Advances in Pharmacological and Pharmaceutical Sciences最新文献

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.

Kidney is an essential organ that is highly susceptible to cellular injury caused by various toxic substances in the blood. Several studies have shown that untreated injuries to this organ can cause glomerulosclerosis, tubulointerstitial fibrosis, and tubular cell apoptosis, leading to kidney failure. Despite significant advancements in modern treatment, there is no fully effective drug for repairing its function, providing complete protection, and assisting in cell regeneration. Furthermore, some available medications have been reported to exacerbate injuries, showing the need to explore alternative treatments. Natural drugs are currently being explored as a new therapeutic strategy for managing kidney diseases. Kaempferol, a polyphenol found in plants, including vegetables, legumes, and fruits, has been extensively studied in various nephrotoxicity protocols. The compound has been reported to have potential as a nephroprotective agent with beneficial effects on various physiological pathways, such as CPL-induced kidney injury, DOX, LPO, ROS, RCC, and diabetic nephropathy. Therefore, this study aims to provide a brief overview of the current nephroprotective effects of kaempferol, as well as its molecular mechanisms of action, biosynthesis pathways, and clinical prospects.

Subchondral defects are often caused by trauma involving cartilage damage, leading to subsequent damage to the underlying bone, specifically the subchondral region. Bilayer scaffolds made from biomaterials, such as bovine hydroxyapatite, possess biocompatible and biodegradable properties that mimic the natural environmental conditions of target tissues so that they can support the formation of new tissues. On the other side, diclofenac as an anti-inflammatory drug potentiates to inhibit the inflammatory excess regarding the damage. This study aims to study the effectiveness of diclofenac scaffold to rabbit joint defect model. The scaffold was implanted in the rabbit femoral trochlear bone hole, which had a diameter of 5 mm and a depth of 4 mm. After 28 days of intervention, the animals were examined using macroscopic evaluation, hematoxylin-eosin (HE) staining, and immunohistochemistry (IHC) for type I collagen and type II collagen. Subsequently, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system. The macroscopic ICRS scores were significantly higher (p < 0.05) in the bilayer scaffold implantation group compared to the monolayer scaffold and control groups. Histological ICRS scores were also significantly higher (p < 0.05) in the bilayer scaffold group compared to the control group. Type II collagen expression was higher (p < 0.05) in the bilayer scaffold group compared to the monolayer scaffold and control groups, although type I collagen expression was lower in comparison. In conclusion, this research suggests that the diclofenac-loaded bilayer scaffold effectively enhances cartilage and subchondral bone regeneration.

Neuroinflammation is important in the pathophysiology of several degenerative brain disorders. This study looked at the potential neuroprotective benefits of cilostazol, a phosphodiesterase inhibitor, against LPS-induced hippocampus damage in rodents and the principal molecular involvement of AKT/GSK3β/CREB signaling pathways. Behavioral tests revealed that cilostazol successfully corrected LPS-induced neurobehavioral impairments. Furthermore, cilostazol therapy lowered hippocampal levels of amyloid beta 1-42 (Aβ1-42) and p-tau protein, both of which are critical pathological indicators of neurodegenerative disorders. Furthermore, cilostazol administration suppressed LPS-induced rises in hippocampus caspase-3 and NF-κB levels while elevating rat B-cell/lymphoma 2 (BCL2) and brain-derived neurotrophic factor (BDNF) levels, which are implicated in neuronal survival and synaptic plasticity. Cilostazol treatment also restored the decreased phosphorylation of protein kinase B (p-AKT) and reduced the elevated levels of phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) and cAMP response element-binding protein (CREB) in the hippocampus of LPS-treated rats. Histopathological examination revealed that cilostazol ameliorated LPS-induced brain damage with reduced neuronal loss and gliosis. Immunohistochemistry analysis showed a decrease in Iba-1 expression, indicating a reduction in microglial activation in the cilostazol-treated group compared to the LPS group. The findings advocate that cilostazol exerts neuroprotective effects against LPS-induced hippocampal injury by modulating the AKT/GSK3β/CREB pathway and curbing neuroinflammation. Cilostazol may hold promise as a therapeutic agent for neuroinflammatory conditions associated with neurodegenerative diseases.

Introduction: Pharmacokinetic studies have shown that rifampin reduces the levels of oral anticoagulants during the initiation of coadministration, raising concerns about an increased thrombotic risk, but there are limited comparative clinical outcomes between rifampin and warfarin compared with direct oral anticoagulants (DOACs). This study aimed to evaluate the effectiveness and safety of concurrent use of rifampin and warfarin versus DOACs, with assessments of outcome-associated factors and oral anticoagulant (OAC) management quality.

Methods: A total of 142 patients given rifampin plus warfarin (n = 56) or DOACs (n = 86) for over 7 days were included, and their clinical data and outcomes were compared.

Results: The median Charlson Comorbidity Index and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) score of the two groups were 2 and 3, respectively. The incidence rate of composite ischemic or thromboembolic events was 2.16 and 1.44 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.02-7.34). The incidence rate of composite major bleeding or clinically relevant nonmajor bleeding events was 1.58 and 1.52 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted HR of 1.12 (95% CI 0.32-4.45). The risk of composite bleeding events increased with a higher HAS-BLED score (HR: 1.62, 95% CI: 1.02-2.63). Moreover, 34.3% of warfarin users maintained a percent time in therapeutic range of above 50%. Furthermore, 77.9% of DOAC users received appropriate dosing.

Conclusion: No significant differences were observed in terms of the incidence of thrombotic or bleeding events between the two groups during coadministration. In addition, a higher HAS-BLED score was associated with a greater risk of bleeding events regardless of the class of OACs used. Finally, close monitoring of bleeding events should be considered.

Sickness behaviour, a set of behavioural changes associated with neuroinflammation, is expressed as decreased mobility and depressed behaviour. Activation of AMP-activated protein kinase (AMPK) is reported to regulate inflammation in conditions such as Alzheimer and traumatic brain injury. Metformin, an antidiabetic agent acting via AMPK activation, possesses anti-inflammatory properties. Similarly, the reported anti-inflammatory activities of berberine could be partially attributed to its ability to activate AMPK. In this study, we investigated the effects of metformin and berberine against lipopolysaccharide (LPS)-induced sickness-like behaviour, associated with neuroinflammation, impaired cognition, and oxidative stress. Swiss albino mice were divided into four groups, normal control, LPS control, metformin treatment, and berberine treatment. The control groups received saline for 7 days. Groups 3 and 4 received metformin (200 mg/kg) and berberine (100 mg/kg), respectively, orally once daily for 7 days. On day 7, 1 h after the treatments, animals received LPS (1.5 mg/kg i.p.) to induce sickness-like behaviour. Open field test (OFT) and forced swim test (FST), were performed within 2 h of LPS administration. Then, proinflammatory cytokines (IL-1β and TNF-α), acetylcholinesterase activity (AChE), and oxidative stress markers were estimated in the brain homogenate. In the LPS control group, immobility state, proinflammatory cytokines, AChE, and lipid peroxidation were significantly increased, whereas the glutathione levels were decreased. Pretreatment with metformin significantly improved immobility in the FST, with reduced IL-1β, oxidative stress markers, and AChE activity. However, no significant changes were observed in OFT. Berberine pretreatment exhibited only an apparent, statistically insignificant, improvement in sickness-like behaviour assessed using FST and OFT, cytokine levels, oxidative markers, and AChE. Several factors affect treatment efficacy, such as treatment duration and administered dose. Considering these, berberine warrants elaborate preclinical evaluation for neuroinflammation. Nevertheless, based on the effects observed, AMPK activators could regulate neuroinflammation, cognition, and oxidative stress linked with sickness-like behaviour.

Salicylic acid (SA) is widely renowned for its efficacy as a beneficial ingredient for skincare, especially for acne and uneven skin texture. The salicylic acid (SA) niosome formulation combined with the essential component of oleoresin from Dipterocarpus alatus Roxb. ex G. Don or Yang-Na (ODA) was developed and investigated for its physical characteristics, biological effects, and stability. The findings demonstrated that SA combined with ODA in the niosome formulation F4 enhanced the entrapment efficiency of SA, as well as the physical properties and stability of the formulation. Furthermore, the release pattern of this combined formulation indicated sustained release of SA. The permeation of SA was higher in the presence of ODA compared to SA-niosome formulations without ODA. Moreover, this F4 could downregulate the secretion of iNOS, COX-2, and TNF-α including anti-Propionibacterium acnes activities. Consequently, the incorporation of ODA into the niosome formulation has the potential to improve the entrapment efficiency of SA, facilitating controlled release and enhancing permeation, nitric oxide inhibition capabilities, and anti-P. acnes activity. Therefore, F4 has the potential to be developed as a topical product for the combined treatment of inflammation and P. acnes-associated conditions in the future.