An investigation into the pharmacological action of P. vicina's active fraction (AFPR) in colorectal cancer (CRC) treatment was undertaken, along with a search for its key components and target molecules.
To evaluate the inhibitory action of AFPR on the growth of colorectal cancer (CRC), the following assays were used: tumorigenesis assays, CCK-8 assays, colony formation assays, and matrix metalloproteinase detection. GC-MS analysis allowed for the determination of AFPR's essential components. To identify active ingredients and key targets of AFPR, network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were employed. Elaidic acid's participation in necroptosis was investigated using siRNA interference and the application of various inhibitors. Using a tumorigenesis experiment, the efficacy of elaidic acid in suppressing CRC growth in vivo was examined.
Repeated studies confirmed that AFPR's action prevented colorectal cancer growth and prompted cell death. As the primary bioactive ingredient in AFPR, elaidic acid was directed towards ERK. SW116 cell colony formation, MMP synthesis, and necroptotic pathways were markedly influenced by the presence of elaidic acid. Furthermore, elaidic acid significantly facilitated necroptosis, primarily by activating the ERK/RIPK1/RIPK3/MLKL cascade.
Our research indicates that AFPR's primary active constituent, elaidic acid, triggers necroptosis in CRC cells, a process mediated by ERK. For colorectal cancer (CRC), this option is a very promising therapeutic alternative. This work offers experimental confirmation of P. vicina Roger's ability to treat colorectal cancer (CRC).
The active component of AFPR, predominantly elaidic acid, was shown to induce necroptosis in CRC cells, this activation being mediated by the ERK pathway. For colorectal cancer, this represents a promising alternative therapeutic intervention. Experimental validation of P. vicina Roger's therapeutic potential in colorectal cancer treatment was provided by this work.
The traditional Chinese medicine compound, Dingxin Recipe (DXR), finds application in the clinical management of hyperlipidemia. Although its curative effects in hyperlipidemia are known, the precise pharmacological mechanisms have yet to be elucidated.
Experiments have shown a significant impact of the gut barrier on the storage of lipids. Considering the interplay between gut barrier integrity and lipid metabolism, this study explored the effects and molecular mechanisms of DXR in hyperlipidemia.
In high-fat diet-fed rats, the effects of DXR were assessed, after identifying its bioactive compounds via ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid and hepatic enzyme serum levels were measured using specific kits, along with colon and liver tissue samples for histological examination. Gut microbiota and metabolites were then analyzed using 16S rDNA sequencing and liquid chromatography-mass spectrometry, and gene and protein expression was determined via real-time PCR, western blotting, and immunohistochemistry, respectively. The pharmacological mechanisms of DXR were investigated further by means of fecal microbiota transplantation and interventions relying on short-chain fatty acids (SCFAs).
Hepatocyte steatosis was mitigated, serum lipid levels were significantly downregulated, and lipid metabolism was improved as a result of DXR treatment. Not only did DXR improve the intestinal barrier, but it also specifically strengthened the colon's physical barrier, resulting in changes to the composition of gut microbiota and a rise in serum SCFA levels. DXR led to an increase in the expression of colon GPR43/GPR109A. Rats treated with DXR, undergoing fecal microbiota transplantation, exhibited a decrease in hyperlipidemia-related characteristics, whereas supplementary short-chain fatty acids (SCFAs) demonstrably enhanced most hyperlipidemia-related phenotypes, concurrently increasing GPR43 expression. click here Additionally, DXR and SCFAs promoted the expression of the colon ABCA1 gene.
A key role of DXR in addressing hyperlipidemia is its fortification of the gut's protective barrier, with a focus on the SCFAs/GPR43 pathway.
Hyperlipidemia is counteracted by DXR, which functions to improve the gut barrier, particularly via the SCFAs/GPR43 pathway.
From antiquity, Teucrium L. species have been frequently employed as traditional remedies, particularly within the Mediterranean realm. The therapeutic scope of Teucrium species extends from addressing gastrointestinal problems and maintaining the health of the endocrine glands to treating malaria and managing serious dermatological conditions. Botanical specimens Teucrium polium L. and Teucrium parviflorum Schreb. are noteworthy examples. click here Two species from this genus have held medicinal value in traditional Turkish practices.
This research delves into the phytochemical profile of the essential oils and ethanol extracts from Teucrium polium and Teucrium parviflorum, collected from disparate locations in Turkey, including assessments of in vitro antioxidant, anticancer, and antimicrobial activities, alongside in vitro and in silico evaluations of their enzyme inhibitory properties.
Teucrium polium aerial parts and roots, as well as Teucrium parviflorum aerial parts, were subjected to ethanol extraction procedures. Essential oil volatile profiling is achieved using GC-MS, and subsequent ethanol extract phytochemical profiling is performed by LC-HRMS. Antioxidant activity (DPPH, ABTS, CUPRAC, and metal chelating) assays, anticholinesterase, antityrosinase, and antiurease enzyme inhibition studies, anticancer activity via SRB cell viability, and antimicrobial activity against bacterial and fungal panels using microbroth dilution techniques are all part of the comprehensive analysis. Employing AutoDock Vina (version unspecified), the molecular docking experiments were completed. Rephrase these sentences ten times, showcasing different grammatical arrangements and sentence constructions, yet preserving their essence.
A wealth of biologically significant volatile and phenolic compounds characterized the studied extracts. In all extracts, the most significant compound was (-)-Epigallocatechin gallate, a molecule highly regarded for its therapeutic potential. The aerial parts extract of Teucrium polium demonstrated a substantial naringenin content, reaching a concentration of 1632768523 g/g of extract. Employing different approaches, all extracts demonstrated a pronounced degree of antioxidant activity. All extracts showcased antibutrylcholinesterase, antityrosinase, and antiurease activity, as evidenced by in vitro and in silico testing. The root extract from Teucrium polium demonstrated a notable capacity to inhibit tyrosinase, urease, and display cytotoxic effects.
The findings from this research across multiple fields corroborate the time-honored use of these two Teucrium species, and the mechanisms are now clear.
The results from this multi-faceted study demonstrate the justification for the traditional use of these two Teucrium species, unveiling the related mechanisms.
Bacteria's ability to survive inside cells poses a major hurdle in the fight against antimicrobial resistance. Currently available antibiotics demonstrate limited membrane permeability through host cells, thus failing to adequately combat intracellular bacteria. The fusogenic properties of liquid crystalline nanoparticles (LCNPs) are generating considerable research interest in their potential for promoting therapeutic cellular uptake; nevertheless, their application in the targeting of intracellular bacteria has not been observed in the literature. An investigation into the cellular internalization of LCNPs in RAW 2647 macrophages and A549 epithelial cells, optimized by the inclusion of the cationic lipid dimethyldioctadecylammonium bromide (DDAB), was undertaken. The structure of LCNPs was honeycombed, but the inclusion of DDAB created an onion-like organization with larger interior openings. Both cells experienced an elevated cellular uptake upon treatment with cationic LCNPs, with a maximum uptake of 90% being achieved. Subsequently, LCNPs were infused with tobramycin or vancomycin, leading to an augmented activity against intracellular gram-negative Pseudomonas aeruginosa (P.). click here In the sample, two bacterial species were found: Pseudomonas aeruginosa, gram-negative, and Staphylococcus aureus (S. aureus), which is gram-positive. The enhanced cellular ingestion of cationic lipid nanoparticles was associated with a noteworthy decrease in the intracellular bacterial population (up to 90% reduction), in contrast to the antibiotic administered in its unadulterated state; conversely, epithelial cells infected with Staphylococcus aureus showed reduced effectiveness. The carefully crafted LCNP molecule can reactivate the ability of antibiotics to target both intracellular Gram-positive and Gram-negative bacteria within a multitude of cellular contexts.
Clinically evaluating novel therapeutics necessitates a comprehensive understanding of plasma pharmacokinetics (PK), a procedure routinely implemented for both small molecules and biologics. Nonetheless, a fundamental deficiency in PK characterization is observed in nanoparticle-based drug delivery systems. The outcome of this is the development of untested theories relating nanoparticle properties to pharmacokinetic pathways. A meta-analysis of 100 nanoparticle formulations administered intravenously to mice explores any correlations between four pharmacokinetic parameters, determined by non-compartmental analysis (NCA), and four cardinal nanoparticle attributes: PEGylation, zeta potential, size, and material. Statistically significant differences were present in the PK of particles, stratified according to nanoparticle properties. In contrast, when employing a linear regression model to explore the relationship between these properties and pharmacokinetic parameters, the model's predictive capability was limited (R-squared value of 0.38, with the exception of t1/2).