Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

Q: What are the key findings of this study?

Juglone pretreatment reduced myocardial infarct area to 10% compared to 55% with isoproterenol alone and normalized cardiac biomarkers in rats.

Q: What is the clinical evidence from this study?

Population: Isoproterenol-induced myocardial infarction in Sprague Dawley rats (n=30). Intervention: Juglone vs. Isoproterenol alone (80 mg/kg subcutaneously), vehicle control (1% DMSO), and active control atenolol (1 mg/kg intraperitoneally). Primary outcome: Percent myocardial infarct area (p=<0.001).

Q: What does this research mean for the field?

Pretreatment with juglone significantly attenuates isoproterenol-induced myocardial infarction in rats by reducing infarct size, restoring electrocardiographic alterations, and normalizing serum cardiac biomarkers. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the cardioprotective efficacy and potential mechanisms of juglone against isoproterenol-induced myocardial infarction in rats.

Taseer Ahmad; Taous Khan; Tahira Tabassum; Yahya S. Alqahtani; Mater H. Mahnashi; Bandar A. Alyami; Ali O. Alqarni; Mohammed Yahia Alasmary; Sultan A. Almedhesh; Abdul Jabbar Shah

doi:10.3390/cimb44070220

July 16, 2022Current Issues in Molecular BiologyOpen Access

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

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Key result

Juglone pretreatment reduces myocardial infarct area by ~45 percentage points in rat models.

P<0.001
n=30

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Why the study?

Phytochemical constituents have gained attention for ischemic heart disease, but the cardioprotective effects and mechanisms of juglone in myocardial injury needed investigation.

Does pretreatment with juglone reduce myocardial infarct size, cardiac biomarker elevation, and histopathological injury in rats with isoproterenol-induced myocardial infarction?

Key Points

To evaluate the cardioprotective efficacy and potential mechanisms of juglone against isoproterenol-induced myocardial infarction in rats.
Sprague-Dawley rats received intraperitoneal pretreatment for 5 days with juglone (1 or 3 mg/kg) or atenolol (1 mg/kg) in separate experiments.
Myocardial injury was induced by administering subcutaneous isoproterenol (80 mg/kg) at 24-hour intervals on days 4 and 5.
Cardioprotective effects were evaluated via lead II electrocardiography, serum cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT, AST), and heart histopathology.
Pretreatment with 1 mg/kg and 3 mg/kg juglone reduced the myocardial infarct area to 15% and 10%, respectively, compared to 55% in the isoproterenol-alone group.
Juglone at 3 mg/kg significantly decreased serum cardiac injury markers, including cTnI (63.23 ± 1.25%), CPK (32.22 ± 2.51%), CK-MB (58.35 ± 3.01%), and LDH (58.85 ± 6.01%).
Juglone pretreatment significantly reduced the heart weight to body weight ratio (p < 0.001), restored abnormal ECG patterns, and reduced myocardial inflammation, edema, and necrosis.

Structured PICO

Does pretreatment with juglone reduce myocardial infarct size, cardiac biomarker elevation, and histopathological injury in rats with isoproterenol-induced myocardial infarction?

P

Population

30 Sprague Dawley rats (8-10 weeks old, 200-250 g) with isoproterenol-induced myocardial injury followed for 5 days.

I

Intervention

Juglone (5-hydroxy-1,4-naphthoquinone) 1 mg/kg/day or 3 mg/kg/day intraperitoneally for 5 consecutive days prior to/during isoproterenol administration.

C

Comparator

Group I (control): 1% DMSO (1 mL/kg/day i.p. for 5 days) + normal saline (1 mL/kg/day s.c. on days 4 and 5); Group II (ISO disease control): 1% DMSO (1 mL/kg/day i.p. for 5 days) + isoproterenol (80 mg/kg s.c. on days 4 and 5); Group III (positive control): atenolol (1 mg/kg/day i.p. for 5 days) + isoproterenol (80 mg/kg s.c. on days 4 and 5).

O

Outcome

Myocardial injury assessed by lead II ECG (ST-segment elevation, deep Q-waves), percent myocardial infarct area, heart-to-body weight ratio, serum cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT, AST), and myocardial histopathology (inflammation, edema, necrosis) at 24 hours after the second dose of isoproterenol.surrogate

Main Result

Absolute Event Rate: 10% vs 55%

p-value: p=<0.001

In a rat model of isoproterenol-induced myocardial infarction, pretreatment with juglone (1 and 3 mg/kg) provided cardioprotective effects comparable to atenolol by reducing infarct size, ECG abnormalities, cardiac enzyme leakage, and myocardial necrosis.

Limitations

Preclinical animal model in rats requiring further validation
Further studies needed to confirm molecular mechanisms such as effects on CAT, GPx, and inflammatory mediators (caspase-3 and 9)
Further electrophysiological studies are needed
Preclinical animal study in rats
Further studies are needed to confirm molecular mechanisms including effects on catalase (CAT) and glutathione peroxidase (GPx)
Further electrophysiological studies and protein expression analyses of inflammatory mediators (e.g., caspase-3 and caspase-9) are required

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Implication

Supports further preclinical evaluation of juglone; leaves open translation to human myocardial infarction.

Abstract

Therapeutic and/or preventive interventions using phytochemical constituents for ischemic heart disease have gained considerable attention worldwide, mainly due to their antioxidant activity. This study investigated the cardioprotective effect and possible mechanism of juglone, a major constituent of the walnut tree, using an isoproterenol (ISO)-induced myocardial infarction (MI) model in rats. Rats were pretreated for five (5) days with juglone (1, 3 mg/kg, i.p) and atenolol (1 mg/kg, i.p) in separate experiments before inducing myocardial injury by administration of ISO (80 mg/kg, s.c) at an interval of 24 h for 2 consecutive days (4th and 5th day). The cardioprotective effect of juglone was confirmed through a lead II electrocardiograph (ECG), cardiac biomarkers (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological study. The results of our present study suggest that prior administration of juglone (1 and 3 mg/kg) proved to be effective as a cardioprotective therapeutic agent in reducing the extent of myocardial damage (induced by ISO) by fortifying the myocardial cell membrane, preventing elevated T-waves, deep Q-waves in the ECG, heart to body weight ratio, infarction and also by normalizing cardiac marker enzymes (cTnI, CPK, CK-MB, LDH, ALT and AST) and histopathological changes, such as inflammation, edema and necrosis. In conclusion, this study has identified phytochemical constituents, in particular juglone, as a potential cardioprotective agent.

Discussion

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Cite This Study

Ahmad et al. (2022) studied Isoproterenol-induced myocardial infarction in Sprague Dawley rats (n=30). Juglone vs. Isoproterenol alone (80 mg/kg subcutaneously), vehicle control (1% DMSO), and active control atenolol (1 mg/kg intraperitoneally) was evaluated on Percent myocardial infarct area (p=<0.001). Juglone pretreatment reduced myocardial infarct area to 10% compared to 55% with isoproterenol alone and normalized cardiac biomarkers in rats.

synapsesocial.com/papers/6a859312f8226fba7f10a1b8 https://doi.org/10.3390/cimb44070220

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Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Juglone from Walnut Produces Cardioprotective Effects against Isoproterenol-Induced Myocardial Injury in SD Rats

Figures

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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