Penehyclidine hydrochloride alleviates LPS-induced inflammatory responses and oxidative stress via ROS/Nrf2/HO-1 activation in RAW264.7 cells
BACKGROUND: Inflammation is a biological response of the immune system to harmful stimuli. Penehyclidine hydrochloride (PCH) can alleviate inflammation and oxidative stress by activating reactive oxygen species (ROS), nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) in animal models, but there is a lack of cellular evidence.
OBJECTIVES: This study investigated the effects of PHC on lipopolysaccharide (LPS)-induced inflammation response and oxidative stress in RAW264.7 cells.
MATERIAL AND METHODS: RAW264.7 cells were treated with 1 μg/mL or 5 μg/mL of PHC, with interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-1β, and prostaglandin E2 (PGE2) levels measured with enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) measured using the Griess test. Reactive oxygen species were examined with flow cytometry and immunofluorescence, and b-related factor 2 (BRF-2) and NAD(P)H-quinone oxidoreductase 1 (NQO1) using western blot.
RESULTS: Penehyclidine hydrochloride partly, but substantially, reversed LPS-related NO and PGE2 production by RAW264.7 cells in a dose-dependent manner and suppressed LPS-induced expression of IL-6, TNF-α and IL-1β messenger ribonucleic acid (mRNA), secretion of IL-6, TNF-α and IL-1β, and ROS production. Lipopolysaccharide stimulation did not affect Nrf2, heme oxygenase 1 (HO-1) or NQO1 protein expression in RWA264.7 cells not treated with PHC. However, PHC treatment significantly elevated Nrf2, HO-1 and NQO1 protein in LPS-treated RWA264.7 cells, an effect that was dose-dependent. The ROS scavenging using N-acetyl-L-cysteine abolished the PHC-induced upregulation of Nrf2 and HO-1.
CONCLUSIONS: Penehyclidine hydrochloride may alleviate LPS-induced inflammation and oxidative stress by activating Nrf2 signaling in RAW264.7 macrophages. These findings suggest that PHC could alleviate inflammation by targeting activated macrophages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Advances in clinical and experimental medicine : official organ Wroclaw Medical University - (2024) vom: 26. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Guo, Qiongmei [VerfasserIn] |
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| Links: |
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| Themen: |
Inflammation |
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| Anmerkungen: |
Date Revised 26.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.17219/acem/183883 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM37019876X |
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| 100 | 1 | |a Guo, Qiongmei |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Penehyclidine hydrochloride alleviates LPS-induced inflammatory responses and oxidative stress via ROS/Nrf2/HO-1 activation in RAW264.7 cells |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 26.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a BACKGROUND: Inflammation is a biological response of the immune system to harmful stimuli. Penehyclidine hydrochloride (PCH) can alleviate inflammation and oxidative stress by activating reactive oxygen species (ROS), nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase 1 (HO-1) in animal models, but there is a lack of cellular evidence | ||
| 520 | |a OBJECTIVES: This study investigated the effects of PHC on lipopolysaccharide (LPS)-induced inflammation response and oxidative stress in RAW264.7 cells | ||
| 520 | |a MATERIAL AND METHODS: RAW264.7 cells were treated with 1 μg/mL or 5 μg/mL of PHC, with interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), IL-1β, and prostaglandin E2 (PGE2) levels measured with enzyme-linked immunosorbent assay (ELISA) and nitric oxide (NO) measured using the Griess test. Reactive oxygen species were examined with flow cytometry and immunofluorescence, and b-related factor 2 (BRF-2) and NAD(P)H-quinone oxidoreductase 1 (NQO1) using western blot | ||
| 520 | |a RESULTS: Penehyclidine hydrochloride partly, but substantially, reversed LPS-related NO and PGE2 production by RAW264.7 cells in a dose-dependent manner and suppressed LPS-induced expression of IL-6, TNF-α and IL-1β messenger ribonucleic acid (mRNA), secretion of IL-6, TNF-α and IL-1β, and ROS production. Lipopolysaccharide stimulation did not affect Nrf2, heme oxygenase 1 (HO-1) or NQO1 protein expression in RWA264.7 cells not treated with PHC. However, PHC treatment significantly elevated Nrf2, HO-1 and NQO1 protein in LPS-treated RWA264.7 cells, an effect that was dose-dependent. The ROS scavenging using N-acetyl-L-cysteine abolished the PHC-induced upregulation of Nrf2 and HO-1 | ||
| 520 | |a CONCLUSIONS: Penehyclidine hydrochloride may alleviate LPS-induced inflammation and oxidative stress by activating Nrf2 signaling in RAW264.7 macrophages. These findings suggest that PHC could alleviate inflammation by targeting activated macrophages | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a lipopolysaccharide | |
| 650 | 4 | |a macrophages | |
| 650 | 4 | |a oxidative stress | |
| 650 | 4 | |a penehyclidine hydrochloride | |
| 700 | 1 | |a Zhang, Chunyan |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Jingui |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Wenjing |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiaozhi |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.17219/acem/183883 |3 Volltext |
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