Liquiritigenin-Loaded Submicron Emulsion Protects Against Doxorubicin-Induced Cardiotoxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activity

Q: What are the key findings of this study?

Liquiritigenin-loaded submicron emulsion increased oral bioavailability (AUC) by 595% in rats and significantly reduced cardiac injury markers (P<0.01) in doxorubicin-challenged mice.

Q: What is the clinical evidence from this study?

Population: Doxorubicin-induced cardiotoxicity (n=40). Intervention: Liquiritigenin-loaded submicron emulsion (Lq-SE) vs. Saline (in mice cardiotoxicity model); unformulated liquiritigenin suspension in water (in rat pharmacokinetic study). Primary outcome: Bioavailability (AUC0-t) and attenuation of doxorubicin-induced cardiac injury biomarkers (CK, CK-MB, ANP, BNP, cTnT) and histopathology (p=<0.01).

Q: What does this research mean for the field?

A liquiritigenin-loaded submicron emulsion enhances oral bioavailability by 595% and protects against doxorubicin-induced cardiotoxicity by reducing oxidative stress, inflammation, and cardiac tissue injury. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

To formulate a liquiritigenin-loaded submicron emulsion with enhanced oral bioavailability and investigate its protective efficacy against doxorubicin-induced cardiotoxicity.

Changcan Shi; Hongjuan Wu; Ke Xu; Ting Cai; Kunming Qin; Wu Li; Baochang Cai

doi:10.2147/ijn.s235832

February 1, 2020International Journal of NanomedicineOpen Access

Liquiritigenin-Loaded Submicron Emulsion Protects Against Doxorubicin-Induced Cardiotoxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activity

View Full Paper

Ask AI

Bookmark

Share

Key result

Liquiritigenin submicron emulsion increases bioavailability ~6-fold and reduces doxorubicin-induced cardiotoxicity in animal models.

P<0.01
n=40

Figures

Why the study?

Clinical use of doxorubicin is severely limited by cardiotoxicity, creating a need for prophylactic and treatment strategies.

Does a liquiritigenin-loaded submicron emulsion (Lq-SE) improve oral bioavailability and attenuate doxorubicin-induced cardiotoxicity in rodent models?

Key Points

To formulate a liquiritigenin-loaded submicron emulsion with enhanced oral bioavailability and investigate its protective efficacy against doxorubicin-induced cardiotoxicity.
Formulated liquiritigenin-loaded submicron emulsion (Lq-SE) using high-pressure homogenization and optimized parameters via central composite design response surface methodology (CCD-RSM).
Evaluated oral pharmacokinetics in rats comparing Lq-SE to free liquiritigenin.
Assessed cardioprotective efficacy in doxorubicin-challenged mice using serum cardiac biomarkers (CK, CK-MB, ANP, BNP, cTnT), histopathology, reactive oxygen species assays, and Western blotting.
Optimized Lq-SE droplets demonstrated a mean particle size of 221.7 ± 5.80 nm, polydispersity index of 0.106 ± 0.068, zeta potential of -28.23 ± 0.42 mV, and a 595% higher oral AUC compared to free liquiritigenin in rats.
Lq-SE (20 or 40 mg/kg) significantly lowered elevated serum CK and CK-MB levels in mice (P < 0.05 and P < 0.01), reduced ANP, BNP, and cTnT at 40 mg/kg, and attenuated myocardial histopathological damage.
Lq-SE reduced reactive oxygen species, inhibited NOX4 and NOX2 protein expression, and improved inflammatory and apoptotic signaling mediated by MAPK/NF-κB pathways.

Structured PICO

Does a liquiritigenin-loaded submicron emulsion (Lq-SE) improve oral bioavailability and attenuate doxorubicin-induced cardiotoxicity in rodent models?

P

Population

40 male C57BL/6 mice (6-8 weeks old) in a preclinical model of doxorubicin-induced cardiotoxicity, alongside 12 female Sprague-Dawley rats for pharmacokinetic evaluation.

I

Intervention

Liquiritigenin-loaded submicron emulsion (Lq-SE) administered intragastrically at 10, 20, or 40 mg/kg once daily for 7 consecutive days prior to doxorubicin challenge and 5 consecutive days after (in mice); single oral dose of 20 mg/kg Lq-SE (in rats).

C

Comparator

Physiological saline administered intragastrically in control (n=8) and doxorubicin model (n=8) mouse groups; oral liquiritigenin suspended in water (20 mg/kg) in the rat pharmacokinetic comparator group (n=6).

O

Outcome

Oral bioavailability/pharmacokinetic parameters (AUC, Cmax, Tmax, t1/2) in rats, and serum cardiac injury biomarkers (CK, CK-MB, ANP, BNP, cTnT) and myocardial histopathology in mice after 12 days of treatment.surrogate

Main Result

Absolute Event Rate: 51082% vs 8586.91%

p-value: p=<0.01

Limitations

Preclinical animal study in rats and mice; not tested in humans
Further stability tests and toxicological studies are required before potential clinical application
Underlying mechanisms of the cardioprotective effect require further elucidation
Preclinical animal study only (mice and rats)
Further stability tests and toxicological studies are required for potential clinical application
Further study is needed to fully elucidate the underlying cardioprotective mechanisms

Implication

Formulating liquiritigenin into a submicron emulsion increases its oral bioavailability nearly 6-fold and provides preclinical cardioprotection against doxorubicin-induced myocardial injury via antioxidant, anti-inflammatory, and anti-apoptotic pathways.

Abstract

BACKGROUND: The clinical use of doxorubicin (DOX) is severely limited due to its cardiotoxicity. Thus, there is a need for prophylactic and treatment strategies against DOX-induced cardiotoxicity. PURPOSE: The purpose of this study was to develop a liquiritigenin-loaded submicron emulsion (Lq-SE) with enhanced oral bioavailability and to explore its efficacy against DOX-induced cardiotoxicity. METHODS: Lq-SE was prepared using high-pressure homogenization and characterized using several analytical techniques. The formulation was optimized by central composite design response surface methodology (CCD-RSM). In vivo pharmacokinetic studies, biochemical analyses, reactive oxygen species (ROS) assays, histopathologic assays, and Western blot analyses were performed. RESULTS: Each Lq-SE droplet had a mean particle size of 221.7 ± 5.80 nm, a polydispersity index (PDI) of 0.106 ± 0.068 and a zeta potential of -28.23 ± 0.42 mV. The area under the curve (AUC) of Lq-SE was 595% higher than that of liquiritigenin (Lq). Lq-SE decreased the release of serum cardiac enzymes and ameliorated histopathological changes in the hearts of DOX-challenged mice. Lq-SE significantly reduced oxidative stress by adjusting the levels of ROS, increasing the activity of antioxidative enzymes and inhibiting the protein expression of NOX4 and NOX2. Furthermore, Lq-SE significantly improved the inflammatory response through the mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) signalling pathway and induced cardiomyocyte apoptosis. CONCLUSION: Lq-SE could be used as an effective cardioprotective agent against DOX in chemotherapy to enable better treatment outcomes.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Shi et al. (2020) studied Doxorubicin-induced cardiotoxicity (n=40). Liquiritigenin-loaded submicron emulsion (Lq-SE) vs. Saline (in mice cardiotoxicity model); unformulated liquiritigenin suspension in water (in rat pharmacokinetic study) was evaluated on Bioavailability (AUC0-t) and attenuation of doxorubicin-induced cardiac injury biomarkers (CK, CK-MB, ANP, BNP, cTnT) and histopathology (p=<0.01). Liquiritigenin-loaded submicron emulsion increased oral bioavailability (AUC) by 595% in rats and significantly reduced cardiac injury markers (P<0.01) in doxorubicin-challenged mice.

synapsesocial.com/papers/6a76f609d2fa2470761e8ab8 https://doi.org/10.2147/ijn.s235832

View Full Paper

Ask AI

Bookmark

Share

Liquiritigenin-Loaded Submicron Emulsion Protects Against Doxorubicin-Induced Cardiotoxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activity

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Liquiritigenin-Loaded Submicron Emulsion Protects Against Doxorubicin-Induced Cardiotoxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Activity

Figures

Key Points

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading