Ifanosine: Olea europaea L. and Hyphaene thebaica L. combination, from traditional utilization to rational formulation: Preclinical and clinical efficacy on hypertensives patients

• Published in: Journal of ethnopharmacology 2024-05, Vol.325, p.117834-117834, Article 117834
• Main Authors: Zakraoui, Mariem, Outman, Ahlam, Kinambamba, Milène Simone, Bouhrim, Mohamed, Ndjib, Rosette Christelle, Al kamaly, Omkulthom, Alshawwa, Samar Zuhair, Seid, Abakar Bechir, Cordier, Janine, Ngoupayo, Joseph, Longo-Mbenza, Benjamin, Gressier, Bernard, Parvez, Mohammad Khalid, Pasković, Igor, Hamrouni, Lamia, Eto, Bruno
• Format: Article
• Language: English
• Subjects: Alternative and combinative polyphytotherapy; Antihypertensive; Hyphaene thebaica L; Ifanosine; Isometric transducer; Olea europaea L
• ISSN: 0378-8741; 1872-7573
• DOI: 10.1016/j.jep.2024.117834

Olea europaea L. and Hyphaene thebaica L. are commonly employed by traditional healers in Africa for treating and preventing hypertension, either individually or in a polyherbal preparation (Ifanosine). The primary aim was to assess the antihypertensive effects of Olea europaea L. leaves aqueous extract (OEL), Hyphaene thebaica L. mesocarp extract (HT), and the Ifanosine on isolated rat aorta rings. The secondary objective was to evaluate the clinical benefits of a new oral formulation of Ifanosine. In vitro studies using an isometric transducer examined the antihypertensive effects of HT, OEL, and Ifanosine on rat aorta. Ussing chambers technic were employed to measure mucosal to serosal fluxes and total transepithelial electrical conductance (Gt) to assess the intestinal bioavailability of HT, OEL, and Ifanosine. HPLC was utilized to determine the phytochemical composition of OEL and HT extracts. Subchronic toxicity investigations involved two groups of rats, treated with either water (control) or Ifanosine at 5 g/kg for 28 days. Clinical benefits of the new Ifanosine formulation were evaluated in an observational study with 32 hypertensive patients receiving a fixed oral dose of 3.5 mg three times a day for 30 days. Aqueous extracts induced dose-dependent relaxation of rat aorta rings, with HT and OEL having higher IC50 values than Ifanosine (IC50 = 44.76 ± 1.35 ng/mL, 58.67 ± 1.02 ng/mL, and 29.46 ± 0.26 ng/mL, respectively). The pA2 values of OEL and HT were 1 and 0.6, respectively, while Ifanosine was 0.06. Intestinal bioavailability studies revealed better Prazosin bioavailability than plant extracts. Toxicological studies demonstrated the safety of Ifanosine, supported by histological examinations and biochemical parameters in rat blood. Biochemical analyses indicated flavonoids and phenolic acids as dominant active constituents. Clinical benefits in humans included reduced SBP, DBP, LDL-c, VLDL-c, and TAG, and increased HDL-c without overt adverse effects. This study validates the traditional use of OEL and HT for hypertension and advocates for alternative and combinatorial polyphytotherapy (ACP) to enhance traditional remedies. [Display omitted] •Mixture of OEL and HT aqueous extracts show a better antihypertensive effect than each extract alone.•The antihypertensive effect of Ifanosine is greater than clinical prescribed medicine prazosin (PRZ).•Clinical benefits were observed after utilization of Ifanosine with a reduction in SBP, DBP, LDL-c, V