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Targeting Epac2 and GluA3-containing AMPARs:a novel therapeutic strategy for Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3223-3224页

作者： Tong Zhang Martina Schmidt department of Molecular Pharmacology Groningen Research Institute of PharmacyUniversity of GroningenGroningenThe Netherlands School of pharmacy Tianjin Medical UniversityTianjinChina

Alzheimer's disease(AD)is a neurodegenerative disease that manifests progressive decline in memory and *** the early stage of AD,memory retrieval is impaired preceding memory acquisition and consolidation(Roy et al.,2016).Prior to the onset of symptoms,pathological amyloid-β(Aβ)plagues and tau protein tangles accumulate in extracellular and intracellular spaces,respectively,leading to *** these hallmark pathologies,Aβ is proposed to be the primary etiology by triggering a cascade of pathogenic events,including neuroinflammation,oxidative stress,tau hyperphosphorylation,synaptic/neuronal dysfunction,and neuronal death(Zhang et al.,2023b).

关键词： Alzheimer impaired Aβ

PI3K/AKT signaling and neuroprotection in ischemic stroke:molecular mechanisms and therapeutic perspectives

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Neural Regeneration Research 2025年第10期20卷 2758-2775页

作者： Tianlong Liu Xiaolin Li Xiaowei Zhou Wei Chen Aidong Wen Minna Liu Yi Ding department of pharmacy Xijing HospitalFourth Military Medical UniversityXi’anShaanxi ProvinceChina department of pharmacy The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina department of pharmacy The 944 Hospital of Joint Logistics Support Forces of Chinese PLAJiuquanGansu ProvinceChina department of Nephrology The 940 Hospital of Joint Logistics Support Forces of Chinese PLALanzhouGansu ProvinceChina

It has been reported that the PI3K/AKT signaling pathway plays a key role in the pathogenesis of ischemic *** a result,the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from *** article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke,with a focus on the PI3K/AKT signaling *** key findings include the following:(1)The complex pathological mechanisms of ischemic stroke can be categorized into five major types:excitatory amino acid toxicity,Ca^(2+)overload,inflammatory response,oxidative stress,and apoptosis.(2)The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke,which primarily involves the NF-κB,NRF2,BCL-2,mTOR,and endothelial NOS signaling pathways.(3)Natural products,including flavonoids,quinones,alkaloids,phenylpropanoids,phenols,terpenoids,and iridoids,show great potential as candidate substances for the development of innovative anti-stroke medications.(4)Recently,novel therapeutic techniques,such as electroacupuncture and mesenchymal stem cell therapy,have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway,providing new possibilities for the treatment and rehabilitation of patients with ischemic *** investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

关键词： apoptosis autophagy inflammation ischemic stroke neuroprotection oxidative stress pathogenesis phosphatidylinositol 3-kinase protein kinase B therapeutics

Flavones in pomelo peel resist fibril formation of human islet amyloid polypeptide

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Chinese Herbal Medicines 2025年第1期17卷 166-177页

作者： Cuiyun Gao Zhiruo Wan Yan Liu Yuting Meng Xu Chen Xiaohan Tang Lingyu Hang Hailong Yuan department of pharmacy Air Force Medical Center Air Force Medical University

Objective:Exploring the formation and aggregation of human islet amyloid polypeptide(hIAPP)(amylin)fibers is significant for promoting the prevention and treatment of type II diabetes mellitus(T2DM).Flavones in pomelo peel have visible biological activity in the anti-diabetes *** present study aimed to investigate the effects of five flavones [naringin(NRG),narirutin(NRR),nobiletin(NOB),sinensetin(SIN),and neohesperidin(NHP)] in pomelo peel on peptide aggregation and explore its possible *** cell viability of flavones against peptide aggregation was also ***:The thioflavin T(ThT) assay and transmission electron microscopy(TEM) were used for evaluating the inhibition and disaggregation of flavones on peptide *** interaction mechanism was analyzed by endogenous fluorescence,molecular dynamics(MD) simulations,ultraviolet spectroscopy(UV) and isothermal titration calorimetry(ITC) *** 3-[4,5-dimethylthiazol-2-y l]-2,5-diphenyl tetrazolium bromide(MTT) and immune assays were performed to characterize the cell viability of flavones against peptide ***:The five flavones showed a decrease in fluorescence intensity,fiber number and size under incubation with different molar ratios of *** compounds can bind to the aromatic tyrosine(Tyr)residueTyr 37,resulting in the intrinsic fluorescence quenching of the *** flavones can form hydrogen bonds with hIAPP,which is likely to be based on their phenolic hydroxyl *** showed strong binding affinity with *** reaction system of NRG and NRR observed an exothermic reaction,and the others were endothermic *** absorption peaks of the compounds with hIAPP changed and showed hypochromic effects,indicating that there may be π-π stacking *** noticeably increased the cell viability in the presence of amyloid peptides and reduced the absorption intensity induced by peptide ***:A total of five flav

关键词： flavones human islet amyloid polypeptide inhibition interaction pomelo peel peptide aggregation

Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina department of pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

Cancer cell membrane-camouflaged biomimetic nanoparticles for enhancing chemo-radiation therapy efficacy in glioma

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Journal of Biomedical Research 2025年第1期39卷 87-102页

作者： Chunming Tang Yanling Wang Min Wu Zhiji Wang Yupeng Zhou Ya Lin Yijun Wang Huae Xu department of Pharmaceutics School of PharmacyNanjing Medical UniversityNanjingJiangsu 211166China department of pharmacy the Second Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210003China

Glioblastoma multiforme(GBM)is a highly aggressive and lethal brain tumor with limited treatment *** improve therapeutic efficacy,we developed a novel multifunctional nanoplatform,GM@P(T/S),comprised of polymeric nanoparticles coated with GBM cell membranes as well as co-loaded with temozolomide(TMZ)and superparamagnetic iron oxide(SPIO)*** successful preparation was confirmed in terms of particle size,morphology,stability,the in vitro drug release,and cellular uptake *** demonstrated that GM@P(T/S)exhibited the enhanced homotypic targeting,the prolonged blood circulation,and efficient bloodbrain barrier penetration in both in vitro and in vivo *** combination of TMZ and SPIO nanoparticles within GM@P(T/S)synergistically improved chemo-radiation therapy,leading to a reduced tumor growth,an increased survival,and minimal systemic toxicity in the orthotopic GBM mouse *** findings suggest that GM@P(T/S)holds a great promise as a targeted and efficient therapeutic strategy for GBM.

关键词： glioblastoma multiforme temozolomide superparamagnetic iron oxide chemo-radiation therapy cancer cell membrane-coating

Sini decoction alleviates inflammation injury after myocardial infarction through regulating arachidonic acid metabolism

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Chinese Herbal Medicines 2025年第1期17卷 148-155页

作者： Cuiping Long Qian Zhou Min Xu Xin Ding Xingxing Zhang Ya Zhang Yuping Tang Guangguo Tan School of pharmacy Shaanxi University of Chinese Medicine department of pharmacy Air Force Medical University department of Traditional Chinese Medicine Xijing Hospital Air Force Medical University The Third Stationed Outpatient department General Hospital of Central Theater Command of PLA

Objective:Myocardial inflammation during myocardial infarction(MI) could be inhibited by regulating arachidonic acid(AA) *** studies demonstrated that Sini Decoction(SND) was identified to be an effective prescription for treating heart failure(HF) caused by *** the anti-inflammatory mechanism of SND remained *** work was designed to investigate the anti-inflammato ry mechanism of SND through the AA metabolism pathway in vitro and in vivo ***:An inflammatory injury model of H9c2 cells was established by lipopolysaccharide(LPS)-stimulated macrophage-conditioned medium(CM).The MI model was built by the ligation of left anterior descending(LAD) branch of coronary artery in ***,the rats were divided into five groups:sham group,MI group,MI+Celecoxib group,MI+low-dose SND group(SND-L) and MI+high-dose SND group(SND-H).Cardiac function,histopathological changes and serum cytokines were examined four weeks *** blot analysis was conducted to verify the key enzymes levels in the AA metabolic pathway,including phospholipase A2(PLA2),cyclooxygenases(COXs) and lipoxygenases(LOXs).Results:These in vivo results demonstrated that SND could improve the cardiac function and pathological changes of rats with MI,and regulate the key inflammatory molecules in the AA metabolism pathway,including sPLA2,COX-1,COX-2,5-LOX and *** vitro,SND could decrease the release of proinflammatory cytokines including TNF-α and IL-6 and inhibit cell apoptosis in CM-induced H9c2 ***,SND could protect H9c2 cells from the damage of CM by regulating nuclear factor kappa-B(NF-κB) signal pathway and the expression of ***: SND may be a drug candidate for anti-inflammatory treatment during MI by regulating the multiple targets in the AA metabolism pathway.

关键词： anti-inflammation arachidonic acid metabolism pathway conditioned medium myocardial infarction Sini Decoction

Understanding Investigational Perspective of Antioxidant and Antibacterial Properties of Rice

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Rice science 2025年第1期32卷 15-31页

作者： Intan FARAHANAH Shariza SAHUDIN Hannis Fadzillah MOHSIN Siti Alwani ARIFFIN Liyana Dhamirah AMINUDDIN department of Pharmaceutical Technology Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia department of Chemistry Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia department of Pharmacology and Life Sciences Faculty of PharmacyUniversiti Teknologi MaraPuncak Alam CampusSelangor 42300Malaysia Faculty of Medicine Universiti Teknologi MaraSungai Buloh CampusSelangor 42300Malaysia

Whole-grain rice has gained significant attention for its potential health benefits,particularly because of its antioxidant and antibacterial *** this growing interest,there remains a pressing need for a comprehensive evaluation of the methods used to analyze these bioactive compounds,considering the diversity of rice types and the influence of environmental *** review aims to provide an in-depth overview of recent analytical methods,particularly those employed over the last five years,to assess the antioxidant and antibacterial properties of *** focuses on commonly used antioxidant assays,such as the 2,2-diphenyl-1-picrylhydrazyl(DPPH)radical scavenging activity assay,which encompasses both single electron transfer and hydrogen atom transfer *** antioxidant assays are also discussed,alongside methods used to evaluate antibacterial properties,including disc diffusion,well diffusion,broth or agar dilution,and advanced techniques such as flow cytofluorometric and bioluminescent *** review further explores the bacterial strains most frequently studied,including Bacillus cereus,Listeria monocytogenes,Escherichia coli,and Salmonella *** highlights the key techniques and parameters employed to ascertain and quantify the antioxidant and antibacterial potential of rice,while critically analysing the strengths and limitations of these *** synthesizing current methods and offering insights into their application,this review can be served as a guide for future research aimed at standardizing and improving the assessment of rice’s bioactive properties,paving the way for broader scientific and practical applications.

关键词： pigmented rice antioxidant activity antibacterial activity

Tianxiangdan(TXD) alleviates myocardial ischemia reperfusion-induced ferroptosis through the activation of estrogen receptor alpha(ERα)

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Chinese Journal of Natural Medicines 2025年第1期23卷 102-110页

作者： Yuanjia Yue Yu Li Xing Rong Zhao Ji Huimin Wang Liang Chen Lin Jiang department of pharmacy The Fourth College of Clinical Medicine Xinjiang Medical University department of pharmacy Xinjiang Uygur Autonomous Region Hospital of Traditional Chinese Medicine State Key Laboratory of Pathogenesis Prevention and Treatment of High Incidence Diseases in Central Asia Xinjiang Medical University department of Neurosurgery ICU Xinjiang Uygur Autonomous Region People's Hospital

Tianxiangdan（TXD）, a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion（I/R）-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. Highperformance liquid chromatography-mass spectrometry（HPLC-MS） identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase（LDH）,malondialdehyde（MDA）, superoxide dismutase（SOD） activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha（ERα）protein expression and estradiol（E2） levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group(300 nmol·L-1AZD9496 and 15% TXD serum) was compared to a TXD group（15% TXD serum）. The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group(1.0 μmol·L-1Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERαproteins. A DCFH-DA probe detected reactive oxygen species（ROS） and Fe2+, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers（LDH, MDA, and SOD）, alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe2+levels, while the AZ group（treated with AZD9496） exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4（GPX4）, with reduced levels of P53

关键词： Estrogen receptor alpha Ferroptosis Myocardial ischemia-reperfusion injury Network pharmacology Tianxiangdan

Context-dependent role of sirtuin 2 in inflammation

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Neural Regeneration Research 2025年第3期20卷 682-694页

作者： NoemíSola-Sevilla Maider Garmendia-Berges MCarmen Mera-Delgado Elena Puerta department of Pharmaceutical Sciences Division of PharmacologySchool of Pharmacy and NutritionUniversity of NavarraPamplonaSpain Navarra Institute for Health Research(IdiSNA) PamplonaSpain

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide(NAD~+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3(NLRP3). However, whether sirtuin 2-mediated pathways induce a pro-or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

关键词： interferon inflammation lipopolysaccharide neuroinflammation NLRP3 nuclear factorκB sirtuin 2