Advances in Pharmacological and Pharmaceutical Sciences最新文献

Phytochemicals present in medicinal plants (herbs, shrubs, and trees) are endowed with high antimicrobial and antioxidant properties. The aim of this work was to study the chemical composition, antioxidant, and antifungal activities of Tristemma mauritianum, Crassocephalum bougheyanum, and Lavigeria macrocarpa. Chemical composition of the plant extracts was determined using standard methods. The antioxidant activities were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), nitric oxide (NO), and hydroxyl (OH) scavenging assays. The antifungal activity of plant extracts and their combinations with antifungals was evaluated against eleven Candida spp. using the broth microdilution method by determining the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC). The quantitative chemical analysis of the extracts of T. mauritianum, L. macrocarpa, and C. bougheyanum showed that they contain phenols, tannins, and flavonoids that vary according to the plant species and extracts. All the plant extracts presented promising antifungal (MIC = 64-2048 µg/mL) and antioxidant activities. The extract of T. mauritianum displayed the highest antifungal (MIC = 64-256 µg/mL) and antioxidant (IC₅₀ = 19.052 ± 1.11 μg/mL) activities which can be explained by its high phenolic content. Interestingly, extracts of T. mauritianum, L. macrocarpa, and C. bougheyanum displayed synergistic effects (fractional inhibitory concentration index, FICI ≤ 0.5) with ketoconazole against clinical resistant isolates. The results of the present study demonstrate promising antifungal and antioxidant activities of the tested plants that are associated to their phenol, tannin, and flavonoid contents. Hence, extracts of T. mauritianum and L. macrocarpa could be deeply investigated as antifungal alone and in combination with conventional antifungal drugs to treat infections caused by Candida spp.

Introduction: Limited aqueous solubility and subsequent poor absorption and low bioavailability are the main challenges in oral drug delivery. Solid dispersion is a widely used formulation strategy to overcome this problem. Despite their efficiency, drug crystallization tendency and poor physical stability limited their commercial use. To overcome this defect, ternary solid dispersions of glyburide: sodium lauryl sulfate (SLS) and polyethylene glycol 4000 (PEG), were developed using the fusion (F) and solvent evaporation (SE) techniques and subsequently evaluated and compared.

Materials and methods: Physicochemical and dissolution properties of the prepared ternary solid dispersions were evaluated using differential scanning calorimetry (DSC), infrared spectroscopy (FTIR), and dissolution test. Flow properties were also assessed using Carr's index and Hausner's ratio. The physical stability of the formulations was evaluated initially and after 12 months by comparing dissolution properties.

Results: Formulations prepared by both methods similarly showed significant improvements in dissolution efficiency and mean dissolution time compared to the pure drug. However, formulations that were prepared by SE showed a greater dissolution rate during the initial phase of dissolution. Also, after a 12-month follow-up, no significant change was observed in the mentioned parameters. The results of the infrared spectroscopy indicated that there was no chemical interaction between the drug and the polymer. The absence of endotherms related to the pure drug from thermograms of the prepared formulations could be indicative of reduced crystallinity or the gradual dissolving of the drug in the molten polymer. Moreover, formulations prepared by the SE technique revealed superior flowability and compressibility in comparison with the pure drug and physical mixture (ANOVA, P  <  0.05).

Conclusion: Efficient ternary solid dispersions of glyburide were successfully prepared by F and SE methods. Solid dispersions prepared by SE, in addition to increasing the dissolution properties and the possibility of improving the bioavailability of the drug, showed acceptable long-term physical stability with remarkably improved flowability and compressibility features.

Multidrug-resistant bacteria have raised global concern about the inability to fight deadly infectious diseases. Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the most common resistant bacteria that are causing hospital infections. The present study was undertaken to investigate the synergistic antibacterial effect of the ethyl acetate fraction of Vernonia amygdalina Delile leaves (EAFVA) with tetracycline against the clinical isolates MRSA and P. aeruginosa. Microdilution was used to establish the minimum inhibitory concentration (MIC). A checkerboard assay was conducted for the interaction effect. Bacteriolysis, staphyloxanthin, and a swarming motility assay were also investigated. EAFVA exhibited antibacterial activity against MRSA and P. aeruginosa with a MIC value of 125 μg/mL. Tetracycline showed antibacterial activity against MRSA and P. aeruginosa with MIC values of 15.62 and 31.25 μg/mL, respectively. The interaction between EAFVA and tetracycline showed a synergistic effect against MRSA and P. aeruginosa with a Fractional Inhibitory Concentration Index (FICI) of 0.375 and 0.31, respectively. The combination of EAFVA and tetracycline induced the alteration of MRSA and P. aeruginosa, leading to cell death. Moreover, EAFVA also inhibited the quorum sensing system in MRSA and P. aeruginosa. The results revealed that EAFVA enhanced the antibacterial activity of tetracycline against MRSA and P. aeruginosa. This extract also regulated the quorum sensing system in the tested bacteria.

Amorphous salt solid dispersion (ASSD) of Dolutegravir amorphous salt (DSSD) was generated using quench cooling and compared to its Dolutegravir free acid solid dispersion (DFSD) to improve the solubility and bioavailability. Soluplus (SLP) was used as a polymeric carrier in both solid dispersions. The prepared DSSD and DFSD, physical mixtures, and individual compounds were characterized by employing DSC, XRPD, and FTIR to assess the formation of the single homogenous amorphous phase and the existence of intermolecular interactions. Partial crystallinity was observed for DSSD, unlike DFSD, which is completely amorphous. No intermolecular interactions were observed between the Dolutegravir sodium (DS)/Dolutegravir free acid (DF) and SLP from the FTIR spectra of DSSD and DFSD. Both DSSD and DFSD improved the solubility of Dolutegravir (DTG) to 5.7 and 4.54 folds compared to the pure forms. Similarly, drug release from DSSD and DFSD was 2 and 1.5 folds higher than that in the pure form, owing to the rapid dissolution of the drug from the formulations. The permeability of DSSD and DFSD was estimated using the dialysis membrane, which enhanced the DTG permeability. The improvement in in vitro studies was translated into in vivo pharmacokinetic profiles of DSSD and DFSD, where 4.0 and 5.6 folds, respectively, improved the C_max of DTG.

The nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) has shown promising pharmacological activities, including inhibition of cancerous cell growth and N-glycosylation. It has been used as a glycolysis inhibitor and as a potential energy restriction mimetic agent, inhibiting pathogen-associated molecular patterns. Radioisotope derivatives of 2-DG have applications as tracers. Recently, 2-DG has been used as an anti-COVID-19 drug to lower the need for supplemental oxygen. In the present review, various pharmaceutical properties of 2-DG are discussed.

Background: The use of Aspilia africana in traditional medicine for the management of ocular diseases has been reported in India and some indigenous communities of Africa. The aim of this study was to investigate the aqueous extract of the flowers of A. africana (AAE) as an anticataract remedy using murine models of diabetic and senile cataracts.

Methods: Preliminary phytochemical screening of the extract, in vitro antioxidant assays, and in vitro aldose reductase inhibitory activity were performed. For anticataract investigations of the extracts, diabetic cataract was induced by galactose administration in 3-week-old Sprague Dawley rats. The evaluation of experimentally induced age-related cataract was performed by administering sodium selenite to 10-day-old rat pups.

Results: The phytochemical analysis revealed the presence of alkaloids, tannins, flavonoids, glycosides, and saponins. In vitro aldose reductase inhibitory property of the extract on rat lenses revealed that the AAE inhibited the enzyme activity with IC₅₀ of 12.12 µg/ml. For the anticataract investigations, 30, 100, and 300 mg·kg^-1AAE-treated rats recorded significantly low (p ≤ 0.0001) cataract scores compared to the negative control rats, indicating a delay in cataractogenesis from the second week of treatment in the galactose-induced cataractogenesis. Similarly, the treatment with AAE caused a significant reduction (p ≤ 0.0001) in cataract scores compared to the negative control rats in the selenite-induced cataractogenesis. Markers of lens transparency, such as aquaporin 0, alpha-A crystallin, and total lens proteins and lens glutathione levels, were significantly preserved (p ≤ 0.05-0.0001) in each cataract model after AAE treatment.

Conclusion: The study established the anticataract potential of the aqueous extract of flowers of A. africana in murine models, hence giving scientific credence to its folkloric use in the management of cataract.

The liver is the body's most critical organ that performs vital functions. Hepatic disorders can affect the physiological and biochemical functions of the body. Hepatic disorder is a condition that describes the damage to cells, tissues, structures, and functions of the liver, which can cause fibrosis and ultimately result in cirrhosis. These diseases include hepatitis, ALD, NAFLD, liver fibrosis, liver cirrhosis, hepatic failure, and HCC. Hepatic diseases are caused by cell membrane rupture, immune response, altered drug metabolism, accumulation of reactive oxygen species, lipid peroxidation, and cell death. Despite the breakthrough in modern medicine, there is no drug that is effective in stimulating the liver function, offering complete protection, and aiding liver cell regeneration. Furthermore, some drugs can create adverse side effects, and natural medicines are carefully selected as new therapeutic strategies for managing liver disease. Kaempferol is a polyphenol contained in many vegetables, fruits, and herbal remedies. We use it to manage various diseases such as diabetes, cardiovascular disorders, and cancers. Kaempferol is a potent antioxidant and has anti-inflammatory effects, which therefore possesses hepatoprotective properties. The previous research has studied the hepatoprotective effect of kaempferol in various hepatotoxicity protocols, including acetaminophen (APAP)-induced hepatotoxicity, ALD, NAFLD, CCl₄, HCC, and lipopolysaccharide (LPS)-induced acute liver injury. Therefore, this report aims to provide a recent brief overview of the literature concerning the hepatoprotective effect of kaempferol and its possible molecular mechanism of action. It also provides the most recent literature on kaempferol's chemical structure, natural source, bioavailability, and safety.

Objective: The prevalence of kidney stones and their complications is high. The review of the literature showed the therapeutic effects of Alhagi maurorum extract on urinary tract stones. This study reviewed the Alhagi plant's hydroalcholic extract's effect on eliminating kidney and ureteral stones compared to hydrochlorothiazide.

Materials and methods: In this randomized prospective study, from March 2019 to September 2021, 80 patients over 18 years of age with kidney stones in the upper ureter with a size of 4-10 mm were divided into two groups based on the block random allocation method. The first group received hydrochlorothiazide tablets (50 mg), and the second group received 1 gram/day of the hydroalcholic areal extract of Alhagi maurorum in a two-divided capsule. The mean size and number of stones, renal function tests, and side effects were checked and compared in both groups before and after the study.

Results: Mean age, sex, serum urea level (P=0.351), serum creatinine (P=0.393), stone size (P=0178), and the number of stones (P=0.052) before intervention were similar. After intervention, the size and number of stones diminished, up to 70% in both groups. However, there was not a statistically significant difference between the two groups.

Conclusion: The study showed that Alhagi maurorum is as effective as hydrochlorothiazide in treatment of kidney and ureteral stones with no significant complications and is promising.