Physiological concentrations of reactive oxygen species (ROS) play vital roles in various normal cellular processes, whereas excessive ROS generation is central to disease pathogenesis. The nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor that regulates the cellular antioxidant systems in response to oxidative stress by governing the expression of genes encoding antioxidant enzymes that shield cells from diverse oxidative alterations. NRF2 and its negative regulator Kelch-like ECH-associated protein 1 (KEAP1) have been the focus of numerous investigations in elucidating whether NRF2 suppresses tumor promotion or conversely exerts pro-oncogenic effects. NRF2 has been found to participate in various pathological processes, including dysregulated cell proliferation, metabolic remodeling, and resistance to apoptosis. Herein, this review article will examine the intriguing role of phase separation in activating the NRF2 transcriptional activity and explore the NRF2 dual impacts on tumor immunology, cancer stem cells, metastasis, and long non-coding RNAs (LncRNAs). Taken together, this review aims to discuss the NRF2 multifaceted roles in both cancer prevention and promotion while also addressing the advantages, disadvantages, and limitations associated with modulating NRF2 therapeutically in cancer treatment.

Clinopodium sericeum is widely used in Peruvian folk medicine in the form of infusion to treat stomach distress, indigestion and antiflu. In this study, the essential oil from C. sericeum was obtained by hydrodistillation, analyzed by GC and GC/MS, and 73 compounds were identified. Major components of the oil were b-germacrene-D (15%), b-caryophyllene (13.8%), and sabinene (11.2%). Furthermore, we assessed the in vitro biological activities displayed by the oil obtained from the aerial parts of C. sericeum, namely the antioxidant, antimicrobial and antiproliferative activities. The antioxidant activities of the essential oil were evaluated by FRAP, CUPRAC, ABTS and DPPH radical scavenging activity. The essential oil displays antibacterial activity against Gram-negative and Gram-positive bacterial strains (MIC 50-200 µg/mL) in a dose-range close to standard antibiotics. Such activity may be related to the presence of terpene compounds. The antiproliferative activity of the essential oil was measured in vitro using the MTT colorimetric assay in healthy non-tumorigenic cells (HEK-293) and in three human cancer cell lines (T24, DU-145, and MCF-7). The calculated IC50 values were around 0.2 mg/mL. Since the essential oil was almost devoid of antioxidant activity, its anti-proliferative action is unlikely related to oxidative stress and relies on other unknown mechanisms.

Organic compounds with antibacterial and antiparasitic properties are gaining significance for biomedical applications. This study focuses on the solvent-free synthesis (green synthesis) of 1,4-naphthoquinone or 2,3-dichloro-1,4-naphthoquinone with different phenylamines using silica gel as an acid solid support. The study also includes in silico PASS predictions and the discovery of antibacterial and antiparasitic properties of phenylaminonaphthoquinone derivatives 1–12, which can be further applied in drug discovery and development. These activities were discussed in terms of molecular descriptors such as hydrophobicity, molar refractivity, and half-wave potentials. The in vitro antimicrobial potential of the synthesized compounds 1–12 was evaluated against a panel of six bacterial strains (three Gram-positive: Staphylococcus aureus, Proteus mirabilis, and Enterococcus faecalis; and three Gram-negative bacteria: Escherichia coli, Salmonella typhimurium, and Klebsiella pneumoniae). Six compounds (1, 3, 5, 7, 10, and 11) showed better activity toward S. aureus with MIC values between 3.2 and 5.7 μg/mL compared to cefazolin (MIC = 4.2 μg/mL) and cefotaxime (MIC = 8.9 μg/mL), two cephalosporin antibiotics. Regarding in vitro antiplasmodial activity, compounds 1 and 3 were the most active against the Plasmodium falciparum strain 3D7 (chloroquine-sensitive), displaying IC₅₀ values of 0.16 and 0.0049 μg/mL, respectively, compared to chloroquine (0.33 μg/mL). In strain FCR-3 (chloroquine-resistant), most of the compounds showed good activity, with compounds 3 (0.12 μg/mL) and 11 (0.55 μg/mL) being particularly noteworthy. Additionally, docking studies were used to better rationalize the action and prediction of the binding modes of these compounds. Finally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed.

Lepidium meyenii Walp. (black maca, BM) is a traditional Andean crop increasingly studied for its bioactive potential. This work characterized the phytochemical profile and evaluated the antioxidant, antinociceptive, and neuroprotective properties of a lyophilized aqueous extract of BM hypocotyls. UHPLC-ESI-QTOF-MS/MS identified twelve major compounds, including macamides, imidazole alkaloids, sterols, and fatty acid amides. BM showed a moderate total phenolic content but strong electron transfer-based antioxidant activity in CUPRAC and FRAP assays, together with moderate radical scavenging capacity in ABTS and DPPH systems. In ovariectomized rats, BM significantly reduced brain malondialdehyde levels, mitigated oxidative stress, and improved spatial learning during acquisition in the Morris water maze, confirming its neuroprotective effect. Antinociceptive assays (hot plate, cold plate, and tail immersion) further revealed a rapid but transient increase in nociceptive thresholds. This study provides experimental evidence supporting the analgesic effect of black maca. Molecular docking highlighted lepidiline B and campesterol as key metabolites with strong interactions with redox enzymes, the μ-opioid receptor, and the FAAH enzyme, supporting their role in the observed bioactivities. ADMET predictions indicated favorable oral bioavailability, CNS penetration, systemic clearance, and acceptable safety profiles. These results substantiate the role of black maca as a neuroprotective nutraceutical and highlight its promise as a novel source of rapidly acting natural analgesic compounds.

Juglans neotropica (Peruvian walnut) has been widely used by Andean populations in the form of infusions and decoctions for its antioxidant, hypoglycemic, hepatoprotective, antifungal, and antibacterial properties. This study aimed to investigate the effect of Juglans neotropica extract (JNE) on the spasmolytic activity in rat ileum. Our experiments demonstrated that JNE displayed spasmolytic activity at high concentrations, but did not exhibit antispasmodic effects. Additionally, we determined the juglone concentration in JNE by HPLC-DAD, synthesized juglone using green chemistry and compared its spasmolytic activity with that displayed by JNE. Juglone displayed spasmolytic activity on isolated rat ileal sections. Juglone produced a relaxant effect after contraction by a mechanism involving the inhibition of M₂ and M₃ muscarinic receptors and the blockade of calcium channels, with no apparent effect on the opening of potassium channels. Finally, in silico molecular docking analyses showed that juglone displayed high docking scores for M₂ and M₃ muscarinic acetylcholine receptors and Ca_V1.2 voltage-gated calcium channels. In summary, JNE exhibits a spasmolytic, but not an antispasmodic, effect, whereas juglone demonstrates both spasmolytic and antispasmodic activities. These findings provide a scientific basis for the potential use of juglone for managing intestinal hypercontractility disorders. Further research is needed to elucidate the precise molecular interactions to explore its therapeutic applications in gastrointestinal dysfunction.

Quinones are natural compounds widely distributed in animals, plants, and microorganisms, where they play essential roles in cellular energy metabolism. Ascorbate (vitamin C) can exert antioxidant or pro-oxidant effects depending on concentration and cellular context. Studies have shown that quinones can undergo redox cycling, leading to the generation of reactive oxygen species (ROS), a process that is further enhanced in the presence of ascorbate. Due to the elevated production of reactive oxygen species (ROS) and compromised antioxidant defenses in cancer cells, redox imbalance has been proposed as a potential "Achilles' heel" of tumors. In this context, the combination of ascorbate and quinones represents a promising strategy for selectively targeting cancer cells through enhanced ROS generation. This review discusses the mechanisms and biological effects of natural and synthetic quinoid compounds, particularly their interactions with ascorbate in cancer cells.