NF-κB and AMPK-Nrf2 pathways support the protective effect of polysaccharides from Polygonatum cyrtonema Hua in lipopolysaccharide-induced acute lung injury

Abstract

Ethnopharmacological relevance: The raw and honey-processed P. cyrtonema recorded in ancient classics of Chinese medicine as having the effect of moisturizing the lungs and relieving coughs, and it has also been proved to have therapeutic effects on lung diseases in modern research. Polysaccharides are the main components with biological activities in raw and honey-processed P. cyrtonema, but there is no research for their lung-protective effect.

Aim of study: This study aimed to investigate the protective effect and the possible mechanism of polysaccharides from raw and honey-processed P. cyrtonema in LPS-induced acute lung injury in mice.

Materials and methods: Polysaccharides, PCP and HPCP, were respectively separated and extracted from raw and honey-processed P. cyrtonema, and the molecular weight, monosaccharide composition and other basic chemical characteristics were analyzed by HPGCP, HPLC, FI-IR, and NMR. The model of ALI mice was established by intratracheal instillation of LPS. Moreover, the protective effects of PCP and HPCP for ALI mice were evaluated by detecting the wet-to-dry ratio and histopathology in the lungs, the content of inflammatory factors TNF-α, IL-6, IL-1β in BLAF, and the content of MPO and SOD in lung tissue. In addition, the lung-protective mechanism of PCP and HPCP was explored by detecting the levels of some proteins and mRNA related to inflammation and oxidative stress pathways.

Results: PCP and HPCP with molecular weights of 8.842 × 10³ and 5.521 × 10³Da were mainly composed of three monosaccharides. Moreover, it is found that fructose and galactose were mainly β-D, and glucose was α-D. Both PCP and HPCP could significantly improve lung injury, reduce the level of inflammatory factors in BALF and the level of MPO in lung tissue, and increase the level of SOD. In addition, PCR and WB indicated that PCP and HPCP at least inhibited pulmonary inflammation through the NF-κB pathway, and reduced the occurrence of pulmonary oxidative stress through the AMPK-Nrf2 pathway.

Conclusions: Polysaccharides from raw and honey-processed P. cyrtonema had a protective effect in LPS-induced lung injury in mice. This effect may be related to the antioxidant and anti-inflammatory activities of PCP and HPCP in the lungs through the NF-κB pathway and AMPK-Nrf2 pathway. And HPCP seems to perform more than PCP.

Keywords: AMPK-Nrf2 pathway; Acute lung injury; NF-κB pathway; Polygonatum cyrtonema Hua; Polysaccharides.