Department of Pharmacy, University of Malakand, Dir (Lower), Chakdara 18800, Khyber Pakhtunkhwa, Pakistan.
Department of Pharmacology, College of Pharmacy, Jouf University, Aljouf 72341, Saudi Arabia.
Molecules. 2022 Feb 18;27(4):1402. doi: 10.3390/molecules27041402.
Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones () and flavonols (), the mono para substituted methoxy containing and exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for and with IC values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* < 0.05, ** < 0.01 and *** < 0.001, = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* < 0.05, ** < 0.01 and *** < 0.001, = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.
天然类黄酮及其一些合成衍生物因其显著的药用特性而受到认可。本研究旨在探究合成类黄酮（黄酮类和黄酮醇类）在小鼠体内的抗氧化和抗应激作用，通过注射乙酸和游泳固定化来诱导应激。在所合成的黄酮类（）和黄酮醇类（）中，含有单对位取代甲氧基的和表现出对 DPPH（2,2-二苯基-1-苦基肼）最大的清除能力，IC 分别为 31.46 ± 1.46 μg/mL 和 25.54 ± 1.21 μg/mL。和的抗氧化能力最小，IC 值分别为 174.24 ± 2.71 μg/mL 和 122.33 ± 1.98 μg/mL，与生育酚相比。所有合成黄酮类和黄酮醇类的 ABTS 清除活性均明显高于 DPPH 测定，表明它们具有良好的抗氧化能力，ABTS（2,2'-连氮-双（3-乙基苯并噻唑啉-6-磺酸））测定在评估化学物质抗氧化能力方面是有效的。黄酮类处理的动物在扭体次数显著减少（* < 0.05，** < 0.01 和 *** < 0.001， = 8），游泳耐力时间增加。应激条件改变了血浆葡萄糖、胆固醇和甘油三酯水平，这些水平可作为动物模型中应激评估的标志物。在用黄酮类和黄酮醇（10 mg/kg）预处理 15 天后，这些标志物的水平几乎恢复正常。这些化合物还显著降低了脂质过氧化（TBARS：硫代巴比妥酸反应物质）的水平，与对照组相比具有统计学意义（* < 0.05，** < 0.01 和 *** < 0.001， = 8）。还观察到处理组中过氧化氢酶和 SOD（超氧化物歧化酶）水平显著升高。地西泮（2 mg/kg）被用作标准药物。此外，黄酮类还显著改变了应激诱导小鼠的肾上腺、脾脏和大脑的重量。研究结果表明，这些类黄酮可作为应激的治疗方法，并能够改善与应激相关的多种生理和生化变化。然而，还需要进一步的实验来确认在其他动物模型中观察到的潜力，特别是在那些与人类更相似的动物模型中。毒理学评价同样重要。
