A systems approach to pigmentation control by ascorbic acid esterified with coconut oil-derived medium-chain fatty acids: Investigated via network pharmacology, molecular dynamics, elastic network and Markov state models

IF 3.1 4区生物学 Q2 BIOLOGY

Computational Biology and Chemistry Pub Date : 2025-07-15 DOI:10.1016/j.compbiolchem.2025.108594

Modhi O. Alotaibi

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引用次数: 0

Abstract

Tyrosinase family enzymes (TYR, TRP1, TRP2) play pivotal roles in melanogenesis, making them targets for pigmentation modulation. Ascorbic acid (ASC) and coconut oil have shown promise in skin whitening. Inspired by these ASC esterified with coconut oil-derived medium-chain fatty acids (MCFAs) such as capric acid (ASC-CAP), caproic acid (ASC-CAPRO), caprylic acid (ASC-CAPRY) and lauric acid (ASC-LAU) are investigated via in silico analysis such as network pharmacology (NP), molecular docking and molecular dynamics (MD) simulation to understand their interaction with tyrosinase family enzymes. This study introduces a novel approach to skin depigmentation by examining the combined effects of ascorbic acid and coconut oil derivatives on the regulation of tyrosinase family enzymes involved in melanogenesis. NP analysis identified a key hub of enzymes-LRRC8A (cell regulation), MITF (melanogenesis), and CD8A (immune signalling)-emphasizing MITF's central role in activating tyrosinase-mediated pathways. Toxicity predictions revealed minimal risk with low LD₅₀ values of the compounds studied. MD simulations showed strong ligand stability at enzyme active sites, supported by RMSD, RMSF, DCCM, RTA, ENM, PCA, FEL, MSM and MM-GBSA binding free energy analyses. Energy landscape analyses identified metastable low-energy states, identifying stable ligand-enzyme interactions. These findings highlight the potential of ASC esterified with MCFAs as safe, and effective agents for pigmentation regulation. The present study reveals that ASC-CAPRO for TRP1 and TRP2; and ASC-LAU for TYR are the most promising candidates, offering insights into therapeutic approaches for hyperpigmentation treatment.

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抗坏血酸与椰子油衍生的中链脂肪酸酯化控制色素沉着的系统方法：通过网络药理学、分子动力学、弹性网络和马尔可夫状态模型进行研究

酪氨酸酶家族酶（TYR, TRP1, TRP2）在黑色素形成中起关键作用，使其成为色素沉着调节的靶点。抗坏血酸（ASC）和椰子油在皮肤美白方面显示出前景。受椰子油衍生中链脂肪酸（MCFAs）如己酸（ASC- cap）、己酸（ASC- capro）、辛酸（ASC- capry）和月桂酸（ASC- lau）酯化ASC的启发，通过网络药理学（NP）、分子对接和分子动力学（MD）模拟等硅分析研究了它们与酪氨酸酶家族酶的相互作用。本研究通过研究抗坏血酸和椰子油衍生物对参与黑色素形成的酪氨酸酶家族酶的调节作用，介绍了一种新的方法来治疗皮肤色素沉着。NP分析确定了lrrc8a（细胞调节）、MITF（黑色素生成）和CD8A（免疫信号传导）这三个酶的关键枢纽，强调了MITF在激活酪氨酸酶介导的途径中的核心作用。毒性预测显示，所研究化合物的LD50值较低，风险最小。通过RMSD、RMSF、DCCM、RTA、ENM、PCA、FEL、MSM和MM-GBSA结合自由能分析，MD模拟显示配体在酶活性位点具有较强的稳定性。能量景观分析确定了亚稳态低能态，确定了稳定的配体-酶相互作用。这些发现强调了与MCFAs酯化的ASC作为安全有效的色素沉着调节剂的潜力。本研究表明，ASC-CAPRO对TRP1和TRP2具有抑制作用；和ASC-LAU治疗TYR是最有希望的候选药物，为色素沉着过度的治疗方法提供了新的见解。

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来源期刊

Computational Biology and Chemistry 生物-计算机：跨学科应用

CiteScore

6.10

自引率

3.20%

发文量

142

审稿时长

24 days

期刊介绍： Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered. Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered. Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.