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The aphid, Schizaphis graminum Rondani (Hemiptera: Aphididae), is one of the most destructive pests of wheat. It is responsible for significant economic losses in the agricultural sector, with an estimated 45% of wheat fields affected. Plant-based insecticides have seen a rapid increase in popularity in recent years due to their efficacy, cost-effectiveness, biodegradability, and lower toxicity compared to synthetic pesticides. The study aimed to evaluate the toxic potential of S. longipedunculata extracts against S. graminum and investigate the insect's feeding behavior on wheat. Initially macerated in methanol, the different extracts of S. longipedunculata organs were fractionated using n-hexane, chloroform, ethyl acetate, and butanol. The feeding behavior was analyzed by comparing the waveforms generated by the EPG with the control. After 72 h of treatment, the ethyl acetate fraction extracted from root had the highest toxicity against aphids, with mean 26 mortality of S. graminum at LC50 of 330 ppm; 25 mortality S. graminum at LC50 of 400 ppm for leaves; and mean 24.5 mortality S. graminum at LC50 of 540 ppm in stem bark. EPG analysis indicated that the extract fractions enhanced plant tissue resistance by significantly preventing aphid access to the phloem. The toxic effect of the botanical extracts significantly enhanced the chemical composition of the leaf medium, resulting in a drastic reduction in the number of tissue attacks by S. graminum. In summary, besides their toxicity to S. graminum, extracts of S. longipedunculata reinforce the plant's defense mechanisms, significantly reducing the S. graminum population. They also reinforce wheat's defense mechanisms. S. longipedunculata can, therefore, be used as a promising agent in the biological control of S. graminum.
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The current study aimed to determine the safety and efficacy of Coag-A through in vivo analysis in CFA induced mice model. Treatment of CFA induced arthritis in mice with Coagulansin-A (10 mg/kg i.p. daily for 28 days), a withanolide obtained from Withania coagulans, as well as standard drug treatment with Dexamethasone (5 mg/kg i.p) was provided. The effect of Coag-A on body weight, relative organ weight, hematology, serum biochemistry, survival rate, oxidative stress markers, and antioxidant enzymes was evaluated. The liver and kidney histopathology were also assessed to ascertain its safety profile. Treatment of arthritic mice with Coag-A considerably improved body weight, relative organ weight of liver, kidney, and spleen, ameliorated hematology and serum biochemistry, and increased survival and antioxidant potential. Coag-A was found to be safer with fewer adverse effects showing hepato-protective, nephroprotective, and anti-inflammatory effect. It also significantly (p < 0.001) improved histopathology of CFA-induced mice when compared with Dexa. In conclusion, compared to dexamethasone, Coag-A has demonstrated a greater therapeutic benefit and fewer side effects in the treatment of arthritis against the CFA-induced model.
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Artrite Experimental , Animais , Camundongos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/induzido quimicamente , Masculino , Vitanolídeos/farmacologia , Vitanolídeos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Dexametasona , Estresse Oxidativo/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/metabolismo , Withania/química , FemininoRESUMO
Artemisinin, artemether, artesunate, and dihydroartemisinin are renowned for their antimalarial potential. The current study aims to repurpose the above-mentioned artemisinic compounds (ACs) by conducting an intercomparison to evaluate their antiinflammatory potential (AIP). In order to develop potential candidates for the evaluation of AIP of ACs (50 and 100 mg/kg BW), carbon tetrachloride (1ml/kg body weight (BW)) was administered intraperitoneally to BALB/c mice. Alterations in animal behavior were assessed weekly through tail suspension test, force swim test, open field test, Y-maze test, inverted screen analysis, and weight lifting test. Aberrations in hematological, serological, endogenous antioxidants, and oxidative stress marker profiles were assessed in all twelve groups. Histological alterations were read using hematoxylin and eosin staining. Levels of inflammatory markers including nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), were determined using immunohistochemical analysis (IHCA). Antioxidant markers i.e., nuclear factor erythroid-2-related factor (Nrf-2) and thioredoxin (TRX) were also quantified through IHCA. Comet assay was performed to quantify DNA damage. Oral administration of ACs to mice significantly alleviated the carbon tetrachloride induced inflammation in comparison with silymarin. Reduced levels of several inflammatory markers including nitric oxide, thiobarbituric acid reactive substances, interleukin-1 beta, NF-κB, TNF-α, and NLRP3, underscore the substantial AIP of ACs. IHCA depicted the revitalized percent relative expression of Nrf-2 and TRX in groups treated with ACs. Behavioral analysis revealed that ACs-treated groups significantly (p<0.05) attenuated the memory deficit, anxiety, and depressive-like behavior. Moreover, histopathological, hematological, serological, and endogenous antioxidant profiles indicated substantial AIP of ACs. Findings of comet assay further bolstered the compelling evidence as DNA damage was significantly (p<0.05) curbed down after ACs (100 mg/kg) treatment. All these outcomes implied that ACs exhibited AIP in a dose-dependent manner with maximal AIP imparted by artemisinin (100 mg/kg). This pre-clinical investigation avers the tremendous AIP of ACs targeting key molecular pathways. The current study divulges artemisinin as the most potent antiinflammatory agent among the tested compounds.
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Thiamethoxam, a second-generation neonicotinoid insecticide is widely used for controlling sap-sucking insect pests including Rhopalosiphum padi. The current study aimed to investigate the life-history parameters and feeding behavior of R. padi following treatments with sublethal concentrations of thiamethoxam. The lethal concentration 50 (LC50) value of thiamethoxam against adult R. padi was 11.458 mg L-1 after 48 h exposure. The sublethal concentrations of thiamethoxam (LC5 and LC10) significantly decreased the adult longevity, fecundity, and reproductive days in the directly exposed aphids (F0 generation). In the progeny R. padi (F1), the developmental durations and total prereproductive period (TPRP) were decreased while the adult longevity, fecundity, and reproductive days (RPd) were increased at both thiamethoxam concentrations. The demographic parameters including the net reproductive rate (R0), intrinsic rate of increase (r), and finite rate of increase (λ) were prolonged only at the LC5 of thiamethoxam. The EPG results indicated that the sublethal concentrations of thiamethoxam increases the total duration of non-probing (Np) while reducing the total duration of E2 in directly exposed aphids (F0). Interestingly, the E2 were significantly increased in the progeny generation (F1) descending from previously exposed parental aphids (F0). Overall, this study showed that thiamethoxam exhibited high toxicity against directly exposed individuals (F0), while inducing intergenerational hormetic effects on the progeny generation (F1) of R. padi. These findings provided crucial details about thiamethoxam-induced hormetic effects that might be useful in managing resurgences of this key pest.
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In agroecosystems, insects contend with chemical insecticides often encountered at sublethal concentrations. Insects' exposure to these mild stresses may induce hormetic effects, which has consequences for managing insect pests. In this study, we used an electrical penetration graph (EPG) technique to investigate the feeding behavior and an age-stage, two-sex life table approach to estimate the sublethal effects of thiamethoxam on greenbug, Schizaphis graminum. The LC5 and LC10 of thiamethoxam significantly decreased longevity and fecundity of directly exposed adult aphids (F0). However, the adult longevity, fecundity, and reproductive days (RPd)-indicating the number of days in which the females produce offspring - in the progeny generation (F1) exhibited significant increase when parental aphids (F0) were treated with LC5 of the active ingredient. Subsequently, key demographic parameters such as intrinsic rate of increase (r) and net reproductive rate (R0) significantly increased at LC5 treatment. EPG recordings showed that total durations of non-probing (Np), intercellular stylet pathway (C), and salivary secretion into the sieve element (E1) were significantly increased, while mean duration of probing (Pr) and total duration of phloem sap ingestion and concurrent salivation (E2) were decreased in F0 adults exposed to LC5 and LC10. Interestingly, in the F1 generation, total duration of Np was significantly decreased while total duration of E2 was increased in LC5 treatment. Taken together, our results showed that an LC5 of thiamethoxam induces intergenerational hormetic effects on the demographic parameters and feeding behavior of F1 individuals of S. graminum. These findings have important implications on chemical control against S. graminum and highlight the need for a deeper understanding of the ecological consequences of such exposures within pest management strategies across the agricultural landscapes.
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Afídeos , Inseticidas , Humanos , Animais , Feminino , Tiametoxam , Reprodução , Inseticidas/toxicidade , Comportamento Alimentar , DemografiaRESUMO
Psoriasis is a common immune-mediated skin condition characterized by aberrant keratinocytes and cell proliferation. The purpose of this study was to explore the FDA-approved drugs by 3D-QSAR pharmacophore model and evaluate their efficiency by in-silico, in vitro, and in vivo psoriasis animal model. A 3D-QSAR pharmacophore model was developed by utilizing HypoGen algorithm using the structural features of 48 diaryl derivatives with diverse molecular patterns. The model was validated by a test set of 27 compounds, by cost analysis method, and Fischer's randomization test. The correlation coefficient of the best model (Hypo2) was 0.9601 for the training set while it was 0.805 for the test set. The selected model was taken as a 3D query for the virtual screening of over 3000 FDA-approved drugs. Compounds mapped with the pharmacophore model were further screened through molecular docking. The hits that showed the best docking results were screened through in silico skin toxicity approach. Top five hits were selected for the MD simulation studies. Based on MD simulations results, the best two hit molecules, that is, ebastine (Ebs) and mebeverine (Mbv) were selected for in vitro and in vivo antioxidant studies performed in mice. TNF-α and COX pro-inflammatory mediators, biochemical assays, histopathological analyses, and immunohistochemistry observations confirmed the anti-inflammatory response of the selected drugs. Based on these findings, it appeared that Ebs can effectively treat psoriasis-like skin lesions and down-regulate inflammatory responses which was consistent with docking predictions and could potentially be employed for further research on inflammation-related skin illnesses such as psoriasis.
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Farmacóforo , Psoríase , Animais , Camundongos , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Simulação por Computador , Psoríase/tratamento farmacológico , Simulação de Dinâmica MolecularRESUMO
For many years, the synthesis of graphene oxide (GO) had involved exfoliating graphite flakes, and the methods applied were expensive and time-consuming. Thus, an attempt had been made to create an inventive, less expensive method for the synthesis of GO using unrefined, raw carbon-containing material. Modified Hummer's method was used to prepare GO from banana peel. In addition, the metallic silver nanocomposite was also synthesized along with laoding of drug Rocephin where they interact with each other through electrostatic hydrogen bond interaction. The degree of crystallinity and the crystallite size were through x-ray diffraction (XRD) analysis and the crystallite size of AgNPs was found to be 40.40 nm. The scanning electron microscopy (SEM) analysis shows that the morphology of the GO gradually changes with the addition of AgNPs and Rocephin. A blue shift was seen in the absorbance maxima of the raw carbon upon the conjugation of Rocephin in UV analysis. The Fourier-transform infrared spectroscopy, and energy dispersive X-ray (EDX) spectroscopy were used to determine the chemical composition of the samples. Furthermore, a broad biological screening of the synthesized samples had been carried out following the total reducing power (TRP), total antioxidant capacity (TAC), antibacterial, antifungal, MTT (Cytotoxicity of biologically synthesized silver nanoparticles in MDA-MB-231 human breast cancer cells) cell viability, brine shrimp lethality, and hemolytic protocols. Significant results were obtained, and the Rocephin-GO-AgNPs had depicted promising activity as compared with their counterparts. RESEARCH HIGHLIGHTS: The GO was prepared from the raw carbon extracted from banana peels and was used as a substrate for the synthesis Graphene oxide silver nanoparticles (GO-AgNPs) and Rocephin-loaded graphene oxide silver nanoparticles (Rocephin-GO-AgNPs) The structural and compositional analysis of the nanomaterial was carried out, and they were screened for several biomedical applications. The Rocephin-GO-AgNPs exhibit the highest activity as compared with their counterparts.
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Grafite , Nanopartículas Metálicas , Nanocompostos , Prata , Grafite/química , Prata/química , Prata/farmacologia , Nanocompostos/química , Animais , Nanopartículas Metálicas/química , Humanos , Artemia/efeitos dos fármacos , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Antioxidantes/farmacologia , Antioxidantes/química , Antibacterianos/farmacologia , Microscopia Eletrônica de Varredura , Musa/química , Anti-Infecciosos/farmacologiaRESUMO
Mycotoxins are toxic mycological products that when consumed, absorbed or inhaled cause sickness or even the death of humans. Therefore, the present study aimed to evaluate the contamination levels of mycotoxins (aflatoxins, AFB1 , AFB2 , AFG1 , AFG2 , and ochratoxin A, OTA) in selected medicinal herbs and shrubs using thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC). A total of 15 samples of medicinal herbs and shrubs were selected. Among them, four samples were aflatoxin contaminated while two samples were ochratoxin A contaminated. The highest level of aflatoxin was detected in Justicia adhathoda (4,704.94 ppb) through HPLC (153.4 ppb) and through TLC, while the lowest level of aflatoxin was detected in Pegnum harmala (205.1 ppb) through HPLC. Similarly, the highest level of OTA was detected in Dodonia viscosa (0.53 ppb) through HPLC (0.5 ppb) and through TLC, while the lowest level was detected in J. adhathoda (O.11 ppb) through HPLC (0.4 ppb) and through TLC. The OTA concentration was very low, being negligible and below permissible limits. The present study concludes that there is a potential risk for the consumption of herbal decoctions. Therefore, regular monitoring and proper management of mycotoxins, including aflatoxins and OTA, in herbal medicines are needed to ensure the safety of herbal drugs to protect consumers.
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Aflatoxinas , Micotoxinas , Plantas Medicinais , Humanos , Micotoxinas/análise , Aflatoxinas/análise , Cromatografia em Camada Fina , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Alimentos/análiseRESUMO
BACKGROUND: The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae) is an economically important polyphagous, quarantine pest endemic to South and South-East Asia. The male annihilation technique (MAT) and the sterile insect technique (SIT) are environmentally benign techniques used to suppress fruit fly populations on an area-wide basis. The MAT and SIT are typically used sequentially to avoid killing released sterile males; however, MAT and SIT potentially could be used simultaneously and thereby increase the overall efficiency of control programmes. Mating competitiveness of sterile males against wild counterparts is critical for the success of the SIT. Feeding on a semiochemical, methyl eugenol (ME) has been reported to enhance the male mating performance of many Bactrocera spp., including B. zonata, but its use in SIT operational programmes is limited owing to the absence of a viable delivery system. RESULTS: In the present study, we demonstrated that ME aromatherapy, a practical method for large-scale delivery of ME olfactorily, enhances the mating success of treated B. zonata males. ME aromatherapy application to 5-day-old immature males for a duration of 5 h resulted in increased mating success of males tested when sexually mature, compared to untreated males. The ME-aromatized males also exhibited reduced attraction to ME-lure. CONCLUSION: A practical delivery system for applying ME by aromatherapy to mass-reared males was developed. ME-aromatherapy enhanced male mating success and suppressed their subsequent attraction to ME, thus enabling the application of MAT and SIT at the same time. © 2023 Society of Chemical Industry.
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Aromaterapia , Tephritidae , Animais , Masculino , Comportamento Sexual Animal , Drosophila , EugenolRESUMO
OBJECTIVE: Berberis lycium is an indigenous plant of Pakistan that is known for its medicinal properties. In the current study, we investigated the anti-Alzheimer's effect of berberine isolated from Berberis lycium. METHODS: Root extract of B. lycium was subjected to acetylcholinesterase inhibition assay and column chromatography for bioassays guided isolation of a compound. The neuroprotective and memory improving effects of isolated compound were evaluated by aluminium chloride induced Alzheimer's disease rat model, elevated plus maze (EPM) and Morris water maze (MWM) tests., Levels of dopamine and serotonin in rats brains were determined using HPLC. Moreover, western blot and docking were performed to determine interaction between berberine and ß-secretase. RESULTS: During fractionation, ethyl acetate and methanol (3:7) fraction was collected from solvent mixture of ethyl acetate and methanol. This fraction showed the highest anti-acetylcholinesterase activity and was alkaloid positive. The results of TLC and HPLC analysis indicated the presence of the isolated compound as berberine. Additionally, the confirmation of isolated compound as berberine was carried out using FTIR and NMR analysis. In vivo EPM and MWM tests showed improved memory patterns after berberine treatment in Alzheimer's disease model. The levels of dopamine, serotonin and activity of antioxidant enzymes were significantly (p<0.05) enhanced in brain tissue homogenates of berberine treated group. This was supported by decreased expression of ß-secretase in berberine treated rat brain homogenates and good binding affinity of berberine with ß-secretase in docking studies. Binding energies for interaction of ß-secretase with berberine and drug Rivastigmine is -7.0 kcal/mol and -5.8 kcal/mol respectively representing the strong interactions. The results of docked complex of secretase with berberine and Rivastigmine was carried out using Gromacs which showed significant stability of complex in terms of RMSD and radius of gyration. Overall, the study presents berberine as a potential drug against Alzheimer's disease by providing evidence of its effects in improving memory, neurotransmitter levels and reducing ß-secretase expression in the Alzheimer's disease model.
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Doença de Alzheimer , Berberina , Berberis , Lycium , Fármacos Neuroprotetores , Ratos , Animais , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Berberina/farmacologia , Berberina/uso terapêutico , Berberis/química , Berberis/metabolismo , Cloreto de Alumínio , Lycium/metabolismo , Simulação de Acoplamento Molecular , Rivastigmina/farmacologia , Rivastigmina/uso terapêutico , Acetilcolinesterase/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Dopamina , Metanol , Serotonina/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Introduction: Natural antioxidants are vital to promote health and treat critical disease conditions in the modern healthcare system. This work adds to the index of natural medicines by exploring the antioxidant potential of Dodonaea viscosa Jacq. (Plant-DV). Material and Methods: The aqueous extract of leaves and flower-containing seeds from plant-DV in freshly prepared phosphate buffer is evaluated for antioxidant potential. In vitro antioxidant potential of the nascent and oxidatively stressed extracts was analyzed through glutathione (GSH) assay, hydrogen peroxide (H2O2) scavenging effect, glutathione-S-transferase (GST) assay, and catalase (CAT) activity. In vivo therapeutic assessment is performed in Wistar Albino rats using vitamin C as a positive control. The livers and kidneys of individual animals are probed for glutathione, glutathione-S-transferase, and catalase activities. Results: flower-containing seeds have GSH contents (59.61 µM) and leaves (32.87 µM) in the fresh aqueous extracts. The hydrogen peroxide scavenging effect of leaves is superior to flower-containing seeds with 17.25% and 14.18% respectively after 30 min incubation. However, oxidatively stressed extracts with Ag(I) and Hg(II) show declining GSH and GST levels. The plant extracts are non-toxic in rats at 5000 mg/Kg body weight. Liver and kidneys homogenate reveal an increase in GSH, GST, and CAT levels after treatment with 150 ± 2 mg/kg and 300 ± 2 mg/kg body weight plant extract compared with normal saline-treated negative and vitamin C treated positive control. Discussion: The crude aqueous extracts of leaves and flower-containing seeds of plant-DV show promising antioxidant potential both in in vitro and in vivo evaluation.
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(1) Background: A possible solution to antimicrobial resistance (AMR) is synergism with plants like Artemisia brevifolia Wall. ex DC. (2) Methods: Phytochemical quantification of extracts (n-hexane (NH), ethyl acetate (EA), methanol (M), and aqueous (Aq)) was performed using RP-HPLC and chromogenic assays. Extracts were screened against resistant clinical isolates via disc diffusion, broth dilution, the checkerboard method, time-kill, and protein quantification assays. (3) Results: M extract had the maximum phenolic (15.98 ± 0.1 µg GAE/mgE) and flavonoid contents (9.93 ± 0.5 µg QE/mgE). RP-HPLC displayed the maximum polyphenols in the M extract. Secondary metabolite determination showed M extract to have the highest glycosides, alkaloids, and tannins. Preliminary resistance profiling indicated that selected isolates were resistant to cefixime (MIC 20-40 µg/mL). Extracts showed moderate antibacterial activity (MIC 60-100 µg/mL). The checkerboard method revealed a total synergy between EA extract and cefixime with 10-fold reductions in cefixime dose against resistant P. aeruginosa and MRSA. Moreover, A. brevifolia extracts potentiated the antibacterial effect of cefixime after 6 and 9 h. The synergistic combination was non- to slightly hemolytic and could inhibit bacterial protein in addition to cefixime disrupting the cell wall, thus making it difficult for bacteria to survive. (4) Conclusion: A. brevifolia in combination with cefixime has the potential to inhibit AMR.
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The bird cherry-oat aphid, Rhopalosiphum padi (L.) (Hemiptera: Aphididae) is one of the most economically important pests of wheat crops worldwide. Thiamethoxam, bifenthrin, and flonicamid are extensively used insecticides for controlling this key pest. However, the indiscriminate use of chemical insecticides has led to the development of resistance in insects. In this study, we assessed the development of selection-induced resistance to bifenthrin, flonicamid, and thiamethoxam under controlled laboratory conditions. Additionally, we employed the age-stage, two-sex life table method to examine the fitness of R. padi. After ten generations of selection, bifenthrin-, flonicamid-, and thiamethoxam-resistant strains of R. padi were developed with resistance levels of 34.46, 31.97, and 26.46-fold, respectively. The life table analysis revealed a significant decrease in adult longevity and fecundity in these resistant strains compared to susceptible strain. Furthermore, the key demographic parameters such as net reproductive rate (R0) and reproductive days exhibited a significant reduction in all resistant strains, while the intrinsic rate of increase (r) and finite rate of increase (λ) were decreased only in resistant strains to bifenthrin and thiamethoxam. Taken together, these findings provide a comprehensive understanding of laboratory-induced insecticide resistance evolution and the associated fitness costs in R. padi. This knowledge could help to design resistance management strategies against this particular pest of wheat.
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BACKGROUND: CoFe2O4 are important magnetic NPs with high coercivity and moderate magnetization. These properties of CoFe2O4 NPs show variation when doped with various metals. Recent studies explained that Cobalt ferrites doped with metal ion like Mn+2, have attracted increasing attention in many applications, particularly in biomedical applications. A relatively simple way is employing plants and their extracts as precursors instead of toxic chemicals to produce NPs with desirable characteristic. In current study we report green synthesis and characterization of magnetic (CoFe2O4, MnCoFe2O4, CoFe2O4@S.C, MnCoFe2O4@S.C) nanoparticles using ethanolic extract of Swertia Chirata. To enhance application as biocompatible magnetic nano drug delivery vector and cell targeting efficacy of drugs, Glimepiride (GLM), Dexamethasone (DXM), Fexofenadine (FEX) and Levofloxacin (LVX) 1were loaded on synthesized NPs. Synthesized CFNPs has been broadly characterized and applied for in vitro anticancer, antidiabetic and antibacterial potential. METHODS: For synthesis of CoFe2O4 (CF), CoMnFe2O4 (CFM), CoFe2O4@S.C (SCF) & CoMnFe2O4 @S.C (SCFM), stochiometric amounts 5 mmol of CoCl2·6 H2O (0.284 g) and 10 mmol FeCl3·6 H2O (0.378 g) were dissolved in 13 mL of deionized water. To this sodium acetate (3.05 g) and urea (0.6 g) were added until complete dissolution. Afterward n-heptane was added, and contents were then transferred to Teflon lining autoclave at 180 °C for 4 h. Black powder CoFe2O4 NPs after washing, were dried and calcined at 450 oC for 2 h. RESULTS: XRD diffractogram of CF have proved the single-phase cubic spinel structure formation for all samples. Swertia Chirata formulations were shown to have effective in vitro antidiabetic activity. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. SCF showed that the value slightly higher than 16 µg/mL compared to standard. Drug loaded CFNPs (L-CFNPs, F-CFNPs, D-CFNPs & G-CFNPs) also effectively inhibited α-glucosidase. IC50 value for CFNPs inhibition of α-glucosidase was 12.4 µg/mL. All synthesized CF NPs showed cytotoxic potential against breast cancer cells MCF-7. About 50-60% cell viability and cytotoxicity 40% were observed for bare CFNPs as compare to Doxorubicin with related toxicity 80% and 20% cell viability. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain. CFM, SCF, SCFM were active against S. aureus at concentration 100 µg/mL, 100 µg/mL, and 50 µg/mL respectively. CONCLUSION: The synthesized CF NPs showed significant cytotoxic potential against MCF-7 breast cancer cell line. Further, drug loaded samples displayed lesser cell viability and slightly increased cytotoxicity in range of 40-50% in comparison with bare CFNPs. However, higher toxicity was observed for CFMGS towards MCF-7 cells with results nearly equal to Doxorubicin with significant decrease in viability. CF, CFM & SCFM showed good inhibition of α-glucosidase with very low concentration 6 µg/mL, 5 µg/mL and 4 µg/mL as compare to 12.41 µg/mL of acarbose. Among synthesized samples almost all samples without conjugation of any drug showed activities against at least one bacterial strain.
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Antineoplásicos , Neoplasias da Mama , Nanopartículas , Humanos , Feminino , Hipoglicemiantes , Acarbose , Staphylococcus aureus , alfa-Glucosidases , Nanopartículas/química , Cobalto/química , Antibacterianos/farmacologia , Antibacterianos/química , Metais , Antineoplásicos/farmacologia , Antineoplásicos/química , DoxorrubicinaRESUMO
OBJECTIVE: The main objective of this study was to develop a highly sensitive, accurate, and reproducible analytical method for the simultaneous detection of LEF and FA in polymeric nanocarriers. SIGNIFICANCE: Leflunomide (LEF), is widely employed in the treatment of rheumatoid arthritis (RA). However, long-term delivery of the drug is associated with systemic side effects. Therefore, folate (FA) conjugated LEF nanocarriers were fabricated for targeting the nanocarriers toward activated macrophages. HPLC is considered one of the most sensitive and precise analytical techniques for the simultaneous detection and estimation of different components in a particular sample. METHODS: Analysis was performed on HPLC (Shimadzu 10 A), having a reversed-phase C-18 column (Beckmen, 250 X 4.6 mm, 5 µm) equipped with a photodiode detector set at a wavelength of 260 nm (LEF) and 285 nm (Folic acid). The isocratic mobile phase was composed of acetonitrile, water, and trimethylamine in a ratio of 65:35:0.5 at pH 4. Rapid analysis of both agents was performed, with a total run time of 10 min (FA = 2.1 ± 0.1 min, LEF = 5.9 ± 1 min) at a 1 mL/min flow rate. RESULTS: The assay demonstrated good linearity of 0.9989 of 0.9997 for LEF and FA respectively with a recovery in the range of 95-100%. The method also depicted good specificity, and intra and inter-day precision based on relative standard deviation (RSD) values. CONCLUSIONS: The study concludes, that the developed method was helpful in the detection and quantitation of lower values of both agents from polymeric nanocarriers.
HighlightsOptimization and validation of the RP-HPLC method were performed for the simultaneous detection of LEF and FA.Validation was performed on the basis of linearity, accuracy, precision, LOD, LOQ, and robustness in accordance with ICH criteria.Validated analytical procedure was employed for the simultaneous detection of LEF and FA from polymeric nanocarriers.The proposed analytical method is reliable, fast, robust, and can be successfully applied for quantification of % EE, and % DL in polymeric nanocarriers.
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Ácido Fólico , Polímeros , Leflunomida , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Preparações FarmacêuticasRESUMO
Materials and Methods: The extract library (n-hexane (NH), ethyl acetate (EA), methanol (M), distilled water (DW), and combined extract (CE)) was standardized using in vitro phytochemical, antioxidant, and α-amylase inhibition assays, after which the protective effect of selected "hit," i.e., CE against metabolic syndrome, was determined in vivo, using rats fed a high-fat diet supplemented with additional cholesterol administration. CE was administered to Sprague Dawley rats in high dose as 100 mg/kg in carboxymethyl cellulose (CMC) (1 ml; 0.75% in DW) and low-dose group as 50 mg/kg in CMC (0.5 ml; 0.75% in DW). After 10 weeks, the effects of CE on insulin resistance, lipid metabolism, nonalcoholic fatty liver disease (NAFLD), oxidative stress, and genotoxicity were assessed through histological, biochemical, and hematological investigations. Results: Phytochemical analysis including RP-HPLC analysis of the extracts showed that flavonoids and phenolics (myricetin, kaempferol, and apigenin), previously known to be effective against obesity and diabetes, are present in the extracts. Antioxidant studies revealed that the plant possesses a highly significant (p < 0.05) concentration of antioxidants. Satisfactory α-amylase inhibitory activity was also observed in in vitro experiments. In vivo studies showed that CE-administered animals had significantly (p < 0.05) lower weight gain and smaller adipocytes than the control group. Moreover, CE resisted any significant (p < 0.05) change in the organ weights. Analogous to findings from its traditional use, the plant extract had a positive modulatory effect on insulin resistance and hyperglycemia. The study also indicated that CE resisted high-fat diet-induced disturbance in lipid profile and countered any pathological changes in liver enzymes caused by fat-infused diet. Furthermore, a study on endogenous antioxidant levels indicated that CE was effective in maintaining catalase and peroxidase levels within the normal range and resisted the effects of lipid peroxidation of thiobarbituric acid reactive substances. Conclusion: In principle, the current study's findings scientifically validate the implication of T. linearis in metabolic syndrome and recommend further studies on molecular insights of the observed therapeutic activity.
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Resistência à Insulina , Síndrome Metabólica , Ratos , Animais , Antioxidantes/metabolismo , Ratos Sprague-Dawley , Síndrome Metabólica/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/química , Estresse Oxidativo , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Compostos Fitoquímicos/metabolismo , alfa-Amilases/metabolismo , Fígado/metabolismoRESUMO
Multidrug resistance and infectious disease have enormous spread despite drug discovery and development advancements. 1, 2, 4 -triazoles have been extensively studied, playing an imperative role in many pathologic conditions. A series of Schiff base triazoles; derived from Indole -3- acetic acid with substituted Benzaldehydes (5a-5g) were designed, synthesized, and evaluated through various Spectroanalytical techniques. SwissADME was used to assess physicochemical properties and pharmacokinetic drug-likeliness behavior. (5a-5g) were evaluated for their varied biological potential through antioxidant, antimicrobial, enzyme inhibition, and cytotoxic evaluation. Schiff bases express drug-like nature as they follow Lipinski's rule of five. 5b showed good antioxidant potential in total antioxidant capacity (TAC) and total reducing power (TRP) assays and was most active in the library in % free radical scavenging assay (%FRSA), showing 32% inhibition at 50 µg/mL concentration. Compounds showed antibacterial activity against various tested strains. 5e and 5f showed a minimum inhibitory concentration (MIC) value of 3.12 µg/mL for P.aeruginosa and K.pneumoniae, respectively. In the antifungal assay, only 5e inhibited one strain with a zone of inhibition >6 mm. These synthetic molecules possess good cytotoxic potential in the Brine Shrimp Lethality screening; 5c, 5d, and 5f exhibited LC50 =5.7 µg/mL. In the protein kinase inhibition assay, 5a, 5b, and 5g demonstrated inhibitory potential, showcasing the zone of inhibition as 7.5-10.5 mm for the bald one and 6-7.5 for the clear zone. These findings suggest that the compounds have antibacterial and cytotoxic potential, and there is a chance for further research and development in this area.
RESUMO
Living donor liver transplant in addition to its lifesaving therapy is a cost-effective alternate to long-term disease management in patients with chronic liver disease. Financial constraint is the biggest hurdle faced by patients in developing countries in availing the liver transplantation. So, we conducted this study to report a government-funded financial support system for liver transplant services. A total of 198 patients who underwent living donor liver transplant with at least 90 days follow-up were included in the study. According to proxy means test score, 52.2% patients were from low and middle socioeconomic groups and 64.6% of patients underwent liver transplantation through government support. Out of 198 patients who underwent liver transplantation 29.6% had monthly income below 25,000 Pakistani rupees ($114). In recipients, 90-day mortality was 7.1% and morbidity was 67.1%. Donor morbidity was 23.2% without any mortality. This financial model can serve as a valuable source for middle and low income group countries to overcome the financial challenge and make liver transplant an accessible, affordable, and economically viable option.
Assuntos
Hepatopatias , Transplante de Fígado , Humanos , Doadores Vivos , Apoio Financeiro , RendaRESUMO
Diabetic neuropathic pain is one of the microvascular complications of diabetes mellitus characterized by symmetrical pain and sensory abnormalities. A steroidal lactone isolated from the datura innoxa plant, withametelin (WMT), exhibited significant neuroprotective, anti-inflammatory, antioxidant, and anticancer properties. The current study aimed to investigate anti-neuropathic pain activity and the molecular mechanism of WMT against streptozotocin (STZ)-induced diabetic neuropathy. Rats were given a single injection of STZ (60 mg/kg, intraperitoneally (i.p.)) for induction of diabetes on the first day of the study. After the onset of diabetic neuropathy, pregabalin (10 mg/kg, i.p.) and WMT (0.1 and 1 mg/kg, i.p.) treatments were started from day 14 up to day 42. It was found that STZ-induced neuropathic pain behaviors were markedly reduced by WMT. It inhibited the STZ-associated histopathological changes and genotoxicity in the sciatic nerve and spinal cord. Additionally, Fourier transforms infrared (FTIR) spectroscopy results revealed that STZ-induced alterations in the biochemical components of the sciatic nerve's myelin sheath were inhibited by WMT. In the spinal cord, it markedly reduced the immunoreactivity of mitogen-activated protein kinases (MAPKs) signaling components such as p38-MAPK, c-Jun N-terminal kinase (JNK), extracellular-signal-regulated-kinase (ERK), and activator-protein 1 (AP-1). It also reduced the expression levels of nuclear factor-kappa-B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). The production of inflammatory cytokines was considerably reduced by WMT. This study provides convincing evidence that WMT treatment attenuated STZ-induced diabetic neuropathic pain by inhibition of MAPK/NF-κB signaling.
Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Neuralgia , Animais , Ratos , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Neuropatias Diabéticas/complicações , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Lactonas , Lipopolissacarídeos , Neuralgia/tratamento farmacológico , Neuralgia/complicações , Neuralgia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , EstreptozocinaRESUMO
Multiple sclerosis (MS) is a debilitating neurodegenerative autoimmune disease of the central nervous system (CNS). The current study aimed to investigate the neuroprotective properties of Ajugarin-I (Aju-I) against the experimental autoimmune encephalomyelitis (EAE) model of MS and explored the underlying mechanism involved. The protective potential of Aju-I was first confirmed against glutamate-induced HT22 cells and hydrogen peroxide (H2 O2 )-induced BV2 cells. Next, an EAE model has been established to investigate the mechanisms of MS and identify potential candidates for MS treatment. The behavioral results demonstrated that Aju-I post-immunization treatment markedly reduced the EAE-associated clinical score, motor impairment, and neuropathic pain. Evans blue and fluorescein isothiocyanate extravasation in the brain were markedly reduced by Aju-I. It effectively restored the EAE-associated histopathological changes in the brain and spinal cord. It markedly attenuated EAE-induced inflammation in the CNS by reducing the expression levels of p-38/JNK/NF-κB but increased the expression of IkB-α. It suppressed oxidative stress by increasing the expression of Nrf2 but decreasing the expression of keap-1. It suppressed EAE-induced apoptosis in the CNS by regulating Bax/Bcl-2 and Caspase-3 expression. Taken together, this study suggests that Aju-I treatment exhibits neuroprotective properties in the EAE model of MS via regulation of MAPK/NF-κB, Nrf2/Keap-1, and Bcl2/Bax signaling.