Current Drug Targets - Current Issue

Currently, Diabetic Nephropathy (DN) stands as the predominant global cause of end-stage renal disease. Many scientists believe that diabetes will eventually spread to pandemic levels due to the rising prevalence of the disease. While the primary factor leading to diabetic nephropathy is vascular dysfunction induced by hyperglycemia, several other pathological elements, such as fibrosis, inflammation, and oxidative stress, also contribute to the progression of the disease. The primary targets of current DN therapy approaches are the underlying abnormalities of hypertension and glucose. With several targets and fewer side effects, curcumin is a commonly utilized antioxidant in DN. The present study emphasizes the critical role of oxidative stress and inflammation in the development of diabetic nephropathy. It reveals how these factors induce damage in key kidney cell types, highlighting their potential as therapeutic targets for this disease. In addition, by concentrating on Nrf2, SIRT1, HMGB1, NF-κB, and NLRP3 of curcumin, has strong anti-inflammatory and antioxidant characteristics. This review describes the role of curcumin in the therapeutic application of diabetic nephropathy. In this attempt, we tried to elaborate on the bench-to-bedside aspects of curcumin in DN, including clinical and preclinical investigations. The rationales of curcumin’s mechanisms in alleviating symptoms of the DN were discussed. Curcumin could serve as the potential therapeutic agent for the patient seeking to recover from DN.

Emerging challenges to human health necessitate a coordinated effort to find both preventative and therapeutic techniques, with natural products at the forefront of attempts to gain novel medicines and minimize disease transmission and related death. The medicinal potential of chemicals contained in plants has been known for centuries, leading to its use in homes and clinics for the treatment of numerous disorders. Despite global advancements, plant-based medicines continue to be utilized to treat various pathological illnesses or as alternatives to contemporary pharmaceuticals. The safety and low toxicity of natural products have led to their increasing acceptability for the prevention or treatment of many ailments. Flavonoids are biologically active compounds that are classified as polyphenols, which are a type of secondary metabolite found in all plants. Icariside II (ICA-II) is one of the secondary metabolites that belong to the flavonoid category of phytochemicals and is present in Epimedium brevicornum Maxim. In recent years, ICA-II has been discovered to show anti-inflammatory, antioxidant, anticancer, renal protecting, and cardiac protective effects, as well as several other biological characteristics. This review is focused on the exploration of the pharmacological activities of ICA-II. ICA-II is considered a prospective candidate for future clinical investigations due to a number of therapeutic properties.

Breast cancer remains the second most prevalent cancer among women in the United States. Despite advancements in surgical, radiological, and chemotherapeutic techniques, multidrug resistance continues to pose significant challenges in effective treatment. Combination chemotherapy has emerged as a promising approach to address these limitations, allowing multiple drugs to target malignancies via distinct mechanisms of action. Increasingly, the use of phytoconstituents alongside chemotherapeutic agents has shown promise in enhancing treatment outcomes. This combination therapy acts on key signaling pathways such as Hedgehog, Notch, Wnt/β- catenin, tyrosine kinases, and phosphatidylinositol 3-kinase (PI3K), which play critical roles in cellular proliferation, apoptosis, angiogenesis, differentiation, invasion, and metastasis. This review explores various signaling pathways involved in breast cancer progression, discusses conventional treatment methods like surgery, adjuvant radiotherapy, hormonal therapy, and chemotherapy, and highlights emerging nanocarrier-based drug delivery systems (DDS). Liposomes, dendrimers, exosomes, polymeric micelles, and nanoparticles (organic, inorganic, gold, magnetic, carbon-based, and quantum dots) are examined as innovative strategies for enhancing drug delivery efficacy. Furthermore, stimuli-responsive DDSs, including reactive oxygen species (ROS), enzyme-, and hypoxia-responsive systems, are presented as cutting-edge approaches to overcoming drug resistance. Special emphasis is placed on the co-delivery of chemotherapeutic agents and plant-based compounds, particularly in estrogen receptor-positive (ER+) breast cancer. This review aims to provide a comprehensive overview of novel combinatorial strategies and advanced nanocarriers for the effective and targeted treatment of breast cancer.

Diseases affecting bone encompass a spectrum of disorders, from prevalent conditions such as osteoporosis and Paget's disease, collectively impacting millions, to rare genetic disorders including Fibrodysplasia Ossificans Progressiva (FOP). While several classes of drugs, such as bisphosphonates, synthetic hormones, and antibodies, are utilized in the treatment of bone diseases, their efficacy is often curtailed by issues of tolerability and high incidence of adverse effects. Developing therapeutic agents for bone diseases is hampered by the fact that numerous pathways regulating bone metabolism also perform pivotal functions in other organ systems. Consequently, the selection of an appropriate target is a complicated process despite the significant demand for novel medications to address bone diseases. Research has shown the role of various cell signaling pathways, including Wnt, PTHR1, CASR, BMPRs, OSCAR, and TWIST1, in the regulation of osteogenesis, bone remodeling, and homeostasis. Disruptions in bone homeostasis can result in decreased bone density and the onset of osteoporosis. There remains a need for the development of drugs that can enhance bone remodeling with improved side effects profiles. The exploration of promising targets to stimulate bone formation has the potential to significantly advance the field of bone-related medical care, thereby improving the quality of life for millions. Additionally, a deeper understanding of anabolic and catabolic pathway mechanisms could enable future studies to explore synergistic effects between unrelated pathways. Herein, we explore potential drug targets that may be exploited therapeutically using small molecule agonists or antagonists to promote bone remodeling and discuss their advantages and limitations.