Umoru Grace Ufedo, Atangwho Item Justin, David-Oku Esien, Uti Daniel Ejim, Agwupuye Eyuwa Ignatius, Obeten Uket Nta, Maitra Swastika, Subramaniyan Vetriselvan, Wong Ling Shing, Aljarba Nada H, Kumarasamy Vinoth
Department of Biochemistry, College of Sciences, Evangel University Akaeze, Okpoto, Ebonyi State, Nigeria.
Department of Biochemistry, Faculty of Basic Medical Sciences, University of Calabar, Calabar, Nigeria.
J Cell Mol Med. 2024 Dec;28(24):e70086. doi: 10.1111/jcmm.70086.
Tetracarpidium conophorum nuts are nutrient-dense Nigerian snacks associated with weight regulation. This study explores the nuts' impact on adipose tissue gene expression associated with low-grade inflammation. Ethanol whole extract (EWE), ethyl-acetate fraction (EAF) and the resulting residue (RES) were orally administered once daily to MSG-induced obese rats for 6 weeks (n = 6). Afterward, the RNA synthesis of inflammation-associated genes was measured, and GC-MS ligands in the extract and fractions were docked against their protein products in silico. The study found that in obese animals, PPAR-γ and Adiponectin expressions were down-regulated, while TNF-α was up-regulated, indicating an increased low-grade inflammatory process in adipose tissue. After 6-week oral treatments with EWE, EAF and RES, PPAR-γ and Adiponectin expressions increased significantly, while TNF-α expression decreased, suggesting the modulation of obesity-induced inflammation in adipose tissue. The in silico molecular docking analysis identified four lead compounds likely responsible for the observed effect, namely 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one, 9,12,15-Octadecatrienoic methyl ester (Z,Z,Z), 9,12,15-Octadecatrienoic acid and Hexanedioic acid, bis(2-ethylhexyl). Of these compounds, 6-Isopropenyl-4,8a-dimethyl-4a,5,67,8,8a-hexahydro-1H-naphthalen-2-one demonstrated the strongest affinity to the binding cavities of PPARγ (-7.3 kcal/mol), Leptin (-5.2 kcal/mol), Adiponectin (-7.1 kcal/mol) and TNF-α (-6.3 kcal/mol) and was better than the standard drug, Orlistat (-6.7, -4.4, -6.8 and - 4.5 kcal/mol, respectively). The study reveals that T. conophorum nuts possess bioactive compounds/drug candidates that can exert positive modulation, at the molecular level, the low-grade inflammatory process associated with obesity, which normally facilitates the outset of complications.
四棱豆坚果是尼日利亚营养丰富的零食，与体重调节有关。本研究探讨了这些坚果对与低度炎症相关的脂肪组织基因表达的影响。将乙醇全提取物（EWE）、乙酸乙酯馏分（EAF）和所得残渣（RES）每日一次口服给予味精诱导的肥胖大鼠，持续6周（n = 6）。之后，测量炎症相关基因的RNA合成，并将提取物和馏分中的气相色谱-质谱配体与它们的蛋白质产物进行计算机对接。研究发现，在肥胖动物中，PPAR-γ和脂联素表达下调，而TNF-α上调，表明脂肪组织中低度炎症过程增加。在用EWE、EAF和RES进行6周口服治疗后，PPAR-γ和脂联素表达显著增加，而TNF-α表达下降，表明对肥胖诱导的脂肪组织炎症有调节作用。计算机分子对接分析确定了四种可能对观察到的效果负责的先导化合物，即6-异丙烯基-4,8a-二甲基-4a,5,6,7,8,8a-六氢-1H-萘-2-酮、9,12,15-十八碳三烯酸甲酯（Z,Z,Z）、9,12,15-十八碳三烯酸和己二酸双（2-乙基己基）酯。在这些化合物中，6-异丙烯基-4,8a-二甲基-4a,5,6,7,8,8a-六氢-1H-萘-2-酮对PPARγ（-7.3 kcal/mol）、瘦素（-5.2 kcal/mol）、脂联素（-7.1 kcal/mol）和TNF-α（-6.3 kcal/mol）的结合腔表现出最强的亲和力，并且优于标准药物奥利司他（分别为-6.7、-4.4、-6.8和-4.5 kcal/mol）。该研究表明，四棱豆坚果含有生物活性化合物/候选药物，它们可以在分子水平上对与肥胖相关的低度炎症过程发挥积极调节作用，而肥胖通常会引发并发症。
