Worenine is an isoquinoline alkaloid isolated from Coptis chinensis[1-2]. Worenine acts as a JNK2 kinase inhibitor to suppress related signaling pathway activation, while also reducing oxidative stress and inflammatory responses by activating the Nrf2 pathway. Worenine can be used in research related to psoriasis and cancer[3-4].
In vitro, Worenine (0-128μM) was used to treat MDA-MB-231 and MDA-MB-468 breast cancer cell lines for 48 hours. Worenine significantly inhibited the expression of the RNF130 protein and induced apoptosis[5]. Worenine (5–20μM) was used to treat HCT116 and SW620 colorectal cancer cell lines for 24–72 hours. Worenine significantly inhibited cancer cell viability and colony formation, induced cell cycle arrest, downregulated the expression of key glycolytic enzymes, and inhibited glucose uptake, consumption, and lactate production[6].
In vivo, a Balb/c mouse model was topically pretreated with Worenine cream (2mM) 3 hours before the back was irradiated with SUV (100KJ/m²) for 2 hours. Worenine significantly inhibited skin epidermal thickening, edema, and immune cell infiltration, while also reducing IL-6 secretion and JNK phosphorylation levels in the skin[7]. ICR mice were intraperitoneally administered Worenine (5mg/kg/day) for 15 consecutive days. Worenine showed significant accumulation in the liver and induced hepatotoxicity, leading to histopathological changes in the liver including fat vacuole infiltration, inflammation, and deep staining of some hepatocytes[8].
References:
[1] Wang Y, Hu Y, Wu T, et al. Recognition of DNA abasic site nanocavity by fluorophore-switched probe: Suitable for all sequence environments. Spectrochim Acta A Mol Biomol Spectrosc. 2016 Jan 15;153:645-50.
[2] Ishaq AR, Younis T, Lin S, et al. Phosphofructokinase-1 in Cancer: A Promising Target for Diagnosis and Therapy. Recent Pat Anticancer Drug Discov. 2025;20(5):667-680.
[3] Lu H, Huang Y, Ni X, et al. TOPK promotes the development of psoriasis and worenine alleviates psoriasiform dermatitis by inhibiting TOPK activity. J Eur Acad Dermatol Venereol. 2024 May;38(5):851-863.
[4] Yang G, Xu M, Wu M, et al. Worenine enhances the sensitivity of non-small cell lung cancer A549/DDP cells to cisplatin via HIF-1α/BNIP3-mediated mitophagy. Gen Physiol Biophys. 2025 Jul;44(4):317-326.
[5] Hu M, Huang L, Deng H, et al. Single-cell transcriptomics uncover RNF130-mediated TNF-α pathway activation and worenine synergy with paclitaxel in breast cancer. Clin Epigenetics. 2026 Jan 24;18(1):32.
[6] Ji L, Shen W, Zhang F, et al. Worenine reverses the Warburg effect and inhibits colon cancer cell growth by negatively regulating HIF-1α. Cell Mol Biol Lett. 2021 May 18;26(1):19.
[7] Xiao J, Lu H, Ma T, et al. Worenine Prevents Solar Ultraviolet-Induced Sunburn by Inhibiting JNK2. Front Pharmacol. 2022 Jul 22;13:881042.
[8] Zhang H, Luo J, Yi Y, et al. Organic cation transporter 1 and cytochrome P450s play crucial roles in coptisine- and worenine-induced hepatotoxicity. Drug Metab Dispos. 2025 Sep;53(9):100134.