Advanced Herbal Medicine, Summer and Autumn 2020; 6(2): 1-16 herbmed.skums.ac.ir Promising Effects of Vitex Agnus-Castus on Quality of Life and Sexual Function in Premenopausal Relapsing Remitting Multiple Sclerosis Patients Sara Rahgooy1, ,Sepideh Arbabi Bidgoli2*, Saeed Shahbeigi3, Shima Tavakol4, Mohammad Hossein Salehi Surmaghi5 1 Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran 2 Department of Toxicology and Pharmacology ,Faculty of Pharmacy Article Original and Pharmaceutical Sciences ,Islamic Azad University, Tehran Medical Sciences (IAUTMU),Tehran-Iran. 3 Loghman Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran 4 Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran 5 Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran Received: 15 November 2020 Accepted: 6 July 2021 Abstract: Background and aims: Current therapeutic regimens are not able to solve hormonal imbalance in young multiple sclerosis (MS) women and the clinical benefits of hormone therapy in MS patients remain controversial. This open labeled pilot study was aimed to find the role of Vitex agnus-castus plant supplement daily regimen in serum testosterone level , Expanded Disability Status Scale (EDSS), sexual function and overall quality of life in premenopausal MS patients. Methods: To achieve these goals, Molecular Docking on Vitex agnus-castus standard fruit extract constitutes performed and 30 eligible patients were selected for the clinical *Corresponding author: Department of Toxicology and Pharmacology ,Faculty of Pharmacy and Pharmaceutical Sciences ,Islamic Azad University, Tehran Medical Sciences (IAUTMU),Tehran-Iran. Tel: +21-88003470. E-mail address: [email protected] Vitex agnus-castus in premenopausal multiple sclerosis women part of this study. Patients received two Vitagnus® film tablets in addition to their drugs for 90 days. Results: Some plant extract components showed strong affinity to Androgen Receptor Ligand binding domain. Significant reduction in EDSS (1.839 vs.1.643, p=0.003) and significant elevation in serum testosterone levels [388.6(±0.16900) vs. 468. (±0.18144) 2ng/dL (p=0.026)] were also observed at the completion of the intervention. Menstrual irregularities disappeared in all 28 patients who completed this study. MSQL-54 criteria at the completion of study (day 91) showed lower stress levels, improved vitality/emotional health and normalized sexual activities without significant effect on sleep disorders and cognitive functions of patients. Vitex agnus-castus treatment by predictable AR LBD affinity improved the emotional state, sexual life, EDSS score and overall quality of life in premenopausal RRMS patients. Conclusion: Our results suggest Vitagnus® film tablet as safe and promising supplement with some benefits in MS women who are suffering from disease induced emotional and sexual impairments. Keywords: Multiple sclerosis, Vitex agnus-castus, Quality of life, Testosterone, Molecular docking INTRODUCTION Diagnosis of MS is associated with lifetime substantial costs to the patients Multiple sclerosis (MS) is an and healthcare systems as well as a immune mediated neurodegerative wide range of psychological, social and disease of the central nervous system cultural difficulties (3). (CNS) with unknown etiology, Lifestyle and environmental factors are increased risk of morbidity and key predisposing factors for the risk of comorbidity and sexual dimorphism (1). MS in people with genetic Different substantial gaps in MS related predisposition to MS (4) but gender, age epidemiological and therapeutically at diagnosis and other demographic knowledge requires more studies to specification act as key factors in investigate the contribution of gender, disease phenotype, lifestyle changes and age, ethnicity and other underlying quality of life of patients (5). factors on MS incidence, on MS Epidemiological studies have also prevalence and to achieve more indicated higher suicide attempts individual therapeutic and rehabilitation (approximately twice) as a self- interventions (2). This hard-to-treat destructive behavior in recently demyelinating disease is often diagnosed MS patients compared with diagnosed in the second or third decade the general population with higher of life and decreases the quality of life incidence in patients with psychological by inducing progressive disability. disorders, impaired sexual life, 2 Advanced Herbal Medicine, Summer and Autumn 2020; 6(2): 1-16 depression, social isolation and of testosterone in the systemic immune tendency for substance abuse (6); response by cell type-specific effects in therefore, more attention should be paid the context of immunological disorders to supplementation and integrative has also been considered before this health for this large group of patients new approach to testosterone hormone worldwide. Iranian MS women and (10). We showed decreased serum other women in neighboring countries testosterone levels in Iranian with similar social and cultural premenopausal MS patients compared characteristics may suffer from to their age-matched healthy destroyed sex life under masks without counterparts and the contribution of necessary sexual support from their serum testosterone levels to underlying partners or during rehabilitation process factors and disease progression. It (7). seems that study on preventive role of sex hormones balance in disease This neurodegenerative disease progression and sexual life as key precipitates in patterns of relapsing- factors in quality of life and remitting (RRMS) or progressive-onset social/familial health of patients (12) but RRMS shows a sex-bias and can assist medical and rehabilitation develops 3–4 times more frequently in teams in controlling diseases and premenopausal women with peak onset improving the life satisfaction of MS after puberty (8) which suggests the patients. extensive involvement of sex hormones in RRMS progression (9). Basic Vitex agnus-castus (VAC) known as knowledge on the contribution of sex Chaste tree is a historical medicinal hormones in disease susceptibility and herb from the Verbenaceae family management has been applied as which grows in Eastern Mediterranean "bedside to bench to bedside" approach region and Central Asia and has been and lead the health practitioners to used for centuries to treat premenstrual newer gender specific treatment syndrome and premenstrual dysphoric insights. Testosterone and estrogens disorder. Many compounds including demonstrate anti-inflammatory effect flavonoids,iridoid glycoside , p- but testosterone has more hydroxybenzoic acid, alkaloids, essential neuroprotective effects by stimulating oils, fatty oils, diterpenoids and steroids myelin formation in glutamate-induced have been identified in the chemical neurotoxicity and oxidative stress and analysis of Vitex agnus-castus(13). makes regeneration of nerve cells Animal studies on hydroalcoholic VAC through binding to neural androgen extract showed the androgenic (14) and receptor (AR) (Collongues N, 2018). osteoprotective effects in male mice by Among sex hormones and gender preserving the cortical and trabecular specific mediators, downregulating role bone as a safe alternative to Hormone 3 Vitex agnus-castus in premenopausal multiple sclerosis women Replacement Therapy (HRT) (15). and SDF) were provided by AR LBD Dopaminergic effects of VAC extract (2PNU) analyzer (19) and investigated (16)and its additional pharmacological by Molegro molecular viewer V2.5 (Fig actions via mu-opiate receptor have 1, A, B, C). been already described (17) but pharmacological studies on its binding Vitex agnus-castus (VAC): capacities to Androgen Receptor (AR) Vitagnus® film tablet with Iran are still missing. Therefore, we Registration Code (IRC) of 1228091827 investigated the binding capacity of were obtained from Poorsina standard VAC to AR using an in silico Pharmaceutical Company in Tehran as model and the possible effects of gift. Each 320 mg tablet contained 200 authorized VAC tablets (Vitagnus®) on mg of fruit extract of Vitex agnus- serum testosterone levels, EDSS, sexual castus. Total fruit extract contains function and overall quality of life in a essential oil compounds including beta- pilot open labeled study in premenopausal cineole, α-pinene, sabinene, limonene MS patients. and pinend, flavonoids including Methods casticin, isovitexin and orientin, iridoids and glycosides but aucubin is the main Structure-based virtual screening of component which should be VAC by Molecular Docking: standardized in VAC pharmaceutical Before starting clinical preparations worldwide. Each interventions on Vitagnus® tablets, Vitagnus® tablet contained 2.1 to 3.3 molecular docking was done to perform mg aqupin according to validated HPLC the structure-based virtual screening of method of analysis and global standards VAC to Androgen Receptor (AR). For of VAC derived pharmaceutical dosage this aim, the main VAC components in forms (20) . standardized fruit extract were collected from two Database (RCSB-PDB and Clinical Studies PubChem) and described by ID codes (Table 1). To detect the total affinity of Study population and design: VAC main constitutes to human AR as To avoid any misdiagnosis, to possible novel androgen receptor achieve maximum homogeneity in the ligands. AR LBD was performed and study population, and to provide the compared with natural human main