Concentration-dependent Activity Research Articles

Exploring the In Vitro Antidiabetic Potential of Metal Oxide Nanoparticles Synthesized Using Lemongrass and Mint Formulation.

Aim This study aimed to compare the antidiabetic effect of metal oxide nanoparticles (CuONPs and ZnONPs)prepared using lemongrass and mint herbal formulations. Introduction The study explores green-synthesized nanoparticles for potential applications in diabetes management, emphasizing sustainable synthesis methods, particularly zinc oxide nanoparticles (ZnONPs) and copper oxide nanoparticles (CuONPs) produced from lemongrass and mint herbal formulations. The study was prompted by the increasing importance of innovative therapeutic strategies, responding to emerging health challenges, and leveraging advancements in nanotechnology and eco-friendly practices to explore the potential of green-synthesized nanoparticles in diabetes management. Methods The methods involve herbal formulation preparation, CuONPs and ZnONPs synthesis, and UV-visible spectrophotometry for characterization. In vitro antidiabetic activity is assessed through α-amylase and β-glucosidase enzyme assays using varied nanoparticle concentrations (10-50 µL). Results Visual observations confirm successful synthesis, with distinct color changes observed in both CuONPs and ZnONPs after 24 hours. UV-visible spectrophotometry reveals absorption peaks at 440 nm and 380 nm for CuONPs and ZnONPs, respectively. In the α-amylase assay, both nanoparticles exhibit concentration-dependent inhibition, with CuONPs ranging from 40% to 77% and ZnONPs ranging from 36% to 80%. The β-glucosidase assay demonstrates similar concentration-dependent inhibition patterns, highlighting significant differences. Conclusion The study concludes that CuONPs and ZnONPs synthesis using lemongrass and mint herbal formulations show concentration-dependent antidiabetic activity. The comparative analysis underscores the need for tailored approaches based on nanoparticle composition. These findings contribute valuable insights into the therapeutic potential of green-synthesized nanoparticles, paving the way for future nanomedicine research and development in diabetes management.

Structural Characterization and Antioxidant Activity of β-Glucans from Highland Barley Obtained with Ultrasonic-Microwave-Assisted Extraction.

In order to efficiently extract β-glucan from highland barley (HBG) and study its structural characterization and antioxidant activity, ultrasonic-microwave-assisted extraction (UME) was optimized by the response surface method (RSM). Under the optimal extraction conditions of 25.05 mL/g liquid-solid ratio, 20 min ultrasonic time, and 480 W microwave intensity, the DPPH radical scavenging activity of HBG reached 25.67%. Two polysaccharide fractions were purified from HBG, namely HBG-1 and HBG-2. Structural characterization indicated that HBG-1 and HBG-2 had similar functional groups, glycosidic linkages, and linear and complex chain conformation. HBG-1 was mainly composed of glucose (98.97%), while HBG-2 primarily consisted of arabinose (38.23%), galactose (22.01%), and xylose (31.60%). The molecular weight of HBG-1 was much smaller than that of HBG-2. Both HBG-1 and HBG-2 exhibited concentration-dependent antioxidant activity, and HBG-1 was more active. This study provided insights into the efficient extraction of HBG and further investigated the structure and antioxidant activities of purified components HBG-1 and HBG-2. Meanwhile, the results of this study imply that HBG has the potential to be an antioxidant in foods and cosmetics.

Discovery of Melittin as Triple-Action Agent: Broad-Spectrum Antibacterial, Anti-Biofilm, and Potential Anti-Quorum Sensing Activities.

The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats

BackgroundPolycystic ovarian syndrome (PCOS) is one of the known causes of anovulatory fertility in the world. Previous research has linked oxidative stress could contribute to PCOS, and vanillic acid has shown antioxidant potential. Hence, the present study evaluated the effect of vanillic acid on letrozole-induced polycystic ovarian syndrome in female rats. Materials and methodsPCOS was induced in Wistar female rats with letrozole (1 mg/kg, orally) in carboxymethoxycellulose (1 % w/v), administered for 21 days. After induction, the standard group received clomiphene citrate (1 mg/kg, orally) while other treatment groups were administered with vanillic acid at doses 25, 50, and 100 mg/kg, orally for 15 days, and without treatment was considered a negative control group. Different parameters studied were body weight, ovary weight, blood glucose, lipid profile, hormonal levels [luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone], markers for oxidative stress (superoxide dismutase, reduced glutathione, catalase, and malonaldehyde), and histopathology of the ovary. Statistical analysis was done for the results and p < 0.05 was considered to indicate the significance. ResultsVanillic acid-treated animals showed a concentration-dependent activity on the tested parameters. The highest tested dose (100 mg/kg) produced a more prominent effect in significantly (P < 0.001) decreasing the body weight, and ovary weight and improving the hormonal imbalance. Also, vanillic acid significantly (P < 0.01) reduced elevated blood sugar and lipid levels. Additionally, vanillic acid reduced oxidative stress significantly (P < 0.001) in the ovaries of female rats. Histopathological reports showed a reduction in cystic follicles and appearance of normal healthy follicles at different stages of development after the administration of vanillic acid. Furthermore, these effects were observed to be comparable with those recorded for standard drug, clomiphene. ConclusionThe current study data suggests that vanillic acid has protected the letrozole-induced polycystic ovarian syndrome. In the event of several side effects associated with conventional treatments used for PCOS, the findings of this study suggest the promising role of vanillic acid. More research in this direction might identify the true potency of vanillic acid in the treatment of PCOS.

Antioxidant and acetylcholinesterase inhibitory activities, in silico analyses, and anti-Alzheimer’s disease potential of leaf extracts of three Nigerian endemic medicinal plants (Spondias mombin, Carica papaya and Kalanchoe crenata)

BackgroundThe evaluation of the correlations between antioxidant and anti-acetylcholinesterase activities of methanol leaf extracts of three Nigerian endemic plants, Spondias mombin, Carica papaya and Kalanchoe crenata, was carried out. Their constituent phytochemicals were identified by HPLC–DAD fingerprinting. The antioxidant activity as typified by 2,2-diphenyl-1-picrylhydrazyl (DPPH·), 2,2′-azino-bis-(3-ethylbenthiazoline-6-sulfonic acid (ABTS·+) and nitric oxide (NO) scavenging activities were evaluated. The acetylcholinesterase (AChE) inhibitory activity of the extracts was also determined.ResultsThe extracts contained appreciable amounts of the flavonoids, quercetin and kaempferol. The extracts of Spondias mombin, Carica papaya and Kalanchoe crenata showed concentration-dependent inhibitory activities against DPPH· and ABTS·+ with IC50 of 43.29 ± 0.443 µg/mL, 59.27 ± 0.644 µg/mL and 80.20 ± 0.414 µg/mL; 25.43 ± 0.325 (µg/mL), 39.84 ± 0.163 µg/mL and 59.02 ± 0.376 (µg/mL), respectively. The IC50 for the NO scavenging activities of the Spondias mombin, Carica papaya and Kalanchoe crenata extracts were 41.99 ± 0.217 µg/mL, 50.44 ± 0.281 µg/mL and 60.12 ± 0.512 µg/mL, respectively. The IC50 for the inhibitory effects on AChE was 53.24 ± 0.327 µg/mL, 60.95 ± 0.290 µg/m and 70.5 ± 0.426 µg/mL, respectively. The effectiveness of the plant in all the experimental tests was in the following order: S. mombin > C. papaya > K. crenata. The total flavonoid and total phenolic contents have extremely significant positive correlations with the antioxidant activities and AChE inhibitory activity. The correlation coefficients (r2) of DPPH scavenging activity and NO scavenging activity with the AChE inhibitory activity were 0.8295 µg/mL and 0.7337 µg/mL, respectively (P < 0.0001). The molecular docking and pharmacokinetic analyses on some constituent phytochemicals showed that quercetin, kaempferol, ferulic acid, leucocyanidin, gallic acid and isorhamnetin fulfilled the requirements for an anti-Alzheimer drug.ConclusionsThe results suggest that the plant species provide a significant source of secondary metabolites that can act as natural antioxidants and acetylcholinesterase inhibitors, which will be helpful in the treatment of Alzheimer’s disease.

The anti-cancer potential of active compounds extracted from Millettia griffoniana on pancreatic and colorectal cancer cells

Pancreatic and colorectal cancer are two of the most lethal cancers; this stems from poor prognosis. Current treatments may lack effectiveness and produce dangerous side effects, hence a need for alternatives. Medicinal plants like Millettia griffoniana may possess anti-cancer properties. This study aimed to isolate and identify compounds from M. griffoniana to test for potential anti-cancer activity on pancreatic and colorectal cancer. Seeds and root bark of M. griffoniana underwent solvent extraction and separation using column chromatography. Isolated compounds were screened using AlamarBlue assays and cytotoxic compounds were identified with 2D NMR. Compounds were subject to cellular viability assays using AlamarBlue and xCELLigence analysis. The Caspase Glo®-3/7 kit measured caspase activity and Real-Time PCR analysis measured apoptosis-related gene expression. 7 compounds were isolated and screened. Compounds 5 and 7 were chosen; identified as durmillone and isojamaicin. Both showed varying concentration-dependent cytotoxic activity, in AlamarBlue and xCELLigence assays, for both cell lines. Caspases 3 and 7 were up-regulated and both compounds up-regulated BAX and down-regulated BCL-2 and p53 in both cell lines. Durmillone and isojamaicin displayed cytotoxic activity on pancreatic and colorectal cancer. Apoptotic activity induced by the compounds was verified by the up-regulation of caspase activity and BAX and down-regulation of BCL-2 and p53. Further studies need to be done towards understanding the mechanisms by which these compounds bring about their cytotoxic activity.

Antifungal effect of Aloe barbadensis Miller gel extract on Candida albicans: Development of an eco-friendly herbal antifungal finish on cotton fabric for medical application

The application of natural antimicrobial agents has garnered significant interest within the healthcare and medical textile industries because they are functionally active textiles that can inhibit the excessive proliferation of microorganisms. The present study aimed to evaluate the antifungal properties of Aloe barbadensis Miller ethanol extract to develop an eco-friendly A. barbadensis Miller ethanolic gel treated cotton fabric against vulvovaginal candidiasis caused by Candida albicans. The antifungal activity of A. barbadensis Miller ethanol extract against C. albicans was evaluated by the well diffusion method, and the highest concentration (5 mg/ml) showed a maximum mean zone diameter of 24.00 ± 1.00 mm. Moreover, the minimum inhibitory concentration was recorded as 3.12 mg/ml by the broth macrodilution method. The cotton fabric (100% cotton) was treated with 4 mg/ml of A. barbadensis Miller ethanol extract using the pad-dry-cure method. The treated fabric exhibited a clear zone of inhibition against C. albicans using the agar diffusion method. The wash durability test showed that treated cotton fabric retained antifungal activity up to 15 washing cycles with a fungal growth reduction rate of 15%. In conclusion, A. barbadensis Miller ethanol extract showed concentration dependent inhibitory activity on C. albicans; furthermore, treated fabric also exhibited effective antifungal activity against vulvovaginal candidiasis caused by C. albicans in vitro.

Investigation of bioactive components responsible for the antibacterial and anti-biofilm activities of Caroxylon volkensii by LC-QTOF-MS/MS analysis and molecular docking.

Caroxylon volkensii is a wild desert plant of the family Amaranthaceae. This study represents the first report of the metabolomic profiling of C. volkensii by liquid chromatography quadrupole-time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The dereplication study of its secondary metabolites led to the characterization of 66 known compounds. These compounds include catecholamines, tyramine derivatives, phenolic acids, triterpenoids, flavonoids, and others. A new tyramine derivative, alongside other known compounds, was reported for the first time in the Amaranthaceae family. The new derivative and the first-reported compounds were putatively identified through MS/MS fragmentation data. Given the notorious taxonomical challenges within the genus Salsola, to which C. volkensii previously belonged, our study could offer a valuable insight into its chemical fingerprint and phylogenetic relationship to different Salsola species. The antibacterial potential of C. volkensii methanolic extract (CVM) against Pseudomonas aeruginosa was screened. The minimum inhibitory concentration (MIC) of CVM ranged from 32 to 256 μg mL-1. The anti-quorum sensing potential of CVM resulted in a decrease in the percentage of strong and moderate biofilm-forming isolates from 47.83% to 17.39%. It revealed a concentration-dependent inhibitory activity on violacein formation by Chromobacterium violaceum. Moreover, CVM exhibited an in vivo protective potential against the killing capacity of P. aeruginosa isolates. A molecular docking study revealed that the quorum-sensing inhibitory effect of CVM can be attributed to the binding of tyramine conjugates, ethyl-p-digallate, and isorhamnetin to the transcriptional global activator LasR.

Exploring marine algae-derived phycocyanin nanoparticles as a safe and effective adjuvant for sunscreen systems

BackgroundUV radiation (UV) exposure risks skin damage and cancer due to DNA damage and oxidative stress. Synthetic chemical sunscreens that protect against UV radiation can have health and environmental concerns. This study explores phycocyanin (PC), a marine algae-derived natural photoprotective compound, and its crosslinked nanoparticles (PCNP) as safe and effective adjuvants for sunscreen systems.MethodsPCNP was synthesized via genipin-crosslinking. PC and PCNP biocompatibility were assessed on mouse embryonic fibroblast cells. ABTS evaluated antioxidant activity, and the UV absorption capacity of PC and PCNP were analyzed. PCNP skin permeability was tested in vitro and in vivo. Gel formulations with PCNP were examined for UV absorption effects.ResultsPCNP showed good biocompatibility, maintaining cell viability above 90% across concentrations. Both PC and PCNP demonstrated concentration-dependent antioxidant activity, efficiently scavenging free radicals. PCNP exhibited enhanced UV absorption in the UVB range compared to PC alone. Skin permeation studies displayed limited PCNP penetration through skin layers. In vivo, absorption assessments indicated PCNP localized mainly in the stratum corneum. PCNP-containing gels displayed improved UV absorption compared to gels without PCNP.ConclusionThis study showcases PCNP’s potential as a natural and safe adjuvant for sunscreen with enhanced UV protection capabilities. PCNP preserved antioxidant activity, displayed limited skin penetration, and enhanced UV absorption. The findings suggest PCNP’s promise as a viable alternative to synthetic sunscreen agents, delivering effective photoprotection while minimizing health and environmental concerns.

&lt;i&gt;Nocardiopsis synnemataformans&lt;/i&gt; NBRM9, an extremophilic actinomycete producing extremozyme cellulase, using lignocellulosic agro-wastes and its biotechnological applications

&lt;abstract&gt; &lt;p&gt;Actinomycetes are an attractive source of lignocellulose-degrading enzymes. The search for actinomycetes producing extremozyme cellulase using cheap lignocellulosic waste remains a priority goal of enzyme research. In this context, the extremophilic actinomycete NBRM9 showed promising cellulolytic activity in solid and liquid assays. This actinomycete was identified as &lt;italic&gt;Nocardiopsis synnemataformans&lt;/italic&gt; based on its phenotypic characteristics alongside phylogenetic analyses of 16S rRNA gene sequencing (OQ380604.1). Using bean straw as the best agro-waste, the production of cellulase from this strain was statistically optimized using a response surface methodology, with the maximum activity (13.20 U/mL) achieved at an incubation temperature of 40 °C, a pH of 9, an incubation time of 7 days, and a 2% substrate concentration. The partially purified cellulase (PPC) showed promising activity and stability over a wide range of temperatures (20–90 °C), pH values (3–11), and NaCl concentrations (1–19%), with optimal activity at 50 °C, pH 9.0, and 10% salinity. Under these conditions, the enzyme retained &amp;gt;95% of its activity, thus indicating its extremozyme nature. The kinetics of cellulase showed that it has a V&lt;sub&gt;max&lt;/sub&gt; of 20.19 ± 1.88 U/mL and a Km of 0.25 ± 0.07 mM. The immobilized PPC had a relative activity of 69.58 ± 0.13%. In the in vitro microtiter assay, the PPC was found to have a concentration-dependent anti-biofilm activity (up to 85.15 ± 1.60%). Additionally, the fermentative conversion of the hydrolyzed bean straw by &lt;italic&gt;Saccharomyces cerevisiae&lt;/italic&gt; (KM504287.1) amounted to 65.80 ± 0.52% of the theoretical ethanol yield. Overall, for the first time, the present work reports the production of extremozymatic (thermo, alkali-, and halo-stable) cellulase from &lt;italic&gt;N. synnemataformans&lt;/italic&gt; NBRM9. Therefore, this strain is recommended for use as a biotool in many lignocellulosic-based applications operating under harsh conditions.&lt;/p&gt; &lt;/abstract&gt;

Antioxidant and hepatoprotective effects of Solanum villosum leaf extracts against acetaminophen-induced mouse model of hepatotoxicity

Solanum villosum is an indigenous vegetable and ethno-medicine source in Africa. Scientific validation of their medicinal potential is required. The current study aimed to assess the antioxidant and hepatoprotective effects of S. villosum leaf methanol extracts (SVE) against acetaminophen-induced mouse model. The SVE antioxidant activities were evaluated by ferric reducing antioxidant capacity and hydroxyl radical scavenging activities in vitro. Hepatoprotective activities were assessed by automated hematological analysis, chemical analysis and specific biochemical assays of liver homogenates. Mice were orally administered with SVE at 30, 100, 300 and 500 mg/kg body weight. Hepatotoxicity was induced by acetaminophen 300 mg/kg bw intraperitoneally while silymarin 25 mg/kg bw orally was a positive control. The SVE exhibited a clear concentration-dependent antioxidant activity. Subsequently, SVE treatment significantly (P≤0.05) lowered granulocyte count, while there was a significant increase in lymphocyte count in acetaminophen-treated mice. Further, SVE significantly lowered the activities of alanine transaminase, aspartate transaminase, and alkaline phosphatase, but significantly increased γ-glutamyl-transferase activity in treated mice compared to the controls. However, SVE led to insignificant change in total proteins. Additionally, SVE treatment led to a significant rise in superoxide dismutase and glutathione peroxidase activities but, an insignificant change in catalase activity. In conclusion, SVE confers liver protection by oxidative stress prevention, antioxidant enzyme activation, immuno-modulation and hepatic tissue preservation. The results also support indigenous use of S. villosum to protect patients against drug-induced liver damage and enhance immunity. Further, dietary supplements of S. villosum could be an adjunct therapy in acetaminophen-induced hepatotoxicity.

An MPM-Based Phase-Field Simulation of Plating and Stripping of Lithium with a Solid Electrolyte Interphase

A methodology for performing phase-field simulations of plating and stripping in the presence of a solid electrolyte interphase (SEI) is presented and applied to a lithium metal electrode. Material point method (MPM) simulations are performed assuming a homogeneous SEI layer and are compared with experiment. Results are consistent with experiment for two electrolytes and confirm the dominance of the SEI layer in determining cell impedance. Notably, in some instances, the SEI potential drop greatly affected activation overpotential, differing from the applied potential. To accurately depict stripping current vs potential for SEI-free systems, the model considered non-ideal electrolyte effects: concentration-dependent salt activity coefficient, salt diffusion coefficient, and electrolyte conductivity. Conversely, systems with SEI layers displayed minimal non-ideal concentration-related electrolyte effects due to impedance originating primarily from the SEI. In plating scenarios, low SEI salt concentration negated the need for non-ideal SEI effects. However, for stripping, non-ideal salt-concentration dependent SEI effects were crucial in reproducing experimental behavior, owing to high salt concentration at the electrode/SEI interface.

Screening of novel carbohydrate-derived thioureas for antibacterial activity

Compounds synthesized from carbohydrate substrates have yielded promising lead molecules for pharmaceutical developments, as many are approved for the clinical management of a wide range of diseases. Among them, thiourea moieties are the gold mines of antibacterial molecules. In view of the lack and need for new antibiotics, a series of 16 D-fructose-based thiourea compounds were synthesized from asymmetric aldol reaction and isopropylidenation. The new compounds were established from nuclear magnetic resonance, Fourier-transform infrared, and electrospray ionization mass spectrometry. Using disk diffusion assay for antibiotic susceptibility, four of the novel compounds were found to have concentration-dependent antibacterial activities. The addition of trifluoromethyl groups at the meta-position on the phenyl ring of the thioureas appeared to promote bacterial inhibitory action. Thiourea 2a exhibited the most potent activity against the Gram-negative species, Klebsiella pneumoniae, Escherichia coli, and Salmonella typhi, as well as the Gram-positive species, Micrococcus luteus; but not against all bacteria tested. Thiourea 2b and 3a had lower efficacy but showed better broad-spectrum activity against most bacteria tested. Thiourea 3b displayed species-specific activity only against K. pneumoniae and S. typhi. Our findings show the benefits and prospects of synthesizing new carbohydrate compounds for therapeutic medication.

Evaluation of the Antidiabetic Activities of the Fruit of Parquetina nigrescens (Afzel.) Bullock and In Silico Identification of Its Antidiabetic Agent.

The study investigated the antidiabetic potentials of the fruit extract of Parquetina nigrescens with the aim of justifying its folkloric antidiabetic usage in some part of Nigeria. Acute toxicity test of the plant extract was assessed using Lorke's method. Its antidiabetic activities were assayed in α-amylase, α-glucosidase, glucose, and streptozotocin-induced diabetic rats' models at various doses with acarbose and glibenclamide (5 mg/kg) as positive controls. Molecular docking studies were performed to identify the antidiabetic constituent of the extract and elucidate its possible mechanism of action. The estimated median lethal dose (LD50) of the extract was above 5000 mg/kg. In the α-amylase, α-glucosidase study, the extract elicited concentration-dependent activity similar to acarbose. In the glucose-induced hyperglycaemic model, 200 mg/kg of the extract was the most effective dose with comparable (P > .05) antihyperglycaemic activity to glibenclamide (5 mg kg) at 1 to 4 h. Also in the streptozotocin-induced diabetic rats model, 100 and 200 mg/kg of the extract gave comparable (P > 0.05) activity on days 4 to 14 that were significantly better than that of glibenclamide on days 4 to 7. The n-hexane and ethylacetate fractions of the extract, both at 200 mg/kg were the most active with comparable activity to glibenclamide at all time points. The molecular docking studies identified isorhoifolin as the best binder against alpha amylase with binding energy (-9.1 kcal/mol), alpha glucosidase (-9.4 kcal/mol), sodium-glucose cotransporter-2 (-9.5 kcal/mol), peroxisome proliferator activated receptor gamma (-10.3 kcal/mol), 11β-Hydroxysteroid dehydrogenase (-10.8 kcal/mol), and dipeptidyl peptidase IV (-9.4 kcal/mol). The results of the antidiabetic study of P nigrescence fruit extract justified its usage in ethnomedicne in diabetes management.

NMDA Receptor Modulation in COVID-19-Associated Acute Respiratory Syndrome in both In Silico and In Vitro Approach.

The normal function of the N-methyl D-aspartate receptors (NMDAR) in human lungs depends on precisely regulated synaptic glutamate levels. Pathophysiology of the lungs is brought on by the changes in homeostasis of glutamate in the synapsis that leads to abnormal NMDAR activity. Severe acute respiratory syndrome (SARS) primarily results in lung infections, particularly lung muscle stiffening, and NMDA receptor potentiation may increase calcium ion influx and support downstream signaling mechanisms. Hence, NMDAR modulators that depend on glutamate levels could be therapeutically useful medications with fewer unintended side effects. A compound called THP (tetrahydropalmatine) that amplifies Ca2+ influx and potentiates NMDA receptors has been identified in the current study. In asthmatic human airway smooth muscle (HASM) cells, THP regulates the NMDA receptor and helps in asthmatic ASM contraction, and the pharmacological stimulation of ASM depends on both brain and respiratory NMDA receptors. Glutamate potency is altered by this substance without any voltage-dependent side effects. Additionally, a GGPP (geranylgeranyl pyrophosphate)-dependent mechanism of THP reduced the production of pro-inflammatory cytokines in ASM. THP is distinctive in terms of its chemical makeup, functioning, and agonist concentration-dependent and allosteric modulatory activity. To treat COVID-19-related SARS, THP, or any future-related compounds will make good drug-like molecule candidates.

Time-kill kinetics of Piper betle L. ethanolic leaf extract on methicillin-sensitive Staphylococcus aureus

Staphylococcus aureus is one of the main pathogens in community and hospital infections that could cause mild skin infections to severe life-threatening bacteremia. Piper betle has shown antibacterial activities against S. aureus but its pharmacodynamics remains unclear despite its widespread availability in many over-the-counter preparations. This study aimed to describe the time-kill kinetics of P. betle extract against methicillin-sensitive Staphylococcus aureus ATCC 29213 (MSSA). Time-kill kinetics were conducted to describe the killing rate of P. betle extract by its effects on MSSA lag time duration, growth rate, and maximum optical density. The surviving colonies at different time-points after exposure to P. betle extract at minimum bactericidal concentration were also determined. Subinhibitory concentrations elucidated its concentration-dependent antibacterial activity by maintaining a trend of increasing lag time, decreasing growth rate, and decreasing maximum optical density as the concentration increases. In particular, concentration at 1250 μg/mL or 0.5 x minimum inhibitory concentration (MIC) showed consistent significant findings across these parameters. Concentrations at MIC and above did not show growth, indicating MSSA growth inhibition or death. P. betle extract’s bactericidal effect started immediately within two (2) hours and was sustained until no growth was observed from the eighth hour and beyond. P. betle extract maintained antibacterial activities against MSSA at subinhibitory concentrations and has also exhibited immediate and sustained bactericidal effect at minimum bactericidal concentration (MBC).

A naturally occurring G11S mutation in the 3C-like protease from the SARS-CoV-2 virus dramatically weakens the dimer interface.

The 3C-like protease (3CLpro ) is crucial to the replication of SARS-CoV-2, the causative agent of COVID-19, and is the target of several successful drugs including Paxlovid and Xocova. Nevertheless, the emergence of viral resistance underlines the need for alternative drug strategies. 3CLpro only functions as a homodimer, making the protein-protein interface an attractive drug target. Dimerization is partly mediated by a conserved glycine at position 11. However, some naturally occurring SARS-CoV-2 sequences contain a serine at this position, potentially disrupting the dimer. We have used concentration-dependent activity assays and mass spectrometry to show that indeed the G11S mutation reduces the stability of the dimer by 600-fold. This helps to set a quantitative benchmark for the minimum potency required of any future protein-protein interaction inhibitors targeting 3CLpro and raises interesting questions regarding how coronaviruses bearing such weakly dimerizing 3CLpro enzymes are capable of replication.

Phytochemical investigation and anti-inflammatory potential of Atriplex leucoclada Boiss

BackgroundThe plant kingdom has long been considered a valuable source for therapeutic agents, however, some plant species still untapped and need to be phytochemically and biologically explored. Although several Atriplex species have been investigated in depth, A. leucoclada, a halophytic plant native to Saudi Arabian desert, remains to be explored for its phytochemical content and biological potentials. Herein, the current study investigated the metabolic content and the anti-inflammatory potential of A. leucoclada.MethodsPowdered aerial parts of the plant were defatted with n-hexane then the defatted powder was extracted with 80% methanol. n-Hexane extract (ATH) was analyzed using GC–MS, while the defatted extract (ATD) was subjected to different chromatographic methods to isolate the major phytoconstituents. The structures of the purified compounds were elucidated using different spectroscopic methods including advanced NMR techniques. Anti-inflammatory activity of both extracts against COX-1 and COX-2 enzymes were examined in vitro. Molecular docking of the identified compounds into the active sites of COX-1 and COX-2 enzymes was conducted using pdb entries 6Y3C and 5IKV, respectively.ResultsPhytochemical investigation of ATD extract led to purification and identification of nine compounds. Interestingly, all the compounds, except for 20-hydroxy ecdysone (1), are reported for the first time from A. leucoclada, also luteolin (6) and pallidol (8) are isolated for the first time from genus Atriplex. Inhibitory activity of ATD and ATH extracts against COX-1 and COX-2 enzymes revealed concentration dependent activity of both fractions with IC50 41.22, 14.40 μg/ml for ATD and 16.74 and 5.96 μg/ml for ATH against COX-1 and COX-2, respectively. Both extracts displayed selectivity indices of 2.86 and 2.80, respectively as compared to 2.56 for Ibuprofen indicating a promising selectivity towards COX-2. Molecular docking study supported in vitro testing results, where purified metabolites showed binding affinity scores ranged from -9 to -6.4 and -8.5 to -6.6 kcal/mol for COX-1 and 2, respectively, in addition the binding energies of GC–MS detected compounds ranged from -8.9 to -5.5 and -8.3 to -5.1 kcal/mol for COX-1 and 2, respectively as compared to Ibuprofen (-6.9 and -7.5 kcal/mol, respectively), indicating high binding affinities of most of the compounds. Analysis of the binding orientations revealed variable binding patterns depending on the nature of the compounds. Our study suggested A. leucoclada as a generous source for anti-inflammatory agents.

Rapid solid-liquid dynamic extraction of Cachrys pungens Jan ex Guss. aerial parts: influence on the photobiological and antioxidant properties

Cachrys pungens Jan ex Guss. (Apiaceae) is a perennial plant native to Italy and Northwestern Africa. This species is known for its content in furanocoumarins, and the methanolic extract obtained with maceration previously demonstrated significant phototoxicity on 375 melanoma cells. Here, in order to better explain the biological effects, the apoptotic responses on melanoma cancer cell line were verified. The aerial parts were extracted with methanol through an innovative solid–liquid extraction technology, the Naviglio extractor®, and the raw extract was tested for its photobiological properties on human melanoma C32 cells irradiated with UVA light. The in vitro antioxidant potential was assessed as well. The sample exerted a concentration-dependent photocytotoxic activity (IC50 value = 3.00 ± 0.16 µg/mL). In line with these evidences, in C32-treated cells subjected to UV irradiation, further data have reported an up-regulation of p53 and PARP, both proteins involved in apoptotic response and DNA repair.

Microwave-Mediated Synthesis and Characterization of Ca(OH)2 Nanoparticles Destined for Geraniol Encapsulation

Nanotechnology presents promising opportunities for enhancing pest management strategies, particularly in protecting active ingredients to prolong their shelf life and effectiveness. Among different approaches, the combination of inorganic nanoparticles with active ingredients such as the main constituents of natural essential oils in one nanoarchitecture is challenging. In this study, hydrophobic calcium hydroxide nanoparticles coated with oleylamime [Ca(OH)2@OAm NPs] were synthesized using microwave-assisted synthesis. These primary NPs were physicochemically characterized and subsequently utilized to prepare nanocapsules (NCs) either alone (Ca NCs) and/or in combination with geraniol at different ratios of Ca(OH)2@OAm NPs and geraniol, i.e. 1:1 (CaGer1 NCs), 1:2 (CaGer2 NCs), and 1:3 (CaGer3 NCs), respectively. Among the formulations, the CaGer2 NCs demonstrated higher encapsulation efficiency (EE) and loading capacity (LC) of 95% and 20%, correspondingly. They exhibited a hydrodynamic size of 306 nm, a ζ-potential of −35 mV, and a monodisperse distribution. Release kinetics of geraniol from CaGer2 NCs indicated a pH-dependent slow release over 96 h at both 25 °C and 35 °C. In vitro antifungal assay against B. cinerea revealed a concentration-dependent activity, and the EC50 values for Ca(OH)2@OAm NPs, Ca NCs, and CaGer2 NCs were estimated to be 654 µg/mL, 395 µg/mL, and 507 µg/mL, respectively. These results underscore the potential of Ca-based nanoformulations to control plant pathogens, suggesting that while Ca NCs showcase potent antifungal attributes, the different architectures/structures play a critical role in the antifungal effectiveness of the nanoformulations that have to be explored further.