Topical Garcinia Mangostana Pericarp Extract Attenuates TPA-Induced Cutaneous Inflammation and Oxidative Stress in Mice: Preclinical Implications for Tumor Promotion-Related Inflammatory Mechanisms

Abstract

Purpose: Persistent cutaneous inflammation and oxidative stress drive the promotion stage of skin carcinogenesis. Most evidence for Garcinia mangostana pericarp comes from purified α-mangostin tested in vitro or given systemically. We evaluated whether a standardized crude G. mangostana pericarp extract (GMPE) applied topically produces concentration-related anti-inflammatory and antioxidant effects in acute 12- O -tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Methods: Thirty-five male Swiss albino mice were randomized to seven groups (n = 5): negative control, TPA control, TPA + vehicle cream, TPA + 1% hydrocortisone, and TPA + GMPE cream at 2.5%, 5%, and 10%. GMPE was standardized for α-mangostin by ultra-performance liquid chromatography. Cutaneous tumor necrosis factor-alpha (TNF-α; ELISA) and malondialdehyde (MDA; TBARS assay) were measured, and epidermal thickness, neutrophil infiltration, and immunohistochemical TNF-α and MDA expression (immunoreactive score, IRS) were assessed by a blinded observer. Results: GMPE contained 17.54 ± 0.03% (w/w) α-mangostin. TPA raised TNF-α from 22.03 ± 11.43 to 77.03 ± 17.50 pg/mL and MDA from 0.48 ± 0.13 to 0.92 ± 0.10 nmol/mL, increased epidermal thickness fivefold, and induced neutrophil infiltration (all p < 0.001). GMPE 10% lowered TNF-α to 24.81 ± 11.85 pg/mL and MDA to 0.48 ± 0.10 nmol/mL, values not different from healthy skin or from hydrocortisone, and restored epidermal thickness (50 ± 20 μm). Immunohistochemistry confirmed these changes. A linear concentration–response was significant for MDA (p = 0.001). Conclusion: In this experimental animal study, topical GMPE exerted concentration-related anti-inflammatory and antioxidant effects in acute TPA-induced skin inflammation, and the 10% cream performed comparably to 1% hydrocortisone. Because signaling pathways and tumor endpoints were not measured, GMPE may serve as a promising preclinical candidate for mechanistic and long-term chemoprevention studies rather than a proven modulator of tumor promotion. Keywords: garcinia mangostana, α-mangostin, tumor necrosis factor-alpha, malondialdehyde, oxidative stress, skin inflammation

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