Phillyrin alleviates high glucose-induced oxidative stress and inflammation in HBZY-1 cells through inhibition of the PI3K/Akt signaling pathway

© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..

BACKGROUND: Phillyrin, the major lignin compound of Forsythia suspense (Thunb.) Vahl, has been shown the effects of anti-inflammatory and antioxidant. Our study was aimed to explore the protective effect of phillyrin on glomerular mesangial cells (HBZY-1) and the potential mechanism.

METHODS: Cell viability, cytokine production, levels of reactive oxygen radicals (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD), as well as autophagy and apoptosis levels were determined to verify the mechanism of phillyrin on HBZY-1 cells.

RESULTS: Our result indicated that phillyrin significantly inhibited HG-induced HBZY-1 proliferation by inhibiting Bcl-2 expression and upregulating Bad, cleaved caspase-3, and -9 expression. Also, phillyrin suppressed HG-induced mesangial extracellular matrix accumulation by inhibiting the expression of fibronectin and transforming growth factor-β1. Further, phillyrin inhibited oxidative stress and inflammation by decreasing ROS, MDA, TNF-α, IL-1β, and IL-6 contents and increasing SOD and GSH expression. Phillyrin also promoted autophagy by increasing LC3-II/LC3-I ratio and down-regulating p62 expression. Furthermore, WB assay showed that phillyrin inhibited oxidative stress caused by HG via activating Nrf2 signaling pathway, while attenuated proliferation and inflammation in HBZY-1 cells through inactivating PI3K/Akt/mTOR and NF-κB pathways.

CONCLUSION: All results showed that phillyrin might be a promising therapeutic agent for the treatment of DN.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - year:2024

Enthalten in:

The Journal of pharmacy and pharmacology - (2024) vom: 20. März

Sprache:

Englisch

Beteiligte Personen:

Yang, Chunjing [VerfasserIn]
Bao, Li [VerfasserIn]
Shi, Zhengyuan [VerfasserIn]
Xv, Xiqiao [VerfasserIn]
Jiang, Dechun [VerfasserIn]
You, Longtai [VerfasserIn]

Links:

Volltext

Themen:

Autophagy
Diabetic nephropathy
Inflammation
Journal Article
Oxidative stress
Phillyrin
Proliferation

Anmerkungen:

Date Revised 20.03.2024

published: Print-Electronic

Citation Status Publisher

doi:

10.1093/jpp/rgae028

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369973542