Current pharmaceutical design最新文献

Osteoporosis is a major global health problem. The increase in the incidence of osteoporosis in the elderly poses a challenge to treat and also results in an economic burden for the nation. Osteoporosis has been given more importance in females, and there is an urgent need to address this disease in males. Various drugs, such as nitrogen-containing phosphonates, RANK ligand inhibitors, parathormones, and alendronate, have been used for effective treatment of osteoporosis. Alendronate (alendronic acid), a nitrogen-containing bisphosphonate that inhibits bone resorption by osteoclasts, was synthesized during the 1970s. In the present review, we discuss the pharmacokinetics, mechanism of action, adverse effects, contraindications, and toxicity monitoring of alendronate. The drug may be effectively used for the treatment of male osteoporosis in order to increase bone mineral density and prevent fractures.

The rise of antimicrobial resistance (AMR) has become a serious global health issue that kills millions of people each year globally. AMR developed in bacteria is difficult to treat and poses a challenge to clinicians. Bacteria develop resistance through a variety of processes, including biofilm growth, targeted area alterations, and therapeutic drug alteration, prolonging the period they remain within cells, where antibiotics are useless at therapeutic levels. This rise in resistance is linked to increased illness and death, highlighting the urgent need for effective solutions to combat this growing challenge. Nanoparticles (NPs) offer unique solutions for fighting AMR bacteria. Being smaller in size with a high surface area, enhancing interaction with bacteria makes the NPs strong antibacterial agents against various infections. In this review, we have discussed the epidemiology and mechanism of AMR development. Furthermore, the role of nanoparticles as antibacterial agents, and their role in drug delivery has been addressed. Additionally, the potential, challenges, toxicity, and future prospects of nanoparticles as antibacterial agents against AMR pathogens have been discussed. The research work discussed in this review links with Sustainable Development Goal 3 (SDG-3), which aims to ensure disease-free lives and promote well-being for all ages.

Background and objective: Alzheimer's Disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti- inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB) for neuroprotection.

Methodology: CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/- day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons.

Results: There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score- 5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), β-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels (p < 0.001), whereas NO, catalase, and LPO levels were significantly (p < 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly (p < 0.001) decreased.

Conclusion: In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.

Introduction: Diabetic retinopathy is the major cause of vision failure in diabetic patients, and the current treatment involves the practice of glucocorticoids or VEGF antagonists that are "off-label". A few small organic molecules against DR were discovered many years ago. Nutraceuticals are naturally available functional foods that endorse different health benefits, including vitamins, antioxidants, minerals, fatty acids, and amino acids that can defer the development of some diseases.

Methods: Numerous studies reported that nutraceuticals encourage multiple therapeutic benefits and provide protection against various diseases. In diabetes, nutraceuticals contribute to improving insulin sensitivity, metabolism regulation, and lower hyperglycemia. The major aim of this study is to discover the most active drug from natural or plant sources. In this work, 42 phytochemical constituents from 4 kinds of plants were docked with the C4 target of diabetic retinopathy by an in silico molecular docking study.

Results: According to the binding energy, all the phytoconstituents possessed good to high attraction towards the target, and 6 phytochemicals, such as terchebulin, punicalagin, chebulagic acid, casuarinin, punicalin, and pedunculagin, disclosed superior binding energy towards the target than standard ruboxistaurin via the interactions of conventional hydrogen bonding, pi-alkyl interactions, etc. Molecular dynamic simulation studies further established the stability of the phytoconstituents, and ADMET studies proved the safety profile of these phytoconstituents.

Conclusion: Hence, the current study suggested that the phytochemicals from various herbs inhibit the C4 target of diabetic retinopathy and can be utilized as lead compounds to develop analogs or repurposed for the treatment of DR.

De Quervain's disease (DQD) is commonly reported in mothers during pregnancy up to delayed postpartum period. A cross-sectional study was conducted to assess infant caregivers who visited the paediatric outpatient department or vaccination centre in two hospitals of Lahore, during the months of May and June, 2021. A total of 190 subjects were interviewed directly and assessed by applying Finkelstein's test on both hands. Data was collected using Numeric Pain Rating Scale (NPRS) and Patient Rated Wrist Evaluation (PRWE) from positive subjects. They were asked to report their pain and difficulty level of the affected hand with worsened symptoms. The results exhibited 26.8% prevalence of DQD in a sample size of 190. Infant's age, lifting frequency and hand dominance were proved significant risk factors. However, caregiver's age, history of wrist pain, infant weight and relationship with infant were proved insignificant. Mean PRWE pain and functional scores were 23.14±7.72 and 18.53±6.09, respectively.

Skin cancer is broadly classified into two categories i.e., non-melanoma skin cancer (NMSC) and malignant melanoma (MM), with MM having a greater fatality rate than NMSC. A large number of treatment strategies currently exist for these skin cancer types, ranging from monotherapies to complex multifaceted synergistic interventions including dual therapies, trimodality therapy, and multicomponent combinations therapy. These combinatorial cancer treatments have delivered more favorable results when compared with monotherapies, and although combination treatments increase the cost of treatment, these regimens have lower side effect profiles, decreased resistance, high efficacy and an improved long-term response. Synergistic combination treatments for skin cancer are often complex, wide-ranging and encompass diverse platforms with various mechanisms of action. An understanding of the physiological potential, as well the efficacy of such treatments, is therefore vital to ensure patients receive the best possible treatment. This review therefore focuses on the current advancements and existing non-surgical combinative drug delivery methods utilized for treating skin cancer. It encompasses the diverse pharmaceutical delivery systems, clinical outcomes, and oncology strategies employed and aims to highlight the role of non-surgical combination therapies in enhancing patient compliance, reducing treatment durations, and improving overall survival rates while addressing relapses and metastasis. The promising outlook of the research being conducted in this field has also been provided, as well as the barriers to the effective treatment of this complex condition.

Introduction: The COVID-19 pandemic represents a significant challenge across scientific, medical, and societal dimensions. The unpredictability of the disease progression, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), underscores the urgent need for identifying compounds that target multiple aspects of the virus to ensure swift and effective treatment. Nyctanthes arbortristis L., a delicate, perennial, deciduous shrub found across various Asian regions, has been recognized for its wide range of pharmacological benefits, including hepatoprotective, antimalarial, antibacterial, anti-inflammatory, antioxidant, and antiviral properties.

Methods: Various in vitro studies revealed the therapeutic significance of Nyctanthes arbortristis against COVID-19. However, the exact molecular mechanism remains unclarified. In the present study, a network pharmacology approach was employed to uncover the active ingredients, their potential targets, and signaling pathways in Nyctanthes arbortristis for the treatment of COVID-19. In the framework of this study, we explored the active ingredient-target-pathway network and figured out that naringetol, ursolic acid, betasitosterol, and daucosterol decisively contributed to the development of COVID-19 by affecting IL6, MAPK3, and MDM2 genes.

Results: The results of molecular docking analysis indicated that Nyctanthes arbortristis exerted effective binding capacity in COVID-19. Further, we disclosed the targets, biological functions, and signaling pathways of Nyctanthes arbortristis in COVID-19. The analysis indicated that Nyctanthes arbortristis could help treat COVID-19 through the enhancement of immunologic functions, inhibition of inflammatory reactions and regulation of the cellular microenvironment. In short, the current study used a series of network pharmacologybased and computational analyses to understand and characterize the binding capacity, biological functions, pharmacological targets and therapeutic mechanisms of Nyctanthes arbortristis in COVID-19.

Conclusion: However, the findings were not validated in actual COVID-19 patients, so further investigation is needed to confirm the potential use of Nyctanthes arbortristis for treating COVID-19.