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Sulfated Cyclocarya paliurus polysaccharides exert Immunomodulatory potential on macrophages via Toll-like receptor 4 mediated MAPK/NF-κB signaling pathways

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Food Science and Human Wellness 2024年第1期13卷 115-123页

作者： Yue Yu Haibin Zhu Mingyue Shen Qiang Yu Yi Chen Shiru Mo Jianhua Xie State Key Laboratory of Food Science and Technology Nanchang UniversityNanchang 330047China International Institute of Food Innovation Nanchang UniversityNanchang 330200China

The biological activity of plant polysaccharides can be enhanced by sulfated modification.In this study,the Immunomodulatory effect of sulfated Cyclocarya paliurus polysaccharides(SCP3)on macrophages RAW264.7 and its potential molecular mechanism were investigated.Results showed that SCP3 at 25-100μg/m L increased viability and improved phagocytosis of RAW264.7 cells.Meanwhile,SCP3 could activate mitogen-activated protein kinase(MAPK)and nuclear factor kappa B(NF-κB)signaling pathways,which increased the phosphorylation of Erk1/2,JNK,p38 and NF-κB p65,promoting secretion of cytokines tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and nitric oxide(NO)as well as the production of reactive oxygen species(ROS).In addition,Toll-like receptor 4(TLR4)receptor inhibitors were able to block the production of NO and TNF-αby SCP3-stimulated macrophages.Based on Western blot analysis and validation using specific inhibitors against MAPK and NF-κB signaling pathways,the results demonstrated that SCP3 induced macrophages activation and enhanced TNF-αand NO production via TLR4-mediated MAPK and NF-κB pathways.In summary,SCP3 has significant Immunomodulatory potential.The underlying molecular mechanism was that SCP3 activates macrophages via TLR4 receptors to promote ROS production,which in turn activates the downstream MAPK/NF-κB signaling pathway and then increases the secretion levels of cytokines and NO.

关键词： Cyclocarya paliurus Sulfated polysaccharides Macrophages Immunomodulatory Mechanism

Amelioration of Alzheimer's disease pathology and cognitive deficits by Immunomodulatory agents in animal models of Alzheimer's disease

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Neural Regeneration Research 2019年第7期14卷 1158-1176页

作者： Bridget Martinez Philip V.Peplow Department of Molecular & Cellular Biology University of California Department of Medicine St.Georges University School of Medicine Department of Physics and Engineering Los Alamos National Laboratory Department of Anatomy University of Otago

The most common age-related neurodegenerative disease is Alzheimer's disease(AD) characterized by aggregated amyloid-β(Aβ) peptides in extracellular plaques and aggregated hyperphosphorylated tau protein in intraneuronal neurofibrillary tangles,together with loss of cholinergic neurons,synaptic alterations,and chronic inflammation within the brain.These lead to progressive impairment of cognitive function.There is evidence of innate immune activation in AD with microgliosis.Classically-activated microglia(M1 state) secrete inflammatory and neurotoxic mediators,and peripheral immune cells are recruited to inflammation sites in the brain.The few drugs approved by the US FDA for the treatment of AD improve symptoms but do not change the course of disease progression and may cause some undesirable effects.Translation of active and passive immunotherapy targeting Aβ in AD animal model trials had limited success in clinical trials.Treatment with Immunomodulatory/anti-inflammatory agents early in the disease process,while not preventive,is able to inhibit the inflammatory consequences of both Aβ and tau aggregation.The studies described in this review have identified several agents with Immunomodulatory properties that alleviated AD pathology and cognitive impairment in animal models of AD.The majority of the animal studies reviewed had used transgenic models of early-onset AD.More effort needs to be given to creat models of late-onset AD.The effects of a combinational therapy involving two or more of the tested pharmaceutical agents,or one of these agents given in conjunction with one of the cell-based therapies,in an aged animal model of AD would warrant investigation.

关键词： Alzheimer’s disease neuropathology cognitive deficits behavioral deficits Immunomodulatory agents animal models amyloid deposits gliosis

Immunomodulatory Activity of Granulocyte Colony-Stimulating Factor and its Therapeutic Effect on Liver Failure

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Infectious Diseases & Immunity 2022年第1期2卷 42-48页

作者： Jinhua Hu Zijian Sun Jingjing Tong Jing Chen Zifeng Liu Senior Department of Hepatolgy The Fifth Medical Center of PLA General HospitalBeijing 100039China Medical School of Chinese PLA Beijing 100853China Department of Emergency Medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Infectious Diseases Beijing Jishuitan HospitalBeijing 100035China

Liver failure is characterized by the rapid deterioration of liver function,often accompanied by ascites,coagulation dysfunction,hepatic encephalopathy,and other critical complications.Owing to the complex multifaceted pathogenesis and consequential clinical manifestations of the disease,liver failure displays poor prognosis and warrants comprehensive clinical treatment and management.Liver transplantation remains the only well-established treatment for liver failure.However,several factors including transplantation cost and low organ donation rates limit the rate of liver transplantation.The development of a suitable therapy for liver failure is a significant challenge and remains a cause of concern for the medical world.Granulocyte colony-stimulating factor(G-CSF),a member of the cytokine family of hematopoietic growth factors,is involved in the migration of hematopoietic stem cells into the damaged liver,and effectuates their dedifferentiation into hepatocytes.Liver regeneration involves a complex crosstalk of multiple cell types,including hepatocytes,endothelial cells,and inflammatory cells.Neutrophils and monocytes/macrophages that present different types of innate immune cells were found to play a crucial role in the progression of inflammation and restoration of the liver tissue.G-CSF,known as the most common used cytokine,may also affect these immune cells by combining G-CSF receptors on their surface.The Immunomodulatory activity of G-CSF should be studied and described in order to ascertain its therapeutic effect on liver failure.

关键词： Granulocyte colony-stimulating factor Immunomodulatory Liver failure

Immunomodulatory and anticancer activity of Bombax ceiba Linn leaf extract

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Asian Pacific Journal of Tropical Biomedicine 2020年第9期10卷 426-432页

作者： Neelima Sharma Sneha Kispotta Papiya Mitra Mazumder Department of Pharmaceutical Sciences&Technology Birla Institute of TechnologyMesraRanchiIndia

Objective:To evaluate the Immunomodulatory and anticancer activity of the methanolic extract of Bombax ceiba leaves in vitro and in vivo.Methods:The antioxidant property of methanolic extract of Bombax ceiba leaves was determined by measuring hydrogen peroxide scavenging and DPPH scavenging activity.The effect on cellular immunity in vivo was determined by measuring neutrophil adhesion,carbon clearance,sheep red blood cell induced DTH response and cyclophosphamide-induced myelosuppression.In vitro anticancer activity was evaluated on human leukaemia cell line(HL-60)by MTT assay,caspase-3 activity,and cell cycle study.Results:The methanolic extract of Bombax ceiba leaves showed antioxidant activity and significantly increased neutrophil adhesion,carbon clearance from blood,DTH response and cyclophosphamideinduced myelosuppression.The MTT assay showed a significant increase in the death of HL-60 cell line.A rise in caspase-3 activity and sub-G1 population in the presence of methanolic extract of Bombax ceiba leaves was observed.Conclusions:The methanolic extract of leaves of Bombax ceiba L possesses anticancer activity,Immunomodulatory activity,and antioxidant properties,proving its therapeutic usefulness in the treatment of immuno-compromised diseases and cancers.

关键词： Anticancer Antioxidative Bombax ceiba Immunomodulatory

Protoscolicidal and Immunomodulatory activity of Ziziphora tenuior extract and its fractions

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Asian Pacific Journal of Tropical Medicine 2016年第11期9卷 1040-1046页

作者： Mojtaba Shahnazi Abbas Azadmehr Ammar Andalibian Reza Hajiaghaee Mehrzad Saraei Mahmood Alipour Department of Parasitology Qazvin University of Medical Sciences Cellular&Molecular Research Institute Qazvin University of Medical Sciences Department of Immunology Babol University of Medical Sciences Department of Pharmacognosy& Pharmaceutics Department of Medicinal Plants Research Center Institute of Medicinal Plants ACECR Department of Social Medicine Qazvin University of Medical Sciences

Objective:To evaluate the scolicidal and Immunomodulatory effect of the Ziziphora tenuior(Z.tenuior) extract and its fractions.Methods:Protoscolices were treated with six concentrations(3,5,10,25,50,and 100 mg/mL) of Z.tenuior extract and its fractions(ethanol,petroleum ether,ethyl acetate and chloroform) in periods of 10,20,30,40,50 and 60 minutes,and viability of protoscolices was evaluated using the 1.0%eosin.To examine the Immunomodulatory effects of Ziziphora and its fractions on macrophage cells,the non-toxic concentration of extract and different fractions determined by MTT assay,and the Griess reaction was used to measure the level of nitrite as an indicator of nitric oxide by the macrophage cells in 10,100 and 200 μg/mL in 24 hours at 37 ℃.Results:In this study,the Z.tenuior extract at 10 mg/mL concentration was able to kill all protoscolices during 20 minutes.By increasing the concentration to 25 mg/mL,the scolicidal time reduced to 10 minutes.Regarding the effect of different fractions of Z.tenuior,the ethanolic fraction showed the highest scolicidal activity.The extract demonstrated an inhibitory effect on the activity of macrophages and reduced nitric oxide production.Although the petroleum ether and ethanolic fractions of the extract reduced nitric oxide production,nevertheless,this effect was only significant at 10 and 100 ug/mL concentrations(P<0.05).Conclusion:The Z.tenuior extract and its fractions were effective against protoscolices yet the effect of total extract was considerable.Our findings indicates that the extract and its ethanolic and petroleum ether fractions could have anti-inflammatory properties.

关键词： Hydatid cyst Protoscolicidal Ziziphora tenuior Immunomodulatory Macrophage Nitric oxide Fraction

Immunomodulatory therapies for acute pancreatitis

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World Journal of Gastroenterology 2014年第45期20卷 16935-16947页

作者： Jing Li Wen-Juan Yang Lu-Ming Huang Cheng-Wei Tang Department of Gastroenterology West China Hospital Sichuan University Division of Peptides Related with Human Diseases Key Laboratory of Biotherapy of Human Diseases Ministry of Education

It is currently difficult for conventional treatments of acute pancreatitis(AP),which primarily consist of antiinflammatory therapies,to prevent the progression of AP or to improve its outcome.This may be because the occurrence and progression of AP,which involves various inflammatory cells and cytokines,includes a series of complex immune events.Considering the complex immune system alterations during the course of AP,it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using Immunomodulatory therapy.This review discusses the recent advances in Immunomodulatory therapies.It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP.The optimal duration of anti-inflammatory therapy may be shorter than previously expected(<24 h),and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the courseof AP.A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy.Additionally,the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis.

关键词： Pancreatitis Immunomodulatory therapy Systemic inf

Immunomodulatory effects and structure-activity relationship of botanical pentacyclic triterpenes:A review

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Chinese Herbal Medicines 2020年第2期12卷 118-124页

作者： Nurul Hikmah Harun Abdi Wira Septama Wan Amir Nizam Wan Ahmad Rapeah Suppian School of Health Sciences Heath CampusUniversiti Sains MalaysiaKubang Kerian 16150Malaysia School of Biomedicine Faculty of Health SciencesUniversiti Sultan Zainal AbidinKuala Nerus 21300Malaysia Research Center for Chemistry Indonesian Institute of SciencesKawasan Puspitek SerpongTangerang Selatan 15314Indonesia

Botanical pentacyclic triterpenes possessed a broad range of pharmacological activities such as antioxidant,anti-tumor,anti-microbial and anti-inflammatory activities.It is believed that the mechanisms involved in these bioactivities are due to the modulation of immune system.Recently,the pharmacological validation on Immunomodulatory of pentacyclic triterpenes derived from higher plants is very limited and several existence review papers related for this group of compound have not been focused for this activity.In this review,we have highlighted several studies on Immunomodulatory potential of botanical pentacyclic triterpenes isolated from wide array of different species of medicinal plants and herbs based on various preclinical in vitro and animal models.This review also attempts to discuss on bioactivities of compouns related with their structure-activity relationship.Hence,the evaluation of pentacyclic triterpenes offers a great opportunity to discover adjuvants and novel therapeutic agents that presented beneficial Immunomodulatory properties.

关键词： botanical Immunomodulatory pentacyclic triterpenes structure activity relationship

Chemistry Behind the Immunomodulatory Activity of Astragalus membranaceus

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Chinese Medicine and Culture 2021年第4期4卷 201-210页

作者： Mallique Qader Jian Xu Yuejun Yang Xiaohua Wu Yuancai Liu Shugeng Cao Department of Pharmaceutical Sciences Daniel K.Inouye College of PharmacyUniversity of Hawai’i at HiloHawaii 96720USA Hubei Provincial Key Laboratory of Quality and Safety of Traditional Chinese Medicine Health Food Jing Brand Research InstituteJing Brand Co.Ltd.Daye 435100HubeiChina

Huang Qi(黄芪Astragalus membranaceus)is a well-known and widely used herb in traditional Chinese medicine(TCM)tonic preparations.It has been used for many ailments over the last 2000 years.Flavonoids,saponins,and polysaccharides have been shown to be the main compounds responsible for the biological and pharmacological activities,especially the Immunomodulatory properties,of such tonic preparations.This review summarizes the published data on Astragalus extracts and fractions and the natural compounds responsible for the Immunomodulatory activity with special reference to the modulation of nuclear factor-kappa B and related pathways(e.g.,Nrf2).In addition,this review highlights the importance of Astragalus membranaceus in TCM for treating patients with diseases related to immunocompromised conditions,such as cancer and diabetes.

关键词： Huang Qi(黄芪Astragalus membranaceus) Immunomodulatory nuclear factor-kappa B phytochemicals

Cycling and Tai Chi Chuan exercises exert greater Immunomodulatory effect on surface antigen expression of human hepatitis B virus

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Chinese Medical Journal 2008年第21期121卷 2172-2179页

作者： CHEN Yu-yawn CHIANG Jasson CHEN Yu-jen CHEN Kung-tung YANG Rong-sen LIN Jaung-geng Department and Graduate School of Physical Education National Taiwan Sport University Taichung Taiwan China Graduate Institute of Sport Coaching Science Chinese Culture University Taipei Taiwan China Department of Medical Research Department of Radiation Oncology Mackay Memorial Hospital Taipei Taiwan China College of Humanities Social and Natural Sciences Ming Hsin University of Sciences and Technology Taiwan China Department of Orthopaedics College of Medicine National Taiwan University & Hospital Taipei Taiwan China Graduate Institute of Chinese Medical Science China Medical University. Taichung 404. Taiwan. China

Background Both athletes with intensive exercise and aged people may have weakened immunity against virus infection. This study aimed to evaluate whether people undergoing aerobic exercises including competitive cyclists with moderate training （CMT） and middle-aged people practicing Tai Chi Chuan （TCC） exercise have higher immunity against hepatitis B virus than age-matched sedentary controls including college students （CSC） and middle-aged people （MSC）. Methods Human peripheral blood mononuclear cells from competitive cyclists and sedentary controls were stimulated by phytohemagglutinin （PHA） to prepare conditioned medium （MNC-CM） for the assessment of inhibitory effects on hepatitis B surface antigen （HBsAg） expression in human hepatoma Hep3B cells. Results The inhibitory effects on the relative HBsAg expression of CMT＇s and TCC＇s MNC-CM were greater than those of the controls. The CMT＇s MNC-CM prepared from 5 μg/ml PHA decreased HBsAg expression to 61.5%, whereas that of CSC remained at 83.8%. Similarly, this expression by treatment of TCC group＇ MNC-CM was 68.4% whereas that of MSC group was 84.3%. The levels of cytokines such as interferon-γ（IFN-γ）, tumor necrosis factor-α （TNF-α）, IFN-α and interleukin-1β （IL-1β） in the MNC-CM from the CMT and TCC groups were greater than those in the controls. Antibody neutralization of CMT＇s MNC-CM and addition of recombinant cytokines into CSC＇s MNC-CM indicated that IFN-γ, TNF-α and IFN-α had synergistic effects against HBsAg expression. Similar blocking effect was noted in TCC versus MSC groups. Conclusion These results suggest that the Immunomodulatory response to suppress HBsAg expression in CMT and TCC with moderate aerobic exercise is greater than that in age-matched sedentary controls.

关键词： competitive cyclists Immunomodulatory hepatitis B surface antigens