RESUMEN

Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.

Asunto(s)

RESUMEN

Despite considerable progress in cancer treatment options, resistance to chemotherapeutic drugs remains a significant challenge. This review focuses on Berberine (BBR), an isoquinoline alkaloid found in various medicinal plants, which has garnered attention in the field of oncology for its anticancer potential either alone or in combination with other compounds and its ability to modulate chemoresistance, acting as a natural chemosensitizer. BBR's ability to modulate chemoresistance is attributed to its diverse mechanisms of action, including inducing DNA breaks, inhibition of drug efflux pumps, modulation of apoptosis and necroptosis, downregulating multidrug resistance genes, enhancing immune response, suppressing angiogenesis and targeting multiple pathways within cancer cells, including protein kinase B/mammalian target of rapamycin (Akt/mTOR), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), poly(ADP-ribose) polymerase (PARP1), janus kinase/signal transducers and activators of transcription (JAK-STAT), Wnt/ß-catenin etc. Moreover, BBR, in combination with other compounds, also offers a promising approach to cancer therapy, enforcing its broad-spectrum anticancer effects. Therefore, this review aims to elucidate the intricate mechanism of action of BBR in combinatorial therapy as a potential chemosensitizer to increase the efficiency of several drugs, including cisplatin, doxorubicin, lapatinib, tamoxifen, irinotecan, niraparib, etc. in various cancers. Additionally, this review briefly covers the origin and biological activities of BBR, exploring the specific actions underlying its anticancer effects. Further, pharmacokinetic properties of BBR are also discussed, providing insight into its therapeutic potential and optimization of its use in cancer treatment.

Asunto(s)

RESUMEN

The need to explore the abundance of natural products cannot be overemphasized particularly in the management of various disease conditions. In traditional medical practice, Vernonia amygdalina has been widely adopted in the management of various inflammatory disorders. The objective of this investigation was to isolate the bioactive principles from the stem-bark and root of V. amygdalina and assess the anti-inflammatory (in vitro) activity of both the crude extracts and the isolated compounds. Following extraction with the methanol, the extract was subjected to gravity column chromatography and the resultant fractions was further purified to obtained pure compounds. The structural elucidation of the compounds were based on data obtained from 1H to 13C nuclear magnetic resonance (NMR) spectroscopies as well as fourier transform infrared (FT-IR). Using diclofenac as a control drug, the albumin denaturation assay was used to determine the in vitro anti-inflammatory activity of the extracts and isolates. Three distinct compounds characterized are vernoamyoside D, luteolin-7-α-o-glucuronide, and vernotolaside, a new glycoside. When compared to diclofenac, which has an IC50 of 167.8 µg/mL, luteolin-7-α-o-glucuronide, vernoamyoside D, and vernotolaside all showed significant inhibitions with respective IC50 values 549.8, 379.5, and 201.7 µg/mL. Vernotolaside is reported for the first time from the root. The assertion that the plant is used in traditional medicine for the management of inflammatory disorder is somewhat validated by the confirmation of the existence of the compounds with the biochemical actions. Further validation of the isolated compounds would be required in animal studies.

RESUMEN

PURPOSE: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. METHODS: A series of SNEDDS formulations were developed using naturally obtained medium-chain/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan®. RESULTS: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28-45 nm globule size, 0.10-0.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73-88 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 ± 27.31 and 1138.66 ± 44.97 µg/mL, as compared to 891.44 ± 26.05 µg/mL (p = 0.05) observed after the IV administration of raw propofol. CONCLUSION: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.

Asunto(s)