Dose-Response Evaluation of Scopoletin, a Phytochemical, in a High-Fructose High-Fat Diet-Induced Dyslipidemia Model in Wistar Rats.

Abstract

The putative hypolipidemic properties of scopoletin have not been fully confirmed due to a lack of validation in an irreversible chronic hyperlipidemia animal model. The druggability also needs to be studied in terms of bioavailability in the vascular compartment. Accordingly, we conducted a study to assess the hypolipidemic and pharmacokinetic behavior of scopoletin in the high-fructose high-fat diet (HFHFD)-induced dyslipidemia model in Wistar rats. A total of 42 rats were studied, with 6 in each of the 7 groups. A 60-day HFHFD opted for induction of dyslipidemia. Group I and groups II-VII received normal rat chow diet and HFHFD, respectively. Oral scopoletin (1, 5, 10 mg/kg) and atorvastatin 5 mg/kg were administered in groups III-VI, respectively, once daily for the next 15 days. A separate group, group VII, was used for the pharmacokinetic assessment comparing the scopoletin 10 mg/kg intraperitoneally (IP) in group VII versus the oral (group V). Pharmacokinetic blood sampling was performed on the 10th day of continuous once-daily therapy. Rats were sacrificed for the histological examination. All three scopoletin dosages significantly decreased the total cholesterol, low-density lipoproteins, and triglycerides (P < .05 for all), but not in a dose-dependent manner. Atherogenic Index of plasma, Castelli's risk indices, and histopathological findings confirmed the protective effect of scopoletin. The IP administration showed a 23.18% higher exposure than the oral route (P < .001 for area under the curve and P < .05 for concentration-maximum). This study confirms the hypolipidemic efficacy of scopoletin in a more robust irreversible model of dyslipidemia. Scopoletin's gut absorption in the disease state may also boost the initial phase exploratory clinical trial.

• Authors: Gurpreet Kaur Batra, Chakrant Mothsara, Swati Sharma, Aishwarya Anand, Alka Bhatia, Shobhit Bhansali, Sant Ram, Arnab Pal, Amol N Patil
• Journal: Journal of medicinal food (J Med Food) Vol. 26 Issue 5 Pg. 319-327 (May 2023) ISSN: 1557-7600 [Electronic] United States
• PMID: 37057968 (Publication Type: Journal Article)

Chemical References

• Scopoletin
• Fructose
• Phytochemicals

Topics

• Rats
• Animals
• Rats, Wistar
• Diet, High-Fat (adverse effects)
• Scopoletin (pharmacokinetics)
• Fructose (adverse effects)
• Dyslipidemias (drug therapy, etiology)
• Phytochemicals