Wound Healing Effect of Supercritical Carbon Dioxide Datura metel L. Leaves Extracts: An In Vitro Study of Anti-Inflammation, Cell Migration, MMP-2 Inhibition, and the Modulation of the Sonic Hedgehog Pathway in Human Fibroblasts

Author:

Ruksiriwanich Warintorn123ORCID,Linsaenkart Pichchapa1ORCID,Muangsanguan Anurak1,Sringarm Korawan234ORCID,Jantrawut Pensak123ORCID,Arjin Chaiwat4ORCID,Sommano Sarana Rose23ORCID,Phimolsiripol Yuthana35ORCID,Barba Francisco J.6ORCID

Affiliation:

1. Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand

2. Cluster of Valorization and Bio-Green Transformation for Translation Research Innovation of Raw Materials and Products, Chiang Mai University, Chiang Mai 50200, Thailand

3. Cluster of Agro Bio-Circular-Green Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand

4. Department of Animal and Aquatic Sciences, Faculty of Agriculture, Chiang Mai University, Chiang Mai 50200, Thailand

5. School of Agro-Industry, Faculty of Agro-Industry, Chiang Mai University, Chiang Mai 50100, Thailand

6. Department of Preventive Medicine and Public Health, Food Science, Toxicology and Forensic Medicine, Faculty of Pharmacy, University of Valencia, Burjassot, 46100 Valencia, Spain

Abstract

Datura metel L. (thorn apple) has been used in Thai folk wisdom for wound care. In this study, we chose supercritical carbon dioxide extraction (scCO2) to develop crude extraction from the leaves of the thorn apple. The phytochemical profiles were observed using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-QTOF-MS). The biological activities of D. metel were performed through antioxidant assays, anti-inflammation based on the Griess reaction, the migration assay, the expression of matrix metalloproteinase-2 (MMP-2), and regulatory genes in fibroblasts. Dm1 and Dm2 extracts were obtained from scCO2 procedures at different pressures of 300 and 500 bar, respectively. Bioactive compounds, including farnesyl acetone, schisanhenol B, and loliolide, were identified in both extracts. The antioxidant properties of both D. metel extracts were comparable to those of l-ascorbic acid in hydrogen peroxide-induced fibroblasts with no significant difference. Additionally, Dm1 and Dm2 significantly inhibited the nitrite production levels of 1.23 ± 0.19 and 1.52 ± 0.05 μM, respectively, against the lipopolysaccharide-treated group (3.82 ± 0.39 μM). Interestingly, Dm1 obviously demonstrated the percentage of wound closure with 58.46 ± 7.61 and 82.62 ± 6.66% after 36 and 48 h of treatment, which were comparable to the commercial deproteinized dialysate from the calf blood extract. Moreover, both extracts were comparable to l-ascorbic acid treatment in their ability to suppress the expression of MMP-2: an enzyme that breaks down collagen. The gene expressions of SHH, SMO, and GLI1 that control the sonic hedgehog pathway were also clearly upregulated by Dm1. Consequently, the scCO2 technique could be applied in D. metel extraction and contribute to potentially effective wound closure.

Funder

Fundamental Fund 2023, Chiang Mai University

Publisher

MDPI AG

Subject

Plant Science,Ecology,Ecology, Evolution, Behavior and Systematics

Reference43 articles.

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5. A new sesquiterpenoid with cytotoxic and anti-inflammatory activity from the leaves of Datura metel L.;Guo;Nat. Prod. Res.,2021

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