De Vass Gunawardane, S. | Search bioRxiv

bioRxiv2026

In vivo pharmacokinetics and tissue distribution profile of a Wnt/β-catenin pathway-targeting anticancer cassane diterpene isolated from Caesalpinia pulcherrima

A cassane diterpene, 6{beta}-cinnamoyl-7-hydroxyvouacapen-5-ol (6{beta}CHV), isolated from Caesalpinia pulcherrima, has emerged as a promising anticancer drug lead with reported Wnt/{beta}-catenin pathway inhibitory activity and in vivo safety. The present study reports the in vivo pharmacokinetics and tissue distribution of 6{beta}CHV in Wistar rats following a single oral dose of 200 mg/kg. A reproducible RP-HPLC-UV method was developed and validated for quantifying 6{beta}CHV in rat plasma and tissues. Chromatographic separation was achieved using a gradient elution of methanol and water. The method was subsequently applied to investigate the pharmacokinetics and tissue distribution of 6{beta}CHV. Plasma pharmacokinetic analysis revealed delayed and moderate absorption, with a Tmax of 4 h and a Cmax of 1314.12 ng/mL. Following absorption, 6{beta}CHV is distributed widely across peripheral tissues, including the liver, heart, lungs, spleen, and kidneys, as well as pharmacological sanctuary sites such as the brain and testes. The highest concentrations were observed in the stomach, small intestine, and liver, with detectable levels persisting up to 24 h, reflecting extensive tissue partitioning and retention. Overall, these findings demonstrate that oral administration of 6{beta}CHV is feasible. However, the delayed absorption suggests that further optimization of formulation or alternative administration routes may enhance systemic exposure. This study provides the first comprehensive pharmacokinetic and tissue distribution profile of 6{beta}CHV, supporting its continued preclinical development as a potential anticancer therapeutic. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC="FIGDIR/small/715187v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@1621f86org.highwire.dtl.DTLVardef@1039b3aorg.highwire.dtl.DTLVardef@1c40175org.highwire.dtl.DTLVardef@13bcf2f_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2025

A network pharmacology-based approach and molecular docking study to explore the therapeutic potential of a nutraceutical formula (Vernolac) in the treatment of cancer

Vernolac is a commercially available polyherbal nutraceutical capsule comprised of Vernonia zeylanica aerial parts, Nigella sativa seeds, Hemidesmus indicus roots, Leucas zeylanica aerial parts, and Smilax glabra rhizome. Different herbal formulations, organic extracts, and many isolated phytochemicals of the above plants have been reported to exhibit anticancer properties. However, the anticancer mechanisms of action of Vernolac, as a polyherbal formulation, remain unexplored. This study employed an integrative network pharmacology-based approach, complemented by in vitro experiments, to investigate the anticancer potential of Vernolac. Phytochemicals in Vernolac were retrieved from databases, screened for drug-likeness and oral bioavailability using SwissADME, yielding 155 drug-like phytochemicals, and their protein targets were predicted via SwissTargetPrediction. The intersection of targets of phytochemicals and cancer-related targets from GeneCards yielded 137 common targets. Protein-protein interaction analysis in STRING and Cytoscape identified key hub nodes, including AKT1, BCL2, CASP3, CTNNB1, EGFR, ESR1, GAPDH, HSP90AA1, HSP90AB1, IL6, JUN, SRC, STAT3, and TNF. Clustering, topology, and formula-herb-compound-target-disease and target-pathway networks highlighted key phytochemicals, including vernolactone, thymoquinone, quercetin, nigellidine, -hederin, and carvacrol. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment revealed that the identified targets are significantly enriched in multiple cancer pathways. Molecular docking and dynamics simulations identified novel target-ligand interactions. Overall, network analysis suggests that Vernolac may exert anticancer effects through apoptosis induction, immune modulation, antioxidant, anti-inflammation, antiproliferative, and chemoradiosensitizing mechanisms. Moreover, Vernolac may exhibit chemoradioprotective potential by alleviating therapy-induced toxicity, supporting its promise as a potential adjunct to conventional cancer treatments. The Sulforhodamine B assay demonstrated selective antiproliferative activity of Vernolac against cancerous cells MCF-7 (IC50 = 54.01 {+/-} 0.02 g/mL), Caco-2 (IC50 = 85.52 {+/-} 0.13 g/mL), NTERA-2 cl.D1 (IC50 = 42.41 {+/-} 0.06 g/mL), and non-cancerous MCF-10A (IC50 = 803.5 {+/-} 0.03 g/mL). Novel target-ligand interactions identified via molecular docking and dynamics simulations, and the underlying mechanisms of Vernolac predicted in this study, require further validation through in vitro and in vivo experiments.

bioinformatics↗