Table 2.

Evidence on effect of RF and its roles for reactive oxygen species in various symptoms and diseases. Upregulation ↑, downregulation ↓.

Model	Dose	Antioxidant Enzymes	Key Findings	References
Anti-aging in Drosophila melanogaster (fruit fly)	RF at 120 µg/mL	SOD1 ↑; CAT ↑; lipofuscin (LF) ↓	RF prolonged the life span and increased reproductive capacity through anti-oxidative stress pathway involving enhancing the activity of SOD1 and CAT and inhibiting lipofuscin accumulation	[11]
Keratoconus corneal stroma cells	Keratoconus cells were treated with low dose of RF at 0.167 µg/mL	Increasing gene expression of antioxidant enzymes: aldehyde dehydrogenase 3A1, CAT, enolase 1, GPx 1, haem oxygenase 1, SOD 1 and transketolase	RF improved the synthesis of a normal extracellular matrix and downregulated ROS level in keratoconus. It was quatified by the total collagen protein in the keratoconic stroma.	[12]
Diabetes-induced cardiac dysfunction	RF at 20 mg/kg was treated after streptozotocin-induced diabetes type I.	SOD↑, MDA↓, HO-1 protein level↑	RFK can reduced the risk of cardiac dysfunction by increasing antioxidant, HO-1 and decreasing CTGF levels as well as improving lipid profile	[16]
Diabetes mellitus type-2	RF at 10 and 20 mg/kg was treated after alloxan-induced DM	SOD↑, catalase↑, GSH↑, MDA↓	Decreased pancreatic activity, restored ant-oxidant enzyme activity, decreased FBG level while calcium level and GLUT-4 expression was increased	[17]
Cardiac abnormalities in experimental atherosclerosis in rat	RF at 40 mg/kg together with CoRNS after hypolipidemic induction	SOD↑, CAT↑, GPx↑	CoRNS significant reduced lipid profile: LDL and cardiac enzymes (LDH, ALT, AST, ALP) with enhanced levels of HDL and antioxidants.	[18]
GTN-induced brain oxidative toxicity	RF at 100 mg/kg was treated before GTN-induced migraine	Lipid peroxidation↓, GSH↑, GPx↑	RF with selenium administration protected against GTN-induced brain oxidative toxicity by protecting brain MMCA activity, inhibiting free radicals and supporting the antioxidant redox system.	[19]
Migraine model	RF 100 mg/kg was treated before GTN-induced migraine	Lipid peroxidation↓, GSH↑	RF and vitamin E had a protective effect on the GTN-induced brain injury by inhibiting free radical production, regulation of calcium-dependent processes, and supporting the antioxidant redox system.	[20]