Molecular mechanisms underlying Tao-Hong-Si-Wu decoction treating hyperpigmentation based on network pharmacology, Mendelian randomization analysis, and experimental verification.

IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY Pharmaceutical Biology Pub Date : 2024-12-01 Epub Date: 2024-03-31 DOI:10.1080/13880209.2024.2330609
Jun Chen, Wenyi Ye
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Abstract

Context: Hyperpigmentation, a common skin condition marked by excessive melanin production, currently has limited effective treatment options.

Objective: This study explores the effects of Tao-Hong-Si-Wu decoction (THSWD) on hyperpigmentation and to elucidate the underlying mechanisms.

Materials and methods: We employed network pharmacology, Mendelian randomization, and molecular docking to identify THSWD's hub targets and mechanisms against hyperpigmentation. The Cell Counting Kit-8 (CCK-8) assay determined suitable THSWD treatment concentrations for PIG1 cells. These cells were exposed to graded concentrations of THSWD-containing serum (2.5%, 5%, 10%, 15%, 20%, 30%, 40%, and 50%) and treated with α-MSH (100 nM) to induce an in vitro hyperpigmentation model. Assessments included melanin content, tyrosinase activity, and Western blotting.

Results: ALB, IL6, and MAPK3 emerged as primary targets, while quercetin, apigenin, and luteolin were the core active ingredients. The CCK-8 assay indicated that concentrations between 2.5% and 20% were suitable for PIG1 cells, with a 50% cytotoxicity concentration (CC50) of 32.14%. THSWD treatment significantly reduced melanin content and tyrosinase activity in α-MSH-induced PIG1 cells, along with downregulating MC1R and MITF expression. THSWD increased ALB and p-MAPK3/MAPK3 levels and decreased IL6 expression in the model cells.

Discussion and conclusion: THSWD mitigates hyperpigmentation by targeting ALB, IL6, and MAPK3. This study paves the way for clinical applications of THSWD as a novel treatment for hyperpigmentation and offers new targeted therapeutic strategies.

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基于网络药理学、孟德尔随机分析和实验验证的桃红四物汤治疗色素沉着的分子机制。
背景:色素沉着是一种以黑色素生成过多为特征的常见皮肤病,目前有效的治疗方法有限:本研究探讨桃红四物汤(THSWD)对色素沉着的影响,并阐明其潜在机制:我们采用网络药理学、孟德尔随机化和分子对接等方法来确定桃红四物汤抗色素沉着的中心靶点和机制。细胞计数试剂盒-8(CCK-8)测定法确定了适合 PIG1 细胞的 THSWD 处理浓度。将这些细胞暴露于不同浓度的含 THSWD 血清(2.5%、5%、10%、15%、20%、30%、40% 和 50%),并用 α-MSH (100 nM)处理,以诱导体外色素沉着模型。评估包括黑色素含量、酪氨酸酶活性和 Western 印迹:结果:ALB、IL6 和 MAPK3 成为主要靶点,而槲皮素、芹菜素和木犀草素则是核心活性成分。CCK-8 检测表明,2.5% 至 20% 的浓度适合 PIG1 细胞,50% 的细胞毒性浓度(CC50)为 32.14%。THSWD 可明显降低 α-MSH 诱导的 PIG1 细胞中的黑色素含量和酪氨酸酶活性,同时下调 MC1R 和 MITF 的表达。THSWD 提高了模型细胞中 ALB 和 p-MAPK3/MAPK3 的水平,降低了 IL6 的表达:THSWD通过靶向ALB、IL6和MAPK3缓解色素沉着。这项研究为 THSWD 作为色素沉着的新型治疗方法应用于临床铺平了道路,并提供了新的靶向治疗策略。
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来源期刊
Pharmaceutical Biology
Pharmaceutical Biology 医学-药学
CiteScore
6.70
自引率
2.60%
发文量
191
审稿时长
1 months
期刊介绍: Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine. Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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