PMID- 37844468
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231102
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 124
IP  - Pt B
DP  - 2023 Nov
TI  - Guggulsterone protects against lipopolysaccharide-induced inflammation and lethal 
      endotoxemia via heme oxygenase-1.
PG  - 111073
LID - S1567-5769(23)01399-1 [pii]
LID - 10.1016/j.intimp.2023.111073 [doi]
AB  - Guggulsterone (GS) is a phytosterol used to treat inflammatory diseases. Although 
      many studies have examined the anti-inflammatory activities of GS, the detailed 
      mechanisms of GS in lipopolysaccharide (LPS)-induced inflammation and endotoxemia 
      have not yet been examined. Therefore, we investigated the anti-inflammatory 
      effects of GS on LPS-induced inflammation. In murine peritoneal macrophages, the 
      anti-inflammatory activity of GS was primarily mediated by heme oxygenase-1 
      (HO-1) induction. HO-1 induction by GS was mediated by GSH depletion and reactive 
      oxygen species (ROS) production. The ROS generated by GS caused the 
      phosphorylation of GSK3beta (ser9/21) and p38, leading to the translocation of 
      nuclear factor erythroid-related factor 2 (Nrf2), which ultimately induced HO-1. 
      In addition, GS pretreatment significantly inhibited inducible nitric oxide 
      synthase (iNOS), iNOS-derived NO, and COX-2 protein and mRNA expression, and 
      production of COX-derived prostaglandin PGE2, interleukin (IL)-1beta, IL-6, and 
      tumor necrosis factor-alpha (TNF-alpha). In a mouse model of endotoxemia, GS treatment 
      prolonged survival and inhibited the expression of inflammatory mediators, 
      including IL-1beta, IL-6, and TNF-alpha. GS treatment also inhibited LPS-induced liver 
      injury. These results suggest that GS-induced HO-1 could exert anti-inflammatory 
      effects via ROS-dependent GSK (ser21/9)-p38 phosphorylation and nuclear 
      translocation of Nrf2.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Kweon, Bitna
AU  - Kweon B
AD  - Department of Pharmacology, School of Korean Medicine, Wonkwang University, 
      Iksan, 54538 Jeonbuk, South Korea; Hanbang Cardio-Renal Syndrome Research Center, 
      Wonkwang University, Iksan, 54538 Jeonbuk, South Korea.
FAU - Kim, Dong-Uk
AU  - Kim DU
AD  - Department of Pharmacology, School of Korean Medicine, Wonkwang University, 
      Iksan, 54538 Jeonbuk, South Korea; Hanbang Cardio-Renal Syndrome Research Center, 
      Wonkwang University, Iksan, 54538 Jeonbuk, South Korea.
FAU - Oh, Jin-Young
AU  - Oh JY
AD  - Department of Pharmacology, School of Korean Medicine, Wonkwang University, 
      Iksan, 54538 Jeonbuk, South Korea; Hanbang Cardio-Renal Syndrome Research Center, 
      Wonkwang University, Iksan, 54538 Jeonbuk, South Korea.
FAU - Bae, Gi-Sang
AU  - Bae GS
AD  - Department of Pharmacology, School of Korean Medicine, Wonkwang University, 
      Iksan, 54538 Jeonbuk, South Korea; Hanbang Cardio-Renal Syndrome Research Center, 
      Wonkwang University, Iksan, 54538 Jeonbuk, South Korea. Electronic address: 
      baegs888@wku.ac.kr.
FAU - Park, Sung-Joo
AU  - Park SJ
AD  - Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan, 54538 
      Jeonbuk, South Korea; Department of Herbology, School of Korean Medicine, 
      Wonkwang University, Iksan, 54538 Jeonbuk, South Korea. Electronic address: 
      parksj08@wku.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20231014
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Lipopolysaccharides)
RN  - A4PW148END (pregna-4,17-diene-3,16-dione)
RN  - 0 (NF-kappa B)
RN  - 0 (Interleukin-6)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Anti-Inflammatory Agents)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Lipopolysaccharides/pharmacology
MH  - NF-kappa B/metabolism
MH  - Interleukin-6/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - *Endotoxemia/chemically induced/drug therapy
MH  - Inflammation/drug therapy/metabolism
MH  - Anti-Inflammatory Agents/pharmacology/therapeutic use
MH  - Nitric Oxide Synthase Type II/genetics/metabolism
OTO - NOTNLM
OT  - Endotoxemia
OT  - Guggulsterone
OT  - Heme Oxygenase-1 (HO-1)
OT  - Lipopolysaccharide
OT  - Reactive Oxygen Species (ROS)
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/10/17 00:42
MHDA- 2023/11/02 12:47
CRDT- 2023/10/16 18:06
PHST- 2023/08/14 00:00 [received]
PHST- 2023/10/10 00:00 [revised]
PHST- 2023/10/10 00:00 [accepted]
PHST- 2023/11/02 12:47 [medline]
PHST- 2023/10/17 00:42 [pubmed]
PHST- 2023/10/16 18:06 [entrez]
AID - S1567-5769(23)01399-1 [pii]
AID - 10.1016/j.intimp.2023.111073 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2023 Nov;124(Pt B):111073. doi: 
      10.1016/j.intimp.2023.111073. Epub 2023 Oct 14.