Bisabolane-type sesquiterpenoids from Curcuma longa L. exert anti-influenza and anti-inflammatory activities through NF-κB/MAPK and RIG-1/STAT1/2 signaling pathways
Bisabolane-type sesquiterpenoids from Curcuma longa L. exert anti-influenza and anti-inflammatory activities through NF-κB/MAPK and RIG-1/STAT1/2 signaling pathways
复制标题
姜黄中的红没药烷型倍半萜类化合物通过 NF-κB/MAPK 和 RIG-1/STAT1/2 信号通路发挥抗流感和抗炎活性。
DOI：
10.1039/d1fo01212f
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发表时间：
2021-06-28
期刊：
影响因子：
6.1
通讯作者：
Shaw, Pangchui
中科院分区：
文献类型：
--
作者：
Ti, Huihui;Mai, Zhitong;Shaw, Pangchui
流感是一种病毒性呼吸道疾病，可引起季节性流行病和偶尔的大流行。疾病的严重程度可能是由流感病毒诱导的细胞因子失调所致。本研究对姜黄中红没药烷型倍半萜类化合物的分离与鉴定进行了研究，它们对H1N1的抗病毒和抗炎活性以及它们在体外调节宿主免疫应答中的潜在作用。从姜黄（Curcumalonga L.）中分离并鉴定了一对新的红没药烷型倍半萜化合物（6S，7S）-3-羟基-3-羟甲基红没药-1，10-二烯-9-酮（18）和17个已知类似物（1-17）。化合物2、11和14可显著抑制A/PR/8/34（H1N1）在MDCK细胞中的复制，化合物2可显著抑制A/PR/8/34（H1N1）在A549细胞中的复制。化合物4、8、9、13和17可以在mRNA和蛋白质水平上显着减少A549细胞中促炎细胞因子（TNF-α、IL-6、IL-8和IP-10）的产生。通过蛋白质组学分析，化合物4调节内质网中类固醇生物合成、氧化磷酸化和蛋白质加工的水平，从而抑制免疫应答。此外，化合物4可抑制信号通路中p-NF-κ B p65、NF-κ B p65、I κ B α、p-p38 MAPK、p-I κ B α、RIG-1、STAT-1/2和p-STAT-1/2的表达。这些结果表明，红没药烷型倍半萜类化合物的C。在体外实验中，龙眼肉可抑制病毒诱导的炎性细胞因子的表达，调节NF-κ B/MAPK和RIG-1/STAT-1/2信号通路的活性。
Influenza is a viral respiratory illness that causes seasonal epidemics and occasional pandemics. Disease severity may be contributed by influenza virus-induced cytokine dysregulation. The study was designed to investigate the isolation and identification of bisabolane-type sesquiterpenoids from Curcuma longa L., their antiviral and anti-inflammatory activities against H1N1 and their potential role in regulating host immune response in vitro. A pair of new bisabolane-type sesquiterpenoids, (6S,7S)-3-hydroxy-3-hydroxymethylbisabola-1,10-diene-9-one (18) together with seventeen known analogs (1-17), was isolated and elucidated from Curcuma longa L. Compounds 2, 11 and 14 could significantly inhibit A/PR/8/34 (H1N1) replication in MDCK cells, and compound 2 could significantly inhibit A/PR/8/34 (H1N1) replication in A549 cells. Compounds 4, 8, 9, 13 and 17 could markedly reduce pro-inflammatory cytokine (TNF-alpha, IL-6, IL-8 and IP-10) production at the mRNA and protein levels in A549 cells. Compound 4 regulated the levels of steroid biosynthesis, oxidative phosphorylation and protein processing in the endoplasmic reticulum, thereby inhibiting immune responses by proteomics analysis. Furthermore, compound 4 could inhibit the expression of p-NF-kappa B p65, NF-kappa B p65, I kappa B alpha, p-p38 MAPK, p-I kappa B alpha, RIG-1, STAT-1/2 and p-STAT-1/2 in the signaling pathways. These findings indicate that bisabolane-type sesquiterpenoids of C. longa could inhibit the expression of inflammatory cytokines induced by the virus and regulate the activity of NF-kappa B/MAPK and RIG-1/STAT-1/2 signaling pathways in vitro.