Pharmaceuticals

Background: Obesity and hypertriglyceridemia are complex metabolic conditions that arise from the expansion of white adipose tissue and dysfunction in lipid metabolism. Given the limitations of conventional therapies, plant-derived extracts have been investigated as promising alternative strategies. Objectives: The present study aimed to characterize the phytochemical profile of the hydroethanolic extract from Anemopaegma arvense leaves (HEAa), assess its toxicological safety, and investigate its effects on metabolic phenotype safety related to lipid accumulation using complementary biological models. Methods: HEAa was chemically characterized by LC-DAD-MS, and its toxicological profile was assessed using complementary in vitro, ex vivo, and in vivo models. Its effects on lipid-related metabolic phenotypes were assessed in adipocytes, Caenorhabditis elegans, and Wistar rats with high-fructose diet (HFrD)-induced body-weight gain and hyperlipidemia after 70 days of treatment. Results: HPLC-DAD-MS analysis revealed a chemically diverse profile composed mainly of flavonol glycosides, hydroxycinnamic acid derivatives, lipid-derived compounds, triterpenoids, megastigmane glycosides, and pheophorbide a; rutin was confirmed by comparison with an authentic standard. HEAa showed no hemolytic activity in human erythrocytes and did not reduce viability in C. elegans under the tested conditions. In 3T3-F442A adipocytes and C. elegans, HEAa produced modest reductions in neutral lipid accumulation. In high-fructose-fed Wistar rats, repeated HEAa administration reduced body-weight gain by approximately 53% and serum triglycerides by approximately 56% compared with untreated high-fructose-fed animals. Increases in ALT and AST levels were observed following prolonged exposure. Conclusions: HEAa modulated lipid accumulation and obesity-related metabolic phenotypes across complementary experimental models, with effects on body-weight gain and hypertriglyceridemia in rats fed a high-fructose diet. These findings support further investigation of A. arvense as a botanical candidate for metabolic disorders, nevertheless, the increases in hepatic enzymes highlight the need for additional studies to define its long-term safety.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which play essential roles in extracellular matrix (ECM) remodeling. Among them, MMP-2 and MMP-9 are mainly associated with tumor invasion, angiogenesis, metastasis, and other pathological processes such as fibrosis and inflammation, making them attractive therapeutic targets for cancer treatment. Marine natural products, particularly seaweed-derived bioactive compounds, have attracted increasing attention because of their structural diversity, broad pharmacological activities, and generally favorable biocompatibility. Seaweeds are a rich source of polysaccharides, phenolic compounds, fatty acids, pigments, vitamins, and other metabolites with anti-inflammatory, anti-oxidant, and anti-cancer properties. Growing evidence indicates that several of these compounds could suppress cancer cell proliferation, invasion, migration, and metastasis by regulating the activity and/or expression of MMP-2 and MMP-9 and their associated signaling pathways, including MAPK signaling pathways. This review comprehensively summarizes current evidence on seaweed-derived bioactive compounds as modulators of MMP 2 and MMP-9 with particular emphasis on their effects on enzymatic activity, expression, and MMP-associated signaling pathways. In addition, current limitations, translational challenges, and future perspectives for developing seaweed-derived compounds as potential MMP-targeted strategies for cancer prevention and therapy are discussed.

Background: The development of resistance to conventional therapies remains one of the major challenges in the treatment of breast and colorectal cancers, highlighting the urgent need for novel anticancer agents with improved efficacy. In the present study, a series of novel aroyl pyrrole derivatives was designed and synthesized, evolving from the previously identified hit compound 1a, in order to investigate the influence of structural modifications on antitumor activity. Methods: The antiproliferative activity of all compounds was evaluated in vitro against two human breast cancer cell lines (MCF7 and MDA-MB231) and two colorectal cancer cell lines (HT-29 and RKO). Result: Among the synthesized derivatives, compound 3 emerged as the most active analog, displaying antiproliferative activity at low micromolar concentrations and significantly improved potency compared with the parent compound 1a in all tested cell lines. Furthermore, 3 did not show any significant cytotoxicity toward non-transformed HaCaT keratinocytes and normal dermal fibroblasts, suggesting a remarkable degree of selectivity for tumor cells. Flow cytometric analysis demonstrated that both 1a and 3 induced cell-cycle arrest at the G0/G1 phase in all four cancer cell lines, indicating inhibition of cell-cycle progression as one of the mechanisms underlying their antiproliferative activity. Furthermore, both compounds induce cell death in a small percentage of cells through a caspase-3/7-independent mechanism. Conclusions: Overall, these findings identify 3 as a promising compound for the development of novel pyrrole-based anticancer agents and provide useful information on structure-activity relationships for the future optimization of this chemical scaffold.