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芩术凉血汤的临床前和临床研究:基于网络药理学的见解及对特应性皮炎治疗的启示

Preclinical and clinical studies on Qin-Zhu-Liang-Xue decoction: insights from network pharmacology and implications for atopic dermatitis treatment.

作者信息

Huang Keke, Liu Qingkai, Zhang Ruoxi, Nian Hua, Luo Ying, Luo Yue, Fei Xiaoya, Kuai Le, Li Bin, Tan Yimei, Li Su, Ma Xin

机构信息

Department of Dermatology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.

Institute of Dermatology, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, China.

出版信息

Front Med. 2025 Feb;19(1):134-148. doi: 10.1007/s11684-024-1101-7. Epub 2024 Dec 11.

Abstract

To investigate the protective effects and underlying mechanisms of Qin-Zhu-Liang-Xue decoction (QZLX) in atopic dermatitis (AD) and glucocorticoid resistance, we conducted a single-blinded, randomized controlled clinical trial to evaluate the efficacy and safety of this concoction. Network pharmacology analysis was performed and validated through clinical studies. The efficacy, safety, and mechanism of action of QZLX and glucocorticoid receptor (GR) α recombinant protein were assessed in AD mice induced by 2,4-dinitrofluorobenzene (DNFB). Correlation analysis was performed to determine the clinical relevance of GRα. The trial demonstrated that patients who received QZLX showed considerable improvements in their Scoring Atopic Dermatitis (SCORAD) and Dermatology Life Quality Index (DLQI) scores compared with those who received mizolastine at week 4. Network pharmacological analysis identified GRα as a key target for QZLX in AD treatment. QZLX administration increased the serum GRα expression in AD patients, alleviated AD symptoms in mice, decreased inflammatory cytokine expression, and increased GRα expression without affecting liver or kidney function. In addition, GRα recombinant protein improved AD-like skin lesions in DNFB-induced mice. A negative correlation was observed between GRα expression and clinical parameters, including SCORAD, DLQI, and serum IgE levels. QZLX alleviates AD symptoms through the upregulation of GRα and thus presents a novel therapeutic strategy for the prevention of glucocorticoid resistance in AD management.

摘要

为了研究芩珠凉血汤(QZLX)在特应性皮炎(AD)和糖皮质激素抵抗中的保护作用及潜在机制,我们进行了一项单盲、随机对照临床试验,以评估该方剂的疗效和安全性。通过临床研究进行了网络药理学分析并验证。在2,4-二硝基氟苯(DNFB)诱导的AD小鼠中评估了QZLX和糖皮质激素受体(GR)α重组蛋白的疗效、安全性及作用机制。进行相关性分析以确定GRα的临床相关性。试验表明,与接受咪唑斯汀治疗的患者相比,接受QZLX治疗的患者在第4周时特应性皮炎评分(SCORAD)和皮肤病生活质量指数(DLQI)得分有显著改善。网络药理学分析确定GRα是QZLX治疗AD的关键靶点。给予QZLX可增加AD患者血清GRα表达,减轻小鼠AD症状,降低炎性细胞因子表达,并增加GRα表达,且不影响肝肾功能。此外,GRα重组蛋白改善了DNFB诱导小鼠的类AD皮肤损伤。观察到GRα表达与包括SCORAD、DLQI和血清IgE水平在内的临床参数之间呈负相关。QZLX通过上调GRα减轻AD症状,从而为AD管理中预防糖皮质激素抵抗提供了一种新的治疗策略。

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