• Journal of Ginseng Research
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• 제43권1호
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• pp.86-94
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• 2019

Background: Ginseng is believed to have antitumor activity. Autophagy is largely a prosurvival cellular process that is activated in response to cellular stressors, including cytotoxic chemotherapy; therefore, agents that inhibit autophagy can be used as chemosensitizers in cancer treatment. We examined the ability of Korean Red Ginseng extract (RGE) to prevent autophagic flux and to make hepatocellular carcinoma (HCC) cells become more sensitive to doxorubicin. Methods: The cytotoxic effects of total RGE or its saponin fraction (RGS) on HCC cells were examined by the lactate dehydrogenase assay in a dose- or time-dependent manner. The effect of RGE or RGS on autophagy was measured by analyzing microtubule-associated protein 1A/1B-light chain (LC)3-II expression and LC3 puncta formation in HCC cells. Late-stage autophagy suppression was tested using tandem-labeled green fluorescent protein (GFP)-monomeric red fluorescent protein (mRFP)-LC3. Results: RGE markedly increased the amount of LC3-II, but green and red puncta in tandem-labeled GFP-mRFP-LC3 remained colocalized over time, indicating that RGE inhibited autophagy at a late stage. Suppression of autophagy through knockdown of key ATG genes increased doxorubicin-induced cell death, suggesting that autophagy induced by doxorubicin has a protective function in HCC. Finally, RGE and RGS markedly sensitized HCC cells, (but not normal liver cells), to doxorubicin-induced cell death. Conclusion: Our data suggest that inhibition of late-stage autophagic flux by RGE is important for its potentiation of doxorubicin-induced cancer cell death. Therapy combining RGE with doxorubicin could serve as an effective strategy in the treatment of HCC.

• Journal of Nutrition and Health
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• 제52권4호
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• pp.323-331
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• 2019

Purpose: Glucocorticoids (GCs) are implicated in secondary osteoporosis, and the resulting fractures cause significant morbidity. Polyunsaturated fatty acids (PUFAs) play a vital role in bone metabolism. However, few trials have studied the impact of omega-3 PUFA-containing oils against GC-induced osteoporosis. Therefore, the present study was undertaken to determine whether supplementation with omega-3 PUFA-containing dietary oils such as fish oil, flaxseed oil or soybean oil can impede the development of GC-induced osteoporosis. Methods: The fatty acids (FAs) content of oils was determined using gas chromatography. Male rats were subdivided into 5 groups (8 rats each): normal control (balanced diet), prednisolone control (10 mg/kg prednisolone daily), soybean oil (prednisolone 10 mg/kg + soybean oil 7% w/w), flaxseed oil (prednisolone 10 mg/kg + flaxseed oil 7% w/w), and fish oil (from cod liver; prednisolone 10 mg/kg + fish oil 7% w/w). Results: The study data exhibited a significant depletion in bone mineral density (BMD) and femur mass in the prednisolone control compared to the normal control, accompanied with a marked decrease in the levels of plasma calcium and 1,25-$(OH)_2$-vitamin $D_3$, and elevated levels of C-terminal telopeptide (CTX), tumor necrosis factor-alpha (TNF-${\alpha}$) and malondialdehyde (MDA). Supplementation with fish oil, soybean oil or flaxseed oil helped to improve plasma calcium levels, and suppress oxidative stress and inflammatory markers. Additionally, bone resorption was suppressed as reflected by the decreased CTX levels. However, fish oil was more effective than the other two oils with a significant improvement in BMD and normal histological results compared to the normal control. Conclusion: This study demonstrated that supplementation with dietary oils containing omega-3 PUFAs such as fish oil, soybean oil or flaxseed oil can play a role in the prevention of bone loss and in the regulation of bone metabolism, especially fish oil which demonstrated a greater level of protection against GC-induced osteoporosis.

• Journal of Ginseng Research
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• 제43권4호
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• pp.692-698
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• 2019

Background: Breast cancer is a severe disease and the second leading cause of cancer death in women worldwide. To surmount this, various diagnosis and treatment options for breast cancer have been developed. One of the most effective strategies for cancer treatment is to induce apoptosis using naturally occurring compounds. Compound K (CK) is a ginseng saponin metabolite generated by human intestinal bacteria. CK has been studied for its cardioprotective, antiinflammatory, and liver-protective effects; however, the role of CK in breast cancer is not fully understood. Methods: To investigate the anticancer effects of CK in SKBR3 and MDA-MB-231 cells, cell viability assays and flow cytometry analysis were used. In addition, the direct targets of CK anticancer activity were identified using immunoblotting analysis and overexpression experiments. Invasion, migration, and clonogenic assays were carried out to determine the effects of CK on cancer metastasis. Results: CK-induced cell apoptosis in SKBR3 cells as determined through 3-(4-5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assays, propidium iodide (PI) and annexin V staining, and morphological changes. CK increased the cleaved forms of caspase-7, caspase-8, and caspase-9, whereas the expression of Bcl-2 was reduced by CK. In assays probing the cell survival pathway, CK activated only AKT1 and not AKT2. Moreover, CK inhibited breast cancer cell invasion, migration, and colony formation. Through regulation of AKT1 activity, CK exerts anticancer effects by inducing apoptosis. Conclusion: Our results suggest that CK could be used as a therapeutic compound for breast cancer.

• 대한본초학회지
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• 제36권1호
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• pp.41-49
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• 2021

Objective : Citrus unshiu peel (Citri Unshius Pericarpium) has been prescribed to suppress coughing and phlegm in Korean medicine. In this study, the effect of ethanol extract of Citrus unshiu peel (CEE) on apoptosis was investigated using cadmium chloride (CdCl2) treated HepG2 cells. Methods : CEE was prepared by extracting 300 g of Citri Unshius Pericarpium in 3 L of ethanol for 72 h. Apoptosis was determined by the TUNEL assay. The mitochondrial membrane potential (MMP) was monitored using the membrane-permeable fluorescent dye Rh123. The expression level of each protein was monitored by Western blot analysis. Results : CEE protected HepG2 cells from apoptosis as determined by the TUNEL assay. A decrease in MMP was observed in cells exposed to cadmium, indicating that mitochondria are involved in the induction of apoptosis. However, CEE recovered the reduction in MMP caused by cadmium. In addition, decreased expression of B-cell lymphoma 2 (Bcl-2), procaspase, and poly(ADP-ribose) polymerase (PARP) by cadmium was increased by CEE. The anti-apoptotic effect of CEE was found to be associated with inhibition of JNK and p38 phosphorylation when examining the expression of phosphorylated MAPK by Western blot. Conclusion : This study showed that CEE exerted anti-apoptotic effects in cadmium-induced HepG2 cells by inhibiting the reduction of MMP and changes in the expression level of apoptotic proteins. These results suggest the potential for CEE to be used for heavy metal-induced liver damage.

• 생약학회지
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• 제51권4호
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• pp.278-290
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• 2020

The purpose of this study is to investigate the hangover relieving effect of HO-series. HO-S1 is an herbal mixture, which consists of extracts from Flower of Pueraria lobata Ohwi, Glycyrrhiza glabra Linné, Fruit of Lycium chinense Miller, Poria cocos Wolf, Acanthopanax sessiliflorum Seeman, Scutellaria baicalensis Georgi, Atractylodes lancea De Candlle and Zingiber officinale Roscoe. HO-S2 is a candidate that has been performed to ultra filtration based on HO-S1. HO-S3 is a mixture of amino acids and vitamins based on HO-S2. HO-01 is the final beverage base produced based on HO-S3. The antioxidant activity of HO-series was similar to that of vitamin C or trolox. The production of t-BHP induced reactive oxygen species(ROS) was significantly blocked in the presence of HO-series. In vivo study, AUC of alcohol and acetaldehyde concentrations in HO-S2 and HO-S3 treated groups significantly decreased. Hepatic alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) activity were significantly higher in HO-S2 and HO-S3 treated groups. And 2E1 activity and glutathione were significantly elevated, while the malondialdehyde level was not significantly in liver tissue. After alcohol exposure, the sensitivity scores of blood alcohol and acetaldehyde concentration and hangover symptoms were significantly decreased in the HO-01 intake group compared with the non-intake group. ALDH activity was significantly increased in the HO-01 intake group. HO-series have antioxidant activity and a protective effect from ROS. HO-S2, HO-S3 and HO-01 are potentially highly beneficial in relieving hangover, as it scavenges reactive free radicals and boosts the endogenous antioxidant system.

• Nutrition Research and Practice
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• 제16권1호
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• pp.46-59
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• 2022

BACKGROUND/OBJECTIVES: Aster yomena (Kitam.) Honda (AY) has remarkable bioactivities, such as antioxidant, anti-inflammation, and anti-cancer activities. On the other hand, the effects of AY against obesity-induced insulin resistance have not been reported. Therefore, this study examined the potential of AY against obesity-associated insulin resistance in high-fat diet (HFD)-fed mice. MATERIALS/METHODS: An obesity model was established by feeding C57BL/6J mice a 60% HFD for 16 weeks. The C57BL6/When ethyl acetate fraction from AY (EFAY) at doses of 100 and 200 mg/kg/day was administered orally to mice fed a HFD for the last 4 weeks. Normal and control groups were administered water orally. The body weight and fasting blood glucose were measured every week. Dietary intake was measured every other day. After dissection, blood and tissues were collected from the mice. RESULTS: The administration of EFAY reduced body and organ weights significantly compared to HFD-fed control mice. The EFAY-administered groups also improved the serum lipid profile by decreasing the triglyceride, total cholesterol, and low-density lipoprotein compared to the control group. In addition, EFAY ameliorated the insulin resistance-related metabolic dysfunctions, including the fasting blood glucose and serum insulin level, compared to the HFD-fed control mice. The EFAY inhibited lipid synthesis and insulin resistance by down-regulation of hepatic fatty acid synthase and up-regulation of the AMP-activated protein kinase pathway. EFAY also reduced lipid peroxidation in the liver, indicating that EFAY protected hepatic injury induced by obesity. CONCLUSIONS: These results suggest that EFAY improved obesity-associated insulin resistance by regulating the lipid and glucose metabolism, suggesting that AY could be used as a functional food to prevent obesity and insulin resistance.

• 대한본초학회지
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• 제28권2호
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• pp.83-92
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• 2013

Objectives : We investigated differances of physiological functionalities in the steamed Schisandrae Fructus. Methods : The samples were extracts of dryed schisandrae fructus without steaming process (S0), extracts of schisandrae fructus with three times steamed (S3), extracts of schisandrae fructus with five times steamed (S5) and extracts of schisandrae fructus with seven times steamed (S7). We analyzed contents of schisandrin, gomisin, total polyphenol and flavonoid and antioxidant activities. We researched antiinflammation effects for Raw264.7 cells. To evaluate liver protective activity, we measured AST, ALT and gamma-GTP in serum of alcoholic mice. Results : As the steaming number of schisandrae fructus increase, the contents of schisandrin and gomisin were more increased. The contents of total polyphenol of S5 and S7 were significantly increased compared to that of S0. DPPH free radical scavenging activities of S5 and S7 were significantly increased compared to that of S0, ABST radical scavenging activities of S3 and S5 were significantly increased compared to that of S0 in vitro. The NO production of all sample was significantly decreased compared to control, PGE2 release of S3, S5 and S7 were significantly decreased compared to control. IL-$1{\beta}$ release of S5 and S7 were significantly decreased. AST, ALT and gamma-GTP of S3, S5 and S7 were significantly decreased compared to control. Conclusions : We think that extracts of schisandrae fructus with steaming process may have more potential efficacy than a schisandrae fructus without steaming process.

• 대한본초학회지
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• 제39권1호
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• pp.39-47
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• 2024

Objectives : This study evaluates how various traditional Korean herbal medicines assess MUC5AC expression for esophageal mucosal defense and analyzes the associated mechanisms involved in inflammation. Methods : Forty types of traditional Korean herbal medicines were assessed for in vitro antioxidant activities, and the real-time PCR method was employed to analyze MUC5AC expression under pH 4.5 conditions in human esophageal epithelial cells (HET-1A). Eight types of Korean herbal medicines were evaluated for in vitro antioxidant activities, and Reactive oxygen specise (ROS) expression was analyzed under bile salt (480 𝜇M) and pH 5.5 conditions in human esophageal epithelial cells (HET-1A). Simulation experiments involving bile salts and acidity were conducted for one hour to assess the efficacy of four drugs, and the activities of Mitogen-activated Protein Kinase (MEK), Nuclear Factor Kappa B (NF-𝜅B), and Cyclooxygenase-2 (COX-2) were detected through Western blot analysis. Results : Compared to the Normal group, the Control group exhibited higher ROS generation. Such increased ROS levels were significantly reduced by four extracts: Citrus Unshius Pericarpium (CUP), Cnidium officinale Rhizoma (CR), Ginseng Radix (GR), and Linderae Radix (LR). The protein expression of COX-2 decreased with the treatment of LR, CUP, and CR. Particularly, CUP and CR exhibited superior effects compared to other groups in inhibiting the phosphorylation of NF-𝜅B. Conclusion : Based on the results obtained, we have identified drugs that inhibit oxidative stress and inflammation caused by bile acid in esophageal epithelial cells. Our future plans involve comparing and analyzing the efficacy of these herbal medicines through animal experiments.

• 생명과학회지
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• 제34권2호
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• pp.138-144
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• 2024

Crocin은 여러 가지 요리에 향미와 색깔을 주는 치자 열매나 사프란에 함유되어 있는 적노란색의 수용성 색소이다. 사프란과 치자는 전통의학 분야에서 부종, 해열, 해독 작용이 있어 바이러스성 간염, 식도염, 관상동맥심장병, 신경쇠약, 불면증, 퇴행성 신경질환, 호흡기 질환, 비뇨기 질환 등을 치료하는데 사용되어 왔다. Crocin (C₄₄H₆₄O₂₄)은 카로테노이드의 복합체로, dicarboxylic acid crocetin과 disaccharide gentiobiose로 이루어진 diester이다. Crocin은 혈액학적인, 병리학적인 독성이나 유전독성이 없다. 현재까지 수많은 생체 내 및 생체 외 연구들을 통해 Crocin의 생물학적인 약리작용이 밝혀지고 있다. 본 총설에서는 염증성 장질환, 위염, 천식, 동맥경화, 류머티스 관절염, 다발성 경화증, 당뇨, 알츠하이머병, 파킨슨병, 우울증 등의 염증 관련 질환에서 Crocin의 보호 효과를 요약한다. Crocin은 다양한 작용 기전을 통해 항염, 항산화, 세포 자살 방지 기능을 함으로써 이들 질환을 개선하는 것으로 추론된다.

• Journal of Preventive Medicine and Public Health
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• 제25권1호
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• pp.13-25
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• 1992

This study was conducted to investigate the mechanism of protective effect by sodium selenite in methylmercuric chloride neurotoxicity, increasing intracellular $Ca^{2+}$concentration of the neuron. Methylmercuric chloride of 3mg/kg of body weight was administered simultaneously with sodium selenite of 5mg/kg and pretreatment of sodium selenite via intraperitoneal injection to rats. Also, effect of methylmercuric chloride($25{\mu}M,\;50{\mu}M,\;100{\mu}M$) and sodium selenite($200{\mu}M$) on free intrasynaptosomal $Ca^{2+}$ concentration were studied using the fluorescent $Ca^{2+}$ indicator fura -2 in vitro. After the treatment, at 6, 24, and 48 hours later, mercury in the cerebral cortex, liver and kidney tissues, succlnic dehydrogenase activities, adenosin-5'-triphosphate concentration, acetylcholinesterase activities, and intracellular $Ca^{2+}$ concentration in the cerebral cortex were determined in vivo. Cerebral synaptosomes of rats were incubated with methylmercuric chloride and sodium selenite in Hepes buffer for 10 minutes and free intrasynaptosomal $Ca^{2+}$ concentration were measured with fura-2 in vitro. The results were summarized as follows ; 1. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time significantly more increased in the cerebral cortex and decreased in the liver, kidney mercury concentrations compared to the administration of $CH_3HgCl$ only. 2. The combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ increased more succinic dehydrogenase and acetylcholinesterase activities compared to the administration of $CH_3HgCl$ only. Particularly pretreatment of $Na_2SeO_3$ significantly more compared to the administration of $CH_3HgCl$ only. The concentration of adenosine-5'-triphosphate in $Na_2SeO_3$ treatment groups revealed a favourable effect compared to the administration of $CH_3HgCl$ only. 3. Intracellular $Ca^{2+}$ concentration in administration of $CH_3HgCl$ only was increased significantly more than control group in all test hours but was increased significantly more at 48 hours only after treatment in combined administration of $CH_3HgCl$ and $Na_2SeO_3$ and pretreatment of $Na_2SeO_3$ according to time interval more decreased significantly intracellular $Ca^{2+}$ concentration compared to the administration of $CH_3HgCl$ only. 4. Free intrasynaptosomal $Ca^{2+}$ concentration in the combined administration of $CH_3HgCl$ and $Na_2SeO_3$ was decreased ($24%{\sim}40%$) significantly more than the administration of $CH_3HgCl$ only. From the above results, the specific dosage of $Na_2SeO_3$ decreased increment of intracellular $Ca^{2+}$ concentration induced by administration of $CH_3HgCl$. These findings suggest the protective mechanism of $Na_2SeO_3$ on the neurotoxicity of $CH_3HgCl$.