Matheus Ribas de Almeida

Background/Objectives: Pyrostegia venusta (Cipó-de-São-João), a native Brazilian Cerrado plant, is rich antioxidant phytochemicals. The efficacy of herbal extracts, particularly their phenolic content and antioxidant potential, is influenced by the extraction method used. This study investigated the effects of two drying methods, hot-air oven drying and freeze-drying, on the antioxidant activity, cytotoxicity, and molecular interactions of aqueous extracts from the flowers and leaves of P. venusta. Methods: antioxidant capacity was assessed using DPPH, FRAP, and Folin–Ciocalteu assays; phenolic profiles were characterized by UHPLC; and cytotoxicity was evaluated via the MTT assay in HaCaT human keratinocyte cells. Additionally, in silico ADMET predictions were conducted to assess pharmacokinetics and potential toxicity, followed by molecular docking to evaluate interactions with the proliferation markers Ki-67 and PCNA. Results: freeze-dried extracts, particularly from the flowers, contained higher concentrations of phenolic compounds and exhibited superior antioxidant activity compared to hot-air oven-dried extracts. UHPLC analysis identified a range of bioactive phenolics including caffeic, chlorogenic, gallic, ferulic, and p-coumaric acids, quercetin, and anthocyanidins such as pelargonidin-3-O-glucoside and peonidin-3-O-glucoside, with distinct compositional differences between leaves and flowers. ADMET analysis revealed generally favorable pharmacokinetic properties for most compounds. Docking simulations indicated that multiple phenolics showed synergistic interactions with Ki-67 and PCNA. Conclusions: our findings highlight freeze-drying as the optimal method for preserving bioactive compounds in P. venusta and support the therapeutic potential of its flower extracts. The evidence supports the notion that the biological effects of P. venusta are driven by synergism among multiple constituents rather than isolated compounds.

Type 2 diabetes mellitus represents a major global health burden and is often preceded by a prediabetic state characterized by insulin resistance and metabolic dysfunction. Mitochondrial alterations, oxidative stress, and disturbances in lipid metabolism are central to the prediabetes pathophysiology. Melatonin, a pleiotropic indolamine, is known to regulate metabolic and mitochondrial processes; however, its therapeutic potential in prediabetes remains poorly understood. This study investigated the effects of melatonin on energy metabolism, oxidative stress, and mitochondrial function in a rat model of prediabetes induced by chronic sucrose intake and low-dose streptozotocin administration. Following prediabetes induction, animals were treated with melatonin (20 mg/kg) for four weeks. Biochemical analyses were conducted to evaluate glucose and lipid metabolism, and mitochondrial function was assessed via gene expression, enzymatic activity, and oxidative stress markers. Additionally, hepatic mitochondrial dynamics were examined by quantifying key regulators genes associated with biogenesis, fusion, and fission. Prediabetic animals exhibited dyslipidemia, hepatic lipid accumulation, increased fat depots, and impaired glucose metabolism. Melatonin significantly reduced serum glucose, triglycerides, and total cholesterol levels, while enhancing the hepatic high-density lipoprotein content. It also stimulated β-oxidation by upregulating hydroxyacyl-CoA dehydrogenase and citrate synthase activity. Mitochondrial dysfunction in prediabetic animals was evidenced by the reduced expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha and mitochondrial transcription factor A, both of which were markedly upregulated by melatonin. The indolamine also modulated mithocondrial dynamics by regulating fusion and fission markers, including mitosuin 1 and 2, optic atrophy protein, and dynamin-related protein. Additionally, melatonin mitigated oxidative stress by enhancing the activity of superoxide dismutase and catalase while reducing lipid peroxidation. These findings highlight melatonin’s protective role in prediabetes by improving lipid and energy metabolism, alleviating oxidative stress, and restoring mitochondrial homeostasis. This study provides novel insights into the therapeutic potential of melatonin in addressing metabolic disorders, particularly in mitigating mitochondrial dysfunction associated with prediabetes.

Carcinogenesis is driven by complex molecular events, often involving key enzymes that regulate oxidative stress (OS). While classical enzymes such as SOD, catalase, and GPx have been extensively studied, other, non-classical oxidative stress-related enzymes (OSRE) may play critical roles in cancer progression. We aimed to explore the role of OSRE involved in an OS scenario and to assess their potential contribution to carcinogenesis in some of the most prevalent cancer types. Through data mining and bioinformatic analysis of gene and protein expression and mutation data, we identified OSRE with altered expression and mutations across cancer types. Functional pathways involving EGFR, MT-ND, GST, PLCG2, PRDX6, SRC, and JAK2 were investigated. Our findings reveal that enzymes traditionally considered peripheral to OS play significant roles in tumor progression. Those OSRE may contribute to cancer initiation and progression, as well as be involved with cancer hallmarks, such as EMT and invasion, proliferation, and ROS production. In addition, enzymes like SRC and JAK2 were found to have dual roles in both promoting ROS generation and being modulated by OS. OSRE also interact with key oncogenic signaling pathways, including Wnt/β-catenin and JAK2/STAT3, linking them to cancer aggressiveness and therapeutic resistance. Future research should focus on translating these findings into clinical applications, including the development of novel inhibitors or drugs targeting these non-classical enzymes.