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Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis

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Abstract

Oral ulcer is a frequent condition that commonly affects the tongue and in which 75% of the patients experience pain, and 25% report taste changes. The available therapies are not sufficiently effective for rapid and complete healing of tongue ulcers. We previously annotated the metabolites of Thymus satureioides (TS) aerial parts and reported their antioxidant, dermacosmeceutical and hepatoprotective properties. In this study, we performed in silico analysis, by applying network pharmacology and molecular docking, followed by experimental validation of the effect of local application of T. satureioides (TS) gel at two different concentrations on the healing of acetic-acid-induced tongue ulcer in rats. Salvianolic acid A, phloretic acid caffeate, rosmarinic acid, apigenin, and luteolin were the top bioactive ingredients of TS extract. Network pharmacology showed that the most relevant targets of these active constituents were TLR4, COX-2, MMP-9, TNF-α, and Caspase-3. Molecular docking showed that rosmarinic acid and salvianolic acid had a relatively strong binding affinity, compared to the other compounds, toward all the target proteins. Experimental validation in tongue ulcer model in rats and immunohistochemistry experiments showed that application of a gel containing TS extract (5 and 10%) was effective in healing the tongue ulcer via downregulation of COX-2, TNF-α, MMP-9, and Caspase-3. This study suggests that T. satureioides extract could act as a topical treatment for tongue ulcers by combating inflammation, apoptosis, and proteolysis. The possible treatment potential of some constituents including rosmarinic acid and salvianolic acid in oral ulcerations awaits further investigations to confirm their potency.

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The datasets generated during and/or analyzed during the current study are available within the manuscript and/or supplementary materials.

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Authors and Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Mahmoud H. Elbatreek & Mona F. Mahmoud

  2. Department of Pharmaceutics, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt

    Ayman M. Fathi

  3. AgroBioSciences Department, College for Sustainable Agriculture and Environmental Science, Mohammed VI Polytechnic University, 43150, Ben Guerir, Morocco

    Ismail Mahdi & Mansour Sobeh

  4. College of Engineering and Technology, American University of the Middle East, Egaila, 54200, Kuwait

    Mohamed A. O. Abdelfattah

Authors
  1. Mahmoud H. Elbatreek
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  2. Ayman M. Fathi
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  3. Ismail Mahdi
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  4. Mohamed A. O. Abdelfattah
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  5. Mona F. Mahmoud
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  6. Mansour Sobeh
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Contributions

Conceptualization, MFM and MS; methodology, MFM and MS; investigation, MHE, AMF, MAOA; writing—original draft preparation, MHE, AMF, IM, and MAOA; writing—review and editing, MFM and MS. All the authors have read and agreed to the published version of the manuscript.

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Correspondence to Mona F. Mahmoud or Mansour Sobeh.

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Elbatreek, M.H., Fathi, A.M., Mahdi, I. et al. Thymus satureioides Coss. combats oral ulcer via inhibition of inflammation, proteolysis, and apoptosis. Inflammopharmacol 31, 2557–2570 (2023). https://doi.org/10.1007/s10787-023-01285-y

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