A glucose-rich heteropolysaccharide from Marsdenia tenacissima (Roxb.) Wight et Arn. and its zinc-modified complex enhance immunoregulation by regulating TLR4-Myd88-NF-κB pathway.

A previously unreported immunological polysaccharide (MTP70-1) was obtained from Marsdenia tenacissima (Roxb.) Wight et Arn. MTP70-1 (2738 Da) is a heteropolysaccharide that mainly consists of (1 → 5)-linked-L-Araf, t-D-Glcp, (1 → 3,5)-linked-L-Araf, (1 → 4)-linked-D-Galp, (1 → 6)-linked-D-Glcp, and (1 → 3,6)-linked-D-Manp. In vitro cell assays revealed that MTP70-1 exhibits moderate immunomodulatory effects at the cellular level, and MTP70-1 was further modified with zinc to improve these effects. These modifications enhanced the immunomodulatory effects of MTP70-1, as phagocytosis was enhanced, the secretion of cytokines (TNF-α, IL-6, IL-1β, and IL-18) was increased, and the generation of chemokines (NO and ROS) in macrophages was enhanced. The intracellular mechanism by which MTP70-1 and MTP70-Zn activate macrophages was further revealed to be closely related to the TLR4-Myd88-NF-κB signaling pathway. In addition, a microscale thermophoresis binding (MST) assay confirmed that Zn modification can effectively enhance the binding affinity of MTP70-1 for TLR4. Ultimately, better immune-enhancing activity was attained with MTP70-Zn than MTP70-1. The immune-enhancing activity of MTP70-Zn was further demonstrated through zebrafish assays, which revealed that MTP70-Zn can effectively enhance the proliferation of macrophages and neutrophils.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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