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.

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.

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.

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.

Assessment of toxicological consequences upon acute inhalation exposure to chemically improvised nonlethal riot control combinational formulation (NCF) containing oleoresin capsicum and skatole.

Sensory irritation is an acute adverse effect leading to temporary disability posed by riot control agents in various deployable forms are utilized by defense personal in violent mob attacks but their irreversible toxic effects and risk assessment have been a matter of concern. These intimidating risks of available riot control agents have led to exploring the pulmonary toxicity profile of the oil in water emulsion formulation developed for vicious crowd controls containing an irritant oleoresin capsicum, a malodorant (skatole), and a commercial dye, followed by characterization using standard methods. Nonlethal riot control combinational formulation (NCF) has been aimed to be the best possible low-lethal alternative for riot control measures. In this study, 30 min of acute inhalation exposure of NCF was given to Wistar rats and various respiratory parameters like lung dynamics, bronchoalveolar lavage fluid (BALF) cytological assays, pro-inflammatory cytokines estimation, antioxidant activity, collagen accumulation, cytotoxicity, in vivo lung imaging, western blot, histology of lung tissue, etc. were investigated to validate its potentiality and rate of irritation reversibility as nonlethal agents. An exaggerated physiological change like sensory irritation, changes in lung functional variables, increased pro-inflammatory cytokines, etc. were noticed initially without airway obstruction as the expression of nociceptive TRPV1 protein did not alter the physiological regulation of protective proteins like Nrf2 and HO-1 and also no abnormality was found in lung tissue architecture. In conclusion, it can be stated that this formulation can be explored as a nonlethal riot control agent intending to generate discomfort but with early reversibility of sensory irritation and no recurrence of toxicity.

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.