Cardioprotective effect of 2-methoxy phenol derivatives against oxidative stress-induced vascular complications: An integrated in vitro, in silico, and in vivo investigation.

BACKGROUND: Oxidative stress and inflammation play crucial roles in macro/microvascular complications. Phenolic compounds and their derivatives show promise as therapeutic agents for diseases like cancer, metabolic disorders, and cardiovascular diseases. With their antioxidant and anti-inflammatory properties, these compounds hold potential for mitigating vascular complications and improving overall health. METHODOLOGY: This study aimed to assess the therapeutic potential of five 2-methoxy phenol derivatives (T2, T5, T6, T7, and T8) as antioxidants, anti-inflammatory agents, and vasorelaxants using in vitro, in silico, and in vivo approaches. RESULTS: Among all, T2 exhibited substantial antioxidant potential against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) radicals with IC50 (27.97 µg/mL), nitric oxide (NO) radicals (IC50 = 34.36 µg/mL), hydroxyl (OH) radicals (IC50 = 34.83 µg/mL) and Iron chelation (IC50 = 24.32 µg/mL). Molecular docking analysis confirms that all derivatives, particularly T2, exhibit favorable binding energies with the target proteins, ACE (-7.7 Kcal/mol), ECE-1 (-7.9 Kcal/mol), and COX-1 (-7.8 Kcal/mol). All of the compounds demonstrated satisfactory physicochemical and pharmacokinetic characteristics, and showed minimal to no toxicity during in silico, in vitro, and in vivo assessments. In isolated aortic rings from Sprague Dawley rats, pre-contracted with high K+ (80 mM), T2 induced vasorelaxation in dose dependent manner and shifted calcium response curves to the right as compared to verapamil. T2 also showed substantial platelet aggregation inhibition in a dose dependent manner with IC50 21.29 µM. All derivatives except T7 exhibited significant conservation of endogenous antioxidants i.e. catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and reduced glutathione (GSH) and significantly suppressed serum levels of inflammatory markers i.e. nitric oxide (NO), peroxides (TBARS), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). CONCLUSION: The study concludes that T2 has significant antioxidant potential and vasorelaxant effects with adequate pharmacokinetics, making it a promising lead compound for further molecular investigation in cardiovascular disorders.

Anti-diabetic Activity of Brucine in Streptozotocin-Induced Rats: In Silico, In Vitro, and In Vivo Studies.

Diabetes mellitus (DM) is a complex and multiple group of disorders, and understanding the molecular mechanisms is a key role in identifying various markers involved in the diagnosis of the disease. Brucine is derived from the seeds of Strychnos nux-vomica L. (Loganiaceae), which has been used in traditional medicine to cure a variety of ailments, such as chronic rheumatism, nervous system diseases, dyspepsia, gonorrhea, anemia, and bronchitis, and has analgesic, anti-inflammatory, anti-oxidant, anti-snake venom, and anti-diabetic properties. The anti-diabetic potential of brucine was studied utilizing in vitro, in silico, in vivo, and molecular methods, including streptozotocin-induced diabetic rat models, α-glucosidase and α-amylase inhibitory assays, and via Auto-DocVina software. Brucine exhibits binding affinities of -5.0 to -10.1 Kcal/mol against chosen protein targets, according to an in silico investigation. In vitro studies revealed that brucine inhibited the enzymes α-amylase and α-glucosidase, and brucine (20 mg/kg) reduced blood glucose levels, oral glucose tolerance overload, body weight, glycosylated hemoglobin levels, total cholesterol, triglycerides, low-density lipoprotein, alanine transaminase, aspartate aminotransferase, total bilirubin, and alkaline phosphatase and elevated high-density lipoprotein levels in in vivo studies. The brucine binding energy against certain protein targets ranges from -5.0 to -10.1 Kcal/mol. It has anti-diabetic, anti-hyperlipidemic, hepatoprotective, anti-oxidant, and anti-inflammatory properties, which are mediated via inhibition of α-glucosidase and α-amylase.

Pharmacological Basis of Rumex hastatus D. Don in Gastrointestinal Diseases with Focusing Effects on H+/K+-ATPase, Calcium Channels Inhibition and PDE Mediated Signaling: Toxicological Evaluation on Vital Organs.

This present study aimed to delineate Rumex hastatus D. Don crude extract (Rh.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rh.n-Hex, Rh.ETAC, Rh.Aq) and rutin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti H. pylori, antiulcer effects, and toxicology. The preliminary phytochemical analysis of Rumex hastatus showed different phytoconstituents and shows different peaks in GC-MC chromatogram. Rumex hastatus crude extract (Rh.Cr), fractions, and rutin attributed dose-dependent (50-300 mg/kg) protection (0-100%) against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance traversed by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, Rh.Cr and Rh.ETAC caused a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contractions at a similar concentration range, whereas Rh.n-Hex, rutin, and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rh.Cr (0.3-1 mg/mL) and Rh.ETAC (0.1-0.3 mg/mL) shifted the isoprenaline-induced inhibitory CRCs to the left. Rh.n-Hex, Rh.ETAC and rutin showed anti-H. pylori effect, also shows an inhibitory effect against H+/K+-ATPase. Rumex hastatus showed gastroprotective and antioxidant effects. Histopathological evaluation showed improvement in cellular architecture and a decrease in the expression of inflammatory markers such as, cyclooxygenase (COX-2), tumor necrosis factor (TN,F-α) and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry and ELISA techniques. In RT-PCR it decreases H+/K+-ATPase mRNA levels. Rumex hastatus was found to be safe to consume up to a dose of 2000 mg/kg in a comprehensive toxicity profile. Docking studies revealed that rutin against H+/K+-ATPase pump and voltage-gated L-type calcium channel showed E-values of -8.7 and -9.4 Kcal/mol, respectively. MD simulations Molecular Mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area (MMPBSA/GBSA) findings are consistent with the in-vitro, in-vivo and docking results.

Effect of Rumex dentatus on Gastrointestinal Protection and Toxicology in Rodents via Investigating H+/K+-ATPase, Calcium Channels, and PDE Mediated Signaling.

This present study aims to delineate Rumex dentatus crude extract (Rd.Cr), n-Hexane, ethyl acetate, aqueous fractions (Rd.n-Hex, Rd.ETAC, and Rd.Aq), and emodin for antidiarrheal, antisecretory effects, anti-spasmodic, gastrointestinal transient time, anti-H. pylori, antiulcer effects, and toxicology. Plant extracts attributed dose-dependent protection against castor oil-induced diarrhea and dose-dependently inhibited intestinal fluid secretions in mice. They decreased the distance transverse by charcoal in the gastrointestinal transit model in rats. In rabbit jejunum preparations, it causes a concentration-dependent relaxation of both spontaneous and K+ (80 mM)-induced contraction, Rd.n-Hex and verapamil were relatively potent against K+-induced contractions and shifted the Ca2+ concentration-response curves (CRCs) to the right, Rd.Cr and Rd.ETAC shifted the isoprenaline-induced inhibitory CRCs to the left, showing potentiating effect similar to papaverine. Rd.n-Hex showed anti-H. pylori effect. Extracts and emodin also show an inhibitory effect against H+/K+-ATPase. Rumex dentatus showed a gastroprotective and antioxidant effect. Histopathological evaluation showed improvement in cellular architecture and decrease in the expression of inflammatory markers such as cyclooxygenase (COX2), tumor necrosis factor (TNF-α), and phosphorylated nuclear factor kappa B (p-NFƙB), validated through immunohistochemistry, ELISA, and western blot techniques. In RT-PCR, it decreases H+/K+-ATPase mRNA levels. Rumex dentatus was analyzed for certain safety aspects and exhibited a relative safety profile as no impairment was observed in kidneys, heart, liver, and brain further assisted by biochemical and hematological analysis. Docking studies revealed that emodin against H+/K+-ATPase pump and voltage gated L-type calcium channel showed E-value of -7.9 and -7.4 kcal/mol, respectively. MD simulations and molecular mechanics Poisson Boltzmann surface area and molecular mechanics Generalized Born surface area MMPBSA/GBSA findings are consistent with the in-vitro, in-vivo, and docking results. In conclusion, Rumex dentatus extracts and its phytoconstituent could be considered a potent antioxidant and anti-inflammatory drug candidates that possess anti-diarrheal, anti-secretary, antispasmodic, anti-H. pylori, and anti-ulcer potential. Toxicity studies were done according to OECD standards 425. It belongs to group 5 (LD50 > 2000 mg/kg), which suggests that it is in the lower toxicity class.

Novel Isoxazole Derivative Attenuates Ethanol-Induced Gastric Mucosal Injury through Inhibition of H+/K+-ATPase Pump, Oxidative Stress and Inflammatory Pathways.

Isoxazole derivatives are significant enough due to their wide range of pharmacological and therapeutic activities. The purpose of the current study is to use computational, in vitro, in vivo, and extensive molecular approaches to examine the possible anti-ulcer activity of 4-benzylidene-3 methyl-1,2-isoxazol-5(4H)-one (MBO). Biovia Discovery Studio visualizer (DSV) was utilized for virtual screening. A tissue antioxidant investigation, H+/K+-ATPase test, and anti-H. pylori activities were carried out. ELISA, immunohistochemistry, and PCR methods were employed for the proteome analysis. An ethanol-induced stomach ulcer model was used to examine the anti-ulcer potential in rats. The binding affinities for MBO ranged from -5.4 to -8.2 Kcal/mol. In vitro findings revealed inhibitory activity against H. pylori and the H+/K+-ATPase pump. It also enhanced levels of glutathione, catalase, and glutathione-S-transferase and reduced lipid peroxidation levels in gastric tissues of rats. In vivo results showed the gastro-protective effect of MBO (30 mg/kg) in ulcerative rat stomachs. The proteomic study revealed decreased expression of inflammatory markers (cyclooxygenase-2, p-NFkB, and TNF-α). In RT-PCR analysis, the expression levels of H+/K+-ATPase were reduced. Furthermore, ADMET (absorption, distribution, metabolism, excretion and toxicity) studies revealed that MBO has high GIT solubility and has a safer profile for cardiac toxicity. This study suggests that MBO displayed anti-ulcer potential, which may have been mediated through the inhibition of the H+/K+-ATPase pump, as well as antioxidant and anti-inflammatory pathways. It has the potential to be a lead molecule in the treatment of peptic ulcers with fewer adverse effects.

Proteomic Analysis and In Vivo Studies Reveal the Potential Gastroprotective Effects of CHCl3 and Aqueous Extracts of Ficus palmata.

Ficus palmata is rich in several phytochemicals such as chromone, isoflavones, terpenes, lignans, coumarins, glycosides, and furanocoumarins and have been traditionally used for the management of different gastrointestinal disorders. This research reveals the effects of Ficus palmata fruit extracts-Ficus palmata chloroform (Fp.CHCl3) and Ficus palmata aqueous (Fp.Aq)-on gut activity through in vivo and in vitro analyses. Antidiarrheal and enteropooling assays were analyzed with castor oil-induced diarrhea and intestinal fluid accumulation. Jejunum tissues of rabbits were isolated (antispasmodic) for in vitro experiments. Antimotility was carried out by charcoal meal for determining transient time, and ethanol-induced ulcer assay was used to measure the ulceration of stomach; molecular pathways were assessed through proteomic approach. Fp.CHCl3 and Fp.Aq extracts attributed dose-dependently protection against diarrhea, and intestinal fluid secretions were inhibited dose dependently. Extracts of Fp.CHCl3 and Fp.Aq produced reduction in spontaneous and K+ (at 80 Mm)-induced contractions in isolated jejunum tissues, along with the decreased length covered by charcoal in charcoal meal transient time activity. The extract exhibited gastroprotective outcome in rats and reduced tumor necrotic factor (TNF-α) levels and IL-18, measured by proteomic approach. Morphological studies' results showed that ethanol induced significant gastritis, apoptosis, swelling of mucosa, and hydropic degeneration leading to cellular degeneration and necrosis, observed through staining techniques. Furthermore, ethanol activated the inflammation pathway in all gastric zones by elevating the levels of cyclooxygenase-2, TNF-α, and nuclear factor kappa light-chain enhancer of activated B-cells. Overall results expressed the antidiarrheal, antispasmodic, enteropooling, antimotility, and antiulcer activities of Ficus palmata fruit extract.

Potential therapeutic natural products against Alzheimer's disease with Reference of Acetylcholinesterase.

Alzheimer's disease (AD), is the most common type of dementia primarily affecting the later years of life. Its prevalence is likely to increase in any aging population and will be a major burden on healthcare system by the mid of the century. Despite scientific and technological breakthroughs in the last 50 years, that have expanded our understanding of the disease on a system, cellular and molecular level, therapies that could stop or slow the progression of the disease are still unavailable. The Food and Drug Administration (FDA), has approved acetylcholinesterase (AChE) inhibitors (donepezil, galantamine, tacrine and rivastigmine) and glutamate receptor antagonist (memantine) for the treatment of AD. In this review we summarize the studies reporting phytocompounds and extracts from medicinal plants that show AChE inhibitory activities and could be of potential benefit in AD. Future research directions are suggested and recommendations made to expand the use of medicinal plants and their formulations to prevent, mitigate and treat AD.

Natural Dietary Supplement, Carvacrol, Alleviates LPS-Induced Oxidative Stress, Neurodegeneration, and Depressive-Like Behaviors via the Nrf2/HO-1 Pathway.

PURPOSE: Major depressive disorder (MDD) is a debilitating human health condition characterized by mood swings and is associated with a high probability of suicide attempts. Several studies have reported a role of neuroinflammation in MMD, yet the efficacy of natural drug substances on neuroinflammation-associated depression has not been well-investigated. The present study examined the neuroprotective effects of carvacrol on lipopolysaccharide (LPS)-induced neuroinflammation, depression, and anxiety-like behavior. METHODS: Male Sprague Dawley rats were divided into two experimental cohorts to determine the effects and the effective dose of carvacrol (whether 20 mg/kg or 50 mg/kg), and further demonstrate the mechanism of action of nuclear factor E2-related factor (Nrf2) in depression. RESULTS: We found marked neuronal alterations in the cortex and hippocampus of LPS-intoxicated animals that were associated with higher inflammatory cytokine expression such as cyclooxygenase (COX2), tumor necrosis factor-alpha (TNF-α), and c-Jun N-terminal kinase (p-JNK). These detrimental effects exacerbated oxidative stress, as documented by a compromised antioxidant system due to high lipid peroxidase (LPO). Carvacrol (20 mg/kg) significantly reverted these changes by positively modulating the antioxidant gene Nrf2, a master regulator of the downstream antioxidant pathway. To further investigate the role of Nrf2, an inhibitor of Nrf2 called all-trans retinoic acid (ATRA) was used, which further exacerbated LPS toxicity with a higher oxidative and inflammatory cytokine level. To further support our notion, we performed virtual docking of carvacrol with the Nrf2-Keap1 target and the resultant drug-protein interactions validated the in vivo findings. CONCLUSION: Collectively, our findings suggest that carvacrol (20 mg/kg) could activate the endogenous master antioxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating LPS-induced neuroinflammation and neurodegeneration.

Pharmacological evaluation of continentalic acid for antidiabetic potential.

BACKGROUND: Diabetes is a complex endocrine and metabolic disorder. Continentalic acid is a natural drug product found in roots of Aralia continentalis (family Araliaceae), which used in traditional medicine for treatment of rheumatic arthritis, lumbag, lameness, inflammation, gastritis, nephritis and diabetes mellitus. PURPOSE: This study is aim to investigate the continentalic acid anti-diabetic potential. METHODS: In-silico, in-vitro, in-vivo and molecular techniques were used to investigate various effects of continentalic acid by Auto Doc Vina, α-amylase and α-glucosidase inhibitory assay and alloxan-induced diabetes rats model. RESULTS: In-silico results revealed that continentalic acid exhibits binding energy values of - 5 to - 9.3Kcal/mol against selected targets. In-vitro assay showed that continentalic acid caused α-amylase and α-glucosidase enzymes inhibition. In-vivo finding exhibits that continentalic acid (50 mg/kg) decreased blood glucose level, body weight, oral glucose tolerance overload, glycosylated hemoglobin, triglycerides, total cholesterol, low density lipoprotein, aspartate transaminase, aspartate aminotransferase, alkaline phosphate, total bilirubin and increased high density lipoprotein (P < 0.05, P < 0.01, P < 0.001 vs. diabetic control group). In animals pancreas and liver tissues, continentalic acid enhanced glutathione-s-transferase, reduced glutathione, catalase and decreased lipid hydroperoxide level, improved cellular architecture in histopathological examination and decrease expression of inflammatory markers: cyclooxygenase 2, tumor necrosis factor alpha, phosphorylated-nuclear factor kappa B, prostaglandins E2, interleukin-18 and increased heme oxygenase-1, as evidenced in immunohistochemistry and enzyme-linked immunosorbent assay molecular investigations. CONCLUSIONS: This study shows that continentalic acid exhibited binding affinities against the different targets and anti-diabetic action, mediated possibly through α-amylase and α-glucosidase inhibition, anti-hyperlipidemic, hepatoprotection, antioxidant and anti-inflammatory pathways.

Biosynthesis of silver capped magnesium oxide nanocomposite using Olea cuspidata leaf extract and their photocatalytic, antioxidant and antibacterial activity.

Green chemistry is a modern area of research which covers synthesis of nanomaterials through useful, environmentally, economically friendly techniques and their use in different fields. The synthesis involves the formation of bimetallic nanomaterials to enhance their synergistic relationship and achieve special modulated properties. That's why bimetallic nanomaterials are extremely important and gaining interest among researchers in the field of medicinal chemistry for the treatment of various diseases. In this particular study, bimetallic nanoparticles synthesis was done by reduction procedure using leaf extract of Olea cuspidata. The phytochemicals in leaf extract act as stabilizing and capping agent in reduction of precursor's salts. The characterization of green synthesized Ag@MgO nanocomposite was done through several analytical techniques such as ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Scanning electron microscope (SEM), High resolution transmission electron microscope (HRTEM) and Zeta potential. To explore the biological potential of synthesized nanocomposite, antibacterial activities against gram negative (Escherichia coli) bacteria and gram positive (Staphylococcus aureus) has been evaluated. The photocatalytic activity in contrary to methylene blue (MB) decomposition was seen efficiently. Moreover, the antioxidant nature of green synthesized Ag@MgO nanocomposite was analyzed by destabilizing and scavenging maximum percentage (93 %) of dangerous and harmful 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The best and surprising results provided the information for the presence of essential and vital components in Olea Cuspidata in the form of organic acids (Citrus Acid) aids in stabilizing the entire structure with enhanced properties. Up to the best of our knowledge, the facts and results obtained regarding the structure of Ag@MgO nanocomposite clearly illustrates the uniqueness of green chemistry and also its role in future developing multifunctional nanoparticles in the field of nanobiotechnology.

Facile and eco-benign fabrication of Ag/Fe2O3 nanocomposite using Algaia Monozyga leaves extract and its' efficient biocidal and photocatalytic applications.

Noble metal/metal oxide nanocomposites are pet and spellbound candidates in biomedical and catalytic fields because of their awestruck properties. This report put forward the facile and environmentally friendly fabrication of Ag/Fe2O3 nanocomposite using the eqeous extract of Algaia Monozyga leaves. The Ag/ Fe2O3 bimetallic nanocomposite was prepared using AgNO3, FeCl3 (anhydrous) and plant leaves extract as a natural source for reduction and stabilization of this nanocomposite. We prepared a separate solution of Silver and Iron salts and upon addition of this solution to the plant extract, the conversion of colour to brown appears within 10 min at constant stirring at 350 rpm. To confirm the synthesis of nanocomposite, UV-vis spectroscopy, Scanning electron microscopy (SEM), EDX and X-ray diffraction spectroscopy were used. The as prepared nanocomposite was used for photocatalytic activity in degradation of Methylene Blue (MB) in the presence of light which shows effective photocatalytic activity. The antimicrobial activities were also determined for nanocomposite which were found to be efficient against human pathogenic multidrug resistant bacteria. The Ag/Fe2O3 nanocomposite significantly preventing the growth of Staphylococcus aureus, E.coli QH4 and Pseudomonas putida with zones of inhibition 23 (±0.5), 21 (±0.4) and 19 (±0.4) mm, respectively.The eco-benignly synthesized Ag/Fe2O3 nanocomposite could be a desired material for efficient remediation of toxic organic pollutants and microbes.

Potent Natural Antioxidant Carveol Attenuates MCAO-Stress Induced Oxidative, Neurodegeneration by Regulating the Nrf-2 Pathway.

Ischemic stroke is a severe neurological disorder with a high prevalence rate in developed countries. It is characterized by permanent or transient cerebral ischemia and it activates syndrome of pathological events such as membrane depolarization, glutamate excitotoxicity, and intracellular calcium buildup. Carveol is widely employed as anti-inflammatory and antioxidant in traditional Chinese medicine. In the present study, the neuroprotective effects of post-treated carveol were demonstrated against transient middle cerebral artery occlusion (MCAO) induced focal ischemic cerebral injury. Male Sprague Dawley (SD) rats were subjected to two different experimental protocols to determine the dose and effects of carveol, and to demonstrate the underlying role of the nuclear factor E2-related factor (Nrf2) pathway. Our results showed that MCAO induced marked neuronal injury in the ipsilateral cortex and striatum associated with higher inflammatory cytokines expression, along with apoptotic markers such as caspase-3 and the phosphorylated c-Jun N-terminal kinase (JNK). Furthermore, MCAO induced a marked increase in oxidative stress as evidenced by high lipid peroxidase (LPO) content accompanied by the depressed antioxidant system. Carveol significantly reversed the oxidative stress and downregulated inflammatory cascades by enhancing endogenous antioxidant mechanisms including the Nrf2 gene, which critically regulates the expression of several downstream antioxidants. Further, to determine the possible involvement of Nrf2 in carveol mediated neuroprotection, we antagonized Nrf2 by all-trans retinoic acid (ATRA), and such treatment abrogated the protective effects of carveol accompanied with exaggerated neuronal toxicity as demonstrated by higher infarction area. The target effects of carveol were further supported by molecular docking analysis of drug-protein interactions. Together, our findings suggest that carveol could activate endogenous master anti-oxidant Nrf2, which further regulates the expression of downstream antioxidants, eventually ameliorating MCAO-induced neuroinflammation and neurodegeneration.

Eco-benign approach to synthesize spherical iron oxide nanoparticles: A new insight in photocatalytic and biomedical applications.

Iron oxide nanoparticles (Fe2O3NPs) are an interested and attractive area of research as they have numerous effective environmental and biomedical applications. Herein we have reported a simple and eco-benign synthesis Fe2O3NPs using Tamarix aphylla extract. The extract of the Tamarix aphylla acts both as a reducing and capping agent which leads to the fast and successful eco-benign synthesis of Fe2O3NPs.UV/Vis spectroscopy, XRD, EDX, SEM and TEM techniques were used to characterize and explore different features of Fe2O3NPs. UV/Vis studies showed asharppeak at 390 nm due to surface plasmon resonance absorption of Fe2O3NPs. XRD studies indicated that Fe2O3NPs were crystalline in nature. Structural features, elemental composition and geometry of Fe2O3NPswere confirmed by SEM, EDX and TEM. The as synthesized Fe2O3NPs showed efficient efficacy to degrade 100% of Methylene blue (MB) dye by 4 mg/25 ml MB and revealed 90% scavenging of the more stable DPPH free radical(1 mg/ml). Furthermore, Fe2O3NPs showed excellent antimicrobial activity against pathogenic multidrug resistant bacterial strains. The results of the present study explored the potential reducing, capping property of Tamarix aphylla extract, photocatalytic and biomedical applications of eco-benignly synthesized Fe2O3NPs which could be an alternative material for effective remediation of lethal organic pollutants and microbes.

Zinc oxide­selenium heterojunction composite: Synthesis, characterization and photo-induced antibacterial activity under visible light irradiation.

The designing of new antibacterial agents with high and long-lasting activities are urgently needed in order to cope with the fast-emerging bacterial resistance. Zinc oxide nanoparticles (ZnO) have shown a significant promise as broad-spectrum antibacterial agents, and are efficient material in compromising bacterial membrane stability that leads to an increased cell permeability to nano-products. However, further engineering is required to improve their biological activities and to minimize their toxicity to healthy cells. In an attempt to resolve this issue, two semiconductor materials, ZnO and selenium (Se), were fabricated into a unique structural composite by a newly developed facile green method, and the designed composite was applied as an antibacterial nanomedicine. The developed methodology involves the initial preparation of ZnO, followed by its fabrication with Se at different temperatures (70 °C to 95 °C). Our experimental data showed that well defined interpenetrated crystalline Se network on ZnO (ZnO-Se) can be obtained at 80 °C for 180 min. The as-prepared ZnO-Se showed promising results in inhibiting the challenged bacterial strains under light irradiation (visible light) as compared to free ZnO. The enhanced biocidal property of ZnO-Se could be ascribed to its improved light-harvesting ability for sustainable induction of reactive oxygen species (ROS) and an active contact killing mechanism. Thus, ZnO-Se composite with a novel architecture could be a promising material in the treatment of bacterial infections by a mutual antibacterial synergy from the incorporated elements. Interestingly, the ZnO-Se has the ability to scavenge the overproduction of hydroxyl radicals, thus protecting the healthy cells from oxidative damage.

In Vivo, Proteomic, and In Silico Investigation of Sapodilla for Therapeutic Potential in Gastrointestinal Disorders.

This study aims to delineate the effects of Manilkara zapota Linn. (Sapodilla) fruit chloroform (Mz.CHCl3) and aqueous (Mz.Aq) extracts tested through different techniques. Antidiarrheal activity and intestinal fluid accumulation were examined by using castor oil-induced diarrhea and castor oil fluid accumulation models. Isolated rabbit jejunum tissues were employed for in vitro experiments. Antimotility and antiulcer were performed through charcoal meal transient time and ethanol-induced ulcer assay, molecular studies were conducted through proteomic analysis, and virtual screening was performed by using a discovery studio visualizer (DSV). Mz.CHCl3 and Mz.Aq extracts attributed dose-dependent (50-300 mg/kg) protection (20-100%) against castor oil-induced diarrhea and dose-dependently (50-300 mg/kg) inhibited intestinal fluid secretions in mice. Mz.CHCl3 and Mz.Aq extracts produce relaxation of spontaneous and K+ (80 Mm) induced contractions in isolated tissue preparations and decreased the distance moved by charcoal in the gastrointestinal transit model in rats. It showed gastroprotective effect in ulcerative stomach of rats and decreased levels of IL-18 quantified by proteomic analysis. Histopathological results showed ethanol-induced significant gastric injury, leading to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all gastric zones using hematoxylin and eosin (H&E) staining. Moreover, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), cyclooxygenase (COX-2), and nuclear factor kappa-light-chain-enhancer of activated B cells (p-NFκB). In silico results were comparative to in vitro results evaluated through virtual screening. Moreover, ethanol increased the activation and expression of tumor necrotic factor, cyclooxygenase, and nuclear factor kappa-light-chain-enhancer of activated B cells. This study exhibits the gastroprotective effect of Manilkara zapota extracts in the peritoneal cavity using a proteomic and in silico approach which reveals different energy values against target proteins, which mediate the gastrointestinal functions.

Pharmacological and computational evaluation of fig for therapeutic potential in hyperactive gastrointestinal disorders.

BACKGROUND: Ficus palmata (Fig), are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including inflammation, tumor, epilepsy, jaundice, influenza and bacillary dysentery. The present study aimed to evaluate the antidiarrheal, antisecretary, antispasmodic, antiulcer and anti motility properties of Ficus palmata. METHODS: In-vivo, in-vitro and in-silico techniques were used to investigate various gastrointestinal effects of Ficus palmata. Antidiarrheal, antisecretary, antispasmodic, antiulcer, anti motility and molecular docking were performed using castor oil induced diarrhea and fluid accumulation, isolated tissue preparations, ethanol-HCl induced ulcer assay, charcoal meal transit time and Auto Doc Vina. RESULTS: Ficus palmata crude extract (Fp.Cr) exhibited protection against castor oil-induced diarrhea in mice and dose-dependently inhibited intestinal fluid secretions. Fp.Cr caused relaxation of spontaneous and K+ (80 Mm)-induced contractions in isolated rabbit jejunum preparations. It showed protective effect against gastric ulcers induced by ethanol-hydrochloric acid in rats. Fp.Cr reduced distance travelled by charcoal meal in the gastrointestinal transit model in mice. The plant constituents: psoralenoside and bergapten showed high binding affinities (E-value ≥ - 6.5 Kcal/mol) against histaminergic H1, calmodulin and voltage gated L-type calcium channels, while showed moderate affinities (E-value ≥7 Kcal/mol) against dopaminergic D2, adrenergic α1, muscranic M3, mu-opioid, whereas revealed lower affinities (E-value ≥9.5 Kcal/mol) vs. muscranic M1, histaminergic H2 and H+/K+ ATPase pump. Germanicol acetate and psoralene exhibited weak affinities against aforementioned targets. CONCLUSION: This study reveals that Ficus palmata possesses anti-diarrheal, anti-secretory, anti-spasmodic, anti-motility and anti-ulcer activities. The various constituents reveal different binding affinities against target proteins, which mediate the gastrointestinal functions.

Facile and eco-benign synthesis of Au@Fe2O3 nanocomposite: Efficient photocatalytic, antibacterial and antioxidant agent.

The development of eco-benign experimental procedures for the synthesis of nanomaterials is a fundamental developing branch of green nanotechnology. In this paper, green synthetic route was followed to synthesize novel Au@Fe2O3nanocomposite using Citrus sinensis fruit extract as a reducing and stabilizing agent. The as synthesized Au@Fe2O3nanocomposite was successfully characterized by UV-visible spectroscopy, X-ray diffraction (XRD), Scanning electron microscope (SEM), Energy-dispersive X-ray (EDX), Fourier transform infrared (FT1R) spectrophotometry and Zeta potential. UV-vis spectroscopy showed two SPR peaks for Fe2O3 and coated Au at 290 and 520 nm respectively. XRD confirmed the crystallinity of Au@Fe2O3. Au@Fe2O3 nanocomposite showed better antioxidant activity to effectively scavenge DPPH. The Au@Fe2O3 has been also tested for antibacterial activity which showed an effective antibacterial activity against multi drug resistant E.coli and Bacillus subtilis. Furthermore, Au@Fe2O3 also demonstrated better photo catalytic activity for methylene blue (MB) degradation. We proposed that the existence of organic acids (citric acids) also played a significant role in the stabilization of Au@Fe2O3, and plant (Citrus sinensis Var Kozan yerly) containing such component may be more effective for the green synthesis of Au@Fe2O3 nanocomposite. The findings of this study prove the overwhelming therapeutic and photocatalytic potential of bio-inspired Au@Fe2O3nanocomposite which can be a novel candidate for the effective remediation of microbes and toxic organic pollutants.

An Updated List of Neuromedicinal Plants of Pakistan, Their Uses, and Phytochemistry.

BACKGROUND: Almost every region of Pakistan is stacked with a large number of medicinal plants. Due to high cost and unavailability of allopathic medicines for the neurological diseases, especially in rural areas, traditional healers prescribe phytotherapy for various neurological diseases like epilepsy, depression, anxiety, insomnia, Alzheimer, and migraine. Such treatments are considered to be most effective by the native people. METHODS: The data was collected from articles published on medicinal plants of various districts of Pakistan, using article search engines like Medline, Pubmed, Web of Science, Science Direct, and Google Scholar. Also, information regarding various neurological uses and mode of applications of medicinal plants was obtained from traditional healers, folk medicine users, and local elderly people having knowledge of medicinal plants. RESULTS: A total of 54 families were found to be used in various neurological diseases, of which the highest use was of Solanaceae (22.22%), Asteraceae (12.96%), Lamiaceae, Papaveraceae, and Poaceae, 9% each, and Caprifoliaceae, Cucurbitaceae, Rhamnaceae, and Rosaceae, 5.5% each. According to districts, 15% of plants that were effective in neurological affections were found in Bahawalpur, 11% in Swat, 8% in Muzaffarabad, 7% in Malakand, and 6% in Bahawalnagar, Dir, Gilgat, and Sarghoda each, with 5% in Dera ghazi khan and Jhelum each. According to the plant's habit, out of total of 103 plants, 61.15% were found to be herbs, 22.33% trees, 11.65% shrubs, and 4.85% climbers. According to the part used of plant, whole plant, leaves, fruits, roots, seeds, and flowers were found to be used 32.03%, 24.27%, 20.38%, 16.50%, 13.59%, and 11.65%, respectively. According to disease's types, 45.63% were found to be effective in insomnia, 31.06% in epilepsy 12.62% in depression, 6.80% in anxiety, 7.77% in hysteria, and 5.88% in migraine. CONCLUSION: Taking into consideration this useful knowledge on medicinal properties of the plants for curing neurologic diseases, it is believed that research in areas of ethnomedicine and ethnopharmacology can bring auspicious results that have potential of adding value to the very rich natural resources of Pakistan. This study will help all the researchers from diverse backgrounds working on plants based medicine for neurological diseases.

Tuber extract of Arisaema flavum eco-benignly and effectively synthesize silver nanoparticles: Photocatalytic and antibacterial response against multidrug resistant engineered E. coli QH4.

Metal nanoparticles, synthesized using Phyto-constituents are the most economically and environmentally benign materials ever. Biogenic silver nanoparticles (AgNPs) from three fractions of Arisaema flavum tuber extract were synthesized and characterized by UV-visible spectroscopy, XRD (X-rays diffraction), FT-IR (Fourier transform infrared spectroscopy) TEM (transmission electron microscopy) and EDX (Energy dispersive Microscopy). XRD pattern show the face centred cubic crystalline (Fcc) structure of AgNPs. FTIR spectra confirmed the presence of different Polyphenolic compounds capping the AgNps. UV-visible spectroscopy result confirmed the presence of Ag because of the particular surface plasmon Resonance (SPR) in the area of 400-430 nm. The electron microscope studies revealed the formation of spherical AgNPs with diameter ranging from 12 nm to 20 nm. Strong signals of AgNPs were confirmed with EDX analysis. The antibacterial properties of the AgNPs prepared with various extracts were tested against multi-drug resistant bacteria. Which showed significant antibacterial activity against all the multidrug resistant bacterial strains and especially multidrug resistant engineered E.ColiQH4. AgNPs synthesized by methanolic, Ethyl Acetate and aqueous Extracts of Areseama Flavum exhibited significant Photocatalytic activity to reduce methylene blue. Small size, spherical shape and high dispersion are the key properties due to which the AgNPs are having significant biological and photocatalytic activity. To the best of our knowledge, it is the first report of biogenic AgNPs regarding antibacterial activity against multidrug resistant Engineered E.Coli QH4.

Greener synthesis of zinc oxide nanoparticles using Trianthema portulacastrum extract and evaluation of its photocatalytic and biological applications.

Synthesis of nanoparticles (NPs) through "green" chemistry is an exciting area of research with wide applications. Trianthema portulacastrum's extract containing greater amount of reducing agents has been explored first time for the synthesis of ZnO-NPs that characterized with UV/Vis, XRD, FT-IR, SEM,EDX, HR-TEM and XPS. The particles of ZnO-NPs are crystalline and having the size in the range of 25-90 nm. The cell viability of ZnO-NPs was studied using Mouse pre-osteoblast cell line MC3T3-E1 sub-clone 14 cells which confirmed its biocompatibility that render for biomedical applications. The antibacterial properties were evaluated against Staphylococcus aureus and Escherichia coli which showed high potency of synthesized ZnO-NPs against these species. The antifungal activities of ZnO-NPs were screened against Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus of fungal species. The antioxidant activity of the as-synthesized NPs was also studied using DPPH (2, 2-diphenyl-1-picrylhydrazyl) substrate. The ZnO-NPs were evaluated for catalytic activity through degradation of Synozol Navy Blue-KBF textile dye using solar irradiation that causes 91% degradation of the dye in 159 min. Mechanistic pathways for the degradation of Synozol Navy Blue-KBF dye using ZnO-NPs were also proposed from the pattern of the degradation of the dye and the resulting by-products. The results concluded that the ZnO-NPs synthesized by green method have high biological and photocatalytic applications.