Farrerol is a typical natural flavanone isolated from the traditional Chinese herb Rhododendron dauricum L.Ericaceae with IC50 values of 57μM and 2.7μM for estrogen receptors ERα and ERβ, respectively[1]. Farrerol, possessing anti-inflammatory, antioxidant, vasoactive, antitumor, and antimicrobial properties, is capable of preventing and treating diseases associated with oxidative stress, cancer, cardiovascular diseases, and bacterial infections[2][3][4][6].
In vitro, murine macrophage RAW 264.7 cells treated with different concentrations of Farrerol (0-20mg/L) for 18h or 24h induced the expression of antioxidant enzymes and increased the expression of HO-1 by activating Nrf2 and reducing the expression of Keap1[2]. Primary bovine mammary epithelial cells (bMEC) were incubated with Farrerol (4-16μg/ml) for 24h before infecting with S. aureus at a multiplicity of infection of 30 (MOI 30:1 bacteria per cell). All concentrations of Farrerol significantly inhibited S. aureus internalization into bMEC in a dose-dependent manner by downregulating the mRNA expression of tracheal antimicrobial peptide (TAP) and bovine neutrophil β-defensin 5 (BNBD5), and also suppressing S. aureus induced NF-kB activation in bMEC[3]. Farrerol (0, 40, 80, and 160μM) incubated human ovarian epithelial cancer SKOV3 cells for 24h or 48h decreased the viability of SKOV3 cells in a dose and time-dependent manner. Farrerol induced G2/M cell cycle arrest and apoptosis in cancer cells[4].
In vivo, hepatic injury mice models were administered Farrerol (40mg/kg) i.p. injections two times, 12h and 1h before the injection of Acetaminophen (APAP). Farrerol pretreatment alleviated acute liver failure and maintained the survival rate of mice by activation of both Nrf2-mediated antioxidative cascades and mitochondrial autophagy[5]. Farrerol (10mg/kg/day) injected intraperitoneally into Angiotensin II (Ang II)-treated mice model of myocardial remodeling for 2 days inhibited Ang II-induced cardiac hypertrophy and reduce heart weight/tibia ratio (HW/TL), inflammation, fibrosis, oxidative stress, the volume of cardiomyocytes and the proliferation and migration of fibroblast[6]. Mice received intraperitoneal injections of Farrerol (20mg/kg) daily for 8 consecutive days, starting 1 day before the unilateral ureteral obstruction (UUO) operation. Farrerol ameliorated renal injury and fibrosis in the UUO model by inhibiting oxidative stress, apoptosis, and inflammation[7].
References:
[1] Li Q Y, Chen L, Zhu YH, et al. Involvement of estrogen receptor-β in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation. Acta Pharmacol Sin. 2011 Apr;32(4):433-40.
[2] Ci X X, Lv H M, Wang L D, et al. The antioxidative potential of Farrerolrrerol occurs via the activation of Nrf2 mediated HO-1 signaling in RAW 264.7 cells. Chem Biol Interact. 2015 Sep 5:239:192-9
[3] Yang Z T, Fu Y H, Liu B, et al. Farrerol regulates antimicrobial peptide expression and reduces Staphylococcus aureus internalization into bovine mammary epithelial cells.Microb Pathog. 2013 Dec:65:1-6.
[4] Chae J B, Kim J S, Choi S T, et al. Farrerol Induces Cancer Cell Death via ERK Activation in SKOV3 Cells and Attenuates TNF-α-Mediated Lipolysis. Int J Mol Sci. 2021 Aug 30;22(17):9400.
[5] Wang L D, Wei W, Xiao Q F, et al. Farrerol Ameliorates APAP-induced Hepatotoxicity via Activation of Nrf2 and Autophagy. Int J Biol Sci. 2019 Jan 29;15(4):788-799.
[6] He J, Xu D Y, Wang L, Yu X H. Farrerol prevents Angiotensin II-induced cardiac remodeling in vivo and in vitro. Front Pharmacol. 2023 Jan 4:13:1079251.
[7] Kim J Y, Leem J C, Park K K. Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Effects of Farrerol in a Mouse Model of Obstructive Uropathy. Curr Issues Mol Biol. 2023 Jan 1;45(1):337-352.
Farrerol是一种从传统中药兴安杜鹃（Rhododendron dauricum L. Ericaceae）中分离出来的典型黄烷酮，对雌激素受体ERα和ERβ的IC50值分别为57μM和2.7μM[1]。Farrerol具有抗炎、抗氧化、血管活性、抗肿瘤和抗菌作用，可用于预防和治疗氧化应激相关疾病、治疗癌症、治疗心血管疾病以及预防和治疗细菌感染[2][3][4][6]。
体外实验中，用不同浓度的Farrerol（0-20mg/L）处理小鼠巨噬细胞RAW 264.7细胞18小时或24小时，可诱导抗氧化酶的表达，并通过激活Nrf2、降低Keap1的表达来增加HO-1的表达[2]。将原代牛乳腺上皮细胞（bMEC）用Farrerol（4-16μg/ml）预处理24小时后，再以感染复数为30（MOI 30:1细菌/细胞）感染金黄色葡萄球菌（S. aureus）。所有浓度的Farrerol均能以剂量依赖性方式显著抑制金黄色葡萄球菌侵入bMEC，通过下调气管抗菌肽（TAP）和牛中性粒细胞β防御素5（BNBD5）的mRNA表达，并抑制金黄色葡萄球菌诱导的bMEC中NF-kB的激活[3]。用Farrerol（0、40、80和160μM）处理人卵巢上皮癌SKOV3细胞24小时或48小时，可呈剂量和时间依赖性地降低SKOV3细胞的活性，并诱导癌细胞G2/M期细胞周期阻滞和细胞凋亡[4]。
体内实验中，肝损伤小鼠模型在注射对乙酰氨基酚（APAP）前12小时和1小时分别腹腔注射Farrerol（40mg/kg）两次，Farrerol预处理通过激活Nrf2介导的抗氧化级联反应和线粒体自噬，减轻急性肝衰竭并维持小鼠的存活率[5]。血管紧张素II（Ang II）处理的小鼠心肌重塑模型中，Farrerol（10mg/kg/day，i.p.，2天）抑制了Ang II诱导的心脏肥大，降低心重/胫骨长比（HW/TL），减轻炎症、纤维化、氧化应激，减少心肌细胞体积以及成纤维细胞的增殖和迁移[6]。小鼠在单侧输尿管梗阻（UUO）手术前1天开始，连续8天每日腹腔注射Farrerol（20mg/kg），Farrerol通过抑制氧化应激、凋亡和炎症，改善UUO模型中的肾脏损伤和纤维化[7]。