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Role of Hemigraphis alternata in wound healing: metabolomic profiling and molecular insights into mechanisms.

ABSTRACT: Hemigraphis alternata (H. alternata), commonly known as Red Flame Ivy, is widely recognized for its wound healing capabilities. However, the pharmacologically active plant components and their mechanisms of action in wound healing are yet to be determined. This study presents the mass spectrometry-based global metabolite profiling of aqueous and ethanolic extract of H. alternata leaves. The analysis identified 2285 metabolites from 24,203 spectra obtained in both positive and negative polarities. The identified metabolites were classified under ketones, carboxylic acids, primary aliphatic amines, steroids and steroid derivatives. We performed network pharmacology analysis to explore metabolite-protein interactions and identified 124 human proteins as targets for H. alternata metabolites. Among these, several of them were implicated in wound healing including prothrombin (F2), alpha-2A adrenergic receptor (ADRA2A) and fibroblast growth factor receptor 1 (FGFR1). Gene ontology analysis of target proteins enriched cellular functions related to glucose metabolic process, platelet activation, membrane organization and response to wounding. Additionally, pathway enrichment analysis revealed potential molecular network involved in wound healing. Moreover, in-silico docking analysis showed strong binding energy between H. alternata metabolites with identified protein targets (F2 and PTPN11). Furthermore, the key metabolites involved in wound healing were further validated by multiple reaction monitoring-based targeted analysis.

SUBMITTER: Devasahayam Arokia Balaya R

PROVIDER: S-EPMC10873326 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Role of Hemigraphis alternata in wound healing: metabolomic profiling and molecular insights into mechanisms.

Devasahayam Arokia Balaya Rex R Palollathil Akhina A Kumar Sumaithangi Thattai Arun STA Chandrasekaran Jaikanth J Upadhyay Shubham Sukerndeo SS Parate Sakshi Sanjay SS Sajida M M Karthikkeyan Gayathree G Prasad Thottethodi Subrahmanya Keshava TSK

Scientific reports 20240216 1

Hemigraphis alternata (H. alternata), commonly known as Red Flame Ivy, is widely recognized for its wound healing capabilities. However, the pharmacologically active plant components and their mechanisms of action in wound healing are yet to be determined. This study presents the mass spectrometry-based global metabolite profiling of aqueous and ethanolic extract of H. alternata leaves. The analysis identified 2285 metabolites from 24,203 spectra obtained in both positive and negative polarities ...[more]

PMID: 38365839

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Project description:BackgroundAlthough the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events.Study designThis study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier--toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days). 17.5K cDNA microarrays were utilized to profile the biopsy material.ResultsFour gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy) were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies) and repair and angiogenesis genes in the later (4 to 8 days) biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated.ConclusionThe initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominantly M2 macrophages, may help the interpretation of the cellular and molecular events occurring in the microenvironment of serially biopsied tissues.

Project description:Benzalkonium bromide (BB) has been widely used as a skin antiseptic for wound management. However, BB had proinflammation and reactive oxygen species (ROS) induction effect, making its role in wound healing complex and unclear. A rat full-thickness skin defect wound model was established. The effects of BB, povidone iodine (PVP-I), chlorhexidine gluconate (CHG), and normal saline (NS) on wound healing and infection control were then evaluated based on wound healing rate (WHr) and bacterial killing. The wound tissues were sectioned for histopathological evaluation and nuclear factor E2 related factor 2 (Nrf2) expression determination. The ROS production, Nrf2 activation, and heme oxygenase 1 (HO-1) expression of the HaCat cells and the cytotoxicity treated with BB were further explored. Compared with NS, PVP-I, and CHG, BB showed the best wound infection control efficiency while delayed wound healing with the WHr of 91.42 ± 5.12% at day 20. The wound tissue of the BB group showed many inflammatory cells but few granulation tissue and capillaries and no obvious collagen deposition, resulting in the lowest histopathological scores of 4.17 ± 0.75 for BB group. BB showed higher cytotoxicity on HaCat cells with the lowest IC25, IC50, and IC75 of 1.90, 4.16, and 9.09 g/mL compared with PVP-I and CHG. TUNEL staining evaluated the cytotoxicity of BB on wound tissue, which indicates the high apoptosis index BB group (5.05 ± 1.77). Compared with PVP-I and CHG, BB induced much more cell apoptosis. The results of flow cytometry and fluorescence staining showed that PVP-I, CHG, and BB induced ROS production in a concentration-dependent manner and cells treated with BB had the highest ROS production at the same inhibition concentration. The cells and the wound tissues treated with BB showed highest Nrf2 activation and HO-1 expression than PVP-I and CHG. BB was highly efficient in wound infection control while delayed wound healing. The prolonged and strengthened inflammation and the raised ROS production originating from BB administration may contribute to delayed wound healing.

Dataset Information

Role of Hemigraphis alternata in wound healing: metabolomic profiling and molecular insights into mechanisms.

Publications

Role of Hemigraphis alternata in wound healing: metabolomic profiling and molecular insights into mechanisms.

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