Effects of cultured Cordyceps mycelia polysaccharide A on tumor neurosis factor-α induced hepatocyte injury with mitochondrial abnormality

•CPS-A was isolated by 65% alcohol extraction and ion-exchange chromatography.•CPS-A was composed of →2-β-d-manp-(1→, →2, 4)-β-D-manp-1→, and (1→4)-linked α-d-Glcp.•CPS-A protected TNF-α induced mitochondria abnormality via TNFR1/ROS/Mfn2 pathway.•CPS-A could up-regulate Mfn2, PGC-1α, and membrane potential.•CPS-A released TNF-α induced apoptosis and ROS production in L02 cells. Cordyceps sinensis mycelia polysaccharide A (CPS-A), was isolated from cultured Cordyceps mycelia by 65% alcohol extraction and ion-exchange column chromatography. The molecular weight of CPS-A was 1.2×104Da and the backbone was mainly composed of (1→2)-linked β-d-mannopyranose, (1→2,4)-linked β-d-mannopyranose and (1→4)-linked α-d-glucopyranose with terminal β-d-mannopyranose and α-d-glucopyranose residues. CPS-A played a protective role against TNF-α induced mitochondria injury in L02 cells via up-regulation of mitofusin 2, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and membrane potential. CPS-A also played a protective role against TNF-α induced L02 cells apoptosis via up-regulation of Bcl-2 and down-regulation of Bid, Bax, cleaved caspase-3, cleaved caspase-9 and ROS production. Moreover, CPS-A attenuated both the normal expression and overexpression of TNF-α receptor 1 (TNFR1) induced by TNF-α administration. In conclusion, CPS-A was involved in TNF-α induced mitochondria abnormality via TNFR1/ROS/Mfn2 pathway.