Hypnotic Activity of Carthamus tinctorius Petal Extracts and Its Purified Components

Abstract

Background and objectives: Sleep disorders are common in industrialized and developing societies. This study aimed to investigate the sleep-inducing potential of Carthamus tinctorius L. (safflower) fractions and purified components on insomnia based on Iranian traditional medicine references. Methods: The methanol extract of safflower petals and the hexane, ethyl acetate, and methanol fractions were prepared. Additionally, a Carthamus red pigment fraction was obtained through alkaline extraction (with sodium carbonate) and acidic precipitation (with citric acid). The red pigment fraction was further isolated using semi-preparative high-performance liquid chromatography. The hypnotic activity of these fractions and purified compounds was assessed using the pentobarbital-induced loss of righting reflex test. Results: Both the ethyl acetate and red pigment fractions at 200 mg/kg demonstrated significant hypnotic activity compared to the control group. In contrast, hexane and methanol fractions showed no significant effects at 200 mg/kg. The hypnotic effect of the red pigment fraction was dose-dependent (100, 150, 200 mg/kg). Purification resulted in three major compounds: EEE (1), EZE (2), and EZZ (3), isomers of N1, N5, N10-tri-p-coumaroylspermidine, which exhibited significant hypnotic activity at 15 mg/kg, antagonized by flumazenil (2 mg/kg). Conclusion: Our findings suggest that safflower extract exhibits a dose-dependent hypnotic effect, with tri-p-coumaroylspermidine identified as the primary active compound. This activity is at least partly linked to gamma-aminobutyric acid (GABA) receptors. However, further investigation is needed to elucidate the underlying mechanism and potential side effects.

Keywords

• coumaroylspermidine
• hypnotic
• lc-ms
• nmr
• safflower