Quercetin inhibits fibroblasts proliferation and reduces surgery-induced epidural fibrosis via the autophagy-mediated PI3K/Akt/mTOR pathway

Abstract

Epidural fibrosis (EF) is a serious complication when the patients suffer from operations of lumbar laminectomy. It is reported that quercetin plays a positive role in the prevention of various fibrotic diseases. However, the role of quercetin in the prevention of epidural fibrosis (EF) and its possible mechanism are unclear. Fibroblast proliferation is considered to be the main cause of epidural fibrosis.Autophagy is a lysosomal degradation pathway that is essential for survival, differentiation, development, and homeostasis.Although autophagy has been associated with fibrosis of different tissues, the effect of autophagy on epidural fibrosis is still unknown.The aim of this study was to investigate the function and mechanism of autophagy induced by quercetin, a polyphenol derived from plants. In vivo, the effect of quercetin on reducing epidural fibrosis was confirmed via histological staining and immunohistochemical analysis. The results showed that quercetin had significant suppressive effects on epidural fibrosis following laminectomy in rats.In vitro,, cell counting kit-8 (CCK-8), Western blot analysis, immunofluorescence and Edu staining, TUNEL staining and transmission electron microscopy were used to detect the effects of quercetin on the proliferation and apoptosis of fibroblasts and explore the possible signal transduction pathway. Results indicated that quercetin could induce autophagy and inhibit proliferation in fibroblasts. In conclusion, Quercetin could regulate fibroblast proliferation, apoptosis, migration and other biological behaviors through autophagy, thereby preventing epidural fibrosis. The specific corresponding pathway may be the PI3K/Akt/mTOR signaling pathway.

Exploring the mechanism of Astragali radix for promoting osteogenic differentiation based on network pharmacology, molecular docking, and experimental validation

“…A previous study revealed that quercetin could exert therapeutic effects on a variety of diseases by modulating the PI3K/ Akt signaling pathway. For example, quercetin could improve T-cell lymphoma (Maurya & Vinayak, 2016), ulcerative colitis (Liu, Tong, et al, 2021) and epidural fibrosis (Cao, Chen, et al, 2022) by inhibiting the activation of the PI3K/Akt signaling pathway. Quercetin could exert neuroprotective effects and improve brain injury (Du et al, 2016), and could improve liver injury by inhibiting fibrosis (Wu, Zhang, et al, 2017), and could repair gastric mucosal injury (Yao et al, 2021), all of which was achieved by activating the PI3K/Akt signaling pathway.…”

Pesticides as a risk factor for cognitive impairment: Natural substances are expected to become alternative measures to prevent and improve cognitive impairment

“…Myricetin (MW: 318.235) is a flavonol compound. The study found that the hydroxyl group of myricetin B ring and C ring can regulate the expression of PI3K, and the ketone group and double bond on the C ring can inhibit the anti-inflammatory activity of COX-2 expression (91), which may also be an important reason why myricetin can improve cognitive impairment.…”

“…This suggests that antioxidants may not be the only mechanism by which natural substances exert neuroprotective effects, and the specific reasons need to be further confirmed. In addition, some studies have shown that the antioxidant activity of myricetin depends not only on the hydroxyl group on the B ring, but also on the hydroxyl group and double bond on the C ring (91), so it can be speculated that the antioxidant effect of galangin may also depend on the hydroxyl group and double bond on the C ring. Quercetin (MW: 302.236) is a flavonol compound.…”

“…Quercetin (MW: 302.236) is a flavonol compound. Its C ring and aromatic A ring are the same as kaempferol and myricetin; the difference is that there are two adjacent hydroxyl groups on the aromatic B ring (91). A simple hypothesis is that the ability of quercetin to improve cognitive impairment is intermediate between kaempferol and myricetin, but it cannot be ruled out that the arrangement of hydroxyl groups will affect its improvement effect.…”

The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release

“…More importantly, flavonoid compounds can selectively bind with the type I receptor of transforming growth factor beta (TGF-β) to reduce collagen hypersecretion, which avoids keloid formation [ 14 ]. Among them, Qu has been demonstrated to regulate the proliferation of fibroblasts to further inhibit keloid development by inactivating the type I receptor [ 15 ]. Furthermore, Qu positively impacts the re-epithelisation process because it can inhibit interleukin-4 (IL-4) and IL-13 [ 8 ].…”