• Korean Journal of Food Science and Technology
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• v.53 no.5
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• pp.544-552
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• 2021

This study investigated the anti-fibrotic and antioxidant effects of Paeonia Radix Alba water extract (PR) on thioacetamide (TAA)-induced liver fibrosis in a mouse model and its underlying mechanisms. Liver fibrosis was induced by intraperitoneal injection of TAA (three times a week) for 8 weeks. Furthermore, silymarin (50 mg/kg body weight) and PR (200 mg/kg body weight) were administered for 8 weeks. PR treatment downregulated aspartate aminotransferase (AST), alanine aminotransferase (ALT), ammonia, and myeloperoxidase levels. Moreover, PR treatment downregulated NOX2 and p47phox and upregulated antioxidant enzymes by activating the Nrf2/Keap1 signaling pathway. Furthermore, PR inhibited the factors associated with fibrosis, such as α-SMA and collagen I. AMPK/SIRT1 was upregulated by PR treatment. Overall, these results suggest that PR attenuates liver fibrosis by regulating the Nrf2/Keap1 and AMPK/SIRT1/NF-κB signaling pathways through the inhibition of oxidative stress. Hence, PR has potential as a remedy for preventing and treating liver fibrosis.

• Journal of Neurogastroenterology and Motility
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• v.24 no.4
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• pp.656-668
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• 2018

Background/Aims MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. Methods We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. Results The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. Conclusions This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

• Journal of Nutrition and Health
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• v.52 no.2
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• pp.139-148
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• 2019

Purpose: Ulcerative colitis is a common inflammatory bowel disease. Prolonged colitis can be a risk factor for the development of colorectal cancer. Mulberry twig (MT, Sangzhi), a dry branch of Morus alba L., which is widely distributed throughout East Asia, has been shown to have anti-inflammatory activities in the cells. However, the effects of MT extracts on colitis in in vivo are limited. Therefore, in this study, we investigated the anti-inflammatory effects of MT extracts in the dextran sulfate sodium (DSS)-induced mouse colitis model. Methods: Six week-old, male ICR mice were divided into 3 groups: Control (n = 5), DSS (n = 7), and DSS+MT (n = 7) groups. Mice in the DSS and DSS+MT groups were administrated 3% DSS in drinking water for 5 days to induce colitis. At the same time, water extracts of MT (5 g/kg body weight/day) were orally administered to mice in the DSS+MT groups for 5 days. Results: The MT extracts significantly reduced the clinical and pathological characteristics of colitis. Disease activity index, mucosal thickness, and colonocyte proliferation were significantly reduced in the DSS+MT group compared with the DSS group. Furthermore, MT administration reduced the levels of plasma $TNF-{\alpha}$, IL-6, and the colonic myeloperoxidase activity as well as mRNA expression of $TNF-{\alpha}$, IL-6, Cox-2, and iNOS. Conclusion: Taken together, these results suggest that MT water extracts have potent anti-colitis activities in the mouse colitis model.

• Korean Journal of Pharmacognosy
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• v.50 no.1
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• pp.37-45
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• 2019

Portulaca oleracea L. (PL) has been used in traditional medicine herb for treatment of various diseases, such as diarrhea, dysentery, and skin inflammation. Previous studies have shown that the PL regulates the inflammation by inhibition of pro-inflammatory cytokines. Although PL might have improvement effects of intestinal function and bioactive effects, there are not enough studies to demonstrate. This study investigated the effects of KDC16-2 on the improvement of intestinal function and anti-inflammatory effects in vivo and in vitro. The improvement effect of intestinal function was measured fecal amount, water content and intestinal transit rate in KDC16-2 treated ICR mice. As results, compared with the control group, the KDC16-2 group showed a significant increase in wet fecal weight, dry fecal weight and fecal water content. The intestinal transit rate of KDC16-2 group was significantly increased. Based on the results, KDC16-2 is considered to have effects on improving intestinal function. The effect of anti-inflammatory demonstrated by using dextran sulfate sodium (DSS)-induced colitis mice. The mice were administered 3% DSS along with KDC16-2 (100, 300 mg/kg) for 14 days. DSS-induced colitis mice were significantly ameliorated in KDC16-2 treated group, including body weight loss, colon length shortening, tight junction protein of colon and histological colon injury. The levels of inflammatory mediators (IgG2a, IgA, C-reactive protein and Myeloperoxidase) and pro-inflammatory cytokines (tumor necrosis factor (TNF)-${\alpha}$, Interleukin (IL)-6) which are involved in inflammatory responses were increased in the DSS-treated group as compared to those in the control group, and the levels were significantly decreased in the KDC16-2 groups. In addition, we investigated the impact of KDC16-2 on lipopolysaccharide (LPS)-induced inflammatory responses in J774A.1 cells. KDC16-2 inhibited production of prostaglandin E2 (PGE2) and reactive oxygen species (ROS). These results suggested that the KDC16-2 could effectively alleviate the dysfunction of intestinal and inflammatory mediators. Thus, these KDC16-2 can be potentially used as health functional food of intestinal.

• Journal of Nutrition and Health
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• v.54 no.4
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• pp.412-421
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• 2021

Purpose: Thioacetamide (TAA) produces reactive oxygen species (ROS) in the liver, and the generated ROS induces liver injury through inflammatory reactions. The current study was undertaken to investigate the hepatoprotective effect of Artemisiae Capillaris Herba water extract (AC), imparted via its antioxidant activity, in an animal model of TAA-induced liver injury. Methods: Animal experiments were conducted in 5 groups: normal, control (TAA 200 mg/kg), SM (TAA 200 mg/kg + silymarin 100 mg/kg), ACL (TAA 200 mg/kg + AC 100 mg/kg), ACH (TAA 200 mg/kg + AC 200mg/kg). TAA (intraperitoneal) and treatment compounds (per oral) were administered for 3 days. Serum levels of ammonia concentration and myeloperoxidase (MPO) activity were subsequently measured. Liver tissues were subjected to western blot analysis for measuring the oxidative stress (NADPH oxidase), anti-oxidative activity (Nrf2, heme oxygenase-1 [HO-1], superoxide dismutase [SOD], catalase, and GPx-1/2), tissue inhibitors of metalloproteinase (TIMP)-1, and matrix metalloproteinases (MMPs) protein expressions. Results: Serum ammonia levels and MPO activity were significantly increased in the TAA-induced control group, whereas groups administered AC treatment showed markedly reduced levels. Western blot analysis revealed significantly increased NOX2 and p22^phox expressions, (oxidative stress-related factors) in the TAA-induced control group. These levels were determined to be significantly decreased after AC exposure. Moreover, antioxidant-related factors including Nrf2, HO-1, SOD, catalase, and GPx-1/2 were significantly decreased in the control group and increased in the AC treated groups. In addition, MMP expressions were significantly suppressed in the AC treatment group due to increased levels of TIMP-1. Conclusion: Taken together, these data indicate that exposure to AC reduces the oxidative stress by inhibiting the expression of NADPH oxidase (NOX2 and p22^phox) through the Nrf2 signaling pathway. We therefore propose the potential of AC for the prevention and treatment of TAA-induced liver injury.

• Korean Journal of Food Science and Technology
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• v.54 no.3
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• pp.288-296
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• 2022

This study aimed to verify the effect of Citrus unshiu peel water extract (CUP) on a mouse model of acute gastritis (AG) induced by HCl/ethanol. Several studies have found that CUP has anti-inflammatory effects. The AG model was induced by oral administration of 150 mM HCl/60% ethanol (550 µL) to all groups except the control group. Also, for drug treatment, sucralfate (10 mg/kg) and CUP (100 or 200 mg/kg) were orally administered for 90 minutes before induction. The effect of CUP treatment was confirmed by gross gastric mucosal damage measurement, and the levels of Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT), and myeloperoxidase were reduced as well as the levels of oxidative stress biomarkers and their related proteins. In addition, the levels of inflammatory proteins, mediators, and cytokines were significantly downregulated byPI3K/Akt signaling. Taken together, these results show that CUP treatment alleviates AG by regulating PI3K/Akt signaling.

• The Korea Journal of Herbology
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• v.29 no.3
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• pp.11-17
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• 2014

Objective : Portulaca oleracea (PO) has been used as an important traditional medicine for inflammatory and bacterial diseases in East Asia. However, the protective effects of PO on acute pancreatitis (AP) is not well-known. Therefore, this study was performed to identify the anti-inflammatory and prophylactic effects of PO on cerulein-induced AP. Methods : AP was induced in mice via intraperitoneal injection of supramaximal concentrations of the stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) given every hour for 6 times. Water extracts of PO (100, 300, or 500 mg/kg) was administrated intra-peritoneally 1 h prior to the first injection of cerulein. The mice were killed at 6 h after the final cerulein injection. Pancreas and lung were rapidly removed for morphologic and histochemical examination, myeloperoxidase (MPO) assay. Blood samples were taken to determine serum amylase and lipase activities. Results : Administration of PO significantly inhibited pancreatic weight/body weight ratio, pancreas and lung histological injury. And MPO activity which indicates neutrophil infiltration was inhibited by PO extracts on cerulein-induced pancreatitis. In addition, PO administration inhibited digestive enzymes such as serum amylase and lipase activity on cerulein-induced pancreatitis. Conclusion : Our results could suggest that pre-treatment of PO reduces the severity of cerulein-induced AP, thereby, PO could be used as a protective agent against AP. Also, this study could give a clinical basis that PO could be a drug or agent to prevent AP.

• The Korea Journal of Herbology
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• v.34 no.1
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• pp.75-80
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• 2019

Objectives : Dictamni Radicis Cortex (DRC) has been used as an important traditional medicine for inflammation and fungal diseases. However, the protective effect of DRC water extract on acute pancreatitis (AP) has not been deeply reported. Therefore, we aimed to evaluate the protective effects of DRC water extract on cerulein-induced AP. Methods : AP was induced via intraperitoneal injection of supramaximal concentrations of stable cholecystokinin analogue cerulein ($50{\mu}g/kg$) every hour for 6 times. DRC water extract (0.05, 0.1, or 0.2 g/kg) or saline was administrated intraperitoneally 1 h before to the first injection of cerulein. The mice were sacrificed at 6 h after the final cerulein injection. Pancreas was rapidly removed for histochemical examination and myeloperoxidase (MPO) assay. In addition, polymerase chain reaction (PCR) was performed to examine mRNA levels of proinflammatory cytokines such as Interleukin $(IL)-1{\beta}$, IL-6 and Tumor necrosis factor $(TNF)-{\alpha}$. Results : Administration of DRC water extract significantly inhibited the pancreatic weight to body weight ratio, pancreas histological damages and increase of pancreatic MPO activity during cerulein-induced AP. In addition, increased pancreatic mRNA levels of $IL-1{\beta}$, IL-6 but not $TNF-{\alpha}$ were significantly inhibited by treatment of DRC water extract against cerulein-induced AP. Conclusions : In conclusion, we have revealed that pre-treatment of DRC water extract reduces the severity of cerulein-induced AP. Accordingly, our results could give a clinical basis that DRC could be used as a drug or agent to prevent AP.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Fisheries and Aquatic Sciences
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• v.26 no.12
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• pp.726-737
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• 2023

Piperine, the main bioactive component of black pepper (Piper nigrum Linn.), has anti-inflammatory, antifungal, and antibacterial properties. This study evaluated the supplemental effects of piperine or black pepper on innate immunity, growth, feed utilization efficiency, and intestinal morphology in red seabream (Pagrus major). Six experimental diets were formulated, supplementing piperine at 0.0, 0.25, 0.5, 1.0, and 2.0 g/kg levels (Con, P25, P50, P100, and P200) or 1.0 g/kg black pepper (BP100). Juvenile fish (7.6 ± 0.1 g) were randomly stocked into 18 circular tanks (220 L), including 30 fish per tank. Each diet was randomly assigned to triplicate groups, and the feeding trial was conducted for 8 weeks. The results showed that final body weight, specific growth rate, weight gain, and feed utilization efficiency were significantly improved (p < 0.05) when piperine was supplemented into diets at 0.25-2.0 g/kg levels compared to the Con group. Compared to the Con diet, condition factor was significantly increased (p < 0.05) in fish fed with dietary piperine at 0.25-2.0 g/kg or BP100 diet. Serum myeloperoxidase activity was increased (p < 0.05) in P25 and P100 groups and antiprotease activity was increased (p < 0.05) in P100 group compared to the Con group. Significantly higher (p < 0.05) lysozyme activity was observed in P50, P100, P200 and BP100 groups, while total immunoglobulin level was increased in P50, P100 and BP100 groups than Con group. Superoxide dismutase activity was increased (p < 0.05) by dietary piperine at 0.25-2.0 g/kg levels and BP100 diet compared to Con diet. Plasma cholesterol was significantly lower (p < 0.05) in fish fed with piperine (0.5-2.0 g/kg) or BP100 compared to the Con diet. Compared to the Con diet significantly longer (p < 0.05) intestinal villi were observed in fish fed with piperine at 0.25-1.0 g/kg levels, and higher goblet cell count was observed in P25 and BP100 groups. Dietary inclusion of piperine would be a potent immunostimulant in fish diet and the optimum supplementation level would be 0.25-1.0 g/kg.