found in ethnobotanical surveys as a traditional resource used for wound healing in southern Brazil, 15 of which were cited more than once. Besides, 14 of these 15 plants were also used as healing agents worldwide. The most cited plant with healing actions in southern Brazil was Symphytum officinale L. (comfrey). From 2000 to date, 44 articles scientifically demonstrated the wound-healing effects of the southern Brazilian plants found in ethnobotanical surveys reviewed. The folk medicine of southern Brazil presents a variety of medicinal plants for wound-healing purposes, and scientific data were found for some of those plants. However, the wound-healing properties of many plants have yet to be investigated, and the current literature still needs more phytochemical information about the plants studied. Aside from this, the future focus should be on the standardization of herbal extracts, and further research is required to investigate the pharmacological mechanisms. Clinical research in this area remains in its infancy and warrants more robust further clinical studies.

Reference

Antonio Pereira, I., Judah Cury, B., Kaio Silva Nunes, R., & Mota da Silva, L. (2023). Traditional Plants Used in Southern Brazil as a Source to Wound Healing Therapies. Chemistry & biodiversity, 20(2), e202201021. https://doi.org/10.1002/cbdv.202201021

Pharmaceutical Nanotechnology
2023, February 1

Modernization of a Traditional Siddha Medicine Paccai eruvai into a Novel Nanogel Formulation for Potent Wound Healing Activity

Abstract

Background

Paccai eruvai formulation has been widely used in traditional Siddha practice to treat ulcerous wounds due to the content of potentially active compounds.

Objective

The present study aimed to determine the enhancement potency of wound healing of nanogels containing Paccai eruvai in an incision and excision wound models.

Methods

Paccai eruvai nanogel was synthesized using the high-energy milling method, and characterization and enhancement of the wound healing potential of Paccai eruvai nanogel were assessed.

Results

Reportedly, Paccai eruvai nanogel has been produced successfully and its chemical properties confirmed, and physical properties characterized. Paccai eruvai nanogel showed homogeneity, green color, transparency, and an average size of 19.73 nm. We observed a significant reduction of wound area (p<0.001) in the Paccai eruvai nanogel-treated rats. The percentage of wound contraction on the 16th day was higher than the traditional formulation and nitrofurazone treatment. Notably, a lesser epithelialization period (14.33 days) and higher hydroxyproline content were observed in the 10% Paccai eruvai nanogel rats. We found that 10 % Paccai eruvai nanogel treatment increased tensile strength suggesting a better therapeutic indication.

Conclusion

The present findings indicate that Paccai eruvai nanogel significantly contributes wound healing activities with the enhancement of collagen synthesis, wound contraction, and wound tensile strength.

Reference

Sakthiganapathi, M., Yoganandam, G. P., & Gopal, V. (2023). Modernization of a Traditional Siddha Medicine Paccai eruvai into a Novel Nanogel Formulation for the Potent Wound Healing Activity-A Phyto- Pharmaceutical Approach. Pharmaceutical nanotechnology, 11(1), 70–81. https://doi.org/10.2174/2211738510666221003113247

Advanced Drug Delivery Reviews
2023, February 23

Why traditional herbal medicine promotes wound healing: Research from immune response, wound microbiome to controlled delivery

Abstract

Impaired wound healing in chronic wounds has been a significant challenge for clinicians and researchers for decades. Traditional herbal medicine (THM) has a long history of promoting wound healing, making them culturally accepted and trusted by a great number of people in the world. However, for a long time, the understanding of herbal medicine has been limited and incomplete, particularly in the allopathic medicine-dominated research system. The therapeutic effects of individual components isolated from THM are found less pronounced compared to synthetic chemical medicine, and the clinical efficacy is always inferior to herbs. In the present article, we review and discuss underlying mechanisms of the skin microbiome involved in the wound healing process; THM in regulating immune responses and commensal microbiome. We additionally propose few pioneer ideas and studies in the development of therapeutic strategies for controlled delivery of herbal medicine. This review aims to promote wound care with a focus on wound microbiome, immune response, and topical drug delivery systems. Finally, future development trends, challenges, and research directions are discussed.

Reference

Xu, Z., Dong, M., Yin, S., Dong, J., Zhang, M., Tian, R., Min, W., Zeng, L., Qiao, H., & Chen, J. (2023). Why traditional herbal medicine promotes wound healing: Research from immune response, wound microbiome to controlled delivery. Advanced Drug Delivery Reviews, 195, 114764. https://doi.org/10.1016/j.addr.2023.114764