• Journal of Korean Medicine Rehabilitation
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• v.30 no.1
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• pp.47-61
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• 2020

Objectives This study is carried out to investigate the effects of Lonicera japonica in wound-induced rats. Methods Rats were divided into 5 groups; normal (Nor), control (Veh), positive comparison (PC), Lonicera japonica 100 mg/kg (LL), Lonicera japonica 200 mg/kg (LH), each n=8. Total polyphenol and flavonoid were quantified. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3 ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radical scavenging activation were measured. Reactive oxygen species (ROS) was measured in serum. Antioxidant factors and inflammatory factors were measured in skin tissue, and also hydroxyproline content. Skin tissue was analyzed by Hematoxylin & Eosin and Masson's trichrome staining method. Results Total polyphenol and flavonoid were 32.86±0.14 mg/g and 67.17±0.57 mg/g. The IC₅₀ values of DPPH and ABTS free radical scavenging activation were 26.69±1.50 ㎍/mL and 49.33±4.52 ㎍/mL. ROS was significantly lower in LL and LH groups. Nuclear factor-erythroid 2-related factor 2 (Nrf2) was significantly higher in LH group and higher in LL group but not significant. Superoxide dismutase 1 (SOD-1), catalase, and heme oxygenase 1 (HO-1) were significantly higher in LL and LH groups. Nuclear factor kappa-B p65 (NF-κBp65), phosphorylated iκBα (p-iκBα), cyclooxygenase 2 (COX-2), and tumor necrosis factor alpha (TNF-α) were significantly lower in LL and LH groups. Hydroxyproline was significantly higher in LL and LH groups. The histopathologic analysis showed that skin tissue had recovered further more in LL and LH groups than in Veh group. Conclusions These results suggest that Lonicera japonica has the anti-oxidant, anti-inflammatory and healing effects in wound-induced rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.41 no.9
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• pp.1226-1234
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• 2012

3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.212-219
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• 2022

Recently, the efficacy of probiotics in treatment of neurodegenerative disorders has been reported in animal and clinical studies. Here, we assessed the effects of Bacillus coagulans JA845 in counteracting the symptoms of D-galactose (D-gal)/AlCl₃-induced Alzheimer's disease (AD) in a mice model through behavioral test, histological assessment and biochemical analysis. Ten weeks of pre-treatment with B. coagulans JA845 prevented cognitive decline, attenuated hippocampal lesion and protected neuronal integrity, which demonstrated the neuroprotective features of B. coagulans JA845 in vivo. We also found that supplementation of B. coagulans JA845 alleviated amyloid-beta deposits and hyperphosphorylated tau in hippocampus of D-gal/AlCl₃-induced AD model mice. Furthermore, B. coagulans JA845 administration attenuated oxidative stress and decreased serum concentration of inflammatory cytokines by regulating the Nrf2/HO-1 and MyD88/TRAF6/NF-κB pathway. Our results demonstrated for the first time that B. coagulans has the potential to help prevent cognitive decline and might be a novel therapeutic approach for the treatment of neurodegenerative diseases.

• Journal of Acupuncture Research
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• v.32 no.1
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• pp.1-11
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• 2015

Objectives : This study was performed to inquire into the protective effects of acupuncture on oxidative stress caused by cadmium accumulation in the kidney. Methods : Sprague-Dawley male($150{\pm}30g$) rats were stabilized for 1 week and divided into 5 groups: normal, control, $LR_3$ acupuncture, $BL_{23}$ acupuncture and sham acupuncture. For three days experimental groups received oral doses of cadmium 2 mg/kg twice a day. Acupuncture was applied bilaterally at each point 10 times for two weeks. The depth of stimulation was 1 mm at right angles and torsion of acupuncture was produced 2 times per second for 1 minute. The kidneys were extracted and weighed after two weeks, and renal function was confirmed through blood urea nitrogen(BUN). We measured reactive oxygen species of the serum and kidney, and compared expression levels of superoxide dismutase(SOD), catalase, glutathione peroxidase(Gpx), nuclear factor erythroid derived 2-related factor 2(Nrf-2), heme oxygenase-1(HO-1), nuclear factor-${\kappa}B$(NF-${\kappa}B)$, cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), Bax and Cytochrome c. Results : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly increased kidney weight, and decreased BUN compared to control group. In terms of oxidative stress, the $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly reduced reactive oxygen species compared to the control group. Conclusions : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced showed the effects of antioxidant, anti-inflammatory and apoptosis protection. The $BL_{23}$ acupuncture group was more effective than $LR_3$ acupuncture group.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.53 no.1
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• pp.123-131
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• 2020

In this study, we investigated the protective effects of a Neutrase enzymatic hydrolysate derived from Korea pen shell Atrina pectinata (APN) against hydrogen peroxide (H₂O₂)-induced oxidative damage in hepatocytes. First, we confirmed that APN has antioxidant activities by scavenging 2,2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid radical (ABTS⁺) and H₂O₂ and increasing oxygen radical absorbance capacity (ORAC) value. Also, the treatment of APN increased the cell viability by reducing the intracellular reactive oxygen species (ROS) production in H₂O₂-stimulated hepatocytes. In addition, APN decreased the sub-G₁ DNA contents and the apoptotic body formation increased by H₂O₂ stimulation. Moreover, APN modulated the protein expression of apoptosis related molecules (Bcl-2, Bax and p53) by suppressing the activation of nuclear factor NFkB and ERK/p38 signaling in H₂O₂-stimulated hepatocytes. Furthermore, APN led to the activation of Nrf2/HO-1signaling known as antioxidant systems. These results suggest APN protects hepatocytes against oxidative damages caused by H₂O₂ stimulation.

• Microbiology and Biotechnology Letters
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• v.43 no.3
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• pp.280-285
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• 2015

Anti-oxidative and anti-inflammatory activities of Cotoneaster horizontalis Decne ethanol extract (CHEE) were evaluated. CHEE possessed a potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl, which was similar to the activity of ascorbic acid which was used as a positive control. CHEE also effectively suppressed hydrogen peroxide-induced reactive oxygen species on RAW 264.7 cells. Furthermore, CHEE induced the expression of the anti-oxidative enzyme heme oxygenase 1, and its upstream transcription factor, nuclear factor-E2-related factor 2. CHEE inhibited LPS induced nitric oxide (NO) formation as a consequence of inducible NO synthase (iNOS) down regulation. Taken together, these results provide us with an important new insight; that C. horizontalis possesses anti-oxidative and anti-inflammatory activities. Therefore, C. horizontalis may be utilized as a promising material in the field of nutraceuticals.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2022.09a
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• pp.114-114
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• 2022

Excessive endogenous endotoxin, especially lipopolysaccharide (LPS) reflux from gastrointestinal (GI) tract to the liver tissue is one of the most serious reasons of severe and acute liver injury which is mainly mediated by Kupffer cell activations. However, there is no clear molecular clues to explain the exact pathophysiological mechanism and effective drugs available till nowadays. We aimed to comprehend the pathophysiological features of LPS-induced liver injury and evaluate the efficacies of potential therapeutic drug, Ga-mi-Yuk-Mi-Jihwang-Tang (GYM), which is composed of herbal plants. GYM remarkably caused to normalize hepatic inflammation and oxidations against LPS-induced liver injury by evidence of serum liver enzymes, histopathological analysis, both hepatic protein and gene expression levels of pro-inflammatory cytokines, nitric oxide levels, and hepatic tissue levels of reactive oxygen species (ROS) levels, malondialdehyde (MDA), and 4-hydroxyneoneal, respectively. To assess molecular events in the hepatic tissue, we further found hepatic Sirtuin6 (Sirt6) levels were considerably depleted by LPS injection with aberrant alterations of Nrf2/HO-1 signaling pathways, whereas administration with GYM notably exerted to normalize these abnormalities. Our results exhibited that GYM would be one of target drug to diminish hepatic inflammation as well as oxidative stress by regulation of hepatic Sirt6 levels.

• Molecules and Cells
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• v.42 no.4
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• pp.292-300
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• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• The Journal of Internal Korean Medicine
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• v.42 no.1
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• pp.1-10
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• 2021

Objective: This study was conducted to investigate the effect of Chaenomelis Fructus (CF) water extract on thioacetamide (TAA)-treated rats. Methods: Rats were divided into five groups: one normal group (n=8) and four with TAA-induced hepatic injury. These treatment groups were administered distilled water (n=8); silymarin 100 mg/kg (n=8); CF 100 mg/kg (n=8); and CF 200 mg/kg (n=8). In the TAA groups, the acute liver injury was induced via IP injection (200 mg/kg), and the silymarin and CF extract were then orally administered for three days. Subsequently, serum levels of GOT, GPT, and ammonia were confirmed as well as protein expressions using liver tissue. Results: In the liver injury-induced rats, CF administration reduced tissue damage and serum levels of GOT, GPT, and ammonia. In addition, CF increased the anti-oxidant proteins Nrf2, Keap1, HO-1, and catalase and significantly regulated matrix metalloproteinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). Conclusions: In this animal model of liver injury induced by TAA, CF extract is determined to have a hepatoprotective effect by increasing anti-oxidant proteins that relieve damage and by regulating the expression of matrix metalloproteinases.