Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2

Xiao，Lingyun1,2; Yao，Jie1,2; Miao，Yuyang1,2; Ou，Baoru1,2; Wang，Jie1,2; Huang，Yongqi1,2; Zhou，Boping1; Ge，Lanlan1,2; Tian，Jun3; Zeng，Xiaobin1,2,4

2022-09-01

10.1016/j.biopha.2022.113414

BIOMEDICINE & PHARMACOTHERAPY   Impact Factor & Quartile

0753-3322

1950-6007

Targeting macrophage M1 polarization is a promising strategy with fewer detrimental effects in COVID-19 curation. Phenylethanoid glycosides (PhGs) of Cistanche tubulosa are a botanical drug to possess various anti-inflammation-related functions, such as immunomodulating, hepatoprotective or neuroprotective functions, whereas their anti-inflammatory activity is rarely understood. A search into their anti-inflammatory characteristics led to the isolation of 49 PhGs along with 15 new PhGs. Their inhibitory effects against M1 polarization induced by LPS plus IFN-γ were explored in RAW264.7 macrophages. Of these PhGs, tubuloside B (Tub B) exerted substantial NO scavenging effect both in chemical- and cell-based assays, and it inhibited massive production of cytokines and chemokines. Tub B decreased ERK1/2 phosphorylation via direct binding and inhibited the MAPK signaling pathway. Tub B also directly binded to Mob1 protein, thereby increased the stability and level of Mob1 protein by inhibiting ubiquitinated degradation. Mob1 was pivotal for the anti-inflammatory activity of Tub B, and it acted independently of the canonical Hippo-YAP pathway. Moreover, ERK1/2 and Mob1 also had a synergic effect on modulating the inflammatory response. Finally, these effects of Tub B were verified in mice with LPS-induced systemic inflammatory response syndrome. Taken together, these results indicated that Tub B acted as a promising agent against M1 macrophage activation by synergistically targeting ERK1/2 and Mob1, and that it may potentially be a drug candidate to prevent/treat inflammatory diseases, especially in COVID-19.

Cistanche tubulosa ERK1/2 Inflammation Macrophage M1 polarization Mob1 Phenylethanoid glycosides

SCI

English

First ; Corresponding

Natural Science Foundation of Guangdong Province[2017A030313659];China Postdoctoral Science Foundation[2019M653300];Natural Science Foundation of Guangdong Province[2021A1515110841];National Natural Science Foundation of China[81503221];National Natural Science Foundation of China[81903760];National Natural Science Foundation of China[81903914];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20160427183814675];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20170307095556333];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20170307100726777];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20170413093108233];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20190806151816859];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20190806153401647];Science and Technology Planning Project of Shenzhen Municipality[JCYJ20210324113003007];

Research & Experimental Medicine ; Pharmacology & Pharmacy

Medicine, Research & Experimental ; Pharmacology & Pharmacy

WOS:000918968700003

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

2-s2.0-85134594708

Scopus

1.Center Lab of Longhua Branch and Department of Infectious Disease,Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,Southern University of Science and Technology),Shenzhen,Guangdong,518020,China
2.Department of Pathology (Longhua Branch),Shenzhen People's Hospital (The Second Clinical Medical College,Jinan University,Southern University of Science and Technology),Shenzhen,Guangdong,518020,China
3.College of Life Science,Jiangsu Normal University,Xuzhou,Jiangsu Province,221116,China
4.Guangdong Provincial Key Laboratory of Regional Immunity and Diseases,Medicine School of Shenzhen University,Shenzhen,Guangdong Province,518037,China

Xiao，Lingyun,Yao，Jie,Miao，Yuyang,et al. Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2[J]. BIOMEDICINE & PHARMACOTHERAPY,2022,153.

Xiao，Lingyun.,Yao，Jie.,Miao，Yuyang.,Ou，Baoru.,Wang，Jie.,...&Zeng，Xiaobin.(2022).Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2.BIOMEDICINE & PHARMACOTHERAPY,153.

Xiao，Lingyun,et al."Tubuloside B, isolated from Cistanche tubulosa, a promising agent against M1 macrophage activation via synergistically targeting Mob1 and ERK1/2".BIOMEDICINE & PHARMACOTHERAPY 153(2022).