This study investigates the potential phytochemicals that modulate bovine peroxisome proliferator-activated receptor gamma (PPARγ) and the mitogen-activated protein kinase (MAPK) pathways to enhance milk fat production in dairy animals. Bovine PPARγ, a key member of the nuclear hormone receptor superfamily, plays a vital role in regulating metabolic, cellular differentiation, apoptosis, and anti-inflammatory responses in livestock, while the MAPK pathway is contributory in cellular processes that impact milk fat synthesis. This approach involved an all-inclusive molecular docking analysis of 10,000 polyphenols to identify potential PPARγ ligands. From this extensive screening, top 10 compounds were selected that exhibited the highest binding affinities to bovine PPARγ. Particularly, curcumin sulfate, isoflavone, and quercetin emerged as the most promising candidates. These compounds demonstrated superior docking scores (−9.28 kcal/mol, −9.27 kcal/mol, and −7.31 kcal/mol, respectively) and lower RMSD values compared to the synthetic bovine PPARγ agonist, 2,4-thiazolidinedione (−4.12 kcal/mol), indicating a strong potential for modulating the receptor. Molecular dynamics simulations (MDS) further affirmed the stability of these polyphenols–bovine PPARγ complexes, suggesting their effective and sustained interactions. These polyphenols, known as fatty acid synthase inhibitors, are suggested to influence lipid metabolism pathways crucial to milk fat production, possibly through the downregulation of the MAPK pathway. The screened compounds showed favorable pharmacokinetic profiles, including nontoxicity, carcinogenicity, and high gastrointestinal absorption, positioning them as viable candidates for enhancing dairy cattle health and milk production. These findings may open new possibilities for the use of phytochemicals as feed additives in dairy animals, suggesting a novel approach to improve milk fat synthesis through the dual modulation of bovine PPARγ and MAPK pathways.

中文翻译：

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多酚的计算机分析调节牛 PPARγ，通过 MAPK 信号通路增加奶牛的乳脂合成


本研究调查了调节牛过氧化物酶体增殖物激活受体 γ （PPARγ） 和丝裂原活化蛋白激酶 （MAPK） 途径以增强奶牛乳脂产生的潜在植物化学物质。牛 PPARγ 是核激素受体超家族的关键成员，在调节家畜的代谢、细胞分化、细胞凋亡和抗炎反应中起着至关重要的作用，而 MAPK 通路在影响乳脂合成的细胞过程中发挥作用。这种方法涉及对 10,000 种多酚进行全包式分子对接分析，以识别潜在的 PPARγ 配体。从这种广泛的筛选中，选择了与牛 PPARγ 结合亲和力最高的前 10 种化合物。特别是，硫酸姜黄素、异黄酮和槲皮素成为最有前途的候选者。与合成牛 PPARγ 激动剂 2,4-噻唑烷二酮 （-4.12 kcal/mol） 相比，这些化合物表现出更高的对接评分（分别为 -9.28 kcal/mol、-9.27 kcal/mol 和 -7.31 kcal/mol）和较低的 RMSD 值，表明具有调节受体的强大潜力。分子动力学模拟 （MDS） 进一步证实了这些多酚-牛 PPARγ 复合物的稳定性，表明它们存在有效和持续的相互作用。这些被称为脂肪酸合酶抑制剂的多酚被认为可能影响对乳脂产生至关重要的脂质代谢途径，可能通过下调 MAPK 途径。筛选的化合物显示出良好的药代动力学特征，包括无毒、致癌性和高胃肠道吸收，使它们成为增强奶牛健康和产奶的可行候选者。 这些发现可能为在奶牛中使用植物化学物质作为饲料添加剂开辟新的可能性，提出了一种通过牛 PPARγ 和 MAPK 途径的双重调节来改善乳脂合成的新方法。