3-n-Butylphthalide reduces the oxidative damage of muscles in an experimental autoimmune myositis animal model

Abstract

3-n-Butylphthalide (NBP) protects the mitochondria and reduces apoptosis in multiple disease models. However, it remains to be determined whether NBP can protect muscle cells from oxidative stress, lipid peroxidation and apoptosis in myositis. In the present study, a myosin immunization protocol was applied to induce experimental autoimmune myositis (EAM) in guinea pigs. After 4 weeks, a low- or high-dose NBP solution was injected intraperitoneally into the guinea pigs, with saline solution serving as the negative control. After 10 days, the guinea pigs were sacrificed and muscle cells were isolated for analysis. The results revealed that NBP increased the superoxide dismutase and catalase activity, and reduced malondialdehyde activity in the EAM model. Furthermore, NBP enhanced ATPase activity in muscle mitochondrial membranes and muscle fiber membranes, reduced the number of apoptotic cells, and differentially regulated the Bcl-2, Bax and BAD mRNA and protein expression levels in muscle tissues and sera. NBP directly protects muscle mitochondria and muscle cells from oxidative damage. Notably, NBP reduced muscle cell apoptosis. Thus, it is speculated that, as an antioxidant treatment, NBP may benefit individuals with myopathy.

Dl‑butylphthalide inhibits rotenone‑induced oxidative stress in microglia via regulation of the Keap1/Nrf2/HO‑1 signaling pathway

“…NBP also works against H 2 O 2 -induced injury in neural stem cells by activation of the PI3K/Akt pathway ( 22 ). NBP increases the superoxide dismutase and catalase activity and reduces malondialdehyde activity in experimental autoimmune myositis model ( 23 ). Despite the above findings, it is unclear how NBP regulates microglia in vitro and the mechanisms involved remain to be elucidated.…”

Application and prospects of butylphthalide for the treatment of neurologic diseases

“…[74] In addition, in a similar model, studies also found that NBP can act as an anti-oxidant to protect muscle mitochondria and muscle cells from oxidative damage, by enhancing SOD and catalase activity, decreasing MDA activity, and enhancing ATPase activity on the mitochondrial membrane and muscle fiber membrane. [75] Further, in a mouse model of autoimmune myelitis, NBP was found to attenuate the progression of this disease by inhibiting phosphoglycerate mutase family member 5-induced necrosis and inflammation in microglia. [76]…”

Neuroprotective mechanisms of 3‑n‑butylphthalide in neurodegenerative diseases (Review)

“…NBP also protects against H 2 O 2 -induced injury in neural stem cells by activation of the PI3K/Akt and the Mash1 signaling pathways (32). Furthermore, NBP has been reported to increase superoxide dismutase and catalase activity, and reduce malondialdehyde activity in the experimental autoimmune myositis (EAM) model, NBP directly protects muscle mitochondria and muscle cells from oxidative damage (33). However, the protective effect of NBP on mitochondrial function is not only limited to neurodegeneration, but also appears in cardiovascular diseases.…”

“…Another study demonstrated that NBP improves cognitive impairment of APP/PS1 mice by inhibiting apoptosis via the PI3K/AKT pathway (39). Additionally, NBP reduces the number of apoptotic cells by regulating Bcl-2 in HUVECs and an EAM model (22,33).…”