Antioxidant, xanthine oxidase (XO) inhibitory, hypouricemic effect evaluation and GCMS analysis of ethanolic extract of Piper chaba stem: Supported by in vitro, in vivo, and molecular docking experiments

Q3 Pharmacology, Toxicology and Pharmaceutics Phytomedicine Plus Pub Date : 2024-10-09 DOI:10.1016/j.phyplu.2024.100652

Sahria Rahman , Umme Kulsum Hridy , Marjana Alam , Rahima Begum , Md Arju Hossain , Kishore Kumar Sarkar , Kamalesh Saha , Apurba Kumar Barman , Nripendra Nath Biswas

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Abstract

Background

Piper chaba has been traditionally using for its potential health benefits. The principal goal of this investigation was to assess the pharmacological characteristics of the EEPCS, focusing on investigating its potential antihyperuricemic effects, ability to inhibit xanthine oxidase (XO) enzyme, and antioxidant properties.

Methods

The antioxidant capability of the extract was assessed using the DPPH radical assay. The extract was evaluated in vitro aimed at its xanthine oxidase inhibitory (XOI) action and further experimented for its antihyperuricemic effect on the Potassium oxonate (PO) induced hyperuricemia murine model. Besides, molecular docking techniques were employed to interpret the inhibitory mechanism of the compounds identified through GCMS analysis of the EEPCS.

Results

There was no safety concern at doses up to 3000 mg/kg of the extract as confirmed by mice model studies. The extract displayed potent the antioxidant properties during quantitative antioxidant test (IC₅₀=104.9 ± 0.99 µg/mL). In XOI test, the extract was found to be effective with an IC₅₀ value of 26.14 μg/mL. In addition, the extract was found to decrease the Serum uric acid (SUA) levels by 36.72 and 61.84 % at 100 and 200 mg/kg body weight respectively, compared to the hyperurecaemic animals. The GCMS analysis of the extract revealed eighteen distinct compounds, which were docked against human peroxiredoxin 5 and xanthin oxidase proteins. Selina-3,7(11)-diene (CID: 6429221) was the most effective phytochemical for the human peroxiredoxin 5 protein having binding score −6.2 Kcal/mol compared to standard ascorbic acid (5.6 Kcal/mol). Besides, gamma-muurolene (-7.9 Kcal/mol) was the most effective phytochemical for the XO protein compared to standard allopurinol (−6.4 Kcal/mol).

Conclusion

Our experimental data showed that the EEPCS has potentiality as an antioxidant and hypouricemic agent that could be contributed to treat and manage oxidative stress (OS), gout and hyperuricemia.

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瓜蒌茎乙醇提取物的抗氧化性、黄嘌呤氧化酶（XO）抑制性、降尿酸作用评估和 GCMS 分析：体外、体内和分子对接实验的支持

背景蒌壳（Piper chaba）因其潜在的健康益处而一直被人们使用。本研究的主要目的是评估 EEPCS 的药理特性，重点研究其潜在的抗高尿酸血症作用、抑制黄嘌呤氧化酶 (XO) 的能力以及抗氧化特性。对黄嘌呤氧化酶（XOI）的抑制作用进行了体外评估，并进一步研究了其对草酸钾（PO）诱导的高尿酸血症小鼠模型的抗高尿酸血症作用。此外，还采用了分子对接技术来解释通过对 EEPCS 进行 GCMS 分析而确定的化合物的抑制机制。在定量抗氧化测试中，该提取物显示出强大的抗氧化特性（IC50=104.9 ± 0.99 µg/mL）。在 XOI 试验中，发现该提取物有效，IC50 值为 26.14 μg/mL。此外，与高尿酸血症动物相比，该提取物在 100 和 200 mg/kg 体重下可使血清尿酸（SUA）水平分别降低 36.72% 和 61.84%。提取物的气相色谱-质谱（GCMS）分析显示，有 18 种不同的化合物与人类过氧化物酶 5 和黄嘌呤氧化酶蛋白对接。硒纳-3,7(11)-二烯（CID：6429221）是对人过氧化物酶 5 蛋白最有效的植物化学物质，与标准抗坏血酸（5.6 Kcal/mol）相比，其结合分数为-6.2 Kcal/mol。此外，与标准别嘌呤醇（-6.4 Kcal/mol）相比，γ-muurolene（-7.9 Kcal/mol）是对 XO 蛋白最有效的植物化学物质。结论我们的实验数据表明，EEPCS 具有抗氧化剂和降尿酸剂的潜力，可用于治疗和控制氧化应激（OS）、痛风和高尿酸血症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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