Elucidating hepatoprotective potential of Cichorium intybus through multimodal assessment and molecular docking analysis with hepatic protective enzymes.

This study employed a comprehensive approach to validate the hepatoprotective potential of phytoconstituents from Cichorium intybus leaves. In vitro, in vivo and in silico techniques were used to confirm the protective effects on liver enzymes. In vitro antioxidant assessment revealed the highest potential in the hydroethanolic leaf extract compared to aqueous and methanolic extracts. The study further investigated the ameliorative efficacy of the hydro-ethanolic extract (HECL) in male Wistar rats exposed to lead (50 mg/kg b wt.) and nickel (4.0 mg/kg b wt.) individually and in combination for 90 days. HECL at 250 mg/kg b wt. mitigated hepatic injury, oxidative stress, DNA fragmentation, ultrastructural and histopathological alterations induced by lead and nickel. Molecular docking explored the interaction of 28 phytoconstituents from C. intybus with hepatoprotective protein targets. Cyanidin and rutin exhibited the highest affinity for liver corrective enzymes among the screened phytoconstituents. These findings underscore the liver corrective potential of C. intybus leaf phytoconstituents, shedding light on their molecular interactions with hepatoprotective targets. This research contributes valuable insights into the therapeutic applications of C. intybus in liver protection.

Genetic diversity, population structure analysis and codon substitutions of Indicine Badri cattle using ddRAD sequencing.

The present study was carried out on 96 animals representing three distinct colour variants of Badri cattle to investigate the genetic diversity, population structure and substitution mutations in the genetic codons due to single nucleotide variations. The DNA samples of 96 Badri cows were genotyped using a double digestion restriction associated DNA (ddRAD) sequencing approach. A standardized bioinformatics pipeline was employed to identify single nucleotide polymorphisms (SNPs), initially detecting 7,168,552 SNPs through alignment with the Bos indicus reference genome assembly. Subsequent stringent quality filtration yielded 65,483 high-confidence SNPs for downstream analysis. Genetic diversity analysis of the Badri cattle population resulted in average values of 0.145, 0.088, and 0.091 for Shannon's diversity Index (I), Simpson's Diversity (h), and Simpson's Unbiased Diversity (uh), respectively. Genetic similarities between the black and brown, black and grey, and brown and grey Badri variants were found to be 0.9972, 0.9980 and 0.9970, respectively. Tajima's D diversity value was observed to be significant and positive for 99.29% of high-confidence SNPs (65,483). STRUCTURE analysis showed admixture among the three Badri colour variants, suggesting a lack of genetic differentiation. Annotation of high-confidence SNPs regarding genetic codon changes indicated maximum substitutions in the GGC with GGT (22 occurrences), followed by AAC to AGC (20 occurrences), GAA to TAA (19 occurrences) and CAA to CAG (19 occurrences). The study concludes there are genetic similarities among colour variants, lack of rare alleles, balancing selection, sudden population contraction and genetic codon substitutions within the Badri cattle population. Insights derived from SNP data analysis hold potential significance for conservation initiatives and breed improvement programs for indicine cattle.

Computational exploration of microsomal cytochrome P450 3A1 enzyme modulation by phytochemicals of Cichorium intybus L.: Insights into drug metabolism.

Drug metabolism plays a crucial role in drug fate, including therapeutic inactivation or activation, as well as the formation of toxic compounds. This underscores the importance of understanding drug metabolism in drug discovery and development. Considering the substantial costs associated with traditional drug development methods, computational approaches have emerged as valuable tools for predicting the metabolic fate of drug candidates. With this in mind, the present study aimed to investigate the potential mechanisms underlying the modulation of microsomal cytochrome P450 3A1 (CYP3A1) enzyme activity by various phytochemicals found in Cichorium intybus L., commonly known as chicory. To achieve this goal, several in silico methods, including molecular docking and molecular dynamics (MD) simulation, were employed to explore computationally the microsomal CYP3A1 enzyme. Schrodinger software was utilized for the molecular docking study, which involved the interaction analysis between CYP3A1 and 28 phytoconstituents of Cichorium intybus. Virtual screening of 28 compounds from chicory led to the identification of the top five ranked compounds. These compounds were evaluated for drug-likeness properties, pharmacokinetic profiles, and predicted binding affinities to CYP3A1. Caffeoylshikimic acid and cichoric acid emerged as promising candidates due to their favorable characteristics, including good oral bioavailability and high binding affinities to CYP3A1. Molecular dynamics simulations were conducted to assess the stability of caffeoylshikimic acid within the CYP3A1 binding pocket. The results demonstrated that caffeoylshikimic acid maintained stable interactions with the enzyme throughout the simulation, suggesting its potential as an effective modulator of CYP3A1 activity. The findings of this study have the potential to provide valuable insights into the complex molecular mechanisms by which Cichorium intybus L. acts on hepatocytes and modulates CYP3A1 enzyme expression or activity. By elucidating the impact of these phytochemicals on drug metabolism, this research contributes to our understanding of how chicory may interact with drugs and influence their efficacy and safety profiles.

Genome-wide identification and annotation of SNPs and their mapping in candidate genes related to milk production and fertility traits in Badri cattle.

This study was conducted in Badri cattle using a double digest restriction-site associated DNA sequencing approach. The study aimed to identify and annotate high confidence single nucleotide polymorphisms (SNPs) and their mapping in candidate genes related to production and fertility in dairy cattle. A total of 7,168,552 genome-wide SNPs were initially identified in Badri cattle by alignment with the Bos indicus reference genome. After filtration of SNPs, 65,483 high confidence SNPs were retained and further used for downstream analysis. Annotation of high confidence SNPs revealed 99.197% SNPs had modifier impact, 0.326% SNPs were low impact, 0.036% were high impact, and 0.441% were moderate impact SNPs. Most SNPs in Badri cattle were found in intergenic, transcript and intronic regions. The candidate genes for milk production PRKCE, ABCG2, GHR, EPS8, CAST and NRXN1 were found to harbour maximum high confidence variants. Among candidate genes for fertility in cattle, ATP2B1, SOX5, WDR27, ARHGAP12, CACNA1D, ANKRD6, GRIA3, ZNF521 and CAST822 have maximum high confidence variants mapped in them. The SNPs found mapped in the candidate genes will be important genetic tools in the search for phenotype-modifying nucleotide changes and will aid in formulating relevant genetic improvement programmes for dairy cattle.

Quantum chemical study of gas-phase reactions of isoprene with OH radicals producing highly oxidised second-generation products.

The formation of secondary organic aerosols caused by atmospheric oxidation of isoprene is harmful to human health and the climate; thus, isoprene oxidation is further mandatory to obtain less harmful or harmless highly oxidised products. In this numerical investigation, 2-hydroperoxy-2-methylbut-3-en-1-ol (ISOPOOH) was considered the model compound to investigate the formation of three RO2 radicals (C5H11O4, C5H11O6 and C5H11O5) and two saturated highly oxidised products (C5H12O6 and C5H10O6). The complete reaction network and its thermodynamics and kinetics were analysed to obtain the most probable and feasible reaction pathways. Four different levels of theories (HF, B3LYP, M06-2X and ωB97XD with basis set of 6-31+g(d,p)) were employed to explore a global minimum of ISOPOOH. All theories provided approximately close energetics; however, because of the novelty of the functional and parameterisation of the basis set, the ωB97XD functional was selected to examine the reaction mechanism. C5H12O6 was formed as the second-generation highly oxidised product during ISOPOOH oxidation.