A Novel Dual Therapy for Diabetic Ischemic Heart Injury: Sinomenine and Liraglutide Restore Mitochondrial Homeostasis and Suppress Pyroptosis
- Design
- Animal study · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidence[Auto] Non-human (animal or cellular) evidence; no direct inference to any human population.
- Could weight loss explain it?
- Unknown[Auto] Non-human study; weight-loss mediation not assessable.
- Study tier
- Study tier 4[Auto] Preclinical evidence; not clinical evidence for any human population.
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 20, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; last sentences of abstract] The cardioprotective effects of the combined therapy were largely abrogated by pretreatment with mitochondrial division inhibitor 1. The combination of sinomenine and liraglutide showed remarkable cardioprotective effects against IR injury in diabetic rats, which were associated with the the attenuation of NLRP3-driven pyroptosis and the enhancement of PINK-1/Parkin-mediated mitophagy, suggesting a mechanistic link warranting further validation.
01Findings
What the study reported
- Drugs
- Liraglutide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Diabetes status
- diabetes mentioned
- Cvd status
- cardiovascular disease present in population (see abstract)
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- no
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- VERY_INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Sub-project of Special Funds from Yunnan Clinical Medical Research Center for Metabolic Diseases; Sub-project of Yunnan Provincial Clinical Research Center for Metabolic Diseases; Science and Technology Talent and Platform Plan
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- not available in metadata
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Type 2 diabetes mellitus (T2DM) significantly amplifies the risk and severity of myocardial ischemia-reperfusion (IR) injury, contributing to the disproportionately high cardiovascular mortality observed in diabetic patients. This study investigated the combined cardioprotective effects of sinomenine and liraglutide in a rat model of T2DM with myocardial IR injury and elucidated the underlying molecular mechanisms. Male Sprague Dawley rats were induced to T2DM with a high-fat diet and low-dose streptozotocin. After the induction of diabetes, the rats underwent 30 min of occlusion of the left anterior descending coronary artery, followed by 24 h of reperfusion. Before the IR procedure, diabetic rats were pretreated with sinomenine and/or liraglutide for 7 days. A comprehensive suite of techniques was employed to evaluate various endpoints, including echocardiographic and hemodynamic profiles, infarct size, histopathological alterations, cardiac troponin I (cTn-I) levels, pyroptosis-related proteins (NLRP3 and cleaved caspase-1), mitophagy-related markers (PINK-1 and Parkin), oxidative stress indicators (MDA, SOD, and GPx), and pro-inflammatory cytokines (IL-18 and IL-1β). The combination of sinomenine and liraglutide significantly improved cardiac function, reduced infarct size, attenuated histopathological damage, and decreased serum cTn-I levels (p < 0.05). It also downregulated the expression of pyroptosis-related proteins, upregulated the expression of mitophagy-related proteins, mitigated oxidative stress, and reduced pro-inflammatory cytokine levels (p < 0.05). The cardioprotective effects of the combined therapy were largely abrogated by pretreatment with mitochondrial division inhibitor 1. The combination of sinomenine and liraglutide showed remarkable cardioprotective effects against IR injury in diabetic rats, which were associated with the the attenuation of NLRP3-driven pyroptosis and the enhancement of PINK-1/Parkin-mediated mitophagy, suggesting a mechanistic link warranting further validation.