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Rumex acetosella Inhibits Platelet Function via Impaired MAPK and Phosphoinositide 3-Kinase Signaling

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Chinese Journal of Integrative medicine 2022年第9期28卷 802-808页

作者： Bo-Ra Jeon Muhammad Irfan Seung Eun Lee Jeong Hoon Lee Man Hee Rhee Laboratory of Physiology and Cell Signaling College of Veterinary MedicineKyungpook National UniversityDaegu41566Republic of Korea department of herbal Crop Research National Institute of Horticultural and Herbal Science(NIHHS)Eumseong27709Republic of Korea

Objective:To examine the antiplatelet and antithrombotic activity of Rumex acetosella extract.Methods:Standard light aggregometry was used for platelet aggregation,intracellular calcium mobilization assessed using Fura-2/AM,granule secretion(ATP release)by luminometer,and fibrinogen binding to integrin α_(Ⅱb)β_(3) detected using flow cytometry.Western blotting is carried out to determine the phosphorylation of mitogen-activated protein kinase(MAPK)and phosphoinositide 3-kinase(PI3K)/Akt signaling.Results:Rumex acetosella displayed the ability to inhibit platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin α_(Ⅱb)β_(3).Rumex acetosella has also down-regulated MAPK and PI3K/Akt phosphorylation(all P<0.01).Conclusion:Rumex acetosella extract exhibits antiplatelet activity via modulating GPVI signaling,and it may protect against the development of platelet-related cardiovascular diseases.

关键词： antiplatelet ethnomedicine integrinα_(Ⅱb)β_(3) mitogen-activated protein kinase Rumex acetosella L.

Neuroprotective effects of Fructus Chebulae extracts on experimental models of cerebral ischemia

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中医杂志：英文版 2014年第1期34卷 69-75页

作者： Bhakta Prasad Gaire Hocheol Kim department of herbal Pharmacology College of Korean MedicineKyung Hee University

OBJECTIVE:To investigate the neuroprotective effects of Fructus Chebulae extract using both in vivo and invitromodels of cerebral ischemia.METHODS:As an in vitro model,oxygen glucose deprivation followed by reoxygenation(OGD-R)and hydrogen peroxide(H2O2)induced cellular damage in rat pheochromocytoma(PC12)cells was used to investigate the neuroprotective effects of extract of Fructus Chebulae.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to calculate cell survival.For in vivo,occlusion of left middle cerebral artery on rats was carried out as a focal cerebral ischemic model.RESULTS:Fructus Chebulae extract increases the PC12 cell survival against OGD-R and H2O2by 68%and 91.4%respectively.Fructus Chebulae also de-creases the cerebral infarct volume by 39%and extent of hemisphere swelling from 17%in control group to 10%in FructusChebulaetreated group.CONCLUSION:Fructus Chebulae,as a traditional medicine,can rescue the neuronal cell death against ischemia related damage.The possible mechanism for the neuroprotection might be the inhibition of oxidative damages occurring after acute phase of cerebral ischemia.

关键词：局灶性脑缺血神经保护作用实验模型提取物诃子细胞存活率细胞损伤神经细胞死亡

Pancreatic melatonin enhances anti-tumor immunity in pancreatic adenocarcinoma through regulating tumor-associated neutrophils infiltration and NETosis

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1554-1567页

作者： Yau-tuen Chan Hor-yue Tan Yuanjun Lu Cheng Zhang Chien-shan Cheng Junyu Wu Ning Wang Yibin Feng School of Chinese medicine the University of Hong KongHong KongChina Centre for Chinese herbal medicine Drug Development School of Chinese MedicineHong Kong Baptist UniversityHong KongChina department of Traditional Chinese medicine Shanghai Jiaotong UniversitySchool of Medicine Affiliated Ruijin HospitalShanghai 200025China

Tumor microenvironment contributes to poor prognosis of pancreatic adenocarcinoma(PAAD)patients.Proper regulation could improve survival.Melatonin is an endogenous hormone that delivers multiple bioactivities.Here we showed that pancreatic melatonin level is associated with patients'survival.In PAAD mice models,melatonin supplementation suppressed tumor growth,while blockade of melatonin pathway exacerbated tumor progression.This anti-tumor effect was independent of cytotoxicity but associated with tumor-associated neutrophils(TANs),and TANs depletion reversed effects of melatonin.Melatonin induced TANs infiltration and activation,therefore induced cell apoptosis of PAAD cells.Cytokine arrays revealed that melatonin had minimal impact on neutrophils but induced secretion of Cxcl2 from tumor cells.Knockdown of Cxcl2 in tumor cells abolished neutrophil migration and activation.Melatonin-induced neutrophils presented an N1-like anti-tumor phenotype,with increased neutrophil extracellular traps(NETs)causing tumor cell apoptosis through cell-to-cell contact.Proteomics analysis revealed that this reactive oxygen species(ROS)-mediated inhibition was fueled by fatty acid oxidation(FAO)in neutrophils,while FAO inhibitor abolished the anti-tumor effect.Analysis of PAAD patient specimens revealed that CXCL2 expression was associated with neutrophil infiltration.CXCL2,or TANs,combined with NET marker,can better predict patients'prognosis.Collectively,we discovered an anti-tumor mechanism of melatonin through recruiting N1-neutrophils and beneficial NET formation.

关键词： Pancreatic adenocarcinoma Melatonin Anti-tumor immunity Tumor-associated neutrophils Tumor microenvironment CXCL2 Neutrophil extracellular traps NETosis

Schizonepeta tenuifolia inhibits collagen stimulated platelet function via suppressing MAPK and Akt signaling

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The Journal of Biomedical Research 2019年第4期33卷 250-257页

作者： Bo-Ra Jeon Muhammad Irfan Minki Kim Seung Eun Lee Jeong Hoon Lee Man Hee Rhee Laboratory of Physiology and Cell Signaling College of Veterinary MedicineKyungpook National UniversityDaegu 41566Republic of Korea department of herbal Crop Research National Institute of Horticultural and Herbal ScienceEumseong 27709Republic of Korea.

The prevalence of cardiovascular diseases(CVDs)is increasing at a rapid pace in developed countries,and CVDs are the leading cause of morbidity and mortality.Natural products and ethnomedicine have been shown to reduce the risk of CVDs.Schizonepeta(S.)tenuifolia is a medicinal plant widely used in China,Korea,and Japan and is known to exhibit anti-inflammatory,antioxidant,and immunomodulatory activities.We hypothesized that given herbal plant exhibit pharmacological activities against CVDs,we specifically explored its effects on platelet function.Platelet aggregation was evaluated using standard light transmission aggregometry.Intracellular calcium mobilization was assessed using Fura-2/AM,and granule secretion(ATP release)was measured in a luminometer.Fibrinogen binding to integrin a_(Ⅱb)β_3,was assessed using flow cytometry.Phosphorylation of mitogen-activated protein kinase(MAPK)signaling molecules and activation of the protein kinase B(Akt)was assessed using Western blot assays.S.tenuifolia,extract potently and significantly inhibited platelet aggregation,calcium mobilization,granule secretion,and fibrinogen binding to integrin a_(Ⅱb)β_3.Moreover,all extracts significantly inhibited MAPK and Akt phosphorylation.S.tenuifolia extract inhibited platelet aggregation and granule secretion,and attenuated collagen mediated GPVI downstream signaling,indicating the potential therapeutic effects of these plant extracts on the cardiovascular system and platelet function.We suggest that S.tenuifolia extract may be a potent candidate to treat platelet-related CVDs and to be used as an antiplatelet and antithrombotic agent.

关键词： S.tenuifolia platelet MAPK Akt natural antithrombotic agent

Phyllanthus emblica叶提取物对慢性应激大鼠睾丸损伤有改善作用（英文）

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2018年第12期19卷 948-959页

作者： Supatcharee ARUN Jaturon BURAWAT Supataechasit YANNASITHINON Wannisa SUKHORUM Akgpol LIMPONGSA Sitthichai IAMSAARD department of Anatomy Faculty of Medicine Khon Kaen University Center for Research and Development of herbal Health Product Faculty of Pharmaceutical Sciences School of medicine Mae Fah Luang University

目的:探讨Phyllanthus emblica L.(PE)叶提取物对慢性应激大鼠睾丸损伤和相关蛋白标志物变化的影响。方法:将成年雄性大鼠分成四组:对照组、慢性应激(CS)组和两组PE提取物治疗组(50或100mg/kg体重(BW))。对各组的精子质量、睾丸和尾附... 详细信息

目的:探讨Phyllanthus emblica L.(PE)叶提取物对慢性应激大鼠睾丸损伤和相关蛋白标志物变化的影响。方法:将成年雄性大鼠分成四组:对照组、慢性应激(CS)组和两组PE提取物治疗组(50或100mg/kg体重(BW))。对各组的精子质量、睾丸和尾附睾的组织学特征、以及血清皮质酮、睾酮和丙二醛(MDA)的水平进行分析比较。并使用免疫印迹分析研究睾丸类固醇合成快速调节蛋白(StAR)和酪氨酸磷酸化蛋白的表达。结论:结果显示,50mg/kgBW的PE能显着增加精子浓度和睾酮水平,同时降低CS大鼠中皮质酮水平、MDA水平、以及精子头异常和顶体反应精子的比例。此外,两种剂量的PE都能缓解CS大鼠的睾丸组织病理学特征。同时我们还发现,50 mg/kg BW的PE可以显著提高StAR蛋白的表达,并改变睾丸中部分酪氨酸磷酸化蛋白的强度。总之,50 mg/kgBW的PE叶提取物可以预防CS大鼠的睾丸损伤。

关键词： Phyllanthusemblica L.叶提取物慢性应激睾丸损伤酪氨酸磷酸化

Acanthopanax senticosus Protects Structure and Function of Mesencephalic Mitochondria in A Mouse Model of Parkinson's Disease

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Chinese Journal of Integrative medicine 2018年第11期24卷 835-843页

作者： LIU Shu-min LI Xu-zhao ZHANG Shuai-nan YANG Zhi-ming WANG Ke-xin LU Fang WANG Chong-zhi YUAN Chun-su Drug Safety Evaluation Center Heilongjiang University of Chinese Medicine department of Pharmacy Guiyang College of Traditional Chinese Medicine Institute of Traditional Chinese medicine Heilongjiang University of Chinese Medicine Tang Center for herbal medicine Research and Department of Anesthesia and Critical Care University of Chicago

Objective： To investigate the neuro-protective effects of Acanthopanax senticosus Harms（EAS） on mesencephalic mitochondria and the mechanism of action, using a mouse model of Parkinson＇s disease（PD）. Methods： The chemical fingerprint analysis of the extract of Acanthopanax senticosus Harms（EAS） was performed using the ultra performance liquid chromatograph and time of flight mass spectrometry. Thirty mice were randomly divided into the control group, the MPTP model group, and the EAS treated group with MPTP（MPTP＋EAS group, 10 in each group）. The MPTP model group and the MPTP＋EAS group received MPTP-HCl（30 mg/kg i.p） once a day for 5 days. The control group received an equal volume of saline（20 m L/kg i.p） once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride daily（MPTP-HCl, 30 mg/kg） for 5 days, the PD mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral testing of mice was carried out using the pole-climbing test. The integrity and functions of neurons were examined in mesencephalic mitochondria in a PD mouse model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone flavoprotein 2（NDUFV2）, mitochondrially encoded nicotinamide adenine dinucleotide dehydrogenase 1（MT-ND1）, succinate dehydrogenase complex subunit A（SDHA）, and succinate dehydrogenase cytochrome b560 subunit（SDHC）. Results： After treatment with EAS, the behavioral changes induced by MPTP were attenuated significantly（P〈0.05）. EAS protected the mesencephalic mitochondria from swelling and attenuated the decreases in their membrane potential（both P〈0.05）, which was supported by an ultra-structural level analysis. The changes in reactive oxygen species（ROS）, malonic dialdehyde（MDA）, oxidative phosphorylation（OXPHOS） system 4 subunits levels and PD-related proteins expressions（parkin, Pink1, DJ-1, α-synuclein, and Lrrk2） reverted to near normal levels（all P〈0.05）, based on the results of immune-histological and Western blotting observations. Conclusions： The neuro-protectiv

关键词： Acanthopanax senticosus Harms Parkinson＇s disease mitochondrial dysfunction mitochondrial structural damage oxidative phosphorylation system

Caulerpa okamurae extract attenuates inflammatory interaction,regulates glucose metabolism and increases insulin sensitivity in 3T3-L1 adipocytes and RAW 264.7 macrophages

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Journal of Integrative medicine 2020年第3期18卷 253-264页

作者： Bikash Manandhar Hyun Jung Kim Dong Young Rhyu department of Oriental medicine Resources and Institute of Korean herbal medicine Industry Mokpo National UniversityJeonnam 58554South Korea College of Pharmacy Mokpo National UniversityJeonnam 58554South Korea

Objective: To examine whether Caulerpa okamurae ethanolic extract(COE) could inhibit obesitymediated inflammation, improve glucose metabolism and increase insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3 T3-L1 adipocytes.Methods: We cocultured 3 T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW264.7 macrophages and induced insulin resistance in 3 T3-L1 adipocytes with tumor necrosis factor-a(TNF-a) in the presence or absence of 250 mg/m L of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide(NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptasepolymerase chain reaction to evaluate m RNA expression.Results: We found that COE(250 mg/m L) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-j B. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-a, interleukin-6 and monocyte chemoattractant protein m RNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4(GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1(IRS1). In the TNF-a-induced insulin resistance model of 3 T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-50 adenosine monophosphate-activated protein kinase a and glycogen synthase kinase-3 b(Ser9) as well as upregulation of GLUT-4.Conclusion: Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.

关键词： Caulerpa okamurae RAW 264.7 macrophages 3T3-L1 adipocytes Coculture Metabolic disorder

Amelioration of altered antioxidant enzyme activity by Satureja khuzistanica essential oil in alloxan-induced diabetic rats

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Chinese Journal of Natural medicines 2014年第9期12卷 672-676页

作者： Hassan Ahmadv Razi herbal Researches Center Lorestan University of Medical Sciences department of Biochemistry Faculty of Medicine Lorestan University of Medical Sciences

AIM: To examine the possible protective effect of Satureja khuzistanica essential oil(SKE) on antioxidant enzyme activity in alloxan-induced Type 1 diabetic rats. METHOD: Thirty Sprague-Dawley male rats were divided into three groups randomly; group one as control, group two diabetic, with no treatment, and group three treatment with SKE at 500 ppm in drinking water, respectively. Diabetes was induced in the second and third groups by alloxan injection subcutaneously. After eight weeks, animals were anaesthetized. Blood samples were also collected before killing to measure antioxidant enzymes activity. RESULTS: SKE significantly increased the serum level of glutathione and the serum activity of glutathione peroxidase, superoxide dismutase, and catalase in the treated group compared with the diabetic untreated group. CONCLUSION: The findings showed that SKE exerts beneficial effects on the antioxidant enzymes activity in alloxan-induced Type 1 diabetic rats.

关键词： Diabetes Antioxidant enzyme activity Satureja khuzistanica Essential oil

Biosynthesis of titanium dioxide nanoparticles using Hypericum perforatum and Origanum vulgare extracts and their main components,hypericin and carvacrol as promising antibacterial agents

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Journal of Traditional Chinese medicine 2022年第2期42卷 167-175页

作者： Mojtaba Khaksarian Mahmoud Bahmani Morovat Taherikalani Behnam Ashrafi Mahmoud Rafieian-Kopaei Naser Abbasi department of Physiology and Pharmacology School of MedicineRazi Herbal Medicines Research CenterLorestan University of Medical SciencesKhorramabadIran Biotechnology and Medicinal Plants Research Center Ilam University of Medical SciencesIlamIran Razi herbal medicines Research Center Lorestan University of Medical SciencesKhorramabadIran department of Microbiology School of MedicineLorestan University of Medical SciencesKhorramabadIran Medical Plants Research Center Basic Health Sciences InstituteShahrekord University of Medical SciencesShahrekordIran department of Pharmacology Faculty of Medicine Ilam University of Medical Sciences IlamIran

OBJECTIVE:To evaluate the anti-bacterial activities of titanium dioxide(Ti O;)nanoparticles of Origanum(O.)vulgare and Hypericum(H.)perforatum extracts,carvacrol and hypericin against Staphylococcus(S.)aureus.METHODS:In this study,Ti O;nanoparticles of O.vulgare and H.perforatum extracts,carvacrol and hypericin,were prepared and their antibacterial effects were evaluated against Staphylococcus(S.)aureus.In this study,scanning electron microscope,fourier transform infrared spectrometer,atomic force microscopy,dynamic light scattering and zeta potential were used to investigate the structure of synthesized drugs.RESULTS:Anti-bacterial activity of synthesized NPs was tested by minimum inhibitory concentration(MIC),minimum bactericidal concentration and disc diffusion method.MICs of Ti O;-NPs synthesized using O.vulgare,H.perforatum,carvacrol and hypericin and Ti O;were obtained 250,62.5,250,and 250,and 500μg/m L,respectively.The MBCs for all of these were obtained 1000μg/m L.CONCLUSION:Green-synthesized of Ti O;nanoparticles provides a promising approach to the use of O.vulgare and H.perforatum,carvacrol and hypericin as novel agents and safer antibacterial compounds,especially anti-S.aureus compounds.

关键词： plant medicinal medicine traditional anti-infective agents active ingredient nano-compounds