Current pharmaceutical design最新文献

Introduction: Traditional Chinese Medicine (TCM) employs various processing methods to enhance the bioactivity of herbs. Rheum palmatum (R. palmatum) is commonly processed to optimize its medicinal properties, yet its antibacterial activity under different processing techniques remains unclear. Standardizing preparation methods is essential for ensuring consistent therapeutic efficacy. This study examines how different processing methods influence the antibacterial activity of R. palmatum, contributing to the standardization of TCM preparation.

Materials and methods: R. palmatum roots underwent 10 different water-based processing methods. Antibacterial activity against S. aureus was assessed using disc diffusion and broth microdilution assays. The most effective extracts were further analyzed via molecular docking to evaluate their binding interactions with bacterial virulence proteins (α-hemolysin and Catalase).

Results: Disc diffusion and MIC results showed that RP-4 (high-pressure steamed with wine) exhibited the largest inhibition zone (11.67 mm) and the lowest MIC (1250 μg/mL). Compared to other tested microorganisms, selective inhibition was also observed against S. aureus. Molecular docking revealed that Rhein, a major active compound identified in the RP-4 extract, exhibited strong binding affinity to α-hemolysin and Catalase, comparable to standard antibiotics.

Discussion: RP-4, processed through high-pressure steaming with wine, showed the strongest antibacterial activity based on ZOI and MIC results. Wine processing enhances the dissolution of active compounds, while high-pressure steaming reduces anthraquinone derivatives that cause digestive problems. Molecular docking also confirmed interactions between Rhein and the virulent proteins α-hemolysin and Catalase, suggesting a potential mechanism for inhibiting S. aureus.

Conclusion: Processing methods significantly influence the antibacterial properties of R. palmatum. RP-4 demonstrated the strongest activity against S. aureus, making it a promising candidate for future TCM formulation and antibacterial drug development.

The main culprit behind cutaneous candidiasis, a fungal infection that can lead to major dermatological and systemic health problems, is Candida albicans. Over the past 20 years, cutaneous candidiasis has become more prevalent, especially in hospitalized or immunocompromised patients. Conventional treatment methods employ antifungal drugs like azoles and polyenes, which are effective but have drawbacks because of their high recurrence rates, negative side effects, and growing antifungal resistance. This study highlights recent advancements in novel treatment techniques for cutaneous candidiasis. New antifungal medications that more precisely target specific fungal pathways, including echinocandins and triazole derivatives, are examples of emerging techniques. The most common symptoms are interdigital candidiasis, cheilitis, intertrigo, and diaper dermatitis, but they can occur elsewhere in the body. Other types of Candida may be the reason for infections that occur from person to person, even though C. Candida albicans is the most frequent culprit. The most typical signs of Candida infections are burning and tingling. Skin symptoms might vary, in any case. The two main signs of candidiasis are bright erythema and skin erosions with satellite pustules. Yeast is the main cause of cutaneous candidiasis. Candida, especially Candida albicans, is characterized by epidermal exposure of the skin, nails, interdigital space, and mucous membranes. This study discusses several species of Candida. parapsilosis, C. kefyr, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis, C. guilliermondii, C. lusitaniae, and C. albicans. The primary targets of antifungal drugs are the nucleic acids, cell walls, and cell membranes of Candida species.

Cholelithiasis, particularly cholesterol-bearing-stones, is one of the gastrointestinal diseases representing a substantial global health burden. The five key primary factors inducing cholesterol-bearing-stones include genetics, hepatic cholesterol hypersecretion, rapid phase transition of cholesterol, gallbladder hypomotility, and specific intestinal factors. To date, laparoscopic cholecystectomy remains the primary treatment approach for cholelithiasis patients. The various non-surgical methods, such as bile acid therapy, novel drug candidates, and herbal remedies, are detailed. Special attention is paid to the development of ursodeoxycholic acid (UDCA)-embedded formulations. Because the UDCA is a biopharmaceutical classification system class II drug, it poses the challenge of low aqueous solubility and thus, limited oral bioavailability. Additionally, promising developments in novel drug candidates (e.g., alirocumab), probiotics, stents, and herbal treatments with purported gallstone-dissolving properties are highlighted. The development of effective non-surgical treatments like various UDCA formulations and novel drug candidates is crucial. Additionally, the integration of herbal remedies into mainstream treatment protocols could offer significant benefits. Future research should focus on optimizing these therapies and exploring personalized treatment. Furthermore, emerging curative approaches such as gene-tailored therapy hold a future direction with a concrete perspective.

Citrullus lanatus (watermelon) is a fruit with remarkable therapeutic potential, as each part of itrind, peel, flesh, and seeds contain bioactive compounds. Despite its wide range of benefits, the utilization of watermelon, particularly its rind, remains limited due to a lack of awareness and an underrated perspective. The rind, situated between the green outer peel and the red flesh, is light green in color and rich in bioactive compounds, minerals, and phytochemicals. These constituents are associated with various therapeutic properties, including antioxidant, antineoplastic, cardiovascular, and neuroprotective effects. In addition to its therapeutic applications, watermelon rind offers significant commercial value in the food, cosmetic, and pharmaceutical industries, as well as in industrial applications such as biofuel production and eco-friendly packaging. Its versatility makes watermelon rind an exciting area of research for uncovering new applications and enhancing existing ones. However, limitations in its usage and handling need to be addressed for its broader adoption. This review comprehensively discusses the global research conducted to date on the nutritional composition, therapeutic potential, environmental impact, and commercial applications of watermelon rind. Additionally, it highlights challenges and future directions for advancing the utilization of this promising resource.

Despite the availability of current peripheral pain medications, patients continue to experience acute pain and often need more potent analgesic options. As a result, the discovery of novel molecules is of significant importance. In recent years, the functional properties of peptides have opened new possibilities for pain treatment. This review explores the peptides derived from venoms that target peripheral pain pathways, while briefly investigating the peptides involved in the pathophysiology of peripheral pain. Key peripheral pain receptors include transient receptor potential vanilloid 1 and 2 (TRPV1 and TRPV2), voltage-gated calcium (Ca++), sodium (Na+), and potassium (K+) channels, as well as acid-sensing ion channels (ASICs). Venoms have shown remarkable potential as a source of new therapeutic molecules. Among venomous creatures, cone snails, snakes, sea anemones, tarantulas, scorpions, and spiders are known to possess analgesic peptides. These peptides exert their pain-relieving effects by influencing ion channels and other receptors. Recent studies have investigated the mechanisms of peptides isolated from venoms in various types of pain. These peptides exhibit robust analgesic effects in animal models. This study demonstrates that analgesic peptides derived from venom effectively reduce peripheral pain intensity, presenting promising new molecules for potential medical applications in peripheral pain management.

Introduction: Ibrutinib is a selective tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). However, it has low oral bioavailability (2.9%), which is attributed to low solubility (0.002 mg/mL) and a first-pass effect. Ibrutinib-loaded nanostructured lipid carriers (IBR-NLCs) were prepared and investigated in this study to overcome the solubility and presystemic metabolism issues. The goal of the current study was to formulate IBR-NLCs for enhanced bioavailability. IBR-NLCs were optimized using a 32 factorial design and evaluated using various in vitro and in vivo parameters.

Methods: IBR interaction with solid lipid (Glyceryl monostearate) and liquid lipid (oleic acid) was studied using molecular docking. The hot-melt ultrasonication method was used to formulate IBR-NLCs, and a 32 factorial design was used for optimization. Particle size, PDI, zeta potential, entrapment efficiency, DSC, XRD, FTIR, SEM, and in vitro study were used to evaluate the NLCs. HepG2 cell lines were used to study the in vitro cytotoxicity of IBR-NLCs and IBR suspension. IBR-NLCs were administered to male Wistar rats in the presence and absence of cycloheximide (CXI) to compare pharmacokinetic parameters.

Results: Molecular docking confirmed good interaction between IBR-GMS and IBR-oleic acid. The optimized IBR-NLCs showed particle size, PDI, zeta potential, and %EE of 154.5 ± 0.7 nm, 0.2 ± 0.0, -25.8 ± 1.1 mV, and 84.0 ± 1.2%, respectively. The IC50 values of IBR suspension and IBR-NLCs were 3.03 and 4.155 μg/mL. The AUC0-24 of IBR-NLCs administered in the absence of CXI was 1.60 times higher than the AUC0-24 values in the presence of CXI, indicating lymphatic transport.

Conclusion: IBR-NLCs appear to be promising as a novel innovative nanocarrier for the management of CLL.

The eye, due to its complex anatomy and physiology, presents numerous barriers that restrict the access of drug molecules to the site of action for the maintenance of optimal concentration. Thus, limited drug bioavailability is one of the significant issues with commercially existing drug delivery systems in achieving overall therapeutic effectiveness. Recently, the field of ocular health and management has garnered much attention for the innovation of efficient nanotechnology approaches to overcome the constraints imposed by the intricate anatomy and physiology of the eye. Hypothesizing that the conjugation of mRNA-based therapies with the latest nano delivery systems can overcome these barriers, this review was designed to explore the outstanding potential of these approaches for the management of ocular disorders. With extensive investigations of current findings, the authors believe that such integrations present exciting opportunities to pave the way for the development of effective approaches for various ocular disorders such as uveitis, Leber congenital amaurosis, age-related macular degeneration, retinitis pigmentosa, and many more. Moreover, the approaches exploiting the combination of mRNA and nanotechnology offer effective solutions to address the limitations of currently available management strategies. This review presents various innovative mRNA-based nanotechnology approaches, their mechanisms, challenges, and prospects for further development, focusing on the immense potential of mRNA-based strategies to revolutionize the landscape of ocular therapeutics.

Background: Rumex nervosus Vahl is a phenomenal plant from Arabian Peninsula and East African areas. It potentially contains massive therapeutic phytochemicals, including Omeprazole, sitosterols, fatty acids, flavonoids and carotenes. Omepazole (a commercial drug) is used to treat stomach ulcers, gastroesophageal reflux and cardiac disorders. Beta-sitosterol (commercial drug) reduces cholesterol levels and body swelling. It is also known to manage rheumatoid arthritis.

Methodology: The present study evaluated the pharmacological potential and metabolite profiling of Rumex nervosus through various extracts. The extraction was performed using different solvents (Petroleum ether, Chloroform, n-Hexane, Butanol, Methanol, and distilled water) through soxhlet extraction method. Serial dilutions of (100-3.125 mg/mL) were prepared. The biological activities, antimicrobial, anti-diabetic, Hemolytic, anti-inflammatory, and antioxidant (DPPH radical Scavenging, Total anti-oxidant and total phenolic content assays) were performed. Statistical analysis of experimental data was carried out by using SPSS Version 20 and Origin 6.0. Data was represented as mean ± standard deviation (n=3). Differences among mean values were determined using Two-way ANOVA and Tukey's test. The level of statistical significance was set at p ≤ 0.05. The potential extracts were further analyzed for phytochemicals through GC-MS and Network pharmacology (In silico approach).

Results: The plant exhibited the best antioxidant activity (86.7% ± 1.92) at 100 mg/mL with distilled water extract. The highest anti-inflammatory activity (90.64 ± 2.34) (88.31 ± 2.37) was given by n-butanol and distilled water extracts at 100 mg/mL. The optimum anti-diabetic activity (92.78 ± 1.89) was observed at 100 mg/mL with n-butanol.

Discussion: The maximum zone of inhibition was measured with n-butanol extract against Pseudomonas aeruginosa (36.67 ± 0.32) at 100mg/mL, and in the case of Xanthomonas oryzae again n-butanol extract showed maximum zone of inhibition (30.47 ± 0.32) at 100 mg/mL. The maximum fungal zone of inhibition (22.33 ± 0.40) was noticed with n-butanol extract against Fusarium oxysporom at 100 mg/mL, and in the case of Aspergillus niger maximum fungal zone of inhibition was measured with n-butanol extract (16.20 ± 0.25) at 100 mg/mL. Hemolysis activity was highest (4.12 ± 0.01) with the methanol extract at 3.125 mg/mL. R. nervosus displayed the best activities with n-butanol and distilled water extract. GCMS and network pharmacology combined approach identified seven phytochemicals associated with oxidative stress and infectious diseases (1-Tetradecanol, Stigmast-5-ene, Phthalic acid 2-ethylhexyl isohexyl ester, A-Norcholestan-3-one, 5-ethenyl-, (5.beta.), 16-Heptadecenal, gamma-Sitosterol, Omeprazole). Degree score method selected 10 top hub genes, including AKT1, TNF, and EGFR, as potential targets fo

Mitochondria are known as the powerhouse of eukaryotic cells. They play a crucial role in several biological processes and maintain cellular health. The ideal condition of mitochondria depends not only on their morphology but also on various micro-environmental factors, including pH, polarity, and temperature. Changes in these factors or malfunctions of mitochondrial species, such as Reactive Oxygen Species (ROS), active nitrogen species, metal cations, anions, and protons, can lead to several diseases in humans, including heart failure, kidney disorders, diabetes, Alzheimer's disease, and Parkinson's disease. Therefore, monitoring Reactive Small Molecules (RSMs), maintaining micro-environmental factors, and estimating ROS levels in mitochondria are essential for understanding physiological behaviour and the pathogenesis of related diseases. Irregularities in mitochondrial function are closely linked to a range of clinical conditions, highlighting the importance of targeting mitochondria for therapeutic benefits. Over the last decade, numerous studies have focused on the development of small organic conjugated systems for mitochondrial imaging, utilizing optical signal transduction pathways. In this review, the design and synthetic strategies for small organic fluorophores conjugated with a pyridinium acceptor, their applications in mitochondrial imaging, and the detection of RSMs in mitochondria have been discussed. Studies have revealed that small-molecule fluorescent probes are being widely used for the detection and imaging of RSMs located in mitochondria. Moreover, this review covers the mechanistic insights, photophysical properties, biological characteristics of fluorophores, and therapeutic strategies targeting the mitochondria of human cells.