• 대한한방내과학회지
• /
• 제35권1호
• /
• pp.70-78
• /
• 2014

Objectives : Hoechunyanggyeok-san (HYS) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory diseases. HYS has been reported to be a useful treatment for diabetes, atherosclerosis and hyperlipidemia in the type 1 diabetic model. However, the mechanism of the effects of HYS against hyperglycemia and hyperlipidemia is poorly understood. In the present study, we investigated the underlying mechanism of ameliorative effect of HYS on hyperglycemia and hyperlipidemia in vivo. Methods : HYS (10, 50 mg/kg/day, p.o.) was administered every day for 2 weeks to db/db mice and its effect was compared with vehicle-treated db/db mice. To confirm serum glucose and triglyceride (TG) changes, serological testing was performed. The levels of sterol regulatory element-binding protein-1 (SREBP-1) activity and Sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$) expression were analyzed by western blot analysis. Results : The administration of HYS significantly decreased the elevated serum glucose and TG in db/db mice. HYS administration increased the levels of SIRT1 and AMPK expression compared with the vehicle-treated group. Moreover, HYS treatment significantly inhibited SREBP-1 activity and $ACC{\alpha}$ expression in the liver, while the vehicle-treated group exhibited their increase. Conclusions : In conclusion, HYS is suggested to have an improvement effect on hyperglycemia and hyperlipidemia by activating the SIRT1/AMPK signaling pathway and inhibiting SREBP-1.

• Biomolecules & Therapeutics
• /
• 제25권6호
• /
• pp.609-617
• /
• 2017

Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.

• 생명과학회지
• /
• 제29권4호
• /
• pp.410-420
• /
• 2019

한의학에서는 진피(陳皮)라고 칭하는 귤의 껍질(Citrus unshiu peel) 추출물은 항산화, 항염증 및 항균 특성을 포함한 다양한 약리학적 효능을 갖는 것으로 알려져 있다. 최근 그들의 항암 활성에 대한 가능성이 보고되었지만 정확한 기전 연구는 여전히 미비한 실정이다. 본 연구에서는 인간 유방암 MDA-MB-231 세포를 대상으로 진피 에탄올(EECU, ethanol extract of C. unshiu peel) 추출물의 항암 효능을 평가하고 그에 따른 기전 연구를 수행하였다. 본 연구의 결과에 의하면 EECU에 의한 MDA-MB-231 세포의 증식억제는 세포사멸(apoptosis) 유도와 관련이 있었다. EECU에 의한 apoptosis는 caspase-8, -9 및 -3의 활성화와 IAPs 계열의 발현 감소에 따른 PARP의 분해와 Bax : Bcl-2 비율의 증가와 연관이 있었다. 또한 EECU는 Bid의 truncation과 함께 미토콘드리아 막 잠재력의 감소와 세포질로 cytochrome c의 이동을 촉진시켰다. 아울러 EECU는 AMPK 및 ACC의 인산화를 촉진시켰으나, AMPK 효소 활성의 저해제는 EECU에 의한 apoptosis 유도와 생존력 저하를 현저하게 억제하였다. 부가적으로 EECU는 AMPK 활성화의 상류 신호로 작용하는 활성산소종(ROS)의 생성을 촉진시켰으며, 강력한 항산화제인 NAC는 EECU에 의한 AMPK의 활성화와 apoptosis를 역전시켰다. 결론적으로 EECU는 ROS/AMPK 의존적인 내인성 및 외인성 apoptosis 경로를 활성화시킴으로써 MDA-MB-231 세포 증식을 억제하였음을 알 수 있었다.

• 한국자원식물학회지
• /
• 제37권4호
• /
• pp.307-313
• /
• 2024

본 연구는 추출용매에 따른 세잎쥐손이풀 추출물의 중성지방 조절에 대한 논문으로 3T3-L1 지방전구세포를 이용해 지방세포로 분화유도한 뒤 lipid accumulation, triglyceride contents, PPARγ, C/EBPα, FAS, SCD-1 및 AMPK 단백질 발현을 확인하였다. 실험결과 다섯가지 조건의 세잎쥐손이풀 추출물 중 NG-GT-T3L lipid accumulation과 triglyceride contents의 가장 높은 억제 효능을 확인하였다. NG-GT-T3L 추출물의 세포내 지방 축적 억제는 지방세포 내 adipogenesis와 lipogenesis를 조절하는 효소 조절을 통해 나타난 결과로 판단된다. 따라서 세잎쥐손이풀 추출물은 PPARγ, C/EBPα, FAS, SCD-1를 억제시키고, AMPK를 증가시켜 세포내 중성지방을 조절함으로서 체지방 감소 후보 소재로의 사용이 가능할 것으로 사료된다.

• 한방비만학회지
• /
• 제24권1호
• /
• pp.25-40
• /
• 2024

Objectives: In the present study, we investigated the effects of clean-diabetes mellitus 3 (C-DM3), a herbal formula with Trichosanthis Radix, Coptidis Rhizoma, Crataegi Fructus, and Cinnamomi Cortex, on the pathological and serological symptoms of diabetes and its related molecular mechanisms in diet-induced obese mice. Methods: We prepared an obese mouse model using a high-fat diet for 8 weeks and then administered the C-DM3 extract for 4 weeks. The changes of pathological and serological biomarkers for diabetes assessment were measured in the mice and histological changes were observed in the liver and pancreas tissues. We also identified the main compounds in the C-DM3 extract using high pressure liquid chromatography (HPLC) and analyzed the molecular mechanism of the disease condition by network pharmacological analysis. Results: In the in vivo, the administration of C-DM extract to obese mice significantly reduced body weight gain, fatty liver symptoms, and muscle loss, and decreased the levels of fasting blood glucose, insulin, aspertate aminotransferase, triglycerides, and low-density lipoprotein-cholesterol. In addition, C-DM extract significantly increased the phosphorylation of insulin receptor substrate 1, protein kinase b (AKT), phosphoinositide 3-kinase (PI3K), adenosine monophosphate-activated protein kinase, and glucose transporter 4 in all pancreatic and liver tissues, with inhibition of histopathological changes in obese mice. HPLC analysis identified hyperoside, berberine, epiberberine, columbamin, coptisine, coumarin, jatrorrhizine, and citric acid as the main compounds. In the network pharmacological analysis, the molecular targets of C-DM3 extract on obesity and diabetes were shown as the insulin, AKT, PI3K, and mitogen-activated protein kinase pathways with the regulation of inflammatory molecules interleukin 6 (IL-6), jun proto-oncogene, and IL-1β, which matched our in vivo targets. Conclusions: Based on these results, C-DM3 extract is expected to be effective in improving obesity and preventing diabetic progression.

• Molecules and Cells
• /
• 제39권3호
• /
• pp.195-203
• /
• 2016

Copper is an essential element required for a variety of functions exerted by cuproproteins. An alteration of the copper level is associated with multiple pathological conditions including chronic ischemia, atherosclerosis and cancers. Therefore, copper homeostasis, maintained by a combination of two copper ions ($Cu^+$ and $Cu^{2+}$), is critical for health. However, less is known about which of the two copper ions is more toxic or functional in endothelial cells. Cubic-shaped $Cu_2O$ and CuO crystals were prepared to test the role of the two different ions, $Cu^+$ and $Cu^{2+}$, respectively. The $Cu_2O$ crystal was found to have an effect on cell death in endothelial cells whereas CuO had no effect. The $Cu_2O$ crystals appeared to induce p62 degradation, LC3 processing and an elevation of LC3 puncta, important processes for autophagy, but had no effect on apoptosis and necrosis. $Cu_2O$ crystals promote endothelial cell death via autophagy, elevate the level of reactive oxygen species such as superoxide and nitric oxide, and subsequently activate AMP-activated protein kinase (AMPK) through superoxide rather than nitric oxide. Consistently, the AMPK inhibitor Compound C was found to inhibit $Cu_2O$-induced AMPK activation, p62 degradation, and LC3 processing. This study provides insight on the pathophysiologic function of $Cu^+$ ions in the vascular system, where $Cu^+$ induces autophagy while $Cu^{2+}$ has no detected effect.

• Journal of Ginseng Research
• /
• 제46권2호
• /
• pp.255-265
• /
• 2022

Background: Ginsenoside Rb1, a bioactive component isolated from the Panax ginseng, acts as a remedy to prevent myocardial injury. However, it is obscure whether the cardioprotective functions of Rb1 are related to the regulation of endogenous metabolites, and its potential molecular mechanism still needs further clarification, especially from a comprehensive metabolomics profiling perspective. Methods: The mice model of acute myocardial ischemia (AMI) and oxygen glucose deprivation (OGD)-induced cardiomyocytes injury were applied to explore the protective effect and mechanism of Rb1. Meanwhile, the comprehensive metabolomics profiling was conducted by high-performance liquid chromatography and quadrupole time-of-flight mass spectrometry (HPLC-Q/TOF-MS) and a tandem liquid chromatography and mass spectrometry (LC-MS). Results: Rb1 treatment profoundly reduced the infarct size and attenuated myocardial injury. The metabolic network map of 65 differential endogenous metabolites was constructed and provided a new inspiration for the treatment of AMI by Rb1, which was mainly associated with mitophagy. In vivo and in vitro experiments, Rb1 was found to improve mitochondrial morphology, mitochondrial function and promote mitophagy. Interestingly, the mitophagy inhibitor partly attenuated the cardioprotective effect of Rb1. Additionally, Rb1 markedly facilitated the phosphorylation of AMP-activated protein kinase α (AMPKα), and AMPK inhibition partially weakened the role of Rb1 in promoting mitophagy. Conclusions: Ginsenoside Rb1 protects acute myocardial ischemia injury through promoting mitophagy via AMPKα phosphorylation, which might lay the foundation for the further application of Rb1 in cardiovascular diseases.

• Journal of Ginseng Research
• /
• 제45권6호
• /
• pp.617-630
• /
• 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.

• 한방재활의학과학회지
• /
• 제32권2호
• /
• pp.19-36
• /
• 2022

Objectives This study is to investigate the effects and mechanisms of Imyo-san (IMS) on the obese mice model induced by high-fat diet. Methods Antioxidative capacity was measured by in vitro method. C57BL/6 mice were randomly assigned into 5 groups (n=7). Normal group was fed general diet (Normal). The other 4 groups were fed high fat diet (HFD) with water (Control), with Garcinia gummi-gutta (GG, Garcinia gummi-gutta 200 mg/kg), with low-dose IMS (IMSL, Imyo-san 0.54 g/kg) and with high-dose IMS (IMSH, Imyo-san 1.08 g/kg). Results IMS showed high radical scavenging activity. After 6 week experiment, body weight, food intake, food efficiency ratio (FER), epididymal fat and liver weight, triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, sterol regulatory element-binding protein-1 (SREBP-1), phospho-acetyl-CoA carboxylase (p-ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), phospho-liver kinase B1 (p-LKB1), phospho-AMP-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor 𝛼 (PPAR𝛼), peroxisome proliferator-activated receptor 𝛾 coactivator-1𝛼 (PGC-1𝛼), uncoupling protein-2 (UCP-2), carnitine palmitoyltransferase 1A (CPT-1A), and histology of liver and epididymal fat were measured and analysed. Body weight gain, FER, liver and epididymal fat weight of IMS groups were significantly decreased. There were significant improvements in blood lipids with less TG, TC, LDL-cholesterol, VLDL-cholesterol and more HDL-cholesterol. Proteins associated with lipid synthesis (SREBP-1, p-ACC, FAS, SCD-1) and cholesterol (SREBP-2, HMGCR) was improved. Factors regulating lipid synthesis and lipid catabolism (p-LKBI, p-AMPK, PPARα, PGC-1α, UCP-2, CPT-1A) were increased. In histological examinations, IMS group had smaller fat droplets than control group. All results increased depending on concentration. Conclusions It can be suggested that IMS has anti-obesity effects with improving lipid metabolism.

• 한국자원식물학회:학술대회논문집
• /
• 한국자원식물학회 2018년도 추계학술대회
• /
• pp.101-101
• /
• 2018

Resveratrol is a polyphenolic compound, which is a naturally occurring phytochemical and is found in a variety of plants, including food such as grapes, berries and peanuts. Although several studies have demonstrated that resveratrol possesses anti-cancer activity against various types of human cancer, the molecular mechanisms of resveratrol-mediated overcome drug resistance potential are unclear. In this study, we determined whether resveratrol attenuates drug resistance responses in 5-fluorouracil-resistant colon cancer (SNUC5/5-FUR) cells. Treatment with resveratrol significantly enhanced apoptosis in a concentration-dependent manner, which was associated with the modulation of anti- and/or pro-apoptotic protein expression, activation of caspases and activation of AMP-activated protein kinase. Resveratrol treatment also increased the induction of autophagy through up-regulation of autophagy-related genes such as Microtubule-associated protein 1A/1B-light chain 3, P62 and beclin-1. However, blocking of autophagy by bafilomycin A1 reduced apoptotic cell death, suggesting that resveratrol-induced autophagy functions as a cell death mechanism in SNUC5/5-FU cells. Although the further studies are needed, these findings suggest that resveratrol may have therapeutic potential to overcome drug resistance in colon cancer patients.