3-Acetyl coumarin alleviate neuroinflammatory responses and oxidative stress in aluminum chloride-induced Alzheimer's disease rat model.

Alzheimer's disease (AD) is a neurodegenerative disorder that impairs mental ability and interrupts cognitive function. Heavy metal exposure like aluminum chloride is associated with neurotoxicity linked to neuro-inflammation, oxidative stress, accumulation of amyloid plaques, phosphorylation of tau proteins associated with AD like symptoms. The objective of the present investigation was to assess the effect 3-acetyl coumarin (3AC) in a rat model of AD. Preliminary screening was performed with SWISS ADME to check for the bioavailability of 3-AC and likeness score which proved favorable. 3-AC docked against Caspase 3, NF-κß and tau protein kinase I exhibited good binding energies. Male rats were divided into six groups (n = 5). AlCl3 (100 mg/kg BW) was administered for 28 days before starting treatment to induce AD. Normal control rats received vehicle. Treatment groups received 10, 20 and 30 mg/kg 3-AC for 28 days. Rivastigmine (2 mg/kg) was the standard. Behavioral tests (EPM, MWM) were performed at 7-day intervals throughout study period. Rats showed improved spatial memory and learning in treatment groups during behavioral tests. Rats were euthanized on day 28. Inflammatory markers (IL-1ß, IL-16 and TNFα) exhibited significant improvement (p < 0.001) in treated rats. Oxidative stress enzymes (SOD, CAT, GSH, MDA) were restored. Caspase3 and NF-κß quantified through qRT-PCR also decreased significantly (p < 0.001) when compared to disease control group. Levels of acetyl cholinesterase, dopamine and noradrenaline were also restored in treated rats significantly (p < 0.001). 3-AC treatment restored neuroprotection probably because of anti-inflammatory, anti-oxidant and anti-cholinesterase potential; hence, this can be considered a promising therapeutic potential alternative.

Pathological effects of feeding aflatoxin-contaminated feed on immune status and reproductive performance of juvenile white leghorn males and its mitigation with ∝-tocopherol and Moringa oleifera.

This study was planned to detect the adverse pathological consequences of aflatoxin B1 in White Leghorn (WLH) layer breeder males. Eight-week-old male layer cockerels were separated into six experimental categories: A group was kept as negative control, offered with normal feed only; group B was fed with 400 ppb amount of aflatoxin, while groups F and D fed with normal feed and supplemented with vitamin E 100 ppm and 1% Moringa oleifera, respectively, whereas groups E and C were fed with 400 ppb aflatoxin containing feed and ameliorated with vitamin E 100 ppm and 1% Moringa oleifera, respectively. This study was continued for 2 months and immunologic disorders and reproductive parameters were observed during the trial. To find out immunological status lymphoproliferative response to phytohemagglutinin-P (PHA-P), antibody titers against sheep red blood cells (SRBCs) and carbon clear assay were performed by collecting samples from five birds from each group. The whole data was measured by ANOVA test, and group means were compared by DMR test by using M-Stat C software. Regarding the reproductive status, spermatogenesis, blood testosterone level, testes weight, testes histology, sperm motility, and morphology were negatively affected by aflatoxins, but these deviations positively ameliorated by vitamin E and Moringa. Vitamin E and Moringa found advantageous in boosting the immune status of affected bird. All the immunological parameters including antibody titers against sheed red blood cells, lymphoproliferative response to avian tuberculin and phagocytic potential of macrophages were suppressed by AFB1 however in control, Moringa and vitamin E groups these immunological responses were significantly higher.

Current Updates on the Role of MicroRNA in the Diagnosis and Treatment of Neurodegenerative Diseases.

BACKGROUND: MicroRNAs (miRNA) are small noncoding RNAs that play a significant role in the regulation of gene expression. The literature has explored the key involvement of miRNAs in the diagnosis, prognosis, and treatment of various neurodegenerative diseases (NDD), such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). The miRNA regulates various signalling pathways; its dysregulation is involved in the pathogenesis of NDD. OBJECTIVE: The present review is focused on the involvement of miRNAs in the pathogenesis of NDD and their role in the treatment or management of NDD. The literature provides comprehensive and cutting-edge knowledge for students studying neurology, researchers, clinical psychologists, practitioners, pathologists, and drug development agencies to comprehend the role of miRNAs in the NDD's pathogenesis, regulation of various genes/signalling pathways, such as α-synuclein, P53, amyloid-ß, high mobility group protein (HMGB1), and IL-1ß, NMDA receptor signalling, cholinergic signalling, etc. Methods: The issues associated with using anti-miRNA therapy are also summarized in this review. The data for this literature were extracted and summarized using various search engines, such as Google Scholar, Pubmed, Scopus, and NCBI using different terms, such as NDD, PD, AD, HD, nanoformulations of mRNA, and role of miRNA in diagnosis and treatment. RESULTS: The miRNAs control various biological actions, such as neuronal differentiation, synaptic plasticity, cytoprotection, neuroinflammation, oxidative stress, apoptosis and chaperone-mediated autophagy, and neurite growth in the central nervous system and diagnosis. Various miRNAs are involved in the regulation of protein aggregation in PD and modulating ß-secretase activity in AD. In HD, mutation in the huntingtin (Htt) protein interferes with Ago1 and Ago2, thus affecting the miRNA biogenesis. Currently, many anti-sense technologies are in the research phase for either inhibiting or promoting the activity of miRNA. CONCLUSION: This review provides new therapeutic approaches and novel biomarkers for the diagnosis and prognosis of NDDs by using miRNA.

Development of a Lateral-Flow Immunochromatographic Strip for the Detection of Oxytetracycline Residues in Biological Fluids.

Oxytetracycline (OTC) is extensively used in veterinary medicine and for growth promotion around the globe. The indiscriminate use of OTC in food-producing animals leaves residues in animal products. The presence of these residues in animal products causes economic losses and harmful effects on consumers. Different regulatory bodies set maximum residue limits (MRLs) for different tetracyclines. To avoid harmful effects, there is a need for a simple, fast, and economical method for the screening of animal products. In this study, a fast, economical, and user-friendly lateral-flow immunochromatographic (LFIC) assay based on gold nanoparticles (AuNPs) was developed to detect the presence of OTC residues in biological fluids. AuNPs provided visual results as red lines in 6-15 min. Polyclonal rabbit IgG antibodies were produced using the immunogen of OTC. These antibodies were purified by the combined ammonium sulfate-octanoic acid precipitation method. Antibodies were conjugated to AuNPs as recognition biomolecules. A LFIC strip was optimized using borate buffer spiked with different concentrations of the OTC. The visual limit of detection (LOD) in different biological samples (milk, serum, and urine) was determined using samples spiked with OTC. The LOD was found to be 15 µg/L, which is very low from the MRL (100 µg/L) set by different regulatory authorities. This LFIC strip can be used to detect OTC residues in biological fluids for point-of-care testing (POCT). These strips are easy to use, cost-effective, and portable and provide quick results without the use of laboratory instruments.

In Vitro, In Silico, and In Vivo Studies of Cardamine hirsuta Linn as a Potential Antidiabetic Agent in a Rat Model.

Diabetes mellitus (T2DM) is a multifaceted metabolic disorder with no definite treatment. In silico characterization can help to explain the interaction between molecules and predict 3D structures. The aim of the present study was to evaluate the hypoglycemic activities of the hydro-methanolic extract of Cardamine hirsuta in a rat model. In vitro antioxidant and α-amylase inhibitory assays were evaluated in the present study. Phyto-constituents were quantified using RP-UHPLC-MS analysis. Molecular docking of compounds into the binding site of different molecular targets, i.e., tumor necrosis factor (TNF-α), glycogen synthase kinase 3 ß (GSK-3ß), and AKT, was carried out. Acute toxicity model, in vivo antidiabetic effect, and the influence on biochemical and oxidative stress parameters were also investigated. T2DM was induced in adult male rats by streptozotocin using a high-fat diet model. Three different doses (125, 250, and 500 mg/kg BW) were orally gavaged for 30 days. Mulberrofuran-M and quercetin3-(6″caffeoylsophoroside) have demonstrated remarkable binding affinity toward TNF-α and GSK-3ß, respectively. 2,2-Diphenyl-1-picrylhydrazyl and α-amylase inhibition assay exhibited IC50 values of 75.96 and 73.66 µg/mL, respectively. In vivo findings exhibited that 500 mg/kg body weight (BW) dose of the extract significantly decreased the blood glucose level, improved biochemical parameters as well as oxidative stress by reduction of lipid peroxidation, and increased high-density lipoproteins. Moreover, activities of glutathione-s-transferase, reduced glutathione, superoxide dismutase were enhanced, and cellular architecture in the histopathological examination was restored in treatment groups. The present study affirmed the antidiabetic activities of mulberrofuran-M and quercetin3-(6″caffeoylsophoroside) present in the hydro-methanolic extract of C. hirsuta, possibly due to the reduction in oxidative stress and α-amylase inhibition.

Pterostilbene reduces the progression of atopic dermatitis via modulating inflammatory and oxidative stress biomarkers in mice.

Atopic dermatitis (AD) is one of the most prevalent chronic skin inflammatory disorders requiring continuous treatment and care. Pterostilbene (PTN) belongs to stilbene and is a polyphenolic compound of natural origin. It is similar to resveratrol and has analogous anti-inflammatory, anti-oxidant, and anti-carcinogenic characteristics. This study was intended to evaluate the effect of PTN against atopic dermatitis. The disease was induced by sensitization with 2,4-dinitrochlorobenzene (DNCB) in mice. The standard control group (SCG) received topical 0.1% tacrolimus (TC), whereas three other treatment groups received daily topical PTN at 0.2, 0.6, and 1% w/w for 28 days. Dermatitis scoring, ear thickness, and body weight of animals were weekly determined while other parameters were assessed at the termination of the experiment. PTN reduced the ear weight, skin thickness, and the weight and size of thymus glands and spleen in comparison with diseased animals. PTN also reduced the elevated immunoglobulin E (IgE) level and blood inflammatory cells in diseased mice. The histopathological findings showed a decreased epidermal thickness in PTN-treated groups. Moreover, treatment with PTN improved the amount of oxidative stress markers in the skin of the diseased mice. The expressions of IL-4, IL-6, TNF-α, and NF-κB in the skin of diseased mice were also reduced by PTN. This study concludes that PTN ameliorated the symptoms of atopic dermatitis through the reduction of inflammation, oxidative damage, and inflammatory cytokines in the skin of diseased animals. Therefore, PTN must be further investigated for the treatment of AD complications and other inflammatory skin disorders.

Reproductive and metabolic toxic effects of polystyrene microplastics in adult female Wistar rats: a mechanistic study.

Microplastics, such as polystyrene microplastics (PS-MPs), have become an emerging environmental hazard for animals and humans. Long-term exposure to PS-MPs has led to neurotoxicity, reproductive dysfunction, and carcinogenesis. The goal of this study was to evaluate the effect of sub-chronic exposure of PS-MPs on metabolic and reproductive functions in female rats. The PS-MPs were prepared by cryogenic technique. The PS-MPs were given orally to female Wistar rats for 45 days at 2.5, 5, and 10 mg/kg/day. The average PS-MPs' size diameter was 876 nm. The PS-MPs administration resulted in a significant decrease in the activity of superoxide dismutase and catalase in the liver and ovary. The effect of PS-MPs on reduced glutathione and lipid peroxidation in the liver and ovarian tissues of rats was statistically insignificant. The PS-MP exposure exhibited an increase in the levels of triglycerides, total cholesterol, and low-density lipoprotein and decrease in high-density lipoprotein. The PS-MPs caused glucose intolerance and increase in insulin. Moreover, the PS-MP exposure increased follicle stimulating hormone, estradiol, and testosterone. Serum level of interleukin-6 and nuclear factor kappa B (NF-κB) was elevated in animals treated with PS-MPs. The PS-MP exposed rats showed normal ovarian histology, but activated hepatic stellate cells and liver fibrosis. It is concluded that the sub-chronic exposure to PS-MPs resulted in metabolic and endocrine disruption in female rats through oxidative damage, hormonal imbalance, and chronic inflammation.

"Ficus johannis Boiss. leaves ethanolic extract ameliorate streptozotocin-induced diabetes in rats by upregulating the expressions of GCK, GLUT4, and IGF and downregulating G6P".

The leaves of Ficus johannis Boiss (F. johannis), commonly known as Fig tree, Anjir, and Teen, are used by the folk medicinal practitioners in Iran for controlling hyperglycemia in diabetic patients. This study investigated the pharmacological basis for antidiabetic effect of the ethanolic extract of F. johannis leaves using in vitro and in vivo experimental models. Qualitative screening of phytochemicals, estimation of total phenolic and flavonoid contents, and in vitro antioxidant and α-amylase inhibition assays were performed. Moreover, the High-performance liquid chromatography (HPLC) quantification, acute toxicity, glucose tolerance, and in vivo antidiabetic effect along with the evaluation of gene expressions involved in diabetes mellitus were carried out. Significant quantities of phenolic (71.208 ± 2.89 mgg-1 GAE) and flavonoid (26.38 ± 3.53 mgg-1 QE) were present. Inhibitory concentration (IC50) of the plant extract exhibited an excellent in vitro antioxidant (IC50 = 33.81 µg/mL) and α-amylase (IC50 = 12.18 µg/mL) inhibitory potential. The HPLC analysis confirmed the gallic acid (257.79 mgg-1) as main constituent of the extract followed by kaempferol (22.86 mgg-1), myricetin (0.16 mgg-1), and quercetin (3.22 mgg-1). Ethanolic extract displayed glucose tolerance in normo-glycemic rats. Streptozotocin-induced hyperglycemia declined dose dependently in the extract treated rats with improvement in lipid profile and liver and renal function biomarkers. The F. johannis-treated groups showed an increase in mRNA expressions of glucose transporter 4 (GLUT-4), glucokinase, insulin growth like factor 1 and peroxisomal proliferator activating receptor gamma in pancreas. However, the Glucose-6-phosphatase was downregulated. Present study suggests that the ethanolic extract of F. johannis leaves demonstrates a good anti-diabetic profile by improving insulin sensitivity, GLUT-4 translocation, and carbohydrate metabolism while inhibiting lipogenesis.

Quercetin-loaded chitosan nanoparticles ameliorate adjuvant-induced arthritis in rats by regulating anti-oxidant enzymes and downregulating pro- and inflammatory cytokines.

Rheumatoid arthritis (RA) is an inflammatory condition and associated with the symmetrical synovitis of the joints and cause joint pain. The use of anti-rheumatic drugs is associated with many adverse effects. Quercetin, an important polyphenolic flavonoid, possess anti-inflammatory and anti-rheumatic effects. Quercetin use is limited due to poor absorption and bioavailability. Nanomedicines are used for the targeted drug delivery, hence it reduces the adverse effects of the drug. Based upon these factors, quercetin-loaded chitosan nanoparticles (Q-NPs) were prepared by solvent evaporation method, characterized and their better anti-rheumatic effect with mechanistic insights was validated in Freund's complete adjuvant (FCA)-induced arthritic rats along with safety studies. The animals were divided into five groups, each containing 5 animals. Group I was normal control, group II was arthritic control, while groups III, IV and V were administered with quercetin (15 mg/Kg) and Q-NPs (10 and 20 mg/Kg), respectively. The reduction in ankle diameter, serum oxidative stress markers as well as pro- and inflammatory cytokines, e.g., tumor necrosis factor (TNFα), interleukin (IL-6) were determined. The prepared Q-NPs showed hydrodynamic size of 83.9 nm, polydispersity index of 0.687, entrapment efficiency 90.5% as well as no interaction between quercetin and chitosan in Fourier transform infrared spectroscopy (FTIR). A significant reduction (p < 0.001) in ankle diameter was observed after administration of high-dose Q-NPs (4.32 ± 0.14 cm to 5.13 ± 0.62 cm). There was also reduction (p < 0.001) in levels of TNFα and IL-6 following high-dose Q-NPs (72.56 ± 2.30 and 308.19 ± 11.5 pg). The effect on biochemical tests, hematological parameters and oxidative stress parameters was also found to be significant. Histopathological changes of kidney, liver and ankle also confirmed the anti-rheumatic effect of high-dose Q-NPs. The study concludes that administration of Q-NPs (20 mg/Kg) may be used for the treatment of FCA-induced RA in rats.

Mechanistic insights on the possible protective role of polyphenols extracted from Tamarix aphylla aerial parts against sodium arsenite-induced hepatotoxicity in rats.

Arsenic exposure is associated with the induction of hepatotoxicity. Current study was aimed to investigate the hepato-protective ability of polyphenolic components of Tamarix aphylla (TA) ethanolic extract against sodium arsenite (SA)-induced liver injury of rats. Significantly higher quantities of phenolic (318.7±2.5 mgg-1GAE) and flavonoid (250.69 ±3.3 mgg-1QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for antioxidant (IC50= 25.99 µg/mL) assay. High performance liquid chromatography (HPLC) confirmed the existence of myercetin (10.40ppm), sinapic acid (2.131ppm), kaempferol (0.486ppm), caffeic acid (5.094 ppm). Forty-two rats were divided into 7 groups. Group 1 received normal saline (2 mL/kg/day, orally for 21 days), Group 2 received SA (10mg/kg/day for 21 days), and Group 3 received SA alone for 7 days (10mg/kg) and continues with silymarine for 21 days (25mg/kg orally). Group 4, 5, 6 received SA alone for 7 days and continue with TA extract up to 21 days (125mg/kg, 250mg/kg, and 500mg/kg orally) respectively, and Group 7 received TA extract (500mg/kg) for 21 days. SA was administered to all treated groups for 21 days. Treatment with polyphenolic ethanolic extract of TA restored the hepatic indices and oxidative markers in a dose-dependent manner. The upregulation in tumor necrosis factor-α, interleukin-6, and cyclooxygenase-2 upon SA treatment suggesting inflammation was normalized by the treatment of rats. Above mentioned biochemical findings were supported well with histopathological screening. Present findings suggest that TA polyphenolic ethanolic extract could mitigate the oxidative stress and inflammation induced by SA in liver tissue.

Anticancer, Cardio-Protective and Anti-Inflammatory Potential of Natural-Sources-Derived Phenolic Acids.

Phenolic acids (PAs) are one of the utmost prevalent classes of plant-derived bioactive chemicals. They have a specific taste and odor, and are found in numerous medicinal and food plants, such as Cynomorium coccineum L., Prunus domestica (L.), and Vitis vinifera L. Their biosynthesis, physical and chemical characteristics and structure-activity relationship are well understood. These phytochemicals and their derivatives exert several bioactivities including but not limited to anticancer, cardioprotective, anti-inflammatory, immune-regulatory and anti-obesity properties. They are strong antioxidants because of hydroxyl groups which play pivotal role in their anticancer, anti-inflammatory and cardioprotective potential. They may play significant role in improving human health owing to anticarcinogenic, anti-arthritis, antihypertensive, anti-stroke, and anti-atherosclerosis activities, as several PAs have demonstrated biological activities against these disease during in vitro and in vivo studies. These PAs exhibited anticancer action by promoting apoptosis, targeting angiogenesis, and reducing abnormal cell growth, while anti-inflammatory activity was attributed to reducing proinflammatory cytokines. Pas exhibited anti-atherosclerotic activity via inhibition of platelets. Moreover, they also reduced cardiovascular complications such as myocardial infarction and stroke by activating Paraoxonase 1. The present review focuses on the plant sources, structure activity relationship, anticancer, anti-inflammatory and cardioprotective actions of PAs that is attributed to modulation of oxidative stress and signal transduction pathways, along with highlighting their mechanism of actions in disease conditions. Further, preclinical and clinical studies must be carried out to evaluate the mechanism of action and drug targets of PAs to understand their therapeutic actions and disease therapy in humans, respectively.

Pathogenic role of cytokines in COVID-19, its association with contributing co-morbidities and possible therapeutic regimens.

The Covid-19, a threatening pandemic, was originated from China in December 2019 and spread quickly to all over the world. The pathogenesis of coronavirus is linked with the disproportionate response of the immune system. This involves the systemic inflammatory reaction which is characterized by marked pro-inflammatory cytokine release commonly known as cytokine release storm (CRS). The pro inflammatory cytokines are involved in cascade of pulmonary inflammation, hyper coagulation and thrombosis which may be lethal for the individual. That's why, it is very important to have understanding of pro inflammatory cytokines and their pathological role in SARS-CoV-2. The pathogenesis of Covid is not the same in every individual, it can vary due to the presence of pre-existing comorbidities like suffering from already an inflammatory disease such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), an immune-compromised patients suffering from Diabetes Mellitus (DM) and Tuberculosis (TB) are more vulnerable morbidity and complications following COVID-19. This review is particularly related to COVID-19 patients having comorbidity of other inflammatory diseases. We have discussed the brief pathogenesis of COVID-19 and cytokines release storm with reference to other co-morbidities including RA, IBD, COPD, DM and TB. The available therapeutic regimens for COVID-19 including cytokine inhibitors, anti-viral, anti-biotic, bronchodilators, JAK- inhibitors, immunomodulators and anti-fibrotic agents have also been discussed briefly. Moreover, newly emerging medicines in the clinical trials have also been discussed which are found to be effective in treating Covid-19.

Therapeutic potential of Ceratonia siliqua extract for the management of asthma and hypertension.

The current work was performed to explore the pharmacological mechanisms involved in the management of asthma and hypertension along with the safety profile of the Ceratonia siliqua (C. siliqua/Carob) pods. The bronchorelaxant, vasorelaxant, and cardioselective activities of C. siliqua pods were investigated using isolated rabbit tracheal, aortic, and paired atrial fragments on the Power lab data acquisition system. Normotensive rats were used to study antihypertensive activity. The plant extract and its fractions relaxed the carbachol-induced contraction in the tracheal fragments and shifted the concentration-response curve of carbachol towards the right confirming the muscarinic receptor antagonist activity. The relaxation of phenylephrine-induced contraction in an aortic fragment by the extract showed α- adrenergic blocking activity. Furthermore, the extract produced a cardio-selective response in the paired atria and decreased the blood pressure in anesthetized normotensive rats. The plant extract proved to be non-toxic in oral acute and chronic toxicity studies and did not demonstrate any sign of histopathological lesions. These results suggested that the plant extract was non-toxic and could be used in the management of lifetime therapies of respiratory and cardiovascular disorders without any unwanted effects.

Berberis aristata DC Extract Counteracts the High Fat Diet-Induced Reproductive Toxicity in Female Wistar Rats via Modulating Oxidative Stress and Resistance to Leptin and Insulin.

BACKGROUND: The plant Berberis aristata is traditionally used and scientifically validated for treating obesity and hyperlipidemia. It is also traditionally used to treat gynecological abnormalities. Therefore, the present study was designed to evaluate the therapeutic potential of Berberis aristata for obesity-related reproductive changes and chemically characterize it. METHODS: High-fat diet was given to 36 female rats for six weeks to induce obesity and infertility. These obese rats were treated with 10 mg/kg orlistat or the plant extract at 125-500 mg/kg for 45 days. RESULTS: The GC-MS analysis of the plant extract included fructose, thymic acid and other hydrocarbons. The plant extract revealed a remarkable free radical scavenging activity. The treated animals exhibited a decrease in total cholesterol and triglycerides (p<0.001), insulin and leptin levels (p<0.05), visceral fat, and body weight while increasing the estradiol level at 500 mg/kg dose of the plant extract as compared with untreated animals as demonstrated from the histology of the ovary. Oxidative stress biomarkers such as superoxide dismutase, nitric oxide, malondialdehyde and reduced glutathione were significantly (p<0.01-0.001) ameliorated in treated rats. CONCLUSION: B. aristata exhibited substantial potential against obesity-inducedreproductive damage in female rats by reducing oxidative stress and resistance to leptin and insulin.

Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund's complete adjuvant-induced arthritic rats.

Methotrexate (MTX), the first-line drug for the treatment of rheumatoid arthritis (RA), can cause considerable toxicity, which limits effective dosage regimens. Moreover, it has rapid clearance, which leads to poor patient compliance. To mitigate such challenges, this study aimed to validate the use of MTX-loaded chitosan nanoparticles (NPs) in treating Freund's complete adjuvant (FCA) arthritis in rats. Healthy Wistar rats (n = 30) were divided into five groups. The first group served as healthy control, while the second group served as arthritic control. Group 3 was administered methotrexate, while groups 4 and 5 were MTX-loaded NP-treated groups. NPs were prepared by solvent evaporation method and characterized by zeta size, potential, polydispersity index (PDI), and Fourier-transform infrared spectroscopy. NPs were 190 nm in size, and PDI was 0.25, confirming the uniform distribution of NPs. A significant increase in paw thickness was noted up to the 21st day of the study, which was reversed by a high dose of MTX-loaded NPs. MTX NPs significantly reduced the level of pro-inflammatory markers, including TNF-α and IL-6, along with improving control of oxidative stress biomarkers. The findings of biochemical, haematological, radiological, and histopathological investigations further confirmed amelioration of necrosis and cellular infiltration. It can be concluded that MTX-loaded chitosan NPs are promising candidates for treating FCA-induced arthritis in a rat model.

Amelioration of hyperglycaemia and modulation of pro-inflammatory cytokines by Tamarix gallica fractions in alloxan induced diabetic rats.

Present study is engrossed in identification of phyto-constituents from aerial part extracts of Tamarix gallica and appraisal of its anti-oxidant, anti-diabetic and anti-inflammatory potential based upon its folktale use. The methanol and n-hexane fractions of aerial parts were analysed using high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) respectively. Inhibitory concentration (IC50) showed better results in case of methanolic extract for both in antioxidant (IC50= 15.47 µg/mL) and alpha amylase (IC50=18.75 µg/mL) assays. Significantly higher quantities of phenolic and flavonoid contents were present in methanolic extract. A significant correlation was found to be existed between these contents and IC50 of antioxidant assay. Alloxan induced hyperglycaemia declined along with improvement in lipid profile, C-reactive proteins (CRP), liver function tests (LFTs) and renal function tests (RFTs). Methanolic fraction (500 mg/kg) was also related to significant reduction in levels of inflammatory markers i.e. tumour necrosis factor-alpha, TNF- α (1.28 ± 0.13 g/L) and interleukin-6, IL-6 (98 ± 10.4 pg/L) as observed in diabetic rats. Based upon the above findings, the study suggests that methanolic fraction from aerial parts of the T. gallica has better anti-diabetic profile which might be attributed to its alpha amylase, anti-oxidant and anti-inflammatory potential.

Cyperus iria aqueous-ethanol extract ameliorated hyperglycemia, oxidative stress, and regulated inflammatory cytokines in streptozotocin-induced diabetic rats.

Type 2 diabetes mellitus is a complicated metabolic disorder with no definite treatment. Cyperus iria (Cyperaceae) possess several traditional therapeutic uses. According to the folklore tales, the whole plant of Cyperus iria possesses antihyperglycemic activity. The present study was undertaken to investigate whether aqueous-ethanol extract of Cyperus iria can ameliorate the altered activities of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats along with appraisal of inflammatory and stress markers involved in endocrine dysfunction. Presence of biophenolics and flavonoids might be responsible for the antidiabetic potential. STZ-induced diabetic rats were treated orally with Cyperus iria extract (125, 250, and 500 mg/kg) for 15 days. Blood samples were collected. Metformin was used as positive control. Significantly higher quantities of phenolic (82.79±0.003 mg/g GAE) and flavonoid (13.61±0.002 mg/g QE) contents were present. Inhibitory concentration (IC50) exhibited an excellent potential for both antioxidant (IC50= 3.22 µg/mL) and alpha amylase (IC50=36.29 µg/mL) inhibitory assays. High-performance liquid chromatography (HPLC) confirmed the existence of myercetin, quercetin, kaempferol, and ferulic acid. Cyperus iria aqueous-ethanol extract exhibits good tolerance against glucose at 90 min in normal rats. Streptozotocin-induced hyperglycemia declined significantly at day 9 (265 mg/dL) along with improvement in inflammatory (TNF-α=15.6± 0.2 g/l, COX-2=357±0.396 U/l, IL-6= 572±0.99 pg/l) and oxidative stress markers (SOD= 163±0.616 and GSH-ST= 95.8±0.44 U/mL) along with biochemical parameters in a dose-dependent manner. Present study suggests that Cyperus iria aqueous-ethanol extract possesses hypoglycemic potential which might be attributed to the decrease in oxidative stress and inflammatory markers.

Outer Membrane Protein-Coated Nanoparticles as Antibacterial Vaccine Candidates.

Nanoformulations are novel therapeutic strategies as compared to traditional treatments. The development of biomimetic nanoparticles by combining the natural cellular material with synthetic nanoparticles has inspired innovative vaccine strategies for modifying the antibacterial immunity. A lot of work has been done in which synthetic nanoparticles are coated with biomimetic cellular membranes for enhancement of biological functions and treatments. Outer membrane protein of bacteria not only act as adjuvant but also contain a large number of immunogenic antigens that play an important role in motivating the native immunity and stimulating the immune responses of the body. Outer membrane protein coating onto the surfaces of synthetic nanoparticles has synergistic effects to produce antibacterial responses. This article reviews the recent improvements related to the bacterial membrane-coated nanoparticles for antibacterial immunization.

Mechanistic insights of snake venom disintegrins in cancer treatment.

Snake venoms are a potential source of various enzymatic and non-enzymatic compounds with a defensive role for the host. Various peptides with significant medicinal properties have been isolated and characterized from these venoms. Few of these are FDA approved. They inhibit tumor cells adhesion, migration, angiogenesis and metastasis by inhibiting integrins on transmembrane cellular surfaces. This plays important role in delaying tumor growth, neovascularization and development. Tumor targeting and smaller size make them ideal candidates as novel therapeutic agents for cancer treatment. This review is based on sources of these disintegrins, their targeting modality, classification and underlying anti-cancer potential.

Biotransformation and toxicity evaluation of functionalized manganese doped iron oxide nanoparticles.

Safe inorganic nanomaterials are tremendously used for diagnosis and therapies. However, essential processing in the microbiological environment changed the physical properties and in situ degradability, which is evaluated meticulously. In this research article, bare, Polyethylene glycol, and citrate coated manganese doped iron oxide nanoparticles are synthesized through the coprecipitation route. Structural, magnetic, optical, and morphological analyses are performed through different characterization tools. X-ray diffraction confirmed the formation of single-phase FeMnO3 with a crystallite size of 48.91 nm. Vibrating sample magnetometer analysis confirmed the formation of soft ferromagnetic behavior of bare and coated nanoparticles (NPs). Scanning electron microscopy and transmission electron microscopy confirmed the formation of spherical shaped nanoparticles. Single-dose in vivo acute toxicity testing is performed through the intraperitoneal route of administration on groups of healthy albino rats. Elevated enzyme levels of kidney and liver are observed at day 1 but a transient decrease is observed at later stages. Through optical follow-up, degradation effects are studied by adding prepared NPs in lysosomal like medium. Finally, metabolization of degraded products based on manganese/iron ions is studied by adding apoferritin into a lysosome like solution. These studies showed partial storage of manganese ions from NPs, while no substantial transfer is observed in the case of manganese salt.