PMID- 36142129
OWN - NLM
STAT- MEDLINE
DCOM- 20220926
LR  - 20230308
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 23
IP  - 18
DP  - 2022 Sep 6
TI  - Icariin Alleviates Escherichia coli Lipopolysaccharide-Mediated Endometritis in 
      Mice by Inhibiting Inflammation and Oxidative Stress.
LID - 10.3390/ijms231810219 [doi]
LID - 10219
AB  - Icariin (ICA) is a naturally occurring phytochemical agent primarily extracted 
      from Epimedium Brevicornum Maxim (Family Berberidaceae) with a broad spectrum of 
      bioactivities. Endometritis is a uterine disease that causes enormous losses in 
      the dairy industry worldwide. In this study, anti-inflammatory and anti-oxidant 
      properties of ICA were investigated against lipopolysaccharide (LPS)-induced 
      endometritis in mice to investigate possible underlying molecular mechanisms. 
      Sixty heathy female Kunming mice were randomly assigned to four groups (n = 15), 
      namely control, LPS, LPS + ICA, and ICA groups. The endometritis was induced by 
      intrauterine infusion of 50 microL of LPS (1 mg/mL). After 24 h of onset of 
      LPS-induced endometritis, ICA groups were injected thrice by ICA 
      intraperitoneally six hours apart. Histopathological examination, enzyme linked 
      immunosorbent assay (ELISA), real time quantitative polymerase chain reaction 
      (RT-qPCR), western blotting, and immunohistochemistry were used in this study. 
      Histological alterations revealed that ICA markedly mitigated uterine tissue 
      injury caused by LPS. The results showed that the ICA inhibited the production of 
      pro-inflammatory cytokines (IL-1ss, IL-6, and TNF-alpha) and boosted the production of 
      anti-inflammatory cytokines (IL-10). Additionally, ICA modulated the expression 
      of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase 1 
      (SOD1), catalase (CAT), and glutathione peroxidase 1 (Gpx1) induced by LPS. The 
      administration of ICA significantly (p < 0.05) improved the mRNA and protein 
      expression of Toll-like receptor (TLR) 4. The western blotting and ELISA finding 
      revealed that the ICA repressed LPS-triggered NF-kappaB pathway activation. Moreover, 
      ICA improved the antioxidant defense system via activation of the Nrf2 pathway. 
      The results revealed that ICA up-regulated the mRNA and protein expression of 
      Nuclear erythroid-2-related factor (Nrf2), NAD(P)H: quinone oxidoreductase 1 
      (NQO1), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit 
      (GCLC) under LPS exposure. Conclusively, our findings strongly suggested that ICA 
      protects endometritis caused by LPS by suppressing TLR4-associated NF-kappaB and Nrf2 
      pathways. Altogether, these innovative findings may pave the way for future 
      studies into the therapeutic application of ICA to protect humans and animals 
      against endometritis.
FAU - Shaukat, Aftab
AU  - Shaukat A
AUID- ORCID: 0000-0003-1670-6916
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
FAU - Shaukat, Irfan
AU  - Shaukat I
AD  - Department of Biochemistry, University of Narowal, Narowal 51600, Pakistan.
FAU - Rajput, Shahid Ali
AU  - Rajput SA
AD  - Department of Animal Feed and Production, Faculty of Veterinary and Animal 
      Sciences, Muhammad Nawaz Shareef University of Agriculture, Multan 66000, 
      Pakistan.
FAU - Shukat, Rizwan
AU  - Shukat R
AD  - Faculty of Food, Nutrition & Home Sciences, University of Agriculture, Faisalabad 
      38000, Pakistan.
FAU - Hanif, Sana
AU  - Hanif S
AD  - Hubei Key Laboratory of Theory and Application of Advanced Materials Mechanics, 
      Wuhan University of Technology, Wuhan 430070, China.
FAU - Huang, Shucheng
AU  - Huang S
AUID- ORCID: 0000-0003-3163-8616
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      China.
FAU - Aleem, Muhammad Tahir
AU  - Aleem MT
AUID- ORCID: 0000-0001-8899-2777
AD  - College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 
      China.
FAU - Li, Kun
AU  - Li K
AD  - College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 
      China.
FAU - Li, Qiao
AU  - Li Q
AD  - College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 
      China.
FAU - Chen, Chao
AU  - Chen C
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
FAU - Zhang, Xinxin
AU  - Zhang X
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
FAU - Lv, Haimiao
AU  - Lv H
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
FAU - Yao, Zhiqiu
AU  - Yao Z
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
FAU - Yang, Liguo
AU  - Yang L
AUID- ORCID: 0000-0003-1389-4640
AD  - National Center for International Research on Animal Genetics, Breeding and 
      Reproduction (NCIRAGBR), Huazhong Agricultural University, Wuhan 430070, China.
LA  - eng
GR  - CARS36/China Agriculture Research System of MOF and MAR and earmarked fund for 
      CARS36/
PT  - Journal Article
DEP - 20220906
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Flavonoids)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Quinones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0U46U6E8UK (NAD)
RN  - 130068-27-8 (Interleukin-10)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - EC 6.3.2.2 (Glutamate-Cysteine Ligase)
RN  - VNM47R2QSQ (icariin)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Antioxidants/metabolism
MH  - Catalase/metabolism
MH  - Cytokines/metabolism
MH  - *Endometritis/chemically induced/drug therapy
MH  - Escherichia coli/metabolism
MH  - Female
MH  - Flavonoids
MH  - Glutamate-Cysteine Ligase/metabolism
MH  - Heme Oxygenase-1/metabolism
MH  - Humans
MH  - Inflammation/drug therapy
MH  - Interleukin-10/metabolism
MH  - Interleukin-6/metabolism
MH  - *Lipopolysaccharides/adverse effects
MH  - Malondialdehyde
MH  - Mice
MH  - NAD/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Oxidative Stress
MH  - Quinones/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase-1/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC9499631
OTO - NOTNLM
OT  - NF-kappaB and Nrf2 pathway
OT  - TLR4
OT  - endometritis
OT  - icariin
OT  - lipopolysaccharide
COIS- The authors declared no conflicts of interest.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/09/06
CRDT- 2022/09/23 01:22
PHST- 2022/07/28 00:00 [received]
PHST- 2022/09/01 00:00 [revised]
PHST- 2022/09/02 00:00 [accepted]
PHST- 2022/09/23 01:22 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/09/06 00:00 [pmc-release]
AID - ijms231810219 [pii]
AID - ijms-23-10219 [pii]
AID - 10.3390/ijms231810219 [doi]
PST - epublish
SO  - Int J Mol Sci. 2022 Sep 6;23(18):10219. doi: 10.3390/ijms231810219.