TY  - JOUR
T1  - Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress
AU  - Erzurumlu, Yalçın
AU  - Doğan, Hatice Kübra
AU  - Çataklı, Deniz
PY  - 2025
DA  - June
JF  - Journal of Research in Pharmacy
JO  - J. Res. Pharm.
PB  - Marmara University
WT  - DergiPark
SN  - 2630-6344
SP  - 722
EP  - 732
VL  - 27
IS  - 2
LA  - en
AB  - Inflammation-induced overexpression of cytokines can lead to cell death by caspase-dependent orindependent 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 thymolregulates the anti-inflammatory, antioxidant and anti-apoptotic responses in lipopolysaccharide (LPS)-induced in vitroand in vivo models. However, there is still a need to investigate the molecular mechanism of inflammation and thedetailed regulatory roles of thymol on inflammation-dependent signal mechanisms. In the present study, the possibleprotective effects of thymol on inflammation-mediated lysosomal stress in the LPS-induced acute kidney inflammationmodel were investigated on HEK293 cells. To mimic the inflammation in HEK293 cells, LPS was applied to the cells for24 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) andphospho-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 proteosome system-associated polyubiquitin, cell death-associated caspase-3 and poly (ADP-ribose) polymerase (PARP-1) protein levels were examined by immunoblotting.We find that LPS-induced acute inflammation caused the suppressing of autophagic flux and reducing degradation ofpolyubiquitinated proteins. Thymol treatment markedly reversed the suppression of autophagy and stacking of poly-ubiquitinated protein by LPS. Also, LPS-induced acute inflammation did not cause caspase activation, it caused anincrease in lysosomal stress-related PARP-1 cleavage pattern and thymol administration efficiently reduced PARP-1cleavage. Our results suggested that LPS-induced acute inflammation triggers blockage of autophagic flux and thymolhas a protective role against LPS-induced lysosomal stress.
KW  - Autophagy
KW  - inflammation
KW  - lysosomal stress
KW  - thymol
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L1  - https://dergipark.org.tr/en/download/article-file/4835210
ER  -