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.

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, ß 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 exvivo 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.

Therapeutic Potential of Skin Stem Cells and Cells of Skin Origin: Effects of Botanical Drugs Derived from Traditional Medicine.

Skin, the largest organ of the body, plays a vital role in protecting inner organs. Skin stem cells (SSCs) comprise a group of cells responsible for multiplication and replacement of damaged and non-functional skin cells; thereby help maintain homeostasis of skin functions. SSCs and differentiated cells of the skin such as melanocytes and keratinocytes, have a plethora of applications in regenerative medicine. However, as SSCs reside in small populations in specific niches in the skin, use of external stimulants for cell proliferation in vitro and in vivo is vital. Synthetic and recombinant stimulants though available, pose many challenges due to their exorbitant prices, toxicity issues and side effects. Alternatively, time tested traditional medicine preparations such as polyherbal formulations are widely tested as effective natural stimulants, to mainly stimulate proliferation, and melanogenesis/prevention of melanogenesis of both SSCs and cells of skin origin. Complex, multiple targets, synergistic bioactivities of the phytochemical constituents of herbal preparations amply justify these as natural stimulants. The use of these formulations in clinical applications such as in skin regeneration for burn wounds, wound healing acceleration, enhancement or decrease of melanin pigmentations will be in great demand. Although much multidisciplinary research is being conducted on the use of herbal formulas as stem cell stimulants, very few related clinical trials are yet registered with the NIH clinical trial registry. Therefore, identification/ discovery, in depth investigations culminating in clinical trials, as well as standardization and commercialization of such natural stimulants must be promoted, ensuring the sustainable use of medicinal plants.