Mpofana Nomakhosi, Paulse Michael, Yalo Masande, Dlova Ncoza Cordelia, Hussein Ahmed, Lanrewaju Adedayo Ayodeji, Lukman Halimat Yusuf, Aribisala Jamiu Olaseni, Rautenbach Fanie, Marnewick Jeanine L, Sabiu Saheed
Dermatology Department, Nelson R. Mandela School of Medicine, University of Kwazulu-Natal, Durban, 4000, South Africa.
Department of Somatology, Durban University of Technology, Durban, 4000, South Africa.
J Exp Pharmacol. 2025 May 31;17:287-306. doi: 10.2147/JEP.S504759. eCollection 2025.
In rural areas of KwaZulu-Natal and Eastern Cape Provinces, South Africa, women have traditionally used bark extracts from , and for skin lightening and sun protection. This study investigates the anti-tyrosinase and antioxidant activities of methanolic bark extracts from these species, aiming to validate their traditional use and identify potential lead compounds for the treatment of skin hyperpigmentation.
Anti-tyrosinase activity was evaluated using half-maximal inhibitory concentration (IC) values, and antioxidant capacity was measured through FRAP, DPPH, and TEAC assays. Polyphenol and flavanol contents were quantified using Folin-Ciocalteu method. Potential lead compounds were identified through molecular docking, pharmacokinetic analysis, and molecular dynamics (MD) simulations. Statistical analyses, including ANOVA and post-hoc tests, compared extract activities.
exhibited the most potent anti-tyrosinase activity (IC: 37.10 µg/mL), though statistical differences among species were non-significant. showed the highest polyphenol (143.68 mg GAE/g) and flavanol (14.67 mg QE/g) content, correlating with superior antioxidant activity (FRAP: 526.07 µmol AAE/g; DPPH: 390.26 µmol TE/g; TEAC: 596.98 µmol TE/g). The isolated compound 7-methoxygeranin A demonstrated lower anti-tyrosinase activity (IC: 45.16 µg/mL) compared to extract, suggesting the presence of more potent metabolites. Molecular docking and MD simulations identified emodin 6,8-dimethyl ether as a thermodynamically stable lead compound (binding free energy: -39.88 kcal/mol), interacting with key catalytic residues over 150 ns. The compound demonstrated prolonged residence at the active site of tyrosinase, indicating strong-binding stability.
While demonstrated the strongest anti-tyrosinase activity, C. gummiflua showed the highest antioxidant potential. Emodin 6,8-dimethyl ether emerged as a promising candidate for skin-lightening applications, warranting further in vitro and in vivo validation. These findings support the traditional use of species and highlight their potential for developing natural skin health products. Further studies are needed to explore the pharmacokinetics, safety, and efficacy of these compounds in clinical settings.
在南非夸祖鲁 - 纳塔尔省和东开普省的农村地区，女性传统上使用[物种名称1]、[物种名称2]和[物种名称3]的树皮提取物来美白皮肤和防晒。本研究调查了这些物种甲醇树皮提取物的抗酪氨酸酶和抗氧化活性，旨在验证其传统用途，并确定治疗皮肤色素沉着过度的潜在先导化合物。
使用半数抑制浓度（IC）值评估抗酪氨酸酶活性，通过铁还原抗氧化能力（FRAP）、二苯基苦味酰基自由基（DPPH）和总抗氧化能力（TEAC）测定法测量抗氧化能力。使用福林 - 西奥尔特法对多酚和黄烷醇含量进行定量。通过分子对接、药代动力学分析和分子动力学（MD）模拟确定潜在的先导化合物。包括方差分析和事后检验在内的统计分析比较了提取物的活性。
[物种名称1]表现出最有效的抗酪氨酸酶活性（IC：37.10μg/mL），尽管物种之间的统计差异不显著。[物种名称2]显示出最高的多酚（143.68mg没食子酸当量/g）和黄烷醇（14.67mg儿茶素当量/g）含量，与优异的抗氧化活性相关（FRAP：526.07μmol抗坏血酸当量/g；DPPH：390.26μmol Trolox当量/g；TEAC：596.98μmol Trolox当量/g）。分离出的化合物7 - 甲氧基香叶木素A与[物种名称1]提取物相比，抗酪氨酸酶活性较低（IC：45.16μg/mL），表明存在更有效的代谢物。分子对接和MD模拟确定大黄素6,8 - 二甲醚为热力学稳定的先导化合物（结合自由能：-39.88kcal/mol），在150ns以上与关键催化残基相互作用。该化合物在酪氨酸酶活性位点的停留时间延长，表明具有强结合稳定性。
虽然[物种名称1]表现出最强的抗酪氨酸酶活性，但[物种名称2]显示出最高的抗氧化潜力。大黄素6,8 - 二甲醚成为皮肤美白应用的有希望的候选物，值得进一步的体外和体内验证。这些发现支持了[物种名称]的传统用途，并突出了它们开发天然皮肤健康产品的潜力。需要进一步研究来探索这些化合物在临床环境中的药代动力学、安全性和有效性。
