Antioxidant Properties Research Articles

Resveratrol Enhances the Efficacy of Combined BM-MSCs Therapy for Rat Spinal Cord Injury via Modulation of the Sirt-1/NF-κB Signaling Pathway.

Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.

Evaluation of pathways involved in the protective effect of trans sodium crocetinate against contrast-induced nephropathy in rats.

Contrast-induced nephropathy (CIN) is the most important side effect following contrast media application. The purpose of this study was to investigate the nephroprotective effects of trans sodium crocetinate (TSC) against sodium amidotrizoate/meglumine amidotrizoate (SAMA).Wistar rats were classified into eight groups (n = 6, male, 220-250g) including (1) sham, injection of solvents (intraperitoneally; i.p.), (2) premedication-control, N(ω)-nitro-L-arginine methyl ester (L-NAME, 10mg/kg, i.p.) + indomethacin (IND, 10mg/kg, i.p.), (3) model (L-NAME + IND + SAMA (12.5ml/kg, i.p.)), (4-6) TSC 10, 20, and 40mg/kg/day, 7 days, i.p., and L-NAME + IND + SAMA, (7) N-acetylcysteine (NAC, 125mg/kg/day, 7 days, i.p.) and L-NAME + IND + SAMA, (8) TSC alone (40mg/kg/day, 7 days, i.p.). Rats were injected with L-NAME, IND, and SAMA 40h after water deprivation.SAMA caused the enhancement of histopathological damage in kidney tissue, biochemical factors (serum blood urea nitrogen and creatinine), and oxidative stress. Moreover, SAMA increased inflammation (TNF-α), apoptosis proteins(Caspase 3-cleaved and Bax/Bcl-2 ratio), and autophagy markers (Beclin-1 and LC3 II/I ratio). TSC declined biochemical factors and oxidative stress. Also, TSC 40mg/kg decreased histopathological damage, inflammation, apoptosis, and autophagy markers.This study demonstrated that TSC has nephroprotective effects through anti-oxidant, anti-inflammatory, and anti-apoptotic properties, as well as regulating autophagy.

Therapeutic Dose of Zinc Aspartate and Zinc Citrate Attenuates Disease Activity Indices in Rheumatoid Arthritis.

Zinc aspartate and zinc citrate have been used as zinc supplements in different health conditions. Taking into consideration their anti-inflammatory, immunomodulatory, anti-oxidant and antimicrobial properties, the present study has been designed to analyse the effect of zinc aspartate and zinc citrate treatment at therapeutic dose level on disease severity index, haematological, serological, antimicrobial and radiological markers of rheumatoid arthritis in Wistar rats. Bactericidal potential of the two organic zinc compounds was analysed in vitro in clinically isolated Escherichia coli. Arthritis was induced in male Wistar rats by intradermal injection of an emulsion containing collagen type II and Complete Freund's Adjuvant (CFA) containing 1mgmL-1 Mycobacterium tuberculosis H37Ra. Zinc aspartate and zinc citrate were orally administered after the onset of the disease for 4weeks. Ameliorative effect of zinc aspartate and zinc citrate was evaluated by analysing indices of severity and disease activity markers of rheumatoid arthritis. The liver and kidney function tests were performed to evaluate any possible adverse effect of compounds. Antimicrobial activity of the zinc compounds was assessed in clinically isolated E. coli by MTT assay. Zinc aspartate and zinc citrate equivalent to a therapeutic dose of 50mg/day of elemental zinc attenuated the clinical characteristic of rheumatoid arthritis in the animal model of arthritis, collagen-induced arthritis (CIA). Both zinc salts also exhibited antimicrobial effects against E. coli. The selected dose of zinc aspartate and zinc citrate showed no adverse effects in treated rats. This study highlights the potentiality of zinc compounds as antiarthritic agents and also point to its preventive effects on microbial growth that has been observed in rheumatoid arthritis patients due to their increased sensitivity for bacterial infection.

Abstract 4137895: Serum High-density Lipoprotein-Associated Paraoxonase-1 Levels Predict Recurrent Cardiovascular Events after Stent Implantation in Patients with Stable Angina Pectoris

Background: Poor clinical outcomes for patients undergoing hemodialysis (HD) after drug-eluting stent (DES) implantation have been reported. High-density lipoprotein (HDL) cholesterol is well-established as a negative risk factor for coronary artery disease, and its anti-oxidant property has been attributed mainly to the HDL-bound enzyme paraoxonase-1 (PON-1). Myeloperoxidase (MPO), a pro-oxidant enzyme released from activated neutrophils, has been shown to alter the atheroprotective function of HDL to a dysfunctional form. The aim of this study was to investigate the relationship between plasma MPO and serum PON-1 levels after implantation of DES in patients with stable angina pectoris (SAP) with and without HD. Methods: Serum PON-1 concentrations and PON-arylesterase activity were measured in 183 patients with SAP after DES implantation (HD group, n=37; non-HD group, n=146) with a sandwich ELISA method. Cardiovascular events were defined as sudden cardiac death, fatal or non-fatal myocardial infarction, cerebral infarction and other non-fatal events including unstable angina pectoris or coronary revascularization. Results: Serum PON-1 concentrations and PON-arylesterase activity were significantly lower in the HD group than in the non-HD group (PON-1 concentrations, P<0.0001; PON-arylesterase activity, P<0.0001). In addition, plasma MPO in patients undergoing HD were significantly higher than in patients not undergoing HD (P<0.0001). Moreover, plasma MPO showed a significant inverse correlation with serum PON-1 concentrations and PON-arylesterase activity (concentration: R= -0.24, P=0.0013; arylesterase-activity: R=-0.24, P=0.0014). Cardiovascular event rates were significantly higher in the HD group than in the non-HD group (67.6% vs. 43.8%, P<0.01). Kaplan-Meier survival analysis showed that the low-PON-1 group (<58.0 mg/mL, median) had a significantly worse outcome than the high-PON-1 group ( P =0.013). Multivariate analysis showed that a low serum PON-1 concentration was the only independent predictor of cardiovascular events (odds ratio, 1.93; 95% confidence interval, 1.10 to 3.40, P =0.024). Conclusions: These findings demonstrate that plasma MPO have a significant inverse correlation with PON-1 in patients undergoing HD and suggest that an imbalance between pro-oxidants and anti-oxidants may contribute to the progression and destabilization of human coronary atherosclerotic lesions in patients with SAP who undergo HD following DES implantation.

Nephroprotective effects of the soluble guanylyl cyclase stimulator, riociguat in doxorubicin-induced acute kidney injury in rats

This study aimed to investigate the potential protective effects of riociguat, a soluble guanylyl cyclase (sGC) stimulator, on kidney function and structure in rats with acute kidney injury (AKI) induced by the chemotherapeutic drug doxorubicin (DX). Rats were subjected to a single intraperitoneal injection of DX (13.5 mg/kg) on the 5th day, either alone or in combination with low-dose riociguat (3 mg/kg/day), or high-dose riociguat (10 mg/kg/day) for 8 consecutive days. Various markers related to kidney function, oxidative stress, and inflammation were measured in plasma and urine. Kidney tissues were examined histopathologically. DX-induced nephrotoxicity was characterized by increased plasma urea, creatinine, uric acid and neutrophil gelatinase-associated lipocalin (NGAL). DX also decreased creatinine clearance and albumin levels and increased urinary N-acetyl-β-D-glucosaminidase (NAG) activity. Furthermore, DX increased the inflammatory markers interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). DX further induced oxidative stress injury evidenced by decreased glutathione reductase (GR) activity, total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels and increased malondialdehyde (MDA) levels. Concomitant treatment with riociguat ameliorated these DX-induced changes with parallel histopathological improvements but the effects were more favorable with high-dose riociguat. The observed renoprotective effects of riociguat can be partly attributed to the anti-inflammatory and anti-oxidant properties of this drug.

Investigation of Antioxidant and Anti-inflammatory Properties of Berberine Nanomicelles: In vitro and In vivo Studies.

In the present study, neuroprotective effects of berberine (BBR) and berberine nanomicelle (BBR-NM) against lipopolysaccharides (LPS)-induced stress oxidative were investigated, and compared by evaluating their antioxidant and anti-inflammatory activities in PC12 cells, and rat brains. A fast, green, and simple synthesis method was used to prepare BBR-NMs. The prepared BBR-NMs were then characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). In vitro experiments were carried out on the LPS-treated PC12 cell lines to investigate the anti-cytotoxic and antioxidant properties of BBR-NM and BBR. The results showed that BBR-NMs with a diameter of ~100 nm had higher protective effects against ROS production and cytotoxicity induced by LPS in PC12 cells in comparison with free BBR. Moreover, in vivo experiments indicated that the activity levels of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), increased in the brain of LPS-treated rats administrated with BBR-NM at the optimum dose of 100 mg.kg-1. BBR-NM administration also resulted in decreased concentration of lipid peroxidation (MDA) and pro-inflammatory cytokines, such as Serum interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Overall, BBR-NM demonstrated higher neuroprotective effects than free BBR, making it a promising treatment for improving many diseases caused by oxidative stress and inflammation.

Yohimbine treatment improves pulmonary fibrosis by attenuating the inflammation and oxidative stress via modulating the MAPK pathway

Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disorder characterized by the accumulation of extracellular matrix and collagen, resulting in significant parenchymal scarring and respiratory failure that leads to mortality. Yohimbine (YBH) is an α-2 adrenergic receptor antagonist with anti-oxidant and anti-inflammatory properties. In the current study, we aimed to investigate the anti-inflammatory, anti-oxidant and anti-fibrotic activity of YBH against LPS/TGF-β-induced differentiation in BEAS-2B/LL29 cells and bleomycin (BLMN) induced pulmonary fibrosis model in rats. Network pharmacology, gene expression, Western-blot analysis, immune-cytochemistry/immunohistochemistry, lung function and histology techniques were used to assess the fibrotic marker expression/levels in cells or rat lung tissues. YBH treatment significantly attenuated the LPS-induced pro-inflammatory (identified through a network-pharmacology approach) and oxidative stress markers expression in lung epithelial cells. TGF-β stimulation significantly elevated the fibrotic cascade of markers and treatment with YBH attenuated these markers’ expression/levels. Intra-tracheal administration of BLMN caused a significant elevation of various inflammatory/oxidative stress and fibrotic markers expression in lung tissues and treatment with YBH significantly mitigated the same. Ashcroft score analysis revealed that BLMN exhibited severe distortion of the lungs, elevation of thickness of the alveolar walls and accumulation of collagen in tissues, further treatment with YBH significantly suppressed these events and improved the lung architecture. Lung functional parameters demonstrated that BLMN-induced stiffness and resistance were reduced considerably upon YBH treatment and restored lung function dose-dependently. Overall, this study reveals that YBH treatment significantly attenuated the BLMN-induced fibrosis by regulating the MAPK pathway and provided insightful information for progressing towards translational outcomes.

Silicone-based AC102-loaded cochlear implant coatings protect residual hearing in an animal model of cochlear implantation

Cochlear implant users with residual hearing benefit synergistically from combined electrical stimulation via the cochlear implant and preserved residual hearing after surgery. However, direct mechanical trauma and subsequent inflammation may deteriorate hearing function. AC102, a novel otoprotective pyridoindole with anti-apoptotic and anti-oxidative properties significantly improved hearing recovery following cochlear implantation when administered intratympanically prior to surgery. Additionally, AC102 exerts neurotrophic effects, possibly aiding in the preservation of auditory nerve fibers and spiral ganglion neurons. Rapid clearance of the drug, however, might be a limiting factor to further attenuate the inflammatory response and maintain neuronal health. The aim of the current study was to design an AC102-loaded electrode array for sustained drug delivery and investigate its effects in hearing preservation cochlear implantation.First, the release-kinetics of AC102 were investigated in vitro and modelled by the Higuchi equation of drug release. An electrode array coated with 10% AC102 was manufactured, its release kinetics evaluated, and subsequently tested in vivo. 20 normal hearing Mongolian gerbils were unilaterally implanted with an AC102-loaded or an unloaded control electrode. Compound action potentials were measured prior to cochlear implantation and serially over 28 days. Hair cells, inner hair cell synapses, and auditory nerve fibers were quantified in cochlear whole-mounts by immunofluorescence staining.AC102 release from silicone coating could be predictably modelled by the Higuchi equation of drug release. The electrode array with an AC102-silicone depot enabled non-linear sustained drug release with initially higher release concentrations. In vivo, the AC102-loaded electrode array significantly recovered auditory threshold shifts near the maximum insertion depth over 28 days. In the apical region, a significant recovery was noticed only until day 14, after which threshold shifts aligned between groups. Histologically, AC102-loaded electrodes significantly preserved outer hair cells apical of the maximum insertion depth and inner hair cells and neuronal structures at the tip of the inserted electrode.In conclusion, the drug-loaded electrode arrays could predictably release AC102 over a period of 28 days. AC102 enabled the restoration of auditory thresholds near the area of maximum insertion, which is the desired region to be preserved in cochlear implant recipients with residual hearing.

Preparation and evaluation of soft gelatin capsules loaded with astaxanthin, niacin and garlic oil for removal of plague in atherosclerosis

Atherosclerosis, a chronic inflammatory disease, is the leading cause of cardiovascular diseases. In atherosclerosis, the arterial walls are characterized by plaque deposits on the inside of arteries. This study focuses on preparing a fill formulation to remove plaque in atherosclerosis, then analyse the pharmaceutical ingredients used and later produce soft gelatin capsules. Soft gelatin capsules are hermetically sealed, one-piece capsule which has a suspension or semi-solid as fill. Oxidative stress and inflammation are factors responsible for the development of atherosclerosis. Hence, the active pharmaceutical ingredients (APIs) chosen for fill formulation need to possess effective anti-oxidant and anti-inflammatory properties. A novel combination of APIs: Astaxanthin, Niacin and Garlic oil were chosen for the removal of plaque in atherosclerosis. Each of these APIs is known to possess a specific function in the control of plaque development. The fill formulation prepared was analysed for its recovery using various analytical techniques like UV spectrophotometry, high-performance liquid chromatography (HPLC) and thin-layer chromatography (TLC). This fill formulation was encapsulated within the gelatin shell prepared to produce soft gelatin capsules. The encapsulated soft gelatin capsules were evaluated based on various parameters which include average net weight, disintegration test, loss on drying and dissolution.

Application of Dietary Anthocyanins in Type 2 Diabetes Mellitus Treatment

Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by impaired glucose control around the world that causes huge health challenges globally with increased morbidity and mortality. Inadequate insulin secretion and decreased insulin sensitivity are considered as main contributors to T2DM. Anthocyanin, a type of flavonoid compound, is one potentially feasible dietary intervention for T2DM treatment in addition to clinical drug interference. Dietary anthocyanins can be found in various berries, vegetables, and beverages, which provide vibrant colors. Anthocyanins are also increasingly used as colorants in the food industry. It is also seen as a supplement because of its antioxidation properties. Meanwhile, several evidence demonstrate the potential relationship between dietary anthocyanin intake and T2DM management. In this work, recent epidemiologic studies on the potential effects of anthocyanins in controlling T2DM have been reviewed, especially focusing on the typical indexes such as glycemic levels, insulin levels, etc. Many studies illustrate that appropriate intake of dietary anthocyanins could control glycemic levels, adjust insulin levels, and reduce insulin resistance. Because of these functions, dietary anthocyanins may trigger positive effects on T2DM treatment. Dietary anthocyanins could be seen as a good dietary intervention in T2DM control that meets the requirement of long-term management for the specific chronic disease.

Red-cell omega-3 fatty acids associate with increased hippocampal volume and superior longitudinal cognition in atrial fibrillation

Abstract Background Atrial fibrillation (AF) is associated with cognitive impairment and dementia. Omega-3 Fatty Acids (n-3 FAs) have anti-thrombotic, anti-inflammatory and anti-oxidative properties; however, their neuroprotective effects remain controversial. Here, we report the association of n-3 FAs with both structural (hippocampal volume) and functional (cognition) readouts in a large cohort of AF pts. Purpose a) To determine the association of n-3 FAs and left and right hippocampal volume at baseline in AF pts. b) To assess the predictive value of HV and n-3 FAs for the risk of cognitive impairment after a 7-year follow-up period. Methods This prospective ongoing multicenter Swiss Atrial Fibrillation study (Swiss-AF) included 2,359 pts with documented AF and baseline red-cell n-3 FAs levels, measured by gas chromatography and mass spectrometry. Hippocampal volume (HV) and segmentation based intracranial volume (ICV) were analyzed by FreeSurfer's (v 7.4.0) subregion segmentation module and Sequence Adaptive Multimodal SEGmentation from brain MRI in 1,736 pts. Detailed neurocognitive assessments in pts at baseline and follow up periods were performed. We used mixed-effect linear regression models to determine the association of n-3 FAs and HV. For conversion to cognitive impairment (defined as MoCA score < 26), we performed cox-proportional hazards regression model. Two adjustment models were applied as described in the figures. Results Patients with AF (mean age, 73 years old [±8.5 SD]; 157 women [27%]) with 9569 cognitive evaluations (mean follow-up, 3.6 years [±2.3 SD]) were assessed. At baseline, we observed statistically significant associations between total n-3 FAs levels (EPA + DHA + ALA + DPA) and individual n-3 FAs (EPA, DHA, DPA) with increased HV after adjustment for ICV and other covariates (Fig1A, 1B). After all adjustments, EPA remained associated with both bilateral HV and right HV. Furthermore, we observed a significant association between HV and neurocognitive assessments, as measured both in global (MoCA, CoCo) and specific tests (TMT-A, TMT-B, DSST, SF) (Fig1C). Over time, quartile 4 (Q4, highest n-3) compared to quartile 1 (Q1, lowest), had a 16% lower risk of cognitive impairment (HR, 0.84 [CI 0.75-0.93]; P=0.001) for total n-3 FAs and even 30% lower specifically for EPA (HR, 0.7 [CI 0.63-0.78]; P<0.001). The risk of cognitive impairment was 47% lower (HR, 0.53 [CI 0.45-0.63]; P<0.001) when the highest HV Q4 was compared to lowest HV Q1 (Fig2A). In combination, the highest quartile of bilateral HV and EPA demonstrated an increased probability of being cognitive impairment-free and they had a 72% lower (HR, 0.28 [0.18-0.43]; P<0.001) risk of cognitive impairment (Fig2B). Conclusions 1. Red cell n-3 FAs levels are associated with higher HV in AF pts. 2. Higher baseline levels of n-3 FAs, particularly of EPA, are associated with both an increased HV and a decreased risk of cognitive impairment after 7 years follow up.

Role of vitamin K2 and vitamin K cycle enzymes in aortic valvular interstitial cell calcification

Abstract Introduction Calcific aortic valve disease (CAVD) is the most common valve disease. Currently, there is no medical treatment available for CAVD. Vitamin K antagonists promote CAVD while population-based studies suggest that dietary intake of vitamin K reduces the incidence of CAVD in adults. However, randomized trials have so far not proven a clear benefit of vitamin K supplementation on the progression of AVS. Consequently, there is a need for a deeper understanding of the role of vitamin K in valvular calcification. This study aims to further investigate mechanisms of action of vitamin K during valvular calcification. Methods and Results Aortic valve samples were obtained from patients undergoing surgical aortic valve replacement for CAVD and valvular interstitial cells (VIC) were isolated by collagenase II digestion (Fig. 1). VIC expressed typical markers like Vimentin and α-SMA and were cultured in a control medium (CM) or further calcified in a pro-calcifying medium (PCM) containing sodium dihydrogen phosphate and ascorbic acid. PCM led to upregulation of Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP) expression, and ALP-activity after 7 and 21 days of culture. Moreover, alizarin red staining visualized significant calcium mineral deposition after 21 days of culture (Fig. 2). The addition of the most potent vitamin K2 derivative (Menaquinone-7, MK-7) improved cell viability under both control and calcifying conditions (Fig. 3). Moreover, MK-7 protected VIC from ferroptotic cell death (Fig. 4) and increased expression of the vitamin K-dependent Matrix-Gla-protein (MGP), a major inhibitor of ectopic calcification (Fig. 5). To fulfill its function as an activator of vitamin K-dependent proteins like MGP, vitamin K needs to be reduced to vitamin K hydroquinone by the vitamin K epoxide reductase enzymes VKORC1 and VKORC1L1. In VIC, using our calcification protocol, treatment with PCM led to the downregulation of VKORC1, but not of VKORC1L1, an enzyme with known anti-oxidative properties (Fig. 6). We next performed siRNA-mediated knockdown of VKORC1 and VKORC1L1 in VIC and observed calcification after 7 and 21 days of culture by measuring expression of ALP, RUNX2, quantifying ALP activity, and staining for calcium minerals (alizarin red). Intriguingly, VKORC1L1-knockdown sharply increased the expression of ALP. To further elucidate these findings, we will perform overexpression experiments to analyze, if VKORC1L1 can alleviate PCM-induced calcification Conclusion: Vitamin K2 inhibits in vitro calcification of valvular interstitial cells and upregulates the calcification inhibitor Matrix-Gla-Protein. Our results suggest the involvement of the vitamin K cycle enzyme VKORC1L1, which is known to exhibit anti-oxidative and cytoprotective effects. Further studies are warranted to shed light on the regulation of the enzymes to improve our understanding.

The Molecular Bases of Anti-Oxidative and Anti-Inflammatory Properties of Paraoxonase 1

The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease.

Zaluzanin-D enriched Vernonia arborea extract mediated copper oxide nanoparticles synthesis and their anti-oxidant, anti-inflammatory and DNA methylation altering properties.

Metal oxide nanoparticles synthesized with the aid of medicinal plant extracts are showing potential as treatment options for inflammatory diseases. Two key benefits of this synthesis method is: the synthesis process is environmentally benign and the utilization of medicinal plant-derived extracts adds to the medicinal value of the synthesized nanoparticle. Earlier, sesquiterpene lactone zaluzanin-D (ZD) has been isolated from leaves of Vernonia arborea. ZD showed ability to reduce inflammation in activated monocytes. Copper oxide nanoparticles (bCuO-NPs) were synthesized using ZD-enriched leaf extract of V. arborea and characterized by UV-vis spectroscopy, FT-IR, XRD, particle size analyzer, and TEM. Synthesized bCuO-NPs did not show significant toxicity to human monocytic cell lines (THP-1) at the tested concentrations. The bCuO-NPs showed radical scavenging ability indicating anti-oxidant properties. Flow cytometry experiments proved the capability of bCuO-NPs to reduce intracellular ROS in peroxide-activated THP-1 cells. The NPs also showed a significant ability to reduce inflammatory adhesion in PMA-activated THP-1 cells. In the DNA methylation studies, bCuO-NPs behaved similarly to ZD and prevented DNA hypomethylation at the MMP-9 promoter region. These properties strongly indicate the ability of bCuO-NPs to reduce inflammation in the activated monocytes. Furthermore, in zebrafish (Danio rerio) embryos, the developmental toxicity of bCuO-NPs was assessed. The studies indicated the reduced toxicity and compatibility of the NPs with biological organisms. Based on the results, it can be concluded that the bCuO-NPs produced from ZD-enriched leaf extract have significant anti-oxidant capabilities and the ability to reduce inflammation in monocytic cell lines. Overall, reduced in vitro and in vivo toxicity, along with its antioxidant and anti-inflammatory properties, makes bCuO-NPs a potential candidate for anti-inflammatory drugs.

Coloprotective effects of chebulic myrobalan extract by regulation of AMPK-SIRT1 signaling: A pharmacological and histopathological evaluation

Ulcerative colitis is a chronic, refractory disease caused by dysregulation of mucosal immune responses to the indigenous bacterial flora as well as genetic and environmental variables. Recently, there has been increasing interest towards the use of herbal medicines for the treatment of ulcerative colitis and the potential benefits could lie in their high patient acceptability, effectiveness, safety, and relatively low cost. It has been reported that Chebulic myrobalan (Terminalia chebula) exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. The present study was designed to evaluate the protective potential of extract of dried fruit pulp of T. chebula against Dextran sulphate sodium (DSS)-induced ulcerative colitis in male BALB/c mice. Three cycles of DSS (3 % w/v in drinking water), each followed by a seven-day remission phase were used to induce ulcerative colitis in mice. Animals were treated with T. chebula (300 mg/kg and 600 mg/kg) starting from Ist remission period to the end of the study. Different biochemical assays, histological evaluation and molecular analysis were performed to evaluate the protective effects of T. chebula extract in DSS induced colitis. T. chebula modulates the expression of nuclear factor kappa B, adenosine monophosphate kinase, tumour necrosis factor-alpha, sirtuin 1 and interleukin-1β. Furthermore, it also accorded coloprotective effects against DNA damage, apoptosis, inflammation and nitrosative stress. Finally, it was found that the high dose of the T. chebula extract (600 mg/kg) was found to be more effective than a low dose (300 mg/kg) in restoring the ulcerative colitis induced colonic damage.

Diammonium glycyrrhizinate ameliorates alcohol-induced liver injury by reducing oxidative stress, steatosis, and inflammation

Alcohol-induced liver injury (ALI) is a serious global health issue. Diammonium glycyrrhizinate (DG), a pharmaceutical form of glycyrrhizic acid, has been reported to have anti-inflammatory and anti-oxidative stress properties. We investigated the potential hepatoprotective effects of DG against ALI and explored the mechanisms of it. In vivo, C57BL/6J mice were used to investigate the protective effect of DG on ALI induced by chronic plus binge alcohol exposure. In vitro, AML-12 cells were applied to evaluate the role of DDX5 in the hepatic protection of DG and explore the possible mechanism of STAT1 activation regulated by DDX5. The results showed that DG significantly alleviated liver injury, inflammation, and lipid deposition in hepatocytes. It also beneficially influenced oxidative stress dysregulation. RNA-seq expression in mouse liver tissue indicated that Dead-box helicase 5 (DDX5) might be a potential target of DG. Compared with the control group, the expression of DDX5 decreased significantly in the ethanol-fed group, while DDX5 was restored in the DG treatment group. In addition, the protective effects of DG against ALI were impaired by DDX5 deficiency. DDX5 inhibited the phosphorylation of signal transducer and activator of transcription 1 (STAT1) by recruiting the protein inhibitor of activated STAT1 (PIAS1) to STAT1. The protective effect of DG against ALI associated with oxidative stress, steatosis, and inflammation was probably via regulating the DDX5/STAT1 axis.

Soluble Epoxide Hydrolase Inhibitor Ameliorates Olfactory Dysfunction, Modulates Microglia Polarization, and Attenuates Neuroinflammation after Ischemic Brain Injury.

Olfactory bulb (OB) microglia activation and inflammation can lead to olfactory dysfunction, which often occurs after an ischemic stroke. Inhibition of soluble epoxide hydrolase (sEH) attenuates neuroinflammation in brain injuries by reducing the degradation of anti-inflammatory epoxyeicosatrienoic acids. However, whether sEH inhibitors can ameliorate olfactory dysfunction after an ischemic stroke remains unknown. Ischemic brain injury and olfactory dysfunction were induced by middle cerebral artery occlusion (MCAO) in Wistar Kyoto rats. The rats were administered 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), a selective sEH inhibitor. Olfactory function, cerebral infarct volume, and the degree of degeneration, microglial polarization and neuroinflammation in OB were evaluated. Following treatment with AUDA, rats subjected to MCAO displayed mild cerebral infarction and OB degeneration, as well as better olfactory performance. In OB, AUDA triggered a modulation of microglial polarization toward the M2 anti-inflammatory type, reduction in proinflammatory mediators, and enhancement of the antioxidant process. The effectiveness of AUDA in terms of anti-inflammatory, neuroprotection and anti-oxidative properties suggests that it may have clinical therapeutic implication for ischemic stroke related olfactory dysfunction.

The Effect of Aloe vera on Skin and Its Commensals: Contribution of Acemannan in Curing Acne Caused by Propionibacterium acnes

Aloe vera is one of the most significant therapeutical plant species that belongs to the family Liliaceae. Aloe vera is composed of a high amount of water, with the remainder being dry matter. The dry matter contains a lot of bioactive compounds like carbohydrates, fats, and enzymes, with various therapeutic and antimicrobial properties. It can enhance the proliferation of cells and prevent cell damage by anti-oxidative properties (stimulating the secretion of superoxide dismutase and peroxidase). Human skin is colonized by microbes like fungi (Candida albicans), bacteria (Propionibacterium acnes, Staphylococcus aureus), and mites. These commensals are responsible for skin characteristics such as acidic pH, the pungent smell of sweat, etc. Human fetuses lack skin microbiota, and their skin is colonized after birth. Commensals present on the skin have a crucial role in training the human immune system against other pathogenic microbes. Propionibacterium acnes act as an opportunistic pathogen when the balance between the commensals is disturbed. We also emphasize the recent progress in identifying the aloe metabolite biosynthesis pathways and the associated enzyme machinery. The hyperproliferation of Propionibacterium acnes causes acne, and acemannan plays a significant role in its cure. Hence, we need to consider a new treatment approach based on the root cause of this dysbiosis.

Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in osteoarthritis by inhibiting ERK, JNK and NF-κB signaling pathways

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin–eosin (H&E) staining, Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.

Anticancer Properties Against Select Cancer Cell Lines and Metabolomics Analysis of Tender Coconut Water.

Tender Coconut Water (TCW) is a nutrient-rich dietary supplement that contains in bioactive secondary metabolites and phytohormones with anti-oxidative and anti-inflammatory properties. Studies on TCW's anti-cancer properties are limited and the mechanism of its anti-cancer effects have not been defined. In the present study, we investigate TCW for its anti-cancer properties and, using untargeted metabolomics, we identify components form TCW with potential anti-cancer activity. Cell viability assay, BrdU incorporation assay, soft-agar assay, flow-cytometery, and Western blotting were used to analyze TCW's anticancer properties and to identify mechanism of action. Liquid chromatography- Tandem Mass Spectroscopy (LC-MS/MS) was used to identify TCW components. TCW decreased the viability and anchorage-independent growth of HepG2 hepatocellular carcinoma (HCC) cells and caused S-phase cell cycle arrest. TCW inhibited AKT and ERK phosphorylation leading to reduced ZEB1 protein, increased E-cadherin, and reduced N-cadherin protein expression in HepG2 cells, thus reversing the 'epithelial-to-mesenchymal' (EMT) transition. TCW also decreased the viability of Hep3B hepatoma, HCT-15 colon, MCF-7 and T47D luminal A breast cancer (BC) and MDA-MB-231 and MDA-MB-468 triplenegative BC cells. Importantly, TCW did not inhibit the viability of MCF-10A normal breast epithelial cells. Untargeted metabolomics analysis of TCW identified 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We demonstrate that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid inhibit the growth of cancer cells. TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling.