Lokalna primjena hemina unapređuje liječenje rana u štakora s dijabetesom izazvanim streptozotocinom

Hemin may be of potential therapeutic value in wound healing management in diabetics. It is an inducer of heme oxygenase-1, an enzyme which degrades heme and participates in cellular protection against oxidative stress, inflammation and apoptosis. Thus, in the present study, hemin (0.5%) was applied topically over excision wounds, and its therapeutic effect in wound healing evaluated in diabetic rats. Topical hemin application significantly increased the percentage of wound contraction on day 2 in diabetic rats, however, povidone-iodine did the same on day 7 compared to the diabetic control. A significant increase in hydroxyproline and glucosamine content was found on day 14 in the hemin treated wounds of diabetic rats vs. the diabetic control. The histology of the hemin treated rats was in agreement with the cellular proliferation and collagen synthesis in granulation tissue. Hemin significantly increases cytokine IL-10 and decreases TNF-α in the granulation tissue of the healed wounds of diabetic rats. The finding showing the pro-healing effects of hemin was endorsed by inhibition of mRNA expression of pro-inflammatory cytokine TNF-α and adhesion molecule ICAM-1, and up-regulation of anti-inflammatory cytokine IL-10 mRNA. Hence, topical hemin application (i) helps in early and fast wound contraction (ii) enhances the hydroxyproline and glucosamine content of wounds and (iii) modulates pro-healing mRNA expression of cytokines.Hemin ima potencijalnu terapijsku vrijednost u liječenju rana u dijabetičara. On potiče hem-oksigenazu-1, enzim koji razgrađuje hem i sudjeluje u staničnoj zaštiti od oksidacijskog stresa, upale i apoptoze. U ovom je istraživanju hemin (0,5 %) primijenjen lokalno na ekscizijske rane te je procijenjen njegov terapijski učinak na cijeljenje rana u dijabetičnih štakora. Lokalna aplikacija hemina znakovito je povećala postotak zatvaranja rana 2. dan u dijabetičnih štakora, što je učinio i povidon-jod 7. dan u kontrolnoj skupini. Znakovit porast sadržaja hidroksiprolina i glukozamina pronađen je 14. dan u dijabetičnih štakora čije su rane tretirane heminom, za razliku od kontrolne skupine. Histologija je u štakora tretiranih heminom bila u skladu sa staničnom proliferacijom i sintezom kolagena u granulacijskom tkivu. Hemin je znakovito povisio citokin IL-10 i smanjio TNF-α u granulacijskom tkivu dijabetičnih štakora sa zacijeljenim ranama. Taj nalaz odgovara ljekovitom učinku hemina što je podržano inhibicijom ekspresije mRNA proupalnog citokina TNF-α i adhezijom molekule ICAM-1 te regulacijom protuupalnog cittokina IL-10 mRNA. Dakle, lokalna primjena hemina pomaže (i) u ranoj i brzoj kontrakciji rana (ii), poboljšava sadržaj hidroksiprolina i glukozamina u ranama i (iii) prilagođuje mRNA ekspresiju citokina u smjeru cijeljenja rane

Trajna primjena fitoestrogena daidzeina poboljšava srednji arterijski tlak i vaskularnu funkciju u L-NAME štakora s povećanim krvnim tlakom.

The ‘silent killer’, hypertension, leads to heart disease, stroke, kidney failure and premature death. The phytoestrogen daidzein has been associated with vaso-protective action similar to oestrogen, with minimal side effects. To explore the vaso-protective activity of daidzein and also its effect on mean arterial pressure (MAP), daidzein was chronically administered in N-G-nitro-L-arginine methyl ester (L-NAME)-hypertensive male Wistar rats for 6 weeks. The male Wistar rats were divided into three groups, namely group-A (control), group-B (L-NAME-treated) and group-C (L-NAME+daidzein treated). After completion of 42 days (6 weeks) of daidzein treatment, MAP and vascular activity were observed in all the groups. Daidzein treatment of L-NAME hypertensive rats (group-C) for 6 weeks significantly decreased the MAP (144 mm Hg) as compared to untreated-L-NAME-hypertensive rats/group-B (173.2 mm Hg), indicating the blood-pressure lowering property of daidzein. Also daidzein significantly increased acetylcholine-induced maximal relaxations of the thoracic aorta isolated from daidzein-treated (Emax = 72.55 %) in comparison to untreated-L-NAME-hypertensive rats (Emax = 39.33 %). The results of the present study suggest that chronic administration of daidzein (0.5 mg/kg/day, s.c.) helps to lower blood pressure, as indicated by a decrease in MAP, and also shows vaso-protective action, as indicated by the improvement in ACh-induced relaxation.Hipertenzija kao „tihi ubojica“ dovodi do bolesti srca, moždanog udara, zatajivanja bubrega i prerane smrti. Fitoestrogen daidzein, slično kao i estrogen, djeluje zaštitno na krvne žile uz minimalne popratne učinke. S ciljem istraživanja zaštite krvnih žila, te učinka na krvni tlak (srednji arterijski tlak - SAT), daidzein je tijekom 6 tjedana bio primjenjivan Wistar štakorima s L-NAME - hipertenzijom. Štakori su bili podijeljeni u tri skupine: skupina A (kontrola), skupina B (L-NAME liječena) i skupina C (L-NAME + liječena daidzeinom). Nakon 42 dana liječenja u svim je skupinama bila analizirana funkcija krvnih žila i SAT. Liječenje štakora oboljelih od L-NAME hipertenzije (skupina C) daidzeinom dovelo je do signifikantnog sniženja srednjega arterijskog tlaka (144 mm Hg) u usporedbi s neliječenim oboljelim štakorima iz skupine B (173,2 mm Hg). Navedeno pokazuje učinke daidzeina na snižavanje krvnog tlaka. Osim toga, daidzein dovodi do signifikantnog povećanja maksimalne relaksacije torakalnog dijela aorte izazvane acetilkolinom. To pokazuju vrijednosti u skupini štakora liječenih daidzeinom (Emaks= 72,55 %), u usporedbi sa skupinom neliječenih štakora (Emaks= 39,33 %). Rezultati istraživanja potvrđuju da trajna primjena daidzeina (0,5 mg/kg/dan s.c.) pomaže snižavanju krvnog tlaka, na što upućuje njegova smanjena arterijska vrijednost. Osim toga, opisana primjena daidzeina djeluje zaštitno na krvne žile, jer poboljšava njihovu relaksaciju izazvanu acetilkolinom

Induction of oxidative stress and lipid peroxidation in rats chronically exposed to cypermethrin through dermal application

Present study was undertaken to study the effect of cypermethrin on oxidative stress after chronic dermal application. The insecticide was applied dermally at 50 mg/kg body weight in different groups of Wistar rats of either sex weighing 150~200 g. Significant (p < 0.05) increase in catalase activity was observed after 30 days of exposure. However, the superoxide dismutase activity declined significantly after 60 days of exposure. The activity of glutathione peroxidase and blood glutathione levels declined significantly (p < 0.05) after 30 days of cypermethrin dermal application. However, the activity of glutathione S-transferase increased significantly (p < 0.05) in all groups after 60 days of dermal exposure. Significant increase in lipid peroxidation was observed from 30 days onwards and reached a peak after 120 days of application

Polyphenolic constituents and antioxidant/antiradical activity in different extracts of Alstonia scholaris (Linn.)

Alstonia scholaris (Linn.) leaves extracted in aqueous, dichloromethane (DCM), methanolic and ethanolic solvents were assessed for different polyphenolic constituents endowed with antioxidant/antiradical activity. Total phenolic, flavonoids and tannin contents were significantly (P&lt;0.05) higher in ethanolic extract as compared to other extracts. The antiradical activity and efficiency was significantly (P&lt;0.05) higher in ethanolic extract followed by methanolic, DCM and aqueous extracts. The ethanolic extract as compared to other extracts also exhibited high total antioxidant capacity, superoxide and nitric oxide anion scavenging activity. However, aqueous extract has shown high hydroxyl radicals scavenging activity as compared to other extracts. Total phenolic content of the ethanolic extract of A. scholaris was positively correlated with total antioxidant capacity (r = 0.901), antiradical activity (r = 0.948) and antiradical efficiency (r = 0.891). Therefore, ethanolic extract showed maximum, contents endowed with high total antioxidant capacity, superoxide and nitric oxide radicals scavenging activity as compared to other solvents. Thus, the dietary supplementation of ethanolic extract may provide protection in preventing the free radicals induced damage besides improve the food quality by retarding oxidative degeneration of food lipids.Keywords: Total phenolics, antioxidant potential, free radicals, Alstonia scholari

Trajna primjena fitoestrogena daidzeina poboljšava srednji arterijski tlak i vaskularnu funkciju u L-NAME štakora s povećanim krvnim tlakom.

The ‘silent killer’, hypertension, leads to heart disease, stroke, kidney failure and premature death. The phytoestrogen daidzein has been associated with vaso-protective action similar to oestrogen, with minimal side effects. To explore the vaso-protective activity of daidzein and also its effect on mean arterial pressure (MAP), daidzein was chronically administered in N-G-nitro-L-arginine methyl ester (L-NAME)-hypertensive male Wistar rats for 6 weeks. The male Wistar rats were divided into three groups, namely group-A (control), group-B (L-NAME-treated) and group-C (L-NAME+daidzein treated). After completion of 42 days (6 weeks) of daidzein treatment, MAP and vascular activity were observed in all the groups. Daidzein treatment of L-NAME hypertensive rats (group-C) for 6 weeks significantly decreased the MAP (144 mm Hg) as compared to untreated-L-NAME-hypertensive rats/group-B (173.2 mm Hg), indicating the blood-pressure lowering property of daidzein. Also daidzein significantly increased acetylcholine-induced maximal relaxations of the thoracic aorta isolated from daidzein-treated (Emax = 72.55 %) in comparison to untreated-L-NAME-hypertensive rats (Emax = 39.33 %). The results of the present study suggest that chronic administration of daidzein (0.5 mg/kg/day, s.c.) helps to lower blood pressure, as indicated by a decrease in MAP, and also shows vaso-protective action, as indicated by the improvement in ACh-induced relaxation.Hipertenzija kao „tihi ubojica“ dovodi do bolesti srca, moždanog udara, zatajivanja bubrega i prerane smrti. Fitoestrogen daidzein, slično kao i estrogen, djeluje zaštitno na krvne žile uz minimalne popratne učinke. S ciljem istraživanja zaštite krvnih žila, te učinka na krvni tlak (srednji arterijski tlak - SAT), daidzein je tijekom 6 tjedana bio primjenjivan Wistar štakorima s L-NAME - hipertenzijom. Štakori su bili podijeljeni u tri skupine: skupina A (kontrola), skupina B (L-NAME liječena) i skupina C (L-NAME + liječena daidzeinom). Nakon 42 dana liječenja u svim je skupinama bila analizirana funkcija krvnih žila i SAT. Liječenje štakora oboljelih od L-NAME hipertenzije (skupina C) daidzeinom dovelo je do signifikantnog sniženja srednjega arterijskog tlaka (144 mm Hg) u usporedbi s neliječenim oboljelim štakorima iz skupine B (173,2 mm Hg). Navedeno pokazuje učinke daidzeina na snižavanje krvnog tlaka. Osim toga, daidzein dovodi do signifikantnog povećanja maksimalne relaksacije torakalnog dijela aorte izazvane acetilkolinom. To pokazuju vrijednosti u skupini štakora liječenih daidzeinom (Emaks= 72,55 %), u usporedbi sa skupinom neliječenih štakora (Emaks= 39,33 %). Rezultati istraživanja potvrđuju da trajna primjena daidzeina (0,5 mg/kg/dan s.c.) pomaže snižavanju krvnog tlaka, na što upućuje njegova smanjena arterijska vrijednost. Osim toga, opisana primjena daidzeina djeluje zaštitno na krvne žile, jer poboljšava njihovu relaksaciju izazvanu acetilkolinom

GC-MS Analysis, Phytochemical Screening, and Antibacterial Activity of <i>Cerana indica</i> Propolis from Kashmir Region

Propolis is a resinous compound produced by honey bees. It contains bioactive molecules that possess a wide range of biological functions. The chemical composition of propolis is affected by various variables, including the vegetation, the season, and the area from which the sample was collected. The aim of this study was to analyze the chemical composition and assess Cerana indica propoli’s antibacterial efficacy from the Kashmir region. Gas chromatography-mass spectrometry (GC-MS) analysis was used to determine the chemical composition of Kashmiri propolis. A range of bacterial strains was tested for antimicrobial activity using different extracts of propolis by agar well diffusion technique. Propolis was found to be rich in alkaloids, saponins, tannins, and resins. The chemical characterization revealed the presence of 68 distinct phytocompounds using GC-MS, and the most predominant compounds were alpha-D-mannopyranoside, methyl, cyclic 2,3:4,6-bis-ethyl boronate (21.17%), followed by hexadecanoic acid, methyl ester (9.91%), and bacteriochlorophyll-c-stearyl (4.41%). The different extracts of propolis showed specific antibacterial efficacy against multidrug-resistant (MDR) strains viz., Pseudomonas aeruginosa (MTCC1688), Escherichiacoli (MTCC443), Klebsiella pneumonia (MTCC19), Cutibacterium acnes (MTCC843), and Staphylococcus aureus (MTCC96). The EEKP showed the highest zone of inhibition against S. aureus (17.33) at 400 µg mL−1. According to the findings of this study, bee propolis contains a variety of secondary metabolites with various pharmacological activities. Furthermore, because of its broad spectrum of positive pharmacological actions and the fact that it is a promising antibacterial agent, more research on propolis is warranted

Phytochemical Profiling and Antibacterial Activity of Methanol Leaf Extract of Skimmia anquetilia

Skimmia anquetilia is a plant species native to the Western Himalaya region that has tremendous potential for phytochemical activities. This study aimed to identify bioactive compounds and assess the antibacterial activity of S. anquetilia. To determine the major bioactive chemicals in the methanol leaf extract of S. anquetilia, we used a gas chromatography&ndash;mass spectrometer (GC-MS). The presence of 35 distinct phytoconstituents was discovered using GC-MS, which could contribute to the therapeutic capabilities of this plant species. The most predominant compound was 2R-acetoxymethyl-1,3,3-trimethyl-4t-(3-methyl-2-buten-1-yl)-1t-cyclohexanol (23.9%). Further, the leaf extract was evaluated for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, and Staphylococcus aureus. The extract showed the highest zone of inhibition against E. coli (19 mm) followed by P. aeruginosa (18 mm) and K. Pneumoniae (17 mm) at 160 mg mL&minus;1. The minimum inhibitory concentration (MIC) of methanol extract against the strain of P. aeruginosa (2 mg mL&minus;1) demonstrated significant antibacterial activity. The findings of the present study highlight the potential of S. anquetilia for the development of herbal medicines for the treatment of various pathogenic infections

Optimisation of a Greener-Approach for the Synthesis of Cyclodextrin-Based Nanosponges for the Solubility Enhancement of Domperidone, a BCS Class II Drug

BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their bioavailability is using cyclodextrin-based nanosponges. This study aimed to optimise and evaluate the feasibility of a microwave-assisted approach to synthesise nanosponges and improve domperidone’s solubility and drug delivery potential. In the production process, microwave power level, response speed, and stirring speed were optimised using the Box-Behnken approach. Ultimately, the batch with the smallest particle size and highest yield was chosen. The optimised method of synthesis of the nanosponges resulted in a product yield of 77.4% and a particle size of 195.68 ± 2.16 nm. The nanocarriers had a drug entrapment capacity of 84 ± 4.2% and a zeta potential of −9.17± 0.43 mV. The similarity and the difference factors demonstrated proof-of-concept, showing that the drug release from the loaded nanosponges is significantly greater than the plain drug. Additionally, spectral and thermal characterisations, such as FTIR, DSC, and XRD, confirmed the entrapment of the drug within the nanocarrier. SEM scans revealed the porous nature of the nanocarriers. Microwave-assisted synthesis could be used as a better and greener approach to synthesise these nanocarriers. It could then be utilised to load drugs and improve their solubility, as seen in the case of domperidone