Study on the neuroprotective effect of curculigoside on rats with spinal cord injury / 中国药房

OBJECTIVE To investigate the neuroprotective effect of curculigoside （CUR） on rats with spinal cord injury （SCI） based on phosphatase and tensin homologue deleted on chromosome ten gene-induced putative kinase 1 （PINK1）/E3 ubiquitin ligase Parkin signaling pathway. METHODS Taking male SD rats as subjects， 15 rats were randomly selected as sham operation group； the rest rats were chosen to establish SCI model by spinal cord impact method， and then were divided into model group， CUR low-dose group （36 mg/kg CUR， gavage）， CUR high-dose group （72 mg/kg CUR， gavage） and CUR high-dose+3- methyladenine （3-MA） group （72 mg/kg CUR， gavage+20 mg/kg autophagy inhibitor 3-MA， intraperitoneal injection）， with 15 rats in each group. Rats in each group were given corresponding liquid/normal saline， once a day， for 28 consecutive days. Basso- Beattie-Bresnahan （BBB） score and Rivlin inclined plate experiment were performed on the 14th and 28th day after administration； the pathological changes of spinal cord tissue in rats were observed in each group； the apoptosis of spinal cord tissue， the levels of oxidative stress factors [malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione （GSH）]， and the protein expressions of brain-derived neurotrophic factor （BDNF）， glial fibrillary acidic protein （GFAP）， PINK1， Parkin， p62 and microtubule- associated protein light chain 3 （LC3） were all determined. RESULTS Compared with the sham operation group， obvious edema and bleeding in the spinal cord tissue of rats were observed in the model group， accompanied by a large number of inflammatory cell infiltration； BBB score and inclined plate angle， SOD and GSH levels， the protein expressions of BDNF， PINK1 and Parkin， and LC3Ⅱ/Ⅰ ratio were significantly reduced； the apoptosis rate， MDA level， the protein expressions of GFAP and p62 in spinal cord tissue were significantly increased （P＜0.05）. Compared with the model group， the edema， bleeding and infiltration of inflammatory cells in the spinal cord tissue of rats were reduced in the administration groups， and the above quantitative indicators had been significantly improved （P＜0.05）； 3-MA could significantly reverse the improvement effects of the above indexes by CUR （P＜0.05）. CONCLUSIONS CUR can promote the recovery of neurological and motor functions in SCI rats， improve the pathological injury of the spinal cord and inhibit apoptosis， which may be related to mitochondrial autophagy mediated by activating the PINK1/Parkin signaling pathway.

Mechanism of Xibining Ⅱ Combined with ADSC-Exos in Improving Knee Osteoarthritis by Regulating Mitochondrial Autophagy / 中国实验方剂学杂志

ObjectiveTo observe the effects of Xibining （XBN） and adipose stem cell exosome （ADSC-Exos） in the cases of separate or joint application on cartilage degeneration and mitochondrial autophagy and explore its mechanism of action to improve knee osteoarthritis （KOA）. MethodSD rats were divided into a sham operation group （sham group）， a model group， an ADSC-Exos group （Exos group）， an XBN group， and an ADSC-Exos+XBN group （Exos+XBN group）. KOA model was established by using anterior cruciate ligament transection （ACLT）. The pain sensitivity status of rats was evaluated， and the degeneration degree of the knee joint and cartilage tissue was detected by Micro-CT and pathological staining. The expression of p62 and LC3B was observed by immunofluorescence， and the serum levels of TNF-α， IL-1β， IL-6， and IL-15 in rats were detected by ELISA. The Western blot was used to detect the protein expression levels of MMP-3， MMP-13， ADAMTS5， ColⅡ， TIMP， ACAN， PINK1， Parkin， p62， and LC3A/B. ResultCompared with the sham group， rats in the model group showed decreased cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， varying degrees of abrasion and loss of cartilage tissue， degeneration of cartilage tissue， elevated serum IL-1β， IL-6， IL-15， and TNF-α levels （P<0.01）， and increased protein expression of MMP-3， MMP-13， and ADAMTS5 in cartilage tissue. In addition， the protein expression of ColⅡ， TIMP1， and ACAN was decreased （P<0.01）. Compared with the model group， rats in each treatment group showed higher cold-stimulated foot-shrinkage thresholds and mechanical pain sensitivity thresholds， reduced cartilage tissue degeneration， lower serum levels of IL-1β， IL-6， IL-15， and TNF-α （P<0.05，P<0.01）， decreased protein expression of MMP-3， MMP-13， and ADAMTS5， and higher protein expression of Cold， TIMP1， and ACAN in cartilage tissue （P<0.05，P<0.01）. Moreover， the changes were the most obvious in the Exos+XBN group. ConclusionBoth ADSCs-Exos and XBN can increase the level of mitochondrial autophagy in chondrocytes and delay cartilage tissue degeneration by promoting the expression of the PINK1/Parkin signaling pathway， and the combination of the two can enhance the therapeutic effect.

The mechanism of extract of ginkgo biloba inducing mitochondrial autophagy in breast cancer cells MCF-7 / 国际肿瘤学杂志

Objective:To investigate the mechanism of extract of ginkgo biloba (EGB) on mitochondrial autophagy in breast cancer cells MCF-7.Methods:Breast cancer MCF-7 cells were divided into four groups. EGB with mass concentrations of 40, 80, 120 mg/L was used to incubate breast cancer MCF-7 cells for 24 h or 48 h, as a low concentration group of EGB, a medium concentration group of EGB, and a high concentration group of EGB. Breast cancer MCF-7 cells without intervention were taken as control group. Cell proliferation was measured using MTT assay; Flow cytometry was used to detect cell apoptosis; Immunofluorescence assay was used to determine the contents of prostacyclin (P62), microtubule-associated protein light chain 3Ⅱ (LC3Ⅱ), and caspase-3; The levels of multidrug resistance-associated protein 1 (MRP1), multidrug resistance gene 1 (MDR1) and breast cancer resistance protein (BCRP) were identified by PCR; Western blotting was used to detect the expression of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MAPK), p-ERK, and p-MAPK proteins in cells.Results:The results of MTT assay for cell proliferation showed that cell proliferation at 24 h in control group, EGB low, medium and high concentration groups were 0.95±0.14, 0.65±0.09, 0.51±0.07, 0.37±0.04, respectively, with a statistically significant difference ( F=43.13, P<0.001), cell proliferation at 48 h were 1.32±0.19, 0.54±0.08, 0.32±0.05, 0.15±0.02, respectively, with a statistically significant difference ( F=141.30, P<0.001). Compared with 24 h, cell proliferation was decreased in EGB low, medium and high concentration groups at 48 h (all P<0.05). Pairwise comparison showed that EGB treatment significantly decreased MCF-7 cell viability and cell proliferation was decreased in turn at 24 and 48 h in control group, low, medium, high EGB groups (all P<0.05). Flow cytometry analysis revealed that the apoptosis rates of MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.12%±0.23%, 9.28%±0.45%, 15.17%±1.28% and 22.21%±2.32%, respectively, with a statistically significant difference ( F=128.80, P<0.001). Pairwise comparison showed that the apoptosis rate of control group, EGB low, medium and high concentration groups were increased in turn (all P<0.05). The results of immunofluorescence assay showed that the protein relative expression levels of P62 protein in MCF-7 cells of control group, EGB low, medium and high concentration groups were 3.34±0.52, 2.85±0.47, 2.02±0.18 and 1.08±0.21, respectively, with a statistically significant difference ( F=41.55, P<0.001). LC3Ⅱ protein relative expression levels were 0.24±0.05, 1.02±0.14, 1.47±0.26, 1.95±0.21, respectively, with a statistically significant difference ( F=94.82, P<0.001). The relative expression levels of caspase-3 protein were 0.25±0.03, 0.68±0.21, 1.12±0.17 and 1.65±0.23, respectively, with a statistically significant difference ( F=68.09, P<0.001). Pairwise comparison showed that LC3Ⅱ and caspase-3 protein expression levels were increased in turn in control group, EGB low, medium and high concentration groups, while P62 protein expression levels were decreased in turn (all P<0.05). The PCR experiment results showed that the MRP1 mRNA level of MCF-7 cells in control group, EGB low, medium and high concentration groups were 1.06±0.14, 0.83±0.18, 0.71±0.11, 0.52±0.08, respectively, with a statistically significant difference ( F=17.41, P<0.001). The mRNA levels of MDR1 were 1.14±0.17, 0.75±0.13, 0.60±0.09, 0.48±0.06, respectively, with a statistically significant difference ( F=34.40, P<0.001). BCRP mRNA levels were 1.09±0.11, 0.88±0.13, 0.69±0.07, 0.57±0.05, respectively, with a statistically significant difference ( F=34.13, P<0.001). Pairwise comparison showed that the levels of MRP1, MDR1 and BCRP mRNA were decreased in turn in control group, EGB low, medium and high concentration groups (all P<0.05). The results of Western blotting showed that the expression of ERK in MCF-7 cells in control group, EGB low, medium and high concentration groups were 2.54±0.38, 1.89±0.25, 1.55±0.21, 1.12±0.16, respectively, with a statistically significant difference ( F=31.18, P<0.001). MAPK expression were 2.47±0.34, 1.96±0.29, 1.63±0.27, 1.20±0.24, respectively, with a statistically significant difference ( F=20.90, P<0.001). p-ERK expression were 2.03±0.29, 1.74±0.21, 1.45±0.11, 1.18±0.24, respectively, with a statistically significant difference ( F=16.31, P<0.001). p-MAPK expression were 2.26±0.47, 1.90±0.41, 1.61±0.33, 1.35±0.16, respectively, with a statistically significant difference ( F=7.01, P=0.002). Pairwise comparison showed that the expressions of ERK, MAPK, p-ERK and p-MAPK in control group, EGB low, medium and high concentration groups were decreased in turn (all P<0.05) . Conclusion:EGB can inhibit the proliferation of breast cancer MCF-7 cells, promote the apoptosis of MCF-7 cells, decrease the expression of P62 protein, increase the expression of LC3Ⅱ and caspase-3 protein, induce mitochondrial autophagy.

Protective effect of 10-HDA on acute cadmium chloride-induced kidney damage and autophagy protein expression / 环境与职业医学

Background Acute cadmium (Cd) exposure can cause damage to multiple tissues, with the kidney being the primary target organ. The development of Cd-induced acute kidney injury involves complex mechanisms, in which autophagy and oxidative stress play crucial roles. Objective To investigate the effect of 10-hydroxy-2-decenoic acid (10-HDA) on kidney injury in mice exposed to cadmium, and provide experimental basis for studying the pathogenesis and prevention of Cd poisoning. Methods Thirty-five male C57BL/6 mice were divided into 7 groups (each of 5 mice): control group (normal saline, intraperitoneal injection), CdCl2 group (4 mg·kg−1, intraperitoneal injection), intervention groups ( 4 mg·kg−1 CdCl2, intraperitoneal Injection + 50, 100, 150, or 200 mg·kg−1 10-HDA, oral gavage), and 10-HDA group (150 mg·kg−1, oral gavage). All treatments were given for 14 d. Twenty-four hours after the last infection, physiological indicators [blood urea nitrogen (BUN), creatinine (CRE), malondialdehyde (MDA), and superoxide dismutase (SOD)], histopathological indicators, autophagy-related proteins (Atg7, Atg5, Beclin-1, and LC3), and mitochondrial autophagy-related proteins (PINK1 and Parkin) were detected to examine the effect of 10-HDA on kidney injury caused by CdCl2. Results Compared with the control group, the body weight of mice in the CdCl2 group was significantly reduced (P<0.01); compared with the CdCl2 group, the body weight of mice after intervention with different concentrations of 10-HDA was significantly increased (P<0.01). CdCl2 significantly increased BUN and CRE in the serum samples compared with the control group (P<0.01), which was significantly reduced to varying degrees after 100, 150, and 200 mg·kg−1 10-HDA intervention (P<0.01). MDA significantly increased and SOD significantly decreased in the renal cortex following CdCl2 administration compared with the control group (P<0.01), which was resolved following 10-HDA administration at different concentrations (P<0.01). In histopathological studies, 10-HDA restored injured kidney tissues induced by CdCl2. The expression levels of autophagy proteins Atg7 and LC3-II/I were significantly increased (P<0.05), and the expression level of Beclin-1 was significantly decreased (P<0.05) in the CdCl2 group compared with the control group. The expression levels of Atg7 were reduced to varying degrees after treatment with designed concentrations of 10-HDA, the expression levels of LC3-II/I were also reduced in the 50, 150, and 200 mg·kg−1 10-HDA intervention groups, and the expression levels of Beclin-1 were increased in the 50, 100, and 150 mg·kg−1 10-HDA intervention groups (P<0.05). The expression levels of PINK1 and Parkin in the CdCl2 group and the 50 mg·kg−1 10-HDA intervention group were lower than those in the control group (P<0.01). Compared with the CdCl2 group, the expression levels of PINK1 increased to varying degrees after 100, 150, and 200 mg·kg−1 10-HDA intervention, and the expression levels of Parkin increased in all 10-HDA intervention groups (P<0.01). Conclusion The intervention using 10-HDA can lessen acute kidney injury caused by CdCl2, reduce the expression of autophagy-related proteins, and increase the expression of mitochondrial autophagy-related proteins.

Role and mechanism of umbilical cord mesenchymal stem cells on polycystic ovary syndrome / 中国组织工程研究

BACKGROUND:At present,many drugs used in the treatment of polycystic ovary syndrome are super-designated drugs,and the treatment of patients with polycystic ovary syndrome still faces great challenges.Studies have shown that human umbilical cord mesenchymal stem cells can repair ovarian function,but few studies have reported their therapeutic effect on polycystic ovary syndrome. OBJECTIVE:To investigate the therapeutic effect of human umbilical cord mesenchymal stem cells on polycystic ovary syndrome,and to preliminarily explore the correlation between mitochondrial autophagy and the improvement of polycystic ovary syndrome by human umbilical cord mesenchymal stem cells. METHODS:Polycystic ovary syndrome mouse model was established by subcutaneous injection of dehydroepiandrosterone for 20 days into C57BL/6J mice.Human umbilical cord mesenchymal stem cells(2×106)were injected through the caudal vein.After treatment,vaginal secretions were collected for 10 consecutive days to detect the estrus cycle of mice.At 2 weeks after treatment,the levels of sex hormones in the peripheral blood of mice,including luteinizing hormone and follicle-stimulating hormone,were detected by ELISA.Hematoxylin-eosin staining was used to evaluate ovarian histopathology.Finally,mitochondrial autophagy in ovaries was observed by transmission electron microscopy. RESULTS AND CONCLUSION:(1)After human umbilical cord mesenchymal stem cell therapy,follicles at different stages(primitive follicles,primary follicles,and secondary follicles)appeared in the ovary of polycystic ovary syndrome mice,and luteal tissue could be seen,indicating that ovulation function of mice was effectively improved.(2)Polycystic ovary syndrome mice treated with human umbilical cord mesenchymal stem cells had sex hormone levels.(3)Untreated polycystic ovary syndrome mice were found to be in the estrous stage for a long time,lacking estrous interphase and estrous phase,but after human umbilical cord mesenchymal stem cell therapy,the estrous cycle returned to a normal level.(4)After treatment with human umbilical cord mesenchymal stem cells,the mitochondrial autophagy of polycystic ovary syndrome mice was significantly reduced.(5)The results show that human umbilical cord mesenchymal stem cells can effectively improve the symptoms of endocrine disorders and promote ovulation in polycystic ovary syndrome mice,which may be related to the inhibition of mitochondrial autophagy.

The role of mitochondrial autophagy-related receptor proteins and signaling pathways in the prevention and treatment of sarcopenia through exercise / 中国组织工程研究

BACKGROUND:Sarcopenia is an age-related degenerative syndrome,and the relationship between mitochondrial autophagy and exercise in preventing and treating sarcopenia has been demonstrated.However,there is a lack of comprehensive reviews detailing the specific receptor proteins and signaling pathways involved in the role of exercise in sarcopenia prevention and treatment. OBJECTIVE:To comprehensively introduce the specific receptor proteins and signaling pathways related to mitochondrial autophagy and their role in the prevention and treatment of sarcopenia through exercise. METHODS:A literature search was conducted between February 1,2023,and April 1,2023,covering literature from database inception to April 2023.Databases included the Web of Science,PubMed,China National Knowledge Infrastructure(CNKI),WanFang Data,and VIP.Keywords used for the search included sarcopenia,muscle wasting,aging,elderly,mitochondria,mitochondrial function,proteins,pathways,and others.After strict inclusion and exclusion criteria,76 articles were ultimately included. RESULTS AND CONCLUSION:Sarcopenia is a disease characterized by a decline in muscle mass and function with age,and its pathogenesis involves neuro-muscular functional decline,chronic inflammation,acid-base imbalance,and mitochondrial dysfunction.Mitochondrial autophagy is an important process for clearing damaged mitochondria in cells,in which receptor proteins and signaling pathways are involved in the regulation of mitochondrial autophagy.Exercise can promote the occurrence of mitochondrial autophagy by regulating the activity of these receptor proteins and signaling pathways,thereby playing an important role in the prevention and treatment of sarcopenia.Exercise can induce mitochondrial autophagy in sarcopenia by upregulating AMPK,phosphorylating ULK1,and reducing mitochondrial energy,enhancing the expression of mitochondrial autophagy-related proteins associated with AMBRA1,and regulating the PINK1/Parkin pathway,to improve mitochondrial dysfunction caused by sarcopenia.In addition,exercise can activate the mTOR pathway to promote muscle growth and increase glucose uptake,thereby preventing and treating sarcopenia.Future studies are needed to further investigate the specific mechanisms and regulatory pathways of mitochondrial autophagy-related receptor proteins and signaling pathways in the prevention and treatment of sarcopenia by exercise,and to conduct more clinical trials in humans,thereby to promote further development in this field.

Mitochondrial dysfunction in Parkinson's disease and the potential ameliorative effects of exercise / 中国组织工程研究

BACKGROUND:Parkinson's disease is a neurodegenerative disease,and its pathogenesis involves mitochondrial dysfunction.Exercise has a potential ameliorative effect on mitochondrial dysfunction related to Parkinson's disease,but there is no comprehensive review and in-depth analysis in this field. OBJECTIVE:To comprehensively review and analyze mitochondrial dysfunction related to Parkinson's disease and the potential ameliorative effect of exercise,thereby providing new ideas and methods for the treatment and prevention of Parkinson's disease. METHODS:We searched the Web of Science,PubMed,CNKI,WanFang,and VIP databases with the keywords of"mitochondria,mitochondrial function,mitochondrial disease,mitochondrial dysfunction,Parkinson's disease,Parkinson,exercise,physical activity,exercise training,exercise therapy,mitochondrial impairment,mitochondrial damage,mitochondrial defects"in Chinese and"mitochondria,Parkinson's disease,Parkinson disease,physical exercise,exercise,physical activity,mitochondrial dysfunction,mitochondrial damage,mitochondrial impairment,athletic training,exercise training,rehabilitation"in English.A total of 89 articles were included for review and analysis. RESLUTS AND CONCLUSION:Parkinson's disease is closely related to mitochondrial dysfunction,including mitochondrial biogenesis inhibition,reduced autophagy,increased apoptosis,abnormal elevation of Ca2+ concentration,and increased oxidative stress in Parkinson's disease patients.Exercise has a positive effect on mitochondrial dysfunction related to Parkinson's disease,by promoting mitochondrial biogenesisand autophagy,regulating mitochondrial morphology,altering the plasticity of the mitochondrial respiratory chain,and reducing oxidative stress,thus helping to improve the development and progression of Parkinson's disease.However,the detailed mechanism between mitochondrial dysfunction and the ameliorative effect of exercise is still not fully understood,and future clinical studies can be conducted to validate the results of animal models and gain insights into the benefits and mechanisms of exercise in patients with Parkinson's disease.

Mechanism of Cinnamaldehyde in Promoting Wound Healing in Diabetes Rats via PINK1/Parkin-mediated Mitochondrial Autophagy / 中国实验方剂学杂志

ObjectiveTo establish a rat model of diabetic wound by feeding on a high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin （STZ） and surgical preparation of full-thickness skin defects， observe the effect of cinnamaldehyde on the wound healing of diabetes rats， and explore the therapeutic mechanism of cinnamaldehyde in improving wound healing of diabetes rats based on the PTEN-induced putative kinase （PINK1）/Parkin pathway-mediated mitochondrial autophagy. MethodForty-eight male SD rats were randomly divided into blank group （n=12） and diabetes group （n=36）. The diabetes group was further randomly divided into model group， cinnamaldehyde group， and Beifuxin group， with 12 rats in each group. The blank group and the model group received routine disinfection with physiological saline after creating the wounds， while the cinnamaldehyde group received topical application of polyethylene glycol 400 （PEG 400） gel containing 4 μmol·L-1 cinnamaldehyde， and the Beifuxin group received topical application of Beifuxin gel. Dressings were changed once daily. The wound healing rate of each group was observed. On the 7th and 14th days after intervention， the wound tissues of the rats were collected. Hematoxylin and eosin （HE） staining was performed to observe the pathological changes in the local tissues. Immunohistochemistry （IHC） was used to detect the expression of interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， vascular endothelial growth factor （VEGF）， and collagen fibers. Immunofluorescence （IF） and Real-time polymerase chain reaction （Real-time PCR） were used to detect the protein， and mRNA expression of PINK1， Parkin， microtubule-associated protein 1 light chain 3 Ⅱ （LC3 Ⅱ）. ResultAfter intraperitoneal injection of STZ， compared with the blank group， the random blood glucose values of rats in the diabetic group increased significantly （P<0.01）， all higher than 16.7 mmol·L-1， and persistently hyperglycemic for some time after modeling. Compared with the blank group， the model group showed poor growth and healing of granulation tissue in the wounds， and the wound healing rate decreased （P<0.01）. On the 7th day after intervention， the blank group had squamous epithelial coverage on the wounds. Compared with the blank group， the model group only had a small amount of scab at the wound edges， with a large number of infiltrating inflammatory cells in the wounds. The protein expression levels of IL-6 and TNF-α in the tissues increased （P<0.01）， and the protein and mRNA levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. On the 14th day after the intervention， the granulation tissue in the wounds of the blank group was mature and well-healed. Compared with the blank group， the model group still had infiltrating inflammatory cells and red blood cell exudation. The protein expression levels of VEGF and collagen fibers in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. Compared with the model group， the cinnamaldehyde group and the Beifuxin group showed better wound healing， with increased wound healing rates （P<0.01）. On the 7th day after intervention， the protein expression levels of IL-6 and TNF-α in the tissues decreased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ increased （P<0.01）. On the 14th day after intervention， the protein expression levels of VEGF and collagen fibers in the tissues increased （P<0.01）， and the protein and mRNA expression levels of PINK1， Parkin， and LC3Ⅱ decreased （P<0.01）. ConclusionCinnamaldehyde can promote the wound healing of diabetes rats by increasing the wound healing rate， reducing the levels of inflammatory factors IL-6 and TNF-α， and increasing the levels of VEGF and collagen fibers. Its mechanism may be related to the regulation of the PINK1/Parkin signaling pathway， activation of mitochondrial autophagy， inhibition of inflammatory responses， and promotion of angiogenesis and collagen synthesis， thereby promoting the wound healing of diabetes rats.

Research progress on the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis / 中国修复重建外科杂志

OBJECTIVE@#To summarize the role of chondrocyte mitochondrial homeostasis imbalance in the pathogenesis of osteoarthritis (OA) and analyze its application prospects.@*METHODS@#The recent literature at home and abroad was reviewed to summarize the mechanism of mitochondrial homeostasis imbalance, the relationship between mitochondrial homeostasis imbalance and the pathogenesis of OA, and the application prospect in the treatment of OA.@*RESULTS@#Recent studies have shown that mitochondrial homeostasis imbalance, which is caused by abnormal mitochondrial biogenesis, the imbalance of mitochondrial redox, the imbalance of mitochondrial dynamics, and damaged mitochondrial autophagy of chondrocytes, plays an important role in the pathogenesis of OA. Abnormal mitochondrial biogenesis can accelerate the catabolic reaction of OA chondrocytes and aggravate cartilage damage. The imbalance of mitochondrial redox can lead to the accumulation of reactive oxygen species (ROS), inhibit the synthesis of extracellular matrix, induce ferroptosis and eventually leads to cartilage degradation. The imbalance of mitochondrial dynamics can lead to mitochondrial DNA mutation, decreased adenosine triphosphate production, ROS accumulation, and accelerated apoptosis of chondrocytes. When mitochondrial autophagy is damaged, dysfunctional mitochondria cannot be cleared in time, leading to ROS accumulation, which leads to chondrocyte apoptosis. It has been found that substances such as puerarin, safflower yellow, and astaxanthin can inhibit the development of OA by regulating mitochondrial homeostasis, which proves the potential to be used in the treatment of OA.@*CONCLUSION@#The mitochondrial homeostasis imbalance in chondrocytes is one of the most important pathogeneses of OA, and further exploration of the mechanisms of mitochondrial homeostasis imbalance is of great significance for the prevention and treatment of OA.

Bloodletting Acupuncture at Jing-Well Points on Hand Induced Autophagy to Alleviate Brain Injury in Acute Altitude Hypoxic Rats by Activating PINK1/Parkin Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the protective effect of bloodletting acupuncture at twelve Jing-well points on hand (BAJP) on acute hypobaric hypoxia (AHH)-induced brain injury in rats and its possible mechanisms.@*METHODS@#Seventy-five Sprague Dawley rats were divided into 5 groups by a random number table (n=15), including control, model, BAJP, BAJP+3-methyladenine (3-MA), and bloodletting acupuncture at non-acupoint (BANA, tail tip blooding) groups. After 7-day pre-treatment, AHH models were established using hypobaric oxygen chambers. The levels of S100B, glial fibrillary acidic protein (GFAP), superoxide dismutase (SOD), and malondialdehyde (MDA) in serum were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling method were used to assess hippocampal histopathology and apoptosis. Transmission electron microscopy assay was used to observe mitochondrial damage and autophagosomes in hippocampal tissues. Flow cytometry was used to detect mitochondrial membrane potential (MMP). The mitochondrial respiratory chain complexes I, III and IV activities and ATPase in hippocampal tissue were evaluated, respectively. Western blot analysis was used to detect the protein expressions of Beclin1, autophagy protein 5 (ATG5), microtubule-associated protein 1 light chain 3 beta (LC3B), phosphatase and tensin homolog induced kinase 1 (PINK1), and Parkin in hippocampal tissues. The mRNA expressions of Beclin1, ATG5 and LC3-II were analyzed by quantitative real-time polymerase chain reaction.@*RESULTS@#BAJP treatment reduced hippocampal tissue injury and inhibited hippocampal cell apoptosis in AHH rats. BAJP reduced oxidative stress by decreasing S100B, GFAP and MDA levels and increasing SOD level in the serum of AHH rats (P<0.05 or P<0.01). Then, BAJP increased MMP, the mitochondrial respiratory chain complexes I, III and IV activities, and the mitochondrial ATPase activity in AHH rats (all P<0.01). BAJP improved mitochondrial swelling and increased the autophagosome number in hippocampal tissue of AHH rats. Moreover, BAJP treatment increased the protein and mRNA expressions of Beclin1 and ATG5 and LC3-II/LC3-I ratio in AHH rats (all P<0.01) and activated the PINK1/Parkin pathway (P<0.01). Finally, 3-MA attenuated the therapeutic effect of BAJP on AHH rats (P<0.05 or P<0.01).@*CONCLUSION@#BAJP was an effective treatment for AHH-induced brain injury, and the mechanism might be through reducing hippocampal tissue injury via increasing the PINK1/Parkin pathway and enhancement of mitochondrial autophagy.

Effects of acupuncture and moxibustion on PINK1/Parkin signaling pathway in substantia nigra of Thy1-αSyn transgenic mice with Parkinson disease / 针灸推拿医学（英文版）

Objective:To observe the effects of acupuncture and moxibustion on phosphatase and PTEN-induced putative kinase 1(PINK1)/Parkin signaling pathway in the midbrain substantia nigra of Thy1-α synuclein(αSyn)transgenic model mice with Parkinson disease(PD). Methods:Twenty-four Thy1-αSyn transgenic mice were randomly divided into a model group,an acupuncture group,an acupuncture + moxibustion group,and a Western medicine group.Six wild-type mice in the same litter were used as the wild-type group.In the acupuncture group,Baihui(GV20)and Yanglingquan(GB34)were selected for acupuncture.In the acupuncture + moxibustion group,Guanyuan(CV4)was added on the basis of the acupuncture group.The Western medicine group was given rapamycin intraperitoneal injection at a dose of 10 mg/(kg·bw).The wild-type group and the model group were fixed without intervention.The overall rod performance(ORP)score of mice was observed in each group.The immunohistochemical method was used to detect the tyrosine hydroxylase(TH)positive neurons in the substantia nigra of mice in each group.The αSyn was detected by the immunofluorescence chemical method.The expression levels of αSyn,microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,autophagy protein sequestosome-1/protein 62(SQSTM-1/p62),PINK1,Parkin,and ubiquitin-specific protease 30(USP30)proteins were detected by Western blotting assay.The expression levels of LC3B,p62,PINK1,Parkin,and USP30 mRNAs were detected by fluorescence quantitative polymerase chain reaction. Results:Compared with the wild-type group,the ORP score,the p62,PINK1,and Parkin protein expression levels decreased significantly(P<0.01),the PINK1 mRNA expression level decreased(P<0.05),while the protein and mRNA expression levels of USP30 increased(P<0.05)in the model group.Compared with the model group,the ORP score in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the expression level of LC3-Ⅱ/LC3-Ⅰ protein in the acupuncture + moxibustion group and the Western medicine group increased(P<0.05);the protein expression levels of p62,PINK1,and Parkin increased(P<0.05),while the USP30 protein expression level decreased significantly(P<0.01)in the acupuncture group,the acupuncture + moxibustion group,and the Western medicine group;the Parkin mRNA expression level in the acupuncture group and the acupuncture + moxibustion group increased(P<0.05);the USP30 mRNA expression level in the acupuncture + moxibustion group decreased(P<0.05). Conclusion:Acupuncture and moxibustion regulate the related molecule expression levels of PINK1/Parkin signaling pathway in the Thy1-αSyn transgenic PD model mice and promote the autophagy degradation of αSyn to exert the protective effect of dopaminergic neurons.

Pterostilbene alleviates renal ischemia-reperfusion injury in mice by activating mitochondrial autophagy / 重庆医学

Objective To study the protective effect and related mechanism of pterostilbene(PTE)on renal ischemia-reperfusion injury(IRI)in mice.Methods Twenty-four C57 mice were randomly divided into 4 groups(n=6),including the sham operation group(S group),the renal ischemia reperfusion group(IR group),the renal ischemia reperfusion+5 mg/kg PTE group(IR+PTE1 group)and the renal ischemia reper-fusion+10 mg/kg PTE group(IR+PTE2 group).Hematoxylin-eosin(HE)and TUNEL staining were used to evaluate renal tissue injury.Creatinine(Cr),blood urea nitrogen(BUN),malondialdehyde(MDA)in renal tissue,inflammatory cytokines tumor necrosis factor(TNF-α),interleukin(IL)-1β and IL-6 levels in serum were detected with relevant kits.The expression of Bcl-2 interacting protein 3(BNIP3)and microtubule-asso-ciated protein light chain(LC)-3 Ⅱ in kidney tissue was detected by Western blot.Results Compared with the S group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR group were increased,renal tu-bule injury score and apoptosis index were increased,and expressions of BNIP3 and LC-3 Ⅱ were down-regula-ted,with statistical significance(P＜0.05).Compared with the IR group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE1 group were decreased,renal tubule injury score and apoptosis index were decreased,and expressions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Compared with the IR+PTE1 group,serum levels of Cr,BUN,MDA,TNF-α,IL-1β and IL-6 in the IR+PTE2 group were decreased,renal tubule injury score and apoptosis index were decreased,and expres-sions of BNIP3 and LC-3 Ⅱ were up-regulated,with statistical significance(P＜0.05).Conclusion PTE has protective effect on renal IRI in mice.

Regulating mechanism of Qishen Yiqi Dripping Pills on mitochondrial autophagy in type 2 diabetic rats / 国际生物医学工程杂志

Objective:To observe the protective effect of Qishen Yiqi Dripping Pills on myocardial ischemia-reperfusion injury in type 2 diabetic rats and its effects on mitochondrial autophagy phosphoglycerate mutase family member 5 (PGAM5)/Fun14 domain-containing protein 1 (FUNDC1) signaling pathway.Methods:48 male SD rats were divided into a blank control group, sham operation group, No.1 myocardial ischemia reperfusion injury (MIRI) group, No.2 MIRI group, inhibitor group, and Qishen Yiqi group. In addition to the blank control group and the No.1 MIRI group, the other 32 rats were fed with a high-fat diet combined with intraperitoneal injection of streptozotocin to establish animal models of diabetes. Then, the rats in the Qishen Yiqi group were ig Qishen Yiqi Gropping Pills 450 mg/kg, once daily. The rats in the inhibitor group were given Qishen Yiqi Gropping Pills and trimethylamine (3-MA) by intraperitoneal injection 100 mmol/L, once daily. And the rats in the other four groups were ig normal saline. One week after intragastric administration, except for the blank control group and the sham operation group, the rats in the other four groups were used to establish the animal model of myocardial ischemia-reperfusion injury by ligating the anterior descending branch of the left coronary artery for 30 min and reperfusion for 2 h. Then, the materials were taken after reperfusion for 2 h. Finally, the mortality of rats was calculated, the changes in creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected, and the expression level of PGAM5/FUNDC1 pathway node protein in myocardial tissue was measured by real-time fluorescence quantitative PCR.Results:Compared with the No.1 MIRI group, serum indicators of the AST, LDH, CK, and MDA levels in the No.2 MIRI model group increased (all P < 0.05), while the level of SOD decreased ( P < 0.05). Compared with the No.1 MIRI group, myocardial tissue indicators of FUNDC1, PGAM5, B cell lymphoma-xL (Bcl-xL), light chain 3 (LC3), autophagy associated protein 5 (ATG5), and Beclin-1 level decreased (all P < 0.05), the level of P62 increased ( P < 0.05), while the level of cysteinyl aspartate specific proteinase-9 (Caspase-9) increased, but he difference is not statistically significant ( P > 0.05). Compared with the No.2 MIRI group and the inhibitor group, serum indicators of the AST, LDH, CK, and MDA levels in the Qishen Yiqi group decreased (all P < 0.05), and the level of SOD increased ( P < 0.05). Compared with the No.2 MIRI group and the inhibitor group, myocardial tissue indicators of FUNDC1, PGAM5, Bcl-xL, LC3, ATG5, and Beclin-1 levels increased (all P < 0.05), while the levels of P62 and Caspase-9 decreased (all P < 0.05). Conclusions:High blood sugar levels can aggravate MIRI. Qishen Yiqi Dripping Pills can regulate mitochondrial autophagy through the PGAM5/FUNDC1 pathway and alleviate myocardial ischemia-reperfusion injury. MIRI plays a protective role in the myocardium of diabetic rats.

Exploring the Protective Effect of Bloodletting Acupuncture at Jing-Well Points on Acute High-Altitude Hypoxia Brain Injury Based on PI3K/AKT/mTOR Signaling Pathway / 世界科学技术-中医药现代化

Objective To investigate the protective effect and molecular mechanism of bloodletting acupuncture at Jing-well points on acute high-altitude hypoxia brain injury through regulating PI3K/AKT/mTOR signaling pathway-mediated mitochondrial autophagy,and to provide an effective target and theoretical basis for the clinical use of bloodletting acupuncture at Jing-well points to prevent and treat acute high-altitude hypoxia brain injury.Methods Male SD rats were randomly divided into Control group(n=15)and experimental group,and the experimental group was divided into Model group(n=15),Bloodletting Acupuncture at Jing-well Points of hand group(BAJP group,n=15),Bloodletting Acupuncture at Non-Acupoint group(BANA group,n=15).The low pressure oxygen chamber was depressurized to 6000 m altitude,and the rats in each experimental group were treated with low-pressure hypoxia for 72 h to replicate the acute high-altitude hypoxia brain injury rat model.The rats in the BAJP group were bled according to the order of"Shaoshang"(LU11),"Shangyang"(LI1),"Zhongchong"(PC9),"Guanchong"(SJ1),"Shaochong"(HT9),"Shaoze"(SI1),once a day for 7 days.The rats in the BANA group were bled by cutting the tail tip daily,and the amount of blood bled was 15-20 μL in both groups.The expression levels of PI3K,AKT and mTOR in hippocampal tissues of rats were detected by Western blot;AKT and mTOR mRNA expression levels in hippocampal tissues of rats were detected by PCR.Results Compared with the Control group,the number of degenerative necrotic vertebral cells in CA1 area of hippocampal tissue,swelling of mitochondria,appearance of autophagosomes,and increase of apoptosis in hippocampal tissue of Acute High-altitude Hypoxia(AHH)rats were significantly increased;After bloodletting acupuncture at Jing-well points of hand treatment,various brain injury manifestations in AHH rats were alleviated;Bloodletting acupuncture at non-acupoint had no significant ameliorating effect on AHH rats′ brain injury.Western blot detected a significant decrease in the phosphorylation levels of PI3K,AKT,and mTOR in the hippocampal tissues of AHH rats compared to Control group rats(P<0.01),and the phosphorylation levels of the three molecules were further decreased after bloodletting acupuncture at Jing-well points of hand treatment(P<0.01),and bloodletting acupuncture at non-acupoint treatment did not have significantly affect on the phosphorylation levels of these molecules(P>0.05),and AKT,mTOR mRNA expression levels further demonstrated the above trend.Conclusion Bloodletting acupuncture at Jing-well points of hand can play a protective role against acute high-altitude hypoxia brain injury with points specificity,and the mechanism may be related to the inhibition of PI3K/AKT/mTOR pathway to promote the elevated level of mitochondrial autophagy,improve mitochondrial physiology,and enhance the body′s ability to resist apoptosis and hypoxia.

The protective effects and mechanisms of melatonin on white matter damage in neonatal rats / 中国新生儿科杂志

Objective:To study the protective effects and mechanisms of melatonin (MTn) on lipopolysaccharide (LPS) and hypoxic-ischemic(HI) induced white matter damage (WMD) in neonatal rats.Methods:Seventy-two 3-day-old newborn Sprague-Dawley (SD) rats were randomly assigned into sham operation group (the sham group), model group (the HI group) and MTn intervention group (the HI+MTn group) ( n=24 for each group). For the sham group, only dissection of the right common carotid artery was performed without ligation. Animal models of WMD were established using LPS pretreatment and HI method in both the HI group and HI+MTn group. The HI+MTn group received MTn intraperitoneal injection (15 mg/kg, 1 h before LPS injection and then once daily). The HI group and the sham group received equal volume of normal saline containing 1% ethanol intraperitoneal injection. The rats were sacrificed on d7 of experiment and periventricular white matter (PVWM) was collected for hematoxylin-eosin (HE) and TUNEL staining to determine WMD and apoptosis. The distribution and morphology of microglial cells in the PVWM were studied using IBA1 immunofluorescence staining. Reactive oxygen species (ROS) kit was used to detect ROS. The expression of nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes, interleukin (IL)-1β, IL-18 and mitochondrial autophagy markers (pink1 and parkin) were determined using real-time quantitative PCR. Results:Compared with the sham group, the HI group showed WMD, cell degeneration and necrosis,increased cell apoptosis and increased expressions of NLRP3 inflammasomes and downstream inflammatory factors (IL-1β and IL-18) in PVWM. Compared with the HI group,the HI+MTn group showed reduced WMD, cell apoptosis, microglia infiltration and inflammatory factors expression. MTn increased pink1 and parkin expression and reduced ROS production in PVWM.Conclusions:MTn reduces ROS production by enhancing mitochondrial autophagy and inhibits NLRP3 inflammasomes hyperactivation to alleviate endotoxin- and HI-induced WMD in neonatal rats.

Mechanism of autophagy induced by osthole through PINK1/Parkin pathway in HeLa cells / 中国药理学通报

Aim To investigate the potential mechanism of osthole promoting autophagy in cervical cancer HeLa cells. Methods HeLa cells were treated with various concentrations of Osthole(0,10,20,40,80,160,240,320 mg·L-1). MTT was used to detect cell vitality. Transmission electron microscopy(TEM)was used to observe the morphology of HeLa cells after osthole intervention. Mondane sulfonyl cadaverine(MDC)staining was used to dectect the level of autophagy. Western blot was employed to analyze the expression levels of mitochondrial protein MFN1 and DPR1. JC-1 flourescence probe was applied to detect mitochondrial membrane potential. Flow cytometry was used to deteminet the release of reactive oxygen species(ROS). A transplanted tumor model of cervical cancer was established in vivo in nude mice. Western blot was used to detect the protein expression levels of PINK1,Parkin and LC3Ⅱ/. Results Osthole could inhibit the proliferation of HeLa cells significantly. Transmission electron microscopy showed that typical autophagosomes were formed in HeLa cells after osthole intervention. The fluorescence intensity of MDC was enhanced. The expression of mitochondrial fusion protein MFN1 was down-regulated after HeLa cells pretreated with osthole,and mitochondrial fission protein DRP1 was up-regulated. Mitochondrial membrane potential decreased. ROS production of HeLa cells was increased by flow cytometry,which could be reversed by autophagy inhibitor 3-MA. Tumor weight in nude mice was inhibited by osthole obviously,which might restrain cervical cancer. Western blot result indicated that the key factors of mitochondrial autophagy PINK1,Parkin and LC3Ⅱ/ratio were up-regulated in HeLa cells. Conclusions Osthole could induce autophagy in HeLa cells and its mechanism may be related to ROS production and PINK1/Parkin pathway.

Effects of total saponins from Trillium tschonoskii maxim on cognition impairment and mitochondrial autophagy in aging rats induced by D-Gal / 中国药理学通报

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

27-P-CAUA induces apoptosis and mitochondrial autophagy in breast cancer cells by inhibiting HER2/PI3K/AKT signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the inhibitory effect of 27-P-coumayl-ursolic acid (27-P-CAUA), the active ingredient in triterpenoids from the leaves of Ilex latifolia Thunb, against breast cancer cells and explore the underlying mechanism.@*METHODS@#CCK-8 assay was used to assess the changes in viability of breast cancer HCC-1806 cells after 27-P-CAUA treatment for 24, 48, or 72 h. The inhibitory effect of 27-P-CAUA on proliferation of the cells was determined by clonogenic assay. JC-1 was used to detect the changes in mitochondrial membrane potential and flow cytometry was performed for analyzing cell apoptosis following 27-P-CAUA treatment. Immunofluorescence assay was used to observe the expression of cl-caspase-3 and P62 in the treated cells. Western blotting was performed to observe the effect of 27-P-CAUA and chloroquine pretreatment on the expressions of LC3I/II, P62 and HER2 signaling pathway proteins in the cells.@*RESULTS@#The results of CCK-8 and clonogenic assays showed that 27-P-CAUA treatment significantly inhibited the proliferation of HCC-1806 cells (P < 0.01) with IC50 values of 81.473, 48.392 and 18.467 μmol/L at 24, 48, and 72 h, respectively. 27-P-CAUA treatment also caused obvious changes in mitochondrial membrane potential (P < 0.01) and induced cell apoptosis in HCC-1806 cells with a 3.34% increase of the early apoptosis rate. Immunofluorescence assay revealed a significant increase of cl-caspase3 expression in 27-P-CAUA-treated HCC-1806 cells, and treatment with 40 μmol/L 27-P-CAUA resulted in significant cell apoptosis (P < 0.01). 27-P-CAUA obviously reduced the expression of LC3II, caused P62 degradation and induced autophagy in HCC-1806 cells. Chloroquine pretreatment obviously blocked the autophagy-inducing effect of 27-P-CAUA. 27-P-CAUA treatment also inhibited the phosphorylation of HER2 and AKT proteins and progressively lowered the expressions of HER2 and phosphorylated AKT protein in HCC-1806 cells (P < 0.01).@*CONCLUSION@#27-P-CAUA can inhibit the proliferation and induce mitochondrial autophagy and apoptosis of HCC-1806 cells by inhibiting the HER2/PI3K/AKT signaling pathway.

Effect of Mitochondrial Autophagy in Clinical Diseases and Intervention by Chinese Medicine： A Review / 中国实验方剂学杂志

Mitochondrial autophagy is a process to clear dysfunctional mitochondria in the cytoplasm to maintain the integrity of mitochondrial function and cell homeostasis. Mitochondrial autophagy is a complex physiological process， which can maintain the balance of mitochondrial quality and quantity， cell survival under starvation and harsh conditions， and the stability of the intracellular environment. Its molecular mechanism involves a variety of proteins. Many factors can induce mitochondrial autophagy， such as starvation， oxidative stress， hypoxia， depolarization， and other stresses. The accumulation of unfolded proteins can also induce mitochondrial autophagy. In recent years， as a research hotspot， the abnormality of mitochondrial morphology and function is closely related to the occurrence of a variety of diseases. The research on mitochondrial autophagy and the pathogenesis of clinical diseases has attracted more attention， such as tumors， cardiovascular diseases， liver diseases， nervous system diseases， and glucose metabolism disorders. It has been found that regulating mitochondrial autophagy may inspire the treatment of some diseases. Meanwhile， clinical researchers have paid more attention to traditional Chinese medicine （TCM）. As revealed by in-depth research， Chinese medicine has a certain value in regulating mitochondrial autophagy. The research on the pathogenesis of mitochondrial autophagy in related diseases and the intervention of Chinese medicine has found that there are many reports on the regulation of mitochondrial autophagy by Chinese medicine in tumors， cardiovascular diseases， and nervous system diseases. However， the mechanism of mitochondrial autophagy， the balance of mitochondrial autophagy， and the difference in the activation or inhibition of mitochondrial autophagy by Chinese medicine remain unclear. The regulation of mitochondrial autophagy has become a new research target strategy of Chinese medicine in the prevention and treatment of diseases. This paper reviewed the available literature in recent years to provide reference materials for the regulation of mitochondrial autophagy by Chinese medicine and ideas for the follow-up research of Chinese medicine in mitochondrial autophagy.

Effect of Mitochondrial Autophagy in Clinical Diseases and Intervention by Chinese Medicine： A Review / 中国实验方剂学杂志

Mitochondrial autophagy is a process to clear dysfunctional mitochondria in the cytoplasm to maintain the integrity of mitochondrial function and cell homeostasis. Mitochondrial autophagy is a complex physiological process， which can maintain the balance of mitochondrial quality and quantity， cell survival under starvation and harsh conditions， and the stability of the intracellular environment. Its molecular mechanism involves a variety of proteins. Many factors can induce mitochondrial autophagy， such as starvation， oxidative stress， hypoxia， depolarization， and other stresses. The accumulation of unfolded proteins can also induce mitochondrial autophagy. In recent years， as a research hotspot， the abnormality of mitochondrial morphology and function is closely related to the occurrence of a variety of diseases. The research on mitochondrial autophagy and the pathogenesis of clinical diseases has attracted more attention， such as tumors， cardiovascular diseases， liver diseases， nervous system diseases， and glucose metabolism disorders. It has been found that regulating mitochondrial autophagy may inspire the treatment of some diseases. Meanwhile， clinical researchers have paid more attention to traditional Chinese medicine （TCM）. As revealed by in-depth research， Chinese medicine has a certain value in regulating mitochondrial autophagy. The research on the pathogenesis of mitochondrial autophagy in related diseases and the intervention of Chinese medicine has found that there are many reports on the regulation of mitochondrial autophagy by Chinese medicine in tumors， cardiovascular diseases， and nervous system diseases. However， the mechanism of mitochondrial autophagy， the balance of mitochondrial autophagy， and the difference in the activation or inhibition of mitochondrial autophagy by Chinese medicine remain unclear. The regulation of mitochondrial autophagy has become a new research target strategy of Chinese medicine in the prevention and treatment of diseases. This paper reviewed the available literature in recent years to provide reference materials for the regulation of mitochondrial autophagy by Chinese medicine and ideas for the follow-up research of Chinese medicine in mitochondrial autophagy.