Scutellarin alleviates type 2 diabetes (HFD/low dose STZ)-induced cardiac injury through modulation of oxidative stress, inflammation, apoptosis and fibrosis in mice

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S460-S474. doi: 10.1177/09603271211045948. Epub 2021 Oct 6.

Abstract

Background: Diabetes is a serious global health concern which severely affected public health as well as socio-economic growth worldwide. Scutellarin (SCU), a bioactive flavonoid, is known for its efficacious action against a range of ailments including cardiovascular problems. The present study was conducted to find out possible protective effect and its associated mechanisms of SCU on experimental type 2 diabetes-induced cardiac injury.

Methods: Type 2 diabetes was induced by treating animals with high fat diet for 4 weeks and a single intraperitoneal dose (35 mg/kg body weight) of streptozotocin and diabetic animals received SCU (10 or 20 mg/kg/day) for 6 weeks.

Results: Scutellarin attenuated type 2 diabetes-induced hyperglycemia, bodyweight loss, hyperlipidaemia, cardiac functional damage with histopathological alterations and fibrosis. Scutellarin treatment to type 2 diabetic mice ameliorated oxidative stress, inflammatory status and apoptosis in heart. Furthermore, the underlying mechanisms for such mitigation of oxidative stress, inflammation and apoptosis in heart involved modulation of Nrf2/Keap1 pathway, TLR4/MyD88/NF-κB mediated inflammatory pathway and intrinsic (mitochondrial) apoptosis pathway, respectively.

Conclusions: The current findings suggest that SCU is effective in protecting type 2 diabetes-induced cardiac injury by attenuating oxidative stress and inflammatory responses and apoptosis, and it is also worth considering the efficacious potential of SCU to treat diabetic cardiomyopathy patients.

Keywords: Type 2 diabetes; apoptosis; fibrosis; heart and mice; inflammation; oxidative stress.

MeSH terms

  • Animals
  • Apigenin / therapeutic use*
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Cardiovascular Agents / therapeutic use
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2 / chemically induced*
  • Diet, High-Fat
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Glucuronates / therapeutic use*
  • Heart Diseases / drug therapy*
  • Heart Diseases / etiology*
  • Inflammation / drug therapy*
  • Lipids / blood
  • Male
  • Mice
  • Oxidative Stress / drug effects*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Biomarkers
  • Blood Glucose
  • Cardiovascular Agents
  • Glucuronates
  • Lipids
  • RNA, Messenger
  • scutellarin
  • Apigenin