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Indonesian Journal of Medical Chemistry and Bioinformatics

Abstract

Background: Fibrosis involves excessive extracellular matrix (ECM) deposition, with matrix metalloproteinase-9 (MMP-9) playing a critical role. Natural compounds targeting MMP-9 may offer therapeutic potential. Objective: This study evaluated the antifibrotic effect of Allium sativum extract on fibroblast cells through in vitro and in silico approaches targeting MMP-9. Methods: Human dermal fibroblasts were treated with A. sativum extract (25, 50, and 100 µg/mL) for 24 and 48 hours. Cell viability was assessed using MTT assay. MMP-9 expression was analyzed via quantitative real-time PCR (qRT-PCR) and immunocytochemistry (ICC). Major garlic compounds were docked to MMP-9 using AutoDock Vina. Results: The 50 µg/mL concentration maintained >85% cell viability and significantly reduced MMP-9 gene and protein expression. S-allyl cysteine exhibited the strongest binding affinity (−6.8 kcal/mol) and formed hydrogen bonds with key residues (Glu402, Ala189, His405) of MMP-9. Conclusion: Allium sativum extract demonstrates antifibrotic activity by downregulating MMP-9 expression and inhibiting its function, supporting its potential as a natural MMP-9 inhibitor for fibrosis-related disorders.

Bahasa Abstract

Latar Belakang: Fibrosis melibatkan deposisi matriks ekstraseluler (ECM) yang berlebihan, dengan matriks metaloproteinase-9 (MMP-9) memainkan peran penting. Senyawa alami yang menargetkan MMP-9 dapat menawarkan potensi terapeutik. Tujuan: Penelitian ini mengevaluasi efek antifibrotik ekstrak Allium sativumpada sel fibroblas melalui pendekatan in vitro dan in silico yang menargetkan MMP-9. Metode: Fibroblas dermal manusia diobati dengan ekstrak A. sativum (25, 50, dan 100 µg/mL) selama 24 dan 48 jam. Viabilitas sel dinilai menggunakan uji MTT. Ekspresi MMP-9 dianalisis melalui qRT-PCR dan imunositokimia (ICC). Senyawa bawang putih utama didokingkan ke MMP-9 menggunakan AutoDock Vina. Hasil: Konsentrasi 50 µg/mL mempertahankan >85% viabilitas sel dan secara signifikan mengurangi ekspresi gen dan protein MMP-9. S-alil sisteina menunjukkan afinitas pengikatan terkuat (−6,8 kkal/mol) dan membentuk ikatan hidrogen dengan residu kunci (Glu402, Ala189, His405) MMP-9. Kesimpulan: Ekstrak Allium sativum menunjukkan aktivitas antifibrotik dengan menurunkan ekspresi MMP-9 dan menghambat fungsinya, mendukung potensinya sebagai inhibitor MMP-9 alami untuk gangguan terkait fibrosis.

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