Advances in Pharmacological and Pharmaceutical Sciences最新文献

The medicinal value of Centella asiatica leaf extract was evaluated as an alternative treatment. The chemical composition of the leaf extract was analyzed, and the biological activities were determined. High-performance liquid chromatography coupled with a photodiode array detector (HPLC-PDA) was used to identify the asiatic acid, madasiatic acid, and madecassic acid/Brahmic acid isolated from the ethanolic extract. The plant extract at 25 mg/disk was found to inhibit both Gram-positive and Gram-negative pathogenic bacteria by the agar disk diffusion test. The MIC and MBC of the ethanolic extracts were better than those of the aqueous extracts. The ethanolic extracts showed antibacterial activity against Gram-positive bacteria with MICs and MBCs ranging from 1.024 to 2.048 mg/mL and 2.048 to 4.096 mg/mL, respectively. The remarkable antibacterial activities were observed against S. mutans. The ethanolic extract at a concentration of 1/2 × MIC exhibited the inhibition effect on S. mutans biofilm formation like the activity of 0.2% chlorhexidine and significantly modified hydrophobicity of the bacterial cell surface. The effects were confirmed via molecular docking analysis. The binding affinities of asiatic acid, madecassic acid, and madasiatic acid with glucosyltransferase C (GtfC) of S. mutans exhibited superior strength in comparison with alpha-acarbose and chlorhexidine. Moreover, the nitric oxide (NO) secretion of RAW247.6 cells was determined after treating the cells with concentrations of the extract. The C. asiatica ethanolic extract can inhibit the secretion of NO, which can inhibit the inflammatory process. The findings indicate the applications of the C. asiatica ethanolic extract as the alternative anti-S. mutans agent and could be used for further formulation for the treatment and prevention of dental diseases and inflammatory injury in the oral cavity.

Asiatic acid (AA) has previously shown its neuroprotective effects, but low oral bioavailability limits its penetration into the brain. This study aimed to investigate the effect of intranasal AA administration in mice with memory dysfunction induced by scopolamine. Mice received either intranasal AA (INAA), oral AA (POAA3 or POAA30), or donepezil, followed by scopolamine for 10 days. Morris water maze (MWM) was performed on days 0-5, 30 min after treatment. Locomotor activity was conducted on day 6 followed by brain collection. In MWM, INAA treatment had significantly reduced escape latency on days 2-4, while POAA3 decreased escape latency on day 3 and POAA30 and donepezil decreased escape latency on day 4. INAA inhibited acetylcholinesterase activity, increased catalase protein expression, and decreased malondialdehyde levels in the brain tissue. Therefore, intranasal administration of AA produced a rapid onset in the protection of learning and memory deficits induced by scopolamine through acetylcholinesterase inhibition and antioxidant effect.

Curcumin has shown beneficial effects on pulmonary diseases with chronic inflammation or abnormal inflammatory responses, including chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. Clinical applications of curcumin are limited due to its chemical instability in solution, low water solubility, poor oral bioavailability, and intestinal and liver first-pass metabolism. Pulmonary delivery of curcumin can address these challenges and provide a high concentration in lung tissues. The purpose of the current work was to prepare a novel inhalable dry powder of curcumin nanocrystals without added excipients using electrospray drying (ED) with improved dissolution and aerosolization properties. ED of curcumin was performed at 2 and 4% w/v concentrations in acetone. Physicochemical properties of the formulated powders were evaluated by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), density and powder flow measurements, and in vitro dissolution. The in vitro deposition studies were conducted using next-generation impactor (NGI) and aerosol performance and aerodynamic particle size parameters were calculated for prepared formulations. ED could produce agglomerates of nanocrystals with a size of about 500 nm at an acceptable yield of about 50%. PXRD and FTIR data revealed that prepared nanocrystals were in a stable crystalline state. The bulk and tapped density of prepared agglomerates were in the range appropriate for pulmonary delivery. Formed nanocrystals could significantly improve the dissolution rate of water-insoluble curcumin. The optimized formulation exhibited acceptable recovered dose percentage, high emitted dose percentage, optimum mean mass median aerodynamic diameter, small geometric standard deviation, and high fine-particle fraction that favors delivery of curcumin to the deep lung regions. The ED proved to be an efficient technique to prepare curcumin nanocrystals for pulmonary delivery in a single step, at a mild condition, and with no surfactant.

Apricot (Prunus armeniaca L.) kernels have been widely employed in phytomedicine for treating different ailments. This study aims to unveil the phytochemical composition by HPLC-ESI-MS, in vitro antioxidant activity, and examine certain pharmacological effects of the hydro-ethanolic extract from bitter apricot kernels (BAK). Obtained results indicated that the BAK extract presents a content of 4.58 ± 0.15 mg GAE/g extract of TPA and 1.68 ± 0.09 mg QUE/g extract of TFA, respectively. HPLC-ESI-MS analysis discovered the presence of 17 phenolic compounds including phenolic acids and flavonoids like 3,4-dihydroxybenzoic acid, gallic acid, caffeic acid, (+)-catechin, epicatechin, and others, with associated antioxidant power. Regarding the studied potential pharmacological effects, notable analgesic activity at a dosage of 100 mg/kg BW was recorded with 63.46% protection. In the anti-inflammatory test, significant inhibition was observed after 6 hours of treatment (77.4%) compared to untreated animals. Moreover, the daily application of ointment formulated with 10% BAK extract resulted in a remarkable healing of wounds and burns in rats. These findings underscore the increasing evidence supporting the potential use of apricot kernel extracts in treating various diseases.

The aim of the present study was to assay the in vivo anthelminthic activity of Anogeissus leiocarpa (Al) family of the Asteraceae and Adansonia digitata (Ad) family of Malvaceae leaf powder against the nematode Haemonchus contortus (Hc) in sheep. Twenty-eight sheep were artificially infected with 3000 Infective larvae (L3) of Hc and divided into four groups. Groups 1 and 2 received 3.2 g/kg of Ad and Al leaf powder according to the body weight for three days by oral route. This treatment was repeated after 14 days. Group 3 received albendazol 5 mg/kg and group 4 received water. The treatment was repeated 14 days later. Examination of faecal samples, packed cell volume and biochemical analyses and necropsy were carried out to determine egg counts, worm burdens, and reduction in worm fecundity and changes in blood parameters. The results showed a reduction in egg excretion of 72.22% and 88.49%, respectively, with Al and Ad leaf powder. Egg laying of adult female worms was reduced by 55.22% and 64.96% with Ad and Al, respectively. FAMACHA score (≤2 in the treated animals) and packed cell volume were improved with Ad and Al. The results of this study revealed that Ad and Al powder may be used as an alternative anthelminthic to control haemonchosis in small ruminants.

Background: Sitagliptin functions similarly to GLP-1RAs by incretin and insulin secretion and has a renoprotective effect. Diabetic kidney disease (DKD) is a kidney complication that increases the mortality rate in type 2 diabetes mellitus (T2DM) patients. The important parameters that predict appropriate sitagliptin treatment are known as factors. This study aimed to assess factors that correlated with the renoprotective effect of sitagliptin in patients with T2DM.

Methods: This retrospective study collected data from a tertiary hospital in Thailand. All T2DM patients who were treated with sitagliptin and had complete data were recruited to analyze the outcome. The primary outcome was a correlation between demographics, laboratory data, and kidney outcome. The secondary outcome was the different laboratory results between pre- and posttreatment of patients treated with sitagliptin.

Results: The number of patients who were treated for T2DM with sitagliptin was 191. Only 102 patients had complete laboratory parameters. Results showed a positive correlation between baseline FBS, Hb_A1c, and Scr change (p value = 0.042 and 0.005) at 6 months and baseline age, TG, and Scr change (p value = 0.010 and 0.022) at 18 months; while a negative correlation was observed between baseline FBS, Hb_A1c, and eGFR change (p value = 0.017 and 0.007) at 6 months and baseline age and eGFR change (p value = 0.010) and between HDL-cholesterol and Scr change at 18 months (p value = 0.044). The eGFR stage 1 subgroup showed a positive correlation between baseline Hb_A1c and Scr change (p value <0.001) and baseline DM duration and eGFR change (p value = 0.004). Moreover, sitagliptin showed statistically significant FBS, Hb_A1c, LDL-cholesterol, and TC reduction. Furthermore, HDL-cholesterol showed statistically significant elevation.

Conclusion: FBS, HbA1c, and age were factors that correlated with the renoprotective effect of sitagliptin. The eGFR ≥90.00 ml/min/1.73 m² patients group showed a duration of DM in which factors correlated with renoprotective effect. Moreover, sitagliptin also can improve glucose levels and lipid profile.

Breast cancer is a condition where breast tissue cells grow uncontrollably. Various natural and synthesized compounds, such as quinazoline, have been studied for their potential as anticancer agents. Quinazoline derivatives have shown diverse bioactivities, including antimalarial, antifungal, antimicrobial, and anticancer properties. This research aims to synthesize substituted tetrazoloquinazoline and evaluate its potential as an anticancer agent using molecular docking studies with the Molecular Operating Environment (MOE) software. Furthermore, molecular dynamic was also performed to analyze the binding stability of this protein-ligand complex. Additionally, the physicochemical and pharmacokinetic properties of quinazoline compounds were assessed using the website https://www.swissadme.ch. The cytotoxic activity of the compounds was evaluated using the MTT assay. The docking results revealed that substituted tetrazoloquinazoline exhibited a significantly different range of binding free energy compared to the positive control. Moreover, the substituted tetrazoloquinazoline compounds comply with Lipinski's Rule of Five (Ro5), indicating that they are easily absorbable and have good permeability. The cytotoxic activity of the compounds was found to have an IC₅₀ value of >1000 ppm, classifying them as noncytotoxic. It therefore paved the way for the discovery of promising next-generation drugs against breast cancer.

This study investigated the medicinal potential of Lavatera cashmeriana, a plant traditionally known for its therapeutic properties. The aim was to identify the phytocompounds in L. cashmeriana leaf extract and evaluate its antibacterial, antioxidant, and anticancer effects. Gas chromatography-mass spectrometry analysis was employed to characterize the phytochemical composition of the ethanol extract derived from L. cashmeriana leaves. The antimicrobial potential was assessed through the well diffusion technique, targeting Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. The 2,2-diphenyl-1-picrylhydrazyl assay was conducted to assess antioxidant capabilities, while cytotoxicity against the A549 cancer cell line was determined via the MTT assay. GC-MS analysis identified ten different compounds, with phytol, 1-Eicosanol, and 2,6,10-trimethyl,14-ethylene-14-pentadecne being the most prevalent. The extract exhibited notable antimicrobial efficacy against all bacteria with MIC values ranging from 62.5 to 250 µg/mL. However, C. albicans did not respond. The extract exhibited antioxidative properties with an IC₅₀ value of 86 µg/mL and cytotoxicity with an IC₅₀ value of 69.95 µg/mL against the A549 cancer cell line. The results derived from this study supported the historical use of L. cashmeriana as a medicinal plant and suggested that it can potentially treat a wide range of medical ailments. The identified phytocompounds and the demonstrated antibacterial, antioxidant, and anticancer effects provide scientific evidence for its medicinal properties. However, further investigations are needed to fully understand its safety profile, efficacy, and mechanism of action before recommending it for therapeutic purposes.

Acinetobacter baumannii was identified by the WHO as a priority pathogen in which the research and development of new antibiotics is urgently needed. Plant phytochemicals have potential as sources of new antimicrobials. The objective of the study was to determine the antibacterial activity of extracts of selected Zimbabwean medicinal plants against A. baumannii and determine their possible mode of action. Extracts were prepared from the leaves of the eight plants including the bark of Erythrina abyssinica using solvents of different polarities. Antibacterial activity was evaluated using the microbroth dilution method coupled with the in vitro iodonitrotetrazolium colorimetric assay. The effect of the extracts on membrane integrity was determined by quantifying the amount of protein and nucleic acid leaked from the cells after exposure to the extracts. The effects of the extracts on biofilms were investigated. Toxicity studies were carried out using sheep erythrocytes and murine peritoneal cells. Seven out of eight evaluated plant extracts were found to have antibacterial activity. The Combretum apiculatum acetonie (CAA) extract showed the highest inhibitory activity against A. baumannii with a minimal inhibitory concentration of 125 µg/mL. The minimum inhibitory concentration (MIC) of the CAA extract caused a protein leakage of 32 µg/mL from A. baumannii. The Combretum apiculatum acetonie (CAA), C. apiculatum methanolic (CAM), Combretum zeyheri methanolic (CZM), and Erythrina abyssinica methanolic (EAM) extracts inhibited A. baumannii biofilm formation. The EAM extract was shown to disrupt mature biofilms. The potent extracts were nontoxic to sheep erythrocytes and mouse peritoneal cells. The activities shown by the extracts indicate that the plants have potential as sources of effective antibacterial and antibiofilm formation agents against A. baumannii.

Hepatic diseases represent a public health problem. Among the approaches to their management is the use of traditional treatments based on the use of medicinal plants. In Benin, several recipes based on Cochlospermum tinctorium are used in the treatment of hepatitis without a real scientific basis. This study aimed to evaluate the hepatoprotective effects and acute oral toxicity of 10 of these recipes. The variables studied were the variety of C. tinctorium (wild form vs. cultivated form), the species associated with C. tinctorium (Combretum micranthum vs. Chromolaena odorata), and the proportion of C. tinctorium in the recipe (1; 4/5; 1/2). The hepatoprotective effect of these extracts at doses of 100, 200, and 400 mg/kg/bw was evaluated in Wistar rats subjected to hepatotoxicity induction through the administration of 5 g/kg of paracetamol. Acute oral toxicity was assessed following the OECD 423 protocol. The results revealed an absence of acute oral toxicity for the 10 recipes. The hepatoprotective tests conducted indicated that the hepatoprotective effect of C. tinctorium is dose dependent. The wild variety of C. tinctorium had a better hepatoprotective effect than the cultivated one. The association with C. micranthum enhances the hepatoprotective effect of C. tinctorium, unlike that with C. odorata. This study emphasizes that the combination of C. tinctorium with C. micranthum in the treatment of hepatitis is scientifically justified and it exhibits a dose-dependent hepatoprotective effect.