Advances in Pharmacological and Pharmaceutical Sciences最新文献

The potential uses of extracting mucilage from plant sources have led to much research in this field. One possible source of mucilage for agri-food-pharma utilization is the fruits of the Phoenix dactylifera, date palm. For developing the plaster gel loaded with nicotine, we, therefore, applied the mucilage from date palm fruits as a gel-forming agent. Other components, however, might be added to increase its properties. Response surface methodology was used for quantifying the effects of a range of variables (date palm mucilage, PVA, and glycerin) on physicochemical parameters (pH value, viscosity, drying time, ultimate tensile strength, elongation at break, and drug content). The optimal formulation was 3.5%:1.8%:30% w/w. The resultants were 6.14 ± 0.05, 45.67 ± 1.75 cp, 14.77 ± 1.19 min, 26.83 ± 2.15 MPa, 38.20 ± 2.39%, and 9.51 ± 0.19 mg/g, respectively. The optimal formulation of nicotine-containing plaster gel had a semicrystalline structure as it was derived from plant mucilage. It was immediately obvious that the formulation might control the release of nicotine, indicating first-order kinetic release. The J _ss and K _p values were 0.30 ± 0.01 mg/cm²/h and 3.13 ± 0.11 × 10^-2 cm/h, respectively, indicating a maximum nicotine permeation of 78.82 ± 13.57%. When stored in a refrigerator as compared to room temperature, the nicotine-loading plaster gel thus showed excellent physical stability.

Heat-shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70's dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal-organic frameworks, demonstrate enhanced targeting and therapeutic efficacy through HSP70 modulation. Functionalized nanocarriers exploit HSP70's tumour-specific overexpression to improve drug delivery, minimise off-target effects and overcome the blood-brain barrier. Emerging strategies such as chemophototherapy, immunotherapy and photothermal therapy leverage HSP70's interactions within the tumour microenvironment, enabling synergistic treatment modalities. The review also highlights translational challenges, including heterogeneity of GBM, regulatory hurdles and variability in the enhanced permeability and retention (EPR) effect. Integrating computational modelling, personalised approaches and adaptive trial designs is crucial for clinical translation. By bridging nanotechnology and molecular biology, HSP70-targeted strategies hold transformative potential to redefine GBM diagnosis and treatment, offering hope for improved survival and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 and NCT04628806.

Our previous study has shown the beneficial effect of the ethanolic extract of Sangyod rice (SE) on lipid accumulation and insulin resistance. However, its effect on vascular inflammation has yet to be explored. The current study aimed to investigate the anti-inflammatory effects of SE in both in vitro and in vivo models, specifically examining its impact on LPS-induced inflammation in RAW264.7 cells and evaluating its efficacy in an animal model of diabetes mellitus induced by a high-fat diet combined with a low-dose streptozotocin. In the in vitro experiments, SE treatment effectively suppressed the LPS-induced activation of key signaling pathways, including Akt, ERK1/2, p38 MAPK, and NF-κB, which are known to play pivotal roles in the inflammatory response. SE was also found to reduce oxidative stress and the production of inflammatory markers in the LPS-stimulated RAW264.7 cells. In the in vivo experiments, the administration of SE (500 mg/kg BW) and metformin (200 mg/kg BW) to high-fat diet/streptozotocin-induced diabetic rats effectively improved dyslipidemia, as evidenced by reductions in serum total cholesterol, LDL-cholesterol, and triglycerides compared to the untreated diabetic control group. Importantly, SE ameliorated the damage to the vascular endothelium and elastic fibers by downregulating the expression of proinflammatory cytokines and oxidative stress markers. Additionally, SE administration attenuated the upregulation of key markers associated with ER stress-mediated apoptotic pathways, with effects comparable to those observed in diabetic rats treated with the standard antidiabetic drug metformin. These findings suggest that SE possesses both anti-inflammatory and vascular protective properties, evident in both in vitro and in vivo studies.

Bleomycin, an antibacterial antibiotic, is used in chemotherapy and is effective against various forms of human carcinomas. However, its use is limited due to its tendency to cause pulmonary fibrosis. Oxidative stress and excessive expression of TGF beta occur in pulmonary fibrosis, leading to cellular death, inflammation, and additional damage to lung tissue. Metformin has the ability to reduce oxidative stress and lower the level of TGF beta by activating AMPK. Additionally, ascorbic acid possesses potent antioxidant characteristics. Consequently, we decided to investigate the effects of these two medications on pulmonary fibrosis and compare with methyl prednisolone. Thirty-six adult mice were categorized into 6 distinct groups: Control, bleomycin (bleo), bleo + methyl prednisolone, bleo + metformin, bleo + ascorbic acid, bleo + metformin + ascorbic acid. Pulmonary fibrosis was induced by the administration of bleomycin in all groups, except for the control group. Subsequently, medications were administered for a duration of 14 days. Ultimately, the mice were sacrificed and lung tissues were obtained for biochemical and histological examination. As shown by biochemical and histological analysis, all treatment groups showed a decrease in oxidative stress factors, inflammation, and lung tissue fibrosis; however, the effects of administering metformin and ascorbic acid together were noticeable. Our study found that administering metformin and ascorbic acid over a period of 14 days, either alone or in combination, may contribute to the repair of pulmonary fibrosis. However, our data indicate that the combined therapy of these drugs provided a better result.

Alzheimer's disease (AD) is a neurological condition that causes neurons and axons in the brain to deteriorate over time and in a specific pattern. The enzyme beta-secretase-1 (BACE-1) plays a crucial role in the onset and progression of AD. In silico approaches, or computer-aided drug design, have become useful tools for reducing the number of therapeutic candidates that need to be evaluated in human clinical trials. Finding chemicals that bind to BACE-1's active site and inhibit its activity is key for preventing AD. A pharmacophore model was developed in this study based on potent BACE-1 inhibitors previously identified, and subsequently employed to screen a commercially available compound database for similar compounds. ZINC35883784 was identified with high binding affinities and hydrogen bonding interactions. Moreover, similar properties to donepezil were found in a compound made by altering the structure of ZINC35883784 called (4R,5R)-2-[1-(2-ethylcyclohexyl)ethyl]-4-hydroxy-5-(4-hydroxybutyl)cyclohexanolate (M4). Compounds were tested for interactions with BACE-1 and favorable properties. Binding scores were confirmed after molecular docking. The assessment of drug-likeness was conducted utilizing Swiss ADME analysis. Molecular dynamics simulations assessed the stability of compound interactions with BACE-1. MMPBSA calculated binding free energy and contribution energy. Results showed that M4 had strong and steady interactions with BACE-1. M4 was also analyzed by predicted NMR and retrosynthesis. However, further experiments are needed to evaluate M4's potential as a BACE-1 inhibitor.

Numerous therapeutic potentials of rutin (RUT) including cardioprotective, neuroprotective, and antihypertension activities have attracted many studies to bring it into clinical use. RUT is phytochemically derived from plants such as apples and tea. It is poorly soluble and very sensible to acidic pH in the stomach environment which leads to conceded oral bioavailability. In contrast, RUT is better soluble in basic environment, thus, encapsulating RUT within enteric microparticles (RUT-MP) using casein (CAS) resolved such problems. The encapsulation by spray-drying employed sugars (lactose, sucrose, and maltodextrin) as bulking agents and for stabilization of the amorphous drug. The developed RUT-MP formulations were prepared in two groups i.e., lower and higher RUT concentrations. The solid states were studied by X-ray diffraction (XRD), differential thermal analysis (DTA) and scanning electron microscopy (SEM). Solubility tests were also carried out on the samples to examine the outcome of the engineered physical modification. The results showed that the RUT-MPs were spherical in morphology. The RUT was transformed into amorphous structure as suggested by the XRD and DTA results indicating that RUT was molecularly dispersed in the RUT-MP. There were no phase separations that occurred as confirmed by the DTA data. Solubility tests carried out on the RUT-MPs showed that the encapsulation with CAS in group with higher concentration of RUT prevented the drug against recovery of the crystallinity and phase separations. The solubility test revealed various substantial enhancements of RUT solubility of the RUT-MPs at pH 7.0. The highest enhancement of RUT solubility was 191,5-fold, with respect to pure RUT. The presence of sugars was beneficial as they improved the yield percentage and might have contributed to the prevention of nano-crystal aggregation which made them a determining aspect for the successful application of spray-dried encapsulation.

Rationale and Objective: The pain-depression dyad is highly prevalent and has reciprocal psychological and behavioral effects, leading to poor quality of life, increased disability, and challenging therapeutic outcomes. In an attempt to find better substances that can target pain-depression comorbidity, we examined the effect of aqueous (AE) and ethanol (EE) extracts from Acacia sieberiana (A. sieberiana) stem bark on reserpinized mice (female and male Swiss albino mice aged 2-3 months). Methods: The dyad was induced with 3 injections (Days 1-3) of reserpine (1 mg/kg/day, s.c.). Then, animals were treated (Days 4-8) with plant extracts (25, 50 and 100 mg/kg/day, p.o.) or L-tryptophane (100 mg/kg/day, i.p.). Pain-like (tactile and cold allodynia) and depression-like (pole, tail suspension, and force swimming tests) behavioral parameters were evaluated on Days 4 and 8. On Day 9, animals were sacrificed for the quantification of acetylcholinesterase activity, oxidative stress parameters, total catecholamines, dopamine, serotonin, IL-1β, and TNF-α levels in the brain or spinal cord. IL-1β and TNF-α were also assayed in the serum. The acute toxicity and phytochemical analysis of EE were conducted. Results: Reserpine-induced tactile and cold allodynia, depression-like behavior, increased serum IL-1β and TNF-α, brain acetylcholinesterase activity, and decreased catecholamine concentration were all reversed by AE and EE. Plant extracts significantly increased dopamine levels and reduced oxidative stress in the brain and/or spinal cord. No significant effect was observed on brain serotonin and TNF-α. EE elicited the best pharmacological activity and was nontoxic. LC-MS/MS molecular networking phytochemical analysis identified 5 compounds with high certainty including piperine, aurantiamide acetate, and asperphenamate. Conclusion: AE and EE are effective against pain and depression. Their pharmacological activities might be related to the modulation of inflammation, oxidative stress and catecholamine, and the presence of bioactive natural products.

Due to its intricacy and long-term usefulness, traditional medicine continues to be practiced in several nations. Among the many medicinal plants found in the Dhofar region of Oman, the aromatic oleo-gum resin generated by Boswellia sacra, commonly referred to as frankincense, stands out for its medical and commercial significance. Resin-carrying ducts are unique to members of the Boswellia family. Boswellia sacra Flueck is one of the 29 species in the genus Boswellia (Burseraceae) and has long been cultivated for its aromatic gums and resins for use as incense. In addition to the resins (60%-80% alcohol soluble), gums (15%-20% water soluble), and essential oil (5%-7%), other components, including polysaccharides and polymeric compounds, also exist in smaller amounts. Physiochemical analyses indicate that Boswellia resin oil is made up of 42.5% diterpenes, 13.1% monoterpenes, and 1% sesquiterpenes. Traditional medicine makes extensive use of frankincense for the treatment of stomach diseases, Alzheimer's disease, and hepatic illnesses. The bioactive chemicals present in frankincense, particularly boswellic acids, are plentiful. The current review examines various compounds present in different species of Boswellia, especially Boswellia sacra, along with their structure.

This study investigated the pharmaceutical potential of extracts from Ammi visnaga (Ammi) and Petroselinum crispum (Parsley), specifically focusing on their antioxidant activity, total phenolic content, and efficacy in disintegrating calcium oxalate kidney stones. Ammi and Parsley extracts, known for their traditional medicinal uses, contain bioactive compounds with significant antioxidant properties that have attracted attention in pharmaceutical research. Oxidative stress, a key factor in various physiological disorders, underscores the importance of antioxidants in the mitigation of cellular damage. Our investigation revealed concentration-dependent enhancements in antioxidant activity and total phenolic content in both Ammi and Parsley extracts, indicating their potential as natural antioxidant agents. Furthermore, both extracts were effective in reducing the size of calcium oxalate stones, with the Ammi extract demonstrating superior stone-disintegration properties. Dissolution studies have provided valuable insights into the release kinetics of phenolic compounds and antioxidant activity, suggesting sustained therapeutic potential. Overall, Ammi and Parsley extracts show promise in pharmaceutical development, offering alternative therapeutic avenues for managing oxidative stress-related conditions and kidney stone formation.

The long-term pathological state known as metabolic syndrome is characterized by hypertension, insulin resistance diabetes, abdominal obesity, and hyperlipidemia. Seeking healthcare strategies with fewer side effects, such as herbal remedies, is preferable in terms of mitigating the negative consequences of synthetic medications. Ziziphus lotus (L.) (Rhamnaceae) or wild jujube, commonly known as "Sedra," is one of the best choices as it contains a variety of phytochemicals and biologically active compounds. Several flavonoids and stilbenes have been recognized as the primary bioactive components in wild jujube, including rutin, hyperin, isoquercitrin, and resveratrol. These polyphenols are pharmacologically active and have broad-spectrum beneficial effects for reducing the risk factors associated with metabolic syndrome. They exhibit antioxidant and anti-inflammatory properties, regulate lipid metabolism, and possess antiobesity, antihypertensive, and antidiabetic characteristics. However, there are certain limitations to their therapeutic application, such as low bioavailability. Various strategies have been proposed to enhance their pharmacokinetic profile and therapeutic potential for future use. The main goal of this review is to explore the underlying mechanisms related to the therapeutic effects of wild jujube and its active compounds in the treatment and prevention of metabolic syndrome.