A drug design strategy based on molecular docking and molecular dynamics simulations applied to development of inhibitor against triple-negative breast cancer by Scutellarein derivatives.

Triple-negative breast cancer (TNBC), accounting for 10-15% of all breast malignancies, is more prevalent in women under 40, particularly in those of African descent or carrying the BRCA1 mutation. TNBC is characterized by the absence of estrogen and progesterone receptors (ER, PR) and low or elevated HER2 expression. It represents a particularly aggressive form of breast cancer with limited therapeutic options and a poorer prognosis. In our study, we utilized the protein of TNBC collected from the Protein Data Bank (PDB) with the most stable configuration. We selected Scutellarein, a bioactive molecule renowned for its anti-cancer properties, and used its derivatives to design potential anti-cancer drugs employing computational tools. We applied and modified structural activity relationship methods to these derivatives and evaluated the probability of active (Pa) and inactive (Pi) outcomes using pass prediction scores. Furthermore, we employed in-silico approaches such as the assessment of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and quantum calculations through density functional theory (DFT). Within the DFT calculations, we analyzed Frontier Molecular Orbitals, specifically the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO). We then conducted molecular docking and dynamics against TNBC to ascertain binding affinity and stability. Our findings indicated that Scutellarein derivatives, specifically DM03 with a binding energy of -10.7 kcal/mol and DM04 with -11.0 kcal/mol, exhibited the maximum binding tendency against Human CK2 alpha kinase (PDB ID 7L1X). Molecular dynamic simulations were performed for 100 ns, and stability was assessed using root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF) parameters, suggesting significant stability for our chosen compounds. Furthermore, these molecules met the pharmacokinetics requirements for potential therapeutic candidates, displaying non-carcinogenicity, minimal aquatic and non-aquatic toxicity, and greater aqueous solubility. Collectively, our computational data suggest that Scutellarein derivatives may serve as potential therapeutic agents for TNBC. However, further experimental investigations are needed to validate these findings.

A Comprehensive Review of the Pharmacological Importance of Dietary Flavonoids as Hepatoprotective Agents.

The liver is a crucial organ that is involved in various kinds of metabolic activity and a very stable accessory gland for the digestive system. Long-term or persistent inflammation and oxidative stress due to any reasons have a substantial impact on the beginning and continuation of chronic diseases such as hepatocellular carcinoma, liver cirrhosis, liver fibrosis, and other hepatic conditions. There are many sources which can help the liver to be healthy and enhance its metabolic potential of the liver. Since the diet is rich origin of bioactive along with antioxidant chemicals including flavonoids and polyphenols, it can control different stages of inflammation and hepatic diseases. Numerous food sources, notably vegetables, nuts, fruits, cereals, beverages, and herbal medicinal plants, are rich in bioactive chemicals called flavonoids and their derivatives like Flavones, Anthocyanins, Iso-flavonoid, Flavanones, Flavanols, and Flavan-3-ols. Most recently occurred research on flavonoids has demonstrated that they can regulate hepatoprotective properties. This is because they are essential parts of pharmaceutical and nutraceutical products due to their hepatoprotective, antioxidative, and immune-modulating characteristics. However, the characteristics of their hepatoprotective impact remain unclear. The purpose of this comprehensive review is to survey the flavonoid structure and enriched sources for their hepatoprotective and antioxidant effects concerning liver toxicity or injury.

Citrus limon L. (lemon) seed extract shows neuro-modulatory activity in an in vivo thiopental-sodium sleep model by reducing the sleep onset and enhancing the sleep duration.

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals.

Opportunities of prebiotics for the intestinal health of monogastric animals.

The goal of prebiotic applications from different sources is to improve the gut ecosystem where the host and microbiota can benefit from prebiotics. It has already been recognized that prebiotics have potential roles in the gut ecosystem because gut microbiota ferment complex dietary macronutrients and carry out a broad range of functions in the host body, such as the production of nutrients and vitamins, protection against pathogens, and maintenance of immune system balance. The gut ecosystem is very crucial and can be affected by numerous factors consisting of dietary constituents and commensal bacteria. This review focuses on recent scientific evidence, confirming a beneficial effect of prebiotics on animal health, particularly in terms of protection against pathogenic bacteria and increasing the number of beneficial bacteria that may improve epithelial cell barrier functions. It has also been reviewed that modification of the gut ecosystem through the utilization of prebiotics significantly affects the intestinal health of animals. However, the identification and characterization of novel potential prebiotics remain a topical issue and elucidation of the metagenomics relationship between gut microbiota alteration and prebiotic substances is necessary for future prebiotic studies.

Impact of Prebiotics on Enteric Diseases and Oxidative Stress.

In animals, the gastrointestinal microbiota are reported to play a major role in digestion, nutrient absorption and the release of energy through metabolism of food. Therefore, microbiota may be a factor for association between diet and enteric diseases and oxidative stress. The gut microbial composition and concentration are affected by diet throughout the life of an animal, and respond rapidly and efficiently to dietary alterations, in particular to the use of prebiotics. Prebiotics, which play an important role in mammalian nutrition, are defined as dietary ingredients that lead to specific changes in both the composition and activity of the gastrointestinal microbiota through suppressing the proliferation of pathogens and by modifying the growth of beneficial microorganisms in the host intestine. A review of the evidence suggests possible beneficial effects of prebiotics on host intestinal health, including immune stimulation, gut barrier enhancement and the alteration of the gastrointestinal microbiota, and these effects appear to be dependent on alteration of the bacterial composition and short-chain fatty acid (SCFA) production. The production of SCFAs depends on the microbes available in the gut and the type of prebiotics available. The SCFAs most abundantly generated by gastrointestinal microbiota are acetate, butyrate and propionate, which are reported to have physiological effects on the health of the host. Nowadays, prebiotics are widely used in a range of food products to improve the intestinal microbiome and stimulate significant changes to the immune system. Thus, a diet with prebiotic supplements may help prevent enteric disease and oxidative stress by promoting a microbiome associated with better growth performance. This paper provides an overview of the hypothesis that a combination of ingestible prebiotics, chitosan, fructooligosaccharides and inulin will help relieve the dysbiosis of the gut and the oxidative stress of the host.