Publications by authors named "Young Jin Jang"

75 Publications

Chemical Composition, Antioxidant, and Anti-Inflammatory Activity of Essential Oil from Omija ( (Turcz.) Baill.) Produced by Supercritical Fluid Extraction Using CO.

Foods 2021 Jul 13;10(7). Epub 2021 Jul 13.

Department of Food Science and Biotechnology, Sungshin Women's University, Seoul 01133, Korea.

(Turcz.) Baill., which is known as omija in South Korea, is mainly cultivated in East Asia. The present study aimed to investigate the chemical composition of essential oil from the omija (OMEO) fruit obtained by supercritical fluid extraction using CO and to confirm the antioxidant and anti-inflammatory activity of OMEO using HaCaT human keratinocyte and RAW 264.7 murine macrophages. As a result of the chemical composition analysis of OMEO using gas chromatography-mass spectrometry, a total of 41 compounds were identified. The detailed analysis results are sesquiterpenoids (16), monoterpenoids (14), ketones (4), alcohols (3), aldehydes (2), acids (1), and aromatic hydrocarbons (1). OMEO significantly reduced the increased ROS levels in HaCaT keratinocytes induced by UV-B irradiation ( < 0.05). It was confirmed that 5 compounds (α-pinene, camphene, β-myrcene, 2-nonanone, and nerolidol) present in OMEO exhibited inhibitory activity on ROS production. Furthermore, OMEO showed excellent anti-inflammatory activity in RAW 264.7 macrophages induced by lipopolysaccharide. OMEO effectively inhibited NO production ( < 0.05) by suppressing the expression of the iNOS protein. Finally, OMEO was investigated for exhibition of anti-inflammatory activity by inhibiting the activation of NF-κB pathway. Taken together, OMEO could be used as a functional food ingredient with excellent antioxidant and anti-inflammatory activity.
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http://dx.doi.org/10.3390/foods10071619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8304754PMC
July 2021

2,6-Dimethoxy-1,4-benzoquinone increases skeletal muscle mass and performance by regulating AKT/mTOR signaling and mitochondrial function.

Phytomedicine 2021 Oct 10;91:153658. Epub 2021 Jul 10.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, South Korea; Division of Food Biotechnology, University of Science and Technology, Daejeon 34113, South Korea. Electronic address:

Background: 2,6-Dimethoxy-1,4-benzoquinone (DMBQ), a natural phytochemical present in fermented wheat germ, has been reported to exert anti-cancer, anti-inflammatory, and anti-adipogenic effects. However, the effect of DMBQ on muscle hypertrophy and myoblast differentiation has not been elucidated.

Purpose: We investigated the effect of DMBQ on skeletal muscle mass and muscle function and then determined the possible mechanism of DMBQ.

Methods: To examine myogenic differentiation and hypertrophy, confluent C2C12 cells were incubated in differentiation medium with or without various concentrations of DMBQ for 4 days. In animal experiments, C57BL/6 mice were fed DMBQ-containing AIN-93 diet for 7 weeks. Grip strength, treadmill, microscopic evaluation of muscle tissue, western blotting, and quantitative real-time PCR were performed.

Results: DMBQ significantly increased fusion index, myotube size, and the protein expression of myosin heavy chain (MHC). DMBQ increased the phosphorylation of protein kinase B (AKT) and p70 ribosomal protein S6 kinase (S6K), whereas the phosphorylation of these proteins was abolished by the phosphoinositide 3-kinase inhibitor LY294002 in C2C12 cells. In addition, DMBQ treatment increased peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), which programs mitochondrial biogenesis, protein levels compared with control C2C12 cells. DMBQ significantly increased maximal respiration and spare respiratory capacity in C2C12 cells. In animal experiments, DMBQ increased skeletal muscle weights and skeletal muscle fiber size compared with the control group values. In addition, the DMBQ group showed increased grip strength and running distance on an accelerating treadmill. The protein expression of total MHC, MHC1, MHC2A, and MHC2B in skeletal muscle was upregulated by DMBQ supplementation. We found that DMBQ increased the phosphorylation of AKT and mammalian target of rapamycin (mTOR), as well as downstream S6K and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in skeletal muscle. DMBQ also stimulated mRNA expression of PGC1α, accompanied by an increase in mitochondrial DNA content, oxidative phosphorylation (OXPHOS) proteins, and oxidative enzyme activity.

Conclusion: Collectively, DMBQ was shown to increase skeletal muscle mass and performance by regulating the AKT/mTOR signaling pathway and enhancing mitochondrial function, which might be useful for the treatment and prevention of skeletal muscle atrophy.
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http://dx.doi.org/10.1016/j.phymed.2021.153658DOI Listing
October 2021

Effect of Korean Red Ginseng through comparative analysis of cardiac gene expression in mice.

J Ginseng Res 2021 May 31;45(3):450-455. Epub 2020 Jul 31.

College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan-city, Jeollabuk-Do, Republic of Korea.

Korean Red Ginseng (KRG) is an herbal oriental medicine known to alleviate cardiovascular dysfunction. To analysis the expression of diabetic cardiac complication-associated genes in mice, we studied the cardiac gene expression following KRG treatment. In result, a total of 585 genes were found to be changed in mice. Among the changed expression, 245 genes were found to 2-fold upregulated, and 340 genes were 2-fold downregulated. In addition, the changed gene expressions were ameliorated by KRG. In conclusion, KRG may be possible to normalize cardiac gene expressions in mice.
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http://dx.doi.org/10.1016/j.jgr.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8134846PMC
May 2021

γ-Oryzanol Improves Exercise Endurance and Muscle Strength by Upregulating PPARδ and ERRγ Activity in Aged Mice.

Mol Nutr Food Res 2021 07 3;65(14):e2000652. Epub 2021 Jun 3.

Natural Materials and Metabolism Research Group, Korea Food Research Institute, Wanju, 55365, Republic of Korea.

Scope: γ-Oryzanol, a well-known antioxidant, has been used by body builders and athletes to boost strength and increase muscle gain, without major side effects. However, the effect of γ-Oryzanol on sarcopenia and the underlying molecular mechanism is poorly understood.

Results: Aged mice fed with the γ-Oryzanol diet do not show significant changes in muscle weight, but show increased running endurance as well as improved grip strength. The expression and activity of PPARδ and ERRγ are increased in skeletal muscle of γ-Oryzanol supplemented mice. γ-Oryzanol upregulates oxidative muscle fibers by MEF2 transcription factor, and PGC-1α and ERRα expressions. Fatty acid oxidation related genes and mitochondria biogenesis are upregulated by γ-Oryzanol. In addition, γ-Oryzanol inhibits TGF-β-Smad-NADPH oxidase 4 pathway and inflammatory cytokines such as TNF-α, IL-1β, IL-6, and p65 NF-κB subunit, which cause skeletal muscle weakness. Collectively, γ-Oryzanol attenuates muscle weakness pathway and increases oxidative capacity by increasing PPARδ and ERRγ activity, which contributes to enhance strength and improve oxidative capacity in muscles, consequently enhancing exercise capacity in aged mice. Particularly, γ-Oryzanol directly binds to PPARδ.

Conclusions: These are the first findings showing that γ-Oryzanol enhances skeletal muscle function in aged mice by regulating PPARδ and ERRγ activity without muscle gain.
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http://dx.doi.org/10.1002/mnfr.202000652DOI Listing
July 2021

Identifying Codium fragile extract components and their effects on muscle weight and exercise endurance.

Food Chem 2021 Aug 7;353:129463. Epub 2021 Mar 7.

Natural Materials and Metabolism Research Group, Korea Food Research Institute, Wanju-gun 55365, Republic of Korea; Major of Food Science & Technology, Seoul Women's University, Seoul 01797, Republic of Korea. Electronic address:

Codium fragile (CF) is a type of green algae consumed as kimchi in Asia. UPLC-QTOF-MS/MS analysis showed that CF contain lysophosphatidyl choline, canthaxanthin, retinoic acid, α-tocopherol, and unsaturated fatty acids, which reportedly improve skeletal muscle health. However, the effect of CF on skeletal muscle mass and function remains to be elucidated. In mice fed with CF extracts, exercise endurance and muscle weight increased. CF extracts enhanced protein synthesis and myogenic differentiation through the mTORC1 pathway. CF extracts also promoted oxidative muscle fiber formation and mitochondrial biogenesis through the PGC-1α-related signaling pathway. Upregulation of PGC-1α by CF extracts was abolished by EX527 SIRT1 inhibitor treatment. Changed signaling molecules in the CF extracts were partially regulated by canthaxanthin, a new compound in CF extracts, suggesting that canthaxanthin contribute synergistically to the effect of CF extracts. Therefore, CF is a potential food source for sport nutrition or prevention of sarcopenia.
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http://dx.doi.org/10.1016/j.foodchem.2021.129463DOI Listing
August 2021

Syk/NF-κB-targeted anti-inflammatory activity of Melicope accedens (Blume) T.G. Hartley methanol extract.

J Ethnopharmacol 2021 May 1;271:113887. Epub 2021 Feb 1.

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Melicope accedens (Blume) Thomas G. Hartley is a plant included in the family Rutaceae and genus Melicope. It is a native plant from Vietnam that has been used for ethnopharmacology. In Indonesia and Malaysia, the leaves of M. accedens are applied externally to decrease fever.

Aim Of The Study: The molecular mechanisms of the anti-inflammatory properties of M. accedens are not yet understood. Therefore, we examined those mechanisms using a methanol extract of M. accedens (Ma-ME) and determined the target molecule in macrophages.

Materials And Methods: We evaluated the anti-inflammatory effects of Ma-ME in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and in an HCl/EtOH-triggered gastritis model in mice. To investigate the anti-inflammatory activity, we performed a nitric oxide (NO) production assay and ELISA assay for prostaglandin E2 (PGE). RT-PCR, luciferase gene reporter assays, western blotting analyses, and a cellular thermal shift assay (CETSA) were conducted to identify the mechanism and target molecule of Ma-ME. The phytochemical composition of Ma-ME was analyzed by HPLC and LC-MS/MS.

Results: Ma-ME suppressed the production of NO and PGE and the mRNA expression of proinflammatory genes (iNOS, IL-1β, and COX-2) in LPS-stimulated RAW264.7 cells without cytotoxicity. Ma-ME inhibited NF-κB activation by suppressing signaling molecules such as IκBα, Akt, Src, and Syk. Moreover, the CETSA assay revealed that Ma-ME binds to Syk, the most upstream molecule in the NF-κB signal pathway. Oral administration of Ma-ME not only alleviated inflammatory lesions, but also reduced the gene expression of IL-1β and p-Syk in mice with HCl/EtOH-induced gastritis. HPLC and LC-MS/MS analyses confirmed that Ma-ME contains various anti-inflammatory flavonoids, including quercetin, daidzein, and nevadensin.

Conclusions: Ma-ME exhibited anti-inflammatory activities in vitro and in vivo by targeting Syk in the NF-κB signaling pathway. Therefore, we propose that Ma-ME could be used to treat inflammatory diseases such as gastritis.
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http://dx.doi.org/10.1016/j.jep.2021.113887DOI Listing
May 2021

MiR-141-3p promotes mitochondrial dysfunction in ovariectomy-induced sarcopenia via targeting Fkbp5 and Fibin.

Aging (Albany NY) 2021 02 3;13(4):4881-4894. Epub 2021 Feb 3.

Research Group of Natural Material and Metabolism, Korea Food Research Institute, Wanju, South Korea.

Post-menopausal conditions exacerbate the biological aging process and this is often accompanied by visceral adiposity with sarcopenia. Mitochondrial impairment is a hallmark of frailty and sarcopenia in the elderly. However, the exact mechanism underlying the development of obesogenic sarcopenia and the involvement of mitochondria remains unclear. This study confirmed that there is a decline in muscle mass and function as well as mitochondrial dysfunction in the quadriceps of ovariectomized (OVX) mice. To investigate the role of microRNA (miRNA) in this process, we performed miRNA and mRNA arrays and found that miR-141-3p directly targets and downregulates FK506 binding protein 5 (Fkbp5) and Fibin. Overexpression of miR-141-3p decreased mitochondrial function and inhibited myogenic differentiation in C2C12 cells. These effects were mediated by Fkbp5 and Fibin inhibition. Conversely, knockdown of miR-141-3p increased mitochondrial respiration and enhanced myogenesis. Treatment with β-estradiol effectively reversed the palmitic acid-induced upregulation of miR-141-3p and subsequent downregulation of Fkbp5 and Fibin. In conclusion, miR-141-3p is upregulated in OVX mice, and this is associated with mitochondrial dysfunction through inhibition of Fkbp5 and Fibin. These findings suggest that inhibiting miR-141-3p could be a therapeutic target for alleviating obesogenic sarcopenia.
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http://dx.doi.org/10.18632/aging.202617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950230PMC
February 2021

Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice.

Phytomedicine 2021 Feb 30;82:153457. Epub 2020 Dec 30.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun, Jeonbuk 55365, Republic of Korea; Department of Food Biotechnology, Korea University of Science and Technology, Daejeon 34113, Republic of Korea. Electronic address:

Background: The enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown.

Purpose: To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway.

Methods: C57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used.

Results: Treatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT.

Conclusion: WFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression.
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http://dx.doi.org/10.1016/j.phymed.2020.153457DOI Listing
February 2021

The antioxidant activities of Korean Red Ginseng () and ginsenosides: A systemic review through and clinical trials.

J Ginseng Res 2021 Jan 10;45(1):41-47. Epub 2020 Oct 10.

Laboratory of Efficacy Research, Korea Ginseng Corporation, 30, Gajeong-ro, Shinseong-dong, Yuseong-gu, Daejeon, Republic of Korea.

A wide range of studies have steadily pointed out the relation of oxidative stress to the primary and secondary causes of human disease and aging. As such, there have been multiple misconceptions about oxidative stress. Most of reactive oxygen species (ROS) generated from chronic diseases cause oxidative damage to cell membrane lipids and proteins. ROS production is increased by abnormal stimulation inside and outside in the body, and even though ROS are generated in cells in response to abnormal metabolic processes such as disease, it does not mean that they directly contribute to the pathogenesis of a disease. Therefore, the focus of treatment should not be on ROS production itself but on the prevention and treatment of diseases linked to ROS production, including types 1 and 2 diabetes, cancer, heart disease, schizophrenia, Parkinson's disease, and Alzheimer's disease. In this regard, Korean Red Ginseng (KRG) has been traditionally utilized to help prevent and treat diseases such as diabetes, cancer, inflammation, nervous system diseases, cardiovascular disease, and hyperlipidemia. Therefore, this review was intended to summarize animal and human clinical studies on the antioxidant activities of KRG and its components, ginsenosides.
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http://dx.doi.org/10.1016/j.jgr.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790892PMC
January 2021

The Anti-Cancer Effect of Linusorb B3 from Flaxseed Oil through the Promotion of Apoptosis, Inhibition of Actin Polymerization, and Suppression of Src Activity in Glioblastoma Cells.

Molecules 2020 Dec 12;25(24). Epub 2020 Dec 12.

Department of Integrative Biotechnology, Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.

Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 ([1-9-NαC]-linusorb B3) was reported to have antioxidative and anti-inflammatory activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.
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http://dx.doi.org/10.3390/molecules25245881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764463PMC
December 2020

Tunisian Olea europaea L. leaf extract suppresses Freund's complete adjuvant-induced rheumatoid arthritis and lipopolysaccharide-induced inflammatory responses.

J Ethnopharmacol 2021 Mar 24;268:113602. Epub 2020 Nov 24.

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address:

Ethnopharmacological Relevance: Olea europaea L. (olive) is traditionally used as a folk remedy and functional food in Europe and Mediterranean countries to treat inflammatory diseases. O. europaea contains phenolic compounds and have been reported to prevent cartilage degradation. However, the function and mechanism of O. europaea in rheumatoid arthritis are not known.

Aim Of The Study: In this study, we aimed to examine anti-inflammatory and anti-arthritic effects of Tunisian O. europaea L. leaf ethanol extract (Oe-EE).

Materials And Methods: To do this, we employed an in vitro macrophage-like cell line and an in vivo Freund's complete adjuvant (AIA)-induced arthritis model. Levels of inflammatory genes and mediators were determined from in vivo samples.

Results: The Oe-EE clearly reduced the production of the lipopolysaccharide-mediated inflammatory mediators, nitric oxide (NO) and prostaglandin E (PGE), in RAW264.7 cells. The results of HPLC showed that Oe-EE contained many active compounds such as oleuropein and flavonoids. In AIA-treated rats, swelling of paws, pain, and cartilage degeneration were alleviated by oral Oe-EE administration. Correlating with in vitro data, PGE production was significantly reduced in paw samples. Furthermore, the molecular mechanism of Oe-EE was dissected, and Oe-EE regulated the gene expression of interleukin (IL)-6, inducible NO synthase (iNOS), and MMPs and inflammatory signaling activation.

Conclusion: Consequently, Oe-EE possesses anti-inflammatory and anti-rheumatic effects and is a potential effective treatment for rheumatoid arthritis.
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http://dx.doi.org/10.1016/j.jep.2020.113602DOI Listing
March 2021

and reciprocally regulate expression and autophagy in nonalcoholic hepatic steatosis.

Autophagy 2020 Oct 20:1-17. Epub 2020 Oct 20.

Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, Republic of Korea.

Macroautophagy/autophagy, a self-degradative process, regulates metabolic homeostasis in response to various stress conditions and is a therapeutic target for nonalcoholic fatty liver disease. We found that autophagic activity was inhibited as a result of a significant reduction in the expression of autophagy-related genes such as in a mouse model and patients with fatty liver. This downregulation was caused by increased levels and decreased mRNA levels in hepatocytes. suppressed expression through direct binding at a 3' untranslated region sequence. directly activated transcription of . We investigated lipid accumulation and the expression of autophagy-related genes in the livers of mice treated with anti-. Hepatic steatosis was alleviated, and mRNA levels were significantly increased by locked nucleic acid-mediated silencing. Additionally, autophagosome formation and MAP1LC3/LC3-II protein levels were increased, indicating an increase in autophagic activity. Interestingly, suppression of did not ameliorate fatty liver under suppression, suggesting that reduced levels mitigate hepatic steatosis through upregulation of . These results demonstrate that inhibition of expression ameliorated fatty liver disease through increased autophagic activity by increasing the expression of . Thus, is a potential therapeutic target for nonalcoholic fatty disease.: AMPK: adenosine monophosphate-activated protein kinase; ATG: autophagy-related; ChIP: chromatin immunoprecipitation; CTSB: cathepsin B; CTSL: cathepsin L; CQ: chloroquine; HFD: high-fat diet; HNF4A: hepatocyte nuclear factor 4, alpha; IF: immunofluorescence; IHC: immunohistochemistry; LDs: lipid droplets; Leup: leupeptin; LFD: low-fat diet; LNA: locked nucleic acid; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; miRNA: microRNA; MTOR: mechanistic target of rapamycin kinase; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PCR: polymerase chain reaction; TEM: transmission electron microscopy; TF: transcription factor; TLDA: TaqMan low-density array; ULK1: unc-51 like kinase 1; UTR: untranslated region.
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http://dx.doi.org/10.1080/15548627.2020.1827779DOI Listing
October 2020

3-Deazaadenosine, an S-adenosylhomocysteine hydrolase inhibitor, attenuates lipopolysaccharide-induced inflammatory responses via inhibition of AP-1 and NF-κB signaling.

Biochem Pharmacol 2020 12 7;182:114264. Epub 2020 Oct 7.

Department of Integrative Biotechnology and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Republic of Korea; Department of Biocosmetics, Sungkyunkwan University, Suwon 16419, Republic of Korea. Electronic address:

3-Deazadenosine (3-DA) is a general methylation inhibitor that depletes S-adenosylmethionine, a methyl donor, by blocking S-adenosylhomocysteine hydrolase (SAHH). In this study, we investigated the inhibitory activity and molecular mechanisms of 3-DA in inflammatory responses. 3-DA suppressed the secretion of inflammatory mediators such as nitric oxide (NO) and prostaglandin E (PGE) in lipopolysaccharide-treated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)-differentiated U937 cells. It also reduced mRNA expression of inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, interleukin-1β (IL-1 β), and IL-6, indicating that 3-DA has anti-inflammatory properties in murine and human macrophages. Moreover, 3-DA strongly blocked AP-1 and NF-κB luciferase activity under PMA-, MyD88-, and TRIF-stimulated conditions and decreased the translocation of c-Jun, c-Fos, p65, and p50 into the nucleus. In addition, the p-ERK level in AP-1 signaling and the p-IκBα level in NF-kB signaling were diminished by 3-DA treatment. Interestingly, 3-DA did not alter the phosphorylation of MEK1/2, an ERK modulator, or IKKα/β, an IκBα regulator. Instead, 3-DA prevented MEK1/2 and IKKα/β from combining with ERK and IκBα, respectively, and directly suppressed MEK1/2 and IKKα/β kinase activity. These results indicate that MEK1/2 and IKKα/β are direct targets of 3-DA. In addition, suppression of SAHH by siRNA or treatment with adenosine dialdehyde, another SAHH inhibitor, showed inhibitory patterns against p-ERK and IκBα similar to those of 3-DA. Taken together, this study demonstrates that 3-DA inhibits AP-1 and NF-κB signaling by directly blocking MEK1/2 and IKKα/β or indirectly mediating SAHH, resulting in anti-inflammatory activity.
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http://dx.doi.org/10.1016/j.bcp.2020.114264DOI Listing
December 2020

Synergistic lipid-lowering effects of and extracts.

Exp Ther Med 2020 Sep 19;20(3):2270-2278. Epub 2020 Jun 19.

Department of Food Biotechnology, University of Science and Technology, Wanju-gun, Jeollabuk-do 55365, Republic of Korea.

The effects of a mixture of (HR) and (ZM) extract (ZH) on intracellular lipid accumulation were investigated and the anti-obesity effects of ZH evaluated in mice with high-fat diet-induced obesity. The results revealed that ZH inhibited lipid accumulation in 3T3-L1 adipocytes and Huh-7 cells by suppressing adipogenic and lipogenic gene and protein expression. To evaluate the anti-obesity effects of ZH, mice fed a high-fat diet were orally administered low and high doses of ZH (low, ZM 400 mg/kg + HR 100 mg/kg; high, ZM 800 mg/kg + HR 200 mg/kg) for 9 weeks. ZH significantly reduced body weight gain and adipose tissue accumulation with no reduction in food intake when compared to control treatment. Furthermore, ZH reduced hepatic triglyceride and total cholesterol levels, as well as adipose cell size, in the liver and epididymal fat pads, respectively, through inhibition of adipogenesis and lipogenesis-related gene expression. These results suggested that ZH inhibits lipid accumulation, thereby indicating its potential for use as a new therapeutic strategy for obesity.
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http://dx.doi.org/10.3892/etm.2020.8913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401869PMC
September 2020

Autophagy Functions to Prevent Methylglyoxal-Induced Apoptosis in HK-2 Cells.

Oxid Med Cell Longev 2020 4;2020:8340695. Epub 2020 Jun 4.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Republic of Korea.

Methylglyoxal (MGO), a reactive carbonyl species, causes cellular damage and is closely related to kidney disease, particularly diabetic nephropathy. Although MGO has been reported to induce autophagy and apoptosis, the relationships between the two pathways are unclear. Here, we evaluated whether autophagy may be the underlying mechanism inhibiting MGO-induced apoptosis. MGO treatment induced concentration- and time-dependent apoptosis in HK-2 cells. Moreover, MGO upregulated the autophagy markers p62 and LC3-II. Apoptosis caused by MGO was increased in ATG5-knockdown cells compared to that in wild-type cells. In contrast, autophagy activation by 5-aminoimidazole-4-carboxamide ribonucleotide resulted in reduced apoptosis, suggesting that autophagy played a role in protecting against MGO-induced cell death. To examine the mechanisms through which autophagy occurred following MGO stimulation, we investigated changes in AKT/mammalian target of rapamycin (mTOR) signaling. Autophagy induction by MGO treatment was not related to AKT/mTOR signaling; however, it did involve autophagy-related gene expression promoted by AMP-activated protein kinase-mediated transcription factors, such as forkhead box 1. Overall, our findings indicate that MGO-induced cellular damage can be mitigated by autophagy, suggesting that autophagy may be a potential therapeutic target for diseases such as diabetic nephropathy.
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http://dx.doi.org/10.1155/2020/8340695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7292969PMC
January 2021

Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB.

Biomolecules 2020 05 10;10(5). Epub 2020 May 10.

Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea.

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.
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http://dx.doi.org/10.3390/biom10050741DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277364PMC
May 2020

Korean Red Ginseng enhances cardiac hemodynamics on doxorubicin-induced toxicity in rats.

J Ginseng Res 2020 May 14;44(3):483-489. Epub 2019 Mar 14.

College of Veterinary Medicine, Biosafety Research Institute, Jeonbuk National University, Iksan-city, Republic of Korea.

Background: Korean Red Ginseng (KRG) has been known to possess many ginsenosides. These ginsenosides are used for curing cardiovascular problems. The present study show the protective potential of KRG against doxorubicin (DOX)-induced myocardial dysfunction, by assessing electrocardiographic, hemodynamic, and biochemical parameters and histopathological findings.

Methods: Animals were fed a standard chow and adjusted to their environment for 3 days before the experiments. Next, the rats were equally divided into five groups (n = 9, each group). The animals were administered with KRG (250 and 500 mg/kg) for 10 days and injected with DOX (20 mg/kg, subcutaneously, twice at a 24-h interval) on the 8th and 9th day. Electrocardiography and echocardiography were performed to study hemodynamics. Plasma levels of superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were measured. In addition, the dose of troponin I and activity of myeloperoxidase in serum and cardiac tissue were analyzed, and the histopathological findings were evaluated using light microscopy.

Results: Administration of KRG at a dose of 250 and 500 mg/kg recovered electrocardiographic changes, ejection fraction, fractional shortening, left ventricular systolic pressure, the maximal rate of change in left ventricle contraction (+dP/dt), and left ventricle relaxation (-dP/dt). In addition, KRG treatment significantly normalized the oxidative stress markers in plasma, dose dependently. In addition, the values of troponin I and myeloperoxidase were ameliorated by KRG treatment, dose dependently. And, KRG treatment showed better histopathological findings when compared with the DOX control group.

Conclusion: These mean that KRG mitigates myocardial damage by modulating the hemodynamics, histopathological abnormality, and oxidative stress related to DOX-induced cardiomyopathy in rats. The results of the present study show protective effects of KRG on cardiac toxicity.
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http://dx.doi.org/10.1016/j.jgr.2019.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195579PMC
May 2020

var. Attenuates Obesity-Induced Skeletal Muscle Atrophy via Regulation of PRMTs in Skeletal Muscle of Mice.

Int J Mol Sci 2020 Apr 17;21(8). Epub 2020 Apr 17.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun 55365, Korea.

As obesity promotes ectopic fat accumulation in skeletal muscle, resulting in impaired skeletal muscle and mitochondria function, it is associated with skeletal muscle loss and dysfunction. This study investigated whether var. (CZH) protected mice against obesity-induced skeletal muscle atrophy and the underlying molecular mechanisms. High-fat diet (HFD)-induced obese mice were orally administered either distilled water, low-dose CZH (125 mg/kg), or high-dose CZH (250 mg/kg) for 8 w. CZH reduced obesity-induced increases in inflammatory cytokines levels and skeletal muscle atrophy, which is induced by expression of atrophic genes such as muscle RING-finger protein 1 and muscle atrophy F-box. CZH also improved muscle function according to treadmill running results and increased the muscle fiber size in skeletal muscle. Furthermore, CZH upregulated mRNA and protein levels of protein arginine methyltransferases (PRMT)1 and PRMT7, which subsequently attenuated mitochondrial dysfunction in the skeletal muscle of obese mice. We also observed that CZH significantly decreased PRMT6 mRNA and protein expression, which resulted in decreased muscle atrophy. These results suggest that CZH ameliorated obesity-induced skeletal muscle atrophy in mice via regulation of PRMTs in skeletal muscle.
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http://dx.doi.org/10.3390/ijms21082811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7215836PMC
April 2020

Undaria pinnatifida extract feeding increases exercise endurance and skeletal muscle mass by promoting oxidative muscle remodeling in mice.

FASEB J 2020 06 15;34(6):8068-8081. Epub 2020 Apr 15.

Natural Materials and Metabolism Research Group, Korea Food Research Institute, Wanju-gun, Republic of Korea.

Dietary habits can alter the skeletal muscle performance and mass, and Undaria pinnatifida extracts are considered a potent candidate for improving the muscle mass and function. Therefore, in this study, we aimed to assess the effect of U pinnatifida extracts on exercise endurance and skeletal muscle mass. C57BL/6 mice were fed a 0.25% U pinnatifida extract-containing diet for 8 weeks. U pinnatifida extract-fed mice showed increased running distance, total running time, and extensor digitorum longus and gastrocnemius muscle weights. U pinnatifida extract supplementation upregulated the expression of myocyte enhancer factor 2C, oxidative muscle fiber markers such as myosin heavy chain 1 (MHC1), and oxidative biomarkers in the gastrocnemius muscles. Compared to the controls, U pinnatifida extract-fed mice showed larger mitochondria and increased gene and protein expression of molecules involved in mitochondrial biogenesis and oxidative phosphorylation, including nuclear respiratory factor 2 and mitochondrial transcription factor A. U pinnatifida extract supplementation also increased the mRNA expression of angiogenesis markers, including VEGFa, VEGFb, FGF1, angiopoietin 1, and angiopoietin 2, in the gastrocnemius muscles. Importantly, U pinnatifida extracts upregulated the estrogen-related receptor γ and peroxisome proliferator-activated receptor gamma co-activator 1-alpha (PGC-1α)/AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1) networks, which are partially increased by fucoxanthin, hesperetin, and caffeic acid treatments. Collectively, U pinnatifida extracts enhance mitochondrial biogenesis, increase oxidative muscle fiber, and promote angiogenesis in skeletal muscles, resulting in improved exercise capacity and skeletal muscle mass. These effects are attributable to fucoxanthin, hesperetin, and caffeic acid, bioactive components of U pinnatifida extracts.
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http://dx.doi.org/10.1096/fj.201902399RRDOI Listing
June 2020

Nutrikinetic study of fermented soybean paste () isoflavones according to the Sasang typology.

Nutr Res Pract 2020 Apr 13;14(2):102-108. Epub 2019 Dec 13.

Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, Jeonbuk 55365, Republic of Korea.

Background/objectives: In Oriental medicine, certain foods may be beneficial or detrimental based on an individual's constitution; however, the scientific basis for this theory is insufficient. The purpose of this study was to investigate the effect of body constitution, based on the Sasang type of Korean traditional medical classification system, on the bioavailability of soy isoflavones of , a quick-fermented soybean paste.

Subjects/methods: A pilot study was conducted on 48 healthy Korean men to evaluate the bioavailability of isoflavone after ingestion of food based on constitution types classified by the Sasang typology. The participants were classified into the Taeeumin (TE; n = 15), Soyangin (SY; n = 15), and Soeumin (SE; n = 18) groups. Each participant ingested 50 g of per 60 kg body weight. Thereafter, blood was collected, and the soy isoflavone metabolites were analyzed by ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Ntrikinetic analysis of individual isoflavone-derived metabolites was performed.

Results: Our nutrikinetic analysis identified 21 metabolites derived from isoflavones in the blood samples from 48 healthy Korean men (age range, 21-29 years). Significant differences were observed in the time to maximum concentration ( ) and elimination half-life ( ) for nine metabolites among the three groups. The and of the nine metabolites were higher in the SE group than in the other groups. Moreover, the absorption rates, as determined by the area under the plasma-level curve (AUC) values of intact isoflavone, were 5.3 and 9.4 times higher in the TE group than in the SY and SE groups, respectively. Additionally, the highest AUC values for phase I and II metabolites were observed in the TE group.

Conclusions: These findings indicate that isoflavone bioavailability, following insgestion, is high in individuals with the TE constitution, and relatively lower in those with the SE and SY constitutions.
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http://dx.doi.org/10.4162/nrp.2020.14.2.102DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7075739PMC
April 2020

Antiobesity effects of the combination of Patrinia scabiosaefolia root and Hippophae rhamnoides leaf extracts.

J Food Biochem 2020 06 30;44(6):e13214. Epub 2020 Mar 30.

Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju-gun, Republic of Korea.

Patrinia scabiosaefolia (PS) and Hippophae rhamnoides (HR) are traditionally used functional foods. Extracts from the root of PS are known for their anti-inflammatory effects, whereas those from the leaf of HR are effective at both preventing and treating obesity. This study investigated whether the extract combination of PS and HR (PHE) affected weight loss in obese mice. In vitro experiments demonstrated that PHE showed a synergistic effect on inhibiting adipocyte differentiation as compared with treatment with the single extracts. Additionally, PHE suppressed adipogenic-related genes in a concentration-dependent manner. In vivo PHE supplementation suppressed body weight gain, inhibited hepatic lipid accumulation, decreased adipose size, serum triglycerides, and improved insulin resistance in obese mice. These results suggest that a treatment strategy using a combination of plant-derived extracts might be effective at ameliorating obesity. PRACTICAL APPLICATIONS: Currently, common methods for reducing obesity are diet and exercise. These can stimulate oxidative phosphorylation and metabolic activation so have significantly effects. However, these are largely due to individual compliance; there is no significant effect of reducing the worldwide obesity rate. Recently, herbal extracts has been reported as alternative medicine about inflammatory and obesity because diet with the herbal extracts can improve obesity with minimal side effects. Of particular, a mixture of herbal products was investigated for the treatment of obesity. Our reports demonstrated the synergistic effects of natural products and emphasizes the need for studies investigating other combinations of herbal extracts in the treatment of obesity. The results of our studies highlight the synergistic effects of combination phytochemical extracts and their role in ameliorating obesity.
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http://dx.doi.org/10.1111/jfbc.13214DOI Listing
June 2020

Red Ginseng Improves Exercise Endurance by Promoting Mitochondrial Biogenesis and Myoblast Differentiation.

Molecules 2020 Feb 16;25(4). Epub 2020 Feb 16.

Korea Food Research Institute, Wanju-gun, Jeollabuk-do 55365, Korea.

Red ginseng has been reported to elicit various therapeutic effects relevant to cancer, diabetes, neurodegenerative diseases, and inflammatory diseases. However, the effect of red ginseng on exercise endurance and skeletal muscle function remains unclear. Herein, we sought to investigate whether red ginseng could affect exercise endurance and examined its molecular mechanism. Mice were fed with red ginseng extract (RG) and undertook swimming exercises to determine the time to exhaustion. Animals fed with RG had significantly longer swimming endurance. RG treatment was also observed to enhance ATP production levels in myoblasts. RG increased mRNA expressions of mitochondrial biogenesis regulators, , , and , which was accompanied by an elevation in mitochondrial DNA, suggesting an enhancement in mitochondrial energy-generating capacity. Importantly, RG treatment induced phosphorylation of p38 and AMPK and upregulated PGC1α expression in both myoblasts and in vivo muscle tissue. In addition, RG treatment also stimulated C2C12 myogenic differentiation. Our findings show that red ginseng improves exercise endurance, suggesting that it may have applications in supporting skeletal muscle function and exercise performance.
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http://dx.doi.org/10.3390/molecules25040865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070955PMC
February 2020

Iridoids of Valeriana fauriei contribute to alleviating hepatic steatosis in obese mice by lipophagy.

Biomed Pharmacother 2020 May 10;125:109950. Epub 2020 Feb 10.

Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Daejoen, 34113, Republic of Korea. Electronic address:

Nonalcoholic fatty liver disease (NAFLD) is a common risk factor for metabolic syndrome that increases the risk of future cardiovascular disease, stroke, and diabetes. Recently, autophagy has been proposed as a means to prevent NAFLD. We investigated whether substances with autophagy-inducing activity alleviate NAFLD. The Valeriana fauriei (V. fauriei) was selected as a potential autophagy inducer among various natural materials using a Cyto-ID autophagy detection kit. V. fauriei 70 % ethanol extract (VFE) increased LC3II levels in the presence of the lysosomal inhibitor and reduced the GFP/mCherry puncta ratio, suggesting that VFE enhanced autophagy. VFE reduced oleic acid (OA)-induced lipid accumulation and increased the number of autophagosome in hepatocytes. Autophagy induction by VFE is due to inhibition of mTORC1 activity. VFE supplementation reduced fatty liver by downregulating lipogenesis-related genes and increased the autophagy, as revealed by TEM and IHC analysis in the fatty liver. We identified iridoids as main compounds of VFE; didrovaltrate (DI), valeriotriate B (VAL B), valeriotetrate C (VAL C), valtrate (VAL), and valechlorine (VC) were shown to enhance autophagy. These compounds also reduced OA-induced lipid accumulation in an Atg5-dependent manner. Taken together, VFE and its iridoids might be effective in alleviating fatty liver by acting as autophagy enhancers to break down LDs.
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http://dx.doi.org/10.1016/j.biopha.2020.109950DOI Listing
May 2020

Extract Enhances Energy Expenditure via Improving Mitochondrial Function in Adipose Tissue and Skeletal Muscle.

Nutrients 2020 Feb 7;12(2). Epub 2020 Feb 7.

Division of Food Functionality Research, Korea Food Research Institute, Wanju-gun, Jeonbuk 55365, Korea.

Withania somnifera (WS), commonly known as ashwagandha, possesses diverse biological functions. WS root has mainly been used as an herbal medicine to treat anxiety and was recently reported to have an anti-obesity effect, however, the mechanisms underlying its action remain to be explored. We hypothesized that WS exerts its anti-obesity effect by enhancing energy expenditure through improving the mitochondrial function of brown/beige adipocytes and skeletal muscle. Male C57BL/6J mice were fed a high-fat diet (HFD) containing 0.25% or 0.5% WS 70% ethanol extract (WSE) for 10 weeks. WSE (0.5%) supplementation significantly suppressed the increases in body weight and serum lipids, and lipid accumulation in the liver and adipose tissue induced by HFD. WSE supplementation increased oxygen consumption and enhanced mitochondrial activity in brown fat and skeletal muscle in the HFD-fed mice. In addition, it promoted browning of subcutaneous fat by increasing mitochondrial uncoupling protein 1 (UCP1) expression. Withaferin A (WFA), a major compound of WS, enhanced the differentiation of pre-adipocytes into beige adipocytes and oxygen consumption in C2C12 murine myoblasts. These results suggest that WSE ameliorates diet-induced obesity by enhancing energy expenditure via promoting mitochondrial function in adipose tissue and skeletal muscle, and WFA is a key regulator in this function.
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http://dx.doi.org/10.3390/nu12020431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071232PMC
February 2020

The unc-51 like autophagy activating kinase 1-autophagy related 13 complex has distinct functions in tunicamycin-treated cells.

Biochem Biophys Res Commun 2020 04 5;524(3):744-749. Epub 2020 Feb 5.

Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Daejeon, 34113, Republic of Korea. Electronic address:

Endoplasmic reticulum (ER) stress and autophagy are regulated by shared signaling pathways, and their dysfunction is directly related to pathological conditions. This study investigated the function of the unc-51 like autophagy activating kinase 1 (ULK1)-autophagy related 13 (ATG13) complex in ER stress conditions through a knockout (KO) approach. Unlike other autophagy genes, KO of ULK1 or ATG13 attenuated ER stress and promoted mammalian target of rapamycin complex 1 (mTORC1) activation. Compared with wild type (WT) cells, ULK1 and ATG13 KO cells displayed increased viability, while beclin 1, ATG14, and ULK1/2 KO cells did not. Tunicamycin treatment upregulated the expression of ER stress markers (DNA damage inducible transcript 3, heat shock protein family A (Hsp70) member 5, and phosphorylated eukaryotic translation initiation factor 2 alpha kinase 3, eukaryotic translation initiation factor 2 subunit alpha, and endoplasmic reticulum to nucleus signaling 1); however, these were decreased in ULK1 and ATG13 KO cells. Insulin treatment upregulates the phosphorylation of ribosomal protein S6 kinase B1 (RPS6KB1) and AKT serine/threonine kinase 1 (AKT1), which was suppressed by tunicamycin. Notably, ATG13 and ULK1 deficiency ameliorated tunicamycin-induced insulin resistance, with enhanced RPS6KB1 and AKT1 phosphorylation in KO cells compared to WT cells. Although ULK1 and ATG13 are necessary for autophagy induction after tunicamycin-induced ER stress, autophagy does not seem to directly affect tunicamycin-induced cell death, ER stress, or insulin resistance. Our results indicate that loss of the ULK1-ATG13 complex attenuates ER stress and cell death and increases mTORC1 signaling.
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http://dx.doi.org/10.1016/j.bbrc.2020.01.160DOI Listing
April 2020

Rhodium(III)-Catalyzed Three-Component 1,2-Diamination of Unactivated Terminal Alkenes.

Synthesis (Stuttg) 2020 ;52(8):1247-1252

Department of Chemistry, Columbia University, New York, NY 10027, USA.

We report a three-component diamination of simple unactivated alkenes using an electrophilic nitrene source and amine nucleophiles. The reaction provides rapid access to 1,2-vicinal diamines from terminal alkenes through a one-pot protocol. The transformation proceeds smoothly with excellent tolerance for a broad array of primary and secondary amines, affording the desired product with good yield and regioselectivity. The mechanism is proposed to proceed through a Rh(III)-catalyzed aziridination of alkenes with subsequent ring opening by primary or secondary amines.
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http://dx.doi.org/10.1055/s-0039-1690756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290961PMC
January 2020

Dry-Fermented Soybean Food (Cheonggukjang) Ameliorates Senile Osteoporosis in the Senescence-Accelerated Mouse Prone 6 Model.

J Med Food 2019 Oct 30;22(10):1047-1057. Epub 2019 Sep 30.

Division of Nutrition and Metabolism Research, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, Korea.

Senile osteoporosis increases the risk of skeletal fractures with age. Cheonggukjang (CGJ), a traditional Korean dry fermented soybean product, has numerous therapeutic effects; however, its effects on bone mineral density (BMD) and bone metabolism in senile osteoporosis are unclear. In this study, we treated the senescence-accelerated mouse prone 6 (SAMP6) model of senile osteoporosis with CGJ to determine its potential for ameliorating and preventing osteoporosis progression. High-performance liquid chromatography analysis for isoflavone profiles revealed that short-term fermentation significantly increased the isoflavone aglycone content in soybeans. Thereafter, we fed 6-week-old SAMP6 mice with experimental diets containing 5% or 10% CGJ for 15 weeks. Microcomputed tomography revealed that CGJ supplementation effectively increased the BMD and relative bone length. , CGJ increased the osteopontin reactivity and upregulated the expression of , , , , , and in osteoblasts, and decreased Cathepsin K reactivity and downregulated and expression in osteoclasts. In addition, CGJ increased the / ratio. Collectively, these results demonstrate that CGJ can ameliorate the detrimental effects of senile osteoporosis by improving osteogenesis and decreasing osteoclast activity.
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http://dx.doi.org/10.1089/jmf.2018.4335DOI Listing
October 2019

Dihydrocapsaicin Inhibits Epithelial Cell Transformation through Targeting Amino Acid Signaling and c-Fos Expression.

Nutrients 2019 Jun 4;11(6). Epub 2019 Jun 4.

Division of Bioengineering, Incheon National University, Incheon 22012, Korea.

Chili peppers are one of the most widely consumed spices worldwide. However, research on the health benefits of chili peppers and some of its constituents has raised controversy as to whether chili pepper compounds possess cancer-promoting or cancer-preventive effects. While ample studies have been carried out to examine the effect of capsaicin in carcinogenesis, the chemopreventive effect of other major components in chili pepper, including dihydrocapsaicin, capsiate, and capsanthin, is relatively unclear. Herein, we investigated the inhibitory effect of chili pepper components on malignant cell transformation. Among the tested chili pepper compounds, dihydrocapsaicin displayed the strongest inhibitory activity against epidermal growth factor (EGF)-induced neoplastic transformation. Dihydrocapsaicin specifically suppressed EGF-induced phosphorylations of the p70S6K1-S6 pathway and the expression of c-Fos. A reduction in c-Fos levels by dihydrocapsaicin led to a concomitant downregulation of AP-1 activation. Further analysis of the molecular mechanism responsible for the dihydrocapsaicin-mediated decrease in phospho-p70S6K1, revealed that dihydrocapsaicin can block amino acid-dependent mechanistic targets of rapamycin complex 1 (mTORC1)-p70S6K1-S6 signal activation. Additionally, dihydrocapsaicin was able to selectively augment amino acid deprivation-induced cell death in mTORC1-hyperactive cells. Collectively, dihydrocapsaicin exerted chemopreventive effects through inhibiting amino acid signaling and c-Fos pathways and, thus, might be a promising cancer preventive natural agent.
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http://dx.doi.org/10.3390/nu11061269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627986PMC
June 2019

Hydrangea serrata Tea Enhances Running Endurance and Skeletal Muscle Mass.

Mol Nutr Food Res 2019 09 28;63(17):e1801149. Epub 2019 May 28.

Research Group of Natural Materials and Metabolism, Korea Food Research Institute, Wanju-gun, 55365, Republic of Korea.

Scope: Skeletal muscle mass and quality can be negatively affected by aging, inactivity, and disease, while a loss of muscle mass is associated with chronic disease status, falls, and mortality. We investigate the effects of Hydrangea serrata on skeletal muscle mass and function, along with the underlying mechanisms.

Methods And Results: H. serrata, identified through MyoD transcription activity screening, increases myogenic differentiation via Akt and p38. C57BL/6 mice are fed a 0.25% or 0.5% H. serrata diet for 8 weeks. H. serrata increased treadmill running distance and maximum speed, as well as skeletal muscle mass. H. serrata promotes the expression of myosin heavy chain 1 (MHC1) and MHC2A but not MHC2B. H. serrata also upregulates the protein expression of peroxisome proliferator-activated receptor δ (PPARδ) and mitochondrial complexes, and enhances citrate synthase and mitochondrial complex І activity. Transforming growth factor-β (TGF-β), myostatin, and growth differentiation factor 11 (GDF11) are attenuated by H. serrata, together with associated downstream signaling factors including phospho-Smad3 and NADPH oxidase 4 (NOX4).

Conclusion: H. serrata enhances exercise endurance by upregulating PPARδ and downregulating TGF-β, myostatin, and GDF11. H. serrata is a potential candidate for the development of functional food to maintain skeletal muscle mass and function.
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http://dx.doi.org/10.1002/mnfr.201801149DOI Listing
September 2019

Differential circulating and visceral fat microRNA expression of non-obese and obese subjects.

Clin Nutr 2020 03 8;39(3):910-916. Epub 2019 Apr 8.

Nutrition and Metabolism Research Division, Korea Food Research Institute, Wanju-gun, Republic of Korea; Department of Food Biotechnology, University of Science and Technology, Daejeon, Republic of Korea. Electronic address:

Background & Aims: Altered microRNA (miRNA) expression is associated with the pathophysiology of obesity; however, little is known about the miRNAs commonly dysregulated in the blood and visceral fat tissue of obese patients. This study compared the circulating and visceral fat miRNA expression in subjects with and without obesity.

Methods: For the circulating miRNA study, 20 healthy control and 30 obese subjects were recruited. For the tissue miRNA expression study, omental fat tissue was collected in ten female subjects each in the control and obese groups. MiRNA expression was measured by TaqMan low-density arrays. Metabolic risk factors were measured. Target genes for selected miRNAs were analyzed using informatics tools and a functional network map was constructed.

Results: 11 miRNAs were down-regulated (miR-133a, -139-5p, -15b, -26a, -301, -30b, -30c, -374, -451, -570, and -636), and one was up-regulated (miR-155) in both depots in obese subjects. These miRNAs had significant associations with BMI, waist circumference, and fat mass. Among them, miR-15b, miR-26a, miR-301, miR-30b, and miR-30c had more predicted obesity-related target genes than other miRNAs. In particular, miR-15b had numerous target genes associated with adipogenesis, mammalian target of rapamycin (mTOR) signaling, diabetes and insulin resistance, and mitochondrial function.

Conclusions: It is suggested that the miRNA alteration in the serum and visceral fat has pathophysiological implications for obesity. Our study identified dysregulated miRNAs that may be novel therapeutic targets to combat obesity.
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http://dx.doi.org/10.1016/j.clnu.2019.03.033DOI Listing
March 2020
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