Streptomyces antiinflammaticus from Rehmannia glutinosa Produces Dual Immunomodulatory Metabolites That Upregulate IL-10 and Inhibit GSK3β/NF-κB
- 1School of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China
- 2College of Plant Protection, Henan Agricultural University, Zhengzhou 450046, China
Abstract
Strain RerS4 was isolated from the rhizosphere of the medicinal plant Rehmannia glutinosa and comprehensively identified for its taxonomic status and anti-inflammatory secondary metabolites. Polyphasic taxonomy combined with genome-based analyses, including average nucleotide identity (82.87–85.87%) and digital DNA-DNA hybridization (26.7–31.9%), confirmed that RerS4 represents a novel Streptomyces species, designated Streptomyces antiinflammaticus. Eight fermentation media were screened using an IL-6/TNF-α inhibitory bioassay in A549 and THP-1 cells, and GYM I medium with optimal anti-inflammatory activity was adopted for large-scale fermentation. Five secondary metabolites were purified from the fermentation broth, including one undescribed amide (1), alongside four known compounds (2–5). Bioactivity assays indicated that compounds 1 and 5 inhibited pro-inflammatory cytokine production. Mechanistically, both compounds suppressed the phosphorylation of p65 (Ser536) and GSK3β (Tyr216) in A549 cells. In THP-1 macrophages, compound 1 selectively targeted p65, while compound 5 inhibited both proteins. qPCR results revealed that compound 1 downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and upregulated the anti-inflammatory cytokine IL-10, whereas compound 5 reduced IFN-γ mRNA expression in A549 cells. This study demonstrates that Streptomyces antiinflammaticus is a valuable resource for distinctive anti-inflammatory and immunomodulatory natural products.
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BibTeX
@article{wang2026streptomyces,
title = {{Streptomyces antiinflammaticus from Rehmannia glutinosa Produces Dual Immunomodulatory Metabolites That Upregulate IL-10 and Inhibit GSK3β/NF-κB}},
author = {Tong Wang and Yu Liang and Feiyan Yang and Yueqing Du and Jiaqi Li and Pengqiang Du and Yanqin Qin and Hairong He},
journal = {Molecules},
year = {2026},
month = oct,
doi = {10.3390/molecules31213869},
url = {https://www.mdpi.com/1420-3049/31/21/3869},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Streptomyces antiinflammaticus from Rehmannia glutinosa Produces Dual Immunomodulatory Metabolites That Upregulate IL-10 and Inhibit GSK3β/NF-κB
AU - Tong Wang
AU - Yu Liang
AU - Feiyan Yang
AU - Yueqing Du
AU - Jiaqi Li
AU - Pengqiang Du
AU - Yanqin Qin
AU - Hairong He
PY - 2026
DA - 2026/10/27
JO - Molecules
DO - 10.3390/molecules31213869
UR - https://www.mdpi.com/1420-3049/31/21/3869
AB - Strain RerS4 was isolated from the rhizosphere of the medicinal plant Rehmannia glutinosa and comprehensively identified for its taxonomic status and anti-inflammatory secondary metabolites. Polyphasic taxonomy combined with genome-based analyses, including average nucleotide identity (82.87–85.87%) and digital DNA-DNA hybridization (26.7–31.9%), confirmed that RerS4 represents a novel Streptomyces species, designated Streptomyces antiinflammaticus. Eight fermentation media were screened using an IL-6/TNF-α inhibitory bioassay in A549 and THP-1 cells, and GYM I medium with optimal anti-inflammatory activity was adopted for large-scale fermentation. Five secondary metabolites were purified from the fermentation broth, including one undescribed amide (1), alongside four known compounds (2–5). Bioactivity assays indicated that compounds 1 and 5 inhibited pro-inflammatory cytokine production. Mechanistically, both compounds suppressed the phosphorylation of p65 (Ser536) and GSK3β (Tyr216) in A549 cells. In THP-1 macrophages, compound 1 selectively targeted p65, while compound 5 inhibited both proteins. qPCR results revealed that compound 1 downregulated pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and upregulated the anti-inflammatory cytokine IL-10, whereas compound 5 reduced IFN-γ mRNA expression in A549 cells. This study demonstrates that Streptomyces antiinflammaticus is a valuable resource for distinctive anti-inflammatory and immunomodulatory natural products.
SN - 1420-3049
ER -