Mesua assamica (King & Prain) kosterm. bark ethanolic extract attenuates rheumatoid arthritis via down-regulating TLR4/NF-κB/COX-2/iNOS and activation of Nrf2/HO-1 pathways: A comprehensive study on in-vitro and in-vivo models.

ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis (RA) is a multifactorial, polygenic inflammatory disease. Mesua assamica (King & Prain) Kosterm. (MA) is an endangered medicinal plant indigenous to South Asia, primarily to Assam in India. The tree bark is claimed to possess anti-inflammatory, anti-diabetic, anti-cancer, and anti-malarial properties; nevertheless, its role in RA has not been elucidated. Hence, this study aims to investigate the in-vitro and in-vivo anti-arthritic effects of Mesua assamica bark ethanolic extract (MAE). AIM OF THE STUDY: This study aims to investigate the anti-rheumatic potential of MAE in-vitro on RAW 264.7 cells for its anti-oxidant and anti-inflammatory activities and in-vivo on the CFA-induced adjuvant arthritis in the rat model. MATERIALS AND METHODS: We investigated the possible therapeutic effects of MAE in-vitro using RAW 264.7 cells triggered by LPS. Meanwhile, adult Wistar rats were injected intradermally with 100 µl of CFA to induce arthritis, and they were given MAE orally at doses of 100 and 200 mg/kg for up to 28 days. Paw volume analysis, X-ray radiography, anti-oxidant levels analysis, gene and protein expression studies, and histological analysis were carried out to assess the effects of MAE in-vivo. RESULTS: MAE significantly mitigated the inflammation by reducing ROS levels and dropped the nitrite, PGE2, and COX-2 levels enhanced by LPS in-vitro. At the same time, MAE treatment reduced the paw and joint inflammation and increased the immune organ index in the CFA rats. Histopathology data revealed that MAE mitigated the CFA-induced lesions of the ankle joints and synovial tissues. Similarly, MAE significantly abated the secretion of pro-inflammatory cytokines, inhibited the protein expression of TLR4, NF-кB, COX-2, and iNOS, as well as improved the Nrf2 and HO-1 levels in-vitro and in-vivo. CONCLUSION: All the results highlighted the anti-rheumatic potential of MAE in RA in-vitro and in-vivo by inhibiting the TLR4/NF-кB/COX-2/iNOS and promoting the Nrf2/HO-1 signaling axis.

Unveiling Green Synthesis and Biomedical Theranostic paradigms of Selenium Nanoparticles (SeNPs) - A state-of-the-art comprehensive update.

The advancements in nanotechnology, pharmaceutical sciences, and healthcare are propelling the field of theranostics, which combines therapy and diagnostics, to new heights; emphasizing the emergence of selenium nanoparticles (SeNPs) as versatile theranostic agents. This comprehensive update offers a holistic perspective on recent developments in the synthesis and theranostic applications of SeNPs, underscoring their growing importance in nanotechnology and healthcare. SeNPs have shown significant potential in multiple domains, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antidiabetic, wound healing, and cytoprotective therapies. The review highlights the adaptability and biocompatibility of SeNPs, which are crucial for advanced disease detection, monitoring, and personalized treatment. Special emphasis is placed on advancements in green synthesis techniques, underscoring their eco-friendly and cost-effective benefits in biosensing, diagnostics, imaging and therapeutic applications. Additionally, the appraisal scrutinizes the progressive trends in smart stimuli-responsive SeNPs, conferring their role in innovative solutions for disease management and diagnostics. Despite their promising therapeutic and prophylactic potential, SeNPs also present several challenges, particularly regarding toxicity concerns. These challenges and their implications for clinical translation are thoroughly explored, providing a balanced view of the current state and prospects of SeNPs in theranostic applications.

Characterization and Biomedical Applications of Green-Synthesized Selenium Nanoparticles Using Tridax procumbens Stem Extract.

Background Selenium nanoparticles (SeNPs) are one of the metal nanoparticles that have been widely utilized for their anti-microbial, anti-oxidant, anti-inflammatory activities, and other biomedical applications. Tridax procumbens (TP) stem extract is a promising herb species rich in flavonoids, tannins, alkaloids, phytosterols, and hydroxycinnamates, which play a major role in wound healing applications.  Aim The study aims to synthesize SeNPs using TP stem extract, characterizations, and its biomedical applications. Materials and methods SeNPs were synthesized using TP stem extract. The green synthesis of SeNPs was confirmed by ultraviolet-visible (UV-vis) spectra analysis. The synthesized SeNPs were characterized using Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The agar well diffusion method was utilized to evaluate the anti-bacterial properties of the green synthesized SeNPs using TP stem extract. The anti-oxidant effect of SeNPs was tested using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, ferric-reducing anti-oxidant power assay (FRAP), and hydroxyl radical scavenging assay (H2O2). The anti-inflammatory effect was investigated using the bovine serum albumin assay and egg albumin denaturation method, and the cytotoxic effect of the green synthesized SeNPs was tested using the brine shrimp lethality (BSL) assay. Results The green synthesis of SeNPs was confirmed using different types of analysis techniques. The characterizations were done by UV-visible spectroscopy analysis, exhibiting a maximum peak at the range of 330 nm. SEM analysis revealed the shape of the nanoparticle to be hexagonal. The agar well diffusion method exhibited the anti-bacterial efficacy of SeNPs against wound microorganisms with a zone of inhibition of 14.6 mm for Escherichia coli (E. coli), 15.8 mm for Staphylococcus aureus (S. aureus), and 15.4 mm for Pseudomonas aeruginosa (P. aeruginosa). The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows very little toxicity. Conclusion Overall, the green synthesis of TP-stem-mediated SeNPs has great potential in biomedical applications. Thus, the synthesized SeNPs exhibit significant anti-bacterial efficacy against wound pathogens. The TP stem-mediated SeNPs showed potential effects in anti-oxidant, anti-inflammatory, and cytotoxic activity, which shows low toxicity. Furthermore, the green-synthesized SeNPs can be utilized in therapeutic management.

Design, Synthesis, and Anti-Prostrate Cancer Potential of 2-(4-nitrobenzyl) malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo.

New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods. We evaluated the compounds' potential anti-prostate cancer activity using the DU145 cell line. The MTT assay determined the cell viability, indicating good anti-proliferative activity. The molecule 3c exhibited the highest potency, with a CTC50 of 11.83 µg/mL. Molecular dynamics simulations were performed to study the stability of the ligand within the protein after docking and the resulting protein-ligand complex. The in vivo analysis of molecule 3c in the DAL xenograft model demonstrated promising results. The increase in life span, reduction in tumor volume, and comparable effects to standard drugs are encouraging features that suggest that molecule 3c may possess significant potential as an anti-cancer agent. The research also implies that these molecules might be potential lead compounds for developing new prostate cancer drugs.

High serum levels of reactive nitrogen species and low total antioxidant capacity in patients with resistant hypertension compared to those in age- gender matched healthy controls, controlled hypertension and follow up with propranolol treatment in the extended APPROPRIATE trial.

OBJECTIVES: To perform a comparative analysis of the extended APPROPRIATE trial of measures of reactive nitrogen species and antioxidant capacity in patients having resistant hypertension with controlled hypertension and healthy controls. RESULTS: Mean serum NO2- and NOx levels were significantly lower and mean AOC was significantly higher in patients with controlled hypertension (n = 38) and healthy controls (n = 38) compared to resistant hypertension (RHTN) patients (n = 40) at the pre-intervention stage (p < 0.001). The serum NO2-, NOx and AOC levels of both controlled hypertension and healthy controls were comparable to those of the RHTN patients following treatment with propranolol (n = 18). Considering all samples (n = 114) we noted that there were significant weak and moderate positive correlations between NO2- levels with systolic blood pressure (SBP) and diastolic blood pressure (DBP) (r = 0.396, p < 0.001 and r = 0.292, p = 0.004) as well as total NOx levels with SBP and DBP (r = 0.636 and r = 0.480 respectively, p < 0.001). Conversely, there was a significant negative correlation between AOC levels with SBP and DBP (r= -0.846 and r = -0.626 respectively, p < 0.001).

Exploring the mechanistic role of silk sericin biological and chemical conjugates for effective acute and chronic wound repair and related complications.

OBJECTIVE: The current review is designed to elaborate and reveal the underlying mechanism of sericin and its conjugates of drug delivery during wounds and wound-related issues. SIGNIFICANCE: Wound healing is a combination of different humoral, molecular, and cellular mechanisms. Various natural products exhibit potential in wound healing but among them, sericin, catches much attention of researchers due to its bio-functional properties such as being biodegradable, biocompatible, anti-oxidant, anti-bacterial, photo-protector, anti-inflammatory and moisturizing agent. METHODS AND RESULTS: Sericin triggers the activity of anti-inflammatory cytokines which decrease cell adhesion and promote epithelial cell formation. Moreover, sericin enhances the anti-oxidant enzymes in the wounded area which scavenge the toxic consequences of reactive species (ROS). CONCLUSIONS: This article highlights the mechanisms of how topical administration of sericin formulations along with 4-hexylresorcinol,\Chitosan\Ag@MOF-GO, polyvinyl alcohol (PVA), platelet lysate and UV photo cross-linked hydrogel sericin methacrylate which recruits a large number of cytokines on wounded area that stimulate fibroblasts and keratinocyte production as well as collagen deposition that led to early wound contraction. It also reviews the different sericin-based nanoparticles that play a significant role in rapid wound healing.

Polyphenols: potent protectors against chronic diseases.

Polyphenols, abundant in plant-based foods like fruits, vegetables, tea, coffee, wine, and chocolate, offer significant health benefits. Known for their potent antioxidant properties, they combat oxidative stress by neutralising free radicals, crucial in preventing chronic noncommunicable diseases (NCDs) such as cancer, cardiovascular issues, obesity, and diabetes. Polyphenols also exhibit anti-inflammatory effects, modulating gene expression and reducing inflammation associated with NCDs. Their anticancer activities involve inhibiting cancer cell growth and promoting apoptosis through various pathways. They enhance cardiovascular health by improving endothelial function, lowering blood pressure, and inhibiting atherosclerosis. Additionally, polyphenols improve metabolic health by enhancing insulin sensitivity and regulating glucose metabolism, aiding in diabetes and obesity management. These bioactive compounds interact with cellular pathways and gut microbiota, highlighting their multifaceted mechanisms. Integrating polyphenol-rich foods into diets could significantly improve health outcomes and alleviate NCD burdens, advocating for their inclusion in public health strategies and further research to optimise their potential.

Protective effect of ellagic acid against high-glucose-induced injury in human umbilical venous endothelial cells.

Objective: There is escalating evidence suggesting the beneficial effects of ellagic acid (EA) on the cardiovascular system. The aim of the present study was to investigate the protective effect of EA in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)- induced endothelial dysfunction and to study the potential roles of adropin and nitric oxide (NO) in this regard. Materials and Methods: The experimental groups consisted of normal and HG (30 mM, 48 hr)-treated HUVECs incubated without or with 5 or 10 µM of EA (6 groups of at least 6 replicates, each). The cell count and viability were studied. Moreover, the markers of the redox state, including malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and catalase enzymes, and ferric reducing anti-oxidant power (FRAP), were assayed. The levels of adropin and eNOS gene expression were also studied using RT-qPCR. Results: A high concentration of glucose reduced cell count and caused lipid peroxidation, reduced anti-oxidant capacity of the cells, decreased NO levels, and downregulated the expression of NOS3 (encoding eNOS) and ENHO (encoding adropin) genes. Ellagic acid reversed all these effects. Conclusion: These results suggest a significant protective effect for EA against HG-induced injury in HUVECs. The improved redox state and upregulation of NOS3 and ENHO genes seem to play critical roles in this regard.

[Research progress in physiological function of the rare sugar D-allose].

D-allose, a rare sugar with anti-oxidant, anti-inflammatory, anti-cancer, immunosuppressing and other physiological functions, has become a research hotspot in recent years. This paper describes the physical and chemical properties, synthesis methods, metabolism, physiological functions, and applications of D-allose, aiming to promote the functional development of D-allose and facilitate the application of D-allose in the food field and clinical treatment.

Potent anti-inflammatory and anti-apoptotic activities of electrostatically complexed C-peptide nanospheres ameliorate diabetic nephropathy.

In the present era of "Diabetic Pandemic", peptide-based therapies have generated immense interest however, are facing odds due to inevitable limitations like stability, delivery complications and off-target effects. One such promising molecule is C-peptide (CPep, 31 amino acid polypeptide with t1/2 30 min); it is a cleaved subunit of pro-insulin, well known to suppress microvascular complications in kidney but has not been able to undergo translation to the clinic till date. Herein, a polymeric CPep nano-complexes (NPX) was prepared by leveraging electrostatic interaction between in-house synthesized cationic, polyethylene carbonate (PEC) based copolymer (Mol. wt. 44,767 Da) and negatively charged CPep (Mol. wt. 3299 Da) at pH 7.4 and further evaluated in vitro and in vivo. NPX exhibited a spherical morphology with a particle size of 167 nm and zeta potential equivalent to +10.3, with 85.70 % of CPep complexation efficiency. The cellular uptake of FITC-tagged CPep NPX was 95.61 % in normal rat kidney cells, NRK-52E. Additionally, the hemocompatible NPX showed prominent cell-proliferative, anti-oxidative (1.8 folds increased GSH; 2.8 folds reduced nitrite concentration) and anti-inflammatory activity in metabolic stress induced NRK-52E cells as well. The observation was further confirmed by upregulation of anti-apoptotic protein BCl2 by 3.5 folds, and proliferative markers (ß1-integrin and EGFR) by 3.5 and 2.3 folds, respectively, compared to the high glucose treated control group. Pharmacokinetic study of NPX in Wistar rats revealed a 6.34 folds greater half-life than free CPep. In in-vivo efficacy study in STZ-induced diabetic nephropathy animal model, NPX reduced blood glucose levels and IL-6 levels significantly by 1.3 and 2.5 folds, respectively, as compared to the disease control group. The above findings suggested that NPX has tremendous potential to impart sustained release of CPep, resulting in enhanced efficacy to treat diabetes-induced nephropathy and significantly improved renal pathology.

Biosynthesized MgONPs using Syzygium cumini seed extract: Characterization, In vitro anti-oxidant and anti-microbial activity.

The present study investigates S. cumini seed extracts which are considered as a promising and valuable source of bioactive compounds were prepared using different solvents such as methanol, ethanol, petroleum ether, acetone, chloroform, and diethyl ether. Among these solvents, methanol exhibited the highest extraction with a yield of 42 %. HPLC analysis revealed the highest concentration of quercetin flavonoids (49.62 mg/gm) in the methanolic S. cumini seed extract. Thus, the current work deals with the MgONPs synthesis through a biological approach using different S. cumini seed extracts. In vitro anti-oxidant properties were evaluated, which showed an IC50 value of 22.46 µg/mL for MgONPs synthesized from methanolic extract, surpassing the anti-oxidant potency of ascorbic acid by threefold. By leveraging the rich repository of bioactive compounds found within S. cumini seed extract, this study presents a novel approach to MgONPs synthesis. Exploring the symbiotic relationship between S. cumini seed extract and MgONPs, this research elucidates the pivotal role of bioactive compounds in guiding the formation and properties of nanostructures. Further anti-microbial studies on MgONPs from methanolic S. cumini seed extract were conducted against four different bacterial strains (Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and S. typhimurium), revealing potent anti-microbial activity with 5.3 mm of inhibition for 100 µl against S. typhimurium. These findings suggest that S. cumini is a source of bioactive compounds responsible for the successful synthesis of MgONPs. Characterization studies of MgONPs were also carried out using UV-vis spectroscopy, FTIR, SEM, XRD, DSC and HPLC.

Identification, Bioaccessibility, and Antioxidant Properties of Phenolic Compounds in Carob Syrup.

Carob syrup is a brown, thick syrup produced from carob pulp that can be directly consumed or used as a sweetener, which also finds applications in folk medicinal practices. In this work, the quali-quantitative phenolic profile of five different carob syrups was elucidated before and after in vitro gastro-intestinal digestion. Moreover, the anti-oxidant properties of undigested and digested carob syrups were investigated. A total of 75 phenolic compounds were identified in undigested carob syrups. The most important phenolic compound in all the samples was gallic acid, the concentration of which ranged between 54.28 and 117.73 mg/100 g. Additional compounds belonging to the classes of hydroxybenzoic acids (in particular glycosylated gallic acid derivatives), hydroxycinnamic acids, and flavonoids (especially flavonols) were also identified. During in vitro gastric digestion, gallic acid mono- and di-hexosides were diglycosylated, releasing gallic acid, which was further degraded in ellagic acid through oxidative polymerization in the intestinal phase of the digestion. Ellagic acid was the major compound detected after in vitro gastro-intestinal digestion of carob syrups. With few exceptions, the anti-oxidant properties of carob syrup were preserved even after digestion. Carob syrup can be considered an important source of phenolic compounds with demonstrated positive effects on human health.

Recent advances on cyanidin-3-O-glucoside in preventing obesity-related metabolic disorders: A comprehensive review.

Anthocyanins, found in various pigmented plants as secondary metabolites, represent a class of dietary polyphenols known for their bioactive properties, demonstrating health-promoting effects against several chronic diseases. Among these, cyanidin-3-O-glucoside (C3G) is one of the most prevalent types of anthocyanins. Upon consumption, C3G undergoes phases I and II metabolism by oral epithelial cells, absorption in the gastric epithelium, and gut transformation (phase II & microbial metabolism), with limited amounts reaching the bloodstream. Obesity, characterized by excessive body fat accumulation, is a global health concern associated with heightened risks of disability, illness, and mortality. This comprehensive review delves into the biodegradation and absorption dynamics of C3G within the gastrointestinal tract. It meticulously examines the latest research findings, drawn from in vitro and in vivo models, presenting evidence underlining C3G's bioactivity. Notably, C3G has demonstrated significant efficacy in combating obesity, by regulating lipid metabolism, specifically decreasing lipid synthesis, increasing fatty acid oxidation, and reducing lipid accumulation. Additionally, C3G enhances energy homeostasis by boosting energy expenditure, promoting the activity of brown adipose tissue, and stimulating mitochondrial biogenesis. Furthermore, C3G shows potential in managing various prevalent obesity-related conditions. These include cardiovascular diseases (CVD) and hypertension through the suppression of reactive oxygen species (ROS) production, enhancement of endogenous antioxidant enzyme levels, and inhibition of the nuclear factor-kappa B (NF-κB) signaling pathway and by exercising its cardioprotective and vascular effects by decreasing pulmonary artery thickness and systolic pressure which enhances vascular relaxation and angiogenesis. Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are also managed by reducing gluconeogenesis via AMPK pathway activation, promoting autophagy, protecting pancreatic ß-cells from oxidative stress and enhancing glucose-stimulated insulin secretion. Additionally, C3G improves insulin sensitivity by upregulating GLUT-1 and GLUT-4 expression and regulating the PI3K/Akt pathway. C3G exhibits anti-inflammatory properties by inhibiting the NF-κB pathway, reducing pro-inflammatory cytokines, and shifting macrophage polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. C3G demonstrates antioxidative effects by enhancing the expression of antioxidant enzymes, reducing ROS production, and activating the Nrf2/AMPK signaling pathway. Moreover, these mechanisms also contribute to attenuating inflammatory bowel disease and regulating gut microbiota by decreasing Firmicutes and increasing Bacteroidetes abundance, restoring colon length, and reducing levels of inflammatory cytokines. The therapeutic potential of C3G extends beyond metabolic disorders; it has also been found effective in managing specific cancer types and neurodegenerative disorders. The findings of this research can provide an important reference for future investigations that seek to improve human health through the use of naturally occurring bioactive compounds.

Cannabidiol and neurodegeneration: From molecular mechanisms to clinical benefits.

Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-ß, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.

The Synthesis and Characterization of Selenium-Doped Bioglass.

Background Bioactive glass, which can form strong bonds with tissues, particularly bones, has become pivotal in tissue engineering. Incorporating biologically active ions like selenium enhances its properties for various biomedical applications, including bone repair and cancer treatment. Selenium's antioxidative properties and role in bone health make it a promising addition to biomaterial. Aim The present study was aimed at the preparation and characterization of selenium-doped bioglass. Materials and methods Tetraethyl orthosilicate (TEOS) was mixed with ethanol, water, and nitric acid to form a silica network and then supplemented with calcium nitrate, selenium acid sodium nitrate, and orthophosphoric acid. Sequential addition ensured specific functionalities. After sintering at 300 °C for three hours, the viscous solution transformed into powdered selenium-doped bioglass. Characterization involved scanning electron microscope (SEM) for microstructure analysis, attenuated total reflection infrared spectroscopy (ATR-IR) for molecular structure, and X-ray diffraction (XRD) for crystal structure analysis. Results SEM analysis of selenium-doped bioglass reveals a uniform distribution of selenium dopants in an amorphous structure, enhancing bioactivity through spherical particles with consistent size, micro-porosity, and roughness, facilitating interactions with biological fluids and tissues. ATR-IR analysis shows peaks corresponding to Si-O-Si and P-O bonds, indicating the presence of phosphate groups essential for biomedical applications within the bioglass network. XRD analysis confirms the amorphous nature of selenium-doped bioglass, with shifts in diffraction peaks confirming selenium incorporation without significant crystallization induction. Conclusion The selenium-infused bioglass displays promising versatility due to its amorphous structure, potentially enhancing interactions with biological fluids and tissues. Further research is needed to assess its impact on bone regeneration activity.

Development of optimized resveratrol/piperine-loaded phytosomal nanocomplex for isoproterenol-induced myocardial infarction treatment.

Cardiovascular disease is a significant and ever-growing concern, causing high morbidity and mortality worldwide. Conventional therapy is often very precarious and requires long-term usage. Several phytochemicals, including Resveratrol (RSV) and Piperine (PIP), possess significant cardioprotection and may be restrained in clinical settings due to inadequate pharmacokinetic properties. Therefore, this study strives to develop an optimized RSV phytosomes (RSVP) and RSV phytosomes co-loaded with PIP (RPP) via solvent evaporation method using Box-Behnken design to enhance the pharmacokinetic properties in isoproterenol-induced myocardial infarction (MI). The optimized particle size (20.976 ± 0.39 and 176.53 ± 0.88 nm), zeta potential (-33.33 ± 1.5 and -48.7 ± 1.6 mV), drug content (84.57 ± 0.9 and 87.16 ± 0.6%), and %EE (70.56 ± 0.7 and 67.60 ± 0.57%) of the prepared RSVP and RPP, respectively demonstrated enhanced solubility and control release in diffusion media. The oral administration of optimized RSVP and RPP in myocardial infarction-induced rats exhibited significant (p < 0.001) improvement in heart rate, ECG, biomarker, anti-oxidant levels, and no inflammation than pure RSV. The pharmacokinetic assessment on healthy Wistar rats exhibited prolonged circulation (>24 h) of RSVP and RPP compared to free drug/s. The enhanced ability of RSVP and RPP to penetrate bio-membranes and enter the systemic circulation renders them a more promising strategy for mitigating MI.

Dihydroquercetin and biochaga reduce H2O2 induced DNA damage in peripheral blood mononuclear cells of obese women in vitro-a pilot study.

Systemic oxidative stress stemming from increased free radical production and reduced antioxidant capacity are common characteristics of obese individuals. Using hydrogen peroxide (H2O2) to induce DNA damage in vitro, in peripheral blood mononuclear cells (PBMCs) from obese subjects and controls, the DNA protective ability of dihidroqercetin (DHQ) and biochaga (B) alone or in combination, were evaluated. The effects of DHQ and B were estimated under two experimental conditions: pre-treatment, where cells were pre-incubated with the substances prior to H2O2 exposure; and post-treatment when cells were first exposed to H2 H2O2, and further treated with the compounds. DNA damage was evaluated using the comet assay. The results of pre- and post-treatment showed a significant decrease in DNA damage produced by H2O2 in the obese group. This decrease was not significant in control group probably due to a small number of subjects in this pilot study. More prominent attenuation was noted in the pre-treatment with DHQ (250 µg/mL). Analysis of antioxidant properties revealed that DHQ's remarkable reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity, and potent ∙OH scavenging properties may contribute to strong attenuation of H2O2 induced DNA damage. Also, B showed strong reducing power, DPPH, and ∙OH scavenging ability, while reducing power and DPPH scavenger effects were increased in the presence of DHQ. Conclusively, DHQ and B may reduce H2O2-induced DNA damage in PBMCs from obese subjects when challenged in vitro, and could be valuable tools in future research against oxidative damage-related conditions.

Potentials of bone marrow cells-derived from naïve or diabetic mice in autoimmune type 1 diabetes: immunomodulatory, anti-inflammatory, anti hyperglycemic, and antioxidative.

BACKGROUND: The scarcity of transplanted human islet tissue and the requirement for immunosuppressive drugs to prevent the rejection of allogeneic grafts have hindered the treatment of autoimmune type 1 diabetes mellitus (T1DM) through islet transplantation. However, there is hope in adoptively transferred bone marrow cells (BMCs) therapy, which has emerged as a propitious pathway for forthcoming medications. BMCs have the potential to significantly impact both replacement and regenerative therapies for a range of disorders, including diabetes mellitus, and have demonstrated anti-diabetic effects. AIM: The main goal of this study is to evaluate the effectiveness of adoptively transferred bone marrow cells derived from either naïve mice (nBMCs) or diabetic mice (dBMCs) in treating a T1DM mice model. METHODS: Male Swiss albino mice were starved for 16 h and then injected with streptozotocin (STZ) at a dose of 40 mg/kg body weight for 5 consecutive days to induce T1DM. After 14 days, the diabetic mice were distributed into four groups. The first group served as a diabetic control treated with sodium citrate buffer, while the other three groups were treated for two weeks, respectively, with insulin (subcutaneously at a dose of 8 U/kg/day), nBMCs (intravenously at a dose of 1 × 106 cells/mouse/once), and dBMCs (intravenously at a dose of 1 × 106 cells/mouse/once). RESULTS: It is worth noting that administering adoptively transferred nBMCs or adoptively transferred dBMCs to STZ-induced T1DM mice resulted in a significant amelioration in glycemic condition, accompanied by a considerable reduction in the level of blood glucose and glycosylated hemoglobin % (HbA1C %), ultimately restoring serum insulin levels to their initial state in control mice. Administering nBMCs or dBMCs to STZ-induced T1DM mice led to a remarkable decrease in levels of inflammatory cytokine markers in the serum, including interferon-γ (INF-γ), tumor necrosis factor- α (TNF-α), tumor growth factor-ß (TGF-ß), interleukin-1 ß (L-1ß), interlekin-4 (IL-4), interleukin-6 (IL-6), and interleukin-10 (IL-10). Additionally, STZ-induced T1DM mice, when treated with nBMCs or dBMCs, experienced a notable rise in total immunoglobulin (Ig) level. Furthermore, there was a significant reduction in the levels of islet cell autoantibodies (ICA) and insulin autoantibodies (IAA). Furthermore, the serum of STZ-induced T1DM mice showed a significant increase in Zinc transporter 8 antigen protein (ZnT8), islet antigen 2 protein (IA-2), and glutamic acid decarboxylase antigen protein (GAD) levels. Interestingly, the administration of nBMCs or dBMCs resulted in a heightened expression of IA-2 protein in STZ-induced T1DM mice treated with nBMCs or dBMCs. Furthermore, the level of malondialdehyde (MDA) was increased, while the levels of catalase (CAT) and superoxide dismutase (SOD) were decreased in non-treated STZ-induced T1DM mice. However, when nBMCs or dBMCs were administered to STZ-induced T1DM mice, it had a significant impact on reducing oxidative stress. This was accomplished by reducing the levels of MDA in the serum and enhancing the activities of enzymatic antioxidants like CAT and SOD. STZ-induced T1DM mice displayed a significant elevation in the levels of liver enzymes ALT and AST, as well as heightened levels of creatinine and urea. Considering the crucial roles of the liver and kidney in metabolism and excretion, this research further examined the effects of administering nBMCs or dBMCs to STZ-induced T1DM mice. Notably, the administration of these cells alleviated the observed effects. CONCLUSION: The present study suggests that utilizing adoptively transferred nBMCs or adoptively transferred dBMCs in the treatment of T1DM led to noteworthy decreases in blood glucose levels, possibly attributed to their capacity to enhance insulin secretion and improve the performance of pancreatic islets. Additionally, BMCs may exert their beneficial effects on the pancreatic islets of diabetic mice through their immunomodulatory, antioxidant, anti-inflammatory, and anti-oxidative stress properties.

Pharmacological investigation of genistein for its therapeutic potential against nitroglycerin-induced migraine headache.

OBJECTIVES: Migraine, typically occurs on one side of the head, lasts for hours to days. Trigemino-vascular system (TVS) plays a vital role in pain generation, with neurogenic inflammation and oxidative stress playing key roles in its pathophysiology. METHODS: This study aimed to investigate genistein's potential as anti-inflammatory and anti-oxidant agent in mitigating migraine pain. Genistein (20 and 50 mg/kg) was administered intraperitoneally (IP) to nitroglycerin (NTG; 10 mg/kg)-induced migraine model in rats. Behavioral analysis, antioxidant assay, immunohistochemistry (IHC), histopathological examination, ELISA, and RT-PCR were conducted to evaluate the antimigraine potential of genistein. KEY FINDINGS: In-silico analysis showed genestien's ACE values of -4.8 to -9.2 Kcal/mol against selected protein targets. Genistein significantly reversed mechanical and thermal nociception, light phobicity, and head scratching; increased the intensities of GST, GSH, catalase; and down regulated lipid peroxidase (LPO) in cortex and trigeminal nucleus caudalis (TNC). It also reduced Nrf2, NF-kB, and IL6 expression, analyzed through IHC, improved histopathological features, and increased COX-2 and decreased PPAR-γ expressions, while RT-PCR analysis revealed increased PPAR-γ expressions in genistein-treated rats. CONCLUSION: Genistein exhibited potent antioxidant and anti-inflammatory properties in migraine treatment, acting through multifactorial mechanisms by modulating the expression of numerous proteins in the region cortex and TNC.

Dermatoprotective effect of Moringa oleifera leaf extract on sodium valproate-induced skin damage in rats.

Valproic acid is an antiepileptic drug associated with skin-related issues like excessive hair growth, hair loss, and skin rashes. In contrast, Moringa oleifera, rich in nutrients and antioxidants, is gaining popularity worldwide for its medicinal properties. The protective properties of M. oleifera extract against skin-related side effects caused by valproic acid were investigated. Female rats were divided into control groups and experimental groups such as moringa, sodium valproate, and sodium valproate + moringa groups. A 70% ethanolic extract of moringa (0.3 g/kg/day) was given to moringa groups, and a single dose of sodium valproate (0.5 g/kg/day) was given to valproate groups for 15 days. In the skin samples, antioxidant parameters (such as glutathione, glutathione-S-transferase, superoxide dismutase, catalase, and total antioxidant capacity), as well as oxidant parameters representing oxidative stress (i.e. lipid peroxidation, sialic acid, nitric oxide, reactive oxygen species, and total oxidant capacity), were examined. Additionally, boron, hydroxyproline, sodium-potassium ATPase, and tissue factor values were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also carried out for protein analysis in the skin samples. The results showed that moringa could increase glutathione, total antioxidant capacity, sodium-potassium ATPase, and boron levels, while decreasing lipid peroxidation, sialic acid, nitric oxide, total oxidant capacity, reactive oxygen species, hydroxyproline, and tissue factor levels. These findings imply that moringa possesses the potential to mitigate dermatological side effects.