Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis

doi:10.1021/acs.jmedchem.3c01759

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	Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis
	Guo,Kai; Zhou,Ting-Ting; Luo,Shi-Hong; Liu,Yan-Chun; Liu,Yan; Li,Sheng-Hong
	2023
Source Publication	JOURNAL OF MEDICINAL CHEMISTRY
ISSN	1520-4804
Volume	67 Issue:1 Pages:513-528
Abstract	Intragastric administration of the total sesterterpenoid extract (TSE) of medicinal plant Leucosceptrum canum at 2.5 g/kg dose protected mice from LPS-induced sepsis. Phytochemical investigation led to the isolation and identification of 47 leucosceptrane sesterterpenoids (1-47) including 30 new compounds (1-30) with complicated oxygenation patterns. Biological screening indicated their immunosuppressive activity via inhibiting IFN-gamma secretion and/or proliferation of T cells with different potencies. Mechanism study of compounds 9, 25, and 32 revealed that they inhibited the activations of AKT-mTOR, JNK, p38 MAPK or ERK pathway in T cells and macrophages. In addition, compounds 9 and 25 induced G0/G1 cell arrest of T cells. The major component, leucosceptroid N (32), significantly lowered the levels of IL-6 and TNF-alpha in peripheral blood serum, and ameliorated the multiorgan damages of LPS-induced sepsis mice at 25 mg/kg dose. These findings suggest that leucosceptrane sesterterpenoids are a new type of potential immunosuppressive agents for sepsis treatment.
Keyword	GLANDULAR TRICHOMES PRODUCTS HARBOR CANUM
Subject Area	193
DOI	10.1021/acs.jmedchem.3c01759
Indexed By	SCI
WOS ID	WOS:001141744000001
Citation statistics	Cited Times:8[WOS] [WOS Record] [Related Records in WOS]
Document Type	期刊论文
Identifier	http://ir.kib.ac.cn/handle/151853/75295
Collection	中国科学院昆明植物研究所
Recommended Citation GB/T 7714	Guo,Kai,Zhou,Ting-Ting,Luo,Shi-Hong,et al. Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis[J]. JOURNAL OF MEDICINAL CHEMISTRY,2023,67(1):513-528.
APA	Guo,Kai,Zhou,Ting-Ting,Luo,Shi-Hong,Liu,Yan-Chun,Liu,Yan,&Li,Sheng-Hong.(2023).Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis.JOURNAL OF MEDICINAL CHEMISTRY,67(1),513-528.
MLA	Guo,Kai,et al."Leucosceptrane Sesterterpenoids as a New Type of Natural Immunosuppressive Agents in Treating Sepsis".JOURNAL OF MEDICINAL CHEMISTRY 67.1(2023):513-528.

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