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抑制多种炎症信号通路对葡聚糖硫酸钠诱导的 BALB/c 小鼠的 Physalin B 的抗结肠炎作用。

Anti-colitic effects of Physalin B on dextran sodium sulfate-induced BALB/c mice by suppressing multiple inflammatory signaling pathways.

机构信息

Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Research Center for Clinical Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, PR China.

Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Research Center for Clinical Pharmacy, First Affiliated Hospital, College of Medicine, Zhejiang University, 79# Qingchun Road, Hangzhou, 310003, PR China.

出版信息

J Ethnopharmacol. 2020 Sep 15;259:112956. doi: 10.1016/j.jep.2020.112956. Epub 2020 May 19.

DOI:10.1016/j.jep.2020.112956
PMID:32442587
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Physalin B is one of the main active withanolide existed in Physalis alkekengi L. var. franchetii (Mast.) Makino, a famous traditional Chinese food and herbal medicine, which has been widely used as heat-clearing and toxin-resolving medicine for the treatment of various inflammatory disease, such as cough, excessive phlegm, pharyngitis, sore throat, pemphigus, eczema, and jaundice.

AIM OF THE STUDY

We aimed to confirm the therapeutic effects of Physalin B on ulcerative colitis (UC) and enrich the further application of its traditional anti-inflammatory effect.

MATERIALS AND METHODS

The anti-UC effects of Physalin B were evaluated in Balb/c mice with dextran sulfate sodium (DSS) induction. The body weight, colon length, disease activity index (DAI) and pathological changes of colon tissue were measured. Cytokine levels were detected by ELISA. NF-κB pathway and protein levels of related pathways, such as signal transducer and activator of transcription 3 (STAT3), β-arrestin1 and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome were detected by western blot.

RESULTS

The dose of Physalin B that is not cytotoxic could dramatically reduce the levels of TNF-α, IL-6 and IL-1β on LPS-stimulated RAW 264.7 cells. Meanwhile, Physalin B dramatically improved clinical signs and symptoms, alleviated body weight loss and colon length shortening in DSS-induced UC mice. Meanwhile, Physalin B also dramatically relieved the pathological damage, reduced in the activity of myeloperoxidase (MPO) and reestablished the balance of pro-inflammatory cytokines. Physalin B could suppress DSS-induced activation of NF-κB. Moreover, Physalin B also markedly suppressed the activation of STAT3, β-arrestin1 and NLRP3 inflammasome.

CONCLUSION

This study preliminary confirmed the therapeutic effect of Physalin B on experimental acute UC mice and provided robust evidence support for the anti-inflammatory effect of Physalin B, suggesting that Physalin B might be a potential agent for the therapeutic efficacy on UC.

摘要

民族药理学相关性

育亨宾 B 是灯笼草 Physalis alkekengi L. var. franchetii(Mast.)Makino 中主要的活性麦角甾二烯类化合物之一,是一种著名的传统中药和草药,被广泛用作清热解毒药,用于治疗各种炎症性疾病,如咳嗽、痰多、咽炎、喉炎、天疱疮、湿疹和黄疸。

研究目的

本研究旨在证实育亨宾 B 对溃疡性结肠炎(UC)的治疗作用,并丰富其传统抗炎作用的进一步应用。

材料和方法

在葡聚糖硫酸钠(DSS)诱导的 Balb/c 小鼠中评估育亨宾 B 的抗 UC 作用。测量体重、结肠长度、疾病活动指数(DAI)和结肠组织的病理变化。通过 ELISA 检测细胞因子水平。通过 Western blot 检测 NF-κB 通路和相关通路的蛋白水平,如信号转导和转录激活因子 3(STAT3)、β-arrestin1 和 NOD 样受体富含亮氨酸重复域蛋白 3(NLRP3)炎性体。

结果

无细胞毒性的育亨宾 B 剂量可显著降低 LPS 刺激的 RAW 264.7 细胞中 TNF-α、IL-6 和 IL-1β 的水平。同时,育亨宾 B 可显著改善 DSS 诱导的 UC 小鼠的临床症状和体征,减轻体重减轻和结肠缩短。同时,育亨宾 B 还显著减轻了病理损伤,降低了髓过氧化物酶(MPO)的活性,并重建了促炎细胞因子的平衡。育亨宾 B 可抑制 DSS 诱导的 NF-κB 激活。此外,育亨宾 B 还明显抑制了 STAT3、β-arrestin1 和 NLRP3 炎性体的激活。

结论

本研究初步证实了育亨宾 B 对实验性急性 UC 小鼠的治疗作用,为育亨宾 B 的抗炎作用提供了有力的证据支持,提示育亨宾 B 可能是 UC 治疗疗效的潜在药物。

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