2. Academic Validation
  3. Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4/MD2/NF-κB pathway

Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4/MD2/NF-κB pathway

  • Int J Biol Macromol. 2024 Jul;273(Pt 1):132931. doi: 10.1016/j.ijbiomac.2024.132931.
Mingjie Sun 1,  Liang Yao 2,  Qimeng Yu 3,  Yuting Duan 1,  Jiajing Huang 1,  Tingting Lyu 1,  Nianjun Yu 1,  Daiyin Peng 4,  Weidong Chen 4,  Yanyan Wang 5,  Lei Wang 6,  Yue Zhang 7
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China.
  • 2 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei 230012, Anhui, China.
  • 3 Institute of Drug Development & Chemical Biology, Zhejiang University of Technology, Hangzhou, 310014 Zhejiang, China.
  • 4 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei 230012, Anhui, China; Institute of Conservation and Development of Traditional Chinese Medicine Resources, Hefei 230012, Anhui, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei 230012, Anhui, China.
  • 5 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei 230012, Anhui, China; Institute of Conservation and Development of Traditional Chinese Medicine Resources, Hefei 230012, Anhui, China. Electronic address: wangyanyan@ahtcm.edu.cn.
  • 6 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei 230012, Anhui, China; Anhui Province Key Laboratory of Chinese Medicinal Formula, Hefei 230012, Anhui, China. Electronic address: wanglei@ahtcm.edu.cn.
  • 7 School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China; MOE-Anhui Joint Collaborative Innovation Center for Quality Improvement of Anhui Genuine Chinese Medicinal Materials, Hefei 230012, Anhui, China. Electronic address: 2017201219031@stu.ahtcm.edu.cn.
PMID: 38942665 DOI: 10.1016/j.ijbiomac.2024.132931
Abstract

PCP-W1, the Poria cocos polysaccharide with the strong immunomodulatory activity, was isolated through column chromatography and screened for in vitro immune activity in RAW 264.7 cells in this study. The structure analysis results revealed that the PCP-W1 were composed of galactose, glucose, fucose and mannose in a molar percentage of 35.87: 28.56: 21.77: 13.64. And it exhibited a random coil and branched conformational features with a molecular weight of 18.38 kDa. The main chain consisted of residues→3)-β-D-Glcp-(1 → 3,6)-β-D-Glcp-(1 → 3)-β-D-Glcp-(1 → 6)-β-D-Glcp-(1 → 6)-α-D-Galp-(1 → 6)-α-D-Galp-(1 → 2,6)-α-D-Galp-(1→6)-α-D-Galp-(1 → 6)-α-D-Galp-(1 → , while branching occurred at β-D-Glcp-(1→, α-D-Manp-(1→, and α-L-Fucp-(1 → 3)- α-L-Fucp-(1→. The pharmacodynamic studies demonstrated that PCP-W1 activated the release of NO, IL-6, IL-β, TNF-α, CD86, and ROS to induce polarization of RAW 264.7 murine macrophages towards M1-type through modulation of the TLR4/MD2/NF-κB pathway. The molecular docking results showed that PCP-W1 could primarily DOCK onto the hydrophobic binding site of TLR4/MD2 complex via its galactose chain. Furthermore, molecular dynamics simulation displayed stable modeling for TLR4-MD2-PCP-W1 complex. Overall, we screened the most immunoactive components of the polysaccharide, analyzed its structure, demonstrated its impact on TLR4/MD2/NF-kB pathway, and studied the interaction between TLR4/MD2 and the polysaccharide fragments. These results provide further support for the structure-activity relationship study of the immunomodulatory effects of Poria cocos polysaccharide.

Keywords

Immunological activity; Poria cocos polysaccharide; Structural characterization.

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