Modulation of multiple cellular signalling pathways as targets for anti-inflammatory and anti-tumorigenesis action of Scopoletin

Abstract

Objectives Scopoletin (6-methoxy-7-hydroxycoumarin) is a naturally occurring coumarin belonging to the category of secondary metabolites. Coumarins are commonly found in several herbs and play a prominent role in the defense mechanism of plants. Beneficial effects of scopoletin including antioxidant, anti-diabetic, hepatoprotective, neuroprotective and anti-microbial activity induced via numerous intracellular signalling mechanisms have been widely studied. However, anti-inflammation and anti-tumorigenesis properties of scopoletin are not well documented in the literature. Therefore, the primary focus of the present review was to highlight the plethora of research pertaining to the signalling mechanisms associated with the prevention of the progression of disease condition by scopoletin. Key findings Multiple signalling pathways like nuclear erythroid factor-2 (NEF2)-related factor-2 (NRF-2), apoptosis/p53 signalling, nuclear factor-κB (NF-κB) signalling, autophagy signalling, hypoxia signalling, signal transducer and activator of transcription-3 (STAT3) signalling, Wnt-β signalling, Notch signalling are coupled with the anti-inflammation and anti-tumorigenesis potential of scopoletin. Summary Understanding crucial targets in these molecular signalling pathways may support the role of scopoletin as a promising naturally derived bioactive compound for the treatment of several diseases.

Scopoletin inhibits PDGF-BB-induced proliferation and migration of airway smooth muscle cells by regulating NF-κκB signaling pathway

“…22 In addition, another study indicated that scopoletin induced cell death via the mitochondrial apoptosis pathway as well as cell cycle arrest. 7 Performing CCK-8, wound closure, and transwell assays, we here found that scopoletin suppressed the viability and motility of PDGF-BB-induced ASMCs. 23 ASMC migration is considered as a key factor in the pathogenesis of asthma.…”

“…6 In addition, its antioxidant activities have been indicated in multiple studies. 7,8 Scopoletin could inhibit the proliferation as well as motility of cervical cancer cells and promote the apoptosis of prostate cancer cells by regulating the PI3K/AKT signaling pathway. 8 Scopoletin also inhibits the proliferation of immature dendritic cells (DC) and has anti-angiogenic effects.…”

Effects of Scopoletin Supplementation and Stocking Density on Growth Performance, Antioxidant Activity, and Meat Quality of Korean Native Broiler Chickens

“…Meanwhile, the reduction of lipid peroxidation in the thigh muscle may be reflected in the decrease of MDA concentration in the SK treatments. Scopoletin also showed high inhibitory activities against anti-inflammatory cytokines by decreasing TNF-α, IL-1β, and IL-6 secretions [ 17 , 19 , 27 ]. It has been reported that the anti-inflammatory influences of scopoletin are associated with a decrease in free radicals production.…”

“…The lower concentration of serum corticosterone may indicate that the chickens fed SK diets had relatively lower stress regardless of SD because the SD did not decrease cooking loss of breast meat. There is a positive relationship between corticosterone production and the secretion of inflammatory cytokines including IL-1b, IL-6, IL-10, IL-12-a, and IL-18 [ 19 , 37 ], which can adversely affect meat quality. Corticosterone secretion has been shown to be a factor to decrease meat quality by degrading protein in muscle and decreasing the fatty acid transport protein expression [ 35 ].…”

“…The root and flower of SK species contain a large quantity of flavonoids [ 14 ], isoflavonoids [ 15 ], and scopoletin [ 16 , 17 ] having anti-oxidative capacity [ 18 ]. Scopoletin is a kind of phenolic coumarin with promising anti-inflammatory effects [ 19 ] that can protect the body from microbial attack and environmental stress, including mechanical injury [ 20 ]. The antioxidant properties of scopoletin were proved by scavenging superoxide anion, which may prevent stressful conditions related to oxidative damage [ 16 ].…”