A Review on Development and Evaluation of a Piper Betle L. Leaf Extract Clay Mask with Molecular Docking Studies for Anti – Acne Activity

Acne vulgaris is a common inflammatory skin disorder characterized by excessive sebum production, abnormal follicular keratinization, microbial colonization, and inflammation. Cutibacterium acnes contributes to inflammatory signaling through pathways involving Toll-like receptors, particularly TLR2 and TLR4. Increased 5α-reductase activity is associated with excessive sebum production, while matrix metalloproteinase-9 (MMP-9) is involved in extracellular matrix degradation and inflammation. Piper betle L. leaves contain various bioactive phytoconstituents, including phenolics, flavonoids, tannins, terpenoids, and essential oils, which have demonstrated antimicrobial, antioxidant, and anti-inflammatory activities. These properties make P. betle a promising candidate for topical anti-acne applications.This review evaluates the phytochemical, pharmacological, formulation, and molecular docking evidence supporting the potential use of P. betle leaf extract in a clay-mask formulation for anti-acne application. Particular attention is given to the possible interactions of P. betle phytoconstituents with acne-associated molecular targets such as TLR2, TLR4, MMP-9, and 5α-reductase. The combination of the biological activities of P. betle extract with the sebum-adsorbing and cleansing properties of clay may provide a promising topical approach for acne management. However, further phytochemical characterization, formulation optimization, acne-specific antimicrobial studies, molecular and experimental validation, safety evaluation, and clinical trials are required to establish its therapeutic efficacy and safety.