Bulletin of Pharmaceutical & Medicinal Research2959-91992958-65182022-10-133152510.58398/0005.000015articleSania JamalAisha TahirJunaid Ali KhanDepartment of Physiology and Pharmacology, University of Agriculture, PakistanDepartment of Biochemistry, University of Health Sciences, PakistanDepartment of Physiology and Pharmacology, University of Agriculture, PakistanExcess fructose intake is a main contributor to metabolic syndrome, which causes dyslipidemia, nonalcoholic fatty liver disease (NAFLD) and insulin resistance. The present study examined the protective effects of quercetin, quinoa seed extract (QSE), and kaempferol against high-fructose diet (HFrD)-induced pancreatic and hepatic alterations in Wistar albino rats. Thirty rats were divided into six groups (n = 5, each group consisted of 5 rats): the control group, HFrD + metformin group, HFrD + kaempferol group, HFrD + quercetin group, and HFrD + QSE group. Treatments were administered orally for 21 days following induction with 61% fructose. Biochemical function tests were performed for hemoglobin (Hb) and alanine aminotransferase (ALT) levels, and histopathological analyses of hepatic and pancreatic architecture were performed. The results showed that HFrD intake significantly increased ALT levels and body weight, accompanied by hepatocellular degeneration and inflammatory changes in pancreatic β-cells. Kaempferol, quercetin, and QSE administration significantly increased the Hb concentration, decreased ALT activity, and reduced vacuolar degeneration and hepatic necrosis. Kaempferol and quercetin resulted in nearly normal hepatocyte morphology among the test compounds, while QSE resulted in the greatest decrease in net weight gain. In the treated groups, pancreatic sections revealed the integrity of the islets of Langerhans and decreased inflammation of the islets. This study demonstrated that flavonoids from plants and the QSE have hepatoprotective and pancreatic protective effects through antioxidant and anti-inflammatory mechanisms; hence, these compounds are potentially useful as therapeutic agents in the management of fructose-induced metabolic dysfunctions.