Cistanche deserticola polysaccharides (CDP)

Cistanche deserticola Ma polysaccharide (CDP) is an active ingredient extracted from Cistanche deserticola Ma (CD) and is believed to have hepatoprotective activity. However, the molecular mechanism of its hepatoprotective effect by intervening in alcoholic fatty liver disease (AFLD) remains unclear. In the present study, three polysaccharides were isolated and purified from CD, and the polysaccharide with the better lipid-lowering and liver-protecting activity and the highest yield, CDPS, was selected by in vitro experiments for subsequent. The efficacy of CDPS in ameliorating AFLD in mice was evaluated using hepatic lipidomics, 16S rRNA analysis and molecular biology experiments. The present study showed that CDPS significantly improved alcohol-induced weight loss, lipid accumulation, ALT, AST, inflammation and dyslipidemia, suggesting that CDPS can prevent AFLD. Lipidomics showed that CDPS improved lipid metabolism disorders by regulating glycerophospholipid metabolism, linoleic acid metabolism, and arachidonic acid metabolism. 16S rRNA analysis showed that CDPS ameliorated alcohol-induced gut microbiota disruption. In particular, CDPS supplementation reduced the abundance of Bacteroides, Parabacteroides, and Escherichia-Shigella and increased the abundance of Ruminococcaceae_UCG-010, Lachnospiraceae_NK4A136_group and Faecalibaculum abundance, and promoted the production of SCFAs. We further used Western blotting to determine the levels of proteins involved in lipogenesis and catabolism, and CDPS intervention resulted in decreased levels of lipid synthesis-associated proteins (SREBP-1c and FAS) and increased levels of lipid catabolism-associated proteins (PPARα) and p-AMPK/AMPK ratio. Our results suggest that CDPS has the potential to prevent AFLD by modulating lipid metabolism, altering the gut microbiota, increasing the content of SCFAs, activating the AMPK signaling pathway to promote fatty acid β-oxidation and limiting fatty acid biosynthesis, which provides a basis for further development of therapeutic drugs for AFLD.

Spinal cord injury (SCI) is a severe trauma in the central nervous system (CNS) that not only affects human health but also imposes a significant burden on families. Several herbal extracts have been ascertained to regulate SCI progression. Cistanche deserticola polysaccharide (CDP), extracted from C. deserticola, exhibits beneficial effects in a variety of diseases. However, the regulatory roles and associated pathways of CDP in the SCI progression remains unclear.

The SCI animal model was successfully established. The Basso-Beattie-Bresnahan scores were determined through locomotion recovery assessment. Histopathological changes in spinal cord tissues were confirmed through hematoxylin eosin staining, while the number of Nissl bodies in ventral horn of spinal cord was verified through Nissl staining. The levels of malondialdehyde, superoxide dismutase, glutathione peroxidase, and catalase were quantified using commercial assay kits. The expression of ionized calcium-binding adapter molecule 1 (Iba-1) or nuclear factor erythroid 2-related factor 2 (Nrf2) was evaluated through immunofluorescence assay, and the protein expressions were inspected through western blot analysis.

CDP treatment significantly improved the histopathological damage of spinal cord tissues following SCI. Additionally, CDP alleviated oxidative stress in spinal cord tissue. It also alleviated microglia activation by reducing Iba-1 expression. Mechanistically, CDP triggered the Nrf2 signaling pathway, which in turn suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, as proved through rescue assays.

CDP alleviates SCI in mice by inhibiting NLRP3 inflammasome activation via the Nrf2 pathway. This finding suggested that CDP may serve as a promising drug for ameliorating SCI.