Comparative effect of resveratrol, carnosic acid and hernandulcin on target enzymes and biochemical markers linked to carbohydrate and lipid metabolism in mice

IF 0.7 4区 农林科学 Q3 AGRONOMY Emirates Journal of Food and Agriculture Pub Date : 2023-06-02 DOI:10.9755/ejfa.2023.3130
N. Villa‐Ruano, S. Ramirez-Garcia, Gerardo Landeta-Cortés, J. M. Cunill-Flores, Guillermo M. Horta-Valerdi, Yesenia Pacheco Hernández
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Abstract

Resveratrol (RV), carnosic acid (CA) and hernandulcin (HE; a non-caloric sweetener) are envisioned as promising nutraceuticals to designnew functional foods for improving lipid and carbohydrate metabolism. This study aimed to investigate the in vitro inhibitory effectof these molecules on specific enzyme targets and their capacity to improve distinctive markers associated to carbohydrate and lipidmetabolism in murine model. The enzymes explored were alpha-amylase, alpha-glucosidase, and pancreatic lipase whereas ICR malemice were used for in vivo testing. Saturation curves (10-200 µM mL-1) and Lineweaver-Burk regressions suggested that RV, CA andHE exerts non-competitive inhibition on pancreatic lipase, alpha-glucosidase and alpha-amylase but, CA produced a strong competitiveactivity on alpha-amylase. RV was more effective to inhibit alpha-glucosidase (IC50, 22.1 µM) whereas CA was the most effective toinhibit both alpha-amylase (IC50, 11.7 µM) and pancreatic lipase (IC50, 31.5 µM). The effects of the oral administration of RV (300 mg/kg) HE (100 mg/kg) and CA (100 mg/kg) as well as the simultaneous administration of the three compounds at the same concentration was also explored in normoglycemic and diabetic mice. In addition, the prolonged administration of these substances combined with hypercaloric/atherogenic diet for 30 days was performed. Our results revealed a clear modulatory activity in both postprandial glucose and triglyceride levels as well an improvement in biochemical markers of mice treated with hypercaloric/atherogenic diet. The administration of HE produced a notable change (p < 0.01) in postprandial glucose assimilation at 60 min post-treatment in diabetic mice, whereas the other two compounds exerted a stronger depletion of glucose levels from 30 to 120 min post-treatment. A similar trend was recorded by RV and CA in postprandial triglyceride content, however, the latter compound was more effective (p < 0.05) at lower doses than RV. The simultaneous administration of the three compounds produced a significant improvement (p < 0.01) in biochemical parameters associated to carbohydrate (insulin and glucose) and lipid metabolism (total cholesterol, LDL-c, HDL-c, triglycerides, leptin, and adiponectin).Outstandingly, the mixture of the three compounds was more effective (p < 0.01) than the administration of sole compounds to amelioratethe side effects of the hypercaloric/atherogenic diet. Finally, the body weight of treated mice significantly decreased (from 5 to 20%; p < 0.05) in comparison with mice only fed with hypercaloric/atherogenic diet. Our results suggest that mixtures of RV, HE and CA may work better than their sole administration in mice and part of their biological activity could be associated with their inhibitory properties on the enzyme targets evaluated in this investigation. Keywords: Carnosic acid; Hernandulcin; Resveratrol; Hypoglycemic; Hypolipidemic; Murine model; Target enzymes
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白藜芦醇、肉毒酚酸和蛇床子甙对小鼠体内与碳水化合物和脂质代谢有关的靶酶和生化指标的比较效应
白藜芦醇(RV)、肉苁蓉酸(CA)和鞘氨醇苷(HE,一种无热量甜味剂)被认为是很有前途的营养保健品,可用于设计新的功能食品,改善脂质和碳水化合物代谢。本研究旨在调查这些分子对特定酶靶的体外抑制作用,以及它们改善小鼠模型中与碳水化合物和脂质代谢相关的独特指标的能力。所研究的酶是α-淀粉酶、α-葡萄糖苷酶和胰脂肪酶,并使用 ICR 小鼠进行体内测试。饱和曲线(10-200 µM mL-1)和 Lineweaver-Burk 回归表明,RV、CA 和 HE 对胰脂肪酶、α-葡萄糖苷酶和α-淀粉酶具有非竞争性抑制作用,但 CA 对α-淀粉酶具有很强的竞争活性。RV 对α-葡萄糖苷酶的抑制作用更强(IC50,22.1 µM),而 CA 对α-淀粉酶(IC50,11.7 µM)和胰脂肪酶(IC50,31.5 µM)的抑制作用最强。此外,还在血糖正常的小鼠和糖尿病小鼠中探讨了口服 RV(300 毫克/千克)、HE(100 毫克/千克)和 CA(100 毫克/千克)以及同时服用相同浓度的这三种化合物的效果。此外,还对这些物质与高热量/高致脂肪饮食联合长期服用 30 天的情况进行了研究。我们的研究结果表明,这些物质对餐后血糖和甘油三酯水平有明显的调节作用,并改善了高热量/高脂饮食小鼠的生化指标。给糖尿病小鼠注射 HE 后 60 分钟,餐后葡萄糖同化发生了显著变化(p < 0.01),而其他两种化合物在治疗后 30 至 120 分钟内对葡萄糖水平的消耗更强。RV 和 CA 对餐后甘油三酯含量的影响趋势相似,但后者在低剂量时比 RV 更有效(p < 0.05)。同时服用这三种化合物可显著改善碳水化合物(胰岛素和葡萄糖)和脂质代谢(总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、甘油三酯、瘦素和脂肪连通素)相关生化指标(p < 0.01)。最后,与只喂食高热量/致动脉粥样硬化饮食的小鼠相比,接受治疗的小鼠体重明显下降(从 5% 降至 20%;p < 0.05)。我们的研究结果表明,RV、HE 和 CA 的混合物对小鼠的作用可能比单独给药更好,它们的部分生物活性可能与它们对本研究中评估的酶靶点的抑制特性有关。 关键词卡诺酸;白藜芦醇;降血糖;降血脂;小鼠模型;靶酶
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来源期刊
Emirates Journal of Food and Agriculture
Emirates Journal of Food and Agriculture AGRONOMYFOOD SCIENCE & TECHNOLOGY&nb-FOOD SCIENCE & TECHNOLOGY
CiteScore
1.80
自引率
0.00%
发文量
18
期刊介绍: The "Emirates Journal of Food and Agriculture [EJFA]" is a unique, peer-reviewed Journal of Food and Agriculture publishing basic and applied research articles in the field of agricultural and food sciences by the College of Food and Agriculture, United Arab Emirates University, United Arab Emirates.
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