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Protective role of fruits of Rosa odorata var. gigantea against WIRSinduced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis

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Chinese Herbal Medicines 2024年第2期16卷 263-273页

作者： Xinnan Liu Zhen Yuan Lifei Luo Teng Wang Feng Zhao Jingze Zhang Dailin Liu National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Tianjin Modern Innovation Chinese Medicine Technology Co. Ltd.Tianjin 300380China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved.Methods: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot.Results: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival.Conclusion: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of

关键词： anti-apoptosis anti-inflammation anti-oxidation gastric mucosal injury Rosa odorata Sweet var.gigantea(Coll.et Hemsl.)Rehd.et Wils water immersion restrained stress

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Protective Effect of Fresh/Dry Dandelion Extracts on APAP-Overdose-Induced Acute Liver Injury

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Chinese Journal of Integrative Medicine 2022年第8期28卷 683-692页

作者： ZHENG Yao LEI Lei LIANG Shuai AI Jiao DENG Xin LI Yan-qiu ZHANG Tian-pei PU Shi-biao REN Yong-shen School of Pharmaceutical Science South-Central University for NationalitiesWuhan430074China College of Chinese Materia Medica Yunnan University of Chinese MedicineKunming650500China

Objecitvie:To compare the liver protective activity of fresh/dried dandelion extracts against acetaminophen(APAP)-induced hepatotoxicity.Methods:Totally 90 Kunming mice were randomly divided into10 groups according to body weight(9 mice for each group).The mice in the normal control and model(vehicle control)groups were administered sodium carboxymethyl cellulose(CMC-Na,0.5%)only.Administration groups were pretreated with high and low-dose dry dandelion extract(1,000 or 500 g fresh herb dried and then decocted into 120 mL solution,DDE-H and DDE-L);low-,medium-and high-dose dandelion juice(250,500,1,000 g/120 mL,DJ-L,DJ-M,and DJ-H);fresh dandelions evaporation juice water(120 mL,DEJW);dry dandelion extract dissolved by pure water(1 kg/120 mL,DDED-PW);dry dandelion extract dissolved by DEJW(120 g/120 mL,DDED-DEJW)by oral gavage for 7 days at the dosage of 0.5 mL solution/10 g body weight;after that,except normal control group,all other groups were intraperitonealy injected with 350 mg/kg APAP to induce liver injury.Twenty hours after APAP administration,serum and liver tissue were collected and serum alanine aminotransferase(AST),aspartate transaminase(ALT),alkaline phosphatase(AKP),malondialdehyde(MDA),glutathione(GSH),superoxide dismutase(SOD)activities were quantified by biochemical kits;tumor necrosis factor(TNF-α),interleukin(IL)-2,and IL-1β contents in liver tissue were determined by enzyme linked immunosorbent assay kits.Histopathological changes in liver tissues were observed by hematoxylin and eosin staining;TUNEL Assay and Hoechst 33258 staining were applied for cell apoptosis evaluation.The expressions of heme oxygenase-1(HO-1),nuclear factor erythroid-2-related factor 2(Nrf-2),caspase-9,B-cell leukemia/lymphoma 2(Bcl-2),Bax and p-JNK were determined by Western blot analysis.Results:Pretreatment with fresh dandelion juice(FDJ,including DJ-L,DJ-M,DJ-H,DEJW and DDED-DEJW)significantly decreased the levels of serum ALT,AST,AKP,TNF-α and IL-1β compared with vehicle control group(P<0.05 or P<0.01).Additionall

关键词： fresh dandelion juice acetaminophen-induced liver injury oxidative stress anti-inflammation anti-apoptosis

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Carrier-free programmed spherical nucleic acid for effective ischemic stroke therapy via self-delivery antisense oligonucleotide

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Nano Research 2023年第1期16卷 735-745页

作者： Wenyan Yu Cuiping Xuan Bingbing Liu Lei Zhou Na Yin Enpeng Gong Zhenzhong Zhang Yinchao Li Kaixiang Zhang Jinjin Shi School of Pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China Key Laboratory of Targeting Therapy and Diagnosis for Critical Diseases Zhengzhou 450001China Collaborative Innovation Center of New Drug Research and Safety Evaluation Zhengzhou 450001China

antisense oligonucleotide(ASO)for anti-apoptosis is emerging as a highly promising therapeutic agents for ischemic stroke with complex pathological environment.However,its therapeutic efficacy is seriously limited by a number of challenges including inefficient internalization,low blood-brain barrier(BBB)penetration,poor stability,and potential toxicity of the carrier.Herein,a carrier-free programmed spherical nucleic acid nanostructure is developed for effective ischemic stroke therapy via integrating multifunctional modules into one DNA structure.By co-encoding caspase-3-ASO and transferrin receptor(TfR)aptamer into circle template,the spherical nucleic acid nanostructure(TD)was obtained via self-assembly.The experimental results demonstrated that the developed TD displayed efficient BBB penetration capability(6.4 times)and satisfactory caspase-3 silence effect(2.3 times)due to the dense DNA packaging in TD.Taken together,our study demonstrated that the carrier-free programmed spherical nucleic acid nanostructure could significantly improve the therapeutic efficacy of ischemic stroke and was a promising therapeutic tool for various brain damage-related diseases.

关键词： antisense oligonucleotide caspase-3 blood-brain barrier(BBB)penetration anti-apoptosis ischemic stroke

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Dalbergia odorifera Essential Oil Protects against Myocardial Ischemia through Upregulating Nrf2 and Inhibiting Caspase Signaling Pathways in Isoproterenol-Induced Rats

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World Journal of Traditional Chinese Medicine 2023年第3期9卷 338-347页

作者： Can-Hong Wang Bao Gong Hui Meng Yu-Lan Wu Xiang-Sheng Zhao Jian-He Wei Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine Hainan Branch of the Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeHaikouChina Key Laboratory of State Administration of Traditional Chinese Medicine for Agarwood Sustainable Utilization Hainan Branch of the Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeHaikouChina Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical College Ministry of Education and National Engineering Laboratory for Breeding of Endangered Medicinal Materials Institute of Medicinal Plant DevelopmentChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Objective:Dalbergia odorifera has long been used as a Chinese herbal medicine for the treatment of cardiovascular and cerebrovascular diseases.This study aimed to determine the potential myocardial protective effect and possible mechanism of action of D.odor ife ra essential oil(DOEO).Materials and Methods:The essential oil of D.odorifera was extracted by hydrodistillation.The cardioprotective effects of DOEO were examined by histopathological observation,myocardial enzyme detection,peroxidation,anti-oxidant level detection,and related protein expression.The compounds in the blood were identified by gas chromatography-mass spectrometry.Results:These results showed that DOEO had significant myocardial cell protection,with IC50 values ranging from 17.64 to 24.78μg/mL in vitro.Compared to the myocardial ischemia group,the DOEO pretreatment groups had lower levels of myocardial injury,creatinine kinase,lactate dehydrogenase,alanine transaminase,aspartate transaminase,hydrogen peroxide,and nitric oxide,and higher levels of glutathione and superoxide dismutase.In addition,DOEO pretreatment significantly increased Na+-K+-ATPase and Ca2+-ATPase levels.Moreove r,immunohistochemical e xperiments showed that DOEO remarkably increased the protein levels of NF-E2-related nuclear factor 2(Nrf2)and heme oxygenase-1(HO-1)and reduced the expression of apoptotic caspases,including caspase 3 and caspase 9.The main components of the blood were transnerolidol and nerolidol oxide.Overall,the study showed that DOEO displayed myocardial protection by upregulating the NF-E2-related nuclear factor-antioxidant response element(Nrf2-ARE)and caspase pathways.DOEO has a therapeutic effect on MI by inhibiting the oxidant and apoptotic effects.Conclusions:D.odorifera may be a potential candidate drug for treating myocardial ischemic injury.

关键词： anti-apoptosis anti-oxidation Dalbergia odorifera essential oil Isoproterenol Myocardial ischemia

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Neuroprotective Effects of Molecular Hydrogen:A Critical Review

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Neuroscience Bulletin 2021年第3期37卷 389-404页

作者： Wei Chen Han-Ting Zhang Shu-Cun Qin Taishan Institute for Hydrogen Biomedicine Shandong First Medical University and Shandong Academy of Medical SciencesTai'an 271000China Key Laboratory of Atherosclerosis in Universities of Shandong and Institute of Atherosclerosis Shandong First Medical University and Shandong Academy of Medical SciencesTai’an 271000China Departments of Neuroscience and Behavioral Medicine and Psychiatry Rockefeller Neurosciences InstituteWest Virginia University Health Sciences CenterMorgantownWV 26506USA

Molecular hydrogen(H_(2))is a physiologically inert gas.However,during the last 10 years,increasing evidence has revealed its biological functions under pathological conditions.More specifically,H_(2) has protective effects against a variety of diseases,particularly nervous system disorders,which include ischemia/reperfusion injury,traumatic injury,subarachnoid hemorrhage,neuropathic pain,neurodegenerative diseases,cognitive dysfunction induced by surgery and anesthesia,anxiety,and depression.In addition,H_(2) plays protective roles mainly through anti-oxidation,anti-inflammation,antiapoptosis,the regulation of autophagy,and preservation of mitochondrial function and the blood-brain barrier.Further,H_(2) is easy to use and has neuroprotective effects with no major side-effects,indicating that H_(2) administration is a potential therapeutic strategy in clinical settings.Here we summarize the H_(2) donors and their pharmacokinetics.Meanwhile,we review the effectiveness and safety of H_(2) in the treatment of various nervous system diseasesbased on preclinical and clinical studies,leading to the conclusion that H_(2) can be a simple and effective clinical therapy for CNS diseases such as ischemia-reperfusion brain injury,Parkinson's disease,and diseases characterized by cognitive dysfunction.The potential mechanisms involved in the neuroprotective effect of H_(2) are also analyzed.

关键词： Molecular hydrogen(H_(2)) Neurological disease Neuroprotection anti-oxidation anti-inflammation anti-apoptosis

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Dandelion polyphenols protect against acetaminophen-induced hepatotoxicity in mice via activation of the Nrf-2/HO-1 pathway and inhibition of the JNK signaling pathway

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Chinese Journal of Natural Medicines 2020年第2期18卷 103-113页

作者： REN Yong-Shen ZHENG Yao DUAN Huan LEI Lei DENG Xin LIU Xin-Qiao MEI Zhi-Nan DENG Xu-Kun School of Pharmaceutical Sciences South-Central University for NationalitiesWuhan 430074China

We investigated the liver protective activity of dandelion polyphenols(DP)against acetaminophen(APAP;Paracetamol)-induced hepatotoxicity.Mice were acclimated for 1 week and randomly divided into the following groups(n=9 per group):Control,APAP,APAP+DP(100 mg·kg^–1),APAP+DP(200 mg·kg^–1),and APAP+DP(400 mg·kg^–1)groups.Mice were pretreated with DP(100,200,and 400 mg·kg^–1)by oral gavage for 7 d before being treated with 350 mg·kg^–1 APAP for 24 h to induced hepatotoxicity.Severe liver injury was observed,and hepatotoxicity was analyzed after 24 h by evaluation of biochemical markers,protein expressions levels,and liver histopathology.Pretreatment with DP was able to restore serum liver characteristics(aspartate transaminase,AST;alanine aminotransferase,ALT;alkaline phosphatase,AKP),improve redox imbalance(superoxide dismutase,SOD;glutathione,GSH;malondialdehyde,MDA),and decrease inflammatory factors(tumor necrosis factor-α,TNF-α;interleukin-1β,IL-1β).Pretreatment with DP also significantly inhibited the expression levels of nitric oxide synthase(iNOS)and cyclooxygenase-2(COX-2).Furthermore,DP pretreatment could inhibit the apoptosis of liver cells caused by APAP through up-regulation of Bcl-2 and down-regulation of Bax and caspase-9 protein.DP also down-regulated p-JNK protein expression levels to inhibit APAP-induced mitochondrial oxidative stress and up-regulated the expression of Nrf-2 and its target gene HO-1.The histopathological staining demonstrated that DP pretreatment could inhibit APAP-induced hepatocyte infiltration,congestion,and necrosis.Our results demonstrate that DP pretreatment could protect against APAP-induced hepatic injury by activating the Nrf-2/HO-1 pathway and inhibition of the intrinsic apoptosis pathway.

关键词： Dandelion polyphenols APAP-induced liver injury Oxidative stress anti-inflammation anti-apoptosis JNK pathways Nrf-2/HO-1 pathways

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antioxidant and antiapoptotic Polyphenols from Green Tea Extract Ameliorate CCl4-Induced Acute Liver Injury in Mice

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Chinese Journal of Integrative Medicine 2020年第10期26卷 736-744页

作者： DIAO Jian-xin OU Jin-ying DAI Huan LI Hai-ye HUANG Wei HUA He-yu XIE Ting WANG Ming YANG Yun-gao School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Department of Internal Medicine Yongxing County People’s HospitalChengzhou(423000)Hunan ProvinceChina Department of Traditional Chinese Medicine Zhujiang Hospital of Southern Medical UniversityGuangzhou(510515)China

Objective To investigate the phenolic composition,antioxidant properties,and hepatoprotective mechanisms of polyphenols from green tea extract(GTP)in carbon tetrachloride(CCl4)-induced acute liver injury mouse model.Methods High-performance liquid chromatography was used to analyze the chemical composition of the extract.antioxidant activity of GTP was assessed by O2∙-,OH∙,DPPH∙,and ferric-reducing antioxidant power(FRAP)assay in vitro.Sixty Kunming mice were divided into 6 groups including control,model,low-,medium-,and high-doses GTP(200,400,800 mg/kg)and vitamin E(250 mg/kg)groups,10 in each group.GTP and vitamin E were administered at a level of abovementioned doses twice per day for 7 days prior to exposure to a single injection of CCl4.Hepatoprotective effects of GTP were evaluated in a CCl4-induced mouse model of acute liver injury,using commercial enzyme linked immunosorbent assay kits,histopathological observation,terminal deoxynucleotidyl transferase-mediated dUTPNick-end labeling(TUNEL)assay and Western blot.Results GTP contained 98.56µg gallic acid equivalents per milligram extract total polyphenols,including epicatechingallate,epigallocatechin gallate,epicatechin,and epigallocatechin.Compared with the model group,low-,medium-,or high doses GTP significantly decreased serum levels of alanine aminotransferase and aspartate transaminase(Papoptosis in the CCl4-exposed liver(P<0.01).Phosphorylated nuclear factor kappa-B(NF-κB),p53,Bcl-2 associated x protein/B-cell lymphoma/leukemia-2 gene,cytochrome C,and cleaved caspase-3 levels were downregulated compared with the model group(P<0.01).Conclusion GTP achieves hepatoprotect

关键词： polyphenol carbon tetrachloride acute liver injury anti-oxidant anti-apoptosis green tea

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Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway

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Neural Regeneration Research 2018年第1期13卷 128-134页

作者： Hong-liang Song Xiang Zhang Wen-zhao Wang Rong-han Liu Kai Zhao Ming-yuan Liu Wei-ming Gong Bin Ning Department of Spinal Surgery Jinan Central Hospital Affiliated to Shandong University Hospital Pharmacy Jinan Central Hospital Affiliated to Shandong University Department of Gynecology and Obstetrics Jinan Maternity and Child Care Hospital

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase （p38 MAPK） pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen’s method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin （30 mg/kg） for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T8–9 spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.

关键词： nerve regeneration spinal cord injury rutin oxidative stress antioxidant anti-inflammation p38 mitogen activated protein kinase pathway anti-apoptosis caspase-3 caspase-9 neural regeneration

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Neuroprotective effects of erythropoietin on neurodegenerative and ischemic brain diseases: the role of erythropoietin receptor

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Neural Regeneration Research 2017年第9期12卷 1381-1389页

作者： Carolina Castillo Hernández Carlos Felipe Burgos Angela Hidalgo Gajardo Tiare Silva-Grecchi Javiera Gavilan Jorge Roberto Toledo Jorge Fuentealba Laboratory of Screening of Neuroactive Compounds Department of Physiology School of Biological Sciences University of Concepción Laboratory of Biotechnology and Biopharmaceutical Department of Pathophysiology School of Biological Sciences University of Concepción

Erythropoietin （Epo） is a fundamental hormone in the regulation of hematopoiesis, and other secondary roles mediated by the binding of the hormone to its specific receptor （EpoR）, which leads to an activation of key signaling pathways that induce an increase in cell differentiation, apoptosis control and neuroprotection. It has been suggested that their ftmction depends on final conformation of glycosylations, related with affinity to the receptor and its half-life. The presence of EpoR has been reported in different tissues including central nervous system, where it has been demonstrated to exert a neuroprotective function against oxidative stress conditions, such as ischemic injury and neurodegenerative diseases. There is also evidence of an increase in EpoR expression in brain cell lysates of Alzheimer＇s patients with respect to healthy patients. These results are related with extensive in vitro experimental data of neuroprotection obtained from cell lines, primary cell cultures and hippocampal slices. Additionally, this data is correlated with in vivo experiments （water maze test） in mouse models of Alzheimer＇s disease where Epo treatment improved cognitive function. These stud- ies support the idea that receptor activation induces a neuroprotective effect in neurodegenerative disorders including dementias, and especially Alzheimer＇s disease. Taken together, available evidence suggests that Epo appears to be a central element for EpoR activation and neuroprotective properties in the central nervous system. In this review, we will describe the mechanisms associated with neuroprotection and its relation with the activation of EpoR in order with identify new targets to develop pharmacological strategies.

关键词： erythropoietin erythropoietin receptor neuroprotection anti-apoptosis Alzheimer＇s disease

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The role of undifferentiated adipose-derived stem cells in peripheral nerve repair

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Neural Regeneration Research 2018年第5期13卷 757-763页

作者： Rui Zhang Joseph M.Rosen Dartmouth Geisel School of Medicine Dartmouth-Hitchcock Medical Center

Peripheral nerve injuries impose significant health and economic consequences, yet no surgical repair can deliver a complete recovery of sensory or motor function. Traditional methods of repair are less than ideal： direct coaptation can only be performed when tension-free repair is possible, and transplantation of nerve autograft can cause donor-site morbidity and neuroma formation. Cell-based therapy delivered via nerve conduits has thus been explored as an alternative method of nerve repair in recent years. Stem cells are promising sources of the regenerative core material in a nerve conduit because stem cells are multipotent in function, abundant in supply, and more accessible than the myelinating Schwann cells. Among different types of stem cells, undifferentiated adipose-derived stem cell（uASC）, which can be processed from adipose tissue in less than two hours, is a promising yet underexplored cell type. Studies of uASC have emerged in the past decade and have shown that autologous uASCs are non-immunogenic, easy to access, abundant in supply, and efficacious at promoting nerve regeneration. Two theories have been proposed as the primary regenerative mechanisms of uASC： in situ trans-differentiation towards Schwann cells, and secretion of trophic and anti-inflammatory factors. Future studies need to fully elucidate the mechanisms, side effects, and efficacy of uASC-based nerve regeneration so that uASCs can be utilized in clinical settings.

关键词： peripheral nerve injury adipose-derived stem cells Schwann cells cell therapy nerve conduits axonal regeneration stem cell differentiation neurotrophic factors anti-apoptosis immunosuppression

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