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.
Worenine是一种从黄连中分离的异喹啉类生物碱[1-2]。Worenine可作为JNK2激酶抑制剂来抑制相关信号通路活化，同时通过激活Nrf2通路以减少氧化应激和炎症反应。Worenine可用于银屑病和癌症的相关研究[3-4]。
在体外，Worenine（0-128μM）处理MDA-MB-231及 MDA-MB-468乳腺癌细胞系48小时。Worenine显著抑制RNF130蛋白的表达，同时诱导细胞凋亡[5]。Worenine（5–20μM）处理HCT116和SW620结直肠癌细胞系24–72小时。Worenine显著抑制癌细胞活力与集落形成，引起细胞周期阻滞，同时下调糖酵解关键酶表达并抑制葡萄糖摄取、消耗和乳酸生成[6]。
在体内，Worenine（2mM；乳膏局部涂抹）于SUV照射前3小时预处理Balb/c小鼠，随后以100KJ/m² SUV照射背部2小时。Worenine显著抑制了皮肤表皮增厚、水肿及免疫细胞浸润，同时降低了皮肤中IL-6的分泌和JNK的磷酸化水平[7]。Worenine（5mg/kg/day；腹腔注射）连续处理15天，用于ICR小鼠。Worenine在肝脏中表现出显著的蓄积，诱导了肝毒性，导致肝脏出现脂肪空泡浸润、炎症和部分肝细胞深染等组织病理学改变[8]。