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Protective effect of carvacrol on liver injury in type 2 diabetic db/db mice.

Abstract
The present study aimed to investigate the protective effect of carvacrol on liver injury in mice with type 2 diabetes mellitus (T2DM) and to assess its potential molecular mechanism. Mice were divided into three groups (n=15/group): Non‑diabetic db/m+ mice group, db/db mice group and db/db mice + carvacrol group. In the db/db mice + carvacrol group, db/db mice were administered 10 mg/kg carvacrol daily by gavage for 6 weeks. Fasting blood glucose and insulin levels were separately examined. Pathological changes were observed using hematoxylin and eosin, Masson's trichrome, periodic acid Schiff and reticular fiber staining. In addition, immunohistochemistry, immunofluorescence and western blotting were used to examine the expression levels of Toll‑like receptor 4 (TLR4), NF‑κB, NALP3, AKT1, phosphorylated (p)‑AKT1, insulin receptor (INSR), p‑INSR, mTOR, p‑mTOR, insulin receptor substrate 1 (IRS1) and p‑IRS1 in the liver tissues. The results revealed that carvacrol improved blood glucose and insulin resistance of T2DM db/db mice. After treatment with carvacrol for 6 weeks, the serum levels of TC, TG and LDL‑C were markedly reduced, whereas HDL‑C levels were significantly increased in db/db mice. Furthermore, carvacrol administration significantly decreased serum ALT and AST levels in db/db mice. Serum BUN, Cre and UA levels were markedly higher in db/db mice compared with those in the control group; however, carvacrol treatment markedly reduced their serum levels in db/db mice. Furthermore, histological examinations confirmed that carvacrol could protect the liver of db/db mice. Carvacrol could ameliorate liver injury induced by T2DM via mediating insulin, TLR4/NF‑κB and AKT1/mTOR signaling pathways. The present findings suggested that carvacrol exerted protective effects on the liver in T2DM db/db mice, which could be related to insulin, TLR4/NF‑κB and AKT1/mTOR signaling pathways.
AuthorsWei Zhao, Li Chen, Heng Zhou, Chunyan Deng, Qizhen Han, Yonghua Chen, Qing Wu, Shanshan Li
JournalMolecular medicine reports (Mol Med Rep) Vol. 24 Issue 5 (11 2021) ISSN: 1791-3004 [Electronic] Greece
PMID34435648 (Publication Type: Journal Article)
Chemical References
  • Antigens, CD
  • Blood Glucose
  • Cymenes
  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NLRP3 protein, human
  • Protective Agents
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • carvacrol
  • INSR protein, human
  • Receptor, Insulin
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
Topics
  • Animals
  • Antigens, CD (metabolism)
  • Blood Glucose
  • Cymenes (pharmacology, therapeutic use)
  • Diabetes Mellitus, Experimental (pathology)
  • Diabetes Mellitus, Type 2
  • Insulin Receptor Substrate Proteins (metabolism)
  • Insulin Resistance
  • Liver (injuries, metabolism, pathology)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • NF-kappa B (metabolism)
  • NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
  • Protective Agents (pharmacology)
  • Proto-Oncogene Proteins c-akt
  • Receptor, Insulin (metabolism)
  • Signal Transduction (drug effects)
  • Toll-Like Receptor 4 (metabolism)

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