Berberine ameliorates doxorubicin-induced cardiac toxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis

Q: What are the key findings of this study?

Berberine significantly attenuated doxorubicin-induced diastolic dysfunction, apoptosis, inflammation, and oxidative stress by inhibiting the SNHG14/miR-9-5p/PDK4 axis (p<0.05).

Q: What is the clinical evidence from this study?

Population: Doxorubicin-induced cardiotoxicity (n=100). Intervention: Berberine vs. Doxorubicin alone (20 mg/kg intraperitoneally) or 0.9% saline control. Primary outcome: Cardiac function (LVEF, LVFS, LVEDD, LVESD, CO) and markers of myocardial injury (CK-MB, cTnI, LDH) (p=<0.05).

Q: What does this research mean for the field?

Berberine alleviates doxorubicin-induced cardiotoxicity, diastolic dysfunction, and cardiomyocyte apoptosis by downregulating the SNHG14/miR-9-5p/PDK4 axis. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

To investigate whether berberine counteracts doxorubicin-induced myocardial damage and to determine the underlying molecular mechanism involving long non-coding RNA SNHG14.

Qianyun Xu

doi:10.36721/pjps.2026.39.10.299.1

July 21, 2026Pakistan Journal of Pharmaceutical SciencesOpen Access

Berberine ameliorates doxorubicin-induced cardiac toxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis

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Key result

Berberine attenuates doxorubicin-induced cardiotoxicity by targeting the SNHG14/miR-9-5p/PDK4 pathway.

P<0.05
n=100

Why the study?

Doxorubicin has limited clinical use due to cardiotoxicity, and the molecular mechanisms by which berberine mitigates this toxicity are not fully understood.

Does Berberine prevent doxorubicin-induced cardiotoxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis in preclinical models?

Key Points

To investigate whether berberine counteracts doxorubicin-induced myocardial damage and to determine the underlying molecular mechanism involving long non-coding RNA SNHG14.
Constructed in vitro models using human AC16 cardiomyocytes and in vivo models using adult male rats exposed to doxorubicin and treated with berberine.
Evaluated cardiac function via echocardiography and assessed myocardial damage markers (CK-MB, cTnI, LDH), cell viability, apoptosis, oxidative stress (SOD, MDA), and inflammatory cytokines (IL-1β, IL-6, TNF-α) (n = 5 per group).
Investigated molecular targets using bioinformatics, RT-qPCR, luciferase reporter assays, RNA immunoprecipitation for Ago2, and transfection with SNHG14-overexpressing plasmids or miR-9-5p mimics/agomirs.
Doxorubicin significantly upregulated SNHG14 by 9.32-fold and increased PDK4 while suppressing miR-9-5p, whereas berberine reversed these alterations in AC16 cells and rat myocardium (P < 0.05).
Mechanistically, SNHG14 acted as a cytoplasmic sponge for miR-9-5p, relieving the repression of its target gene PDK4.
Berberine significantly attenuated cardiac diastolic dysfunction in vivo, reduced apoptosis, restored SOD, and lowered MDA, IL-1β, TNF-α, and IL-6 levels (P < 0.05); however, SNHG14 overexpression reversed these protective effects, which were subsequently rescued by miR-9-5p restoration.

Structured PICO

Does Berberine prevent doxorubicin-induced cardiotoxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis in preclinical models?

P

Population

100 male Sprague-Dawley rats and human AC16 cardiomyocytes were used as in vivo and in vitro models to evaluate the protective effects of berberine against doxorubicin-induced cardiotoxicity over a 10-day period.

I

Intervention

Berberine (20 mg/kg daily via gavage for 10 days in rats; 1 μM for 24h in AC16 cells) administered prior to or alongside doxorubicin.

C

Comparator

Doxorubicin alone (20 mg/kg intraperitoneally on days 2, 4, and 6) or 0.9% saline control.

O

Outcome

Echocardiographic parameters of cardiac function (LVEF, LVFS, LVEDD, LVESD, CO) and cellular markers of myocardial injury (CK-MB, cTnI, LDH).surrogate

Main Result

p-value: p=<0.05

Berberine demonstrated significant cardioprotective effects against doxorubicin-induced injury in preclinical models by inhibiting the SNHG14/miR-9-5p/PDK4 axis, highlighting a potential therapeutic mechanism to mitigate chemotherapy-induced cardiotoxicity.

Implication

Berberine may attenuate doxorubicin cardiotoxicity via SNHG14/miR-9-5p/PDK4 in models; leaves open clinical translation and efficacy.

Abstract

BACKGROUND: Doxorubicin (Dox) has limited clinical application due to its cardiotoxicity. Berberine (Ber) counteracts Dox-induced myocardial injury. OBJECTIVES: This study uncovers molecular mechanisms through which Ber mitigates Dox-induced myocardial damage by modulating the long non-coding RNAs small nucleolar RNA host gene 14 (SNHG14). METHODS: To construct Dox-induced cardiotoxicity models in vitro (AC16 cells) and in vivo (male adult rats) for assessing the effects of Ber. Echocardiography was performed to assess the severity of cardiac injury in the rats. RT-qPCR analysis was performed to examine SNHG14 expression. CCK-8, flow cytometry, ELISA and other kits were used to evaluate cell viability, apoptosis, inflammation, oxidative stress and myocardial damage markers. RESULTS: Dox boosted SNHG14 and PDK4 in rat myocardial tissues and cultured cardiomyocytes, while suppressing miR-9-5p. Ber reversed the situation, lowering SNHG14 and PDK4 expression and raising miR-9-5p levels. Mechanistically, SNHG14 acts as a miR-9-5p sponge, which leads to the attenuation of miR-9-5p-mediated inhibition of PDK4, ultimately promoting PDK4 expression. The Ber significantly attenuated Dox-induced diastolic dysfunction in rats. It also attenuated apoptosis, inflammation and oxidative stress in AC16 cells; however, this attenuation was substantially reversed by SNHG14, which was partially abolished by miR-9-5p. CONCLUSION: Ber may alleviate Dox-induced cardiac toxicity by inhibiting the SNHG14/miR-9-5p/PDK4 axis and reducing the apoptosis, inflammation and oxidative stress in cardiomyocytes.

Discussion

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Cite This Study

Qianyun Xu (2026) studied Doxorubicin-induced cardiotoxicity (n=100). Berberine vs. Doxorubicin alone (20 mg/kg intraperitoneally) or 0.9% saline control was evaluated on Cardiac function (LVEF, LVFS, LVEDD, LVESD, CO) and markers of myocardial injury (CK-MB, cTnI, LDH) (p=<0.05). Berberine significantly attenuated doxorubicin-induced diastolic dysfunction, apoptosis, inflammation, and oxidative stress by inhibiting the SNHG14/miR-9-5p/PDK4 axis (p<0.05).

synapsesocial.com/papers/6ad0fc2515427f6a8403ff06 https://doi.org/10.36721/pjps.2026.39.10.299.1

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Berberine ameliorates doxorubicin-induced cardiac toxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis

Key Points

Structured PICO

Main Result

Implication

Abstract

Discussion

Cite This Study

Berberine ameliorates doxorubicin-induced cardiac toxicity via regulation of the SNHG14/miR-9-5p/PDK4 axis

Key Points

Structured PICO

Main Result

Implication

Abstract

Discussion

Cite This Study

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