Murugananthan, A. | 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

Preclinical Safety Evaluation of Vernolac, a Commercially Available Polyherbal Nutraceutical Comprising Vernonia zeylanica, Nigella sativa, Hemidesmus indica, Smilax glabra, and Leucas zeylanica, in Wistar Rats

Vernolac is a commercially available polyherbal formulation comprising Vernonia zeylanica aerial parts, Nigella sativa seeds, Hemidesmus indica roots, Smilax glabra rhizome, and Leucas zeylanica aerial parts. Although previous in vitro studies have demonstrated anticancer potential of Vernolac and its active ingredients, safety data are available only for some of the plant ingredients of Vernolac. In the present study, acute and 28-day repeat-dose toxicity of Vernolac were evaluated in Wistar rats following OECD guidelines 420 and 407, respectively. Acute toxic effect was investigated during 14 days after administering a single oral dose of 2000 mg/kg to 10 animals (5 males, 5 female) which was followed by repeat-dose study where a human equivalent therapeutic dose HED (165 mg/kg/day), a mid-dose (2x HED, 330mg/kg/day) and a high dose (4x HED, 660 mg/kg/day) were administered separately to a group of 10 fresh animals (5 male, 5 female) for 28 days. In both acute and repeat-dose studies, no morbidity, mortality, changes in food and water intake, relative organ weights, microscopic changes in organs, hematological changes, or clinical signs of toxicity were observed. In the acute study, significant differences appeared only in AST and ALT levels in males, indicating the liver may be a target organ of toxicity at extremely high doses. In 28-days repeated dose study, a significant reduction in ALT was observed only in females receiving high doses, with no changes in males. In summary, a dose up to four times the therapeutic daily dose is non-toxic in Wistar rats over a 28-day period.

pharmacology and toxicology↗