Chitosan-based topical formulation integrated with green-synthesized silver nanoparticles utilizing Camellia sinensis leaf extracts: A promising approach for managing infected wounds.

This study explores the eco-friendly biosynthesis of silver nanoparticles (AgNPs) utilizing Camellia sinensis leaf extract. We assess their antioxidant and antibacterial properties. Furthermore, we impregnated AgNPs into 2 % chitosan (CHS) gel and assessed their wound-healing potential in Escherichia coli and Staphylococcus aureus infected wounds. Optimized AgNPs demonstrated a mean particle size of 36.90 ± 1.22 nm and a PDI of 0.049 ± 0.001. Green-synthesized AgNPs exhibited enhanced free radical inhibition (IC50: 31.45 µg/mL, 34.01 µg/mL, 27.40 µg/mL) compared to leaf extract (IC50: 52.67 µg/mL, 59.64 µg/mL, 97.50 µg/mL) in DPPH, hydrogen peroxide, and nitric oxide free radical scavenging assays, respectively. The MIC/MBC values of AgNPs against E. coli and S. aureus were 5 ppm/ 7.5 ppm and 10 ppm/ 15 ppm, respectively. Furthermore, our study showed that green-synthesized AgNPs at MIC significantly reduced the biofilm production of E. coli (70.37 %) and S. aureus (67.40 %). The CHS/AgNPs gel exhibited potent wound healing activities, comparable to a commercial cream with the re-epithelialization period of 8.16 ± 0.75. Histological analysis demonstrated enhanced skin regeneration with a thicker epidermal layer, well-defined papillary dermal structure, and organized collagen fibers. In summary, these findings hold promise for addressing bacterial infections, particularly those associated with biofilms-related wound infections.

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.

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.

Green Synthesis of Titanium Dioxide Nanoparticles Using Ocimum sanctum Leaf Extract: In Vitro Characterization and Its Healing Efficacy in Diabetic Wounds.

Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.

Cancer Chemotherapy via Natural Bioactive Compounds.

BACKGROUND: Cancer-induced mortality is increasingly prevalent globally, which skyrocketed the necessity to discover new/novel, safe and effective anticancer drugs. Cancer is characterized by the continuous multiplication of cells in the human, which is unable to control. Scientific research is drawing its attention toward naturally-derived bioactive compounds as they have fewer side effects compared to the current synthetic drugs used for chemotherapy. OBJECTIVE: Drugs isolated from natural sources and their role in the manipulation of epigenetic markers in cancer are discussed briefly in this review article. METHODS: With advancing medicinal plant biotechnology and microbiology in the past century, several anticancer phytomedicines were developed. Modern pharmacopeia contains at least 25% herbal-based remedies, including clinically used anticancer drugs. These drugs mainly include the podophyllotoxin derivatives vinca alkaloids, curcumin, mistletoe plant extracts, taxanes, camptothecin, combretastatin, and colchicine artesunate, homoharringtonine, ellipticine, roscovitine, maytansine, tapsigargin,and bruceantin. RESULTS: Compounds (psammaplin, didemnin, dolastin, ecteinascidin, and halichondrin) isolated from marine sources and animals such as microalgae, cyanobacteria, heterotrophic bacteria, invertebrates. They have been evaluated for their anticancer activity on cells and experimental animal models and used chemotherapy.Drug-induced manipulation of epigenetic markers plays an important role in the treatment of cancer. CONCLUSION: The development of a new drug from isolated bioactive compounds of plant sources has been a feasible way to lower the toxicity and increase their effectiveness against cancer. Potential anticancer therapeutic leads obtained from various ethnomedicinal plants, foods, marine, and microorganisms are showing effective yet realistically safe pharmacological activity. This review will highlight important plant-based bioactive compounds like curcumin, stilbenes, terpenes, other polyphenolic phyto-compounds, and structurally related families that are used to prevent/ ameliorate cancer. However, a contribution from all possible fields of science is still a prerequisite for discovering safe and effective anticancer drugs.

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.

Integrating pharmacophore mapping, virtual screening, density functional theory, molecular simulation towards the discovery of novel apolipoprotein (apoE ε4) inhibitors.

AIM: An integrated protocol of virtual screening involving molecular docking, pharmacophore probing, and simulations was established to identify small novel molecules targeting crucial residues involved in the variant apoE ε4 to mimic its behavior as apoE2 thereby eliminating the amyloid plaque accumulation and facilitating its clearance. MATERIALS AND METHODS: An excellent ligand-based and structure-based approach was made to identify common pharmacophoric features involving structure-based docking with respect to apoE ε4 leading to the development of apoE ε4 inhibitors possessing new scaffolds. An effort was made to design multiple-substituted triazine derivatives series bearing a novel scaffold. A structure-based pharmacophore mapping was developed to explore the binding sites of apoE ε4 which was taken into consideration. Subsequently, virtual screening, ADMET, DFT searches were at work to narrow down the proposed hits to be forwarded as a potential drug likes candidates. Further, the binding patterns of the best-proposed hits were studied and were forwarded for molecular dynamic simulations of 10 ns for its structural optimization. RESULTS: Selectivity profile for the most promising candidates was studied, revealing significantly C13 and C15 to be the most potent compounds. The proposed hits can be forwarded for further study against apoE ε4 involved in neurological disorder Alzheimer's.