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Phytochemical, Antidiabetic, Antioxidant, Antibacterial, Acute and Sub-Chronic Toxicity of Moroccan Arbutus unedo Leaves

  • Latifa Doudach;Hanae Naceiri Mrabti;Samiah Hamad Al-Mijalli;Mohamed Reda Kachmar;Kaoutar Benrahou;Hamza Assaggaf;Ahmed Qasem;Emad Mohamed Abdallah;Bodour Saeed Rajab;Khouloud Harraqui;Mouna Mekkaoui;Abdelhakim Bouyahya;Moulay El Abbes Faouzi
    • Journal of Pharmacopuncture
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    • v.26 no.1
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    • pp.27-37
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    • 2023
  • Objectives: Moroccan Arbutus unedo is an essential medicinal plant; however, little is known about the biological properties of its leaves mentioned in Moroccan traditional medicine. Methods: Various standard experiments were performed to evaluate the phytochemical, antidiabetic, antioxidant, antibacterial, and acute and sub-chronic toxicity characteristics of A. unedo leaves. Results: Phytochemical screening led to the identification of several phytochemical classes, including tannins, flavonoids, terpenoids, and anthraquinones, with high concentrations of polyphenols (31.83 ± 0.29 mg GAEs/g extract) and flavonoids (16.66 ± 1.47 mg REs/g extract). Further, the mineral analysis revealed high levels of calcium and potassium. A. unedo extract demonstrated significant antioxidant and anti-diabetic activities by inhibiting α-amylase (1.350 ± 0.32 g/mL) and α-glucosidase (0.099 ± 1.21 g/mL) compared to the reference drug Acarbose. Also, the methanolic extract of the plant exhibited significantly higher antibacterial activity than the aqueous extract. Precisely, three of the four examined bacterial strains exhibited substantial susceptibility to the methanolic extract . Minimum bactericidal concentration (MBC)/minimum inhibitory concentration (MIC) values indicated that A. unedo harbor abundant bactericidal compounds. For toxicological studies, mice were administered with A. unedo aqueous extract at single doses of 2,000 and 5,000 mg/kg. They did not exhibit significant abnormal behavior, toxic symptoms, or death during the 14-day acute toxicity test and the 90-day sub-chronic toxicity test periods. The general behavior, body weight, and hematological and biochemical status of the rats were assessed, revealing no toxicological symptoms or clinically significant changes in biological markers observed in the mice models, except hypoglycemia, after 90 days of daily dose administration. Conclusion: The study highlighted several biological advantages of A. unedo leaves without toxic effects in short-term application. Our findings suggest that conducting more comprehensive and extensive in vivo investigations is of utmost importance to identify molecules that can be formulated into pharmaceuticals in the future.

Reparative, Neuroprotective and Anti-neurodegenerative Effects of Granulocyte Colony Stimulating Factor in Radiation-Induced Brain Injury Model

  • Gokhan Gurkan;Ozum Atasoy;Nilsu Cini;Ibrahim Halil Sever;Bahattin Ozkul;Gokhan Yaprak;Cansin Sirin;Yigit Uyanikgil;Ceren Kizmazoglu;Mumin Alper Erdogan;Oytun Erbas
    • Journal of Korean Neurosurgical Society
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    • v.66 no.5
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    • pp.511-524
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    • 2023
  • Objective : This animal model aimed to compare the rat group that received brain irradiation and did not receive additional treatment (only saline) and the rat group that underwent brain irradiation and received Granulocyte colony stimulating factor (G-CSF) treatment. In addition, the effects of G-CSF on brain functions were examined by magnetic resonance (MR) imaging and histopathologically. Methods : This study used 24 female Wistar albino rats. Drug administration (saline or G-CSF) was started at the beginning of the study and continued for 15 days after whole-brain radiotherapy (WBRT). WBRT was given on day 7 of the start of the study. At the end of 15 days, the behavioral tests, including the three-chamber sociability test, open field test, and passive avoidance learning test, were done. After the behavioral test, the animals performed the MR spectroscopy procedure. At the end of the study, cervical dislocation was applied to all animals. Results : G-CSF treatment positively affected the results of the three-chamber sociability test, open-space test and passive avoidance learning test, cornu Ammonis (CA) 1, CA3, and Purkinje neuron counts, and the brain levels of brain-derived neurotrophic factor and postsynaptic density protein-95. However, G-CSF treatment reduced the glial fibrillary acidic protein immunostaining index and brain levels of malondialdehyde, tumor necrosis factor-alpha, nuclear factor kappa-B, and lactate. In addition, on MR spectroscopy, G-CSF had a reversible effect on brain lactate levels. Conclusion : In this first designed brain irradiation animal model, which evaluated G-CSF effects, we observed that G-CSF had reparative, neuroprotective and anti-neurodegenerative effects and had increased neurotrophic factor expression, neuronal counts, and morphology changes. In addition, G-CSF had a proven lactate-lowering effect in MR spectroscopy and brain materials.

Cardioprotective Potential of Gracilaria Verrucosa Extract in Myocardial Infarction-Induced Heart Failure Model (심근 경색 유발 심부전 모델에서 강리 추출물의 심장 보호 가능성)

  • Youn Jae Jang;Hye Yoom Kim;Jung Joo Yoon;Byung Hyuk Han;Je Kuk Yu;Nam Geun Cho;Ho Sub Lee;Dae Gill Kang
    • Herbal Formula Science
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    • v.31 no.3
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    • pp.157-169
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    • 2023
  • Gracilaria Verrucosa (GV), a seaweed used in traditional Korean medicine, was studied for its effects on MI-induced heart failure in rats. MI is caused by a blocked coronary artery, leading to severe cardiac dysfunction. The study used a rat model to assess cardiac changes over time and evaluate the impact of GV on heart failure. Ischemia was induced through LAD ligation surgery, and the extent of ischemic area was measured as a prognostic factor. GV extract administration significantly improved cardiac morphology and reduced cardiac weight compared to the MI group. GV treatment also improved cardiac function, as evidenced by positive effects on chamber dilation during MI-induced heart failure. Parameters such as ejection fraction (EF) and fractional shortening (FS) were measured. The MI group showed decreased EF and FS compared to the sham group, while these parameters improved in the GV group. GV treatment also reduced levels of LDH, CPK, and CK-MB in the serum, indicating reduced myocardial damage. Histological analysis revealed that GV treatment attenuated cardiac hypertrophy and fibrosis, with reduced collagen deposition in the myocardium. Immunohistochemistry analysis showed suppressed expression of TGF-β1 and collagen 1, involved in fibrosis. In conclusion, GV showed potential in improving cardiac function in a rat model of MI-induced heart failure. It alleviated myocardial damage, attenuated cardiac hypertrophy and fibrosis, and suppressed fibrotic markers. Further studies are needed to explore its clinical efficacy and underlying mechanisms in cardiac diseases beyond animal models.

The Effects of Isocaloric High-Fat Diet and Endurance Exercise on Insulin Resistance and Mitochondria Biogenesis (Isocaloric high-fat diet와 지구성 운동이 인슐린 저항성과 미토콘드리아 생합성에 미치는 영향)

  • Jung, Su-Ryun;Kwon, Dae-Yong;Kim, Jin-Hwan;Kang, Ho-Youl
    • 한국체육학회지인문사회과학편
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    • v.51 no.3
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    • pp.353-362
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    • 2012
  • The purpose of this research was to find effects of high fat diet and endurance exercise on mitochondria biosynthesis and insulin resistance in male Wister rat. Th rats were randomly separated into 4 groups: A, Isocaloric high fat diet group (50% of calories from fat), B. Chow group, C. Isocaloric high fat diet with endurance exercise (treadmill running, slop 8%, 23 m/min, 120 min/day, 5 days per week), D. Chow group with endurance exercise. Both Isocaloric high fat diet group and chow group were given an equal caloric composition with 3.2kcal/g. equal amount of food were checked every day and given to both groups. 4 weeks of high fat diet did not show any change in body weight and amount of body fat. Further the level of glucose and insulin in blood, and insulin-stimuilated glucose transport rate in epitrochlearis muscle was not affected by Isocaloric high fat diet. However, the endurance exercise showed statistically significant change in the level of insulin in blood. Although either Isocaloric high fat diet or endurance exercise alone did not change on mitochondria biogenesis marker, Isocaloric high fat diet with endurance exercise could induce the increased level of marker (p<0.05). Also, plasma free fatty acids were increased in this group. From this investigation, Isocaloric high fat diet with moderate-intensity endurance exercise is effective way to induce mitochondrial biogenesis.

The Effect on the Change of Liver and Serum Cholesterol Contents of Albino Rats by the Feeding of the Suerose and Glucose (蔗糖과 葡萄糖이 白鼠肝臟 및 血淸 Cholesterol의 含量에 미치는 影響)

  • Koh, Jin Bog;Lee, Kyung Ro
    • The Korean Journal of Zoology
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    • v.13 no.2
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    • pp.44-50
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    • 1970
  • This experiment was made in order to observe the change in contents of the total cholesterol, free cholesterol and ester cholesterol in the liver and serum by the feeding of glucose and sucrose. The animals used for the experiment were adult male albino rat from a pure strain, weighing 285-332g. The animals were divided into standard, glucose and sucrose diet groups. The glucose and sucrose diet groups were redivided into 10%, 25% and 40% diet groups. Their liver and serum were used as sample after they were fed with the corresponding diets, respectively, for two months. 1. In the liver, the total cholesterol and ester cholesterol contents in the 40% glucose diet group were significantly increased and the free cholesterol contents in all diets were respectively increased, compared with the standard diet group. 2. In the serum, the total cholesterol contents in both diet groups, the 10% glucose and 10% sucrose, were decreased but the content in the 40% sucrose diet group was increased, compared with the standard diet group. The free cholesterol contents in the 10 and 40% glucose diet and 10% sucrose diet group were decreased, compared with the standard diet group. The ester cholesterol contents in the 10% glucose and 10% sucrose diet groups were decreased but the content in the 40% sucrose diet group was increased, compared with the standard diet group. Being taken into consideration of the above facts it was acquired that the cholesterol contents are affected by the amounts and kinds of dietary carbohydrate when the protein contents in each diet were constant.

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The Effect of Glycyrrhizic acid on Vascular Contractility (혈관수축에 대한 감초산 Glycyrrhizic acid의 효과)

  • Hyun Dong Je;Young Sil Min
    • Journal of Industrial Convergence
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    • v.21 no.10
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    • pp.57-63
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    • 2023
  • This study aims to elucidate the effect of glycyrrhizic acid on smooth muscle contraction and to determine the detailed mechanism incorporated. We hypothesized that glycyrrhizic acid played a role in the agonist-sensitive management of smooth muscle contraction. Stripped smooth muscles of Sprague-Dawley rats were prepared in organ baths and isometric tensions were converted, stored and analyzed by using isometric transducers, a physiograph and one way ANOVA. Interestingly, glycyrrhizic acid attenuated the thick filament regulating agonist (fluoride or thromboxane mimetic)-sensitive contraction (p=0.113, 0.008, 0.004 (Student's t-test), p=0.113, 0.008, 0.004 (One way ANOVA) at 0.01, 0.03, 0.1 mM fluoride, and p=0.156, 0.004, 0.003 (Student's t-test), p=0.156, 0.004, 0.003 (One way ANOVA) at 0.01, 0.03, 0.1 mM thromboxane mimetic) and did not attenuate the thin filament regulating agonist (phorbol ester)-induced contraction (p=0.392, 0.086, 0.065 (Student's t-test), p=0.392, 0.086, 0.065 (One way ANOVA) at 0.01, 0.03, 0.1 mM phorbol ester). It is suggesting that endothelial EDRF (NO) synthesis and accessory pathways besides endothelial EDRF (NO) synthesis such as ROCK restriction might be incorporated in the glycyrrhizic acid-induced modulation of smooth muscle contraction inhibiting acto-myosin interaction.

Secreotory Leukocyte Protease Inhibitor Regulates Bone Formation via RANKL, OPG, and Runx2 in Rat Periodontitis and MC3T3-E1 Preosteoblast

  • Seung-Yeon Lee;Soon-Jeong Jeong;Myoung-Hwa Lee;Se-Hyun Hwang;Do-Seon Lim;Moon-Jin Jeong
    • Journal of dental hygiene science
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    • v.23 no.4
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    • pp.282-295
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    • 2023
  • Background: Secretory leukocyte protease inhibitor (SLPI) protects tissues from proteases and promotes cell proliferation and healing. SLPI also reduces periodontal inflammation and alveolar bone resorption by inhibiting proinflammatory cytokine expression in rat periodontal tissues and osteoblasts. However, little is known of the role of SLPI in the expression of osteoclast regulatory factors from osteoblasts, which are crucial for the interaction between osteoblasts and osteoclasts. Therefore, we aimed to determine the effects of SLPI on the regulation of osteoclasts and osteoblasts in LPS-treated alveolar bone and osteoblasts. Methods: Periodontitis was induced in rats using LPS. After each LPS injection, SLPI was injected into the same area. Immunohistochemical analysis was performed with antibodies against SLPI, RANKL, OPG, and Runx2 in the periodontal tissue. RT-PCR and western blotting were performed to determine the expression levels of SLPI, RANKL, OPG, and Runx2 in LPS- and SLPI/LPS-treated MC3T3-E1 cells. SLPI/LPS-treated MC3T3-E1 cells were also stained with Alizarin Red S. Results: Immunohistochemical analysis showed that the expression levels of SLPI, OPG, and Runx2 were higher while that of RANKL was lower in the LPS/SLPI group relative to those in the LPS group. The mRNA and protein expression of SLPI, OPG, and Runx2 was higher in SLPI/LPS/MC3T3-E1 cells than in LPS/MC3T3-E1 cells, and RANKL expression was lower. During differentiation, OPG and Runx2 protein levels were higher whereas RANKL levels were lower in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 cells on days 0, 4, 7, and 10. In addition, mineralization and matrix deposition were higher in SLPI/LPS/MC3T3-E1 than in LPS/MC3T3-E1 on days 7 and 10. SLPI decreased RANKL expression in LPS-treated alveolar bone and osteoblasts but increased the expression of OPG and Runx2. Conclusion: SLPI can be considered as a regulatory molecule that indirectly regulates osteoclast activation via osteoblasts and promotes osteoblast differentiation.

Protective Effect of Rubus crataegifolius Extracts Against Obesity and Non-alcoholic Fatty Liver Disease via Promotion of AMPK/ACC/CPT-1 Pathway in HFD-induced C57BL/6J Obese Mice (HFD 유도 C57BL/6J 비만 mice에서 AMPK/ACC/CPT-1 경로 촉진을 통한 산딸기 추출물의 비만 및 비알코올성 지방간 질환에 대한 보호 효과)

  • Young Ik Lee;Hui Jin Lee;Su Jin Pyo;Yong Hyun Park;Myng Min Lee;Ho-Yong Sohn;Jin Sook Cho
    • Journal of Life Science
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    • v.33 no.12
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    • pp.967-977
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    • 2023
  • Rubus crataegifolius (RC) is a traditional Asian medicinal plant belonging to the Rosaceae family. The fruits of RC are known to prevent adult diseases through antioxidants. In this study, the effects of RC extract (RCex) on obesity and nonalcoholic fatty liver disease (NAFLD) were evaluated in animal models. Twenty-eight male C57BL/6J mice were induced to become obese for 8 weeks and then the extract was orally administered for 8 weeks. RCex reduced body weight, adipose tissue, liver weight. RCex improved biochemical biomarkers including lipid metabolism (alanine aminotransferase (ALT), aspartate aminotransferase (AST), plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol). The activation of AMP-activated protein kinase (AMPK) reduced the expression of adipogenesis genes (liver × receptor (LXR), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthesis (FAS), acetyl-CoA carboxylase 1 (ACC1) and the effect of enhancing carnitine palmitoyltransferase (CPT) activity by RCex was verified. RCex also influence on plasma production of hormones (adiponectin & leptin) related on energy expenditure and metabolism. In addition, we confirmed that RCex improved glucose intolerance in HFD-induced obese rats. RCex was first demonstrated to have anti-obesity as well as anti-NAFLD effects by regulating fatty acid oxidation and fatty acid synthesis by phosphorylation of AMPK. This suggests that RCex could be a good supplement for the prevention of obesity and related NAFLD.

The purified extract of steamed Panax ginseng protects cardiomyocyte from ischemic injury via caveolin-1 phosphorylation-mediating calcium influx

  • Hai-Xia Li;Yan Ma;Yu-Xiao Yan;Xin-Ke Zhai;Meng-Yu Xin;Tian Wang;Dong-Cao Xu;Yu-Tong Song;Chun-Dong Song;Cheng-Xue Pan
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.755-765
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    • 2023
  • Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca2+ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca2+ ([Ca2+]i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca2+]i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca2+]i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca2+]i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca2+ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca2+]i.

Cardioprotection via mitochondrial transplantation supports fatty acid metabolism in ischemia-reperfusion injured rat heart

  • Jehee Jang;Ki-Woon Kang;Young-Won Kim;Seohyun Jeong;Jaeyoon Park;Jihoon Park;Jisung Moon;Junghyun Jang;Seohyeon Kim;Sunghun Kim;Sungjoo Cho;Yurim Lee;Hyoung Kyu Kim;Jin Han;Eun-A Ko;Sung-Cherl Jung;Jung-Ha Kim;Jae-Hong Ko
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.3
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    • pp.209-217
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    • 2024
  • In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.