PMID- 34364580 OWN - NLM STAT- MEDLINE DCOM- 20220105 LR - 20220105 IS - 1879-1344 (Electronic) IS - 0144-8617 (Linking) VI - 271 DP - 2021 Nov 1 TI - Cordyceps polysaccharide marker CCP modulates immune responses via highly selective TLR4/MyD88/p38 axis. PG - 118443 LID - S0144-8617(21)00830-4 [pii] LID - 10.1016/j.carbpol.2021.118443 [doi] AB - Cordyceps, one of the most expensive natural health supplements, is popularly used to modulate immune function. However, little is known regarding the underlying mechanism of its immunomodulatory activity. We newly reported a Cordyceps quality marker CCP (Mw 433.778 kDa) which was characterized as a 1,4-alpha glucan by chemical and spectral analysis and is able to induce significant immune responses of macrophages. Herein, we further investigated the molecular mechanism of CCP's immunomodulatory effects. The results indicate that CCP modulates the TLR4/MyD88/p38 signaling pathway of macrophages, where TLR4 plays a crucial role as verified on TLR4-deficient (TLR4(-/-)) bone marrow-derived macrophages (BMDMs) and TLR4(-/-) mice. These findings provide a precise understanding of the molecular mechanism of Cordyceps' immunomodulatory benefits. CI - Copyright (c) 2021. Published by Elsevier Ltd. FAU - Zhang, Quanwei AU - Zhang Q AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Liu, Man AU - Liu M AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Li, Lifeng AU - Li L AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Chen, Miaomiao AU - Chen M AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Puno, Pema Tenzin AU - Puno PT AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. FAU - Bao, Wanrong AU - Bao W AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Zheng, Hongming AU - Zheng H AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Wen, Xin AU - Wen X AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Cheng, Huiyuan AU - Cheng H AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Fung, Hauyee AU - Fung H AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Wong, Tinlong AU - Wong T AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Zhao, Zhongzhen AU - Zhao Z AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. FAU - Lyu, Aiping AU - Lyu A AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: aipinglu@hkbu.edu.hk. FAU - Han, Quanbin AU - Han Q AD - School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: simonhan@hkbu.edu.hk. FAU - Sun, Handong AU - Sun H AD - State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China. LA - eng PT - Journal Article DEP - 20210716 PL - England TA - Carbohydr Polym JT - Carbohydrate polymers JID - 8307156 RN - 0 (Biomarkers) RN - 0 (Fungal Polysaccharides) RN - 0 (Immunologic Factors) RN - 0 (Interleukin-6) RN - 0 (Myd88 protein, mouse) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Tlr2 protein, mouse) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (interleukin-6, mouse) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Animals MH - Biomarkers MH - Cordyceps/*chemistry MH - Fungal Polysaccharides/*pharmacology MH - Immunity/drug effects MH - Immunologic Factors/*pharmacology MH - Interleukin-6/metabolism MH - Macrophages/drug effects MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Moths MH - Myeloid Differentiation Factor 88/metabolism MH - RAW 264.7 Cells MH - Signal Transduction/*drug effects MH - Toll-Like Receptor 2/deficiency/metabolism MH - Toll-Like Receptor 4/deficiency MH - Tumor Necrosis Factor-alpha/metabolism MH - p38 Mitogen-Activated Protein Kinases/metabolism OTO - NOTNLM OT - Cordyceps OT - Immune responses OT - Macrophage OT - Polysaccharide OT - TLR4/MyD88/p38 EDAT- 2021/08/09 06:00 MHDA- 2022/01/06 06:00 CRDT- 2021/08/08 20:24 PHST- 2021/06/03 00:00 [received] PHST- 2021/06/28 00:00 [revised] PHST- 2021/07/12 00:00 [accepted] PHST- 2021/08/08 20:24 [entrez] PHST- 2021/08/09 06:00 [pubmed] PHST- 2022/01/06 06:00 [medline] AID - S0144-8617(21)00830-4 [pii] AID - 10.1016/j.carbpol.2021.118443 [doi] PST - ppublish SO - Carbohydr Polym. 2021 Nov 1;271:118443. doi: 10.1016/j.carbpol.2021.118443. Epub 2021 Jul 16.