• Food Science and Preservation
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• v.30 no.5
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• pp.797-810
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• 2023

Elaeagnus umbellata leaves have been reported to suppress inflammation, allergic responses, lung cancer proliferation and oral bacterial growth. Cadmium (Cd) is a heavy metal that has been found to cause many toxicities, including liver toxicity. The aim of this study was to evaluate the capacity of 70% ethanol extract of E. umbellata leaves (EUL) to protect human hepatocytes from Cd toxicity. After exposure of HepG2 cells to Cd at 10 𝜇M for 24 h, cell viability, expression levels of apoptosis- and antioxidant-related proteins, reactive oxygen species (ROS) accumulation and Cd uptake were assessed. EUL protected HepG2 cells from Cd-induced apoptosis as determined by MTT assay. A decrease in caspase-3 and p-p53 protein levels was observed in cells pretreated with EUL prior to Cd exposure. Furthermore, the Cd-induced increase in intracellular DCF fluorescence was attenuated by EUL, indicating that the Cd-induced apoptosis preventing effect was associated with the suppression of ROS accumulation. Moreover, EUL's effects on the inhibition of p38, JNK, and AKT phosphorylation also appear to be associated with protection against Cd toxicity. Moreover, EUL upregulated Cd-depressed expression of Nrf2, HO-1, catalase, and MT-1,2 proteins, suggesting that Cd uptake-induced apoptosis in HepG2 cells may be inhibited by EUL's antioxidative potential.

• The Korea Journal of Herbology
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• v.35 no.4
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• pp.25-36
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• 2020

Objective : Reflux esophagitis is a disease caused by the reflux of gastric acid and inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of Phellodendri Cortex (PC) on chronic reflux esophagitis (CRE) in rats. Methods : The anti-oxidant activity of PC was measured by total polyphenol, total flavonoid contents, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), and 2, 2'-azinobis-3-ethyl-enzothiazoline-6-sulfonic acid (ABTS) radical scavenging activity. A CRE was established surgically in SD rats. And then CRE rats were treated with water or PC 200 mg/kg body weight for 14 days. Besides, the anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : PC reduced esophagus tissues injury. The total polyphenol (36.05 ± 0.25 mg/g) and total flavonoid (72.90 ± 0.61 mg/g) of PC showed a high content. PC strongly reduced radical scavenging activities (DPPH IC₅₀ 43.58 ± 1.54 ㎍/㎖; ABTS IC₅₀ 36.75 ± 0.35 ㎍/㎖). Moreover, reactive oxygen species (ROS) and peroxynitrite (ONOO^-) levels in serum, the protein expression of inducible nitric oxide synthases (iNOS) were significantly reduced. In addition, the protein expression of NADPH oxidases related to oxidative stress were significantly reduced in PC compared to CRE control. PC effectively reduced inflammatory factors including, TNF-α, and IL-6 via NF-κBp65 inactivation through the inhibition of p-IκBα and increased anti-oxidant enzyme such as HO-1, SOD, catalase, and GPx-1/2 via Nrf2 activation. Conclusions : Taken together, these results show that PC can alleviate the esophageal mucosal ulcer though the inhibition of NF-κB inflammatory and the enhancement of Nrf2 anti-oxidant pathway.

• The Journal of Internal Korean Medicine
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• v.42 no.1
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• pp.11-24
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• 2021

Objective: Chronic reflux esophagitis (CRE), characterized by esophageal mucosa ulcer, is caused by continuous backflow of gastric acid and consequent inflammation due to unstable gastroesophageal sphincter. The aim of the present study was to clarify the effect of an Arecae Semen and Coptidis Rhizoma mixture (AC-mix) on CRE. Methods: CRE was surgically induced in SD rats with three experimental groups used: normal; CRE control; and CRE treatment (200 mg/kg AC-mix). Blood and esophageal tissue were collected after two weeks of drug administration. The anti-oxidant activity of the AC-mix was measured by total polyphenol and total flavonoid contents as well as by radical scavenging activity with protein levels evaluated using western blotting. Results: CRE damage to the esophageal mucosa was significantly reduced in the AC-mix group as compared with the controls, and administration of the AC-mix was seen to inhibit NF-κBp65 activity. Consequently, the inactivation of NF-κBp65 significantly inhibited inflammatory mediators such as COX-2 and iNOS. Moreover, the anti-oxidant enzyme HO-1 significantly increased through activation of the Nrf2-Keap1 pathway. Matrix metalloproteinase-2 (MMP-2), which can break down collagen from the basement membrane and extracellular matrix, was decreased following AC-mix treatment, and elevated levels of MMP-2 were regulated by its tissue inhibitor. Conclusions: These results show that AC-mix can alleviate esophageal mucosa ulcer though inhibition of the NF-κBp65 inflammatory pathway and enhancement of the anti-oxidant Nrf2-Keap1 pathway.

• The Korea Journal of Herbology
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• v.35 no.6
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• pp.21-28
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• 2020

Objectives : The objective of this study was to investigate the improvement effect of Sprout of Coix lacryma-jobi var. mayuen Stapf water extract (SC) on the dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Methods : The antioxidant activity of SC was measured through total polyphenol and total flavonoid content in vitro. The experiment was conducted with seven-week-old male Balb/c mice. After 1 week adaptation, acute colitis was induced by oral administration of 5% DSS dissolved in drinking water, for 7 days. And normal mice received drinking water without DSS throughout the entire experimental period. For each experiment, the mice were divided into 4 groups and 24 colitis mice were arbitrarily allocated into 3 groups (n = 8/group); Normal group, Control group, SC 100 mg/kg treated group (SCL), SC 200 mg/kg treated group (SCH). Serum and colon tissues were collected after one weeks of drug administration. Results : ROS levels, ONOO^- levels, AST, and ALT in serum were decreased in SC treated groups compared to the control group. Western blotting measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2, IL-4, IL-10, and Bcl2 showed that the SC treated groups was increased compared to the Control group. Also, western blot measurements of NF-κBp65, p-IκBα, COX-2, iNOS, TNF-α, IL-1β, Bax, and Caspase-3 showed that the SC treated groups was reduced compared to the Control group. Conclusion : Taken together, these results suggest that SC treatment can attenuate the DSS-induced colitis though inhibiting NF-κB pathway and enhancing Nrf2 pathway. Therefore, SC was the potential to be used as a natural therapeutic drug.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.2
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• pp.288-298
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• 2016

Resveratrol acts as a free radical scavenger and a potent antioxidant in the inhibition of numerous reactive oxygen species (ROS). The function of resveratrol and resveratrol-loaded nanoparticles in protecting human lung cancer cells (A549) against hydrogen peroxide was investigated in this study. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay was performed to evaluate the antioxidant properties. Resveratrol had substantially high antioxidant capacity (trolox equivalent antioxidant capacity value) compared to trolox and vitamin E since the concentration of resveratrol was more than $50{\mu}M$. Nanoparticles prepared from ${\beta}$-lactoglobulin (${\beta}$-lg) were successfully developed. The ${\beta}$-lg nanoparticle showed 60 to 146 nm diameter in size with negatively charged surface. Non-cytotoxicity was observed in Caco-2 cells treated with ${\beta}$-lg nanoparticles. Fluorescein isothiocynate-conjugated ${\beta}$-lg nanoparticles were identified into the cell membrane of Caco-2 cells, indicating that nanoparticles can be used as a delivery system. Hydrogen peroxide caused accumulation of ROS in a dose- and time-dependent manner. Resveratrol-loaded nanoparticles restored $H_2O_2$-induced ROS levels by induction of cellular uptake of resveratrol in A549 cells. Furthermore, resveratrol activated nuclear factor erythroid 2-related factor 2-Kelch ECH associating protein 1 (Nrf2-Keap1) signaling in A549 cells, thereby accumulation of Nrf2 abundance, as demonstrated by western blotting approach. Overall, these results may have implications for improvement of oxidative stress in treatment with nanoparticles as a biodegradable and non-toxic delivery carrier of bioactive compounds.

• Journal of Ginseng Research
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• v.39 no.3
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• pp.250-256
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• 2015

Background: It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. Methods: To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Results: Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and interleukin-$1{\beta}$ expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. Conclusion: The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.617-630
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• 2021

Chemotherapy-induced side effects affect the quality of life and efficacy of treatment of cancer patients. Current approaches for treating the side effects of chemotherapy are poorly effective and may cause numerous harmful side effects. Therefore, developing new and effective drugs derived from natural nontoxic compounds for the treatment of chemotherapy-induced side effects is necessary. Experiments in vivo and in vitro indicate that Panax ginseng (PG) and its ginsenosides are undoubtedly non-toxic and effective options for the treatment of chemotherapy-induced side effects, such as nephrotoxicity, hepatotoxicity, cardiotoxicity, immunotoxicity, and hematopoietic inhibition. The mechanism focus on anti-oxidation, anti-inflammation, and anti-apoptosis, as well as the modulation of signaling pathways, such as nuclear factor erythroid-2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), P62/keap1/Nrf2, c-jun Nterminal kinase (JNK)/P53/caspase 3, mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinases (ERK), AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase kinase 4 (MKK4)/JNK, and phosphatidylinositol 3-kinase (PI3K)/AKT. Since a systemic review of the effect and mechanism of PG and its ginsenosides on chemotherapy-induced side effects has not yet been published, we provide a comprehensive summarization with this aim and shed light on the future research of PG.

• Journal of Life Science
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• v.20 no.5
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• pp.736-744
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• 2010

The root of Playtcodon grandiflorum, called Platycodi radix, has been a favorite edible plant in Asia and contains a large amount of saponins. Melanoma cells (B16F10) were used to investigate the inhibitory effect of aged black Platycodi radix extract (ABPRE) on oxidative stress and matrix metalloproteinases (MMPs). Platycodon radix has been known to have a variety of medicinal effects such as prevention of gastric ulcers, antiallergenic activities, histamine release inhibition, and antioxidant effects. However, the mechanism of its action remains unclear in humans. ABPRE was prepared using ethanol extraction of aged black Platycodi radix. In an antioxidant effect study of ABPRE, it was observed that ABPRE specifically exhibited the scavenging activity of DPPH radical, but did not inhibit the production of malondialdehyde from lipid peroxidation. DNA oxidation was also blocked in the presence of ABPRE. In addition, ABPRE decreased the expression and activation of MMP-2 stimulated by phenazine methosulfate. Furthermore, ABPRE revealed the inhibitory effect on melanin production induced by L-dopa via antioxidant effect and the reduction of tyrosinase expression. Especially, the expression of antioxidant enzymes such as SOD-1 and SOD-2 regulated by Nrf2 was increased in the presence of ABPRE. Therefore, it appears that ABPRE may be a possible chemopreventive agent for the prevention of metastasis related to oxidative stress.

• Korean Journal of Plant Resources
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• v.31 no.5
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• pp.466-477
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• 2018

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

• Korean Journal of Pharmacognosy
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• v.43 no.1
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• pp.39-45
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• 2012

Cirsium japonicum var. ussuriense has long been used in herbal medicine for the treatment of arthritis, dyspepsia, and bleeding in Korea. In the present study, we investigated anti-inflammatory effects of C. japonicum var. ussuriense against lipopolysaccharide(LPS)-induced activation in RAW264.7 cells by the expression of heme oxygenase (HO)-1. The 70% EtOH extract of the aerial parts of C. japonicum var. ussuriense (CJE), showed the potent anti-inflammatory effects on LPS-induced inflammation in RAW264.7 cells. The anti-inflammatory effect of CJE was demonstrated by the suppression of pro-inflammatory mediators, including pro-inflammatory enzymes (inducible nitric oxide synthase and cyclooxygenase-2). Furthermore CJE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increased HO activity in RAW264.7 macrophages. The effects of CJE on LPS-induced NO and $PGE_2$ productions were partially reversed by an HO-1 inhibitor, tin protoporphyrin (SnPP). Therefore, it is suggested that CJE-induced HO-1 expression plays a role of the resulting anti-inflammatory effects in macrophages. These results suggest that CJE may be a promising candidate for the treatment of inflammatory diseases.