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光甘草定,一种从甘草根中提取的富含异甘草素的提取物,可减轻大鼠巨噬细胞中的炎症以及胶原诱导的关节炎。

Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats.

作者信息

Babu Vineet, Kapkoti Deepak Singh, Binwal Monika, Bhakuni Rajendra S, Shanker Karuna, Singh Manju, Tandon Sudeep, Mugale Madhav N, Kumar Narendra, Bawankule Dnyaneshwar U

机构信息

Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, Post Office-CIMAP, Near Kukrail Picnic Spot, Lucknow, Uttar Pradesh, 226015, India.

Phytochemistry Division, Central Institute of Medicinal and Aromatic Plants (CSIR), Lucknow, 226015, India.

出版信息

Inflammopharmacology. 2023 Apr;31(2):983-996. doi: 10.1007/s10787-023-01152-w. Epub 2023 Mar 22.

Abstract

Liquiritigenin (LTG) and its bioprecursor isoliquiritigenin(ISL), the main bioactives from roots of Glycyrrhiza genus are progressively documented as a potential pharmacological agent for the management of chronic diseases. The aim of this study was to evaluate the pharmacological potential of liquiritigenin, isoliquiritigenin rich extract of Glycyrrhiza glabra roots (IVT-21) against the production of pro-inflammatory cytokines from activated macrophages as well as further validated the efficacy in collagen-induced arthritis model in rats. We also performed the safety profile of IVT-21 using standard in-vitro and in-vivo assays. Results of this study revealed that the treatment of IVT-21 and its major bioactives (LTG, ISL) was able to reduce the production of pro-inflammatory cytokines (TNF-α, IL-6) in LPS-activated primary peritoneal macrophages in a dose-dependent manner compared with vehicle-alone treated cells without any cytotoxic effect on macrophages. In-vivo efficacy profile against collagen-induced arthritis in Rats revealed that oral administration of IVT-21 significantly reduced the arthritis index, arthritis score, inflammatory mediators level in serum. IVT-21 oral treatment is also able to reduce the NFкB-p65 expression as evidence of immunohistochemistry in knee joint tissue and mRNA level of pro-inflammatory cytokines in paw tissue in a dose-dependent manner when compared with vehicle treated rats. Acute oral toxicity profile of IVT-21 demonstrated that it is safe up to 2000 mg/kg body weight in experimental mice. This result suggests the suitability of IVT-21 for further study in the management of arthritis and related complications.

摘要

甘草根素(LTG)及其生物前体异甘草根素(ISL)是甘草属植物根中的主要生物活性成分,越来越多的文献表明它们是治疗慢性疾病的潜在药物。本研究的目的是评估甘草根中富含甘草根素和异甘草根素的提取物(IVT - 21)对活化巨噬细胞产生促炎细胞因子的药理作用,并进一步验证其在大鼠胶原诱导性关节炎模型中的疗效。我们还使用标准的体外和体内试验对IVT - 21进行了安全性评估。本研究结果显示,与单独使用赋形剂处理的细胞相比,IVT - 21及其主要生物活性成分(LTG、ISL)能够以剂量依赖的方式降低脂多糖激活的原代腹腔巨噬细胞中促炎细胞因子(TNF-α、IL-6)的产生,且对巨噬细胞无任何细胞毒性作用。在大鼠胶原诱导性关节炎模型中的体内疗效评估显示,口服IVT - 21可显著降低关节炎指数、关节炎评分以及血清中炎症介质水平。与赋形剂处理的大鼠相比,IVT - 21口服治疗还能够以剂量依赖的方式降低膝关节组织中NFкB - p65的免疫组化表达以及爪组织中促炎细胞因子的mRNA水平。IVT - 21的急性口服毒性评估表明,在实验小鼠中,其体重高达2000 mg/kg时是安全的。这一结果表明IVT - 21适合进一步研究用于关节炎及相关并发症的治疗。

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