Treatment with Qiangji Jianli (QJJL) decoction, a traditional Chinese medicine, improved energy metabolism and the structure of mitochondria in a rat model of myasthenia gravis (MG), researchers in China report, suggesting it might be a promising therapy for the condition.
The study, “Effect of Qiangji Jianli decoction on mitochondrial respiratory chain activity and expression of mitochondrial fusion and fission proteins in myasthenia gravis rats,” appeared in the journal Scientific Reports.
Patients with MG develop autoantibodies against the body’s own acetylcholine receptors (AChRs) at the neuromuscular junction, the site of communication between nerve cells and muscle fibers.
However, antibody concentration (the amount of antibody molecules per volume of blood) does not correlate with disease severity. This lack of correlation, in addition to the severe side effects that patients may experience with immunosuppressive medications (which block the immune system), indicates that the immune system is not the only system involved in MG, the scientists reported.
Research has shown that mitochondria, the cell’s power plants, are involved in MG development. Mitochondria are dynamic structures that continually move, fuse and divide, which determines their shape and enables them to adapt to the cell’s energy needs. These processes are regulated by mitochondrial fusion and fission (MFF)-related proteins, including Mfn1/2, Opa1, Drp1, and Fis1.
Changes in the levels of these MFF proteins result in marked disruption of mitochondrial fusion, fission, and structure, as shown in animal models. Altered levels of MFF proteins also influence mitochondrial energy metabolism and respiration. Abnormal MFF further leads to nerve fiber degeneration and neuromuscular diseases.
QJJL decoction is a traditional Chinese medicine that contains active components that restore mitochondrial function and metabolism, repair DNA damage, inhibit oxidative stress, and provide neuroprotection, among other benefits.
This medicine has been used in clinical trials of MG patients. QJJL capsules have been shown to reduce AChRs antibody levels and improve various types of muscle damage. However, the effects of QJJL decoction at the molecular level remain unexplored.
The scientists tested QJJL decoction in a rat model of MG and examined its effects on enzymes involved in mitochondrial respiration. They also assessed protein and messenger RNA – the molecule generated from DNA – levels of Mfn1/2, Opa1, Drp1 and Fis1 in mitochondria.
Overall, they analyzed whether QJJL decoction helps maintain the balance between mitochondrial fusion and fission to “stabilize mitochondrial morphology [shape] and thus improve mitochondrial energy metabolism to repair muscle cell damage in MG,” the researchers wrote.
Due to their abnormal energy metabolism, rats with MG showed limb weakness, withered hair, and weight loss.
In comparison to control animals, the disease model rats had lower enzymatic activity of mitochondrial complexes involved in energy production. QJJL treatment led to marked improvement of this enzymatic activity, particularly at higher doses. Treatment also improved mitochondrial and muscle cells’ structure.
The decoction also increased protein and mRNA levels of Mfn1/2, Opa1, Drp1 and Fis1 in the rat model of MG. According to the authors, these results demonstrate the close association between MG and MFF.
“QJJL decoction may be a promising therapy for MG,” the scientists wrote. “Future studies directed at determining the exact molecular signaling mechanisms underlying MG development, particularly in vitro studies regarding the factors that control mitochondrial biosynthesis and energy metabolism, are warranted,” they added.