PMID- 32801633
OWN - NLM
STAT- MEDLINE
DCOM- 20210701
LR  - 20220416
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Loratadine Alleviates Advanced Glycation End Product-Induced Activation of NLRP3 
      Inflammasome in Human Chondrocytes.
PG  - 2899-2908
LID - 10.2147/DDDT.S243512 [doi]
AB  - BACKGROUND: Chondrocytes in joint tissue are responsible for the synthesis and 
      degradation of the cartilage matrix. Chondrocytes have been closely linked to the 
      pathogenesis of osteoarthritis and cartilage damage. Targeted drug intervention 
      directed at chondrocyte function is a promising strategy for the treatment of 
      osteoarthritis. The effects of histamine receptor H1 (H1R) and its antagonist 
      loratadine in osteoarthritic chondrocytes are less known. MATERIALS AND METHODS: 
      The inhibitory effects of loratadine on NLRP3 inflammasome and the NADPH oxidase 
      subunit NOX4 were assessed in advanced glycation end products (AGEs)-treated 
      SW1353 chondrocytes by real-time PCR, ELISA, and Western blot experiments. The 
      mitochondrial ROS level was measured using the specific probe MitoSOX Red. The 
      dependent effect of loratadine on the transcriptional factor nuclear factor 
      erythroid 2-related factor 2 (NRF2) was evaluated through an oligo-based siRNA 
      knockdown approach and Western blot analysis. RESULTS: The expression of H1R was 
      dose-responsively induced by AGEs in chondrocytes. Treatment with loratadine 
      mitigated AGEs-induced oxidative stress, as revealed by suppressed production of 
      mitochondrial ROS and the NADPH oxidase subunit NOX4. Loratadine treatment 
      inhibited the expression of TxNIP and several components of the NLRP3 
      inflammasome complex, including NLRP3, ASC, and cleaved caspase 1 (P10). 
      Moreover, loratadine suppressed the expression of NRF2, and the silencing of NRF2 
      abolished the suppressive effect of loratadine on NLRP3 inflammasome activation. 
      CONCLUSION: Our study demonstrates that loratadine protects chondrocytes from 
      AGEs-induced TxNIP/NLRP3 inflammasome activation by modulating the expression of 
      the transcriptional factor NRF2. This finding implies that loratadine has 
      therapeutic potential in the treatment of osteoarthritis and cartilage injury.
CI  - (c) 2020 Gao and Zhang.
FAU - Gao, Feng
AU  - Gao F
AD  - Department of Orthopedics, The Second Hospital of Jilin University, Changchun 
      City, Jilin Province 130041, People's Republic of China.
FAU - Zhang, Shanyong
AU  - Zhang S
AD  - Department of Spine Surgery, The Second Hospital of Jilin University, Changchun 
      City, Jilin Province 130041, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20200721
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Histamine H1 Antagonists, Non-Sedating)
RN  - 0 (Inflammasomes)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (NLRP3 protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 7AJO3BO7QN (Loratadine)
SB  - IM
MH  - Chondrocytes/*drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Glycation End Products, Advanced/*antagonists & inhibitors/metabolism
MH  - Histamine H1 Antagonists, Non-Sedating/*pharmacology
MH  - Humans
MH  - Inflammasomes/*antagonists & inhibitors/metabolism
MH  - Loratadine/*pharmacology
MH  - NF-E2-Related Factor 2/antagonists & inhibitors/genetics/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & 
      inhibitors/metabolism
MH  - Reactive Oxygen Species/antagonists & inhibitors/metabolism
MH  - Structure-Activity Relationship
MH  - Tumor Cells, Cultured
PMC - PMC7382759
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - NRF2
OT  - chondrocyte
OT  - histamine H1 receptor
OT  - loratadine
COIS- The authors report no conflicts of interest in this work.
EDAT- 2020/08/18 06:00
MHDA- 2021/07/02 06:00
PMCR- 2020/07/21
CRDT- 2020/08/18 06:00
PHST- 2019/12/23 00:00 [received]
PHST- 2020/04/27 00:00 [accepted]
PHST- 2020/08/18 06:00 [entrez]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/07/02 06:00 [medline]
PHST- 2020/07/21 00:00 [pmc-release]
AID - 243512 [pii]
AID - 10.2147/DDDT.S243512 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Jul 21;14:2899-2908. doi: 10.2147/DDDT.S243512. 
      eCollection 2020.