Biomaterials-based anti-inflammatory treatment strategies for Alzheimer's disease

The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.

Oxygen tension modulates cell function in an in vitro three-dimensional glioblastoma tumor model

Hypoxia is a typical feature of the tumor microenvironment,one of the most critical factors affecting cell behavior and tumor progression.However,the lack of tumor models able to precisely emulate natural brain tumor tissue has impeded the study of the effects of hypoxia on the progression and growth of tumor cells.This study reports a three-dimensional(3D)brain tumor model obtained by encapsulating U87MG(U87)cells in a hydrogel containing type I collagen.It also documents the effect of various oxygen concentrations(1%,7%,and 21%)in the culture environment on U87 cell morphology,proliferation,viability,cell cycle,apoptosis rate,and migration.Finally,it compares two-dimensional(2D)and 3D cultures.For comparison purposes,cells cultured in flat culture dishes were used as the control(2D model).Cells cultured in the 3D model proliferated more slowly but had a higher apoptosis rate and proportion of cells in the resting phase(G0 phase)/gap I phase(G1 phase)than those cultured in the 2D model.Besides,the two models yielded significantly different cell morphologies.Finally,hypoxia(e.g.,1%O2)affected cell morphology,slowed cell growth,reduced cell viability,and increased the apoptosis rate in the 3D model.These results indicate that the constructed 3D model is effective for investigating the effects of biological and chemical factors on cell morphology and function,and can be more representative of the tumor microenvironment than 2D culture systems.The developed 3D glioblastoma tumor model is equally applicable to other studies in pharmacology and pathology.

Adsorption,in vitro digestion and human gut microbiota regulation characteristics of three Poria cocos polysaccharides

Poria cocos(PC)is a famous traditional Chinese medicine(TCM)and a widely used healthcare ingredient,which has antiobesity,enhancing immunity and improving sleep effects.Traditionally,only water-soluble poria polysaccharide(WSP)is extracted and applied for clinical application,while insoluble polysaccharide(alkali-soluble poria polysaccharide,ASP)is discarded as herb residue.However,the whole PC has also been historically utilized as functional herbal food.Considering the beneficial role of dietary fiber and the traditional use of PC,ASP may also contribute substantially to the therapy function of PC.Compared to WSP,little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide(CMP)which has been used as an antitumor adjuvant drug.In this study,the oil,cholesterol,metal ions and polyphenols adsorption ability,in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP,ASP and CMP were studied to evaluate the functional values of three P.cocos polysaccharides(PCPs).The results showed that all three PCPs had good adsorption capacity on cholesterol,polyphenols and metal ions(Cd^(2+)/Zn^(2+)/Mg^(2+)),among which ASP showed the highest capacity than WSP and CMP.The adsorption capacity of all three PCPs on heavy metal ions(Cd^(2+)/Zn^(2+))was stronger than that of non-heavy metal ions(Mg^(2+));The in vitro digestibility of all three PCPs was very low,but WSP was slightly higher than ASP and CMP;Moreover,the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota,among which ASP had the greatest influence.In general,ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful bacteria.The gut microbiota diversity of CMP was reduced,but the richness of probiotics,especially Parabacteroides distasonis was significantly enhanced compared with the ASP group,and the growth of harmful bacteria Klebsiella pneumoniae was inhibited after CMP treatment.The short-chain fatty acids(SCFAs)analysis results showed that all three PCPs could significantly promote the production of acetic acid,propionic acid and the total acid content compared with blank control group,and SCFAs producing activity was positively correlated with the proliferative capacity of probiotics.Taken together,the good adsorption characteristics and gut microbiota regulatory activity of ASP may lay foundation for its lipid-lowering and immune-improving function.Additionally,the probiotic effect of CMP and ASP indicated that except for only use the water extract of PC in clinic,CMP and ASP also can be used in healthcare to take full advantage of this valuable medicine.

Effect of wall-disruption on nutrient composition and in vitro digestion of camellia and lotus bee pollens

The nutrient digestion,absorption and biological activity of bee pollen may be limited due to the complex pollen wall.Here,the effect of superfine grinding technology on the release of nutrients from bee pollen were investigated,and their antioxidant activities and in vitro digestion were explored in this study.Results showed that the content of nutrients in bee pollen increased after wall disruption.Among them,fat content increased by 22.55%-8.31%,protein content increased by 0.54%-4.91%,starch content increased by 36.31%-48.64%,soluble sugar content increased by 20.57%-29.67%,total phenolic acid content increased by 11.73%-86.98%and total flavonoids content increased by 14.29%-24.79%.At the same time,the antioxidant activity increased by 14.84%-46.00%.Furthermore,the active components such as phenolic compounds in the wall-disruption bee pollen were more readily to be released during the in vitro digestion,and easier to be absorbed because of their higher bioaccessibility.Antioxidant activities during in vitro digestion were also improved in walldisruption bee pollen.These findings provide evidence that bee pollen wall disruption was suggested,thus,it is more conducive to exerting the value of bee pollen in functional foods.

Simulation and fabrication of in vitro microfluidic microelectrode array chip for patterned culture and electrophysiological detection of neurons

To enable the detection and modulation of modularized neural networks in vitro,this study proposes a microfluidic microelectrode array chip for the cultivation,compartmentalization,and control of neural cells.The chip was designed based on the specific structure of neurons and the requirements for detection and modulation.Finite-element analysis of the chip’s flow field was conducted using the COMSOL Multiphysics software,and the simulation results show that the liquid within the chip can flow smoothly,ensuring stable flow fields that facilitate the uniform growth of neurons within the microfluidic channels.By employing MEMS technology in combination with nanomaterial modification techniques,the microfluidic microelectrode array chip was fabricated successfully.Primary hippocampal neurons were cultured on the chip,forming a well-defined neural network.Spontaneous electrical activity of the detected neurons was recorded,exhibiting a 23.7%increase in amplitude compared to neuronal discharges detected on an open-field microelectrode array.This study provides a platform for the precise detection and modulation of patterned neuronal growth in vitro,potentially serving as a novel tool in neuroscience research.

Isolation and bioactivity screening of soy isoflavones from soybean glycolipids identifies daidzin as a promising anti-inflammatory agent

Background:Soybean has long been utilized in the realm of traditional Chinese medicine.One of its extracts,soybean glycolipids,serves as a vital by-product of soybean oil refining,but its chemical composition and pharmacological potential have yet to be fully elucidated.Methods:In this study,the chemical components were isolated,and the inhibitory effects of these isolates were explored in different zebrafish inflammatory models by survival rate,Histological examination assay and quantitative Real-time PCR assay.The cytotoxicity of daidzin in RAW264.7 cells was evaluated by cell viability assay,and the effect of daidzin on the release of inflammatory cytokines in RAW264.7 cells was detected by enzyme linked immunosorbent assay(ELISA).Western blotting,immunofluorescence assay and alpha7 nicotinic acetylcholine receptors siRNA transfection assay were used to further explore the anti-inflammatory mechanism of daidzin.Results:Four compounds(verticilloside,soya-cerebroside I,soya-cerebroside II and daidzin)were firstly isolated from the soybean glycolipids,among which verticilloside and daidzin inhibited the lipopolysaccharide,CuSO4-and tail cut-stimulated zebrafish inflammation.Noticeably,daidzin exhibited anti-inflammatory activities by increasing the survival rate,alleviating the inflammatory cells infiltration,and down-regulating the expression of pro-inflammatory cytokines and nuclear factor kappa-B,NF-kappa-B inhibitor alpha,and signal transducer and activator of transcription3 in zebrafish.Moreover,daidzin decreased the secretion of IL-6 and TNF-α,inhibited the nuclear translocations of nuclear factor kappa-B p65 and p-signal transducer and activator of transcription3 as well as the NF-kappa-B inhibitor alpha phosphorylation at Ser32 in RAW 264.7 cells.More importantly,it elevated the expression level of alpha7 nicotinic acetylcholine receptors in both zebrafish and RAW 264.7 cells,and the inhibitory effect of daidzin was attenuated after the addition of alpha7 nicotinic acetylcholine receptors siRNA.Conclusion:Our study revealed that daidzin inhibited inflammation by activating the cholinergic anti-inflammatory pathway and further inhibiting the nuclear factor kappa-B and signal transducer and activator of transcription3 signaling.At the same time,it also promotes the recycling of crude soybean glycolipids and supports the potential use of daidzin as a functional food or natural dietary anti-inflammatory agent.

Antibacterial, Anti-Inflammatory and Antioxidant Activities of an ACAZY Herbal Formula Used in Traditional Medicine to Treat Respiratory Infections

ACAZY is a plant formula used in traditional medicine in Burkina Faso to treat respiratory infections. After phytochemical analysis, this study evaluated extracts’ anti-inflammatory, antioxidant and antibacterial properties from the ACAZY recipe. Three extractions, an aqueous macerate (AM), an aqueous decoction (AD) and an hydroethanolic macerate (HEM) of the ACAZY recipe powder were carried out. Phytochemical screening of the extracts was carried out using high-performance thin-layer chromatography (HPTLC) and the determination of phenolic compounds. The anti-inflammatory potential was assessed in vitro using pro-inflammatory enzyme inhibition tests. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) antioxidant properties were also determined. The antibacterial activity was evaluated on Staphylococcus aureus and Streptococcus pneumoniae strains. Phytochemical analysis revealed the presence of flavonoids, saponins, tannins, anthracenosids, sterols and triterpenes in the extracts. The extracts inhibited pro-inflammatory enzymes by more than 40% at only 100 µg/mL. The extracts also showed potent antibacterial activity with a minimum inhibitory concentration 1 mg/mL on Staphylococcus aureus and 2 mg/mL on Streptococcus pneumoniae. The extracts in the ACAZY formula have shown anti-inflammatory and antioxidant properties in vitro. The AD also showed an antibacterial activity. This justifies its use in traditional medicine to treat acute respiratory infections.

Anti-inflammatory Mechanism of Yao Medicine Laggerae Alatae Herba

[Objectives]To study the anti-inflammatory effect of Laggerae Alatae Herba extract and its mechanism.[Methods]Inflammation models of xylene-induced ear edema in mice,acetic acid-induced increased permeability of abdominal capillaries in mice,and carrageenan-induced paw edema in mice were established;xylene-induced ear swelling model in bilateral adrenalectomized mice was established.The levels of MDA,NO and SOD in inflammatory tissues of paw were measured.[Results]Compared with the model group,the high and medium dose groups of Laggerae Alatae Herba extract had significant inhibitory effect on xylene-induced ear edema in mice,except for the low dose group(P>0.05);Laggerae Alatae Herba extract inhibited the increase of celiac capillary permeability induced by acetic acid and paw edema induced by carrageenan in mice.Compared with the model group,in the mice model with bilateral adrenal glands removed,the high and medium dose groups of Laggerae Alatae Herba extract could significantly inhibit the xylene induced ear swelling of the mice.The high and medium dose groups of Laggerae Alatae Herba extract could significantly decrease the levels of MDA and NO,and significantly increase the level of SOD in the paw tissue.[Conclusions]The Laggerae Alatae Herba extracts have anti-inflammatory activity,and the anti-inflammatory effect of the extracts does not depend on the hypothalamic-pituitary-adrenal axis(HPAA)system.In addition,the anti-inflammatory mechanism of Laggerae Alatae Herba extract is related to the decrease of MDA and NO and the increase of SOD.

The Effects of Zinc Sulfate on the in Vitro Digestibility of Feeds in Cervids

The captive white-tailed deer industry has an estimated impact of 1.6 billion USD in the state of Texas alone. However, nutritional requirements for cervids are determined through research based on sheep and goats. The objective of this study was to determine the effects of zinc on differences in dry matter digestibility in vitro for white-tailed does (Odocoileus virginianus). Deer (n = 2) were ethically harvested, rumens were collected, and placed into a cooler containing warm water. Rumen contents were agitated, and fluid was filtered using cheese cloth while applying CO2. Fluid was placed into four separate incubator jars with filter bags containing a 1:1 alfalfa to coastal hay blend. Zinc doses of 0.073 mg/kg/d equivalents were added to two of the jars ( Zn), and the additional two jars received 0.00 mg/kg/d (CON). Following 48 h of incubation, in vitro true digestibility (IVTD) showed no significant differences between the control and the treatment groups. Average dry matter digested in vitro was 91.87% and 95.13%, respectively. There were no differences detected in ADF, NDF, IVTD, or OM between the treatment groups. While no detectable differences were observed in this study, this methodology did prove to be viable and functional for microbial digestion in vitro. This study can be replicated with multiple experimental units to confirm the observations of increased digestibility. Formal nutritional guidelines can be created to allow for more efficient feeding of cervids thereby reducing feed costs and continuing the growth of the captive deer industry.

Corrosion and in vitro cytocompatibility investigation on the designed Mg-Zn-Ag metallic glasses for biomedical application

In the present work,seven Mg-Zn-Ag alloys with the nominal composition of Mg_(96-x)Zn_(x)Ag_(4)(x=17,20,23,26,29,32,35 in at.%)were prepared by induction melting and single-roller melt-spinning.The X-ray diffraction(XRD)analyses indicate the metallic glasses with three composition of Mg_(73)Zn_(23)Ag_(4),Mg_(70)Zn_(26)Ag_(4),and Mg_(67)Zn_(29)Ag_(4)were obtained successfully.The differential scanning calorimetry(DSC)measurement was used to obtain the characteristic temperature of Mg-Zn-Ag metallic glasses for the glass-forming ability analysis.The maximum glass transition temperature(Trg)was found to be 0.525 with a composition close to Mg_(67)Zn_(29)Ag_(4),which results in the best glass-forming ability.Moreover,the immersion test in simulated body fluid(SBF)demonstrate the relative homogeneous corrosion behavior of the Mg-Zn-Ag metallic glasses.The corrosion rate of Mg-Zn-Ag metallic glasses in SBF solution decreases with the increase of Zn content.The sample Mg_(67)Zn_(29)Ag_(4)has the lowest corrosion rate of 0.19mm/yr,which could meet the clinical application requirement well.The in vitro cell experiments show that the Madin-Darby canine kidney(MDCK)cells cultured in sample Mg_(67)Zn_(29)Ag_(4)and its extraction medium have higher activity.However,the Mg-Zn-Ag metallic glasses exhibit obvious inhibitory effect on human rhabdomyosarcoma(RD)tumor cells.The present investigations on the glass-forming ability,corrosion behavior,cytocompatibility and tumor inhibition function of the Mg-Zn-Ag based metallic glass could reveal their biomedical application possibility.

Preclinical Verification of Modulated Electro-Hyperthermia —Part I. In Vitro Research

Modulated electro-hyperthermia (mEHT) targets tissue’s natural electric and thermal heterogeneities to heat the cancer cells selectively. The applied 13.56 MHz radiofrequency (RF) is a carrier of the low-frequency modulation. The high-frequency part was chosen to select the malignant lesion using the specialties of the tumor: the higher conductivity and dielectric constant of the tumor than its host. The electric field selects the tumor, and the low-frequency amplitude modulation polarizes and excites the transmembrane proteins of the malignant cells. The dominant absorption of the energy by the microscopic clusters of the membrane rafts acts like nanoparticle heating. Exciting the membrane produces various apoptotic signals. The processes were modeled using silico and phantom experiments, which proved the concept. The preclinical verification was made in vitro and in vivo, and in the end, clinical proofs validated the method. Our objective is to follow all the development steps from the laboratory to the clinics in a trilogy of articles. This present is the first part, which deals with in silico, phantom, and in vitro research.

The in vitro digestion fates of diacylglycerol under different intestinal conditions:a potential lipid source for lipid indigestion patients

The in vitro digestion models mimicking the gastrointestinal(GI)tract of general population and lipid indigestion patients(with lower levels of bile salts or pancreatic lipase)were selected to investigate whether diacylglycerols(DAGs)are potential good lipid sources for these patients.Linseed oil-based DAG(LD)and linseed oil(LT)were selected.LD-based emulsion((83.74±1.23)%)had higher lipolysis degree than LT-based emulsion((74.47±1.16)%)when monitoring the GI tract of normal population as previously reported.Indigestion conditions seriously decreased the digestive degree of LT-based emulsion((40.23±2.48)%-(66.50±3.70)%)while showed less influence on LD-based emulsion((64.18±2.41)%-(81.85±3.45)%).As opposed to LT-based emulsion,LD-based emulsion exhibited preference for releasing unsaturated fatty acids(especially oleic acid andα-linolenic acid)due to their different glycerolipid compositions.LD-based emulsion showed potential for providing lipids and nutrients(including essential fatty acids)for lipid indigestion patients.

In vitro engineered models of neurodegenerative diseases

Neurodegeneration is a catastrophic process that develops progressive damage leading to functional andstructural loss of the cells of the nervous system and is among the biggest unavoidable problems of our age.Animalmodels do not reflect the pathophysiology observed in humans due to distinct differences between the neuralpathways,gene expression patterns,neuronal plasticity,and other disease-related mechanisms in animals andhumans.Classical in vitro cell culture models are also not sufficient for pre-clinical drug testing in reflecting thecomplex pathophysiology of neurodegenerative diseases.Today,modern,engineered techniques are applied to developmulticellular,intricate in vitro models and to create the closest microenvironment simulating biological,biochemical,and mechanical characteristics of the in vivo degenerating tissue.In THIS review,the capabilities and shortcomings ofscaffold-based and scaffold-free techniques,organoids,and microfluidic models that best reflect neurodegeneration invitro in the biomimetic framework are discussed.

Association between Exposure of Rare Earth Elements and Outcomes of In Vitro Fertilization-Embryo Transfer in Beijing

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses.Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann–Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes.Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy.Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Network pharmacology study and in vitro experimental validation of Xiaojianzhong decoction against gastric cancer

BACKGROUND Cancer is one of the most serious threats to human health worldwide.Conventional treatments such as surgery and chemotherapy are associated with some drawbacks.In recent years,traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians,and has become an indispensable part of the comprehensive treatment for gastric cancer.AIM To investigate the mechanism of Xiaojianzhong decoction(XJZ)in the treatment of gastric cancer(GC)by utilizing network pharmacology and experimental validation,so as to provide a theoretical basis for later experimental research.METHODS We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics.Subsequently,we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8,apoptosis,cell cycle,and clone formation assays.Additionally,we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins.RESULTS XJZ mainly regulates IL6,PTGS2,CCL2,MMP9,MMP2,HMOX1,and other target genes and pathways in cancer to treat GC.The inhibition of cell viability,the increase of apoptosis,the blockage of the cell cycle at the G0/G1 phase,and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment.In addition,XJZ induced a decrease in the mRNA expression of IL6,PTGS2,MMP9,MMP2,and CCL2,and an increase in the mRNA expression of HOMX1.XJZ significantly inhibited the expression of IL6,PTGS2,MMP9,MMP2,and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein.CONCLUSION XJZ exerts therapeutic effects against GC through multiple components,multiple targets,and multiple pathways.Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

The Identification of Phenylalanine Ammonia-Lyase(PAL)Genes from Pinus yunnanensis and an Analysis of Enzyme Activity in vitro

Phenylalanine ammonia lyase(PAL)is the rate-limiting and pivotal enzyme of the general phenylpropanoid path-way,but few reports have been found on PAL genes in Pinus yunnanensis.In the present study,three PAL genes were cloned and identified from P.yunnanensis seedlings for thefirst time,namely,PyPAL-1,PyPAL-2,and PyPAL-3.Our results indicated that the open-reading frames of PyPAL genes were 2184,2157,and 2385 bp.Phylogenetic tree analysis revealed that PyPALs have high homology with other known PAL genes in other plants.In vitro enzymatic analysis showed that all three PyPAL recombinant proteins could catalyze the deamination of L-phenylalanine to form trans-cinnamic acid,but only PAL1 and PAL2 can catalyze the conversion of L-tyrosine toρ-coumaric acid.Three PyPAL genes were expressed in different tissues in 1-year-old P.yunnanensis,and such genes had different expression patterns.This study lays a foundation for further understanding of the biosynthesis of secondary metabolites in P.yunnanensis.

Study on the effect and mechanism of Swertia mussotii Franch. in the treatment of primary biliary cholangitis based on bioinformatics and in vitro experiments

Background:Primary biliary cholangitis(PBC)is a chronic biliary autoimmune liver disease characterized by intrahepatic cholestasis.Swertia mussotii Franch.(SMF)is a Tibetan medicine with hepatoprotective and anti-inflammatory activities.In this study,the therapeutic effect and potential mechanisms of SMF on PBC were investigated by bioinformatics analysis and in vitro experimental validation,with the aim of promoting the progress of SMF and PBC research.Methods:We first explored the therapeutic effects and key targets of SMF on PBC using a network pharmacology approach,further screened the core targets using the GSE79850 dataset,and finally validated the results using molecular docking techniques and in vitro experiments.Results:By bioinformatics analysis,we identified core targets of SMF for PBC treatment(STAT3,JAK2,TNF-α,and IL-1β)and important signaling pathways:JAK-STAT,TNF,and PI3K-AKT.The molecular docking results showed that the significant components of SMF had good binding properties to the core targets.In vitro experiments showed that SMF extracts improved the extent of epithelial-mesenchymal transition in human intrahepatic biliary epithelial cells and had a significant reversal effect on epithelial-mesenchymal transition process markers and potential targets in PBC.Conclusion:SMF may exert its therapeutic effects on PBC by acting on important targets such as STAT3,JAK2,TNF-α,IL-1β,Vimentin,and E-cadherin and the pathways in which they are involved.

Progress in experimental models to investigate the in vivo and in vitro antidiabetic activity of drugs

Diabetes mellitus is one of the world's most prevalent and complex metabolic disorders,and it is a rapidly growing global public health issue.It is characterized by hyperglycemia,a condition involving a high blood glucose level brought on by deficiencies in insulin secretion,decreased activity of insulin,or both.Prolonged effects of diabetes include cardiovascular problems,retinopathy,neuropathy,nephropathy,and vascular alterations in both macro-and micro-blood vessels.In vivo and in vitro models have always been important for investigating and characterizing disease pathogenesis,identifying targets,and reviewing novel treatment options and medications.Fully understanding these models is crucial for the researchers so this review summarizes the different experimental in vivo and in vitro model options used to study diabetes and its consequences.The most popular in vivo studies involves the small animal models,such as rodent models,chemically induced diabetogens like streptozotocin and alloxan,and the possibility of deleting or overexpressing a specific gene by knockout and transgenic technologies on these animals.Other models include virally induced models,diet/nutrition induced diabetic animals,surgically induced models or pancreatectomy models,and non-obese models.Large animals or non-rodent models like porcine(pig),canine(dog),nonhuman primate,and Zebrafish models are also outlined.The in vitro models discussed are murine and human beta-cell lines and pancreatic islets,human stem cells,and organoid cultures.The other enzymatic in vitro tests to assess diabetes include assay of amylase inhibition and inhibition ofα-glucosidase activity.

Changes in Polyphenols and Antioxidant Activities of Yingshan Yunwu Tea during Digestion in Vitro

[Objectives]To explore the change rule of polyphenol content and antioxidant activity of coarse old leaves of Yingshan Yunwu Tea in the process of human digestion.[Methods]The coarse and old leaves of Yunwu tea in Yingshan,Huanggang,Hubei Province were selected as the research object,and their digestion in vitro was simulated.The total polyphenol content was determined by Folin-phenol reagent colorimetric method,and the DPPH radical scavenging activity and total antioxidant activity were determined.[Results]After simulated gastrointestinal digestion in vitro,the polyphenol content and antioxidant activity of coarse old leaf tea soup showed a downward trend.After gastrointestinal digestion,the polyphenol content in tea infusion separately decreased by 31.8%and 8.5%;the scavenging rate of DPPH free radical was 97%before digestion,decreased to 92%after gastric digestion and 65%after intestinal digestion,which decreased by 5%and 27%,respectively;after gastrointestinal digestion,the total antioxidant capacity of tea soup decreased by 4.7%and 3.1%,respectively.[Conclusions]This study provided a reference for the development and application of coarse old leaves of Yingshan Yunwu tea,and provided a reference for the nutritional value evaluation and comprehensive utilization of coarse old leaves,so as to make the best use of coarse tea leaves and reduce the waste of resources.

Proximate analyses,in vitro antioxidant activity and GC-MS analyses of fermented Pentaclethra macrophylla seeds

The present study assessed the proximate composition,in vitro antioxidant activity and GC-MS analyses of fermented Pentaclethra macrophylla seeds extract(FPMSE).The in vitro antioxidant activity was assessed using 2,2-diphenyl-1-picrylhydrazl(DPPH)while Gas Chromatography-Mass Spectrophotometry(GC-MS)technique was used to identify the volatile compounds in FPMSE.FPMSE revealed a dose dependent percentage inhibition of the extract on DPPH assay.Proximate composition of FPMSE constitutes respectively;ash(0.33±0.12%),protein(2.19±0.08%),fats and oil(80.60±0.00%),carbohydrate(16.88±0.00%)while moisture and fibre were not detected.However,the pulverised sample constitute respectively;ash(1.27±0.58%),protein(10.51±0.60%),moisture(8.27±0.12%),fats and oil(32.33±0.12%),fibre(7.27±0.12%)and carbohydrate(40.35±0.00%).GC-MS analyses revealed fourteen(14)fatty acids including Octadecanoic acid(1.95%),Benzyloxymethylimine(43.89%),2-Allylpent-4-enoic acid benzyl ester(26.25%),Hexadecanoic acid,methyl ester(1.09%),Oleic Acid(0.25%),9,12-Octadecadienoic acid,methyl ester(Omega-6-fatty acid)(1.52%).The bioactive compounds identified in FPMSE could contribute to the pharmacological properties of P.macrophylla seeds and hence,could be of considerable interest for the development of new drugs.