Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress

Yalçın Erzurumlu; Hatice Kübra Doğan; Deniz Çataklı

Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress

Abstract

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 signal 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 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 of polyubiquitinated 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 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

References

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Details

Primary Language

English

Subjects

Medical Pharmacology

Journal Section

Research Article

Authors

Yalçın Erzurumlu ^*
0000-0001-6835-4436
Türkiye

Hatice Kübra Doğan
0000-0002-6061-1300
Türkiye

Deniz Çataklı
0000-0001-7327-5396
Türkiye

Publication Date

June 27, 2025

Submission Date

November 5, 2022

Acceptance Date

December 19, 2022

Published in Issue

Year 2023 Volume: 27 Number: 2

IZ

https://izlik.org/JA45KL45GJ

Cite

RIS / Bibtex

APA

Erzurumlu, Y., Doğan, H. K., & Çataklı, D. (2025). Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. Journal of Research in Pharmacy, 27(2), 722-732. https://izlik.org/JA45KL45GJ

AMA

1.Erzurumlu Y, Doğan HK, Çataklı D. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. 2025;27(2):722-732. https://izlik.org/JA45KL45GJ

Chicago

Erzurumlu, Yalçın, Hatice Kübra Doğan, and Deniz Çataklı. 2025. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy 27 (2): 722-32. https://izlik.org/JA45KL45GJ.

EndNote

Erzurumlu Y, Doğan HK, Çataklı D (June 1, 2025) Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. Journal of Research in Pharmacy 27 2 722–732.

IEEE

[1]Y. Erzurumlu, H. K. Doğan, and D. Çataklı, “Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress”, J. Res. Pharm., vol. 27, no. 2, pp. 722–732, June 2025, [Online]. Available: https://izlik.org/JA45KL45GJ

ISNAD

Erzurumlu, Yalçın - Doğan, Hatice Kübra - Çataklı, Deniz. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy 27/2 (June 1, 2025): 722-732. https://izlik.org/JA45KL45GJ.

JAMA

1.Erzurumlu Y, Doğan HK, Çataklı D. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. 2025;27:722–732.

MLA

Erzurumlu, Yalçın, et al. “Thymol Reduces the Lipopolysaccharide-Induced Acute Kidney Inflammation by Modulating Lysosomal Stress”. Journal of Research in Pharmacy, vol. 27, no. 2, June 2025, pp. 722-3, https://izlik.org/JA45KL45GJ.

Vancouver

1.Yalçın Erzurumlu, Hatice Kübra Doğan, Deniz Çataklı. Thymol reduces the lipopolysaccharide-induced acute kidney inflammation by modulating lysosomal stress. J. Res. Pharm. [Internet]. 2025 Jun. 1;27(2):722-3. Available from: https://izlik.org/JA45KL45GJ