Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD resulted in irreversible ...vision loss and blindness with no available treatment options. However, there have been breakthrough advances in the drug development of anti-angiogenic biological agents over the last two decades. The primary target molecule for treating nAMD is the vascular endothelial growth factor (VEGF), and there are currently several anti-VEGF drugs such as bevacizumab, ranibizumab, and aflibercept, which have made nAMD more manageable than before, thus preventing vision loss. Nevertheless, it should be noted that these anti-VEGF drugs for nAMD treatment are not effective in more than half of the patients, and even those who initially gain visual improvements lose their vision over time, along with potential deterioration in the geography of atrophy. As a result, there have been continuous endeavors to improve anti-VEGF agents through better efficacy, fewer doses, expanded intervals, and additional targets. This review describes past and current anti-VEGF therapeutics used to treat nAMD and outlines future directions to improve the effectiveness and safety of anti-VEGF agents.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The present study evaluated the effects of acid-treated rutin on hyperlipidemia and obesity in high-fat diet (HFD)-induced obese mice. The mice consumed a HFD with or without acid-treated rutin for 7 ...weeks. Body weight gain considerably decreased, by approximately 33%, in the acid-treated rutin (AR) and quercetin (Q) groups compared to that in the HFD group. The adipocytes' size in epididymal fat in AR and Q groups was significantly reduced compared to that in the HFD group (
< 0.05). Treatment with AR decreased the levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol compared to the HFD group. In particular, administration of AR significantly decreased serum triglyceride (36.82 mg/dL) by 46% compared to HFD (69.30 mg/dL). The AR group also showed significantly decreased atherogenic indices and cardiac risk factors. These results suggest that deglycosylated rutin generated by acid treatment enhances the anti-obesity and hypolipidemic effects in obese mice, and provides valuable information for improving the functional properties of glycosidic flavonoids.
Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced lung fibrosis, is the most common side effect of radiation therapy. RILI is a complicated ...process that causes the accumulation, proliferation, and differentiation of fibroblasts and, finally, results in excessive extracellular matrix deposition. Currently, there are no approved treatment options for patients with radiation-induced pulmonary fibrosis (RIPF) partly due to the absence of effective targets. Current research advances include the development of small animal models reflecting modern radiotherapy, an understanding of the molecular basis of RIPF, and the identification of candidate drugs for prevention and treatment. Insights provided by this research have resulted in increased interest in disease progression and prognosis, the development of novel anti-fibrotic agents, and a more targeted approach to the treatment of RIPF.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
In this study, the cytoprotective effect of gamma‐aminobutyric acid (GABA) via inducing phase II enzymes in C2C12 myoblasts was evaluated. The highest concentration of GABA (100 μM) significantly ...increased the cell viability by approximately 90% in hydrogen peroxide‐induced C2C12 cells. The treatment with GABA (100 μM) effectively decreased the glutathione (GSH) depletion and the activities of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). And, reactive oxygen species (ROS) levels were effectively reduced by about 50% in GABA‐treated cells. In addition, the protein expression of phase II enzymes, such as NADPH:quinone oxidoreductase 1 and heme oxygenase‐1 was significantly increased by GABA treatment. Moreover, GABA treatment increased the nuclear factor erythroid 2‐related factor 2 (Nrf2) protein expression in the nucleus of C2C12 myoblasts. Altogether, the results in this study indicate that GABA possesses the cytoprotective effects against oxidative insults by regulating the GSH levels, CAT and SOD activities, ROS scavenging activities, and expression of phase II enzymes through the activation of Nrf2 in C2C12 cells. Hence, this study suggests that the GABA supplementation could be effective in alleviating oxidative stress‐induced muscle damage.
Practical applications
GABA exists in the germ and bran layers of rice and is well‐known as the inhibitory neurotransmitter in the central nervous system. GABA also has various health beneficial effects, such as preventing chronic alcohol‐related diseases and lowering blood pressure. The present study shows the cytoprotective effect of GABA against oxidative stress in C2C12 myoblasts, and suggests that GABA has great potential as a functional food ingredient for attenuating oxidative stress‐induced muscle damage.
This study showed that GABA possesses the cytoprotective effects against oxidative insults by regulating GSH levels, CAT and SOD activities, ROS scavenging activities, and expression of phase II enzymes through activation of Nrf2 in C2C12 cells. Therefore, this study suggest that GABA supplementation could be effective in alleviating oxidative stress‐induced muscle damage.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cathepsin S (CTSS), a lysosomal protease, belongs to a family of cysteine cathepsin proteases that promote degradation of damaged proteins in the endolysosomal pathway. Aberrant CTSS expression and ...regulation are associated with the pathogenesis of several diseases, including lung diseases. CTSS overexpression causes a variety of pathological processes, including pulmonary fibrosis, with increased CTSS secretion and accelerated extracellular matrix remodeling. Compared to many other cysteine cathepsin family members, CTSS has unique features that it presents limited tissue expression and retains its enzymatic activity at a neutral pH, suggesting its decisive involvement in disease microenvironments. In this review, we investigated the role of CTSS in lung disease, exploring recent studies that have indicated that CTSS mediates fibrosis in unique ways, along with its structure, substrates, and distinct regulation. We also outlined examples of CTSS inhibitors in clinical and preclinical development and proposed CTSS as a potential therapeutic target for pulmonary fibrosis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this study, we investigated the cytoprotective effects of acid-treated sesame leaf extracts against oxidative damage in HepG2 cells. Treatment with 0.1 M HCl of sesame leaves significantly ...increased their verbascoside content (4.398 g/100 g) compared to non-acid-treated leaves (3.950 g/100 g). Acid-treated sesame leaf extract (ASLE) showed no cytotoxicity in HepG2 cells. ASLE conferred a greater cytoprotective effect against oxidative insult than a methanol extract of sesame leaves (SLE), verbascoside, and a vehicle control group. ASLE treatment also significantly inhibited reactive oxygen species generation in response to oxidative stress. Treatment with tert-butyl hydroperoxide increased malondialdehyde (MDA) levels, and depleted reduced glutathione (GSH). However, ASLE treatment significantly ameliorates this MDA and GSH depletion. Moreover, ASLE increased the activities of antioxidant enzymes including catalase, glutathione reductase, and glutathione peroxidase. Phenolic compounds in ASLE and SLE were characterized using UPLC-Q-TOF/MS analysis. A total of 29 iridoid and phenol compounds were tentatively identified in ASLE, and 27 compounds were observed in SLE. These results suggest that acid treatment of sesame leaves enhances the protective effects of their extract against oxidative stress by modulating antioxidant enzymes in HepG2 cells.
•Esculetin inhibited lipid accumulation and the expression of adipogenic specific proteins.•Esculetin increased phosphorylation of AMPK and acetyl-CoA carboxylase.•Pretreatment with AMPK inhibitor ...abolished the inhibitory effects of esculetin on PPARγ expression.•Esculetin has anti-adipogenic effects through modulation of PPARγ and C/EBPα via the AMPK signaling pathway.
Obesity is one of the most serious health problems in both Westernized and developing countries. AMP-activated protein kinase (AMPK) has emerged as a major regulator of appetite, body weight, and cellular energy balance. In this study, we investigated the effect of esculetin (ECT) on adipogenesis via activation of AMPK in 3T3-L1 cells. ECT markedly inhibited lipid accumulation and suppressed the expression of adipogenic specific proteins including peroxisome proliferator-activated receptors (PPARγ), CCAAT/enhancer binding protein a (C/EBPα), and adipocyte fatty acid binding protein (aP2). Moreover, ECT significantly increased phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and intracellular reactive oxygen species (ROS) production. However, pretreatment with compound C, a specific AMPK inhibitor, abolished the inhibitory effects of ECT on PPARγ and C/EBPα expression. Therefore, these results indicate that ECT has anti-adipogenic effects through modulation of PPARγ and C/EBPα via the AMPK signaling pathway.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of this study was to investigate the effects of different cooking methods on the hepatoprotective effects of purple sweet potatoes against alcohol-induced damage in HepG2 cells. Purple sweet ...potatoes (Ipomeoea batatas L. Danjami) were subjected to different cooking methods, including steaming, roasting, and microwaving. Steaming resulted in a higher cytoprotective effect against alcohol damage than the other cooking methods. Additionally, the highest inhibition of glutathione depletion and production of reactive oxygen species against alcohol-induced stress were observed in raw and/or steamed purple sweet potatoes. Compared to roasted and/or microwaved samples, steamed samples significantly increased the expression of NADPH quinone oxidoreductase 1, heme oxygenase 1, and gamma glutamate-cysteine ligase in alcohol-stimulated HepG2 cells via the activation of nuclear factor erythroid 2-related factor 2. Moreover, ten anthocyanins were detected in the raw samples, whereas five, two, and two anthocyanins were found in the steamed, roasted, and microwaved samples, respectively. Taken together, steaming purple sweet potatoes could be an effective cooking method to protect hepatocytes against alcohol consumption. These results provide useful information for improving the bioactive properties of purple sweet potatoes using different cooking methods.
Morinda citrifolia
L. (Noni) has been widely used in traditional medicine in tropical zones and has become increasingly popular globally owing to its health benefits. Most noni fruits are consumed as ...juice, which is traditionally produced by the natural fermentation of noni fruits. In this study, the metabolic profiles of noni fruit juice (NJ1) and fermented noni fruit juices (NJ2 and NJ3) was compared. A total of 74, 83, and 91 compounds including anthraquinones, coumarins, flavonoids, phenolic acids, phenolics, terpenoids, and miscellaneous (acids, carbohydrates, vitamins, fatty acids, etc.) were tentatively identified from NJ1, NJ2, and NJ3 in both positive and negative electrospray ionization modes. The phenolic compound composition differed significantly between noni juice and fermented noni juice. The results of the unsupervised principal component analysis and hierarchical clustering analysis showed that the non-fermented juice group clustered with the fermented juice groups. Asperulosidic acid, isoasperulosidic acid, and rutin levels were higher in the NJ1 group than those in the NJ2 group. Deacetylasperulosidic acid and monotropein contents in NJ2 were higher than those in NJ1. Similarly, NJ1 had higher asperulosidic acid and isoasperulosidic acid than those in NJ3. The findings from this study have the potential to enhance the quality of fermented noni juice.
► Polymeric procyanidin fraction (PPF) was prepared from crude phenolic extract from defatted grape seeds. ► Cytoprotective activity of PPF was evaluated in HepG2 cell lines. ► Cellular generation of ...ROS, formation of malondialdehyde, and depletion of GSH were reduced by PPF pretreatment. ► Pretreatment with PPF modulated antioxidant enzyme activity.
Oligomeric and polymeric procyanidins have been reported to possess different antioxidant capacities. However, the intracellular antioxidant mechanisms of oligomeric and polymeric procyanidins are still poorly understood. In this study, we evaluated the cytoprotective effects of the oligomeric procyanidin fraction (OPF) and the polymeric procyanidin fraction (PPF) from grape seeds against the oxidative damage induced by tert-butyl hydroperoxide (TBHP) in HepG2 cells. The levels of cellular reactive oxygen species (ROS), cellular lipid peroxidation, glutathione (GSH), and antioxidant enzyme activities were measured as biomarkers of cellular oxidative status. HepG2 cells were treated with different concentrations of procyanidin samples (0–20μg/ml) for 6h prior to treatment with TBHP for 3h. The incubation of HepG2 cells with TBHP led to an approximately 60% decrease in cell viability. However, pretreatment of the cells with the samples, at 5–20μg/ml, rescued cell viability in a dose-dependent manner. Cellular generation of ROS, formation of malondialdehyde (MDA), and depletion of GSH were reduced by OPF and PPF. Moreover, TBHP treatment increased the activities of glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). However, a 6h pretreatment with each of the samples at 20μg/ml significantly decreased the activities of these enzymes. These results clearly showed that treatment with OPF and PPF protected against oxidative damage by modulating ROS production, GSH levels, MDA generation, and antioxidant enzyme activities in HepG2 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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