From Hypertension to Beyond: Unraveling the Diverse Mechanisms of Olmesartan in Disease Modulation.

Olmesartan, originally known for its antihypertensive properties, exhibits promising potential in addressing inflammation-mediated diseases. As an angiotensin II receptor blocker (ARB), Olmesartan influences pivotal pathways, including reactive oxygen species, cytokines, NF-κB, TNF-α, and MAPK. This suggests a viable opportunity for repurposing the drug in conditions such as ulcerative colitis, neuropathy, nephropathy, and cancer, as supported by multiple preclinical studies. Ongoing clinical trials, particularly in cardiomyopathy and nephropathy, suggest a broader therapeutic scope for Olmesartan. Repurposing efforts would entail comprehensive investigations using disease-specific preclinical models and dedicated clinical studies. The drug's established safety profile, wide availability, and well-understood ARB mechanism of action offer distinct advantages that could facilitate a streamlined repurposing process. In summary, Olmesartan's versatile impact on inflammation-related pathways positions it as a promising candidate for repurposing across various diseases. Ongoing clinical trials and the drug's favorable attributes enhance its appeal for further exploration and potential application in diverse medical contexts.

Material matters: exploring the interplay between natural biomaterials and host immune system.

Biomaterials are widely used for various medical purposes, for instance, implants, tissue engineering, medical devices, and drug delivery systems. Natural biomaterials can be obtained from proteins, carbohydrates, and cell-specific sources. However, when these biomaterials are introduced into the body, they trigger an immune response which may lead to rejection and failure of the implanted device or tissue. The immune system recognizes natural biomaterials as foreign substances and triggers the activation of several immune cells, for instance, macrophages, dendritic cells, and T cells. These cells release pro-inflammatory cytokines and chemokines, which recruit other immune cells to the implantation site. The activation of the immune system can lead to an inflammatory response, which can be beneficial or detrimental, depending on the type of natural biomaterial and the extent of the immune response. These biomaterials can also influence the immune response by modulating the behavior of immune cells. For example, biomaterials with specific surface properties, such as charge and hydrophobicity, can affect the activation and differentiation of immune cells. Additionally, biomaterials can be engineered to release immunomodulatory factors, such as anti-inflammatory cytokines, to promote a tolerogenic immune response. In conclusion, the interaction between biomaterials and the body's immune system is an intricate procedure with potential consequences for the effectiveness of therapeutics and medical devices. A better understanding of this interplay can help to design biomaterials that promote favorable immune responses and minimize adverse reactions.

Alpha-linolenic acid based nano-suspension protect against lipopolysaccharides induced mastitis by inhibiting NFκBp65, HIF-1α, and mitochondria-mediated apoptotic pathway in albino Wistar rats.

The purpose of this study was to investigate the therapeutic effects and underlying mechanism of alpha-linolenic acid based intra-mammary nano-suspension (ALA-NS) on both in vitro antimicrobial and in vivo activity. The ALA-NS formulated and optimized for parameters like particle size, zeta potential, polydispersity index, sedimentation volume, and stability studies. In vitro, our results showed that ALA-NS (F1 and F2) have the higher zone of inhibition and lower minimum inhibitory concentration (MIC) value than ALA and cefotaxime alone against mastitis-causing pathogens. In vivo, our results showed that ALA-NS (F1 and F2) restored the altered oxidative biomarkers (superoxide dismutase, catalase, glutathione, TBARs, and protein carbonyl) along with histopathological changes in lipopolysaccharides (LPS) treated rats. Western blot results indicated that ALA-NS (F1 and F2) inhibited LPS induced inflammatory proteins (NFκBp65, COX, LOX, and IFN-γ) in rat mammary epithelial cells. ALA-NS (F1 and F2) also suppressed the hypoxia inducible factor-1α (HIF-1α) and upregulated prolyl-hydroxylase (PHD-2), sterol regulatory element binding protein (SREBP-1c), and fatty acid synthase (FASN) protein expression. In addition, ALA-NS upregulated the pro-apoptotic (BAX and BAD) and downregulated anti-apoptotic (BCL-2 and BCL-XL) proteins expression in rat mammary epithelial tissue. In conclusion, we found that ALA-NS (F1 and F2) have in vitro antimicrobial activity and protective effects on LPS-induced mastitis in rats.

Antidiabetic activity of mefloquine via GLP-1 receptor modulation against STZ-NA-induced diabetes in albino wistar rats.

Mefloquine was retrieved as a glucagon -like peptide-1 receptor agonist and, therefore, evaluated for its antidiabetic potential against non-insulin-dependent diabetes mellitus (NIDDM) in experimental animals. NIDDM was induced by single intraperitoneal injection of streptozotocin and nicotinamide (60 + 110 mg/kg) in albino wistar rats. The experimental animals were scrutinised for electrocardiographic (ECG) and heart rate variability (HRV) factors to study the autonomic dysfunction along with blood glucose, serum insulin, and liver glycogen levels for glycemic control. Simultaneously, antioxidant markers (TBARs, protein carbonyl, GSH, SOD, catalase) and inflammatory markers (COX, LOX, NO) were scrutinized as well. Oral administration of mefloquine normalised the heart rate with favourable regulation of time and frequency domain HRV parameters. Mefloquine restored the blood glucose, serum insulin, and liver glycogen levels favourably in diabetic rats. Treatment with mefloquine curtailed the antioxidant markers with favourable regulation of inflammatory signals. Mefloquine was also found to be less hepatotoxic in contrast to the standard metformin, providing an integrated advantage as an antidiabetic agent.

Modulation of oxidative stress response by flaxseed oil: Role of lipid peroxidation and underlying mechanisms.

Polyunsaturated fatty acids (PUFA's) are majorly classified as ω-3 and ω-6 fatty acids. The eicosapentaenoic acid (EPA, ω-3:20-5), docosahexaenoic acid (DHA, ω-3:22-6) and alpha-linolenic acid (ALA, ω-3:18-3) are known ω-3 fatty acids, extracted from animal (e.g fish oil) and plant sources (e.g flaxseed oil). Furthermore, linoleic acid (LA, ω-6:18-2) is recognized as ω-6 fatty acid and the most prominent biological fatty acid with a pro-inflammatory response. Flaxseed oil has variety of biological roles, due to the significant amount of ω-3/ω-6 fatty acids. Numerous studies have reported that ALA (ω-3:18-3) and LA (ω-6:18-2) has diverse pharmacological activities. The ALA (ω-3:18-3) and LA (ω-6:18-2) are recognised to be the pharmacological antagonist. For example, ALA (ω-3:18-3) is recognised as anti-inflammatory, whereas LA (ω-6:18-2) is considered to be pro-inflammatory. PUFA's get oxidized in three ways; firstly, free radical-mediated pathway, secondly non-free radical non-enzymatic metabolism, and lastly enzymatic degradation. The present report is an attempt to summarize various modes of PUFA's metabolism and elaborate biological effects of the associated metabolites concerning flaxseed oil.

GLA supplementation regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DMBA induced mammary gland carcinoma.

The aim of the present study is to evaluate the effect of gamma linolenic acid (GLA) on mitochondrial mediated death apoptosis, hypoxic microenvironment and cholinergic anti-inflammatory pathway against 7, 12-dimethylbenz (a) anthracene (DMBA) induced mammary gland carcinoma. The effects of GLA were evaluated morphologically and biochemically against DMBA induced mammary gland carcinoma. The metabolic study was done for evaluation of biomarkers using 1H NMR. The present study was also verified through immunoblotting and qRT-PCR studies for the evaluation of various pathways. GLA treatment has a delineate implementation upon morphology of the tissues when evaluated through carmine staining, hematoxyline and eosin staining and scanning electron microscopy. GLA also demarked a commendatory proclamation of the fifteen key serum metabolites analogous with amino acid metabolism and fatty acid metabolism when recognized through1H NMR studies. The immunoblotting and qRT-PCR studies accomplished that GLA mediated mitochondrial death apoptosis, curtail hypoxic microenvironment along with hindrance of de novo fatty acid synthesis and also mediate the cholinergic anti-inflammatory pathway to proclaim its anticancer effects.

Alpha-linolenic acid stabilizes HIF-1 α and downregulates FASN to promote mitochondrial apoptosis for mammary gland chemoprevention.

Alpha linolenic acid is an essential polyunsaturated fatty acid and is reported to have the anti-cancer potential with no defined hypothesis or mechanism/s. Henceforth present study was in-quested to validate the effect of alpha linolenic acid on mitochondrial apoptosis, hypoxic microenvironment and de novo fatty acid synthesis using in-vitro and in-vivo studies. The IC50 value of alpha linolenic acid was recorded to be 17.55µM against ER+MCF-7 cells. Treatment with alpha linolenic acid was evident for the presence of early and late apoptotic signals along with mitochondrial depolarization, when studied through acridine orange/ethidium bromide and JC-1 staining. Alpha linolenic acid arrested the cell cycle in G2/M phase. Subsequently, the in-vivo efficacy was examined against 7, 12-dimethylbenz anthracene induced carcinogenesis. Treatment with alpha linolenic acid demarcated significant effect upon the cellular proliferation as evidenced through decreased in alveolar bud count, restoration of the histopathological architecture and loss of tumor micro vessels. Alpha linolenic acid restored the metabolic changes to normal when scrutinized through 1H NMR studies. The immunoblotting and qRT-PCR studies revealed participation of mitochondrial mediated death apoptosis pathway and curtailment of hypoxic microenvironment after treatment with alpha linolenic acid. With all above, it was concluded that alpha linolenic acid mediates mitochondrial apoptosis, curtails hypoxic microenvironment along with inhibition of de novo fatty acid synthesis to impart anticancer effects.

Phytochemistry, pharmacology, toxicology, and clinical trial of Ficus racemosa.

Ficus racemosa is an important medicinal plant, found in India, Australia, and Southeast Asia. It is popularly known as 'gular.' It reduces blood glucose concentration due to the presence of ß-sitosterol. Many active constituents that have been isolated from various parts of this plant possess useful pharmacological activities. The literature survey proposed that it has multiple pharmacological actions that include antidiabetic, antioxidant, antidiarrhoeal, anti-inflammatory, antipyretic, antifungal, antibacterial, hypolipidemic, antifilarial, and hepatoprotection. This review article elaborately describes the traditional uses, phytochemistry, pharmacology, and toxicology of this plant. We also provide useful structures of the secondary metabolites along with their nuclear magnetic resonance (NMR) data. Some clinical trial data have also been provided in this review. This review would assist researchers to gather scientific information in future.