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从甘蓝中分离出的尼古丁在类风湿性关节炎中的抗炎活性。

Anti-inflammatory activity of nicotine isolated from Brassica oleracea in rheumatoid arthritis.

机构信息

Council of Industrial Research (CSIR)-Institute of Genomics and Integrative Biology, Mall Road, Delhi University Campus, Delhi 110007, India.

Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.

出版信息

Biosci Rep. 2022 Apr 29;42(4). doi: 10.1042/BSR20211392.

Abstract

OBJECTIVES

Rheumatoid arthritis (RA) is an autoimmune disease, associated with chronic inflammation of synoviocytes. Tumor necrosis factor α (TNF-α) plays a crucial role in the pathogenesis of RA through pro-inflammatory cytokines. Nicotine, an alkaloid used as herbal medicine, often worked as an anti-inflammatory agent. In the present study, we tried to uncover the anti-inflammatory impact of nicotine against RA.

MATERIALS AND METHODS

Nicotine was isolated from Brassica oleracea, purified by high profile/phase liquid chromatography (HPLC). In-silico docking was carried out using bioinformatics tools SwissADME (absorption, distribution, metabolism and excretion), PASS, and Drug-induced Gene Expression Profile (DIGEP)-Pred to determine drug likeliness of nicotine. The in-vitro study was performed in TNFα-induced SW982 synoviocytes by qPCR. mRNA expression of pro-inflammatory cytokines (TNF, IL6, IL1β) and proteins (TRAF2, P50, P65) were analyzed followed by validation of P65 (RELA), pP65, IkBα by Western blot analysis.

RESULTS

Nicotine compound was extracted from Brassica oleracea and purified by HPLC method (Rt values at 2.67 min). The physicochemical, pharmacokinetic properties and drug-likeliness of nicotine were studied by in-silico analysis. In-vitro studies revealed that nicotine lowers the expression of inflammatory cytokines (TNF, IL6, IL1β) and proteins (TNF receptor-associated factor 2 (TRAF2), P50, P65) at 1 µg/ml in TNFα-induced SW982 cells.

CONCLUSION

Nicotine from natural sources (Brassica oleracea) has been found to be an effective anti- inflammatory compound at a low dosage; thus, identifying the role of nicotine present in the natural sources as a therapeutic option for RA, may be recommended as remedial drug instead of synthetic drug.

摘要

目的

类风湿关节炎(RA)是一种自身免疫性疾病,与滑膜细胞的慢性炎症有关。肿瘤坏死因子α(TNF-α)通过促炎细胞因子在 RA 的发病机制中起关键作用。尼古丁作为草药使用的一种生物碱,通常具有抗炎作用。在本研究中,我们试图揭示尼古丁对 RA 的抗炎作用。

材料和方法

尼古丁从甘蓝中分离出来,通过高效/相液相色谱(HPLC)纯化。使用生物信息学工具 SwissADME(吸收、分布、代谢和排泄)、PASS 和 Drug-induced Gene Expression Profile(DIGEP)-Pred 进行计算机对接,以确定尼古丁的药物相似性。在 TNFα诱导的 SW982 滑膜细胞中进行体外研究,通过 qPCR 进行。分析促炎细胞因子(TNF、IL6、IL1β)和蛋白质(TRAF2、P50、P65)的 mRNA 表达,然后通过 Western blot 分析验证 P65(RELA)、pP65、IkBα。

结果

尼古丁化合物从甘蓝中提取,通过 HPLC 方法纯化(Rt 值为 2.67 分钟)。通过计算机分析研究了尼古丁的物理化学、药代动力学特性和药物相似性。体外研究表明,尼古丁在 1μg/ml 的 TNFα诱导的 SW982 细胞中降低了炎症细胞因子(TNF、IL6、IL1β)和蛋白质(TNF 受体相关因子 2(TRAF2)、P50、P65)的表达。

结论

从天然来源(甘蓝)中提取的尼古丁在低剂量下已被证明是一种有效的抗炎化合物;因此,确定天然来源中存在的尼古丁作为 RA 的治疗选择的作用,可以推荐作为替代合成药物的治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ea7/9069442/e9d019e51bee/bsr-42-bsr20211392-g1.jpg

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