Farrerol is a natural product isolated and purified from the leaves of Rhododendron dauricum L. with antioxidative activity. It inactivates KEAP-1 or activates the Akt, p38 and ERK to facilitate the release of Nrf2 from Keap1 and subsequent reduces the intracellular production of reactive oxygen species via the induction of HO-1 expression. Farrerol has protective effects against H2O2-induced apoptosis in EA.hy926 cells, and suggests that farrerol is a potential candidate for the intervention of endothelial-injury-associated cardiovascular diseases.
Farrerol/杜鹃素 细胞实验
Cell Line
Concentration
Treated Time
Description
References
HepG2 cells
5, 10, 20 µM
1 hour
To evaluate the protective effect of Farrerol against H2O2-induced cytotoxicity, results showed that Farrerol pretreatment significantly suppressed cytotoxicity caused by H2O2 in a dose-dependent manner.
Int J Biol Sci. 2019 Jan 29;15(4):788-799.
RAW264.7 cells
25, 50, 100 µM
1 hour
Farrerol significantly reduced the production of inflammatory mediators (IL-1β, IL-6, TNF-α, COX-2, and iNOS) in LPS-induced RAW264.7 cells by suppressing AKT, ERK1/2, JNK1/2, and NF-κB p65 phosphorylation.
Int J Mol Sci. 2018 Jul 13;19(7):2037.
Mouse mammary epithelial cells (mMECs)
90, 110, 130 µM
1 hour pretreatment followed by LPS stimulation for 4 hours
Inhibited inflammatory response and phosphorylation of AKT, NF-κB p65, p38, and ERK1/2
Int J Mol Sci. 2018 Jun 14;19(6):1770.
Bone marrow-derived macrophages (BMDM)
20 µM
15 minutes
To investigate the inhibitory effect of FA on NLRP3 inflammasome activation in macrophages. Results showed that FA significantly reduced IL-1β release and caspase-1 activation.
Front Pharmacol. 2022 Apr 13;13:879232.
HepG2 cells
5, 10, 20 µM
18 hours
To evaluate the inhibitory effect of Farrerol on H2O2-induced ROS generation, results showed that Farrerol pretreatment significantly reduced H2O2-induced ROS generation in a dose-dependent manner.
Int J Biol Sci. 2019 Jan 29;15(4):788-799.
Human proximal tubule cells (HK-2)
5, 10, 20 µM
18 hours
Farrerol pretreatment significantly attenuated cisplatin-induced cytotoxicity, particularly at a concentration of 20 μM.
Front Physiol. 2019 Nov 26;10:1419.
Mouse tubular epithelial cells (MTECs)
5, 10, 20 µM
18 hours
Farrerol pretreatment significantly attenuated cisplatin-induced cytotoxicity, particularly at a concentration of 20 μM.
Front Physiol. 2019 Nov 26;10:1419.
Rat thoracic aorta vascular smooth muscle cells (VSMCs)
0.3–10 µM
2 hours pretreatment followed by 48 hours stimulation
Inhibited FBS-induced VSMC proliferation and DNA synthesis, associated with G1 cell cycle arrest, down-regulation of cell cycle proteins, and reduction in FBS-induced ERK1/2 phosphorylation
Acta Pharmacol Sin. 2011 Apr;32(4):433-40.
HaCaT cells
4.7 µM (IC50)
20 hours
Evaluate inhibition of Farrerol on VEGF-induced wound healing, results showed IC50 of 4.7 µM
Molecules. 2025 Jan 10;30(2):257.
HCA2-hTERT cells
0.1 µM
24 hours
Farrerol promoted the recruitment of RAD51 at DNA damage sites and accelerated γH2AX foci clearance via UCHL3
Nat Commun. 2023 Apr 3;14(1):1838.
HEK293 cells
20 µM
24 hours
Confirmed UCHL3 as the direct target of Farrerol via CETSA assay, Farrerol increased the thermal stability of UCHL3
Farrerol significantly inhibited Ang II-induced fibroblast migration and proliferation and reduced the expression of Collagen III and α-SMA.
Front Pharmacol. 2023 Jan 4;13:1079251.
Neonatal rat cardiomyocytes (NRCM)
20 µM
24 hours
Farrerol reduced the Ang II-induced increase in cardiomyocyte surface area and decreased mitochondrial ROS levels.
Front Pharmacol. 2023 Jan 4;13:1079251.
Human renal tubular epithelial cells (HK-2)
20 µM
24 hours
To evaluate the effect of Farrerol on the expression of Nrf2 and PINK1
Front Pharmacol. 2021 Nov 11;12:768700.
HepG2 cells
20 µM
24 hours
To investigate the effect of Farrerol on PAOA-induced lipid accumulation in HepG2 cells. Results showed that Farrerol reduced lipid accumulation by targeting PTPN1 and decreasing INSR dephosphorylation.
J Cell Mol Med. 2024 Sep;28(18):e70096.
Rat tenocytes
1, 5, 10, 20 and 40 μ M
24 hours
To evaluate the protective effect of Farrerol against RSL3-induced ferroptosis. Results showed that Farrerol at 10-40 μM concentrations was non-toxic and significantly inhibited RSL3-induced cell death and lipid peroxidation.
J Cell Mol Med. 2022 Jun;26(12):3483-3494.
RAW264.3 cells
1 µM, 10 µM, 25 µM
24 hours
Evaluate inhibition of Farrerol on VEGF-induced NF-κB activity, results showed dose-dependent suppression
Molecules. 2025 Jan 10;30(2):257.
HaCaT cells
1 µM, 10 µM, 25 µM, 50 µM, 100 µM
24 hours
Evaluate cytotoxicity, results showed Farrerol did not induce significant apoptosis at concentrations up to 100 µM
Molecules. 2025 Jan 10;30(2):257.
EA.hy926 cells
40-160 µM
24 or 48 hours
FA did not significantly affect the viability of EA.hy926 cells.
Int J Mol Sci. 2021 Aug 30;22(17):9400.
SKOV3 cells
40-160 µM
24 or 48 hours
FA decreased the viability of SKOV3 cells in a dose- and time-dependent manner, inducing G2/M cell cycle arrest and apoptosis.
Int J Mol Sci. 2021 Aug 30;22(17):9400.
A549 cells
0-64 µg/mL
3 hours
Evaluate the effect of Farrerol on the survival of A549 cells infected with MRSA USA300. Results showed that Farrerol significantly reduced LDH release, indicating decreased cell damage.
To study the metabolites of Farrerol, 15 in vitro metabolites were identified
Molecules. 2019 Sep 24;24(19):3470.
3T3-L1 cells
15 or 30 µM
8 days
FA significantly increased adipocyte differentiation and intracellular lipid accumulation, and reversed TNF-α-mediated lipolysis.
Int J Mol Sci. 2021 Aug 30;22(17):9400.
Neofusicoccum laricinum
0.10 g/L, 0.25 g/L, 0.5 g/L, 1 g/L, 2 g/L
8 days
Evaluate the inhibitory effect of Farrerol on Neofusicoccum laricinum. The results showed that the inhibitory effect increased with the concentration of Farrerol, with 2 g/L achieving nearly 100% inhibition rate.
Plants (Basel). 2024 Oct 28;13(21):3004.
Rat aortic vascular smooth muscle cells (VSMCs)
14.02 µM
To study the effect of Farrerol on L-type voltage-gated Ca2+ channels (LVGC) using whole-cell patch clamp, results showed Farrerol significantly inhibited Ca2+ influx current.
Int J Mol Sci. 2014 Apr 17;15(4):6641-56.
Farrerol/杜鹃素 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Embryo model
Added to culture medium
0.05, 0.1 μM
24 hours
Improves SpCRISPR/Cas9-mediated gene targeting efficiency and supports efficient generation of gene-targeted mice
Elife. 2020 Jul 9;9:e56008.
C57BL/6J mice
Angiotensin II (Ang II)-induced cardiac remodeling model
Intraperitoneal injection
10 mg/kg
Once daily for 2 weeks
Farrerol inhibited Ang II-induced cardiac hypertrophy, inflammation, fibrosis, and oxidative stress, and improved cardiac function.
Front Pharmacol. 2023 Jan 4;13:1079251.
C57BL/6 wild-type and Nrf2 knockout mice
Cisplatin-induced chronic kidney disease (CKD) model
Intraperitoneal injection
10 mg/kg
Once daily until the day of harvest or 5 days after the second cisplatin injection
To evaluate the protective effect of Farrerol on cisplatin-induced CKD and its mechanism
Front Pharmacol. 2021 Nov 11;12:768700.
C57BL/6J mice
Myocardial ischemia/reperfusion (I/R) injury model
Intraperitoneal injection
10 mg/kg or 40 mg/kg
Once daily for 7 days
To investigate the protective effect of FA on myocardial I/R injury. Results showed that FA significantly alleviated myocardial tissue damage, reduced the secretion of myocardial injury factors (CK-MB, LDH, troponin-1, and NT-proBNP), and inhibited the release of inflammatory factors (IL-1β, IL-6, and TNF-α).
Front Pharmacol. 2022 Apr 13;13:879232.
Sprague-Dawley rats
Collagenase-induced tendinopathy model
Local injection
2 µg/100 μl
Once a week for 4 weeks
To evaluate the therapeutic effect of Farrerol on tendinopathy. Results showed that Farrerol significantly reduced inflammatory cell infiltration, promoted tenogenesis, and improved tendon mechanical properties. Additionally, Farrerol alleviated tendinopathy by inhibiting iron accumulation and ferroptosis.
J Cell Mol Med. 2022 Jun;26(12):3483-3494.
C57BL/6 mice
Cisplatin-induced acute kidney injury model
Intraperitoneal injection
20 mg/kg
Farrerol was administered 1 hour after cisplatin, and again at 24 and 48 hours, with sacrifice 24 hours after the last dose.
Farrerol significantly improved cisplatin-induced renal damage, including recovery of BUN, SCr, KIM-1, and NGAL levels, and alleviated pathological damage.
Front Physiol. 2019 Nov 26;10:1419.
Rats
Oral administration model
Oral
20 mg/kg
Single dose, sampling time from 0.083 to 24 hours
To study the in vivo metabolism of Farrerol, 42 in vivo metabolites were identified
Molecules. 2019 Sep 24;24(19):3470.
BALB/c mice
LPS-induced mastitis model
Intraperitoneal injection
20, 30, 40 mg/kg
Second dose administered 12 h after LPS injection
Improved pathological injury of mammary gland, reduced MPO activity, inhibited pro-inflammatory mediators and phosphorylation of AKT, NF-κB p65, p38, and ERK1/2
Int J Mol Sci. 2018 Jun 14;19(6):1770.
B6 mice
APAP-induced hepatotoxicity model
Intraperitoneal injection
40 mg/kg
Twice, at 12 h and 1 h intervals
To evaluate the protective effect of Farrerol against APAP-induced hepatotoxicity, results showed that Farrerol significantly reduced mortality, histopathological liver changes, and ALT and AST levels caused by APAP.
Int J Biol Sci. 2019 Jan 29;15(4):788-799.
C57BL/6J mice
High-fat diet-induced MAFLD model
Intraperitoneal injection
40 mg/kg
Once daily for 8 weeks
To investigate the effect of Farrerol on insulin resistance and hepatic steatosis in high-fat diet-induced MAFLD mice. Results showed that Farrerol improved insulin sensitivity, glucose tolerance, and alleviated hepatic steatosis and lipid accumulation.
J Cell Mol Med. 2024 Sep;28(18):e70096.
C57BL/6 mice
TNBS-induced colitis model
Oral
45 mg/kg
Once daily for 3 days
Farrerol significantly improved weight change, clinical scores, colon length, and intestinal epithelium barrier damage, and markedly decreased inflammatory cytokines production in TNBS-induced mice.
Int J Mol Sci. 2018 Jul 13;19(7):2037.
C57BL/6J mice
S. aureus-induced pneumonia model
Intraperitoneal injection
50 mg/kg
Every 12 hours for 96 hours
Evaluate the protective effects of Farrerol combined with cefepime in mice with S. aureus-induced pneumonia. Results showed that the combination therapy significantly improved survival rates, reduced bacterial load in the lungs, and ameliorated tissue damage.
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