Astragaloside IV protects against autoimmune myasthenia gravis in rats via regulation of mitophagy and apoptosis

Zhang,Jingjing; Huang,Jiayan; Lan,Jinlian; Li,Qing; Ke,Lingling; Jiang,Qilong; Li,Yanwu; Zhang,Han; Zhong,Huiya; Yang,Peidan; Chen,Tongkai; Song,Yafang

doi:10.3892/mmr.2024.13253

Astragaloside IV protects against autoimmune myasthenia gravis in rats via regulation of mitophagy and apoptosis

Authors:
- Jingjing Zhang
- Jiayan Huang
- Jinlian Lan
- Qing Li
- Lingling Ke
- Qilong Jiang
- Yanwu Li
- Han Zhang
- Huiya Zhong
- Peidan Yang
- Tongkai Chen
- Yafang Song
View Affiliations

Affiliations: Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, Department of Gastrosplenic Diseases, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China, School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, P.R. China
Published online on: May 24, 2024 https://doi.org/10.3892/mmr.2024.13253
Article Number: 129
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Astragaloside IV (AS‑IV) has various pharmacological effects, including antioxidant and immunoregulatory properties, which can improve myasthenia gravis (MG) symptoms. However, the potential mechanism underlying the effects of AS‑IV on MG remains to be elucidated. The present study aimed to investigate whether AS‑IV has a therapeutic effect on MG and its potential mechanism of action. By subcutaneously immunizing rats with R97‑116 peptide, an experimental autoimmune (EA) MG rat model was established. AS‑IV (40 or 80 mg/kg/day) treatment was then applied for 28 days after modeling. The results demonstrated that AS‑IV significantly ameliorated the weight loss, Lennon score and pathological changes in the gastrocnemius muscle of EAMG rats compared with the model group. Additionally, the levels of acetylcholine receptor antibody (AChR‑Ab) were significantly decreased, whereas mitochondrial function [ATPase and cytochrome c (Cyt‑C) oxidase activities] and ultrastructure were improved in the AS‑IV treated rats. Moreover, the mRNA and protein expression levels of phosphatase and tensin homolog‑induced putative kinase 1, Parkin, LC3II and Bcl‑2, key signaling molecules for mitophagy and apoptosis, were upregulated, whereas the mRNA and protein expression levels of p62, Cyt‑C, Bax, caspase 3 and caspase 9 were downregulated following AS‑IV intervention. In conclusion, AS‑IV may protect against EAMG in a rat model by modulating mitophagy and apoptosis. These findings indicated the potential mechanism underlying the effects of AS‑IV on MG and provided novel insights into treatment strategies for MG.

View Figures

View References

1	Payet CA, You A, Fayet OM, Dragin N, Berrih-Aknin S and Le Panse R: Myasthenia gravis: An acquired interferonopathy? Cells. 11:12182022. View Article : Google Scholar : PubMed/NCBI
2	Gilhus NE, Tzartos S, Evoli A, Palace J, Burns TM and Verschuuren J: Myasthenia gravis. Nat Rev Dis Primers. 5:302019. View Article : Google Scholar : PubMed/NCBI
3	Huijbers MG, Marx A, Plomp JJ, Le Panse R and Phillips WD: Advances in the understanding of disease mechanisms of autoimmune neuromuscular junction disorders. Lancet Neurol. 21:163–175. 2022. View Article : Google Scholar : PubMed/NCBI
4	Cortés-Vicente E, Álvarez-Velasco R, Segovia S, Paradas C, Casasnovas C, Guerrero-Sola A, Pardo J, Ramos-Fransi A, Sevilla T, López de Munain A, et al: Clinical and therapeutic features of myasthenia gravis in adults based on age at onset. Neurology. 94:e1171–e1180. 2020. View Article : Google Scholar : PubMed/NCBI
5	Gilhus NE and Verschuuren JJ: Myasthenia gravis: Subgroup classification and therapeutic strategies. Lancet Neurol. 14:1023–1036. 2015. View Article : Google Scholar : PubMed/NCBI
6	Punga AR, Maddison P, Heckmann JM, Guptill JT and Evoli A: Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders. Lancet Neurol. 21:176–188. 2022. View Article : Google Scholar : PubMed/NCBI
7	García Estévez DA and Pardo Fernández J: Myasthenia gravis. Update on diagnosis and therapy. Med Clin (Barc). 161:119–127. 2023. View Article : Google Scholar : PubMed/NCBI
8	Mahic M, Bozorg A, DeCourcy J, Golden K, Gibson G, Taylor C and Scowcroft A: Physician- and patient-reported perspectives on myasthenia gravis in Europe: A real-world survey. Orphanet J Rare Dis. 18:1692023. View Article : Google Scholar : PubMed/NCBI
9	Petersson M, Feresiadou A, Jons D, Ilinca A, Lundin F, Johansson R, Budzianowska A, Roos AK, Kågström V, Gunnarsson M, et al: Patient-Reported symptom severity in a nationwide myasthenia gravis cohort: Cross-sectional analysis of the swedish GEMG study. Neurology. 97:e1382–1391. 2021. View Article : Google Scholar : PubMed/NCBI
10	Verschuuren JJ, Palace J, Murai H, Tannemaat MR, Kaminski HJ and Bril V: Advances and ongoing research in the treatment of autoimmune neuromuscular junction disorders. Lancet Neurol. 21:189–202. 2022. View Article : Google Scholar : PubMed/NCBI
11	Walker BR and Moraes CT: Nuclear-mitochondrial interactions. Biomolecules. 12:4272022. View Article : Google Scholar : PubMed/NCBI
12	de Beauchamp L, Himonas E and Helgason GV: Mitochondrial metabolism as a potential therapeutic target in myeloid leukaemia. Leukemia. 36:1–12. 2022. View Article : Google Scholar : PubMed/NCBI
13	Xiang L, Shao Y and Chen Y: Mitochondrial dysfunction and mitochondrion-targeted therapeutics in liver diseases. J Drug Target. 29:1080–1093. 2021. View Article : Google Scholar : PubMed/NCBI
14	Yang X, Xue P, Yuan M, Xu X, Wang C, Li W, Machens HG and Chen Z: SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy. Cell Death Dis. 12:8052021. View Article : Google Scholar : PubMed/NCBI
15	Martignago S, Fanin M, Albertini E, Pegoraro E and Angelini C: Muscle histopathology in myasthenia gravis with antibodies against MuSK and AChR. Neuropathol Appl Neurobiol. 35:103–110. 2009. View Article : Google Scholar : PubMed/NCBI
16	Shichijo K, Mitsui T, Kunishige M, Kuroda Y, Masuda K and Matsumoto T: Involvement of mitochondria in myasthenia gravis complicated with dermatomyositis and rheumatoid arthritis: A case report. Acta Neuropathol. 109:539–542. 2005. View Article : Google Scholar : PubMed/NCBI
17	Sousa-Soares C, Noronha-Matos JB and Correia-de-Sá P: Purinergic tuning of the tripartite neuromuscular synapse. Mol Neurobiol. 60:4084–4104. 2023. View Article : Google Scholar : PubMed/NCBI
18	Ferrari R, Rodrigues-Simioni L and da Cruz Höfling MA: Guanidine affects differentially the twitch response of diaphragm, extensor digitorum longus and soleus nerve-muscle preparations of mice. Molecules. 17:7503–7522. 2012. View Article : Google Scholar : PubMed/NCBI
19	Jiao W, Hu F, Li J, Song J, Liang J, Li L, Song Y, Chen Z, Li Q and Ke L: Qiangji Jianli Decoction promotes mitochondrial biogenesis in skeletal muscle of myasthenia gravis rats via AMPK/PGC-1α signaling pathway. Biomed Pharmacother. 129:1104822020. View Article : Google Scholar : PubMed/NCBI
20	Ke L, Li Q, Song J, Jiao W, Ji A, Chen T, Pan H and Song Y: The mitochondrial biogenesis signaling pathway is a potential therapeutic target for myasthenia gravis via energy metabolism (Review). Exp Ther Med. 22:7022021. View Article : Google Scholar : PubMed/NCBI
21	Li L, Cai D, Zhong H, Liu F, Jiang Q, Liang J, Li P, Song Y, Ji A, Jiao W, et al: Mitochondrial dynamics and biogenesis indicators may serve as potential biomarkers for diagnosis of myasthenia gravis. Exp Ther Med. 23:3072022. View Article : Google Scholar : PubMed/NCBI
22	Song J, Lei X, Jiao W, Song Y, Chen W, Li J and Chen Z: Effect of Qiangji Jianli decoction on mitochondrial respiratory chain activity and expression of mitochondrial fusion and fission proteins in myasthenia gravis rats. Sci Rep. 8:86232018. View Article : Google Scholar : PubMed/NCBI
23	Zheng Z, Guo C, Li M, Yang L, Liu P, Zhang X, Liu Y, Guo X, Cao S, Dong Y, et al: Hypothalamus-habenula potentiation encodes chronic stress experience and drives depression onset. Neuron. 110:1400–1415.e6. 2022. View Article : Google Scholar : PubMed/NCBI
24	Su L, Zhang J, Gomez H, Kellum JA and Peng Z: Mitochondria ROS and mitophagy in acute kidney injury. Autophagy. 19:401–414. 2023. View Article : Google Scholar : PubMed/NCBI
25	Gupta R, Ambasta RK and Pravir K: Autophagy and apoptosis cascade: Which is more prominent in neuronal death? Cell Mol Life Sci. 78:8001–8047. 2021. View Article : Google Scholar : PubMed/NCBI
26	Lai Y, Xu X, Zhu Z and Hua Z: Highly efficient siRNA transfection in macrophages using apoptotic body-mimic Ca-PS lipopolyplex. Int J Nanomedicine. 13:6603–6623. 2018. View Article : Google Scholar : PubMed/NCBI
27	Zhang J, Ma G, Guo Z, Yu Q, Han L, Han M and Zhu Y: Study on the apoptosis mediated by apoptosis-inducing-factor and influencing factors of bovine muscle during postmortem aging. Food Chem. 266:359–367. 2018. View Article : Google Scholar : PubMed/NCBI
28	Piras A, Schiaffino L, Boido M, Valsecchi V, Guglielmotto M, De Amicis E, Puyal J, Garcera A, Tamagno E, Soler RM and Vercelli A: Inhibition of autophagy delays motoneuron degeneration and extends lifespan in a mouse model of spinal muscular atrophy. Cell Death Dis. 8:32232017. View Article : Google Scholar : PubMed/NCBI
29	Kuno A, Hosoda R, Sebori R, Hayashi T, Sakuragi H, Tanabe M and Horio Y: Resveratrol ameliorates mitophagy disturbance and improves cardiac pathophysiology of Dystrophin-deficient mdx Mice. Sci Rep. 8:155552018. View Article : Google Scholar : PubMed/NCBI
30	De Palma C, Morisi F, Cheli S, Pambianco S, Cappello V, Vezzoli M, Rovere-Querini P, Moggio M, Ripolone M, Francolini M, et al: Autophagy as a new therapeutic target in Duchenne muscular dystrophy. Cell Death Dis. 3:e4182012. View Article : Google Scholar : PubMed/NCBI
31	Bloemberg D and Quadrilatero J: Autophagy, apoptosis, and mitochondria: Molecular integration and physiological relevance in skeletal muscle. Am J Physiol Cell Physiol. 317:C111–C130. 2019. View Article : Google Scholar : PubMed/NCBI
32	Jing H, Xie R, Bai Y, Duan Y, Sun C, Wang Y, Cao R, Ling Z and Qu X: The mechanism actions of astragaloside IV prevents the progression of hypertensive heart disease based on network pharmacology and experimental pharmacology. Front Pharmacol. 12:7556532021. View Article : Google Scholar : PubMed/NCBI
33	Song J, Li Q, Ke L, Liang J, Jiao W, Pan H, Li Y, Du Q, Song Y, Ji A, et al: Qiangji jianli decoction alleviates hydrogen peroxide-induced mitochondrial dysfunction via regulating mitochondrial dynamics and biogenesis in L6 myoblasts. Oxid Med Cell Longev. 2021:66606162021. View Article : Google Scholar : PubMed/NCBI
34	Costa IM, Lima FOV, Fernandes LCB, Norrara B, Neta FI, Alves RD, Cavalcanti JRLP, Lucena EES, Cavalcante JS, Rego ACM, et al: Astragaloside IV supplementation promotes A neuroprotective effect in experimental models of neurological disorders: A systematic review. Curr Neuropharmacol. 17:648–665. 2019. View Article : Google Scholar : PubMed/NCBI
35	Zhu T, Wang L, Wang LP and Wan Q: Therapeutic targets of neuroprotection and neurorestoration in ischemic stroke: Applications for natural compounds from medicinal herbs. Biomed Pharmacother. 148:1127192022. View Article : Google Scholar : PubMed/NCBI
36	Zhong Y, Liu W, Xiong Y, Li Y, Wan Q, Zhou W, Zhao H, Xiao Q and Liu D: Astragaloside IV alleviates ulcerative colitis by regulating the balance of Th17/Treg cells. Phytomedicine. 104:1542872022. View Article : Google Scholar : PubMed/NCBI
37	Bolduc JA, Collins JA and Loeser RF: Reactive oxygen species, aging and articular cartilage homeostasis. Free Radic Biol Med. 132:73–82. 2019. View Article : Google Scholar : PubMed/NCBI
38	Jiang B, Yang YJ, Dang WZ, Li H, Feng GZ, Yu XC, Shen XY and Hu XG: Astragaloside IV reverses simvastatin-induced skeletal muscle injury by activating the AMPK-PGC-1α signalling pathway. Phytother Res. 34:1175–1184. 2020. View Article : Google Scholar : PubMed/NCBI
39	National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals, . Guide for the care and use of laboratory animals. 8th edition. Washington (DC): National Academies Press (US); 2011
40	Baggi F, Annoni A, Ubiali F, Longhi R, Milani M, Mantegazza R, Cornelio F and Antozzi C: Immunization with rat-, but not Torpedo-derived 97–116 peptide of the AChR alpha-subunit induces experimental myasthenia gravis in Lewis rat. Ann N Y Acad Sci. 998:391–394. 2003. View Article : Google Scholar : PubMed/NCBI
41	He X, Zhou S, Ji Y, Zhang Y, Lv J, Quan S, Zhang J, Zhao X, Cui W, Li W, et al: Sorting nexin 17 increases low-density lipoprotein receptor-related protein 4 membrane expression: A novel mechanism of acetylcholine receptor aggregation in myasthenia gravis. Front Immunol. 13:9160982022. View Article : Google Scholar : PubMed/NCBI
42	Wang CC, Li H, Zhang M, Li XL, Yue LT, Zhang P, Zhao Y, Wang S, Duan RN, Li YB and Duan RS: Caspase-1 inhibitor ameliorates experimental autoimmune myasthenia gravis by innate dendric cell IL-1-IL-17 pathway. J Neuroinflammation. 12:1182015. View Article : Google Scholar : PubMed/NCBI
43	Claussen GC, Fesenmeier JT, Hah JS, Brooks J and Oh SJ: The accessory nerve repetitive nerve stimulation test: A valuable second-line test in myasthenia gravis. Eur J Neurol. 2:492–497. 1995. View Article : Google Scholar : PubMed/NCBI
44	Nie Q, Zhu L, Zhang L, Leng B and Wang H: Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation. Life Sci. 232:1166622019. View Article : Google Scholar : PubMed/NCBI
45	Liu YL, Zhang QZ, Wang YR, Fu LN, Han JS, Zhang J and Wang BM: Astragaloside IV improves High-Fat Diet-Induced hepatic steatosis in nonalcoholic fatty liver disease rats by regulating inflammatory factors level via TLR4/NF-κB signaling pathway. Front Pharmacol. 11:6050642020. View Article : Google Scholar : PubMed/NCBI
46	Yang J, Wang HX, Zhang YJ, Yang YH, Lu ML, Zhang J, Li ST, Zhang SP and Li G: Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol-induced myocardial hypertrophy. J Ethnopharmacol. 150:1062–1070. 2013. View Article : Google Scholar : PubMed/NCBI
47	Laferriere CA and Pang DS: Review of intraperitoneal injection of sodium pentobarbital as a method of euthanasia in laboratory rodents. J Am Assoc Lab Anim Sci. 59:254–263. 2020. View Article : Google Scholar : PubMed/NCBI
48	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
49	van der Bliek AM, Sedensky MM and Morgan PG: Cell biology of the mitochondrion. Genetics. 207:843–871. 2017. View Article : Google Scholar : PubMed/NCBI
50	Mansilla N, Racca S, Gras DE, Gonzalez DH and Welchen E: The complexity of mitochondrial Complex IV: An update of cytochrome c oxidase biogenesis in plants. Int J Mol Sci. 19:6622018. View Article : Google Scholar : PubMed/NCBI
51	Ni GX, Liang C, Wang J, Duan CQ, Wang P and Wang YL: Astragaloside IV improves neurobehavior and promotes hippocampal neurogenesis in MCAO rats though BDNF-TrkB signaling pathway. Biomed Pharmacother. 130:1103532020. View Article : Google Scholar : PubMed/NCBI
52	Shi YH, Zhang XL, Ying PJ, Wu ZQ, Lin LL, Chen W, Zheng GQ and Zhu WZ: Neuroprotective effect of Astragaloside IV on cerebral Ischemia/Reperfusion injury rats through Sirt1/Mapt pathway. Front Pharmacol. 12:6398982021. View Article : Google Scholar : PubMed/NCBI
53	Yin Y, Qu H, Yang Q, Fang Z and Gao R: Astragaloside IV alleviates Schwann cell injury in diabetic peripheral neuropathy by regulating microRNA-155-mediated autophagy. Phytomedicine. 92:1537492021. View Article : Google Scholar : PubMed/NCBI
54	Kuo YC, Chen IY and Rajesh R: Astragaloside IV- and nesfatin-1-encapsulated phosphatidylserine liposomes conjugated with wheat germ agglutinin and leptin to activate anti-apoptotic pathway and block phosphorylated tau protein expression for Parkinson's disease treatment. Mater Sci Eng C Mater Biol Appl. 129:1123612021. View Article : Google Scholar : PubMed/NCBI
55	Tian Y, Jin S, Promes V, Liu X and Zhang Y: Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro. Naunyn Schmiedebergs Arch Pharmacol. 394:1019–1029. 2021. View Article : Google Scholar : PubMed/NCBI
56	Smith EF, Shaw PJ and De Vos KJ: The role of mitochondria in amyotrophic lateral sclerosis. Neurosci Lett. 710:1329332019. View Article : Google Scholar : PubMed/NCBI
57	Attia M, Maurer M, Robinet M, Le Grand F, Fadel E, Le Panse R, Butler-Browne G and Berrih-Aknin S: Muscle satellite cells are functionally impaired in myasthenia gravis: Consequences on muscle regeneration. Acta Neuropathol. 134:869–888. 2017. View Article : Google Scholar : PubMed/NCBI
58	Truffault F, de Montpreville V, Eymard B, Sharshar T, Le Panse R and Berrih-Aknin S: Thymic germinal centers and corticosteroids in myasthenia gravis: An immunopathological study in 1035 cases and a critical review. Clin Rev Allergy Immunol. 52:108–124. 2017. View Article : Google Scholar : PubMed/NCBI
59	Menon D and Bril V: Pharmacotherapy of generalized myasthenia gravis with special emphasis on newer biologicals. Drugs. 82:865–887. 2022. View Article : Google Scholar : PubMed/NCBI
60	Mantegazza R and Antozzi C: When myasthenia gravis is deemed refractory: Clinical signposts and treatment strategies. Ther Adv Neurol Disord. 11:17562856177491342018. View Article : Google Scholar : PubMed/NCBI
61	Lorenzoni PJ, Kay CSK, Zanlorenzi MF, Ducci RD, Werneck LC and Scola RH: Myasthenia gravis and azathioprine treatment: Adverse events related to thiopurine S-methyl-transferase (TPMT) polymorphisms. J Neurol Sci. 412:1167342020. View Article : Google Scholar : PubMed/NCBI
62	Tao X, Wang W, Jing F, Wang Z, Chen Y, Wei D and Huang X: Long-term efficacy and side effects of low-dose tacrolimus for the treatment of Myasthenia Gravis. Neurol Sci. 38:325–330. 2017. View Article : Google Scholar : PubMed/NCBI
63	Stępnik K, Kukula-Koch W, Plazinski W, Gawel K, Gaweł-Bęben K, Khurelbat D and Boguszewska-Czubara A: Significance of astragaloside IV from the roots of astragalus mongholicus as an acetylcholinesterase inhibitor-from the computational and biomimetic analyses to the in vitro and in vivo studies of safety. Int J Mol Sci. 24:91522023. View Article : Google Scholar : PubMed/NCBI
64	Yuan F, Yang Y, Liu L, Zhou P, Zhu Y, Chai Y, Chen K, Tang W, Huang Q and Zhang C: Research progress on the mechanism of astragaloside IV in the treatment of asthma. Heliyon. 9:e221492023. View Article : Google Scholar : PubMed/NCBI
65	Rivner MH, Pasnoor M, Dimachkie MM, Barohn RJ and Mei L: Muscle-Specific tyrosine kinase and myasthenia gravis owing to other antibodies. Neurol Clin. 36:293–310. 2018. View Article : Google Scholar : PubMed/NCBI
66	Howard FM Jr, Lennon VA, Finley J, Matsumoto J and Elveback LR: Clinical correlations of antibodies that bind, block, or modulate human acetylcholine receptors in myasthenia gravis. Ann N Y Acad Sci. 505:526–538. 1987. View Article : Google Scholar : PubMed/NCBI
67	Lindstrom JM, Seybold ME, Lennon VA, Whittingham S and Duane DD: Antibody to acetylcholine receptor in myasthenia gravis. Prevalence, clinical correlates, and diagnostic value. Neurology. 26:1054–1059. 1976. View Article : Google Scholar : PubMed/NCBI
68	Gilhus NE, Skeie GO, Romi F, Lazaridis K, Zisimopoulou P and Tzartos S: Myasthenia gravis-autoantibody characteristics and their implications for therapy. Nature Rev Neurology. 12:259–268. 2016. View Article : Google Scholar : PubMed/NCBI
69	Anagnostou ME and Hepple RT: Mitochondrial mechanisms of neuromuscular junction degeneration with aging. Cells. 9:1972020. View Article : Google Scholar : PubMed/NCBI
70	Xiao Y, Zhang J, Shu X, Bai L, Xu W, Wang A, Chen A, Tu WY, Wang J, Zhang K, et al: Loss of mitochondrial protein CHCHD10 in skeletal muscle causes neuromuscular junction impairment. Hum Mol Genet. 29:1784–1796. 2020. View Article : Google Scholar : PubMed/NCBI
71	Finsterer J, Oberman I and Reitner A: Respiratory chain complex-I defect mimicking myasthenia. Metab Brain Dis. 17:41–46. 2002. View Article : Google Scholar : PubMed/NCBI
72	Jang YC, Lustgarten MS, Liu Y, Muller FL, Bhattacharya A, Liang H, Salmon AB, Brooks SV, Larkin L, Hayworth CR, et al: Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB. 24:1376–1390. 2010. View Article : Google Scholar
73	Holper L, Ben-Shachar D and Mann JJ: Multivariate meta-analyses of mitochondrial complex I and IV in major depressive disorder, bipolar disorder, schizophrenia, Alzheimer disease, and Parkinson disease. Neuropsychopharmacology. 44:837–849. 2019. View Article : Google Scholar : PubMed/NCBI
74	Ferreira N, Andoniou CE, Perks KL, Ermer JA, Rudler DL, Rossetti G, Periyakaruppiah A, Wong JKY, Rackham O, Noakes PG, et al: Murine cytomegalovirus infection exacerbates complex IV deficiency in a model of mitochondrial disease. PLoS Genet. 16:e10086042020. View Article : Google Scholar : PubMed/NCBI
75	Hatakeyama H and Goto YI: Respiratory chain complex disorganization impairs mitochondrial and cellular integrity: Phenotypic variation in cytochrome c oxidase deficiency. Am J Pathol. 187:110–121. 2017. View Article : Google Scholar : PubMed/NCBI
76	Wang XL, Feng ST, Wang ZZ, Chen NH and Zhang Y: Role of mitophagy in mitochondrial quality control: Mechanisms and potential implications for neurodegenerative diseases. Pharmacol Res. 165:1054332021. View Article : Google Scholar : PubMed/NCBI
77	Chu CT: Mechanisms of selective autophagy and mitophagy: Implications for neurodegenerative diseases. Neurobiol Dis. 122:23–34. 2019. View Article : Google Scholar : PubMed/NCBI
78	Evans CS and Holzbaur ELF: Autophagy and mitophagy in ALS. Neurobiol Dis. 122:35–40. 2019. View Article : Google Scholar : PubMed/NCBI
79	Carrascoso I, Sánchez-Jiménez C, Silion E, Alcalde J and Izquierdo JM: A heterologous cell model for studying the role of T-Cell intracellular antigen 1 in welander distal myopathy. Mol Cell Biol. 39:e00299–18. 2019. View Article : Google Scholar : PubMed/NCBI
80	Wang TS, Coppens I, Saorin A, Brady NR and Hamacher-Brady A: Endolysosomal targeting of mitochondria is integral to BAX-Mediated mitochondrial permeabilization during apoptosis signaling. Developmental cell. 53:627–645.e7. 2020. View Article : Google Scholar : PubMed/NCBI
81	Yin W, Li R, Feng X and James Kang Y: The Involvement of cytochrome c Oxidase in mitochondrial fusion in primary cultures of neonatal rat cardiomyocytes. Cardiovasc Toxicol. 18:365–373. 2018. View Article : Google Scholar : PubMed/NCBI
82	Wang XR, Wang C and Wang XW, Qian LX, Chi Y, Liu SS, Liu YQ and Wang XW: The functions of caspase in whitefly Bemisia tabaci apoptosis in response to ultraviolet irradiation. Insect Mol Biol. 27:739–751. 2018. View Article : Google Scholar : PubMed/NCBI
83	Huang G, Li H and Zhang H: Abnormal expression of mitochondrial ribosomal proteins and their encoding genes with cell apoptosis and diseases. Int J Mol Sci. 21:88792020. View Article : Google Scholar : PubMed/NCBI
84	Hazafa A, Batool A, Ahmad S, Amjad M, Chaudhry SN, Asad J, Ghuman HF, Khan HM, Naeem M and Ghani U: Humanin: A mitochondrial-derived peptide in the treatment of apoptosis-related diseases. Life Sci. 264:1186792021. View Article : Google Scholar : PubMed/NCBI
85	Bock FJ and Tait SWG: Mitochondria as multifaceted regulators of cell death. Nat Rev Mol Cell Biol. 21:85–100. 2020. View Article : Google Scholar : PubMed/NCBI
86	Zheng M, Kuang N, Zeng X, Wang J, Zou Y and Fu Y: Daphnetin induces apoptosis in fibroblast-like synoviocytes from collagen-induced arthritic rats mainly via the mitochondrial pathway. Cytokine. 133:1551462020. View Article : Google Scholar : PubMed/NCBI
87	Xia ML, Xie XH, Ding JH, Du RH and Hu G: Astragaloside IV inhibits astrocyte senescence: Implication in Parkinson's disease. J Neuroinflammation. 17:1052020. View Article : Google Scholar : PubMed/NCBI
88	Yin Y, Qu H, Yang Q, Fang Z and Gao R: Corrigendum to ‘Astragaloside IV alleviates Schwann cell injury in diabetic peripheral neuropathy by regulating microRNA-155-mediated autophagy’. Phytomedicine. 97:1539162022. View Article : Google Scholar : PubMed/NCBI
89	Lin J, Pan X, Huang C, Gu M, Chen X, Zheng X, Shao Z, Hu S, Wang B, Lin H, et al: Dual regulation of microglia and neurons by Astragaloside IV-mediated mTORC1 suppression promotes functional recovery after acute spinal cord injury. J Cell Mol Med. 24:671–685. 2020. View Article : Google Scholar : PubMed/NCBI
90	Li H, Xu J, Zhang Y, Hong L, He Z, Zeng Z and Zhang L: Astragaloside IV alleviates senescence of vascular smooth muscle cells through activating Parkin-mediated mitophagy. Hum Cell. 35:1684–1696. 2022. View Article : Google Scholar : PubMed/NCBI
91	Feng M, Lv J, Zhang C, Chen D, Guo H, Tu Y, Su L and Wang Z: Astragaloside IV protects sepsis-induced acute kidney injury by attenuating mitochondrial dysfunction and apoptosis in renal tubular epithelial cells. Curr Pharm Des. 28:2825–2834. 2022. View Article : Google Scholar : PubMed/NCBI
92	Li H, Yao C, Shi K, Zhao Y, Du J, Hu D and Liu Z: Astragaloside IV attenuates hypoxia/reoxygenation injury-induced apoptosis of type II alveolar epithelial cells through miR-21-5p. Bioengineered. 12:7747–7754. 2021. View Article : Google Scholar : PubMed/NCBI
93	Wang F, Zhao Y, Chen S, Chen L, Sun L, Cao M, Li C and Zhou X: Astragaloside IV alleviates ammonia-induced apoptosis and oxidative stress in bovine mammary epithelial cells. Int J Mol Sci. 20:6002019. View Article : Google Scholar : PubMed/NCBI
94	Qin S, Yin J, Huang S, Lin J, Fang Z, Zhou Y and Huang K: Astragaloside IV protects ethanol-induced gastric mucosal injury by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway apoptosis in rats. Front Pharmacol. 10:8942019. View Article : Google Scholar : PubMed/NCBI
95	Yoshii SR and Mizushima N: Monitoring and measuring autophagy. Int J Mol Sci. 18:18652017. View Article : Google Scholar : PubMed/NCBI