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Ocimum Gratissimum Linn. Leaves Reduce the Key Enzymes Activities

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Ocimum Gratissimum Linn. Leaves Reduce the Key Enzymes Activities Ojo et al. BMC Complementary and Alternative Medicine (2019) 19:71 https://doi.org/10.1186/s12906-019-2481-0 RESEARCH ARTICLE Open Access Ocimum gratissimum Linn. Leaves reduce the key enzymes activities relevant to erectile dysfunction in isolated penile and testicular tissues of rats Oluwafemi Adeleke Ojo1,2* , Adebola Busola Ojo3, Babatunji Emmanuel Oyinloye1,6, Basiru Olaitan Ajiboye1, Omosola Olufisayo Anifowose4, Ayodeji Akawa5, Oluranti Esther Olaiya5, Oluwaseun Ruth Olasehinde5 and Abidemi Paul Kappo6 Abstract Background: Ocimum gratissimum L. is a medicinal plant widely grown in tropical and subtropical regions with the leafdecoctionusuallytakeninfolkmedicinetoenhanceerectileperformanceinmenalthoughtheprobable mechanism of actions remains undetermined. This study examined the inhibitory potentials of Ocimum gratissimum leaves on some key enzymes associated with erectile dysfunction in penile and testicular tissues of the rat. Methods: Inhibitory effect of aqueous extract (1:10 w/v)ofO. gratissimum leaves on the activities of phosphodiesterase-5 (PDE-5), arginase, angiotensin I –converting enzyme (ACE), and acetylcholinesterase (AChE) in penile and testicular tissues were assessed. Also, the extract was investigated for ferric reducing antioxidant property(FRAP) and 1,1-diphenyl-2-picryl- hydrazil (DPPH) radical scavenging abilities. Results: The extract showed higher PDE-5 (IC50 =43.19μg/mL), ACE (IC50 = 44.23 μg/mL), AChE (IC50 = 55.51 μg/mL) and arginase (IC50 = 46.12 μg/mL) inhibitory activity in thepeniletissuethanPDE-5(IC50 = 44.67 μg/mL), ACE (IC50 = 53.99 μg/ mL), AChE (IC50 = 60.03 μg/mL) and arginase (IC50 =49.12μg/mL) inhibitory activity in the testicular tissue homogenate. Furthermore, the extract scavenged free radicals and in a dose-dependent manner. Conclusion: Theenzymeactivitiesdisplayedmightbeassociatedwiththebioactivecompoundspresentintheextract which could possibly explain its use in the management of erectile dysfunction (ED). Keywords: Erectile dysfunction, Angiotensin I –converting enzyme (ACE), Phosphodiesterase-5 (PDE-5), Acetylcholinesterase (AChE), Arginase, Ocimum gratissimum Background result of the decrease in bioavailability of nitric oxide The occurrence of erection involves the neuronal, vascu- (NO) due to decreased expression of endothelial tissue lar, endocrine and local secretory interplay. The pro- nitric oxide synthase (NOS) activity and/or increased cesses involved are blood vessel dilation, trabecular elimination of NO [3]. However, NOS and arginase vie smooth muscle relaxation, and activation of the for L-arginine as a substrate in cells. In the urea cycle, veno-occlusive mechanism of the corpus carvenosum L-arginine is converted to ornithine and urea and the and spongiosum tissues [1]. Erectile dysfunction (ED) is conversion is catalyzed by the enzyme arginase [4]. The the inability to achieve and maintain penile tumescence fast hydrolysis of secondary messengers such as cyclic adequate for the suitable erotic act [2]. It occurs as a adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) have been linked to pathologies * Correspondence: [email protected] like ED [5]. Cyclic nucleotide phosphodiesterase (PDE) 1Department of Biochemistry, Afe Babalola University, Ado-Ekiti, Nigeria enzymes regulate the cytosolic levels of secondary mes- 2Department of Biochemistry, University of Ilorin, Ilorin, Nigeria Full list of author information is available at the end of the article sengers [4, 6]. Predominantly in the smooth muscle of © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Ojo et al. BMC Complementary and Alternative Medicine (2019) 19:71 Page 2 of 10 corpora cavernosum is phosphodiesterase type-5. Hence, rats. According to the authors, a combination of the two the mitigation of phosphodiesterase-5 (PDE-5) can also plant extracts thus provides a cheap alternative to treating be a therapeutic approach in the management of ED [6]. diabetes-associated testicular damage and sexual dysfunc- Additionally, acetylcholinesterase (AChE) inhibition is tion [31]. The plant leaf extract is used in alternative an alternative technique for managing ED because it medicine for the management of erectile dysfunction [31]. controls the levels of acetylcholine [7]. Moreover, the in- However, there is limited information on the possible creasing AChE activity decreases the level of acetylcho- mechanisms of actions of O. gratissimum on the penile line on conversion to its products acetate and choline [8, and testicular function. Thus, this study investigated the 9]. Earlier studies reported that inhibition of AChE can inhibitory effects of aqueous extract from O. gratissimum increase the level of acetylcholine thereby improving leaves on enzymes such as (phosphodiesterase-5 (PDE-5), erection [10, 11]. Moreover, the renin–angiotensin sys- angiotensin-1 converting enzyme (ACE), acetylcholin- tem (RAS) is also a key aspect in the development of esterase (AChE), and arginase) relevant to ED in penile erectile dysfunction. Increase in the angiotensin-I con- and testicular tissue homogenates. Antioxidant activity verting enzyme (ACE) caused by erectile dysfunction (ferric reducing antioxidant property (FRAP) and simultaneously leads to the generation of angiotensin-II 1,1-diphenyl-2-picryl-hydrazil (DPPH)) of the leaves were [12–14]. Hence, ACE activity inhibition leads to an in- also examined. crease in erectile performance and a significant reduc- tion of angiotensin-II levels in patients with ED [15]. Methods Oxidative stress-induced ED occurs when reactive oxy- Plant collection − gen species such as superoxide anion (O2 ) reacting with O. gratissimum leaves were bought from a King’s market, nitric oxide gas, forms peroxynitrite (ONOO2) and re- Ado-Ekiti in November 2017. It was authenticated by duces the biological presence of NO [16]. Adequate in- Mr. Omotayo with herbarium number (UHAE 15) and take of natural plant products may protect against deposited at the Department of Plant Science, Ekiti State oxidative stress and reduce the chance of developing University, Ado-Ekiti, Nigeria. The Ocimum gratissimum several diseases like male sexual dysfunction [17]. Fur- leaves were dried and pulverized using a blender. The thermore, the management of ED with conventional powder obtained weighing 70 g was macerated in 700 medicine is connected with adverse side effects and tox- mL of distilled water for 24 h at room temperature as icities. Thus, the need to continuously explore medicinal described by [32]. It was then filtered and the resulting plants with sexual enhancing properties may serve as a filtrate was concentrated on a steam bath to give a yield cheap and safe alternative therapy [18]. of 40.45 g of the residue. Ocimum gratissimum (OG) is a perennial herb that be- longs to the family Lamiaceae. It is thought to originate Chemicals and reagents from Asia and Africa [19]. In Nigeria and other parts of Chemicals such as acetylthiocholine iodide, 5,5′-dithio-bis the world, it is used as a traditional vegetable condiment (2- nitrobenzoic acid) (DTNB), thiobarbituric acid (TBA), and oral care products. Furthermore, OG had been shown trichloroacetic acid (TCA), and 1,1-diphenyl-2 picrylhy- to possess numerous pharmacological properties hence its drazyl (DPPH) were sourced from Sigma-Aldrich, Chemie use in traditional or alternative medicine. These properties GmbH (Steinheim, Germany). Acetic acid was procured include antioxidant [20–24]; anti-anemic [25]; antidiar- from BDH Chemical Ltd., (Poole, England). A Jenway rhoeal [26] and protective effects on hepato-renal indices UV-visible spectrophotometer (Model 6305; Jenway, Barlo [27]. In a study conducted by Iweala and Obidoa [29], World Scientific, Dunmow, United Kingdom) was used to using Ocimum gratissimum-supplemented diet (OGSD), measure absorbance. rats fed with OGSD for 6 months showed an increased number of spermatozoa suggesting the capacity of OG to Handling of experimental animals enhance reproductive ability [28]. Another study con- Twenty adult male Wistar albino rats (weighing between ducted by Pande and Pathak [29] revealed that ethanolic 290 ± 5 g) of about 10–14 weeks old were obtained from extract of OG, significantly increased the sexual behaviors Animal breeding house of Afe Babalola University and five of normal male albino mice at a dose of 100, 250, and 500 [5] rats were used for each of the assays carried out. They mg/kg body weight for 7 days with 500 mg/kg having the were handled in accordance with the guide for Care and most noticeable effect, without any gastric ulceration and Use of Laboratory Animals formulated by the National adverse effects [29, 30]. In addition to this, Ebong et al. Academy of Science, issued by the National Institute of [31]reportedthatcombinedextractsofMoringa oleifera Health (USA). The ethical guidelines were followed in ac- and Ocimum gratissimum had better ameliorative effects cordance with National and Institutional
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