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Cited by 28Myasthenia Gravis and ThymomaMitochondrial Function and PathologyMuscle Physiology and Disorders

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Effect of Qiangji Jianli decoction on mitochondrial respiratory chain activity and expression of mitochondrial fusion and fission proteins in myasthenia gravis rats

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Song, Jingwei, Lei, Xiaowen, Jiao, Wei, Song, Yafang, Chen, Weijing, Li, Jinqiu, Chen, Zhiwei·2018·Scientific Reports
DOI 10.1038/s41598-018-26918-zPMC PMC5988663
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Abstract

Myasthenia gravis (MG) is an autoimmune neuromuscular disease characterized by the production of antibodies against acetylcholine receptors (AChRs). Qiangji Jianli (QJJL) decoction is an effective traditional Chinese medicine (TCM) that is used to treat MG. Our study aimed to investigate the effect of QJJL decoction on MG and to clarify the mechanism by which QJJL regulates mitochondrial energy metabolism and mitochondrial fusion and fission (MFF). SPF female Lewis rats were administered Rat 97–116 peptides to induce experimental autoimmune myasthenia gravis (EAMG). The treatment groups received QJJL decoction (7.8 g/kg, 15.6 g/kg and 23.4 g/kg). Mitochondria were extracted from gastrocnemius tissue samples to detect respiratory chain complex enzymatic activity. Quantitative PCR and western blot analysis were performed to detect Mfn1/2, Opa1, Drp1 and Fis1 mRNA and protein expression, respectively, in the mitochondria. Transmission electron microscopy examination was performed to show the improvement of mitochondria and myofibrils after QJJL treatment. The results indicated that QJJL decoction may attenuate MG by promoting the enzymatic activity of respiratory chain complexes to improve energy metabolism. Moreover, QJJL decoction increased Mfn1/2, Opa1, Drp1 and Fis1 mRNA and protein expression to exert its curative effect on MFF. Thus, QJJL decoction may be a promising therapy for MG.

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Figure 1 Evaluation of the EAMG rat model. Before immunization, the weight of the normal group rats remained stable, and the rats exhibited sustained growth. The model group rats grew slowly during the week of the first immunization, and their weights tended to be stable and thus did not increase after the second booster immunization (a). Before QJJL treatment, 8 rats in the model group died due to severe myasthenia gravis (MG) symptoms, and 54 rats remained alive. During the second week after the first immunization, some of the rats in the model group began to display symptoms of MG and were found to have Lennon scores up to 0.5. With the passage of time, the MG symptoms displayed by the rats in the model group gradually worsened. At 1 week after the last immunization, virtually all of the model group rats had a Lennon score of 0.5 or greater. Specifically, 94.44% of the rats had a score of 0.5 or higher, and 75.93% of the rats had a score of 1.0 or higher. The rats in the blank control group had a score of 0 (b). The degree of electrical attenuation was detected by repetitive nerve stimulation (RNS) in both the normal and model groups at one week after the third immunization. The percentage change between the first and fifth action potentials was the attenuation value D, and a percentage change > 10% was considered positive (c,d).
Figure 1 Evaluation of the EAMG rat model. Before immunization, the weight of the normal group rats remained stable, and the rats exhibited sustained growth. The model group rats grew slowly during the week of the first immunization, and their weights tended to be stable and thus did not increase after the second booster immunization (a). Before QJJL treatment, 8 rats in the model group died due to severe myasthenia gravis (MG) symptoms, and 54 rats remained alive. During the second week after the first immunization, some of the rats in the model group began to display symptoms of MG and were found to have Lennon scores up to 0.5. With the passage of time, the MG symptoms displayed by the rats in the model group gradually worsened. At 1 week after the last immunization, virtually all of the model group rats had a Lennon score of 0.5 or greater. Specifically, 94.44% of the rats had a score of 0.5 or higher, and 75.93% of the rats had a score of 1.0 or higher. The rats in the blank control group had a score of 0 (b). The degree of electrical attenuation was detected by repetitive nerve stimulation (RNS) in both the normal and model groups at one week after the third immunization. The percentage change between the first and fifth action potentials was the attenuation value D, and a percentage change > 10% was considered positive (c,d).CC BY · PubMed Central
Figure 2 Transmission electron microscopy examination (TEM). Normal mitochondria and myofibrils in skeletal muscle of normal group (a,f). Transmission electron microscopy examination of the model (b,g), high- (c,h), middle- (d,i), low-dose (e,j) group.
Figure 2 Transmission electron microscopy examination (TEM). Normal mitochondria and myofibrils in skeletal muscle of normal group (a,f). Transmission electron microscopy examination of the model (b,g), high- (c,h), middle- (d,i), low-dose (e,j) group.CC BY · PubMed Central
Figure 3 Skeletal muscle mitochondrial respiratory chain complex enzymatic activity in EAMG rats after 4 weeks of treatment (nmol·min−1·gpro−1, Mean ± SD, n = 8). Compared with normal group, *P < 0.01; compared with model group, ★P < 0.01, ▲P < 0.05.
Figure 3 Skeletal muscle mitochondrial respiratory chain complex enzymatic activity in EAMG rats after 4 weeks of treatment (nmol·min−1·gpro−1, Mean ± SD, n = 8). Compared with normal group, *P < 0.01; compared with model group, ★P < 0.01, ▲P < 0.05.CC BY · PubMed Central
Figure 4 Effect of Qiangji Jianli (QJJL) decoction on Mfn1, Mfn2, Opa1, Drp1 and Fis1 mRNA expression in the skeletal muscle of the EAMG rats in the normal, model, high-dose, middle-dose and low-dose groups. (a) Mfn1, (b) Mfn2, (c) Opa1, (d) Drp1, and (e) Fis1 mRNA expression after 4 weeks of treatment (Mean ± SD). Compared with normal group, *P < 0.05; compared with model group, ▲P < 0.05.
Figure 4 Effect of Qiangji Jianli (QJJL) decoction on Mfn1, Mfn2, Opa1, Drp1 and Fis1 mRNA expression in the skeletal muscle of the EAMG rats in the normal, model, high-dose, middle-dose and low-dose groups. (a) Mfn1, (b) Mfn2, (c) Opa1, (d) Drp1, and (e) Fis1 mRNA expression after 4 weeks of treatment (Mean ± SD). Compared with normal group, *P < 0.05; compared with model group, ▲P < 0.05.CC BY · PubMed Central
Figure 5 Effect of QJJL decoction on skeletal muscle mitochondrial dynamics of the Lewis rats. Representative Western blot images and quantification of (a) Mfn1, (b) Mfn2, (c) Opa1, (d) Drp1 and (e) Fis1 protein levels. (Mean ± SD), GAPDH was used as a loading control. Compared with normal group, *P < 0.01; compared with model group, ▲P <0.01, ※P <0.05.
Figure 5 Effect of QJJL decoction on skeletal muscle mitochondrial dynamics of the Lewis rats. Representative Western blot images and quantification of (a) Mfn1, (b) Mfn2, (c) Opa1, (d) Drp1 and (e) Fis1 protein levels. (Mean ± SD), GAPDH was used as a loading control. Compared with normal group, *P < 0.01; compared with model group, ▲P <0.01, ※P <0.05.CC BY · PubMed Central

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Citations

Cites

Research works printed but not linked: 10

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Metadata

Authors
Song, J., Lei, X., Jiao, W., Song, Y., Chen, W., Li, J., & Chen, Z.
Affiliations
Guangzhou University of Chinese Medicine (CN)
Corresponding author
Song, Yafang
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-06-05
Volume
8
Issue
1
Pages
8623-8623
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-26918-z
PMC
PMC5988663
OpenAlex
W2805869944
Cited by
28
References
36
Citations by year
2026: 2 · 2025: 4 · 2024: 4 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 6 · 2019: 3 · 2018: 1
FWCI
2.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Natural Science Foundation of China (XH20160106, 81473568)
  • Guangzhou University of Chinese Medicine (XH 20160106, 81473568)
  • Guangzhou University
  • Environment Building for Science and Technology Industries
Topics
  • Health Sciences › Medicine › Clinical Neurology › Myasthenia Gravis and Thymoma
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
myasthenia gravis, traditional Chinese medicine, mitochondrial fission and fusion, mitochondrial respiratory chain, mitochondrial bioenergetics, OPA1, Drp1, Fis1, experimental autoimmune myasthenia gravis, gastrocnemius, acetylcholine receptor antibodies
MeSH terms
Animals, Disease Models, Animal, Electron Transport, Energy Metabolism, Mitochondria, Myasthenia Gravis, Plant Extracts, Plants, Medicinal, Rats, Inbred Lew, Gene Expression, Treatment Outcome, Gene Expression Profiling, Mitochondrial Proteins, Real-Time Polymerase Chain Reaction, Mitochondrial Dynamics

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