2,4,6-Trihydroxy-3-geranyl acetophenone suppresses vascular leakage and leukocyte infiltration in lipopolysaccharide-induced endotoxemic mice
CONTEXT: Lipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro.
OBJECTIVE: This study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice.
MATERIALS AND METHODS: BALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively.
RESULTS: tHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC50=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC50=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction.
DISCUSSION AND CONCLUSIONS: tHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:59 |
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| Enthalten in: |
Pharmaceutical biology - 59(2021), 1 vom: 15. Dez., Seite 732-740 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chan, Yee Han [VerfasserIn] |
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| Links: |
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| Themen: |
2,4,6-trihydroxy-3-geranylacetophenone |
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| Anmerkungen: |
Date Completed 10.12.2021 Date Revised 24.04.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1080/13880209.2021.1933083 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327033444 |
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| 100 | 1 | |a Chan, Yee Han |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 2,4,6-Trihydroxy-3-geranyl acetophenone suppresses vascular leakage and leukocyte infiltration in lipopolysaccharide-induced endotoxemic mice |
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| 500 | |a Date Completed 10.12.2021 | ||
| 500 | |a Date Revised 24.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a CONTEXT: Lipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro | ||
| 520 | |a OBJECTIVE: This study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice | ||
| 520 | |a MATERIALS AND METHODS: BALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively | ||
| 520 | |a RESULTS: tHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC50=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC50=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction | ||
| 520 | |a DISCUSSION AND CONCLUSIONS: tHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a LPS | |
| 650 | 4 | |a endothelial hyperpermeability | |
| 650 | 4 | |a tHGA | |
| 650 | 4 | |a vascular inflammation | |
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| 650 | 7 | |a Acetophenones |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a Phloroglucinol |2 NLM | |
| 650 | 7 | |a DHD7FFG6YS |2 NLM | |
| 700 | 1 | |a Musa, Nazmi Firdaus |e verfasserin |4 aut | |
| 700 | 1 | |a Chong, Yi Joong |e verfasserin |4 aut | |
| 700 | 1 | |a Saat, Siti Arfah |e verfasserin |4 aut | |
| 700 | 1 | |a Hafiz, Faizul |e verfasserin |4 aut | |
| 700 | 1 | |a Shaari, Khozirah |e verfasserin |4 aut | |
| 700 | 1 | |a Israf, Daud Ahmad |e verfasserin |4 aut | |
| 700 | 1 | |a Tham, Chau Ling |e verfasserin |4 aut | |
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