Advances in Pharmacological and Pharmaceutical Sciences最新文献

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.

A safer alternative made of plant extracts is needed, as evidenced by the negative effects of using synthetic sunscreen. Antioxidant properties of plants with high phenolic content have been reported. The goal of this research was to ascertain the phenolic content and antioxidant characteristics of ethanolic extracts made from grape and olive leaves under various extraction settings. The extracts were subjected to both qualitative and quantitative analyses using HPLC. Soxhlet extraction with 80% ethanol (v/v) as the solvent produced a result that was satisfactory. Four components of grape leaf extract and one component of olive leaf extract were identified. Expressed as gallic acid equivalents (GAEs), the total phenolic content (TPC) of the samples, as determined by using the Folin-Ciocalteu's reagent, ranged from 38.39 to 72.78 mg/g dry extract of olive and 65.918-132.7 mg/g dry extract of grape. An ethanolic extract of Salmoni (grape leaves) had the highest TPC (132 mg GAE/g), while an ethanolic extract of Zaity (olive leaves) had the lowest (72.66 ± 0.46 GAE/g). The Folin-Ciocalteu method proved the existence of antioxidants in the plant. By scavenging free radicals such as DPPH (2,2-diphenyl-1-picrylhydrazyl), the antioxidant capacity of the plant extracts was determined. Next, the ethanolic extracts of various cultivars of grape and olive leaves were analyzed to determine their sun protection factor (SPF) value. It was 28.8 and 29.96 for grape leaf extract and olive leaf extract, respectively.

Compared with the use of a single herb alone, herb combinations can significantly increase their effectiveness in treating various diseases. The objective of this research was to determine the appropriate proportions of Garcinia mangostana (GM), Curcuma comosa (CC), and Acanthus ebracteatus (AE) to enhance their antioxidant and anti-inflammatory properties. The study employed computer modeling (in silico) and laboratory testing (in vitro). The optimal levels of phenolic and flavonoid compounds were achieved with a ratio of 15 parts GM, 5 parts CC, and 10 parts AE. In contrast, the 10 : 15 : 5 ratio resulted in the highest antioxidant activity, reducing DPPH radicals by 80.33% and ABTS radicals by 92.20%. The ratio had a synergistic effect and was within the safe range, ranging from 82.97 to 147.04 µg/mL. The ratio of 5 : 10 : 15 had the greatest anti-inflammatory effects, with an exceptional activity level of 98.86%. It effectively suppressed 23 genes or proteins, including the prominent NFE2L2 gene, and had a synergistic effect. This combination effectively inhibits inflammation (IC₅₀: 12.05 µg/mL) and is safe for macrophages at concentrations up to 50 µg/mL. These findings emphasize the potential of these herbal mixtures for antioxidant and anti-inflammatory applications.

The Trikaysornmas formula (TKM) represents a prevalent Thai traditional remedy utilized extensively in Thailand. Its traditional uses include appetite enhancement, functions as a nourishing tonic, and exhibits adaptogenic properties. Comprising Aegle marmelos fruit, Nelumbo nucifera stamen, and Jatropha multifida bark, this formula embodies the synergy among these three herbs. The objective of this study was to optimize the extraction method, determine the active compounds in the TKM, and evaluate its antioxidant activity. The optimization of the extraction method for this formula was studied using an experimental design. Phytochemical components such as total phenolics, total flavonoids, total carotenoids, and total alkaloids were assessed utilizing a colorimetric method. Antioxidant activities were assessed through DPPH free radical scavenging, ABTS radical cation decolorization, oxygen radical absorbance capacity, ferric reducing antioxidant power, metal chelating activity, and lipid peroxidation assay. For the analysis of active constituents in the formula, gallic acid, kaempferol-3-o-glucoside, imperatorin, vitexin, and scopoletin, a validated reversed-phase column high-performance liquid chromatography (HPLC) method was developed. The total active contents including phenolic, flavonoid, carotenoid, and alkaloid compounds were found in the formula. The developed HPLC method exhibited reliable results in all validation parameters. TKM demonstrated antioxidant activity in the models used in this research. The findings from this study can serve as valuable tools for standardization and quality control measures. Additionally, they can contribute to maximizing the possibilities inherent in this traditional Thai formulation.

Colitis-associated colon cancer (CAC) arises from prolonged inflammation of the inner colon lining. An alternative approach to treating or preventing CAC involves the use of natural products such as Manilkara zapota (L.) P. Royen or M. zapota, which has been studied for its medicinal and pharmacological properties. Previous research has demonstrated the anticancer effects of M. zapota leaf aqueous extract (MZLAE) on colon cancer cells. However, no animal study has investigated the effects of MZLAE on CAC. Therefore, this study aimed to assess the potential anti-inflammatory effects of MZLAE on CAC in mice. In the present study, CAC was induced using azoxymethane (AOM) and dextran sodium sulphate (DSS). The mice were randomly assigned into five groups: (a) normal, (b) AOM/DSS, (c) AOM/DSS + 50 mg/kg MZLAE, (d) AOM/DSS + 100 mg/kg MZLAE, and (e) AOM/DSS + 200 mg/kg MZLAE. Various parameters including disease activity index (DAI), colon length and weight, reactive oxygen species (ROS), superoxide, superoxide dismutase (SOD), histopathological assessment, and proinflammatory cytokines expression were analysed. The results indicated that MZLAE improved DAI scores, colon length, colon histological dysplasia and inflammation scores, and SOD level, while also reducing ROS production and expression of proinflammatory cytokines (tumour necrosis factor-alpha (TNF- α) and interleukin 6 (IL-6)). In conclusion, this study suggests that MZLAE may serve as a promising source of antioxidants and anti-inflammatory agents for alleviating CAC.