In silico, in vitro, and in vivo acute and sub-acute toxicity profiling of whole plant methanol extract of Equisetum diffusum D. Don from the sub-Himalayan West Bengal, India, having ethnobotanical uses.

IF 3.3 2区 医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE BMC Complementary Medicine and Therapies Pub Date : 2024-08-30 DOI:10.1186/s12906-024-04606-y
Sourav Sarkar, Debabrata Modak, Sudipta Kumar Roy, Anupam Biswas, Mafidul Islam, Rinku Baishya, Sujoy Bose, John J Georrge, Soumen Bhattacharjee
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Abstract

Background: Equisetum diffusum D. Don commonly known as 'Himalayan horsetail', has been traditionally used in the treatment of back pain, bone fracture and dislocation, and arthritis by various tribal communities of India. Our previous study confirmed the anti-inflammatory efficacy of the plant through in silico, in vitro, and in vivo model studies. Therefore, the current research is focused on safety dose evaluation for the first-time of the whole-plant methanol extract (EDME) of E. diffusum through appropriate in silico, in vitro, and in vivo approaches.

Method: The whole plant, along with its rhizomes, was collected, and the methanol extract was prepared. The in silico ADMET study was performed to predict the pharmacokinetics profile and toxicity of all the identified phyto-compounds of EDME previously screened by GC-MS study. In vitro cytotoxicity study of EDME was performed using two cell lines: kidney (HEK293) and liver (Huh7) cell lines. The in vivo toxicity study of EDME was validated by the acute toxicity (OECD 423, 2002) and sub-acute toxicity assays (OECD 407, 2008) in the Wistar Albino rat model.

Results: The in silico ADMET study of all 47 bioactives predicted good pharmacokinetic and low toxicity profiles. In vitro cytotoxicity showed higher IC50 values of EDME viz., 672 ± 15.7 μg/mL and 1698 ± 6.54 μg/mL for both kidney (HEK293) and liver (Huh7) cell lines, respectively, which were considered as low-toxic. Based on acute oral toxicity, the LD50 value of the extract was considered "non-toxic" up to a feeding range of 2000 mg/kg of body weight. The regular consumption of the extract for an extended period (28 days) was also qualified as safe based on the body and organ weight, hematological, biochemical, and histoarchitecture results in the sub-acute toxicity assay.

Conclusion: The detailed in silico, in vitro, in vivo (acute and sub-acute oral toxicity) studies gave us a new insight to the safety dose evaluation of Equisetum diffusum, which may serve as a reliable documentation for undertaking the experimental validation of the ethnobotanical uses of the plant which would help in the field of drug development for the treatment of inflammation related complications.

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对印度西孟加拉邦亚喜马拉雅山地区具有民族植物学用途的Equisetum diffusum D. Don全草甲醇提取物进行硅学、体外和体内急性和亚急性毒性分析。Don的全草甲醇提取物。
背景介绍Equisetum diffusum D.Don 俗称 "喜马拉雅马尾草",印度各部落社区传统上一直用它来治疗背痛、骨折和脱臼以及关节炎。我们之前的研究通过硅学、体外和体内模型研究证实了该植物的抗炎功效。因此,目前的研究重点是通过适当的硅学、体外和体内方法,首次对 E. diffusum 的全草甲醇提取物(EDME)进行安全剂量评估:方法:采集全草及其根茎,制备甲醇提取物。对先前通过气相色谱-质谱研究筛选出的 EDME 植物化合物进行硅学 ADMET 研究,以预测其药代动力学特征和毒性。使用肾脏(HEK293)和肝脏(Huh7)两种细胞系对 EDME 进行了体外细胞毒性研究。在 Wistar Albino 大鼠模型中,通过急性毒性(OECD 423,2002 年)和亚急性毒性试验(OECD 407,2008 年)对 EDME 的体内毒性进行了验证:结果:对所有 47 种生物活性物质进行的硅学 ADMET 研究表明,它们具有良好的药代动力学特征和低毒性特征。体外细胞毒性显示,EDME 对肾脏(HEK293)和肝脏(Huh7)细胞株的 IC50 值较高,分别为 672 ± 15.7 μg/mL 和 1698 ± 6.54 μg/mL,属于低毒性。根据急性口服毒性,提取物的半数致死剂量(LD50)在每千克体重 2000 毫克的喂养范围内被认为是 "无毒 "的。根据亚急性毒性试验中的体重和器官重量、血液学、生物化学和组织结构结果,长期(28 天)定期食用该提取物也被认为是安全的:详细的硅学、体外、体内(急性和亚急性口服毒性)研究为我们提供了一个关于马钱子安全性剂量评估的新视角,可作为对该植物的民族植物学用途进行实验验证的可靠文件,这将有助于治疗炎症相关并发症的药物开发领域。
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来源期刊
BMC Complementary Medicine and Therapies
BMC Complementary Medicine and Therapies INTEGRATIVE & COMPLEMENTARY MEDICINE-
CiteScore
6.10
自引率
2.60%
发文量
300
审稿时长
19 weeks
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