Rapanone naturally occurring hydroxyl-benzoquinone with a privileged chelating structure, having a broad spectrum of biological actions, highlighting its anti-inflammatory, anthelmintic, and cytotoxic activities[1]. Rapanone exhibits antioxidant potential by oxidizing Fe(II) and O2⁻ radicals, thereby inhibiting Fenton-Haber-Weiss reactions. Rapanone’s antioxidant capacity is enhanced upon interaction with Fe(II) or mitochondria, and it prevents iron or free radical-induced mitochondrial damage through multiple mechanisms[1-2].
In vitro, Rapanone (25 and 50μM) induces apoptosis in the MCF-7 cell line after 24 hours of treatment[3]. In the hepatic carcinoma (HepG2), 24 hours of Rapanone (20-40μM) treatment induced a concentration-dependent mitochondrial membrane potential dissipation, ATP depletion, hydrogen peroxide generation and phosphatidyl serine externalization[4].
In vivo, oral administration of Rapanone to female albino mice at doses of 60mg/kg and 120mg/kg induced uterine alterations in both the first and second gestation periods and decreased the pregnancy rate in a dose-dependent manner[5]. In female Swiss mice, treatment with Rapanone (2.5, 5, 10mg/kg; i. p.) significantly inhibited the formation of oedema as well as the content of elastase and Prostaglandin E2 (PGE2) in a dose-dependent manner[6]. After exposing zebrafish embryos to Rapanone (160μM) for 96 hours, the embryo survival rate was 90-98%, and Rapanone showed low toxicity[7].
References:
[1] de la Vega-Hernández K, Antuch M, Cuesta-Rubio O, Núñez-Figueredo Y, Pardo-Andreu GL. Discerning the antioxidant mechanism of rapanone: A naturally occurring benzoquinone with iron complexing and radical scavenging activities. J Inorg Biochem. 2017;170:134-147.
[2] Wróbel-Biedrawa D, Grabowska K, Galanty A, Sobolewska D, Żmudzki P, Podolak I. Anti-melanoma potential of two benzoquinone homologues embelin and rapanone - a comparative in vitro study. Toxicol In Vitro. 2020;65:104826.
[3] Arunachalam A, Sankar M, Pandi B, Paul S, Thilagar S. Evaluation of Rapanone and Nectandrin B as novel inhibitors for targeting the metastatic regulator protein BACH1 using breast cancer cell line Mcf-7. J Biomol Struct Dyn. 2024;42(20):11185-11200.
[4] Pardo Andreu GL, Reis FZD, González-Durruthy M, et al. Rapanone, a naturally occurring benzoquinone, inhibits mitochondrial respiration and induces HepG2 cell death. Toxicol In Vitro. 2020;63:104737.
[5] Calle J, Olarte J, Pinzon R, Ospina LF, Mendoza MC, Orozco MJ. Alterations in the reproduction of mice induced by rapanone. J Ethnopharmacol. 2000;71(3):521-525.
[6] Ospina LF, Calle J, Arteaga L, Pinzón R, Alcaraz MJ, Payá M. Inhibition of acute and chronic inflammatory responses by the hydroxybenzoquinonic derivative rapanone. Planta Med. 2001;67(9):791-795.
[7] Mariyappan V, Munuswamy-Ramanujam G, Ramasamy M. Synthesis of novel rapanone derivatives via organocatalytic reductive C-alkylation: biological evaluation of antioxidant properties, in vivo zebrafish embryo toxicity, and docking studies. RSC Med Chem. 2023;15(2):623-635.
Rapanone是一种天然存在的具有优势螯合结构的羟基苯醌，具有广泛的生物活性，特别是其抗炎、驱虫和细胞毒性活性[1]。Rapanone通过氧化Fe(Ⅱ)和O2⁻自由基，抑制芬顿-哈伯-魏斯反应，从而显示出抗氧化潜力。Rapanone的抗氧化能力在与Fe(Ⅱ)或线粒体相互作用时得到增强，并且通过多种机制防止铁或自由基诱导的线粒体损伤[1-2]。
在体外，Rapanone（25和50μM）在处理24小时后可诱导MCF-7细胞系发生凋亡[3]。在肝癌（HepG2）细胞中，24小时的Rapanone（20-40μM）处理诱导了线粒体膜电位的浓度依赖性耗散、ATP耗竭、过氧化氢生成以及磷脂酰丝氨酸外翻[4]。
在体内，对雌性白化小鼠口服给予Rapanone，剂量分别为60mg/kg和120mg/kg，可在第一和第二个妊娠期诱导子宫发生改变，并以剂量依赖性方式降低怀孕率[5]。在瑞士雌性小鼠中，用Rapanone（2.5、5、10mg/kg；腹腔注射）处理显著抑制了水肿的形成以及弹性蛋白酶和前列腺素E2（PGE2）含量，且呈剂量依赖性[6]。将斑马鱼胚胎暴露于Rapanone（160μM）96小时后，胚胎存活率为90-98%，且Rapanone显示低毒性[7]。