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Interleukin-6 expression and its modulation by diacerein in a rat model of chronic stress induced cardiac dysfunction
Vipul Agarwal1, Arjun Singh Kaushik1, Mujeeba Rehman1
1Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow, 226025, UP, India.
Insights
Chronic stress increases inflammation and cardiovascular disease risk. Diacerein, an IL-6 modulator, prevented stress-induced heart dysfunction in rats, suggesting its potential for preventing stress-related cardiovascular issues.
Area of Science:
- Cardiovascular Pharmacology
- Stress Physiology
- Immunology
Background:
- Chronic stress elevates pro-inflammatory cytokines, increasing cardiovascular disease susceptibility.
- Interleukin-6 (IL-6) is implicated in stress-related inflammation and cardiovascular dysfunction.
- The therapeutic potential of diacerein, an IL-6 modulator, in stress-induced cardiovascular diseases remains unassessed.
Purpose of the Study:
- To establish a rat model of chronic unpredictable stress (CUS) exhibiting cardiovascular dysfunction.
- To evaluate the efficacy of diacerein in mitigating cardiovascular impairments in CUS-exposed rats.
- To investigate the molecular interaction between diacerein and the IL-6 pathway.
Main Methods:
- Male Wistar rats were subjected to 8 weeks of CUS to induce stress and cardiovascular changes.
- Molecular docking (AutoDock, SwissDock) assessed diacerein's binding affinity to the IL-6 receptor.
- Diacerein (50 mg/kg/day) was administered post-CUS; serum IL-6 levels (ELISA) and heart function (ECG-HRV) were analyzed.
Main Results:
- CUS exposure significantly increased serum corticosterone and IL-6 levels (two-fold).
- ECG-HRV analysis revealed altered heart rhythm, elevated heart rate, blood pressure, and sympathetic tone in CUS rats.
- Molecular docking confirmed high binding affinity of diacerein to the IL-6 receptor.
- Diacerein treatment effectively prevented CUS-induced cardiovascular dysfunctions.
Conclusions:
- Interleukin-6 plays a significant role in chronic stress-induced cardiovascular dysfunctions.
- Diacerein demonstrates potential as a preventive therapeutic agent for stress-related cardiovascular conditions.
- Targeting the IL-6 pathway with diacerein may offer a novel strategy for managing stress-induced cardiovascular risks.
Abstract:
People with chronic stress have higher levels of pro-inflammatory cytokines, which enhance their susceptibility to cardiovascular diseases. Diacerein has ability to modulate pro-inflammatory cytokines such as IL-1β and IL-6; however, its efficacy in chronic stress associated cardiovascular diseases is not yet assessed. In this study, we standardized a rat model of chronic unpredictable stress (CUS) demonstrating cardiovascular dysfunctions and further assessed the effect of IL-6 modulator, diacerein, on cardiovascular functions in CUS exposed rats. The CUS procedure consisted of exposing male albino Wistar rats to random stressors, everyday for 8 weeks. The binding affinity of diacerein with IL-6 was ascertained using Docking tools viz AutoDock and SwissDock. Moreover, diacerein was administered (50 mg/kg/day x 20 days P.O) post CUS exposure to rats and the serum IL-6 levels and heart functions of CUS rats were determined by ELISA and ECG-HRV analysis, respectively. 8 weeks of CUS exposure resulted in two-fold increase in serum corticosterone and IL-6 levels in rats. The ECG and HRV analysis of CUS rats showed altered sinus rhythm, elevated heart rate, systolic blood pressure and sympathetic tone. Molecular docking studies revealed diacerein high binding affinity towards IL-6 receptor. The post-treatment of diacerein in CUS rats prevented these cardiovascular dysfunctions. Our findings thus suggests that IL-6 may have a prominent role in chronic stress induced cardiovascular dysfunctions and diacerein, could be used as a preventive measure for such conditions.
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