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富含没食子的 Commiphora leptophloeos 酚提取物对炎症性肠病的化学预防和免疫调节作用:临床前证据。

Chemopreventive and immunomodulatory effects of phenolic-rich extract of Commiphora leptophloeos against inflammatory bowel disease: Preclinical evidence.

机构信息

Health Sciences Center, Postgraduate Program in Development and Technological Innovation in Medicines, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

Biosciences Center, Federal University of Rio Grande do Norte, Natal, RN, Brazil.

出版信息

J Ethnopharmacol. 2024 Jun 28;328:118025. doi: 10.1016/j.jep.2024.118025. Epub 2024 Mar 7.

Abstract

ETHNOPHARMACOLOGY RELEVANCE

Commiphora leptophloeos (Mart.) J.B. Gillet (Burseraceae) is a medicinal plant native to Brazil, popularly known as "imburana". Homemade leaf decoction and maceration were used to treat general inflammatory problems in the Brazilian Northeast population. Our previous research confirmed the anti-inflammatory activity of the C. leptophloeos hydroalcoholic leaf extract.

AIM OF THE STUDY

Inflammatory bowel disease (IBD) is a chronic and relapsing inflammatory disorder of the gut with no ideal treatment to maintain the remissive status. This work aimed to characterize the phytochemical composition and physicochemical properties of the C. leptophloeos hydroalcoholic leaf extract and its efficacy in chemopreventive and immunomodulatory responses in inflammatory bowel disease in non-clinical models.

MATERIALS AND METHODS

Mass spectrometry and physicochemical tests determined the phytochemical profile and physicochemical characteristics of the Commiphora leptophloeos (CL) extract. The chemopreventive and immunomodulatory effects of CL extract (50 and 125 μg/mL) were evaluated in vitro in the RAW 264.7 lipopolysaccharide (LPS) induced cell assay and in vivo in the model of intestinal inflammation induced by 2,4-Dinitrobenzenesulfonic acid (DNBS) in mice when they were treated with CL extract by intragastric gavage (i.g.) at doses of 300, 400 and 500 mg/kg.

RESULTS

Phytochemical annotation of CL extract showed a complex phenolic composition, characterized as phenolic acids and flavonoids, and satisfactory physicochemical characteristics. In addition, CL extract maintained the viability of RAW macrophages, reduced ROS and NO production, and negatively regulated COX-2, iNOS, TNF-α, IL-1β, IL-6, and IL-17 (p < 0.05). In the intestinal inflammation model, CL extract was able to downregulate NF-κB p65/COX-2, mTOR, iNOS, IL-17, decrease levels of malondialdehyde and myeloperoxidase and cytokines TNF-α, IL-1β and IL-6 (p < 0.05).

CONCLUSION

Based on these findings, CL extract reduced inflammatory responses by down-regulating pro-inflammatory markers in macrophages induced by LPS and DNBS-induced colitis in mice through NF-κB p65/COX-2 signaling. CL leaf extract requires further investigation as a candidate for treating inflammatory bowel disease.

摘要

民族药理学相关性

Commiphora leptophloeos (Mart.) J.B. Gillet(柏科)是一种原产于巴西的药用植物,俗称“imburana”。巴西东北部的人们使用自制的叶浸剂和浸渍剂来治疗一般炎症问题。我们之前的研究证实了 C. leptophloeos 水醇叶提取物的抗炎活性。

研究目的

炎症性肠病(IBD)是一种慢性复发性肠道炎症性疾病,目前尚无理想的治疗方法来维持缓解状态。本工作旨在表征 C. leptophloeos 水醇叶提取物的植物化学成分和物理化学性质及其在非临床模型中对炎症性肠病的化学预防和免疫调节作用。

材料和方法

质谱和物理化学测试确定了 Commiphora leptophloeos (CL) 提取物的植物化学成分谱和物理化学特性。通过 LPS 诱导的 RAW 264.7 细胞测定和 2,4-二硝基苯磺酸 (DNBS) 诱导的肠道炎症模型中,评估了 CL 提取物(50 和 125μg/mL)的化学预防和免疫调节作用,在这些模型中,CL 提取物通过灌胃(i.g.)以 300、400 和 500mg/kg 的剂量给予小鼠。

结果

CL 提取物的植物化学注释显示出复杂的酚类成分特征,包括酚酸和类黄酮,并具有令人满意的物理化学特性。此外,CL 提取物维持 RAW 巨噬细胞的活力,降低 ROS 和 NO 的产生,并负调控 COX-2、iNOS、TNF-α、IL-1β、IL-6 和 IL-17(p<0.05)。在肠道炎症模型中,CL 提取物能够下调 NF-κB p65/COX-2、mTOR、iNOS、IL-17,降低丙二醛和髓过氧化物酶水平以及 TNF-α、IL-1β 和 IL-6 的水平(p<0.05)。

结论

基于这些发现,CL 提取物通过下调 LPS 诱导的巨噬细胞和 DNBS 诱导的结肠炎中促炎标志物的表达,减少了炎症反应,通过 NF-κB p65/COX-2 信号通路。CL 叶提取物作为治疗炎症性肠病的候选药物,需要进一步研究。

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