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Representative TEM images of mitochondria. Normal mitochondria with intact outer membrane and dense cristae in normal group. Severely impaired mitochondria with fuzzy cristae and swelling matrix in model group and blank serum group. QJJLD-containing serum treatment improves mitochondria morphologies in low-, middle-, and high-dose groups (bar=200 nm). The low-dose group has more mitochondrial cristae and little swelling matrix than model group. Moreover, the mitochondrial cristae and matrix in middle-dose group are better than that in low-dose group. The high-dose group also has more good contrast than middle-dose group.
Source publication
Oxidative stress can cause the excessive generation of reactive oxygen species (ROS) and has various adverse effects on muscular mitochondria. Qiangji Jianli decoction (QJJLD) is an effective traditional Chinese medicine (TCM) that is widely applied to improve muscle weakness, and it has active constituents that prevent mitochondrial dysfunction. T...
Citations
... MDA, a lipid peroxide formed as a result of ROS, can affect the mitochondrial respiratory chain and the activity of key mitochondrial enzymes associated with H 2 O 2 -induced ROS generation [26]. To assess the strength of the oxidative stress response in the aneurysm walls on day 28 after administration, ELISAs were conducted to determine the MDA content of the aortas from each group. ...
Objectives
Glucagon-like peptide-1 (GLP-1) has a cardiovascular protective effect by preventing abdominal aortic aneurysm (AAA) formation. However, it is unclear at what point the agent should be administered to achieve the optimal effect. In this study, we aimed to determine whether administering the GLP-1 receptor agonist liraglutide during the earlier stages would more efficiently inhibit AAA progression in mice.
Methods
Depending on the group, mice were given a daily dose of 300 μg/kg liraglutide for 28 days at 7, 14, and 28 days after aneurysm induction. The morphology of the abdominal aorta was monitored using 7.0 T magnetic resonance imaging (MRI) during the administration of liraglutide. After 28 days of administration, the AAA dilatation ratio was calculated, and histopathological examination was performed. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA) and matrix metalloproteinases (MMPs). The inflammatory response was also evaluated.
Results
Liraglutide treatment led to a decrease in AAA formation, including a reduction in abdominal aorta expansion, elastin degradation in the elastic laminae, and vascular inflammation caused by leukocyte infiltration. The expression of MDA and the activity of MMPs (MMP-2, MMP-9) also decreased. Notably, administering liraglutide during the early stages resulted in a significant reduction in the dilatation rate of the aortic wall, as well as in MDA expression, leukocyte infiltration, and MMP activity in the vascular wall.
Conclusions
The GLP-1 receptor agonist liraglutide was found to inhibit AAA progression in mice by exerting anti-inflammatory and antioxidant effects, particularly during the early stages of AAA formation. Therefore, liraglutide may represent a potential pharmacological target for the treatment of AAA.
... MDA is a lipid peroxide of ROS, so it may affect the mitochondrial respiratory chain and the activity of key enzymes in mitochondria associated with H 2 O 2 -induced ROS generation 23 . To evaluate the oxidative stress response expression in aneurysm walls on day 28 after administration, ELISAs were performed to determine the MDA content of the aorta from each group. ...
Objectives
Glucagon‑like peptide‑1 (GLP-1) has a cardiovascular-protective effect in preventing Abdominal Aortic Aneurysm (AAA) formation. However, the administration time to maximize the optimal effect has not been determined. We conducted this study to determine whether the GLP-1 receptor agonist, liraglutide, inhibited AAA progression of mice more efficiently during the earlier stages.
Methods Mice were treated with 300ug/kg/day liraglutide 7, 14 and 28 days after aneurysm preparation. The morphology of abdominal aorta were followed up with 7.0 T magnetic resonance imaging (MRI) during the liraglutide administration. 28 days after administration, the AAA dilatation ratio calculation and histopathological examination were then conducted. Oxidative stress levels were evaluated by the expression of malondialdehyde (MDA). The inflammatory responses were also determined.
Results Treatment with liraglutide decreased AAA formation. Specifically, expansion of the abdominal aorta, elastin lamina degradation and vascular inflammation by leukocyte infiltration decreased. Additionally, MDA expression and matrix metalloproteinase (MMP) activity reduced. Furthermore, the dilatation rate of aortic, MDA expression, leukocyte infiltration, and MMPs activity in the vascular wall decreased significantly in early stage.
Conclusions GLP-1 treatment inhibited AAA progression in mice through its anti-inflammatory and anti-oxidant effects, especially during the earlier stages of AAA formation. Thus, GLP-1 may be a potential pharmacological target for AAA treatment.
... Unbalanced mitochondrial dynamics, inclined to fission and fragmentation, were found in the models of myocardial injury and heart failure (86)(87)(88). Among many regulatory proteins, Mfn2 and Drp1 are involved in mitochondrial fusion and mitochondrial fission, respectively (89,90). Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), a powerful transcription factor, is the major regulator of mitochondrial biogenesis due to its regulatory effect on processes like energy metabolism and dynamics (91). ...
Introduction
Modified Linggui Zhugan Decoction (MLZD) is a Traditional Chinese Medicine prescription developed from Linggui Zhugan Decoction (LZD) that has been used for the clinical treatment of ischemic cardiovascular diseases. However, the cardioprotective mechanism of MLZD against post-myocardial infarction (MI) ventricular remodeling remains unclear.
Methods
We explored the effects of MLZD on ventricular remodeling and their underlying mechanisms, respectively, in SD rats with MI models and in H9c2 cardiomyocytes with oxygen-glucose deprivation (OGD) models. The cardiac structure and function of rats were measured by echocardiography, HE staining, and Masson staining. Apoptosis, inflammation, mitochondrial structure and function, and sirtuin 3 (SIRT3) expression were additionally examined.
Results
MLZD treatment significantly ameliorated cardiac structure and function, and thus reversed ventricular remodeling, compared with the control. Further research showed that MLZD ameliorated mitochondrial structural disruption, protected against mitochondrial dynamics disorder, restored impaired mitochondrial function, inhibited inflammation, and thus inhibited apoptosis. Moreover, the decreased expression level of SIRT3 was enhanced after MLZD treatment. The protective effects of MLZD on SIRT3 and mitochondria, nevertheless, were blocked by 3-TYP, a selective inhibitor of SIRT3.
Discussion
These findings together revealed that MLZD could improve the ventricular remodeling of MI rats by ameliorating mitochondrial damage and its associated apoptosis, which might exert protective effects by targeting SIRT3.
... During PD, the activities of SOD and the CAT and GSH-Px of the antioxidant defense system are relatively weak, and the improvement of their activities is an important approach in the prevent of PD progression and development (Wang et al., 2018;Chen et al., 2021). Monoamine oxidase promotes the generation of H 2 O 2 , which increases high levels of oxidative stress state and cause injury in PD patients (Youdim, 2018 (Song et al., 2021). MDA is one of the final products of polyunsaturated fatty acid peroxidation and a well-established marker of oxidative stress, which is associated with PD injury. ...
Purpose: Parkinson’s disease (PD) is closely associated with oxidative stress and inflammatory situation. Apolipoprotein A-I mimetic peptides (ApoAI MP) have antioxidant and anti-inflammatory properties. We aimed to study the therapeutic effect of ApoAI MP on PD mice, and to explore the related mechanisms.
Methods: PD mice were induced by using 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP). The model mice were treated with different concentrations of ApoAI MP. The open-field behavioral test assesses the total distance moved, the rest time, and the number of crossings and Rota-rod was used to evaluate motor coordination. Oxidative stress was identified by measuring the levels of superoxide dismutase (SOD), catalase (CAT), glutathionperoxidase (GSH-Px), malondialdehyde, ROS and H 2 O 2 . Inflammatory situation was analyzed by measuring the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Meanwhile, the scavenging activities of ApoAI MP for ABTS, DPPH, hydroxyl radical and superoxide anion, and the effects of the peptide on neurotransmitters were evaluated.
Results: PD model establishment increased oxidative stress and inflammatory status by increasing the concentrations of ROS and H 2 O 2 production, and the levels of TNF-α, IL-1β and IL-6 ( p < 0.05). ApoAI MP intervention improved PD symptoms by reducing the total moved distance and the number of passes ( p < 0.01), and the falling times from Rota-rod, and increasing rest time ( p < 0.05). ApoAI MP increased antioxidant properties by increasing the activities of SOD, CAT and GSH-Px, and reducing MDA concentration ( p < 0.05). ApoAI MP addition reduced oxidative stress by scavenging ABTS, DPPH, hydroxyl radicals and superoxide anion and reducing the concentrations of ROS and H 2 O 2 production ( p < 0.05). ApoAI MP treatment increased anti-inflammatory capacities by reducing the concentrations of TNF-α, IL-1β and IL-6 ( p < 0.05). HPLC analysis showed that the peptide treatment improved neurotransmitters.
Conclusion: ApoAI MP can improve the behavioral performance of PD mice by improving antioxidant and anti-inflammatory capacities.
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.
Obesity is a major global health concern because of its strong association with metabolic and neurodegenerative diseases such as diabetes, dementia, and Alzheimer's disease. Unfortunately, brain insulin resistance in obesity is likely to lead to neuroplasticity deficits. Since the evidence shows that insulin resistance in brain regions abundant in insulin receptors significantly alters mitochondrial efficiency and function, strategies targeting the mitochondrial quality control system may be of therapeutic and practical value in obesity-induced cognitive decline. Exercise is considered as a powerful stimulant of mitochondria that improves insulin sensitivity and enhances neuroplasticity. It has great potential as a non-pharmacological intervention against the onset and progression of obesity associated neurodegeneration. Here, we integrate the current knowledge of the mechanisms of neurodegenration in obesity and focus on brain insulin resistance to explain the relationship between the impairment of neuronal plasticity and mitochondrial dysfunction. This knowledge was synthesised to explore the exercise paradigm as a feasible intervention for obese neurodegenration in terms of improving brain insulin signals and regulating the mitochondrial quality control system.
