Lan Yuejia, Wang Huan, Wu Jiasi, Meng Xianli
State Key Laboratory of Southwestern Chinese Medicine Resources, Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2022 Sep 6;13:973587. doi: 10.3389/fphar.2022.973587. eCollection 2022.
Coronavirus disease (COVID-19) has spread worldwide and its effects have been more devastating than any other infectious disease. Importantly, patients with severe COVID-19 show conspicuous increases in cytokines, including interleukin (IL)-6, monocyte chemoattractant protein (MCP)-1, IL-8, tumor necrosis factor (TNF)-α, IL-1, IL-18, and IL-17, with characteristics of the cytokine storm (CS). Although recently studied cytokine inhibitors are considered as potent and targeted approaches, once an immunological complication like CS happens, anti-viral or anti-inflammation based monotherapy alone is not enough. Interestingly, certain isoquinoline alkaloids in Franch. (CCFIAs) exerted a multitude of biological activities such as anti-inflammatory, antioxidant, antibacterial, and immunomodulatory etc, revealing a great potential for calming CS. Therefore, in this timeline review, we report and compare the effects of CCFIAs to attenuate the exacerbation of inflammatory responses by modulating signaling pathways like NF-ĸB, mitogen-activated protein kinase, JAK/STAT, and NLRP3. In addition, we also discuss the role of berberine (BBR) in two different triggers of CS, namely sepsis and viral infections, as well as its clinical applications. These evidence provide a rationale for considering CCFIAs as therapeutic agents against inflammatory CS and this suggestion requires further validation with clinical studies.
冠状病毒病（COVID-19）已在全球范围内传播，其影响比任何其他传染病都更具破坏性。重要的是，重症COVID-19患者的细胞因子显著增加，包括白细胞介素（IL）-6、单核细胞趋化蛋白（MCP）-1、IL-8、肿瘤坏死因子（TNF）-α、IL-1、IL-18和IL-17，具有细胞因子风暴（CS）的特征。尽管最近研究的细胞因子抑制剂被认为是有效且有针对性的方法，但一旦发生像CS这样的免疫并发症，仅基于抗病毒或抗炎的单一疗法是不够的。有趣的是，中华青牛胆中的某些异喹啉生物碱（CCFIAs）具有多种生物活性，如抗炎、抗氧化、抗菌和免疫调节等，显示出缓解CS的巨大潜力。因此，在本综述中，我们报告并比较了CCFIAs通过调节NF-κB、丝裂原活化蛋白激酶、JAK/STAT和NLRP3等信号通路来减轻炎症反应加剧的作用。此外，我们还讨论了黄连素（BBR）在CS的两种不同触发因素即脓毒症和病毒感染中的作用及其临床应用。这些证据为将CCFIAs视为针对炎症性CS的治疗药物提供了理论依据，这一建议需要通过临床研究进一步验证。
