Phytomedicine ( IF 6.7 ) Pub Date : 2022-09-06 , DOI: 10.1016/j.phymed.2022.154449 Danni Feng 1 , Zhongxiang Fang 1 , Pangzhen Zhang 1
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Background
Melanin plays an important role in protecting human skin, while excessive synthesis of melanin can cause abnormal pigmentation and induce skin diseases. Long-term use of commercial whitening agents in managing skin melanin such as kojic acid and arbutin can lead to some negative effects such as dermatitis and liver cancer. Although past studies have researched the melanin inhibitory effect of plant extracts, the effective dose and mechanisms are not well summarized and discussed. This study aims to explore the melanin inhibitory property of phytochemicals and tries to answer the following research questions: (1) Which plant extracts and phytochemicals could inhibit melanin biosynthesis in the skin? what is the mechanism of action? (2) Have human trials been conducted to confirm their melanin inhibitory effect? (3) If not, which phytochemicals are recommended for further human trials? This article would provide information for future research to develop natural and safe skin whitening products.
Methods
A preferred reporting items for systematic reviews and meta-analyses (PRISMA) systematic review method and OHAT risk-of-bias tool were applied to screen literature from 2000 to 2021 and 50 research articles met the selection criteria.
Results
Flavonoids, phenolic acids, stilbenes and terpenes are main classes of phytochemicals responsible for the melanin inhibitory effects. The in vitro/in vivo melanin inhibitory effects of these plant extracts/phytochemicals are achieved via three main mechanisms: (1) the ethyl acetate extract of Oryza sativa Indica cv., and phytochemicals such as galangin and origanoside could manage melanin biosynthesis through competitive inhibition, non-competitive inhibition or mixed-type inhibition of tyrosinase; (2) phytochemicals such as ginsenoside F1, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde could inhibit melanogenesis through down-regulating microphthalmia-related transcription factor (MITF) gene expression via different signalling pathways; (3) the ethanolic extracts of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius have a good ultraviolet absorption ability and high sun protective factor (SPF) values, thereby inhibiting UV induced melanogenesis in the skin.
Conclusion
Although many plant extracts and phytochemicals have been found to inhibit melanin production, most of the results were only proved in cellular and/or animal models. Only the ethyl acetate extract of Oryza sativa Indica cv. panicle, and ginsenoside F1 were proved effective in human trials. Animal studies proved the effectiveness of galangin, origanoside, ginsenoside Rb1 and 4‑hydroxy-3-methoxycinnamaldehyde with effective dose below 3 mM, and therefore recommended for future human trial. In addition, cellular studies have demonstrated the effectiveness of oxyresveratrol, mulberroside A, kurarinol, kuraridinol, plumbagin, (6aR,11aR)-3,8-dihydroxy-9‑methoxy pterocarpan, ginsenoside Rh4, cardamonin, nobiletin, curcumin, β-mangostin and emodin in inhibiting melanin synthesis at low concentrations of 20 µM and proved the low SPF values of Dimorphandra gardneriana, Dimorphandra gardneriana, Lippia microphylla and Schinus terebinthifolius extracts, and therefore recommended for further animal and human trials.
中文翻译：
植物和植物化学物质的黑色素抑制作用：系统评价
背景
黑色素在保护人体皮肤方面发挥着重要作用，而黑色素的过度合成会导致色素沉着异常，诱发皮肤病。长期使用商业美白剂管理皮肤黑色素，如曲酸和熊果苷，会导致一些负面影响，如皮炎和肝癌。虽然过去的研究已经研究了植物提取物的黑色素抑制作用，但其有效剂量和作用机制并未得到很好的总结和讨论。本研究旨在探讨植物化学物质的黑色素抑制特性，并试图回答以下研究问题：（1）哪些植物提取物和植物化学物质可以抑制皮肤中黑色素的生物合成？作用机制是什么？(2) 是否进行了人体试验以确认其黑色素抑制作用？(3) 如果没有，哪些植物化学物质被推荐用于进一步的人体试验？本文将为未来的研究提供信息，以开发天然和安全的皮肤美白产品。
方法
系统评价和荟萃分析（PRISMA）系统评价方法和 OHAT 偏倚风险工具的首选报告项目应用于筛选 2000 年至 2021 年的文献，50 篇研究文章符合选择标准。
结果
黄酮类化合物、酚酸、二苯乙烯和萜烯是负责黑色素抑制作用的主要植物化学物质。这些植物提取物/植物化学物质的体外/体内黑色素抑制作用是通过三种主要机制实现的：(1) Oryza sativa Indica cv的乙酸乙酯提取物。，植物化学物质如高良姜素和牛至果苷可以通过竞争性抑制、非竞争性抑制或酪氨酸酶的混合抑制来控制黑色素的生物合成；(2)人参皂甙F1、人参皂甙Rb1和4-羟基-3-甲氧基肉桂醛等植物化学物质可以通过不同的信号通路下调小眼相关转录因子(MITF)基因的表达来抑制黑色素生成；(3)加德纳、加德纳、小叶千金和石竹的乙醇提取物具有良好的紫外线吸收能力和较高的防晒系数(SPF)值，从而抑制紫外线诱导的皮肤黑色素生成。
结论
尽管已经发现许多植物提取物和植物化学物质可以抑制黑色素的产生，但大多数结果仅在细胞和/或动物模型中得到证实。只有Oryza sativa Indica cv的乙酸乙酯提取物。圆锥花序和人参皂甙 F1 在人体试验中被证明是有效的。动物研究证明了高良姜甙、牛至果苷、人参皂甙 Rb1 和 4-羟基-3-甲氧基肉桂醛的有效性，有效剂量低于 3 mM，因此推荐用于未来的人体试验。此外，细胞研究已证明氧白藜芦醇、桑椹苷 A、kurarinol、kuraridinol、白杨素、(6aR,11aR)-3,8-dihydroxy-9-methoxy pterocarpan、人参皂甙 Rh4、cardamonin、nobiletin、姜黄素、β- 山竹素和大黄素在 20 µM 的低浓度下抑制黑色素合成， 并证明了Dimorphandra gardneriana、Dimorphandra gardneriana、Lippia microphylla 和 Schinus terebinthifolius提取物的低 SPF 值，因此推荐用于进一步的动物和人体试验。
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