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采用β-细胞毒性物质(STZ)处理大鼠,对龙葵叶治疗氧化损伤的临床前疗效进行生物化学和组织病理生理学评估。

Biochemical and tissue physiopathological evaluation of the preclinical efficacy of Solanum torvum Swartz leaves for treating oxidative impairment in rats administered a β-cell-toxicant (STZ).

机构信息

Department of Biochemistry, Faculty of Biological Science, Alex Ekwueme Federal University Ndufu Alike Ikwo, PMB 1010 Abakalike, Ebonyi State, Nigeria.

PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei 11031, Taiwan; Graduate Institute of Cancer Biology & Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei 11031, Taiwan.

出版信息

Biomed Pharmacother. 2022 Oct;154:113605. doi: 10.1016/j.biopha.2022.113605. Epub 2022 Aug 26.

DOI:10.1016/j.biopha.2022.113605
PMID:36030588
Abstract

The current study evaluated the protective role of Solanum torvum Swartz against diabetes-induced oxidative stress and tissue impairment in streptozotocin (STZ)-intoxicated rats. Rats with STZ (40 mg/kg intraperitoneally (i.p.))-induced diabetes were divided into five groups (n = 5) and treated with (i) normal saline, (ii) 150 mg/kg body weight (BW) of the ethanol extract of S. torvum leaf (EESTL), (ii) 300 mg/kg BW EESTL, (iv) 100 mg/kg BW metformin, and (v) 50 m/kg BW metformin + 100 mg/kg BW EESTL orally for 21 days. Our results revealed that the EESTL displayed dose-dependent ferric-reducing antioxidant power (FRAP) activity, scavenged DPPH radicals (IC) = 13.52 ± 0.45 µg/mL), and inhibited lipid peroxidation in an in vitro models. In addition, the EESTL demonstrated dose-dependent inhibitory activity against α-amylase (IC =138.46 ± 3.97 µg/mL) and promoted glucose uptake across plasma membranes of yeast cells in a manner comparable to that of metformin. Interestingly, the extract demonstrated in vivo blood glucose normalization effects with concomitant increased activities of antioxidant parameters (superoxide dismutase (SOD), catalase, and reduced glutathione (GSH)) while decreasing malondialdehyde (MDA) levels when compared to untreated rats. Similarly, serum biochemical alterations, and tissues (liver, kidney, and pancreases) histopathological aberrations in untreated rats with STZ-induced diabetes were attenuated by treatment with the EESTL. Biometabolite characterization of the extract identified gallic acid (45.81 ppm), catechin (1.18 ppm), p-coumaric acid (1.43e ppm), DL-proline 5-oxo-methyl ester (9.16 %, retention time (RT): 8.57 min), salicylic acid (3.26% and 7.61 min), and butylated hydroxytoluene (4.75%, RT: 10.18 min) as the major polyphenolic compounds in the plant extract. In conclusion, our study provides preclinical evidence of the antioxidant properties and oxidative stress-preventing role of S. torvum in STZ-dosed diabetic rats. Taken together, the EESTL represents a reserve of bioactive metabolites for managing diabetes and associated complications.

摘要

本研究评估了龙葵(Solanum torvum Swartz)对链脲佐菌素(STZ)诱导的糖尿病大鼠氧化应激和组织损伤的保护作用。用 STZ(40mg/kg 腹腔注射(i.p.))诱导糖尿病的大鼠分为五组(n=5),分别用(i)生理盐水、(ii)150mg/kg 体重(BW)龙葵叶乙醇提取物(EESTL)、(ii)300mg/kg BW EESTL、(iv)100mg/kg BW 二甲双胍和(v)50mg/kg BW 二甲双胍+100mg/kg BW EESTL 口服治疗 21 天。我们的结果表明,EESTL 表现出剂量依赖性铁还原抗氧化能力(FRAP)活性,清除 DPPH 自由基(IC=13.52±0.45μg/mL),并在体外模型中抑制脂质过氧化。此外,EESTL 对α-淀粉酶表现出剂量依赖性抑制活性(IC=138.46±3.97μg/mL),并以类似于二甲双胍的方式促进酵母细胞质膜的葡萄糖摄取。有趣的是,与未治疗的大鼠相比,该提取物具有体内降血糖作用,同时增加抗氧化参数(超氧化物歧化酶(SOD)、过氧化氢酶和还原型谷胱甘肽(GSH))的活性,同时降低丙二醛(MDA)水平。同样,用 EESTL 治疗可减轻未经处理的 STZ 诱导的糖尿病大鼠的血清生化改变和组织(肝、肾和胰腺)组织病理学异常。提取物的生物代谢产物特征鉴定出没食子酸(45.81ppm)、儿茶素(1.18ppm)、对香豆酸(1.43e ppm)、DL-脯氨酸 5-氧-甲基酯(9.16%,保留时间(RT):8.57min)、水杨酸(3.26%和 7.61min)和丁基化羟基甲苯(4.75%,RT:10.18min)作为植物提取物中的主要多酚化合物。总之,我们的研究为龙葵在 STZ 给药的糖尿病大鼠中的抗氧化特性和抗氧化应激预防作用提供了临床前证据。综上所述,EESTL 代表了用于治疗糖尿病及其相关并发症的生物活性代谢物的储备。

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