The pharmacological properties and corresponding mechanisms of farrerol: a comprehensive review.

CONTEXT: Farrerol, a typical natural flavanone isolated from the traditional Chinese herb 'Man-shan-hong' [Rhododendron dauricum L. (Ericaceae)] with phlegm-reducing and cough-relieving properties, is widely used in China for treating bronchitis and asthma. OBJECTIVE: To present the anti-inflammatory, antioxidant, vasoactive, antitumor, and antimicrobial effects of farrerol and its underlying molecular mechanisms. METHODS: The literature was reviewed by searching PubMed, Medline, Web of Knowledge, Scopus, and Google Scholar databases between 2011 and May 2021. The following key words were used: 'farrerol,' 'flavanone,' 'anti-inflammatory,' 'antioxidant,' 'vasoactive,' 'antitumor,' 'antimicrobial,' and 'molecular mechanisms'. RESULTS: Farrerol showed anti-inflammatory effects mainly mediated via the inhibition of interleukin (IL)-6/8, IL-1ß, tumour necrosis factor(TNF)-α, NF-κB, NO, COX-2, JNK1/2, AKT, PI3K, ERK1/2, p38, Keap-1, and TGF-1ß. Farrerol exhibited antioxidant effects by decreasing JNK, MDA, ROS, NOX4, Bax/Bcl-2, caspase-3, p-p38 MAPK, and GSK-3ß levels and enhancing Nrf2, GSH, SOD, GSH-Px, HO-1, NQO1, and p-ERK levels. The vasoactive effects of farrerol were also shown by the reduced α-SMA, NAD(P)H, p-ERK, p-Akt, mTOR, Jak2, Stat3, Bcl-2, and p38 levels, but increased OPN, occludin, ZO-1, eNOS, CaM, IP3R, and PLC levels. The antitumor effects of farrerol were evident from the reduced Bcl-2, Slug, Zeb-1, and vimentin levels but increased p27, ERK1/2, p38, caspase-9, Bax, and E-cadherin levels. Farrerol reduced α-toxin levels and increased NO production and NF-κB activity to impart antibacterial activity. CONCLUSIONS: This review article provides a theoretical basis for further studies on farrerol, with a view to develop and utilise farrerol for treating of vascular-related diseases in the future.

Farrerol Modulates Aorta Gene Expression Profile in Spontaneously Hypertensive Rats.

Farrerol, a typical natural flavanone and major active component in Rhododendron dauricum var. ciliatum, has been shown to possess vasoactive ability in vitro. The aim of this study was to investigate its effect on aorta gene expression in spontaneously hypertensive rats. Twelve-week-old male normotensive Wistar Kyoto rats and spontaneously hypertensive rats were treated with orally administered farrerol (50 mg/kg body weight) for 8 wk before they were sacrificed. We found that aorta samples showed 444 upregulated genes in control spontaneously hypertensive rats compared with the control Wistar Kyoto rats. Administration of farrerol in spontaneously hypertensive rats increased the expression of 2329 genes in the aorta compared with the control spontaneously hypertensive rats. Gene expression profiles performed on the aorta revealed that farrerol induced changes in vascular smooth muscle contraction, mitogen-activated protein kinase signaling pathway, regulation of actin cytoskeleton, vascular endothelial growth factor signaling pathway, calcium signaling pathway, and renin angiotensin system. Furthermore, 10 genes involved in the pathway of vascular smooth muscle contraction were verified using real-time polymerase chain reaction technique, and several novel potential target genes for the farrerol treatment of hypertension were identified. The findings of this study lend support to the potential use of farrerol as a novel therapeutic and antihypertensive candidate drug to prevent the development of hypertension.