Ferutinine

• CAT Number: T000114
• CAS Number: 41743-44-6
• Molecular Formula: C22H30O4
• Molecular Weight: 358.5
• Purity: ≥95%
• Synonyms: [(3R,3aS,4S,8aR)-3-hydroxy-6,8a-dimethyl-3-propan-2-yl-1,2,3a,4,5,8-hexahydroazulen-4-yl] 4-hydroxybenzoate; Jaeschkeanadiol p-hydroxybenzoate
• Target: Apoptosis
• Solubility: In chloroformSlightly in 95 % alcoholNot in water
• Storage: Store at +4°C, in dark place
• IUPAC Name: [(3R,3aS,4S,8aR)-3-hydroxy-6,8a-dimethyl-3-propan-2-yl-1,2,3a,4,5,8-hexahydroazulen-4-yl] 4-hydroxybenzoate
• InChI: InChI=1S/C22H30O4/c1-14(2)22(25)12-11-21(4)10-9-15(3)13-18(19(21)22)26-20(24)16-5-7-17(23)8-6-16/h5-9,14,18-19,23,25H,10-13H2,1-4H3/t18-,19+,21-,22+/m0/s1
• InChIKey: CYSHNJQMYORNJI-YUVXSKOASA-N
• SMILES: OC1=CC=C(C(O[C@H]2CC(C)=CC[C@]3(C)[C@]2([H])[C@@](C(C)C)(O)CC3)=O)C=C1

Ferutinine(CAS: 41743-44-6) has estrogenic activity and is half agonist of estradiol receptors. Complex esters of phenolcarbon acids,, from plants of the Ferula genus, Umbelliferae. Ferutinine has a comparable type and level of activity with Diethylstilbestrol.
The specific estrogen-receptors in the cytoplasmic fraction of the hypothalamic area possesses a high affinity with estradiol and Ferutinine. Their association constant is respectively 3.4 x 108.M-1 and 2.0 x 108.M-1; in the cytosol of the mediobasal hypothalamus, it is 3.8 x 108.M-1 and 1.4 x 108.M-1.
It is clearly indicated that Ferutinine may exert its estrogenic effect through the regulatory centres of hypothalamus.
Experiments have estabished that cytosolic estrogen-receptors from human decidua interacts with Ferutinine with a low affinity: 1.58 % affinity. This low level is characteristic of a class of estrogen-like products.
It has also been established that Ferutinine increases the secretion rate of luteinizing hormone in male rats, parallel to the activation of the gonadotropin synthesis in the adenohypophysis.
Ferutinine does not seem to have carcinogenic nor teratogenic properties. Administering of Ferutinine during 6 months at 0.1, 1 and 10 mg/kg does not provoke marked modifications in the internal organs nor in the peripheric blood.
In the first days of pregnancy, administration of Ferutinine at 10 to 100 mg/kg to rats leads to embryotoxic effects.

Reference

[1]. Biochem Biophys Res Commun. 2002 Feb 22;291(2):354-60. doi: 10.1006/bbrc.2002.6446.
Terpenoids found in the umbelliferae family act as agonists/antagonists for ER(alpha) and ERbeta: differential transcription activity between ferutinine-liganded ER(alpha) and ERbeta.
Ikeda K(1), Arao Y, Otsuka H, Nomoto S, Horiguchi H, Kato S, Kayama F.
Author information: (1)Department of Health Science, Jichi Medical School, 3311-1 Yakushiji, Minamikawachi-machi, Kawachi-gun, Tochigi 329-0498, Japan.
Phytoestrogens are assumed to affect the endocrine system of animal species similarly to other man-made endocrine disrupters and to exert their effects through estrogen receptors, specifically ER(alpha) and ERbeta. However, these molecular mechanisms are not fully understood. In this study, 19 phytochemicals were surveyed for agonist and antagonist activities of ER(alpha) and ERbeta using an ERE-luciferase reporter assay. The results showed that ferutinine is an agonist for ER(alpha) and an agonist/antagonist for ERbeta, tschimgine is an agonist for both ER(alpha) and ERbeta, and tschimganidine is an agonist for only ER(alpha). Ferutinine and tschimganidine are sesquiterpenoids, and tschimgine is a monoterpenoid derived from the Umbelliferae family. A competitive binding assay showed that ferutinine has higher binding affinities than tamoxifen for both ERs. Co-transfections of coactivators such as SRC-1, TIF2, AIB1, and TRAP220 in 293T cells and use of the luciferase assay revealed that TRAP220 failed to enhance the transcription mediated by ERbeta in the presence of ferutinine. Moreover, a GST pull-down assay showed that TRAP220 marginally bound to ERbeta ligand binding domain in the presence of ferutinine. These results suggest that the conformation of ferutinine-liganded ERbeta is difficult for TRAP220 to recognize. Taken together, this suggests that some terpenoids can modulate estrogen signaling as ER subtype-selective phytoestrogens similar to SERMs (selective estrogen receptor modulators).
DOI: 10.1006/bbrc.2002.6446 PMID: 11846412

[2]. J Ethnopharmacol. 2006 Jul 19;106(3):327-32. doi: 10.1016/j.jep.2006.01.025. Epub 2006 Mar 30.
Ferutinin stimulates nitric oxide synthase activity in median eminence of the rat.
Colman-Saizarbitoria T(1), Boutros P, Amesty A, Bahsas A, Mathison Y, Garrido Mdel R, Israel A.
Author information: (1)Laboratory of Bioassays and Natural Products, Laboratory of Molecular Modeling, School of Pharmacy, Universidad Central de Venezuela, Caracas, Venezuela.
Several species of Ferula genus have been used in folk medicine in digestive disorders, rheumatism, headache, arthritis, and as tranquilizers, antispasmodic and aphrodisiac. From the dry and powdered roots of Ferula hermonis Boiss was extracted the oxygenated sesquiterpene 1,5-trans-daucane type: ferutinine (1). The structure of (1) was established by spectroscopic methods as: IR, (1)H RMN, (13)C RMN, COSY, HMBC, HMQC, NOESY, EIMS, and CIMS. The possible signaling pathway of ferutinin (1) in nervous tissue in vitro was assessed and the results showed that this compound is able to increase nitric oxide synthase activity and inositol monophosphate accumulation (49%, each) in the median eminence of the rat brain, suggesting that compound (1) is associated to the activation of phosphoinositide breakdown and nitric oxide production (NO), the last is a gaseous intercellular messenger known to play a broad role in human biology from homeostasis to pathology.
DOI: 10.1016/j.jep.2006.01.025 PMID: 16574358

[3]. Curr Drug Targets. 2020;21(5):499-508. doi: 10.2174/1389450120666191029155053.
Ferula hermonis: A Review of Current Use and Pharmacological Studies of its Sesquiterpene Ester Ferutinin.
Safi R(1)(2), El-Sabban M(1), Najjar F(2).
Author information: (1)Department of Anatomy, Cell Biology and Physiological Sciences, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. (2)Department of Chemistry and Biochemistry, Laboratoire d'Innovation Thérapeutique, Faculty of Sciences II, Lebanese University, Beirut, Lebanon.
Ferula hermonis Boiss, is an endemic plant of Lebanon, locally known as "shilsh Elzallouh". It has been extensively used in the traditional medicine as an aphrodisiac and for the treatment of sexual impotence. Crude extracts and isolated compounds of ferula hermonis contain phytoestrogenic substances having a wide spectrum of in vitro and in vivo pharmacological properties including anti-osteoporosis, anti-inflammatory, anti-microbial and anti-fungal, anti-cancer and as sexual activity enhancer. The aim of this mini-review is to highlight the traditional and novel applications of this plant's extracts and its major sesquiterpene ester, ferutinin. The phytochemical constituents and the pharmacological uses of ferula hermonis crude extract and ferutinin specifically will be discussed.
DOI: 10.2174/1389450120666191029155053 PMID: 31663476