Genetic algorithm-back propagation artificial neural network model- and response surface methodology-based optimization of crude Lophatherum gracile Brongn. polysaccharides extraction and their anti-NAFLD effects via regulating liver-adipose tissue crosstalk.

This study aimed to explore the therapeutic effects of crude polysaccharides from Lophatherum gracile Brongn. (LGP) on non-alcoholic fatty liver disease (NAFLD). Optimal extraction conditions for ultrasonic-assisted extraction of LGP using polyethylene glycol 400 (PEG400) were determined through response surface methodology and genetic algorithm-back propagation artificial neural network, achieving a yield of 5.12 %. Structural characterization revealed LGP as a heteropolysaccharide dominated by galactose, arabinose, and glucose, with crystallinity and functional groups analyzed by XRD, SEM, FT-IR, and NMR. In vitro studies showed that LGP treatment significantly reduced lipid accumulation in HepG2 cells. High-fat diet-induced NAFLD mice were also developed, and anti-NAFLD effects of LGP were evaluated through biochemical, histological, western blot, RT-qPCR, and ELISA analyses. The results showed that LGP significantly reduced body weight, improved glucose tolerance, normalized lipid levels, and decreased hepatic lipid deposition. LGP modulated hepatic fatty acid metabolism by regulating p-AMPKα, PPARγ, PGC1-α, ACOX1, and CPT1-α expression, fatty acid synthesis and oxidation in liver and eWAT. LGP also promoted eWAT browning and activated brown adipose tissue. Further assays indicated that LGP might act by activating hepatic PPARα/FGF21 pathway. These results suggested that LGP was a promising therapeutic strategy for NAFLD by regulating liver-adipose tissue interactions.