Casticin, a flavonoid isolated from Vitex rotundifolia, inhibits prolactin release in vivo and in vitro

Abstract

Aim: To investigate the anti-hyperprolactinemia activity of casticin, a flavonoid isolated from Vitex rotundifolia, and elucidate its molecular mechanism. Methods: Hyperprolactinemia (MIHP) was induced by administration of metoclopramide dihydrochloride (50 mg/kg, tid, ip, for 10 d) in SD rats and the primary pituitary cells were prepared from the pituitary glands of the SD rats. Prolactin concentrations were measured using a radioimmunoassay. Cell viability was measured using an MTT assay. The mRNA expression of estrogen receptor alpha and beta in rat pituitary cells was measured using semi-quantitative RT-PCR analysis. Results: The level of serum prolactin in the MIHP model group was 2.1 fold higher than that in the untreated control group (P<0.01). Casticin (10, 20, and 40 mg/kg, ip, for 7 d) reduced serum prolactin levels by 33.9%, 54.3%, and 64.7%, respectively (P<0.01). The positive control drug bromocriptine 1 mg/kg decreased the serum prolactin concentration in MIHP rats by 44.9%. 17β-Estradiol (E2) significantly increased the proliferation of pituitary cells and casticin (1 and 10 μmol/L) markedly inhibited E2-induced pituitary cell proliferation by 27.7% and 42.1%, respectively. Stimulation of pituitary cells with E2 increased prolactin secretion into the cell culture supernatants, and casticin (0.1, 1, and 10 μmol/L) significantly inhibited the prolactin release stimulated by E2 in a concentration-dependent manner. Casticin (1 and 10 μmol/L) significantly inhibited ERα mRNA expression in pituitary cells stimulated with E2 (P<0.01) but increased ERβ mRNA expression at a concentration of 10 μmol/L (P<0.01). However, casticin had no effects on proliferation and prolectin release of the unstimulated primary pituitary cells in vitro. Conclusion: Casticin inhibited the release of prolactin from pituitary cells of SD rats stimulated with E2 in vivo and in vitro. These effects might be related with inhibiting the ERα mRNA expression and increasing the ERβ mRNA expression.

Casticin treatment inhibits squamous cell carcinoma cell proliferation and arrests cell cycle in S phase

“…Casticin, treatment in leukemic carcinoma cells induces apoptosis through mitotic catastrophe and inhibits secretion of prolactin (Ye et al, 2010). It inhibits viability of glioma stem-like cells by inducing apoptosis (Yang et al, 2011;Feng et al, 2012).…”

“…Casticin (3',5-dihydroxy-3,4',6,7-tetrame-thoxyflavone), exhibits inhibitory effect on the secretion of prolactin and induces apoptosis in leukemic carcinoma cells through mitotic catastrophe (Ye et al, 2010). It also interacts with phosphatidylinositol-3-kinase in synergistic manner to inhibit cancer cell growth (Shen et al, 2009).…”

Molecular Mechanisms of Casticin Action: an Update on its Antitumor Functions

“…As shown in Figure 1, accumulated data indicate that casticin was isolated from many plant species such as, namely Vitex agnus castus (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), Daphne genkwa (Xie et al, 2011), Achillea millefolium (Haidara et al, 2006;Csupor-Loffler et al, 2009), Ficus microcarpa , Vitex rotundifolia (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), Fructus viticis (Hu et al, 2007b;Guan et al, 2010;Chen et al, 2011b;Yang et al, 2011;Zeng et al, 2012;Zhou et al, 2013a), Vitex negundo (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013), Crataegus pinnatifida (Kao et al, 2005), Pavetta crassipes (Mali and Dhake, 2011), Nelsonia canescens, Butea frondosa Koen , Dalbergia odorifera (Mali and Dhake, 2011), Bryonia laciniosa (Aggarwal et al, 2011), Citrus unshu (Mali and Dhake, 2011;Nagoor et al, 2011), Centipeda minima (Mali and Dhake, 2011), Clausena excavate (Manosroi et al, 2005), Croton betulaster (de Sampaio e Spohr et al, 2010;Freitas et al, 2011), Dimorphandra mollis (Freitas et al, 2011), Artemisia abrotanum L. (Hernandez et al, 1999), Artemisia annua L …”

“…It inhibited eosinophil migration and activity of chemokines and adhesion of molecules involved in the inflammatory process of asthma by suppressing the NF-κB pathway (Koh et al, 2011). Casticin's biological effects have been reported in wide spectrum of indications (Table 1), including inflammation (Lin et al, 2007b;Koh et al, 2011;Lee et al, 2012), asthma (Koh et al, 2011), tumor (Ono et al, 2002;Hu et al, 2007b;Shen et al, 2009;Ye et al, 2010;Koh et al, 2011), pre-menstrual syndrome (Hu et al, 2007b;Webster et al, 2011), immunomodulation (You et al, 1998), headache (Choudhary et al, 2009;Mesaik et al, 2009;Webster et al, 2011;Righeschi et al, 2012;Hogner et al, 2013), rheumatoid arthritis (You et al, 1998), conjunctivitis (Remberg et al, 2004), trachoma, gonorrhoea, and toothache (Diaz et al, 2003;Kunwar et al, 2010;Velpandian et al, 2013).…”

“…Casticin (3', 5-dihydroxy-3, 4', 6, 7-tetramethoxyflavone) is one of the bioactive flavonoids obtained from polyphenol plants, which are composed of a wide variety of molecules that are classified into several categories, according to their chemical type, such as phenolic acids, flavonoids, stilbenes, and lignans (Siasos et al, 2013 ). Casticin is a main active compound in roots, aerial parts, seed, wood, stems, leaves and fruits of variety of plants ( Figure 1 and Table 1), has been reported to be responsible for a wide spectrum of biological and pharmacological activities including immunomodulatory (Mesaik et al, 2009;Ling et al, 2012), anti-hyperprolactinemia (Hu et al, 2007b;Ye et al, 2010), anti-tumor (Haidara et al, 2006;Shen et al, 2009;Ling et al, 2012;Zeng et al, 2012), neuroprotetective (Ling et al, 2012), anti-inflammatory (Lin et al, 2007b;Choudhary et al, 2009;Velpandian et al, 2013) and analgesic activities (Lee et al, 2012).…”