• BMB Reports
• /
• v.54 no.10
• /
• pp.528-533
• /
• 2021

Osteoarthritis (OA) is a degenerative disorder that can result in the loss of articular cartilage. No effective treatment against OA is currently available. Thus, interest in natural health products to relieve OA symptoms is increasing. However, their qualities such as efficacy, toxicity, and mechanism are poorly understood. In this study, we determined the efficacy of avenanthramide (Avn)-C extracted from oats as a promising candidate to prevent OA progression and its mechanism of action to prevent the expression of matrix-metalloproteinases (MMPs) in OA pathogenesis. Interleukin-1 beta (IL-1β), a proinflammatory cytokine as a main causing factor of cartilage destruction, was used to induce OA-like condition of chondrocytes in vitro. Avn-C restrained IL-1β-mediated expression and activity of MMPs, such as MMP-3, -12, and -13 in mouse articular chondrocytes. Moreover, Avn-C alleviated cartilage destruction in experimental OA mouse model induced by destabilization of the medial meniscus (DMM) surgery. However, Avn-C did not affect the expression of inflammatory mediators (Ptgs2 and Nos) or anabolic factors (Col2a1, Aggrecan, and Sox9), although expression levels of these genes were upregulated or downregulated by IL-1β, respectively. The inhibition of MMP expression by Avn-C in articular chondrocytes was mediated by p38 kinase and c-Jun N-terminal kinase (JNK) signaling, but not by ERK or NF-κB. Interestingly, Avn-C added with SB203580 and SP600125 as specific inhibitors of p38 kinase and JNK, respectively, enhanced its inhibitory effect on the expression of MMPs in IL-1β treated chondrocytes. Taken together, these results suggest that Avn-C is an effective candidate to prevent OA progression and a natural health product to relieve OA pathogenesis.

• Journal of Animal Reproduction and Biotechnology
• /
• v.34 no.1
• /
• pp.20-29
• /
• 2019

Soy isoflavones have been reported to possess many physiological activities such as antioxidant activity and inhibition of cancer cell proliferation. This study investigated the photoprotective effects of soybean extract in human fibroblast cell line and hairless mice model. Human fibroblast was treated with soybean extract before and after ultraviolet B (UVB; 290-302 nm) irradiation. In the soybean extract treated group, the cells showed better resistance to ultraviolet (UV) than control group. The amount of type I collagen recovered from the soybean treated group was higher than the vehicle group exposed to UV-induced damage. Moreover, increased expression of metalloproteinases-1 as a result of UV irradiation was suppressed by the soybean extract. Female mice were orally administered soybean extract and irradiated with UVB light for 8 weeks. The effects of the soybean extract on the skin appearance, collagen deposition and epidermal thickness in the UV-damaged mouse skin were analyzed using histopathological methods. In soybean extract treated group, the skin had a better morphology than that of the control group. Furthermore, the amount of type I collagen was increased and overexpression of MMP-1 was reduced in the soybean extract group compared to vehicle group. Additionally, up-regulation of pro-inflammatory cytokines induced by UV irradiation was suppressed by dietary soybean extract treatment. It appears that soybean extract had a photoprotective effect, including anti-aging and anti-inflammatory effect, from UV-induced damage in not only human fibroblast, but also hairless mice. We confirmed that these effects were possibly due to promotion of collagen synthesis and inhibition of MMP-1 expression.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.33 no.1
• /
• pp.56-62
• /
• 2019

To investigate the effect of Bombycis Corpus on male osteoporosis, we performed Dual Energy X-Ray Absorptiometry(DEXA) and histochemical methods. The animals were used ICR-based male mice of 8 weeks and 50 weeks, respectively. ICR male mice at 8 weeks were used in the control group, and ICR male mice at 50 weeks were used in aging group and Bombycis Corpus group(BC group). In the aging group, 0.5 ml of distilled water was administered once a day for 6 months. In BC group, Bombycis Corpus(0.78g/kg) was dissolved in distilled water for 6 months once a day. As a result, Bombycis Corpus decreased bone loss, increased bone density by reducing the loss of bone matrix in the femur due to aging, and increased osteoblast - induced osteopontin(OPN) and osteocalcin(OPC) positivite reaction. In addition, administration of Bombycis Corpus decreased Reaction of activation of nuclear factor kappa B ligand(RANKL) positive reaction, increased osteoprotegerin(OPG) positive reaction, and decreased matrix metalloproteinase-3(MMP-3) and 8-hydroxy-2'-deoxyguanosine(8-OHdG) positivite reaction. Taken together, Bombycis Corpus increases the activity of osteoblasts, inhibits osteoclast function, promotes osteoblast function, inhibits bone tissue degradation, and inhibits bone loss due to oxidative stress. It was observed that Bombycis Corpus reduced bone loss and increased bone density caused by aging to improve male osteoporosis. Therefore, Bombycis Corpus may be used as a preventive and therapeutic agent for male osteoporosis.

• Current Optics and Photonics
• /
• v.6 no.3
• /
• pp.227-235
• /
• 2022

To investigate the aging-related physiological functions of organic light-emitting diodes (OLEDs), we examined mRNA expression changes in aging-related genes due to oxidative stress inhibition by 630-nm red light OLEDs. As a result of irradiating 630-nm OLED with an intensity of 5 mW/cm² for 15 min, the viability of dermal fibroblasts significantly increased by 1.3-fold. In addition, reactive oxygen species generated by H₂O₂ were significantly reduced about 4.9-fold by irradiation with 630-nm OLED. Quantitative reverse-transcription polymerase chain reaction results showed that 630-nm OLEDs altered aging-related gene mRNA expression levels through antioxidant activity. The mRNA expression levels of matrix metalloproteinase1 (MMP1) and MMP9 decreased significantly, by about 2.2- and 2.5-fold, compared to the control group, whereas those of collagen, type I, and alpha 1 increased significantly, by 4.9-fold. The mRNA expression levels of cancer suppression genes p16 and p53 in dermal fibroblasts were also significantly reduced by 630-nm OLED irradiation, by about 1.4- and three-fold, respectively, compared to the control. Overall, it was confirmed that 630-nm OLED irradiation lowered the level of ROS formation induced by H₂O₂ in dermal fibroblasts, and that this antioxidant effect could regulate the mRNA expression levels of aging- and tumor suppression-related genes. This study shows a link between 630-nm OLED irradiation and anti-aging physiological functions such as antioxidant function, and suggests the potential of OLEDs as a useful light source for skin care.

• The Korea Journal of Herbology
• /
• v.38 no.1
• /
• pp.21-30
• /
• 2023

Objective : Gardeniae Fructus (GF) has bitter and cold nature. Thus, it has been traditionally prescribed in processed form roasted with ginger juice for patients with a weak stomach. This study investigated the effects of processed GF in tert-butyl hydroperoxide (tBHP)-treated gastric epithelial cells. Methods : Processed GF was made by applying 40% ginger juice or 10% ethanol for 24 h and then roasting at 150℃ for 5 minutes. Apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Mitochondrial membrane potential (MMP) was monitored by flow cytometry using the membrane permeable fluorescent dye Rh123. Protein expression was measured by Western blot analysis. Results : Cell viability was reduced by tBHP and restored by ethanol extract of GF (GFE). In the TUNEL assay, it was found that cell death by tBHP was due to apoptosis, and GFE had an anti-apoptotic effect. Processed GF roasted with ginger juice showed the best anti-apoptotic effect. Processed GF also inhibited MMP loss and restored tBHP-induced changes in expression levels of apoptosis-related proteins. Increased ROS production and GSH depletion after tBHP treatment were significantly reduced by processed GF. In addition, tBHP-induced activation of mitogen-activated protein kinase (MAPK) was inhibited by processed GF. Conclusion : These results demonstrate that the processed GF is able to protect gastric epithelial cells from oxidative stress-induced cell death with antiapoptotic and antioxidant activity. In addition, it shows that the processing of GF, which have been traditionally used for gastrointestinal protection, partially have scientific validity.

• Animal Bioscience
• /
• v.37 no.4
• /
• pp.640-654
• /
• 2024

Objective: The purpose of this study was to explore the effect of sodium salicylate (SS) on semen preservation and metabolic regulation in goats. Methods: Under the condition of low temperature, SS was added to goat semen diluent to detect goat sperm motility, plasma membrane, acrosome, antioxidant capacity, mitochondrial membrane potential (MMP) and metabonomics. Results: The results show that at the 8th day of low-temperature storage, the sperm motility of the 20 μM SS group was 66.64%, and the integrity rates of the plasma membrane and acrosome were both above 60%, significantly higher than those of the other groups. The activities of catalase and superoxide dismutase in the sperm of the 20 μM SS group were significantly higher than those of the control group, the contents of reactive oxygen species and malondialdehyde were significantly lower than those in the control group, the MMP was significantly higher than that in the control group, and the contents of Ca²⁺ and total cholesterol were significantly higher than those in the control group. Through metabonomics analysis, there were significant metabolic differences between the control group and the 20 μM SS group. Twenty of the most significant metabolic markers were screened, mainly involving five metabolic pathways, of which nicotinic acid and nicotinamide metabolic pathways were the most significant. Conclusion: The results indicate that SS can effectively improve the low-temperature preservation quality of goat sperm.

• The Korean Journal of Physiology and Pharmacology
• /
• v.28 no.3
• /
• pp.239-252
• /
• 2024

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

• BMB Reports
• /
• v.57 no.5
• /
• pp.244-249
• /
• 2024

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway.

• Oncology Reports
• /
• v.43 no.2
• /
• pp.625-634
• /
• 2020

While exploring new angiogenesis inhibitors from microbial metabolites, we recently isolated ahpatinins C, E, and G from a soil-derived Streptomyces sp. 15JA150. Ahpatinins C, E and G are known to have pepsin and renin inhibitory activities; however, their antiangiogenic activities and underlying molecular mechanisms have not been fully elucidated. In the present study, the antiangiogenic properties of ahpatinins C, E and G were investigated. The results revealed that the natural compounds significantly inhibited the vascular endothelial growth factor (VEGF)-induced proliferation, invasion, adhesion, and tube formation of human umbilical vein endothelial cells (HUVECs) without exhibiting any cytotoxicity. It was also revealed that ahpatinin E effectively suppressed the neovascularization of the chorioallantoic membranes in growing chick embryos. Notably, ahpatinins C, E, and G led to the downregulation of VEGF-induced activation of VEGF receptor 2 (VEGFR2) and its downstream signaling mediators, including AKT, ERK1/2, JNK, p38, and NF-κB, in HUVECs. Moreover, they reduced the expression of matrix metalloproteinase (MMP)-2 and MMP-9 in the HUVECs following stimulation with VEGF. Furthermore, ahpatinins C, E, and G reduced the tumor cell-induced invasion and tube forming abilities of HUVECs, as well as the expression of VEGF, by suppressing hypoxia-inducible factor-1α (HIF-1α) activity in U87MG glioblastoma cells. Collectively, the present findings indicated that ahpatinins C, E, and G may be used in anticancer therapy by targeting tumor angiogenesis through the inhibition of both VEGFR2 and HIF-1α pathways.

• The Korean Journal of Physiology and Pharmacology
• /
• v.71 no.1
• /
• pp.155-165
• /
• 2020

Ataxia telangiectasia (A-T) is an inherited neurodegenerative disease caused by mutation in the ataxia telangiectasia mutated (ATM) gene, leading to loss of function in the encoded protein ATM. Because ATM functions to reduce oxidative stress by up-regulating antioxidant enzymes, oxidative stress is a prevalent A-T phenotype and a mediator of the inflammation that drives A-T pathology. Reactive oxygen species (ROS) levels and the expression of pro-inflammatory cytokine interleukin-8 (IL-8) were higher in A-T cells than in normal cells. ROS are related to mitochondrial dysfunction and activation of nuclear factor kappa B (NF-κB) to induce IL-8 expression. Alpha-lipoic acid (α-LA), a naturally occurring thiol compound, shows an antioxidant effect in various cells. This study is aimed to determine if α-LA confers protection against NF-κB activation, IL-8 expression, and mitochondrial dysfunction in A-T cells which are exposed to the inflammatory cytokine IL-1β. A-T fibroblasts were treated with or without α-LA. The levels of intracellular and mitochondrial ROS, mRNA and protein levels of IL-8, mitochondrial membrane potential (MMP), ATP levels, and DNA binding activity of NF-κB were determined. As a result, IL-1β increased NF-κB activation, IL-8 expression, intracellular and mitochondrial ROS levels, but decreased MMP and ATP level in A-T cells. Pretreatment of A-T cells with α-LA inhibited IL-1β-induced activation of NF-κB, IL-8 expression, and mitochondrial dysfunction by reducing ROS levels. In conclusion, supplementation with α-LA may be beneficial for reducing the oxidative stress-induced mitochondrial dysfunction and IL-8 production associated with A-T.