Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2023 , Vol 27 , Issue 1
Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress
Yalcin ERZURUMLU1,Hatice Kubra DOGAN2,Deniz CATAKLI3
1Department of Biochemistry, Faculty of Pharmacy, Suleyman Demirel University, Merkez 32260 Isparta, Türkiye
2Department of Bioengineering, Institute of Science, Suleyman Demirel University, Merkez 32260 Isparta, Türkiye
3Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Merkez 32260 Isparta, Türkiye
DOI : 10.29228/jrp.319 Inflammation-induced overexpression of cytokines can lead to cell death by caspase-dependent or independent signaling pathways. Numerous natural products are used to suppress/re-modulate inflammation. Phenolic monoterpene thymol is widely used in cosmetics and for medical purposes. It has been shown that thymol regulates the anti-inflammatory, antioxidant and anti-apoptotic responses in lipopolysaccharide (LPS)-induced in vitro and in vivo models. However, there is still a need to investigate the molecular mechanism of inflammation and the detailed regulatory roles of thymol on inflammation-dependent signaling mechanisms. In the present study, the possible protective effects of thymol on inflammation-mediated lysosomal stress in the LPS-induced acute kidney inflammation model were investigated on HEK293 cells. To mimic the inflammation in HEK293 cells, LPS was applied to the cells for 24 h. Following, cells were treated with various doses of thymol and total protein was isolated from the cells. Inflammation-associated interleukin-6 (IL-6), tumor necrosis factor-⍺ (TNF-⍺), nuclear factor kappa B (Nf-κB) and phospho-Nf-κB protein levels, autophagy-related Beclin-1, autophagy-related 5 (Atg5), p62/SQSTM1 and microtubule-associated protein 1A/1B-light chain 3 (LC3-I/II), ubiquitin proteasome system-associated polyubiquitin, cell death-associated caspase-3 and poly (ADP-ribose) polymerase (PARP-1) protein levels were examined by immunoblotting. We found that LPS-induced acute inflammation caused the suppressing of autophagic flux and reducing degradation of polyubiquitinated proteins. Thymol treatment markedly reversed the suppression of autophagy and stacking of poly-ubiquitinated protein by LPS. While, LPS-induced acute inflammation did not cause caspase activation, it caused an increase in lysosomal stress-related PARP-1 cleavage pattern and thymol administration efficiently reduced PARP-1 cleavage. Our results suggested that LPS-induced acute inflammation triggers blockage of autophagic flux and thymol has a protective role against LPS-induced lysosomal stress. Keywords : Autophagy, Inflammation, Lysosomal stress, Thymol
Marmara University