A novel polysaccharide from Dendrobium devonianum serves as a TLR4 agonist for activating macrophages

Dendrobium devonianum has been used as herbal medicines and nutraceutical products since ancient time in China. However, its chemical composition and pharmacological mechanisms are not fully known. In present studies, by chemical purification and characteristic identification, we discovered a novel polysaccharide from D. devonianum, which was designated as DvP-1 with molecular weights of 9.52 x 10(4) Da. DvP-1 is a homogeneous heteropolysaccharide consisting of D-mannose and o-glucose in the molar ration of 10.11: 1. The main glycosidic linkages were beta-1,4-Manp, which were substituted with acetyl groups at the O-2, O-3 and/or O-6 positions. DvP-1 was found to directly stimulate the activation of macrophages in vitro, as evidenced by inducing morphologic change, thereby promoting the production of cytokines TNF-alpha, IL-6 and NO, and enhancing the pinocytic activity of macrophages. By establishing a zebrafish model, we also found that DvP-1 could alleviate vinorelbine-induced decrease of macrophages in vivo. Further findings indicated that DvP-1 activated macrophages through several toll-like receptors (TLRs), but mainly through TLR4. DvP-1 served as a TLR4 agonist and induced ERK, JNK, p38, and I kappa B-alpha phosphorylation, suggesting the activation of MAPK and NE kappa B signaling pathways downstream of TLR4. These findings could help us further understand the immunomodulating effects of D. devonianum in Chinese medicines or health foods for immunocompromised persons. They also show the medicinal value of DvP-1 for the treatment of cancer and infectious diseases caused by TLR4 dysfunction. (C) 2019 Elsevier B.V. All tights reserved.