Current Pharmaceutical Design - Online First

Skin ageing is influenced by intrinsic factors such as genetics and hormones, as well as extrinsic factors like environmental exposure, ultraviolet (UV) radiation, and diet. These factors lead to biochemical, biological, and structural changes in the skin. Plant-derived compounds with antioxidant and anti-inflammatory properties have emerged as potential anti-ageing agents. This comprehensive review, spanning data from 1997 to 2024, explores the role of nutraceuticals in skin anti-ageing. The research data were drawn from Google, PubMed, PubMed Central, Scopus, and various journal databases, including ScienceDirect, Springer, and Taylor Francis. This review specifically examines plant-derived polyphenols, carotenoids, and other bioactive compounds, analysing their mechanisms through signalling pathways and cellular processes, using data from in vitro, in vivo, and clinical studies. Polyphenols like quercetin, curcumin, and epigallocatechin gallate (EGCG) have antioxidant and anti-inflammatory properties, helping to reduce oxidative stress, inflammation, UV-induced collagen degradation, and inflammatory cytokines. Notably, curcumin enhances collagen production and decreases the number of senescent cells. Carotenoids such as β-carotene, lutein, zeaxanthin, and lycopene protect against UV damage, and lycopene-rich tomato paste was specifically noted for its ability to reduce erythema and DNA damage. Additionally, compounds like resveratrol, fisetin, and wogonin exert protective effects against oxidative stress and inflammation, with resveratrol improving collagen synthesis and reducing the appearance of wrinkles. These plant-derived compounds can effectively combat skin ageing through various mechanisms, including the inhibition of oxidative stress, inflammation, and extracellular matrix degradation. They present a natural and sustainable approach to skincare in accord with the growing trend of conscious consumption. Future research should focus on understanding the long-term effects and determining the optimal dosage for clinical applications, highlighting the potential of integrating plant-based nutraceuticals into skincare regimens.

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disease primarily characterized by insufficient insulin secretion or reduced insulin sensitivity in the body's cells, leading to persistently high blood glucose levels. Ganoderma lucidum triterpenoids, as important secondary metabolites of Ganoderma lucidum, have shown preliminary potential efficacy in the treatment of T2DM according to existing research. However, due to the structural complexity and diversity of these triterpenoid compounds, as well as the intricate interactions between their therapeutic targets and active ingredients, the precise molecular and pharmacological mechanisms remain to be further explored.

Objective: In the present research, we aim to fully employ the integrated approach of network pharmacology and molecular docking methodologies, delving deeply into the potential therapeutic targets and their underlying pharmacological mechanisms in the management of T2DM via Ganoderma lucidum triterpenoids.

Methods: The active compounds were sourced from prior research and the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Their potential targets were predicted with the aid of Swiss Target Prediction. Genes linked to T2DM were gathered from DisGeNET and GeneCards. Using Cytoscape, we established the network connecting active ingredients, targets, and pathways, and the target protein-protein interaction (PPI) network was created using data from the STRING database. The core targets of Ganoderma lucidum triterpenoids underwent gene enrichment analysis via DAVID. Lastly, to validate our chosen Ganoderma lucidum triterpenoids, we conducted molecular docking experiments between the compounds and their targets.

Results: A total of 53 Ganoderma lucidum triterpenoids and 116 associated targets were identified. Among these, SRC, MAPK1, MAPK3, HSP90AA1, TP53, PIK3CA, and AKT1 emerged as pivotal targets. We retrieved 447 Gene Ontology (GO) functional annotations and 153 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, notably including the PI3K-Akt signaling pathway, Endocrine resistance, Rap1 signaling pathway, and Lipid and Atherosclerosis, which are known to be associated with T2DM. Our findings suggest that Ganoderma lucidum triterpenoids may confer resistance to T2DM through mechanisms related to hyperexcitability, cell death, cell survival, proliferation, differentiation, and inflammation.

Conclusion: A comprehensive, interdisciplinary, and multi-technology approach has been established, which uncovers the collaborative effects and underlying principles of Ganoderma lucidum triterpenoids in the management and therapy of T2DM from a holistic perspective. This approach provides new insights into the development of novel biological control products for Type 2 Diabetes Mellitus (T2DM) and lays the foundation for future systematic studies on the interactions between Ganoderma triterpenes and different targets, elucidating their primary and secondary pathways for lowering blood glucose.

Nanoemulsions have gained popularity as drug delivery vehicles owing to the enhanced solubility of insoluble drugs, the augmented stability of photo- and thermosensitive substances, and the facilitation of transdermal permeation of efficacy substances. As the cell surfaces of the skin, cornea, gastrointestinal mucosa, and other cells in living organisms carry negative charges, cationic nanoemulsions (CNE) mainly promote drug absorption through electrostatic effects. In this review, a brief characterization of CNEs is provided, and the types of cationic agents and their roles in nanoemulsions, including cationic surfactants, cationic lipids, cationic polymers, cationized polysaccharides, and phytosphingosine (PS), are discussed. In addition, the current application circumstances of CNEs in ocular drug delivery, mucosal drug delivery, and transdermal drug delivery systems are elaborated on, and the crucial matters that require attention during the research process are briefly discussed. Eventually, the extensive application prospects of CNEs are envisioned.

Chronic Kidney Disease (CKD) affects about 37 million Americans. Approximately 20% of patients with high blood pressure and 33% of patients with diabetes have kidney disease. CKD is most common among people aged 65 or older and is slightly more common in women. It substantially impacts certain ethnic groups more than others and is associated with a huge financial burden. End-Stage Kidney Disease (ESKD) is treated with dialysis or a kidney transplantation. CKD and ESKD are very detrimental and expensive illnesses, demanding creative therapeutic interventions to enable better management and enhanced clinical outcomes. Toward this goal, agents from various novel drug classes showed promising safety and efficacy in patients with varying severity of CKD in several phase 2 studies. This concise review will shed light on the clinical trials of runcaciguat, cotadutide, osocimab, and Endothelin Receptor Antagonists (ERAs) in patients with CKD and/or ESKD. These drugs were retrieved following surveying the Clinical Trial database as well as the Pubmed database, both maintained by the US National Library of Medicine.

The field of cancer therapy has witnessed significant strides with the emergence of innovative drug delivery systems and one such promising avenue is solid lipid-based nanoparticle (SLN) technology. This abstract provides a complete overview of current advances in developing SLNs for effective cancer treatment solid lipid nanoparticles (NPs) represent a novel drug delivery platform characterized by their unique composition which includes biocompatible lipids as the main carrier material. This technology addresses challenges related to standard chemotherapy such as low bioavailability limited medicine stability and non-specific targeting. The incorporation of lipids in SLNs ensures enhanced drug encapsulation, protection of therapeutic agents from degradation-controlled release profiles. Recent breakthroughs in SLN technology have focused on optimizing formulation parameters to achieve superior drug loading capacities stability and sustained release kinetics. Advanced fabrication techniques including high-pressure homogenization and microemulsion methods have been pivotal in tailoring SLN properties for specific cancer types and therapeutic agents. Furthermore, SLNs' capacity to passively build up in tumor tissues using increased penetration and retention effects has been harnessed for targeted drug transport. Surface modifications using ligands or antibodies to facilitate active targeting, enhancing medication delivery's selectivity to tumor cells decreasing unwanted effects on normal tissues. This abstract highlights recent preclinical and clinical studies demonstrating the efficacy of SLN-based formulations in enhancing the therapeutic outcomes of various anticancer agents. The versatile nature of SLN technology makes it a viable option for the advancement of personalized and precision cancer therapies, marking a significant stride toward overcoming the limitations of conventional cancer treatments. As research in this domain progresses, the integration of SLNs holds immense potential for revolutionizing tumor treatment strategies.

Thrombomodulin (TM) is a single-chain transmembrane glycoprotein with anticoagulant effects. TM has two forms: membrane type existing on the cell surface and blood type free in plasma and urine. TM functions as an anticoagulant cofactor for thrombin activation of protein C on the surface of vascular endothelial cells. Due to the excellent anti-coagulant effects in modulating the coagulation and fibrinolytic system, the recombinant human soluble TM (rhsTM) has been used for the treatment of disseminated intravascular coagulation (DIC). In addition to anti-coagulation, many studies have shown that TM can also exert anti-inflammatory and anti-tumor effects. TM has a lectin-like domain at its N-terminus that has been shown to exhibit direct anti-inflammatory functions. At the same time, due to its special structure, thrombomodulin plays an important role in vascular-related mechanistic diseases by participating in the regulation of inflammatory pathways, complement, HMGB1, etc. In this article, changes in TM expression in the body after injury, composition of TM structural domains, anticoagulant, anti-inflammatory, and antitumor effects, and related mechanisms of TM were systematically reviewed, to provide a theoretical basis and reference for the potential clinical implications of TM in treating various diseases.