Advances in Pharmacological and Pharmaceutical Sciences最新文献

Colorectal cancer (CRC) is a multifactorial disease driven by genetic and epigenetic alterations that modulate specific metabolic pathways. Despite the availability of effective treatments like 5-fluorouracil (5-FU), pharmacological therapy for CRC still faces significant challenges, including drug resistance, toxicity, and limited specificity. Therefore, discovering new compounds remains critical to overcoming these barriers and expanding treatment options. This study evaluated the cytotoxicity of fluorinated quaternary ammonium salts (FQAS) library in CRC-derived cell lines with premetastatic and metastatic phenotypes. The genetic and epigenetic background of the CRC cell lines and the selectivity of cytotoxicity compared to nontumor cells and between different CRC stages were also assessed. Additionally, the in silico pharmacological properties of these FQASs were analyzed. Results showed that FQASs 9-14 exhibited significant cytotoxic activity against both premetastatic and metastatic CRC cell lines, with FQASs 9, 13, and 14 displaying selective toxicity toward CRC cells over normal murine colorectal cells. However, in silico studies indicated poor oral bioavailability for these compounds, suggesting that an injection-based delivery route may be more effective for targeting CRC cells. In conclusion, CF₃-containing FQASs are promising therapeutic candidates for CRC treatment.

Pinocembrin (PCB), a flavonoid known for its anti-inflammatory properties, has been approved for various clinical trial applications. To evaluate deeper into the anti-inflammatory potential of the specific enantiomer of natural PCB, we conducted the first investigation into the efficacy of the pure enantiomer (2S)-PCB in modulating inflammatory mediators induced by lipopolysaccharide (LPS) in both murine RAW 264.7 and human U937 macrophage cell lines. This particular compound was isolated from Goniothalamus macrophyllus (Annonaceae), a native plant of Indonesia. This plant has been used traditionally as an herbal medicine to alleviate inflammation. (2S)-PCB was isolated from the stem bark of G. macrophyllus by defatting with n-hexane followed by maceration with methanol. Purification was performed using several chromatographic techniques. The absolute configuration was determined using electronic circular dichroism (ECD) spectroscopy. This compound was then tested for its inhibitory activity on prostaglandin E₂ (PGE₂) and subjected to docking simulations. The results indicated that (2S)-PCB significantly suppressed the production of PGE₂ induced by LPS in both RAW 264.7 and U937 cell lines. The docking simulations revealed that (2S)-PCB reduced PGE₂ levels by suppressing mitogen-activated protein kinase (MAPK) activation through inhibiting p38 and extracellular signal-regulated kinases (ERK). These findings suggest that the compound may prevent worsening of septic shock caused by bacterial infection.

Tea is a rich source of phytochemicals; their composition in tea extracts varies depending on the cultivar, climate, production region, and processing and handling processes. The method of extraction plays a crucial role in determining the biological effects of the bioactive compounds in tea leaves. However, reports on the catechin profiles and antioxidant activities of the extracts obtained from leaves at different stages of maturity are limited. Here, we aimed to evaluate the effect of ultrasound-assisted extraction (UAE) and different drying methods, freeze drying (FD) and spray drying (SD), on the composition of bioactive compounds, phenolic composition, and antioxidant activity of extracts obtained from different part of leaves, top (TT), middle (ML), and mature (MT), of Assam tea cultivar (Camellia sinensis var. assamica) cultivated in Thailand (Thai Assam tea). High-performance liquid chromatography analysis showed that the extracts obtained by UAE with FD from TT leaves (UAEFD-TT) had the highest catechins (341.38 ± 0.11 mg/g extract) and caffeine (93.20 ± 0.36 mg CF/g extract) contents compared with those extracted from ML and MT using the same method as well those obtained by SD. The total phenolic and total flavonoid contents were the highest in UAEFD-TT extracts (456.78 ± 4.31 mg GAE/g extract and 333.98 ± 0.83 mg QE/g extract, respectively). In addition, UAEFD-TT exhibited the highest antioxidant activity; the IC₅₀ values obtained by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays were 1.31 ± 0.02 and 7.51 ± 0.03 μg/mL, respectively. In the ferric-reducing antioxidant power (FRAP) assay, the UAEFD-TT extract demonstrated the highest antioxidant activity (324.54 ± 3.33 μM FeSO₄/mg extract). These results suggest that extraction from TT using UAE followed by FD produced the highest amount of antioxidant compounds in Thai Assam tea extracts.

Background/Aims: Long-term acid suppression with proton pump inhibitors (PPI) leads to hypochlorhydria and facilitates the growth of bacterial flora in the small intestine. Novel acid-suppressants called potassium-competitive acid blockers (P-CABs) seem to be superior to PPIs. However, data on the risk of small intestinal bacterial overgrowth (SIBO) in patients taking P-CABs are limited. Method: We retrospectively analyzed a consecutive series of patients with long-term acid-suppressant (PPIs or P-CABs) use for gastroesophageal reflux disease or nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. All of them underwent endoscopic examinations and Helicobacter pylori testing and took PPIs or P-CABs for at least 3 months. Glucose hydrogen breath tests (GBT) were performed to check for SIBO, and newly developed SIBO-related symptoms including bloating, postprandial discomfort, diarrheas, and constipation, were evaluated. Results: A total of 142 patients were enrolled. Six patients were excluded due to equivocal Helicobacter pylori infection results. The frequency of positive GBTs was 31.7% (25/79) for PPI and 22.8% (13/57) for P-CAB use (p=0.15). Regarding GBT positivity, age-related factor was found to be significant in multivariate analysis (p=0.02). The results of multivariate analysis in cases of SIBO-related symptoms showed that GBT positivity and PPI use were significant (p < 0.01). Conclusion: Long-term use of gastric acid suppressants resulted in positive GBT in approximately 30% of patients, and the risk was particularly high in elderly patients. The occurrence of SIBO-related symptoms was significant in long-term use of PPIs and in patients with positive GBT.

Herbal medicine could be an option for atopic dermatitis (AD) treatment for those suffering from global public health. HMB is a new combination of three herb extracts, consisting of the Ha-Rak (HR) remedy extract, Piper betle (PB) extract, and Garcinia mangostana (GM) extract in equal proportions, using Thai traditional medicine theory, that uses a combination of medications that can improve therapeutic efficacy and reduce side effects and toxicity. HMB extract has anti-inflammatory and antiallergic properties, is a component for AD treatment, and tends to develop topical products. Drug registration requires stability data. Results from drug stability testing affect not only the efficacy of the drug but also its safety. The aim of this study was to investigate stability through forced degradation and an accelerated study of extracts. Chemical content analysis and in vitro biological activities such as anti-inflammatory and antiallergic activities determined the effects of all examined samples. Anti-inflammatory and antiallergic effects were assessed by inhibiting nitric oxide synthesis in RAW 264.7 cells and β-hexosaminidase release in RBL-2H3 cells, respectively. High-performance liquid chromatography (HPLC) assessed content indicators. Moisture and temperature hydrolysis had no significant differences in the chemical or biological properties of the HMB. However, the HMB demonstrated sensitivity to alkaline hydrolysis, showed low anti-inflammatory activity, and decreased hydroxychavicol, eugenol, and α-mangostin contents. The contents of the three compounds also decrease with acid hydrolysis. For the accelerated study, anti-inflammatory and antiallergic effects and hydroxychavicol amount were not significantly different after 180 days at 40°C and 75% RH. Therefore, the contents of eugenol and α-mangostin were changed. Eugenol in HMB decreased significantly from the 15^th day until the 180^th day of storage. In addition, α-mangostin amounts in HMB decreased slightly on 180^th day. Fortunately, reducing the two chemicals did not affect anti-inflammatory or antiallergic effects. For stability, combination extract should be stored in a closed container in the refrigerator at a low temperature and protected from light, high temperature, oxygen, and pH. Further HMB development should avoid pH or oxidation processes or components.

Wound healing comprises an intricate process to repair damaged tissue. Research on plant extracts with properties to expedite wound healing has been of interest, particularly their ability to enhance the stemness of keratinocyte stem cells. Hence, the present study aims to determine the wound healing and stemness potentiation properties of an ethanolic extract derived from Cucurbita moschata fruit pulp (PKE). Human keratinocytes (HaCaT) and primary skin fibroblast cells were used in this study. The migration of the cells was examined by using a scratch wound healing assay, and spheroid behavior was determined by using a spheroid formation assay. The proteins related to migration and stemness were further measured by using Western blotting to explore the mechanism of action of PKE. The methods used to evaluate PKE's antioxidant properties were 2,2-diphenyl-2-picrylhydrazyl (DPPH) scavenging, ABTS radical scavenging activity, and superoxide anion radical scavenging (SOSA) assays. The phytochemistry of the PKE was investigated using phytochemical screening and high-performance liquid chromatography (HPLC) analysis. The results of this study indicate that nontoxic concentrations of PKE increase the rate of migration and spheroid formation. Mechanistically, PKE increased the expression of the migratory-related protein active FAK (phosphorylated FAK), and the subsequence increased the level of p-AKT. The expression of stem cell marker CD133, upstream protein signaling β-catenin, and self-renewal transcription factor Nanog was increased. The PKE also possessed scavenging properties against DPPH, ABTS, and SOSA. The phytochemistry analyses exhibited the presence of alkaloids, glycosides, xanthones, triterpenes, and steroids. Additionally, bioactive compounds such as ɑ-tocopherol, riboflavin, protocatechuic acid, β-carotene, and luteolin were detected. The presence of these chemicals in PKE may contribute to its antioxidant, stem cell potentiation, and wound-healing effects. The findings could be beneficial in the identification of valuable natural resources that possess the capacity to be used in the process of wound healing through the potentiation of stemness via a readily detectable molecular mechanism.

This study investigated the anti-inflammatory properties of Ajuga integrifolia, an herbal preparation. Qualitative and quantitative phytochemical analyses were conducted to identify active compounds in the preparation. The researchers also assessed its ability to inhibit the production of pro-inflammatory enzymes, cyclooxygenases (COX-1, COX-2), and lipoxygenase (5-LOX) in vitro. The extracts demonstrated dose-dependent inhibition of these enzymes, with some extracts showing IC₅₀ values comparable to standard anti-inflammatory drugs. The ethanol extract exhibited significant inhibition of 5-LOX (52.99 μg/mL), compared to the standard drug zileuton (32.41 μg/mL), while the inhibition of COX-1 (66.00 μg/mL) and COX-2 (71.62 μg/mL) was comparable to the standard drug indomethacin (40.57 and 54.39 μg/mL, respectively). These findings suggest that A. integrifolia has the potential to be used as a herbal remedy for treating inflammatory conditions. By inhibiting pro-inflammatory enzymes, the extracts may effectively reduce inflammation and promote tissue healing or repair. The inhibition potential of extract of this plant can be taken as a good candidate of anti-inflammatory agent.

Ganoderma species have been studied for their pharmacological approaches, such as anticancer, antitumor, antiproliferative, and antioxidant activity. Elicitors are used to increase Ganoderma bioactive composite production. This study aims to evaluate the antiproliferative activity of ethanolic extracts from mycelium of Ganoderma tuberculosum (G. tuberculosum) grown in a liquid medium with vineyard pruning waste (VPW) extracts as elicitors. Ethanolic and aqueous VPW extracts contain resveratrol dimer 4, resveratrol tetramer 1, and naringenin, while toluene and chloroform extracts contain tetradecanoic acid, hexadecanoic acid, and octadecanoic acid. Polar and nonpolar extracts could be promising elicitors for increasing bioactive molecules. Catechin gallate showed the highest correlation (r = 0.66) with biomass. Mycelial ethanolic extracts of G. tuberculosum (native strain from the Sonoran Desert) and Ganoderma lucidum (G. lucidum) (control) were analyzed by ESI-IT-MS, and 27 molecules were identified for the two species. They showed antiproliferative activity against the A549 and C-33 A cell lines but not for ARPE-19. G. tuberculosum culture with VPW had quinic acid, ganodermenonol, ganoderic acid I (GA-I), C2 (GA-C2), and 20-hydroxylucidenic acid P, among others. Molecular docking of ganodermenonol, GA-I, and GA-C2 demonstrates significant interaction with tumor necrotic factor (TNF-α). These ethanolic extracts of Ganoderma are promising sources of bioactive triterpenoids. Their antiproliferative activity did not change between species or treatment. Likewise, the G. tuberculosum and G. lucidum extracts only affected cancer cell lines. This property seems promising for pharmacological applications of these fungal extracts.

Orodispersible tablet (ODT) is a promising avenue for drug delivery, offering a dosage form that can be disintegrated instantaneously in the mouth and released the drug that dissolves or disperses in the saliva without the addition of water. ODT can effectively boost the dissolution rate and consequently the bioavailability of several hydrophobic drugs. Additionally, ODT is very attractive and suitable for specific patients who are unable to swallow the traditional tablet. The basic approach in the fabrication of oral tablets for hydrophobic drugs relies on the utilization of superdisintegrants which allow prompt disintegration of tablets after swallowing. In the present investigation, escitalopram oxalate was chosen as a model drug, which is a hydrophobic, antidepressant, selective serotonin reuptake inhibitor (SSRI) drug. Nine formulas of escitalopram oxalate ODTs were prepared by varying the concentrations of three different superdisintegrants: sodium starch glycolate, croscarmellose sodium, and crospovidone to improve the dissolution and release of escitalopram oxalate. Each was used in three different concentrations (2.5%, 5%, and 7.5%), and all the ODTs were prepared by the direct compression method. The micrometric characterization of the powder blend used in the formulations was investigated such as angle of repose, bulk and tapped densities, compressibility percent (Carr's index), and Hausner ratio. Furthermore, the prepared ODTs were characterized in terms of weight variation, thickness, diameter, hardness, friability, in vitro disintegration, wetting time, water absorption ratio, drug content, in vitro dissolution, and accelerated stability study. The results showed that the formula (ODT9) that contained 7.5% of the superdisintegrant sodium starch glycolate had superior characteristics in almost all the tests, with a dissolution rate of 100% after 6 minutes. Also, it was stable under the accelerated stability conditions.

The treatment of human immunodeficiency virus (HIV) in children has persistently been complex and tedious on a global scale. This is because adult and pediatric HIV treatments follow a similar therapeutic approach. Due to the dearth of clinically licensed pediatric antiretroviral drug (ARVD) therapy, children with HIV worldwide are prescribed unlicensed drugs each year. This has triggered likelihood of poor drug adherence, therapeutic failure, and even adverse reactions brought on by a variety of factors, including pill size and quantity, which is the main cause of swallowing difficulties, repeated administration of these various ARVDs, many of which have poor solubility and cause severe side effects in children, and unpalatability of the drug, which is one of the criteria for pediatric formulations. Thus, there is a necessity for investigation into several advanced microencapsulation techniques that could curb these challenges. Microencapsulation techniques have explored in drug delivery for encapsulation and manufacture of different nanoparticles that have shown significant potential in mitigating and surmounting different constraints, such as taste masking, enhanced drug solubility and bioavailability, and production of micronized fine powders for treatment of varying diseases. Nevertheless, the usage of these technologies in HIV pediatric formulations has garnered relatively little attention. Thus, this review has paid a keen interest in examining several microencapsulation strategies for potential utilization in the development of HIV pediatric formulations.