Veronicastrum sibiricum (L.) Pennell extract alleviates inflammation‑induced muscle atrophy through NLRP3 inflammasome regulation and mitochondrial function restoration.

Inflammation‑induced sarcopenia pathophysiology is associated with the NLR family pyrin domain containing 3 (NLRP3) inflammasome, and the concomitant mitochondrial dysfunction is a notable symptom that requires control. The Veronicastrum genus has anti‑inflammatory and antioxidant effects; however, to the best of our knowledge, the specific mechanism associated with the seed activities and the effects on muscle have not been elucidated. Therefore, the present study aimed to evaluate how Veronicastrum sibiricum (L.) Pennell seed extract (VSE) can improve muscle strength under conditions of inflammation‑induced muscle atrophy. The sepsis‑induced sarcopenia model was used to elucidate the muscle atrophy‑attenuating effects of VSE in vitro and in vivo. The mechanism of action of VSE was revealed in vitro by assessing the expression of associated factors at the mRNA and protein levels. Mice were administered lipopolysaccharide (LPS) intraperitoneally in vivo to mimic the disease state of sepsis. H&E staining was carried out to examine the cross‑section of muscle tissues. ELISAs were carried out to investigate cytokine expression in mouse serum. Significant muscle atrophy was observed under the LPS‑induced inflammatory state, whereas VSE decreased the expression levels of the muscle atrophy markers muscle‑specific RING finger protein 1 and muscle atrophy F‑box protein. Furthermore, VSE reduced the expression levels of factors involved in the NLRP3 inflammasome, such as NLRP3, GSDMD, cleaved‑GSDMD, caspase‑1 and cleaved‑caspase‑1. Additionally, the present study revealed that VSE improved mitochondrial function.