# Hinokiflavone as a Potential Antitumor Agent: From Pharmacology to Pharmaceutics

## TL;DR

Hinokiflavone shows strong antitumor potential by targeting multiple cancer pathways, but its clinical use is limited by poor solubility and bioavailability.

## Contribution

This review comprehensively outlines the pharmacological mechanisms and formulation advances of hinokiflavone as a multifunctional antitumor agent.

## Key findings

- Hinokiflavone targets multiple oncogenic pathways including MDM2-p53, MAPK/JNK/NF-κB, and mitochondrial apoptosis pathways.
- Nanotechnology-based formulations like polymeric micelles improve hinokiflavone's bioavailability and antitumor efficacy.
- Hinokiflavone also exhibits antioxidant, anti-inflammatory, and antimicrobial properties that enhance its therapeutic potential.

## Abstract

Hinokiflavone (HF), a natural C-O-C-linked biflavonoid originally isolated from Chamaecyparis obtusa, is a promising multifunctional antitumor agent. Despite challenges posed by multidrug resistance and tumor heterogeneity, HF demonstrates notable therapeutic potential through a multifaceted pharmacological profile. HF exerts broad-spectrum anticancer effects by targeting multiple oncogenic pathways, including the MDM2-p53 axis, MAPK/JNK/NF-κB signaling, ROS/JNK-mediated apoptosis, and Bcl-2/Bax-regulated mitochondrial pathways. These actions are further complemented by inhibition of cell proliferation through cell cycle arrest and suppression of metastasis via downregulation of matrix metalloproteinases and reversal of epithelial–mesenchymal transition. Additionally, HF displays antioxidant, anti-inflammatory, and antimicrobial activities, enhancing treatment efficacy. However, its clinical translation remains limited by poor aqueous solubility, low oral bioavailability, and incomplete pharmacokinetic characterization. Recent advances in nanotechnology-based formulation strategies, such as polymeric micelles and metal–organic frameworks, have enhanced HF’s bioavailability and in vivo antitumor efficacy. This review comprehensively delineates HF’s molecular mechanisms of anticancer action, evaluates its pharmacokinetics and bioformulation developments, and highlights challenges and prospects for clinical application. Integration of tumor microenvironment-responsive delivery systems with synergistic therapeutic strategies is essential to fully realize HF’s therapeutic potential, positioning it as a valuable scaffold for novel anticancer drug development.