scholarly journals Mitochondrial Transplantation Modulates Inflammation and Apoptosis, Alleviating Tendinopathy Both In Vivo and In Vitro

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 696
Author(s):  
Ji Min Lee ◽  
Jung Wook Hwang ◽  
Mi Jin Kim ◽  
Sang Youn Jung ◽  
Kyung-Soo Kim ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Tendon Healing ◽  
Nuclear Factor Κb ◽  
Therapeutic Effects ◽  
Matrix Metalloproteinase 1 ◽  
Anti Inflammatory

Tendinopathy is a common musculoskeletal condition causing pain and dysfunction. Conventional treatment and surgical procedures for tendinopathy are insufficient; accordingly, recent research has focused on tendon-healing regenerative approaches. Tendon injuries usually occur in the hypoxic critical zone, characterized by increased oxidative stress and mitochondrial dysfunction; thus, exogenous intact mitochondria may be therapeutic. We aimed to assess whether mitochondrial transplantation could induce anti-inflammatory activity and modulate the metabolic state of a tendinopathy model. Exogenous mitochondria were successfully delivered into damaged tenocytes by centrifugation. Levels of Tenomodulin and Collagen I in damaged tenocytes were restored with reductions in nuclear factor-κB and matrix metalloproteinase 1. The dysregulation of oxidative stress and mitochondrial membrane potential was attenuated by mitochondrial transplantation. Activated mitochondrial fission markers, such as fission 1 and dynamin-related protein 1, were dose-dependently downregulated. Apoptosis signaling pathway proteins were restored to the pre-damage levels. Similar changes were observed in a collagenase injection-induced rat model of tendinopathy. Exogenous mitochondria incorporated into the Achilles tendon reduced inflammatory and fission marker levels. Notably, collagen production was restored. Our results demonstrate the therapeutic effects of direct mitochondrial transplantation in tendinopathy. These effects may be explained by alterations in anti-inflammatory and apoptotic processes via changes in mitochondrial dynamics.

scholarly journals Olive Polyphenols: Antioxidant and Anti-Inflammatory Properties

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1044
Author(s):  
Monica Bucciantini ◽  
Manuela Leri ◽  
Pamela Nardiello ◽  
Fiorella Casamenti ◽  
Massimo Stefani
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Meta Analysis ◽  
Virgin Olive Oil ◽  
Bioactive Molecules ◽  
Therapeutic Effects ◽  
Molecular Signaling ◽  
Anti Inflammatory

Oxidative stress and inflammation triggered by increased oxidative stress are the cause of many chronic diseases. The lack of anti-inflammatory drugs without side-effects has stimulated the search for new active substances. Plant-derived compounds provide new potential anti-inflammatory and antioxidant molecules. Natural products are structurally optimized by evolution to serve particular biological functions, including the regulation of endogenous defense mechanisms and interaction with other organisms. This property explains their relevance for infectious diseases and cancer. Recently, among the various natural substances, polyphenols from extra virgin olive oil (EVOO), an important element of the Mediterranean diet, have aroused growing interest. Extensive studies have shown the potent therapeutic effects of these bioactive molecules against a series of chronic diseases, such as cardiovascular diseases, diabetes, neurodegenerative disorders and cancer. This review begins from the chemical structure, abundance and bioavailability of the main EVOO polyphenols to highlight the effects and the possible molecular mechanism(s) of action of these compounds against inflammation and oxidation, in vitro and in vivo. In addition, the mechanisms of inhibition of molecular signaling pathways activated by oxidative stress by EVOO polyphenols are discussed, together with their possible roles in inflammation-mediated chronic disorders, also taking into account meta-analysis of population studies and clinical trials.

scholarly journals Physalin A Inhibits MAPK and NF-κB Signal Transduction Through Integrin αVβ3 and Exerts Chondroprotective Effect

2021 ◽  
Vol 12 ◽  
Author(s):  
Rui Lu ◽  
Xiaojun Yu ◽  
Shuang Liang ◽  
Peng Cheng ◽  
Zhenggang Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Integrin Αvβ3 ◽  
The Elderly ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Therapeutic Effects ◽  
Anti Inflammatory ◽  
Chondroprotective Effect

Osteoarthritis (OA) is a common articular ailment presented with cartilage loss and destruction that is common observed in the elderly population. Physalin A (PA), a natural bioactive withanolide, exerts anti-inflammatory residences in more than a few diseases; however, little is known about its efficacy for OA treatment. Here, we explored the therapeutic effects and potential mechanism of PA in mouse OA. After the in vitro administration of PA, the expression of inflammation indicators including inducible nitric oxide synthase and cyclooxygenase-2 was low, indicating that PA could alleviate the IL-1β-induced chondrocyte inflammation response. Moreover, PA reduced IL-1β-induced destruction of the extracellular matrix by upregulating the gene expression of anabolism factors, including collagen II, aggrecan, and sry-box transcription factor 9, and downregulating the gene expression of catabolic factors, including thrombospondin motif 5 and matrix metalloproteinases. In addition, the chondroprotective effect of PA was credited to the inhibition of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. Furthermore, in vivo experiments showed that intra-articular injection of PA could alleviate cartilage destruction in a mouse OA model. However, the anti-inflammatory, anabolism enhancing, catabolism inhibiting, and MAPK and NF-κB signaling pathway inhibiting properties of PA on IL-1β-induced chondrocytes could be reversed when integrin αVβ3 is knocked down by siRNA. In conclusion, our work demonstrates that PA exhibits a chondroprotective effect that may be mediated by integrin αVβ3. Thus, PA or integrin αVβ3 might be a promising agent or molecular target for the treatment of OA.

scholarly journals Emerging Antioxidant Paradigm of Mesenchymal Stem Cell-Derived Exosome Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Chen Xia ◽  
Zhanqiu Dai ◽  
Yongming Jin ◽  
Pengfei Chen
Keyword(s):  
Oxidative Stress ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Direct Reduction ◽  
Antioxidant Properties ◽  
Therapeutic Effects ◽  
Diverse Range ◽  
Anti Inflammatory

Mesenchymal stem cell-derived exosomes have been under investigation as potential treatments for a diverse range of diseases, and many animal and clinical trials have achieved encouraging results. However, it is well known that the biological activity of the exosomes is key to their therapeutic properties; however, till date, it has not been completely understood. Previous studies have provided different explanations of therapeutic mechanisms of the exosomes, including anti-inflammatory, immunomodulatory, and anti-aging mechanisms. The pathological effects of oxidative stress often include organ damage, inflammation, and disorders of material and energy metabolism. The evidence gathered from research involving animal models indicates that exosomes have antioxidant properties, which can also explain their anti-inflammatory and cytoprotective effects. In this study, we have summarized the antioxidant effects of exosomes in in vivo and in vitro models, and have evaluated the anti-oxidant mechanisms of exosomes by demonstrating a direct reduction in excessive reactive oxygen species (ROS), promotion of intracellular defence of anti-oxidative stress, immunomodulation by inhibiting excess ROS, and alteration of mitochondrial performance. Exosomes exert their cytoprotective and anti-inflammatory properties by regulating the redox environment and oxidative stress, which explains the therapeutic effects of exosomes in a variety of diseases, mechanisms that can be well preserved among different species.

scholarly journals Non-alcoholic fatty liver disease in mice with hepatocyte-specific deletion of mitochondrial fission factor

Diabetologia ◽  
2021 ◽  
Author(s):  
Yukina Takeichi ◽  
Takashi Miyazawa ◽  
Shohei Sakamoto ◽  
Yuki Hanada ◽  
Lixiang Wang ◽  
...  
Keyword(s):  
Er Stress ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Primary Hepatocytes ◽  
Alcoholic Fatty Liver ◽  
Expression Of Genes ◽  
Specific Deletion

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract

scholarly journals Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Andra-Diana Andreicut ◽  
Alina Elena Pârvu ◽  
Augustin Cătălin Mot ◽  
Marcel Pârvu ◽  
Eva Fischer Fodor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Stress Index ◽  
Tnf Alpha ◽  
Phytochemical Analysis ◽  
Anti Inflammatory ◽  
Mahonia Aquifolium ◽  
Antioxidant Effects

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.

scholarly journals Modulatory effect of Syzygium aromaticum and Pelargonium graveolens on oxidative stress and inflammation

2018 ◽  
Author(s):  
Ilias Marmouzi ◽  
El Mostafa Karym ◽  
Rachid Alami ◽  
Meryem El Jemli ◽  
Mourad Kharbach ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Essential Oils ◽  
Toxic Effect ◽  
Tetrahymena Pyriformis ◽  
Syzygium Aromaticum ◽  
Minimal Risk ◽  
Pelargonium Graveolens ◽  
Anti Inflammatory

AbstractBackgroundTherapy combination is defined as disease treatment with two or more medication to acheive efficacy with lower doses or lower toxicity. Regarding its reported toxicities and efficacy, the Essential Oils (EOs) from Syzygium aromaticum (SA) and Pelargonium graveolens (PG) were combined for in vitro and in vivo assays and toxicities.MethodsThe Essential Oils and mixture were tested for in vivo/in vitro antioxidant and anti-inflammatory activities. The assays included the animal model of acute inflammation (carrageenan model), the protective effect on H2O2/Sodium nitroprissude induced stress in Tetrahymena pyriformis, and the in vitro antioxidant assays.ResultsThe chemical analysis of the investigated Oils has lead to the identification of Eugenol (74.06%), Caryophyllene (11.52%) and Carvacrol acetate (7.82%) as the major element in SA; while PG was much higher in Citronellol (30.77%), 10-epi-γ-Eudesmol (22.59%), and Geraniol (13.95%). In our pharmacological screening of samples, both Oils demonstrated good antioxidant effects. In vivo investigation of the antioxidant activity in the protozoa model (T. pyriformis) demonstrated a lesser toxic effect of EOs mixture with no significant differences when oxidative stress markers and antioxidant enzymes (MDA, SOD and CAT) were evaluated. On the other hand the in vivo model of inflammatory response to carrageenan demonstrated a good inhibitory potential of both EOs. The EOs Mixture demonstrated equivalent bioactivity with lower toxic effect and minimal risk for each compound.ConclusionsThe results from this study indicate that EOs mixture from SA and PG demonstrated promising modulatory antioxidant/anti-inflammatory effect, which suggest an efficient association for therapy.

scholarly journals MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress

2019 ◽  
Vol 2 (4) ◽  
pp. e201900308 ◽  
Author(s):  
Shun Nagashima ◽  
Keisuke Takeda ◽  
Nobuhiko Ohno ◽  
Satoshi Ishido ◽  
Motohide Aoki ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Microglial Activation ◽  
Developmental Disorders ◽  
Inflammatory Diseases ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Three Dimensional ◽  
Abnormal Behavior ◽  
Mitochondrial Abnormalities

Mitochondrial abnormalities are associated with developmental disorders, although a causal relationship remains largely unknown. Here, we report that increased oxidative stress in neurons by deletion of mitochondrial ubiquitin ligase MITOL causes a potential neuroinflammation including aberrant astrogliosis and microglial activation, indicating that mitochondrial abnormalities might confer a risk for inflammatory diseases in brain such as psychiatric disorders. A role of MITOL in both mitochondrial dynamics and ER-mitochondria tethering prompted us to characterize three-dimensional structures of mitochondria in vivo. In MITOL-deficient neurons, we observed a significant reduction in the ER-mitochondria contact sites, which might lead to perturbation of phospholipids transfer, consequently reduce cardiolipin biogenesis. We also found that branched large mitochondria disappeared by deletion of MITOL. These morphological abnormalities of mitochondria resulted in enhanced oxidative stress in brain, which led to astrogliosis and microglial activation partly causing abnormal behavior. In conclusion, the reduced ER-mitochondria tethering and excessive mitochondrial fission may trigger neuroinflammation through oxidative stress.

Ergosterol attenuates cigarette smoke extract-induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo

2019 ◽  
Vol 133 (13) ◽  
pp. 1523-1536 ◽  
Author(s):  
Xiao Sun ◽  
Xiuli Feng ◽  
Dandan Zheng ◽  
Ang Li ◽  
Chunyan Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cigarette Smoke ◽  
Cigarette Smoke Extract ◽  
Cordyceps Sinensis ◽  
Chronic Obstructive ◽  
Therapeutic Effects ◽  
Related Proteins ◽  
And Oxidative Stress

Abstract Cigarette smoke (CS) is the major cause of chronic obstructive pulmonary disease (COPD). CS heightens inflammation, oxidative stress and apoptosis. Ergosterol is the main bioactive ingredient in Cordyceps sinensis (C. sinensis), a traditional medicinal herb for various diseases. The objective of this work was to investigate the effects of ergosterol on anti-inflammatory and antioxidative stress as well as anti-apoptosis in a cigarette smoke extract (CSE)-induced COPD model both in vitro and in vivo. Our results demonstrate that CSE induced inflammatory and oxidative stress and apoptosis with the involvement of the Bcl-2 family proteins via the nuclear factor kappa B (NF-κB)/p65 pathway in both 16HBE cells and Balb/c mice. CSE induced epithelial cell death and increased the expression of nitric oxide (NO), interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), malondialdehyde (MAD) and the apoptosis-related proteins cleaved caspase 3/7/9 and cleaved-poly-(ADP)-ribose polymerase (PARP) both in vitro and in vivo, whereas decreased the levels of superoxide dismutase (SOD) and catalase (CAT). Treatment of 16HBE cells and Balb/c mice with ergosterol inhibited CSE-induced inflammatory and oxidative stress and apoptosis by inhibiting the activation of NF-κB/p65. Ergosterol suppressed apoptosis by inhibiting the expression of the apoptosis-related proteins both in vitro and in vivo. Moreover, the usage of QNZ (an inhibitor of NF-κB) also partly demonstrated that NF-κB/p65 pathway was involved in the ergosterol protective progress. These results show that ergosterol suppressed COPD inflammatory and oxidative stress and apoptosis through the NF-κB/p65 pathway, suggesting that ergosterol may be partially responsible for the therapeutic effects of cultured C. sinensis on COPD patients.

scholarly journals Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo

2020 ◽  
Vol 21 (21) ◽  
pp. 7876
Author(s):  
Andrey V. Markov ◽  
Aleksandra V. Sen’kova ◽  
Valeriya O. Babich ◽  
Kirill V. Odarenko ◽  
Vadim A. Talyshev ◽  
...  
Keyword(s):  
Acute Inflammation ◽  
Nuclear Factor Κb ◽  
Raw264.7 Cells ◽  
Migration Activity ◽  
Akt Phosphorylation ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory ◽  
And Migration

Plant-extracted triterpenoids belong to a class of bioactive compounds with pleotropic functions, including antioxidant, anti-cancer, and anti-inflammatory effects. In this work, we investigated the anti-inflammatory and anti-oxidative activities of a semisynthetic derivative of 18βH-glycyrrhetinic acid (18βH-GA), soloxolone methyl (methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate, or SM) in vitro on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and in vivo in models of acute inflammation: LPS-induced endotoxemia and carrageenan-induced peritonitis. SM used at non-cytotoxic concentrations was found to attenuate the production of reactive oxygen species and nitric oxide (II) and increase the level of reduced glutathione production by LPS-stimulated RAW264.7 cells. Moreover, SM strongly suppressed the phagocytic and migration activity of activated macrophages. These effects were found to be associated with the stimulation of heme oxigenase-1 (HO-1) expression, as well as with the inhibition of nuclear factor-κB (NF-κB) and Akt phosphorylation. Surprisingly, it was found that SM significantly enhanced LPS-induced expression of the pro-inflammatory cytokines interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW264.7 cells via activation of the c-Jun/Toll-like receptor 4 (TLR4) signaling axis. In vivo pre-exposure treatment with SM effectively inhibited the development of carrageenan-induced acute inflammation in the peritoneal cavity, but it did not improve LPS-induced inflammation in the endotoxemia model.

scholarly journals Mitochondrial pathogenic mechanism and degradation in optineurin E50K mutation-mediated retinal ganglion cell degeneration

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Myoung Sup Shim ◽  
Yuji Takihara ◽  
Keun-Young Kim ◽  
Takeshi Iwata ◽  
Beatrice Y. J. T. Yue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Open Angle Glaucoma ◽  
Mitochondrial Fission ◽  
Retinal Ganglion ◽  
Cell Degeneration ◽  
Transport Dynamics

Abstract Mutations in optineurin (OPTN) are linked to the pathology of primary open angle glaucoma (POAG) and amyotrophic lateral sclerosis. Emerging evidence indicates that OPTN mutation is involved in accumulation of damaged mitochondria and defective mitophagy. Nevertheless, the role played by an OPTN E50K mutation in the pathogenic mitochondrial mechanism that underlies retinal ganglion cell (RGC) degeneration in POAG remains unknown. We show here that E50K expression induces mitochondrial fission-mediated mitochondrial degradation and mitophagy in the axons of the glial lamina of aged E50K−tg mice in vivo. While E50K activates the Bax pathway and oxidative stress, and triggers dynamics alteration-mediated mitochondrial degradation and mitophagy in RGC somas in vitro, it does not affect transport dynamics and fission of mitochondria in RGC axons in vitro. These results strongly suggest that E50K is associated with mitochondrial dysfunction in RGC degeneration in synergy with environmental factors such as aging and/or oxidative stress.

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