Protective Effect of Areca catechu Leaf Ethanol Extract Against Ethanol-Induced Gastric Ulcers in ICR Mice

이강파,최난희,Wardani Sudjarwo,안상현,박인식,이상락,홍희옥 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.2

Gastric ulcer is a common digestive disorder that results in considerable suffering. Hence, this digestive pathology has been the focus of a number of recent studies. Although numerous drugs have been developed to treat gastric ulcers, therapeutic approaches for many of the complications associated with these drugs remain to be identified. For this reason, many natural compounds have been explored as alternatives for these drugs. In this study, we have investigated the effectiveness of Areca catechu leaf ethanol extract (ACE) for treating ethanol-induced gastric ulcers in mice. We performed histological as well as immunohistochemical examinations to explore the therapeutic properties of ACE. We also examined the levels of inflammatory signaling molecules to confirm the anti-inflammatory effects of ACE. The histochemical data demonstrate that ACE can protect the mucosal epithelium as well as the vascular supply in the gastric tract. Furthermore, ACE significantly reduced the expression levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 receptor (IL-6R), inducible NO synthase (iNOS), cyclooxygenase 2 (COX2), and nuclear factor-kappa B (NF-κB). Taken together, these data suggest that ACE administration may have the potential as an alternative treatment for gastric ulcer because of its cytoprotective and anti-inflammatory effects and ability to promote the rejuvenation and revascularization of the damaged gastric epithelium.

Piperine Inhibits Platelet-Derived Growth Factor-BB-Induced Proliferation and Migration in Vascular Smooth Muscle Cells

이강파,이관,박원환,김혁,홍희옥 한국식품영양과학회 2015 Journal of medicinal food Vol.18 No.2

The proliferation and migration of vascular smooth muscle cells (VSMCs) in blood vessels are important in the pathogenesis of vascular disorders such as atherosclerosis and restenosis. Piperine, a major component of black pepper, has antioxidant, anticancer, and anti-inflammatory activity. However, the antiatherosclerotic effects of piperine have not been investigated. In this study, the effects of piperine on platelet-derived growth factor (PDGF)-BB-induced proliferation and migration of VSMCs were investigated. The antiproliferative effects of piperine were determined using MTT assays, cell counting, real-time polymerase chain reaction, and western blots. Our results showed that piperine significantly attenuated the proliferation of VSMCs by increasing the expression of p27kip1, regulating the mRNA expression of cell cycle enzymes (cyclin D, cyclin E, and PCNA), and decreasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in a noncytotoxic concentration-dependent manner (30–100 μM). Moreover, we examined the effects of piperine on the migration of PDGF-BB-stimulated VSMCs, as determined by the Boyden chamber assay, H2DCFDA staining, and western blots. Our results showed that 100 μM piperine decreased cell migration, the production of reactive oxygen species (ROS), and phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Taken together, our results suggest that piperine inhibits PDGF-BB-induced proliferation and the migration of VSMCs by inducing cell cycle arrest and suppressing MAPK phosphorylation and ROS. These findings suggest that piperine may be beneficial for the treatment of vascular-related disorders and diseases.

Pharmacological systemic analysis of gardenia fructus against non- alcoholic fatty liver disease and validation of animal models

이강파,김기봉,윤은희,백수지,안상현 한국운동영양학회 2022 Physical Activity and Nutrition (Phys Act Nutr) Vol.26 No.1

[Purpose] We aimed to investigate the systemic pharmacological analysis of gardenia fructus (GF) and the proof of concepts. We examined the antioxidant and anti-inflammatory effects in high-fat (HF) diet mice. [Methods] The active compounds of GF and the target genes were identified using the Traditional Chinese Medicine Database and Analysis Platform (oral bioavailability ≥ 30%, Caco-2 permeability ≥ -0.4, and drug-likeness ≥ 0.18). The rats were divided into four groups: untreated group, HF group, HF and metformin (17 mg/kg) treated group, and HF and treated with GF (28 mg/kg) for 8 weeks group. Hepatic lesion changes and markers were analyzed using hematoxylin and eosin staining and immunohistochemistry assay. [Results] In the systemic analysis, we identified 14 active compounds including A, B, and C. From these 14 compounds, 242 biological target genes were identified. The top 10 GOs were analyzed using GO-biological process analysis: removal of superoxide radicals, regulation of endothelial cell apoptotic process, and cellular response to lipopolysaccharide. GF extracts in high-fat diet-induced non-alcoholic fatty liver disease (NAFLD) mice models significantly regulated hepatic lesion markers, such as mTOR, 8-Hydroxy-2'-deoxyguanosine as well as oxidative stress activities, TGF-β, and phosphorylation of ERK1/2. [Conclusion] These results suggest that GF, as an exercise supplement, can alleviate NAFLD disease or fatty liver inflammation. Further studies are required to verify the synergistic effect of GF treatment combined with exercise, which is known to alleviate NAFLD and fatty liver inflammation.

RAW 264.7 세포에서 Heme Oxygenase-1 발현 유도를 통한 송절(松節) 약침액의 항염증 효능

이강파 ( Kang Pa Lee ),문진영 ( Ji Young Moon ) 대한경락경혈학회 2012 Korean Journal of Acupuncture Vol.29 No.1

Objectives : The gnarl of Pinus densiflora, called Songjeol in Korea, has been used as a medicinal herb for the treatment of inflammatory-related diseases such as arthralgia, myalgia and bruise. However, the molecular actions and mechanisms have not been clearly investigated. The aim of this study was to clarify the anti-inflammatory activity of Pinus densiflora gnarl pharmacopuncture (PDGP) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Methods : Cytotoxicity was assessed by XTT assay. The amount of nitric oxide (NO) production was determined by nitrite assay. The mRNA expressions of interleukin-1β (IL-1β), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and heme oxygenase-1 (HO-1) were analyzed by RT-PCR. Reactive oxidative species (ROS) generation was measured using the fluorescence microscopy. In addition, inducible nitric oxide synthase (iNOS) and redox factor-1 (Ref-1) protein expressions were detected by Western blotting. Results : PDGP inhibited NO production and ROS generation in LPS-stimulated RAW264.7 cells. At the mRNA level, PDGP suppressed IL-1β, IL-6 and COX-2 expression. On the other hand, PDGP induced HO-1 mRNA expression. Furthermore, PDGP suppressed iNOS and Ref-1 protein expression. Conclusions : This result suggests that PDGP can act as a suppressor agent on NO and iNOS through induction of HO-1, and play an useful role in blocking inflammatory responses.

Dansameum regulates hepatic lipogenesis and inflammation in vitro and in vivo

안상현,이강파,김기봉,최준용,박선영,천진홍 한국식품과학회 2019 Food Science and Biotechnology Vol.28 No.5

Although the clinical guidelines for nonalcoholic fatty liver disease (NAFLD) therapy recommended hepato-protection and exercise to reduce body weight, no established medication exists for NAFLD treatment. Thus, the effect of a candidate substance, dansameum (DSE), using an in vitro and NAFLD mouse model (that is, apolipoprotein E-Knockout mice), were investigated. The molecular pathways for lipogenesis and inflammation were evaluated using Nile staining, Western blotting, reverse transcription-polymerase chain reaction, and immunohistochemistry. It was shown that DSE significantly ameliorated the production of lipogenesis-related factors, including liver X receptor-α, peroxisome proliferator-activated receptor-γ, sterol regulatory element binding protein-1, fatty acid synthase, acetyl-CoA carboxylase 1, and CD36. In addition, DSE significantly reduced the production of inflammation factors, including interleukin-1β, interleukin-6, and nuclear factor kappa B. Furthermore, DSE significantly reduced the phosphorylation of c-Jun amino terminal kinase. Taken together, this suggests that DSE may be a functional food candidate for regulating NAFLD, based on its effects.

The Effect of Pinus Densiflora Gnarl Extract for Pharmacopuncture on Human LDL Oxidation Induced by Free Radical and Metal Ion

임선희,이강파,문진영,Leem, Sun-Hee,Lee, Kang-Pa,Moon, Jin-Young Society for Meridian and Acupoint 2011 Korean Journal of Acupuncture Vol.28 No.1

목적 : 이 연구는 관절 및 심혈관계 질환 치료에 사용되는 송절(松節)(Pinus densiflora Gnarl)을 약침용 시료로 조제하여 본 약물의 항산화 효능을 규명하고자 하였으며 이를 다양한 시스템에서 검토하였다. 방법 : $FeCl_2$-ascorbic acid system에서 흰쥐 간조직의 지질과산화 반응을 관찰하였고, Fenton reaction system에서 자유기에 의한 plasmid DNA 분절을 유도하였다. 또한 deoxyribose assay를 통해 hydroxyl radical 소거능을 관찰하였고, NBT reduction assay로 superoxide radical 소거능을 검토하였다. 또한 human low-density lipoprotein(LDL)의 산화를 유도하기 위해 $CuSO_4$와 AAPH를 사용하였으며 relative electrophoretic mobility (REM) assay로 LDL 산화 억제 효능을 대조 항산화물질과 비교 검토하였다. 결과 : 송절 약침액은 자유기에 의한 간조직의 지질과산화(p < 0.01)및 DNA 분절을 현저하게 억제하였으며, hydroxyl radical, superoxide radical (p < 0.01), nitric oxide 및 peroxynitrite를 강하게 소거하였다. 또한 $CuSO_4$ ($IC_{50}=9.2{\pm}0.2\;{\mu}g/ml$)와 AAPH ($IC_{50}=34.8{\pm}5.1\;{\mu}g/ml$)에 의해 유도된 human LDL의 산화를 억제하였고, REM assay에서도 산화 억제 효능을 재확인할 수 있었다. 결론 : 송절 약침액은 활성산소종 및 활성질소종를 소거하였고, 지질과산화를 억제하였으며, 특히 human LDL의 산화적 손상을 방어하였다. 이에 본 약물은 자유기에 의한 심혈관의 산화적 손상을 효과적으로 보호할 것으로 판단된다.

Feasibility of mixed herbal medicine for improving gastric function in an alcohol-induced gastritis model

김기봉,이강파,백수지,박선영,김지수,안상현 한국운동영양학회 2023 Physical Activity and Nutrition (Phys Act Nutr) Vol.27 No.1

[Purpose] Excessive exercise causes various gastric dysfunction. Gastritis is common among athletes who perform high-intensity training. Gastritis is a digestive disease involving mucosal damage caused by inflammatory reactions and oxidative stress. In this study, the effects of a complex natural extract on gastric mucosal damage and the expression of inflammatory factors were evaluated in an animal model of alcohol-induced gastritis. [Methods] A mixed herbal medicine (Ma-al-gan; MAG) was prepared with four natural products (Curcumae longae Rhizoma, Schisandrae chinensis Fructus, Artemisiae scopariae herba, and Gardeniae Fructus) identified by a systemic analysis using the Traditional Chinese Medicine Systems Pharmacology platform. The effects of MAG on alcohol-induced gastric damage were evaluated. [Results] MAG (10–100 μg/mL) significantly reduced the mRNA and protein levels of inducible nitric oxide synthase and cyclooxygenase-2 in lipopolysaccharide-stimulated RAW264.7 cells. MAG (500 mg/kg/d) effectively prevented alcohol-induced gastric mucosal injury in vivo. [Conclusion] MAG regulates inflammatory signals and oxidative stress and is a potential herbal medicine for gastric disorders.

Hyaluronic acid-based biodegradable microneedles loaded with epidermal growth factor for treatment of diabetic foot

백수지,이강파,한충수,권승해,이승준 한국고분자학회 2024 Macromolecular Research Vol.32 No.1

Pain relief and effective methods of treating patients with diabetic foot wounds have yet to be established. Improved surgical treatment, other than suturing, and medical (drug) treatments, are required to address severe symptoms. In this study, we developed a drug delivery system using biodegradable microneedles that are suitable for delivering drugs to sensitive skin and reducing pain. First, we successfully fabricated a silicon mold using a microneedle metal master. The dimensions of the microneedle are width 200 μm × height 250 μm, as confirmed by election microscopy. A microneedle loaded with epidermal growth factor (EGF; 10 ppm) in biodegradable hyaluronic acid, prepared using a silicon mold, was also established for drug delivery. The characteristics of the EGF-loaded microneedles (MPEGF) were also confirmed using porcine back skin and polymer membranes, demonstrating a skin permeability of more than 95%. Finally, MPEGF showed a skin-healing effect and angiogenesis in vitro and ex vivo experiments. Taken together, we suggest that MPEGF may be a new treatment method for patients with diabetic feet for wound healing and blood vessel regeneration.

Inhibitory effect of modified silkworm pupae oil in PDGF-BB-induced proliferation and migration of vascular smooth muscle cells

김영진,이강파,이도영,김윤태,백수지,윤명식 한국식품과학회 2020 Food Science and Biotechnology Vol.29 No.8

Silkworm pupae oil (SPO) has been reported tohave various biological activities in improving blood circulation. However, the protective action of SPO againstvascular disorders remains unknown. A new formulation ofSPO was prepared through an esterification and saponificationprocess. The composition of unsaturated fatty acidsin silkworm pupae oil sodium salt (SPOS) was then analyzedby LC/MS to show a-linolenic acid (11.0%), linoleicacid (73.2%), palmitic acid (3.1%), oleic acid (12.0%), andstearic acid (0.7%). The in vitro studies were performed tofind out the efficacy of SPOS on platelet-derived growthfactor (PDGF-BB) induced vascular smooth muscle cell(VSMC) migration and proliferation. PDGF-BB (10 ng/mL) induced abnormal migration and proliferation ofVSMCs, whereas exposure to SPOS (30 lg/mL)significantly reduced the PDGF-BB-induced cell migrationand proliferation. The extracellular signal-regulatedkinase1/2 (ERK1/2) and phosphorylation of ERK1/2 weredetermined by immunoblot analysis and the ERK1/2phosphorylation in PDGF-BB-stimulated VSMCs wasdownregulated by SPOS (30 lg/mL) treatment. Theseresults indicate that SPOS may be a helpful and usefulagent as a functional food and drug against vasculardisorders.

Effect of black chokeberry on skeletal muscle damage and neuronal cell death

김지수,이강파,백수지,강혜라,김용균,임기원 한국운동영양학회 2019 Physical Activity and Nutrition (Phys Act Nutr) Vol.23 No.4

[Purpose] Numerous epidemiological studies have shown that it is possible to prescribe exercise for neurodegenerative disease, such as Alzheimer's disease and Parkinson’s disease. However, despite the availability of diverse scientific knowledge, the effects of exercise in this regard are still unclear. Therefore, this study attempted to investigate a substance, such as black chokeberry (Aronia melanocapa L.) that could improve the ability of the treatment and enhance the benefits of exercising in neurodegenerative diseases. [Methods] The cell viability was tested with 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolim-5-carboxanilide and the cells were stained with ethidium homodimer-1 solution. The mRNA expression levels were evaluated by microarray. The active compounds of black chokeberry ethanolic extract (BCE) were analyzed by gas chromatography. The chemical shift analysis in the brain was performed using magnetic resonance spectroscopy. [Results] BCE treatment decreased hydrogen peroxide-induced L6 cell death and beta amyloid induced primary neuronal cell death. Furthermore, BCE treatment significantly reduced the mRNA levels of the inflammatory factors, such as IL-1α, Cxcl13, IL36rn, Itgb2, Epha2, Slamf8, Itgb6, Kdm6b, Acvr1, Cd6, Adora3, Cd27, Gata3, Tnfrsf25, Cd40lg, Clec10a, and Slc11a1, in the primary neuronal cells. Next, we identified 16 active compounds from BCE, including D-mannitol. In vivo, BCE (administered orally at a dosage of 50 mg/kg) significantly regulated chemical shift in the brain. [Conclusion] Our findings suggest that BCE can serve as a candidate for neurodegenerative disease therapy owing to its cyto-protective and anti-inflammatory effects. Therefore, BCE treatment is expected to prevent damage to the muscles and neurons of the athletes who continue high intensity exercise. In future studies, it would be necessary to elucidate the effects of combined BCE intake and exercise.