Current Issue : January-March Volume : 2026 Issue Number : 1 Articles : 5 Articles
Background/Objectives: The rise of multidrug-resistant bacteria and fungi, or “superbugs”, makes the development of new antimicrobial compounds of continued importance. In this context, we have explored structural variants of the plant-derived phytocompound berberine, seeking higher antimicrobial activity and selectivity. Our prior work prepared fourteen protoberberine variants (B1–B14), and found that a partially reduced dihydroprotoberberine (B14) was significantly more active against Gram-positive bacteria. To further investigate this trend, we prepared a series of protoberberines and related dihydroprotoberberines, with the goal of better understanding the effects of the partial reduction of the protoberberine core. Methods: Protoberberines were prepared from a cyclization between glyoxal and substituted N-benzyl-phenethylamines, prepared by reductive amination. Dihydro-derivatives were obtained via NaBH4 reduction. Biological activity was assessed with a Kirby–Bauer assay to determine zones of inhibition against a panel of twelve microorganisms. Cytotoxicity was also assessed using an MTT assay against a T84 human colon carcinoma cell line. Results: The majority of the prepared compounds showed greater Gram-positive antibacterial activity compared to original berberine, and nearly all dihydro-protoberberines had improved Gram-positive antibacterial activity over their unreduced form. Additionally, the reduced variants were less active against fungi, indicating a step towards higher microbial selectivity. All variants showed greater potency against cancer cells. Conclusions: The present work highlights a significant improvement in antibacterial activity and selectivity for this set of dihydro-protoberberines over their unreduced counterparts....
Chicoric and chlorogenic acids (CRA and CGA), two caffeic acid derivatives found in a large variety of plants, particularly in Asteraceae, are known to modulate glucose-6- phosphatase (G6Pase) in hepatic and muscle cells. The aim of the present study is to use CRA/CGA to explore the modulation role and molecular mechanism of endocrine pancreatic beta-cells’ insulin secretion. The G6Pase enzyme activity influenced by caffeic and derivatives alone or in combination was assessed on microsomal fractions of INS1-betacells and hepatocytes. Overall, our results show inverse effects of CGA/CRA, allowing us to investigate the G6Pase activity modulation under low and high glucose concentrations. Our data strongly suggests the existence of two putative forms of the G6Pase enzyme. Based on these observations, we formulate the hypothesis of an adaptative bi-conformational model of G6Pase enzyme activity modulation depending on the level of the beta-cell glucose exposure....
Background/Objectives: Colorectal carcinoma (CRC) is among the most commonly diagnosed cancers in both men and women. Although CRC mortality is generally decreasing, new therapeutic options are needed for unresponsive subgroups of CRC patients. Methods: A series of known and new tyrphostin derivatives was tested for their efficacy against three CRC cell lines with varying KRAS, p53, and/or BRAF statuses. Growth inhibition, apoptosis induction, and inhibition of EGFR and VEGFR-2 were investigated. Results: Tyrphostin A9, the known RG13022-related tyrphostin 1a and its dichlorido(p-cymene)ruthenium(II) complex 1b, and the new SF5-substituted compounds 2a and 2b showed selective antiproliferative activity against KRAS-mutant HCT-116 CRC cells expressing wildtype p53, while p53-knockout HCT-116 and KRAS-wildtype BRAF/p53-mutant HT-29 CRC cells were distinctly less sensitive. In HCT-116 cells, only tyrphostin A9 increased mRNA expression of caspases 3 and 8, as well as the kinases MEK1 and MEK2, whereas 2a reduced caspase 8 mRNA levels. Tyrphostin A9 increased caspase 3 activity and induced apoptosis in HCT-116 p53-wildtype cells while simultaneously inhibiting the receptor tyrosine kinases EGFR and VEGFR-2 at low nanomolar concentrations. Conclusions: Tyrphostin A9 could be a promising therapeutic option for the treatment of KRAS-mutant CRC that expresses wildtype p53....
Background: Ferulic acid (FA) is a natural phenolic compound that has demonstrated effectiveness against Huntington’s disease (HD). However, its exact mechanism remains unclear. Therefore, the current study aims to investigate FA’s potential mechanism of action against 3-nitropropionic acid (3NP)-induced HD. Methods: Adult male Wistar albino rats were administered FA orally (100 mg/kg) for 3 weeks, and 3NP (10 mg/kg) was intraperitoneally administered during the last 2 weeks to induce HD. Behavioral performance was assessed using the open field and hanging wire tests. Striatal tissue was analyzed using ELISA, qRT-PCR, Western blotting, histopathology, and immunohistochemistry. Results: Administration of 3NP led to weight loss, neurobehavioral deficits, oxidative damage, apoptotic cell death, and neuroinflammation. FA treatment mitigated these pathological changes by activating Nrf2/HO-1 signaling, a critical player in cellular redox balance. This beneficial effect was mirrored in restoring TAC levels and suppressing MDA. Moreover, FA suppressed TLR4/NF-κB inflammatory signaling, thereby reducing TNF-α and IL-1β levels. In addition, the anti-apoptotic properties of FA were confirmed by modulating SIRT1/ p53 signaling, leading to Bcl-2 enhancement and caspase-3 downsizing. Furthermore, FA enhanced neuronal survival and plasticity confirmed by neurotrophic BDNF elevation. Histopathological and immunohistochemical analyses confirmed improved neuronal survival and reduced gliosis following FA treatment. Conclusion: The current research demonstrates that FA exhibits potent neuroprotective effects in experimental HD by modifying Nrf2/HO-1, TLR4/NF- κB, and SIRT1/p53 signaling pathways. These findings provide new mechanistic insights into FA’s potential role in managing HD....
Background: Ethanol intake leads to cognitive deficits. Recent research demonstrated that a dysregulation of synaptic vesicle glycoprotein 2A (SV2A) expression seems to be linked to anxiety and memory disorders. Levetiracetam and brivaracetam are two antiseizure drugs that affect the SV2A protein. This study aimed to assess the impact of these drugs on associative learning and anxiety-like behaviors in ethanol-treated rats. Methods: Adult maleWistar rats (n = 64) were given brivaracetam or levetiracetam via i.g. for three weeks at doses of 300 mg/kg or 6 mg/kg, respectively. Ethanol was administered as a 20% solution twice a day, via i.g., at a morning dose of 1.5 g/kg b.w. and an afternoon dose of 3.5 g/kg b.w. Additionally, 5% ethanol was available ad libitum between 4:00 p.m. and 8:00 a.m. Associative learning was evaluated using the passive avoidance test during the alcohol administration period, as well as the contextual fear conditioning and cued fear conditioning tests during the withdrawal period. The level of anxiety was determined using the elevated plus maze test in withdrawal rats. Results: Ethanol consumption resulted in impaired associative memory, and its withdrawal was linked to increased anxiety levels. Levetiracetam enhanced memory performance in the passive avoidance test, but brivaracetam disturbed memory associated with unpleasant stimuli in the contextual fear conditioning. Additionally, withdrawal-induced disturbance of locomotor activity persisted, particularly in animals receiving levetiracetam in the elevated plus maze. Conclusions: Levetiracetam appears to provide certain beneficial effects, whereas brivaracetam may worsen memory disturbances in rats....
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