A Review on in-vivo and in-vitro Models of Obesity and Obesity-Associated Co-Morbidities.

BACKGROUND: Obesity is becoming a global pandemic with pandemic proportions. According to the WHO estimates, there were over 1.9 billion overweight individuals and over 650 million obese adults in the globe in 2016. In recent years, scientists have encountered difficulties in choosing acceptable animal models, leading to a multitude of contradicting aspects and incorrect outcomes. This review comprehensively evaluates different screening models of obesity and obesity-associated comorbidities to reveal the advantages and disadvantages/limitations of each model while also mentioning the time duration each model requires to induce obesity. METHODOLOGY: For this review, the authors have gone through a vast number of article sources from different scientific databases, such as Google Scholar, Web of Science, Medline, and PubMed. RESULTS: In-vivo models used to represent a variety of obesity-inducing processes, such as diet-induced, drug-induced, surgical, chemical, stress-induced, and genetic models, are discussed. Animal cell models are examined with an emphasis on their use in understanding the molecular causes of obesity, for which we discussed in depth the important cell lines, including 3T3-L1, OP9, 3T3-F442A, and C3H10T1/2. Screening models of obesity-associated co-morbidities like diabetes, asthma, cardiovascular disorders, cancer, and polycystic ovarian syndrome (PCOS) were discussed, which provided light on the complex interactions between obesity and numerous health problems. CONCLUSION: Mimicking obesity in an animal model reflects multifactorial aspects is a matter of challenge. Future studies could address the ethical issues surrounding the use of animals in obesity research as well as investigate newly developed models, such as non-mammalian models. In conclusion, improving our knowledge and management of obesity and related health problems will require ongoing assessment and improvement of study models.

Oleoresin Capsicum (OC) Spray: An Assessment of Respiratory Health and its Management Following Accidental and Deliberate Exposures.

Introduced into law enforcement in 1976, the oleoresin capsicum (OC) spray has been labeled as one of the most significant and radical developments in law enforcement. However, epidemiological research on OC health effects is deficient, receiving little public support. The major responses to acute exposure to OC spray can be found in the pulmonary system. The molecular mechanism(s) involved in the action of capsaicinoids, the active constituents in OC, are complex cascades of reactions which end up in necrosis or apoptosis. OC may also damage and deplete biological redox systems in the epithelial lining fluids and within cells and mitochondria, modifying structural proteins and nucleic acids and leading to enzyme inactivation. Since there are no characteristic laboratory tests available for identification or confirmation of OC exposure, and on the basis of prevailing data, reassessment of the health risks of OC exposures in vulnerable populations and in-depth study of the molecular mechanics of receptors is the need of the hour for the development of effective countermeasures. This review aims to consider evidence for adverse effects of OC spray used in ways comparable to their application by law enforcement personnel and civilians, with possible treatment recommendations that are precedent for improved management.

Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein-mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.

Design, QSAR Methodology, Synthesis and Assessment of Some Structurally Different Xanthone Derivatives as Selective Cox-2 Inhibitors for their Anti-inflammatory Properties.

INTRODUCTION: Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential. METHODS: The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization. RESULTS: The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially. CONCLUSION: With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.

Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions.

Obesity is rapidly becoming a global health problem affecting about 13% of the world's population affecting women and children the most. Recent studies have stated that obese asthmatic subjects suffer from an increased risk of asthma, encounter severe symptoms, respond poorly to anti-asthmatic drugs, and ultimately their quality-of-life decreases. Although, the association between airway hyperresponsiveness (AHR) and obesity is a growing concern among the public due to lifestyle and environmental etiologies, however, the precise mechanism underlying this association is yet to establish. Apart from aiming at the conventional antiasthmatic targets, treatment should be directed towards ameliorating obesity pathogenesis too. Understanding the pathogenesis underlying the association between obesity and AHR is limited, however, a plethora of obesity pathologies have been reported viz., increased pro-inflammatory and decreased anti-inflammatory adipokines, depletion of ROS controller Nrf2/HO-1 axis, NLRP3 associated macrophage polarization, hypertrophy of WAT, and down-regulation of UCP1 in BAT following down-regulated AMPKα and melanocortin pathway that may be correlated with AHR. Increased waist circumference (WC) or central obesity was thought to be related to severe AHR, however, some recent reports suggest body mass index (BMI), not WC tends to exaggerate airway closure in AHR due to some unknown mechanisms. This review aims to co-relate the above-mentioned mechanisms that may explain the copious relation underlying obesity and AHR with the help of published reports. A proper understanding of these mechanisms discussed in this review will ensure an appropriate treatment plan for patients through advanced pharmacological interventions.

Herbal medicine for the treatment of obesity-associated asthma: a comprehensive review.

Obesity is fast growing as a global pandemic and is associated with numerous comorbidities like cardiovascular disease, hypertension, diabetes, gastroesophageal reflux disease, sleep disorders, nephropathy, neuropathy, as well as asthma. Studies stated that obese asthmatic subjects suffer from an increased risk of asthma, and encounter severe symptoms due to a number of pathophysiology. It is very vital to understand the copious relationship between obesity and asthma, however, a clear and pinpoint pathogenesis underlying the association between obesity and asthma is scarce. There is a plethora of obesity-asthma etiologies reported viz., increased circulating pro-inflammatory adipokines like leptin, resistin, and decreased anti-inflammatory adipokines like adiponectin, depletion of ROS controller Nrf2/HO-1 axis, nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) associated macrophage polarization, hypertrophy of WAT, activation of Notch signaling pathway, and dysregulated melanocortin pathway reported, however, there is a very limited number of reports that interrelates these pathophysiologies. Due to the underlying complex pathophysiologies exaggerated by obese conditions, obese asthmatics respond poorly to anti-asthmatic drugs. The poor response towards anti-asthmatic drugs may be due to the anti-asthmatics approach only that ignores the anti-obesity target. So, aiming only at the conventional anti-asthmatic targets in obese-asthmatics may prove to be futile until and unless treatment is directed towards ameliorating obesity pathogenesis for a holistic approach towards amelioration of obesity-associated asthma. Herbal medicines for obesity as well as obesity-associated comorbidities are fast becoming safer and more effective alternatives to conventional drugs due to their multitargeted approach with fewer adverse effects. Although, herbal medicines are widely used for obesity-associated comorbidities, however, a limited number of herbal medicines have been scientifically validated and reported against obesity-associated asthma. Notable among them are quercetin, curcumin, geraniol, resveratrol, ß-Caryophyllene, celastrol, tomatidine to name a few. In view of this, there is a dire need for a comprehensive review that may summarize the role of bioactive phytoconstituents from different sources like plants, marine as well as essential oils in terms of their therapeutic mechanisms. So, this review aims to critically discuss the therapeutic role of herbal medicine in the form of bioactive phytoconstituents against obesity-associated asthma available in the scientific literature to date.

Nanotheranostics: application of nanosensors in diabetes management.

Objectives: The objective of the present study is to discuss the use of nanomaterials like nanosensors for diagnosing Diabetes and highlight their applications in the treatment of Diabetes. Methods: Diabetes mellitus (D.M.) is a group of metabolic diseases characterized by hyperglycemia. Orally administered antidiabetic drugs like glibenclamide, glipalamide, and metformin can partially lower blood sugar levels, but long-term use causes kidney and liver damage. Recent breakthroughs in nanotheranostics have emerged as a powerful tool for diabetes treatment and diagnosis. Results: Nanotheranostics is a rapidly developing area that can revolutionize diabetes diagnosis and treatment by combining therapy and imaging in a single probe, allowing for pancreas-specific drug and insulin delivery. Nanotheranostic in Diabetes research has facilitated the development of improved glucose monitoring and insulin administration modalities, which promise to improve the quality of life for people with Diabetes drastically. Further, nanomaterials like nanocarriers and unique functional nanomaterials used as nano theranostics tools for treating Diabetes will also be highlighted. Conclusion: The nanosensors discussed in this review article will encourage researchers to develop innovative nanomaterials with novel functionalities and properties for diabetes detection and treatment.

Transient Receptor Potential Vanilloid (TRPV4) channel inhibition: A novel promising approach for the treatment of lung diseases.

Research on transient receptor potential vanilloid-4 (TRPV4) can provide a promising potential therapeutic target in the development of novel medicines for lung disorders. TRPV4 expresses in lung tissue and plays an important role in the maintenance of respiratory homeostatic function. TRPV4 is upregulated in life-threatening respiratory diseases like pulmonary hypertension, asthma, cystic fibrosis, and chronic obstructive pulmonary diseases. TRPV4 is linked to several proteins that have physiological functions and are sensitive to a wide variety of stimuli, such as mechanical stimulation, changes in temperature, and hypotonicity, and responds to a variety of proteins and lipid mediators, including anandamide (AA), the arachidonic acid metabolite, 5,6-epoxyeicosatrienoic acid (5,6-EET), a plant dimeric diterpenoid called bisandrographolide A (BAA), and the phorbol ester 4-alpha-phorbol-12,13-didecanoate (4α-PDD). This study focused on relevant research evidence of TRPV4 in lung disorders and its agonist and antagonist effects. TRPV4 can be a possible target of discovered molecules that exerts high therapeutic potential in the treatment of respiratory diseases by inhibiting TRPV4.

Therapeutic potential of bioactive phytoconstituents found in fruits in the treatment of non-alcoholic fatty liver disease: A comprehensive review.

Nonalcoholic fatty liver disease (NAFLD), a chronic liver condition affects a large number of people around the world with a frequency of 25% of all the chronic liver disease worldwide. Several targets viz. anti-inflammatory, anti-apoptotic and, anti-fibrotic factors, anti-oxidant and insulin-sensitizing pathways, metabolic regulators as well as repurposing traditional medications have been studied for the pharmacologic therapy of NAFLD. Newer pharmacotherapies like caspases blockade, agonists of PPAR and farnesoid X receptor agonists are currently being investigated in treating human NAFLD. However, NAFLD has no FDA-approved pharmacological therapy, therefore there is a considerable unmet therapy need. Apart from the conventional treatment regime, the current approaches to treating NAFLD include lifestyle interventions including healthy diet with adequate nutrition and physical activity. Fruits are known to play a key role in the well-being of human health. Fruits are loaded with a repertoire of bioactive phytoconstituents like catechins, phytosterols, proanthocyanidin, genestin, daidzen, resveratrol, magiferin found in fruits like pear, apricot, strawberries, oranges, apples, bananas, grapes, kiwi, pineapple, watermelon, peach, grape seed and skin, mango, currants, raisins, dried dates, passion fruit and many more. These bioactive phytoconstituents are reported to demonstrate promising pharmacological efficacy like reduction in fatty acid deposition, increased lipid metabolism, modulation of insulin signaling pathway, gut microbiota and hepatic inflammation, inhibition of histone acetyltransferase enzymatic activity to name a few. Not only fruits, but their derivatives like oils, pulp, peel, or their preparations are also found to be equally beneficial in various liver diseases like NAFLD, NASH. Although most of the fruits contains potent bioactive phytoconstituents, however, the presence of sugar in fruits put a question mark on the ameliorative property of the fruits and there has been contrasting reports on the glycemic control post fruit consumption in type 2 diabetic patients. This review is an attempt to summarize the beneficial effects of fruit phytoconstituents on NAFLD based on epidemiological, clinical and experimental evidence, focusing especially on their mechanisms of action.

Natural Flavonoids as Potential Therapeutics in the Management of Diabetic Wound: A Review.

Flavonoids are important bioactive phenolic compounds abundant in plants and exhibit different therapeutic potentials. A wound is a significant problem in diabetic individuals. A hyperglycaemic environment alters the normal wound-healing process and increases the risk of microbial infection, leading to hospitalization, morbidity, and amputation. Flavonoids are an important class of phytochemicals with excellent antioxidant, anti-inflammatory, antimicrobial, antidiabetic, antitumor, and wound healing property. Quercetin, hesperidin, curcumin, kaempferol, apigenin, luteolin, morin, etc. have shown their wound healing potential. Flavonoids effectively exhibit antimicrobial activity, scavenge reactive oxygen species, augment endogenous antioxidants, reduce the expression and synthesis of inflammatory cytokines (i.e. IL-1ß, IL-6, TNF-α, NF-κB), inhibit inflammatory enzymes, enhance anti-inflammatory cytokine (IL-10), enhance insulin section, reduce insulin resistance, and control blood glucose level. Several flavonoids like hesperidin, curcumin, quercetin, rutin, naringin, and luteolin have shown their potential in managing diabetic wounds. Natural products that maintain glucose haemostatic, exert anti-inflammatory activity, suppress/inhibit microbial growth, modulate cytokines, inhibit matrix metalloproteinase (MMP), stimulate angiogenesis and extracellular matrix, and modulate growth factor can be considered as a potential therapeutic lead to treat diabetic wound. Flavonoids were found to play a positive role in management of diabetic wounds by regulating MMP-2, MMP-8, MMP-9, MMP-13, Ras/Raf/ MEK/ERK, PI3K/Akt, and nitric oxide pathways. Therefore, it can be assumed that flavonoids could be potential therapeutics to prevent devastating effects of diabetic wounds. This paper focused on the potential role of flavonoids in managing diabetic wounds and discussed their possible mechanism of action.

Recent Advances on Natural and Non-Natural Xanthones as Potential Anticancer Agents: A Review.

BACKGROUND: Xanthones, natural or synthetic, due to their wide range of biological activities, have become an interesting subject of investigation for many researchers. Xanthonic scaffold has proven to have a vital role in anticancer drug development since many of its derivatives have shown anticancer activities on various cell lines. In addition, targeting epigenetic markers in cancer has yielded promising results. There have also been reports on the impact of xanthone and related polyphenolic compounds on epigenetics markers in cancer prevention and therapy. OBJECTIVE: The objective of this review is to comprehensively highlight the main natural and nonnatural sources of xanthones having potential anti-cancer effects along with their key structural elements, structure-activity relationships (SARs), mechanisms of action, and epigenetic profile of xanthone- based anti-cancer compounds. The challenges and future directions of xanthone-based therapies are also discussed briefly. METHOD: The methods involved in the preparation of the present review included the collection of all recent information up to November 2021 from various scientific databases, indexed periodicals, and search engines such as Medline Scopus, Google Scholar, PubMed, PubMed Central, Web of Science, and Science Direct. RESULTS: Exploration of the diversity of the xanthone scaffold led to the identification of several derivatives having prominent anti-cancer activity. Their unique structural diversity and synthetic modifications showed the ongoing endeavour of enriching the chemical diversity of the xanthone molecular framework to discover pharmacologically interesting compounds. However, studies regarding their modes of action, pharmacokinetic properties, clinical data, epigenetics, and safety are limited. CONCLUSION: Elucidation of the exact biological mechanisms and the associated targets of xanthones will yield better opportunities for these compounds to be developed as potential anticancer drugs. Further clinical studies with conclusive results are required to implement xanthones as treatment modalities in cancer.

Ethnomedicinal Practices and Traditional Medicinal Plants of Barak Valley, Assam: a systematic review.

Objectives: The Barak Valley is well known for its rich diversity of medicinal plants. Ethnomedicinal practices are prominent among Barak Valley's major and minor ethnic groups. This systemic review focuses on traditionally used medicinal plants found in the Barak Valley as reported in different ethnobotanical surveys. Methods: We searched various databases, including PubMed, Web of Science, and Google Scholar, to find ethnomedicinal surveys conducted in the Barak Valley. The search was performed using different terms, including ethnomedicinal survey, folk medicine, indigenous knowledge, and Barak Valley. Potential articles were identified following the exclusion and inclusion criteria. Results: A total of eight ethnobotanical surveys were included in this study. We identified a total of 216 plant species belonging to 167 genera and 87 families, which are widely used by the ethnic communities who live in the rural areas of Barak Valley for the treatment of various diseases and ailments. Conclusion: Folk medicine is the result of decades of accumulated knowledge and practices by people who live in rural communities based on their needs and provides an important source of information to assist the search for new pharmaceuticals. Therefore, available information on traditional medicinal plants needs to be explored scientifically to find effective and alternative treatments for different diseases.

Immunomodulatory effect of mushrooms and their bioactive compounds in cancer: A comprehensive review.

Despite enormous development in the field of drug development, cancer still remains elusive. Compromised immunity stands as a roadblock to the successful pharmacological execution of anti-cancer drugs used clinically currently. Recently some breakthrough cancer treatment strategy like nano-formulation, extracellular vesicles treatment, natural antioxidant therapy, targeted immunotherapy, gene therapy, thermal ablation and magnetic hyperthermia, and pathomics and radiomics has been developed and tested pre-clinically as well as clinically. However, clinical efficacy of such therapies is yet to establish and some are too costly to be utilized by patients from poor and developing countries. At this juncture, researchers are heading towards the search of medicines from natural sources that is higher safety margin and multitarget pharmacological efficacy compared to conventional treatments. Mushroom is used traditionally as food as well as drug since time immemorial due to its immunomodulatory effect which is loaded with proteins, low fat content and cholesterol. Mushrooms are recommended as one of the best vegetarian diets for immunosuppressed cancer and HIV/AIDS patients. Mushrooms are well-known for their anti-cancer activity that impacts hematopoietic stem cells, lymphocytes, macrophages, T cells, dendritic cells (DCs), and natural killer (NK) cells in the immune system. This comprehensive review article emphasizes on the molecular mechanisms of cancer genesis, conventional anti-cancer therapy as well as reported some significant breakthrough in anti-cancer drug development, anti-cancer activity of some selected species of mushrooms and their bioactive phytoconstituents followed by a brief discussion of recent anti-cancer efficacy of some metallic nanoparticles loaded with mushrooms.

Diabetes mellitus and COVID-19: Understanding the association in light of current evidence.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have posed a problematic healthcare situation worldwide since December 2019. Diabetes mellitus is associated with an increased risk and severity of coronavirus disease 2019 (COVID-19). While interacting with various other risk factors, high blood sugar was found to reduce immunity and increase the replication of SARS-CoV-2. Oxidative stress and the release of pro-inflammatory cytokines are greater in diabetic individuals than in healthy people, worsening the outcome of SARS-CoV-2 infection in diabetics. Increased expression of furin and angiotensin converting enzyme 2 (ACE-2) receptor in the hyperglycemic environment may promote the entry of SARS-CoV-2 in the host cell. COVID-19 infection primarily modulates immune and inflammatory responses, and may cause a cytokine storm, resulting in possible lethal outcomes in diabetics. An experimental report suggests that ACE expressed in the pancreas and the SARS-CoV-2 virus invariably destroy ß-cells which contain ACE-2 receptors and results in acute diabetes. Moreover, COVID-19 also causes hyperglycemia in an individual with diabetes which may be related to insulin resistance and destruction of ß-cells during SARS-CoV-2 infection. Early observations also suggest a correlation between oral hypoglycemic agents and the risk of COVID-19. This review focused on the possible cause and mechanism involved in SARS-CoV-2 infection in diabetics and the role of antidiabetic drugs in COVID-19.

Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by ß-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions.

Mast cell activation is initiated by two signalling pathways: immunoglobulin E (IgE)-dependent and IgE-independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 have been identified as G-protein-coupled receptors (GPCRs). Interestingly, APN replenishment is reported to activate the Nrf2/HO-1 signalling axis. However, no study has been performed interlinking the role of APN and the Nrf2/HO-1 signalling axis in pseudo-allergic reaction. In the present study, we evaluated the anti-pseudo-allergic effects of ß-caryophyllene, an FDA-approved food additive, in activating AdipoR1/AdipoR2 and Nrf2/HO-1 axis signalling pathway. Compound 48/80 (C48/80)-induced systemic and cutaneous anaphylaxis-like shock in BALB/c mice was performed to assess the efficacy of ß-caryophyllene (BCP). To assess the effect of BCP in anaphylactic hypotension, mean arterial pressure was measured in Wistar rats. Inhibitory properties of BCP in mast cell degranulation were estimated in rat peritoneal mast cells (RPMCs). ELISA was performed to estimate interleukin (IL)-6, tumour necrosis factor (TNF), IL-1ß, IgE, ovalbumin (OVA)-IgE and APN and western blotting for protein expression of Nrf2/HO-1 and AdipoR1-AdipoR2. BCP dose-dependently inhibited systemic and cutaneous anaphylaxis-like shock induced by C48/80. BCP dose-dependently inhibited the mast cell degranulation followed by inhibition of histamine release. Also BCP dose-dependently activated the Nrf2/HO-1 and AdipoR1-AdipoR2 signalling axis pathway. Moreover, BCP reversed the drop in blood pressure when the haemodynamic parameters were accessed. Our findings suggest that BCP is a potent AdipoR1/AdipoR2-Nrf2/HO-1 axis pathway agonist that may suppress the IgE-independent pathway towards allergic response to secretagogues.

ß-caryophyllene ameliorated obesity-associated airway hyperresponsiveness through some non-conventional targets.

BACKGROUND: Obesity worsens airway hyperresponsiveness (AHR) in asthmatic subjects by up-regulating macrophage polarization that leads to excessive secretion of pro-inflammatory adipokines from white adipose tissue followed by generation of oxidative stress in the respiratory system. Treatment through conventional signaling pathways proved to be inadequate in obese asthmatics, so a therapeutical approach through a non-conventional pathway may prove to be effective. PURPOSE: This study aimed to investigate the efficacy of a FDA-approved food additive, ß-caryophyllene (BCP) in obesity-associated AHR. METHOD: A repertoire of protein expression, cytokine and adiponectin estimation, oxidative stress assays, histopathology, and fluorescence immune-histochemistry were performed to assess the efficacy of BCP in C57BL/6 mice model of obesity-associated AHR. Additionally, human adipocyte was utilized to study the effect of BCP on macrophage polarization in Boyden chamber cell culture inserts. RESULTS: Obesity-associated AHR is ameliorated by administration of BCP by inhibition of the macrophage polarization by activation of AMPKα, Nrf2/HO-1 and AdipoR1 and AdipoR2 signaling pathway, up-regulation of adiponectin, GLP-1, IFN-γ, SOD, catalase and down-regulation of NF-κB, leptin, IL-4, TNF, and IL-1ß. Browning of eWAT by induction of thermogenesis and activation of melanocortin pathway also contributed to the amelioration of obesity-associated AHR. We conclude that BCP ameliorated the obesity-associated AHR via inhibition of macrophage polarization, activation of AMPKα, Nrf2/HO-1, and up-regulation of AdipoR1 and AdipoR2 expression and down-regulation of NFκB expression in lung of animal. CONCLUSION: Being an FDA-approved food additive, BCP may prove to be a safe and potential agent against obesity-associated AHR.

bFGF and collagen matrix hydrogel attenuates burn wound inflammation through activation of ERK and TRK pathway.

Burn injuries are most challenging to manage since it causes loss of the integrity of large portions of the skin leading to major disability or even death. Over the years, hydrogels are considered as a significant delivery system for wound treatment because of several advantages over other conventional formulations. We hypothesized that the bFGF-collagen-AgSD incorporated hydrogel formulation can accelerate the rate of burn healing in animal model and would promote fibroblast cell proliferation. Neovascularization and re-epithelialization is a hall mark of burn wound healing. In the present study, histopathological investigation and scanning electron microscopy of skin tissue of Wistar rats showed almost complete epithelialisation after 16 days in the treatment group. The developed hydrogel showed significantly accelerated wound closure compared with a standard and control group. The faster wound closure resulted from increased re-epithelialization and granulation tissue formation because of the presence of collagen and growth factor. Expressions of proteins such as TrkA, p- TrkA, ERK1/2, p-ERK1/2, NF-kß, and p-NF-kß involved in nerve growth factor (NGF) signalling pathway were analysed by western blot. All the findings obtained from this study indicated that the hydrogel can be considered as a promising delivery system against second degree burn by faster healing.

Cardiopulmonary function and dysregulated cardiopulmonary reflexes following acute oleoresin capsicum exposure in rats.

Cardiopulmonary functions such as respiratory depression, severe irritation, inflamed respiratory tract, hyperventilation and, tachycardia are the most affected ones when it comes to the riot control agent oleoresin capsicum (OC) exposure. However, no studies have been done to elucidate the mechanism underlying deterioration of the combined cardiopulmonary functions. Parameters such as acute respiratory, cardiac, parameters and ultrasonography (USG) measurements were investigated in an in vivo setup using Wistar rats at 1 h and 24 h post inhalation exposure to 2%, 6% and 10% OC, whereas, cell migration in rat peritoneal mast cells (RPMCs), metabolomics and eosinophil peroxidase (EPO) activity in bronchoalveolar lavage fluid (BALF) were investigated in an in vitro setup. Results obtained from electrophysiological recording indicated that OC exposure produces apnea and decrease in mean arterial pressure (MAP) was obtained from hemodynamic parameters whereas cardiac parameters assessment revealed increase in the level of cardiac output (CO) and decrease in stroke volume (SV) with recovery towards the post-exposure period. A decrease in the percentage area of certain fatty acid pathway metabolites in BALF appropriately linked the lung injury following OC exposure which was further cemented by increasing concentration of EPO. Histopathology and SEM also proved to be favorable techniques for the detection of OC induced physiological cardiac and pulmonary modifications respectively. Furthermore, Boyden chamber experiment established the chemoattractant property of OC. It may be concluded from the above studies that these newly reported facets may be utilized pharmacologically to mitigate cardiopulmonary adverse effects owing to OC exposure.

Contentious role of 'Good Adiponectin' in pulmonary and cardiovascular diseases: Is adiponectin directed therapy a boon or a bane?

After two decades of its discovery, numerous facts of adiponectin (APN) biology has been uncovered, yet, APN remains an elusive adipokine. Findings from clinical studies and animal models established APN's ameliorative role in cardiovascular disease (CVD) and pulmonary disease (PD) but the same condition is prognostic for mortality in the same set of patients which cornered APN towards a dubious state. A repertoire of mechanisms associated with the positive association of APN in both lean/cachectic or obese CVD and PD patients from past publications are evaluated. Newer pharmacological agent may be explored to regulate elevated blood APN concentration in COPD or CHF patients whereas administration of recombinant APN as well as growth hormone may augment blood APN concentration in obese subjects associated with low blood and intracellular APN concentration. However, some APN directed therapy in clinical as well as in pre-clinical setup has pronounced some contentious effects. After reviewing the mechanisms of the contentious role of APN functioning in pathologic conditions of CVD and PD in both lean and obese conditions, the authors came to conclusion that APN directed therapy may be utilized with caution keeping in mind the different age group, sex and the different CVD as well as pulmonary diseases they are suffering from.

Innate inflammatory response to acute inhalation exposure of riot control agent oleoresin capsicum in female rats: An interplay between neutrophil mobilization and inflammatory markers.

Aim: The use of oleoresin capsicum (OC) sprays, due to their irreversible health effects has now grown into a matter of heated debate. In the present study, the early phase pulmonary events involving chemotactic and inflammatory mediators after short-exposure duration to OC have been presented.Materials and methods: Female Wistar rats used in the evaluation of respiratory parameters at 1 h, 3 h, and 24 h post-exposure, were sacrificed for the evaluation of blood cell counts, BALF cytokine estimation, lung capillary leakage, study of oxidative stress and histopathology of the lungs.Results: Results confirmed a dose-dependent effect of OC exposure on serum clinical chemistry and hematological parameters. Subsequent upregulation of IL-l and TNF-α indicated lung's responses to acute oxidant-induced injury and inflammation after OC exposure. Significant alterations in the pulmonary levels of reactive oxygen intermediates were seen following the inhalation of OC. Infiltration of polymorphonuclear leukocytes, mostly neutrophils, into the site of infection was evident in the cytocentrifuged samples of BALF. Histological samples of rat lung sections revealed the recruitment of inflammatory cells in the airways and around blood vessels in the subepithelium of conducting airways.Conclusion: Results of the present study demonstrated that, exposure to OC spray may mitigate inflammatory response and development of acute lung injury in rats. However, it can be concluded that although OC spray causes pulmonary hazards in the aforementioned concentrations, it can be used as a non-lethal riot control agent in minimal concentration. Understanding the in-depth mechanism of action in the molecular and receptor level will help in developing effective antagonist against OC.