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Cordia Lutea L. Flowers: a Promising Medicinal Plant As Chemopreventive in Induced Prostate Carcinogenesis in Rats

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Cordia Lutea L. Flowers: a Promising Medicinal Plant As Chemopreventive in Induced Prostate Carcinogenesis in Rats Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2020, Article ID 5062942, 8 pages https://doi.org/10.1155/2020/5062942 Research Article Cordia lutea L. Flowers: A Promising Medicinal Plant as Chemopreventive in Induced Prostate Carcinogenesis in Rats Juan Pedro Rojas-Armas ,1 Jorge Luis Arroyo-Acevedo,1 Jose´ Manuel Ortiz-Sa´nchez,2 Miriam Palomino-Pacheco,3 Oscar Herrera-Caldero´n ,4 James Calva,5 Agustı´n Rojas-Armas,6 Hugo Jesu´ s Justil-Guerrero,1 Ame´rico Castro-Luna,4 and Julio Hilario-Vargas7 1Department of Dynamic Sciences, Laboratory of Pharmacology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru 2Laboratory of Physiology, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru 3Laboratory of Biochemistry, Faculty of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru 4Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima, Peru 5Department of Chemistry and Exact Sciences, Technical Particular University of Loja, Loja, Ecuador 6Instituto Regional de Enfermedades Neopla´sicas, Trujillo, Peru 7Department of Physiology, Faculty of Medicine, Universidad Nacional de Trujillo, Trujillo, Peru Correspondence should be addressed to Oscar Herrera-Caldero´n; [email protected] Received 7 April 2020; Accepted 6 May 2020; Published 26 May 2020 Guest Editor: Rˆomulo Dias Novaes Copyright © 2020 Juan Pedro Rojas-Armas et al. -is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. -e objective of this study was to evaluate the chemopreventive effect of the ethanolic extract of Cordia lutea flowers (EECL) on N-methyl-N-nitrosourea- (MNU), cyproterone-, and testosterone-induced prostate cancer in rats. 40 Holtzman male rats were used and assigned to 5 groups (n � 8). In Group I, rats received normal saline (10 mL/Kg); Group II: rats were induced for prostate cancer with cyproterone, testosterone, and NMU; Groups III, IV, and V: rats received EECL daily, at doses of 50, 250, and 500 mg/ kg body weight, respectively. After the period of treatment, animals were sacrificed by an overdose of pentobarbital and blood samples were collected for determination of prostate-specific antigen (PSA). -e prostate was dissected and weighed accurately. -e ventral lobe of the prostate was processed for histopathology analysis. -e somatic prostate index decreased with EECL at dependent dose, from 0.34 ± 0.04 to 0.23 ± 0.05 (P < 0:05). -e PSA levels also decreased significantly at doses of 250 and 500 mg/ kg. Histopathological analysis showed a decrease in the number of prostatic layers with high-grade prostatic intraepithelial neoplasia (HG-PIN) and low-grade prostatic intraepithelial neoplasia (LG-PIN) at the dose of 500 mg/kg. -e ethanolic extract of Cordia lutea flowers had a chemopreventive effect on induced prostate cancer in rats. 1. Introduction noncommunicable diseases (NCDs), which are responsible for seven out of every 10 deaths in the world [2]. One of the main Cancer is a large group of diseases that can start in almost any causes of death from NCDs is cancer, which in 2018 affected organ or tissue in the body when abnormal cells grow un- 18.1 million people worldwide and produced 9.6 million deaths. controllably, go beyond their usual limits to invade adjacent Estimating by 2040, these numbers will be almost double, the parts of the body, and/or spread to other organs, the latter. -is largest increase being in low- and middle-income countries, process is called metastasis and is a major cause of cancer death where more than two-thirds of cancers in the world will occur [1]. Population growth and increased longevity are globally [3]. Lung, prostate, colorectal, stomach, and liver cancer are the increasing the number of older people; aging is associated with most common types of cancer in men, while breast, colorectal, 2 Evidence-Based Complementary and Alternative Medicine lung, cervical, and thyroid cancer are the most common in to a mass spectrometer 5973N (Santa Clara, CA, USA) and women [1]. equipped with a DB-5MS capillary column (5% phenyl methyl In the United States, cancer is the second leading cause of silox, 30 m, 0.25 mm internal diameter, 0.25 μm film thickness; death, with 1,806,590 new cancer cases and 606,520 cancer J&W Scientific, Folsom, CA, USA). For the separation of volatile deaths projected in 2020, of which 191,930 will be new cases components, the following temperature program was used: of prostate cancer causing 33,330 deaths [4]. In Peru, death 5 min at 60°C, 3°C/min up to 165°C, and 15°C/min up to 250°C rates from prostate cancer increased from 20.9 (2005–2009) and kept for 10 min. Injector and detector temperatures were to 24.1 (2010–2014) per 100,000 men, an increase of 15.2%. maintained at 220°C. -e carrier gas was helium, at a flow rate According to the regions, during the period 2010–2014, the of 1 mL/min. -e injector was operated in split mode, with a coast had the highest mortality rate (28.9 per 100,000), while division ratio of 1 : 50. -e acquisition mass range was set at the rain forest had the lowest (7.43 per 100,000) [5]. 40–350 m/z. Ionization mode: impact of electrons (70 eV). -e -e drugs used in cancer treatment have no selectivity to extract was diluted to 1 :100 v/v in dichloromethane (Fisher destroy tumor cells and also damage nontumor cells, pro- Scientific, 99.9% pure) and 1 µL of the solution was injected [14]. ducing many side effects, mainly gastrointestinal, neuro- logical, hematological, dermatological, etc. [6,7]. Furthermore, toxicity extends to people who are exposed to 2.3. Animals. Healthy male Holtzman adult rats weighing the chemotherapy area for job or another reason [8]. On the 200 ± 20 g were used. -e animals were purchased from the other hand, the cost of drugs for the treatment of prostate National Institute of Health, housed in polypropylene cages cancer is high [9]. -is situation motivates the search for and air-conditioned environment with a 12 h light/dark new agents with a better safety profile and lower cost. In this cycle. -ey were allowed free access to drinking water context, an alternative source is natural resources. throughout the experimental period. -e animals were fed Cordia lutea (Family: Boraginaceae) is an indigenous plant with standard feed for rats. -e specifications and recom- of Peru, sometimes a shrub or tree, whose flowers are yellow; it mendations proposed by the guide for the Care and Use of is known by the common name of overo, alkka mallki, biyuyo, Laboratory Animals were followed and in compliance with caujaro, gomo, yellow gomo, muercielago, or ubito. In traditional the current regulations of the Animal Protection Law (Law Peruvian medicine, Cordia lutea has been widely used for the no. 27265) [15]. treatment of hepatic disorders [10] and in northern Peru for prostate inflammation [11]. In traditional Peruvian medicine, 2.4. Induction of Prostate Cancer. Prostate cancer induction Cordia lutea is known as “overo” flower, which have been widely was carried out with carcinogen and hormone, in a se- used for the treatment of liver disorders and in northern Peru quential process that began with temporary chemical cas- for prostate inflammation [11]. tration with cyproterone acetate, followed by prostate -e phytochemical study of the flower revealed the stimulation with testosterone propionate, and finally car- presence of terpenic and phenolic compounds, such as cinogenesis with N-methyl-N-nitrosourea (MNU). -e flavonoids and leucoanthocyanidins, of which the majority method of Sharmila et al. [16] and Banudevi et al. [17] was compound was rutin [12]. Other research also reported the followed with slight modification; rats received cyproterone presence of rutin and quercetin in the whole plant as the acetate (50 mg/kg body weight in sesame oil) daily by in- main constituents [10]. -e anticancer effect of quercetin traperitoneal injection for 18 consecutive days; one day after and rutin has been reported in several animal models, the final dose of cyproterone acetate, rats received daily retarding, inhibiting, or suppressing tumor growth [13]. -is subcutaneous injections of testosterone propionate (100 mg/kg background motivated us to propose the evaluation of the of weight in sesame oil) for 3 days; the day after testosterone chemopreventive effect of the ethanolic extract from Cordia propionate administration, each rat received a single in- lutea flowers on NMU-induced prostate cancer in rats. traperitoneal injection of N-methyl-N-nitrosourea (MNU) at a dose of 50 mg/kg body weight in sterile saline, pH 5.0. 2. Material and Methods -e cancer developed in the following 5 months and was evidenced at the end of this period through the histo- 2.1. Preparation of Extract of Cordia lutea Flowers. Cordia pathological study. lutea L. (C. lutea) flowers were collected in the city of Trujillo, Peru. -e material was identified at the Herbarium of the National University of San Marcos, Lima, Peru. -e 2.5. Experimental Design. A total of 40 rats were randomly flowers were washed, dried at 40°C, and pulverized in an assigned to 5 groups (n � 8). Group I: rats received NS electric mill. Phytochemicals were extracted in 96% ethanol. (normal saline); Group II : rats were induced for prostate -e extract was collected, filtered, and concentrated on a cancer with cyproterone, testosterone, and NMU; Groups rotary evaporator; finally, it was stored in aliquots and kept III, IV, and V: rats were induced for cancer and received in freezer until further use. treatment with the flower extract of C.
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