Skip to main content
Download PDF

Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia

BMC Complementary Medicine and Therapies volume 23, Article number: 187 (2023) Cite this article

Abstract

Introduction

This study was motivated by the increasing global incidence of benign prostatic hyperplasia (BPH) and the promising potential of nutraceuticals as complementary therapies in ameliorating its burden. We report the safety profile of C. esculenta tuber extracts, a novel nutraceutical in benign prostate hyperplasia in a rat model.

Methods

In this study, forty-five male albino rats were randomly assigned to 9 groups of 5 rats each. Group 1 (normal control) received olive oil and normal saline. Group 2 (BPH untreated group) received 3 mg/kg of testosterone propionate (TP) and normal saline, and group 3 (positive control) received 3 mg/kg of TP and 5 mg/kg of finasteride. Treatment groups 4, 5, 6, 7, 8, and 9 received 3 mg/kg of TP and a middle dose (200 mg/kg) of LD50 of ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE respectively for a period of 28 days.

Results

The negative controls showed a significant (p < 0.05) increase in mean relative prostate weight (approximately 5 times) as well as a reduction in relative testes weight (approximately 1.4 times less). There was no significant (p > 0.05) difference in the mean relative weights of most vital organs: liver, kidneys, and heart. This was also observed in hematological parameters: RBC, hemoglobin, HCT, MCV, MCH, MCHC, and platelets counts. In general, we note that the effects of the well-established drug finasteride on the biochemical parameters and histology of selected organs are comparable to those of C. esculenta fractions.

Conclusion

This study demonstrates that C. esculenta tuber extracts provide potentially safe nutraceutical if applied in the management of benign prostate hyperplasia based on a rat model.

Peer Review reports

Introduction

The increasing trend of life expectancies across the world [1] has been accompanied by increasing prevalence and incidence of benign prostate hyperplasia (BPH) [2,3,4]. Benign prostate hyperplasia as defined histologically by an overgrowth of prostate tissue [5], is among the commonest noncancerous form of abnormal prostate cell growth affecting older men globally [6,7,8]. In men over 50 years of age, global prevalence of BPH ranges between 20 and 62% [4, 9,10,11]. As the prostate enlarges, it constricts the urethra leading to symptoms which usually result into BPH associated lower urinary tract symptoms (LUTS) [2, 8, 12, 13]. In Uganda, the prevalence rates for LUTS in men above 55 years of age were estimated to be as high as 40.5% in a study published in 2018 [14]. Apart from the cost [10, 15] and health systems challenges, poor treatment outcomes in BPH have been linked to real and perceived side effects of commonly used pharmacological regimens [15,16,17,18].

Conventional pharmacological management of BPH usually involves use of alpha-blockers comprising alpha-adrenoceptor antagonists, or 5-alpha-reductase inhibitor or a combination of both [15, 17, 19]. These treatment options are associated with severe side effects including but not limited to organ toxicity and sexual dysfunction [20,21,22]. Moreover most of these patients are older adults with multiple co-morbidities and medications [23]. There is an urgent need for additional research into novel approaches to treatment of BPH which could involve incorporation of alternative or complementary therapies [8].

There are vast quantities of unexplored novel phytotherapeutic agents from commonly consumed foods that could provide better options for management and/or prevention of BPH [24, 25]. Such options are usually associated with fewer side effects due to long history of traditional use as foods [24] although more data is required to get a better understanding of their safety profiles [26]. C. esculenta (English name cocoyam or Taro, local name in Buganda region of Uganda, ‘Obukopa’ and in Igbo (Onitsha) Nigeria is among the neglected but important foods across the African continent [27,28,29]traditionally used in the management of BPH especially in West African countries [29,30,31]. Medicinal properties of C. esculenta in-vitro and in-vivo have previously been reviewed by Prajapati et al. (2011) [29]. Moreover, studies by Brown et al. (2005) suggest that C.esculenta has novel tumor specific anti-cancer activities on rat YYT colon cancer cell line [32]. Furthermore, using animal models, Kalariya et al.(2015) [33] reported that (25 and 50 mg/kg, i.p.) of hydroalcoholic extract of leaves of C. esculenta decreases obsessive-compulsive disorder in mice. Some studies have also demonstrated the anti-diabetic properties of C.esculenta tuber and leaves in rat model [34,35,36,37].

Fig. 1
figure 1

Effect of ethanol crude Tuber extract of Colocasia esculenta and Fractions on Serum Total Protein concentration in Testosterone propionate induced benign prostate hyperplasic Rats. Data are shown as mean ± S.D (n = 5). Mean values of different groups were compared with the control using Dunnet ANOVA with significantly difference at P < 0.05 (indicated by *). Testosterone propionate (TP), Ethanol crude Tuber extract of Colocasia esculenta (ECTECE), Hexane fraction(HF), Dichloromethane fraction( DCMF), Butanone fraction(BF), Ethyl acetate fraction(EAF) and Aqueous Fraction (AF)

Full size image

Previous studies by Eleazu and others [38] based on a rat animal model demonstrated that C. esculenta contains anti-inflammatory agents that may remediate BPH associated inflammation. Studies by Nzebang et al.(2018) [39] suggest that the aqueous extract from C. esculenta leaves infected by Phytophthora colocsiae would be no major health risk with estimated LD50 of more than 4000 mg/kg in rats Although our previous studies have demonstrated that the ethanol crude extract of C. esculenta has the capacity to reduce prostate weight, total protein as well as serum concentration of prostate specific antigen [40] there was need to further explore the safety profile and associated biochemical mechanisms. This study was therefore designed to investigate the safety profile of C. esculenta in crude and semi purified form for the management and / or prevention of BPH.

Fig. 2
figure 2

Effect of ethanol crude Tuber extract of C. esculenta and Fractions on Relative Prostrate Weight in Testosterone propionate induced benign prostate hyperplasic Rats. Relative prostate weight was calculated by dividing the weight of the prostate of the animal divided by the body weight of the animal. Mean values of different groups were compared with the control using Dunnet ANOVA with significantly difference at P < 0.0002 (****) and P < 0.002 (***). Testosterone propionate (TP), ethanol crude Tuber extract of C. esculenta (ECTECE), hexane fraction (HF), dichloromethane fraction (DCMF), butanone fraction (BF), ethyl acetate fraction (EAF) and aqueous fraction (AF)

Full size image

Materials and methods

Collection and Identification of Plant Materials: Mature (6–8 months old) fresh tubers of C. esculenta were collected with permission from the selected farmers and local authorities including agricultural extensions officer as guided by the Office of Research, Innovation and Institutional Ethics Committee of Ebonyi state university, Nigeria (EBSU/BCH/ET/21/001). This was done in accordance with guidelines from the Nigerian Federal Environmental Protection Agency and the International Union for Conservation of Nature (IUCN) policy on Research Involving Species at Risk of Extinction. This was followed by authentication by a taxonomist, Professor S.O. Onyekwelu at the department of Applied Biology, Ebonyi state University (Colocasia esculenta (L) Schott, Family Araceae, common name: Cocoyam Local name; Ede ofe, voucher number: EBSU-H-206, Department of applied biology herbarium, Ebonyi State university, Nigeria ; Herbarium curator, Mr. Nwanko Onyebuchi Ephraim.

Fig. 3
figure 3

(a-d): Effect of ethanol crude Tuber extract and Fractions of C. esculenta on Relative Organs weights in Testosterone propionate induced benign prostate hyperplasic Rats. Data are shown as mean ± S.D (n = 5). Mean values of different groups were compared with the control using Dunnet ANOVA with significantly difference at P < 0.05 although none of them was significant. Testosterone propionate (TP), Ethanol crude Tuber extract of C. esculenta (ECTECE), Hexane fraction (HF), Dichloromethane fraction (DCMF), Butanone fraction (BF), Ethyl acetate fraction (EAF) and Aqueous Fraction (AF).

Full size image

Preparation of Plant materials:

C. esculenta tubers were washed, boiled, peeled, sliced into chips, air-dried to a constant weight at a room temperature and processed into flour.

Extraction of plant materials

The powdered tuber 1280 g of C. esculenta were extracted with 8 L of 50% ethanol (Emsure®) overnight in a big stopper bottle with occasional stirring at room temperature. It was then sieved using muslin cloth. The filtrates were air dried for 24 h to get the ethanol (crude) extracts.

Purification by Solvent extraction using partition coefficient:

The crude natural ethanol product was extracted with solvents of increasing polarity, first, hexane (Blulux), dichloro methane (UNILAB), ethyl acetate (UNILAB) and butanol (AnalaR®) which depended on the chemical and physical nature of the target compounds.

Fig. 4
figure 4

(a-g): Effect of ethanol crude Tuber extract of Colocasia esculenta and Fractions on Haematological indices in Testosterone propionate induced benign prostate hyperplasic Rats. Mean values of different groups were compared with the control using Dunnet ANOVA with significantly difference at P < 0.003 (***) and P < 0.001 ( ****). Testosterone propionate (TP), Ethanol crude Tuber extract of Colocasia esculenta (ECTECE), Hexane fraction(HF), Dichloromethane fraction( DCMF), Butanone fraction(BF), Ethyl acetate fraction(EAF) and Aqueous Fraction (AF)

Full size image

This study was done under the supervision and approval by the Office of Research, Innovation and Institutional Ethics Committee of Ebonyi state university, Nigeria (EBSU/BCH/ET/21/001). All procedures for animal studies were performed following guidelines and legislations consistent with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23, revised in 1996) [33] as well as the National guidelines for the use of laboratory animals for research and teaching based on the principles of 3Rs, reduce refine or replace.

Fig. 5
figure 5

(a-f): Effect of ethanol crude Tuber extract of Colocasia esculenta and Fractions on WBC level and differential counts in Testosterone propionate induced benign prostate hyperplasic Rats. Data are shown as mean ? S.D (n=5). Mean values of different groups were compared with the control using Dunnet ANOVA with significantly difference at P<0.05. Testosterone propionate (TP), Ethanol crude Tuber extract of Colocasia esculenta (ECTECE), Hexane fraction(HF), Dichloromethane fraction( DCMF), Butanone fraction(BF), Ethyl acetate fraction(EAF) and Aqueous Fraction (AF), BPH( Benign prostate hyperplasia)

Full size image

Laboratory animals

The study used 45 male Wistar albino rats of about 6 weeks old which were sourced from the Animal House of Ebonyi state university, Nigeria. They were kept in stainless cages (size: 16 × 9 = 144inches) in a well-ventilated animal house. They were acclimatized for seven days under good laboratory conditions (12 h light/dark cycle; room temperature) before the start of the experiments. All animals were allowed free access to standard rodent chow and water ad libitum. All animals were humanely sacrificed using halothane.

Fig. 6
figure 6

Haematoxylin and Eosin stain on histological sections of prostate gland representative image from three rats selected from each of the group. (I) (NC) Normal control group (magnification, x200); (II) (TP + Finasteride) Positive control group (magnification, x200); (III) TP + ECTECE (magnification, x200); iv. (BPH) Negative control group (magnification, x200). Blue arrows show the prostate glands with no proliferating prostate cells while the red arrows show proliferating prostate cell, BPH- Benign prostatic hyperplasia, ethanol crude tuber extract of C. esculenta

Full size image

Induction of benign prostatic hyperplasia

We induced Benign Prostatic Hyperplasia in rats using testosterone propionate (TP) [34, 35]. The dose for induction was formulated as 3 mg/kg body weight and it was given by subcutaneous injection every day for 28 days. We prepared stock by dissolving 25 mg of TP in 8.33ml olive oil. Three rats each from the groups were randomly selected for confirmation of BPH before treatment. Prostate Specific Antigen (PSA) concentrations of the rats were determined using the method by Stowell et al. [41].

Grouping of animals

The rats were grouped as follows, with five rats in each group: Rats in group 1 (Normal control) received subcutaneously 1ml of olive oil. BPH was induced in groups 2–9 with 3 mg/kg TP subcutaneously. Group 2 (BPH untreated group) was not treated. Group 3 (Finasteride group) had rats which were treated with 5 mg/kg finasteride. The middle dose of 200 mg/kg was used for this study as reported by Eleazu et al. (2021). Group 4 had rats which were treated with 200 mg/kg body weight (b.w) of ethanol crude tuber extract of C. esculenta (ECTECE). Group 5 had rats that were treated with 200 mg/kg b.w of n-hexane fraction (HF). Group 6 had rats that were treated with 200 mg/kg b.w of dichloromethane fraction (DCMF). Group 7 had rats that were treated with 200 mg/kg b.w of ethyl acetate fraction (EAF). Group 8 had rats that were treated with 200 mg/kg b.w of butanone fraction (BF). And finally, group 9 had rats that were treated with 200 mg/kg b.w of aqueous fraction (AF). Oral administration of the extract or fractions or finasteride was done using oral gavage and all animal diets were provided ad libitum.

Fig. 7
figure 7

(I-III). Haematoxylin and Eosin stain on histological sections of the liver. (I) Normal control group (NC) (magnification, x200); (II) BPH untreated group (magnification, x200); and (III) TP + ECTECE group (magnification, x200). BPH- Benign prostatic hyperplasia, ethanol crude tuber extract of C. esculenta

Full size image

Laboratory analysis

After 28 days, the rats were fasted overnight, sacrificed after being anesthetized with halothane and dissected to collect vital organs which included liver, kidney, heart as well as prostate and testes. All organs were weighed and immediately placed in 10% neutral buffered formalin for fixation until histopathological examination. We also collected blood samples from animals by cardiac puncture, using 5ml syringes into EDTA vacutainers for complete blood count. Anticoagulated blood samples were stored at 2 to 80c for two days after which a complete blood count was performed.

Total protein was determined using the method in Tietz [42]. The body weights, prostrate, liver, kidney, heart and testes weights of the rats were recorded on a daily basis, using an electronic weighing balance (Model Scout Pro, Ohaus Corporation, USA), and were calculated as follow: Relative prostrate weight (g/100 g) = Total Prostrate weight/Final body weight x100; Relative liver weight (g/100 g) = Total liver weight/Final body weight × 100; Relative kidney weight (g/100 g) = Total kidney weight/ Final body weight × 100; Relative heart weight (g/100 g) = Total heart weight/ Final body weight × 100 and Relative Testes weight (g/100 g) = Total Testes weight/ Final body weight × 100.

For complete blood count, we used a five-part differential fully automated analyser, Sysmex XN550, Japan. Sample tubes with caps closed were placed in sample adapters. We then used the start/stop switch to execute automatic sample mixing, aspiration, analysis and printing of results.

Fig. 8
figure 8

(I-IV) showed no demonstrable hyperplasia, atrophy or hypertrophy of heart tissue in the normal control group (NC), neither was it demonstrated in the BPH untreated group nor TP + Finasteride groups. The same was observed in TP + ECTECE group

Full size image

Histopathological examination

The histopathological examination of the organs was done using standard procedures [42]. Tissues were grossed and small pieces were cut out and placed in tissue cassettes for processing. Tissue processing included completion of fixation in 10% neutral buffered formalin, dehydration in increasing concentrations of ethanol, clearing in two changes of xylene and impregnation with molten paraffin wax. Tissues were then embedded using Tissue-Tek embedding moulds and sectioned using a microtome set at 5 μm. Tissue sections were stained using the Haematoxylin and Eosin (H and E) stain and later examined under a microscope. Three animals were selected from each group and taken for analysis. Technicians were blinded to the group. Each section was reviewed by two independent pathologists. Pictures were taken at x200 magnification. Representative images were selected with the expert guidance of the pathologist.

Fig. 9
figure 9

(I-IV). Haematoxylin and Eosin stain on histological sections of kidney tissue. (I) Normal control (NC) group (magnification, x200); (II) BPH control group (magnification, x200); (III) TP + Finasteride (magnification, x200) and (IV) TP + ECTECE (magnification, x200). BPH- Benign prostatic hyperplasia, ethanol crude tuber extract of C. esculenta

Full size image

Quality control

For the complete blood count, we used control blood and normal samples to monitor daily variation. We also employed the XN check levels 1, 2 and 3. In addition, we followed manufacturer’s instruction and standard operating procedures for equipment start-up, self-check, as well as sample preparation and loading.

For histopathology, we ensured use of standard operating procedures and all stains and reagents were used after filtration. Examination of slides was done by two qualified pathologists and in cases of a discrepancy, a third pathologist was involved.

Statistical data analyses

Data were analyzed using Prism software (Graph-Pad Software; San Diego, CA) to determine statistical significance. Dunnet ANOVA test was used to compare the mean values of the individual groups and control at P < 0.005. The results are shown as mean ± SD of 5 rats per group.

Results

Effect of ethanol crude tuber extract of colocasia esculenta and fractions on serum prostate specific antigen (PSA) and total protein in testosterone propionate (TP) induced benign prostate hyperplasic (BPH) rats

Administration of TP in male Wistar albino rats significantly (p < 0.05) elevated serum PSA level in Table 1. Co-administration of TP and ethanol crude Tuber extract of Colocasia esculenta (ECTECE), hexane fraction (HF), dichloromethane fraction (DCMF), butanone fraction (BF), Ethyl acetate fraction (EAF) and aqueous fraction (AF) in male rats significantly (p < 0.05) reduced the level of serum PSA in comparison to the normal control group with no significant change (p > 0.05) in total protein concentration in the serum. Interestingly, significant (p < 0.05) reductions in the level of serum PSA were observed in all the fractions except butanone fraction when compared with the normal control group (Table 1).

Table 1 Effect of ethanol crude tuber extract of C. esculenta and Fractions on serum prostate specific antigen in TP induced BPH Rats
Full size table

C. esculenta protection against BPH is comparable to finasteride

In general C. esculanta fractions induced changes in serum total protein which were comparable to the standard treatment (finasteride) (Fig. 1). The mean serum total protein of normal controls (6.57 ± 0.56 mg/dl) were in the same range as C. esculanta treatments and significantly higher than the mean of testosterone propionate (TP) treatment group (6.18 ± 0.19 mg/dl). This was also observed in mean total body weight of the animals (Fig. 2B). The mean body weight of the rats in the normal control group was 166.8 ± 17.90 g which was significantly higher than in the TP group (127.76 ± 10.20 g). The mean weight of those treated with the various fractions were significantly higher than the TP group (TP + finasteride: 136.50 ± 32.80, TP + ECTECE: 154.60 ± 13.70, TP + HF: 136.30 ± 16.80, TP + DCMF: 137.06 ± 18.94, TP + BF: 142.60 ± 16.40, TP + EAF: 135.02 ± 16.90, TP + AF: 143.08 ± 8.90). Although the mean relative prostate weight (weight of each prostate divided by body weight of the animal) significantly (P < 0.05) increased by approximately 5 times (Fig. 2A) on treatment with testosterone propionate, this increase was moderated by C.esculenta extracts to levels comparable to that achieved by finasteride treatment.

The effect of ethanol crude Tuber extract of c. esculenta and Fractions on the weights of vital organs

Administration of TP in male Wistar albino rats showed no significant (p > 0.05) difference on the relative liver, kidneys and heart weights although there was a significant (p < 0.05) reduction in mean relative testes weight by approximately 1.4 times less (Fig. 3(a-d)). Co-administration of TP and ethanol crude Tuber extract of C. esculenta (ECTECE), hexane fraction (HF), dichloromethane fraction (DCMF), butanone fraction (BF), ethyl acetate fraction(EAF) and aqueous fraction(AF) showed no significant (p < 0.05) difference on the relative organs weights (Fig. 3(a-d)).

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Red blood cell and Platelet counts

Administration of TP in male Wistar albino rats showed no significant (p > 0.05) difference on RBC, haemoglobin, HCT, MCV, MCH, MCHC and platelets levels (Fig. 4(a-g)). Co-administration of TP and ethanol crude Tuber extract of C. esculenta (ECTECE), hexane fraction (HF), dichloromethane fraction (DCMF), butanone fraction (BF), Ethyl acetate fraction (EAF) and aqueous fraction(AF) in male rats showed no significant(p < 0.05) difference on the haematological parameters as shown in Fig. 4(a-g). A significant (p < 0.05) reduction in MCV level was recorded in the group that received TP + ECTECE while significant differences were recorded in groups that received TP + Finasteride and TP + AF (Fig. 4g).

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Red Blood cells and Leukocyte counts

Administration of TP in male Wistar albino rats significantly (p > 0.05) reduced the WBC, monocytes and lymphocytes counts with a significant (p < 00.05) elevation on the counts of neutrophils, eosinophil and basophiles (Fig. 5 (a-f)). Co-administration of TP and ethanol crude Tuber extract of C. esculenta (ECTECE), hexane fraction (HF), dichloromethane fraction (DCMF), butanone fraction (BF), Ethyl acetate fraction (EAF) and aqueous fraction (AF) in male rats significantly (p < 0.05) elevated the counts of WBC, monocytes and lymphocytes with significantly (p < 0.05) reduced neutrophil, eosinophil and basophil counts as shown in Fig. 5. There was no significant (p > 0.05) difference on WBC counts in group that received TP + ECTECE and non-significant (p > 0.05) difference on lymphocyte counts (Fig. 5(a-f)).

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Histopathological features of the Prostate Gland

The results of histopathological examination of the prostate glands of the rats that were studied are shown in Fig. 6. Histopathological examination of the prostates of the control (Fig. 6 (I)) revealed no demonstrable prostatic hyperplasia and increased reduction in the number of cells that rimmed the prostatic gland with no proliferation of the glandular cells of the prostate. The group that received TP + finasteride group showed demonstrable prostatic hyperplasia as well as mild proliferation of the glandular cells of the prostate as shown in Fig. 6(II). The group that received TP + ECTECE (Fig. 6(III)) showed a mild proliferation of the glandular cells of the prostate and evidence of reduced production of prostatic gland fluids. There was also normal prostate gland and increased reduction of the number of cells that rimmed the prostate gland with increased eosinophilic secretions at the center. And finally, BPH untreated group showed increased proliferation, multiplication of the prostate gland and demonstrable hyperplasia (Fig. 6(IV)).

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Histopathological features of liver

Liver histopathological examination showed no demonstrable features of hyperplasia, hypertrophy or atrophy in biopsies obtained from the normal control (Fig. 7 (I.NC)), BPH untreated group (Fig. 7(II.BPH)) as well as in the group that received TP + ECTECE (Plate 2 (III)). This demonstrated the safety of the extract to the liver. The only observed feature was congestion as shown in Fig. 7 (I-III).

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Histopathological features of heart

Figure 8 (I-IV). Haematoxylin and Eosin stain on histological sections of heart tissue. (I) Normal control (NC) group (magnification, x200); (II) BPH control group (magnification, x200); (III) TP + Finasteride (magnification, x200) and (iv) TP + ECTECE (magnification, x200). BPH- Benign prostatic hyperplasia, ethanol crude tuber extract of C. esculenta.

Effect of ethanol crude Tuber extract of c. esculenta and Fractions on Histopathological feature of kidneys

Histopathological examination of kidney tissue showed no demonstrable features of hyperplasia, hypertrophy or atrophy in biopsies obtained from the normal control, BPH control group, TP + Finasteride and TP + ECTECE as shown in Fig. 9 (I-IV). This demonstrated the safety of the extract to the kidneys.

Discussion

This study was aimed at investigating the safety profile of C. esculenta in crude and semi purified form for the management and or prevention of BPH. Our results show that C esculenta is effective and widely tolerated as an anti BPH nutraceutical in the rat model. Although the exact natural products in C. esculenta that could explain its pharmacological actions have not been completely characterised, the methanol/chloroform extract has been reported to contain many bioactive compounds: hexadecanoic acid methyl ester, octadecanoic acid, 9,12-octadecadienoyl chloride, 11-octadecenoic acid methyl ester, 9-octadecenoic acid, 3-hexadecyloxycarbonyl-5-(2-hydroxylethyl)-4-methylimidazolium, hexanedioic acid, bis(2-ethylhexyl)ester and 3,5-di-t-butyl phenol. This is in addition to the high phenolic compounds content composed of Gallic Acid, Quercetin and Catechin [43, 44]. Many of these compounds have antioxidant (phenolic compounds), anti-inflammatory, anti-alopecic, 5-α-reductase inhibitory, anemiagenic, anti-tumor, immuno-stimulatory, anti-leucotriene-D4, anti-androgenic, lipoxygenase inhibitory and hypocholesterolemic properties ( organic compounds such as 9-octadecenoic acid ) [40].

Data from the biochemical and hematological parameters of our study do not show evidence of toxicity. However, we observed decrease in body weights of the treatment group. This is suggestive of a potential cellular response to arrest BPH through breakdown of tissue proteins [40]. In addition, we observed, an increase in the body weights of the groups that received finasteride, or ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE which suggest bioactivity by the crude extract and fractions of ECTECE in halting the breakdown of tissue proteins.

More to this the elevated prostate weights as observed in the BPH untreated group could have resulted from pathological alterations in the prostatic tissue linked to BPH [40, 45]. However, the lower relative prostate weights of the BPH + finasteride, BPH + ECTECE, or BPH + hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE groups indicate that these treatments may be able to reduce prostatic hyperplasia at the lower doses utilized in this investigation. Although we cannot rule out the possibility that increase in body weights of some rats contributed to the decrease in relative prostate weights, given that their bodyweights were much higher than those of the BPH untreated group.

According to the present study, non-significant (p > 0.05) differences in relative liver, kidney and heart weights were observed in both BPH untreated group and the treated groups. This non-significant difference in the relative’s organs weight may demonstrate nontoxic effect of the crude extract of cocoyam and fractions to the organs [46, 47]. This particular result confirms a previous report by Eleazu et al. (2013) [46] which showed no significant differences (𝑃 > 0.05) in the liver, kidney and heart weights of the diabetic rats administered cocoyam feed and diabetic control rats. Eleazu et al. (2014) [36] which reported that the diabetic rats fed with cocoyam had significant elevation (P < 0.05) of hepatic AST, ALT, ALP and serum proteins and albumin, but had significant reduction (P < 0.05) of blood glucose, serum urea, creatinine, amylase, lipase, AST, ALT and ALP compared with the diabetic control rats also support the safety of cocoyam in the management of diseases.

Reduction in the testes weight in the BPH untreated group as observed in this study could be as a result of exogenous effect of TP as a potential male contraceptive [48]. On the contrary the study revealed that crude extract cocoyam tuber and fractions were able to modulate the negative effect on the testes weight.

Increased counts of neutrophils, eosinophils, basophils and reduction in white blood cell, monocytes and lymphocytes counts; no significant (p > 0.05) difference on RBC, haemoglobin, HCT, MCV, MCH, MCHC and platelets counts could be attributed to the BPH induction in BPH untreated group. The treatment with crude extract of cocoyam tuber and fractions modulated the immune and haematological parameters showing the safety of the cocoyam extract and fractions. This result is similar with Princewill-Ogbonna et al. (2016) [49] which reported non-significant difference in haematological parameters in rats feed with cocoyam made feed. Azubuike et al. (2018) [47] also reported the safety of usage of C. esculenta leaves in the reduction of fat adipose tissues and its ameliorative effect on HFD-induced liver damage.

Conclusion and recommendation

Our results suggest that C.esculenta has a potential for use as a nutraceutical in benign hyperplasia thus we recommend further studies on mechanism and the active components present. Given that C.esculenta is a commonly consumed food in many African countries it would be nice to do epidemiological studies in these areas with higher consumption of this important food. And probably be subjected to clinical trials aimed complementing standard therapies as a nutraceutical.

Data Availability

All data generated or analyzed during this study are included in this published article.

References

  1. Global regional. National age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the global burden of Disease Study 2017. Lancet (London England). 2018;392(10159):1684–735.

    Article  Google Scholar 

  2. Chughtai B, Forde JC, Thomas DDM, Laor L, Hossack T, Woo HH, Te AE, Kaplan SA. Benign prostatic hyperplasia. Nat reviews Disease primers. 2016;2(1):1–15.

    Google Scholar 

  3. Sohlberg EM, Thomas IC, Yang J, Kapphahn K, Daskivich TJ, Skolarus TA, Shelton JB, Makarov DV, Bergman J, Bang CK, et al. Life expectancy estimates for patients diagnosed with prostate cancer in the Veterans Health Administration. Urol Oncol. 2020;38(9):734e731–734e710.

    Article  Google Scholar 

  4. Launer BM, McVary KT, Ricke WA, Lloyd GL. The rising worldwide impact of benign prostatic hyperplasia. 2021, 127(6):722–8.

  5. Barry MJ, Roehrborn CG. Benign prostatic hyperplasia. BMJ. 2001;323(7320):1042–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gossel TA, Wuest JR. New drugs of 2004 for treatment of benign prostatic hyperplasia: Avodart and Uroxatal. Contin Educ Pharm. 2004;22:1–4.

    Google Scholar 

  7. Liu Q, He H, Yang J, Feng X, Zhao F, Lyu J. Changes in the global burden of depression from 1990 to 2017: findings from the Global Burden of Disease study. J Psychiatr Res. 2020;126:134–40.

    Article  PubMed  Google Scholar 

  8. Lokeshwar SD, Harper BT, Webb E, Jordan A, Dykes TA, Neal DE Jr, Terris MK, Klaassen Z. Epidemiology and treatment modalities for the management of benign prostatic hyperplasia. Translational Androl Urol. 2019;8(5):529.

    Article  Google Scholar 

  9. Chokkalingam AP, Yeboah ED, Demarzo A, Netto G, Yu K, Biritwum RB, Tettey Y, Adjei A, Jadallah S, Li Y, et al. Prevalence of BPH and lower urinary tract symptoms in West Africans. Prostate Cancer Prostatic Dis. 2012;15(2):170–6.

    Article  CAS  PubMed  Google Scholar 

  10. Yeboah ED, PREVALENCE OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATE CANCER IN AFRICANS AND AFRICANS IN THE DIASPORA. J West Afr Coll Surg. 2016;6(4):1–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Peter N, Michael C. Benign Prostatic Hyperplasia (BPH) in an elderly ugandan male. MMJ 2014, 46(1).

  12. Pais P. Potency of a novel saw palmetto ethanol extract, SPET-085, for inhibition of 5α-reductase II. Adv therapy. 2010;27(8):555–63.

    Article  Google Scholar 

  13. Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin. 2011;95(1):87–100.

    Google Scholar 

  14. Bajunirwe F, Stothers L, Berkowitz J, Macnab AJ. Prevalence estimates for lower urinary tract symptom severity among men in Uganda and sub-saharan Africa based on regional prevalence data. Can Urol Association journal = Journal de l’Association des urologues du Can. 2018;12(11):E447–e452.

    Google Scholar 

  15. Corona G, Rastrelli G, Maseroli E, Balercia G, Sforza A, Forti G, Mannucci E, Maggi M. Inhibitors of 5α-reductase-related side effects in patients seeking medical care for sexual dysfunction. J Endocrinol Investig. 2012;35(10):915–20.

    CAS  Google Scholar 

  16. Ogunbiyi OJ. Impact of health system challenges on prostate cancer control: health care experiences in Nigeria. Infect Agents Cancer. 2011;6(2):5.

    Article  Google Scholar 

  17. Yu Z-J, Yan H-L, Xu F-H, Chao H-C, Deng L-H, Xu X-D, Huang J-B, Zeng T. Efficacy and side effects of drugs commonly used for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Front Pharmacol. 2020;11:658.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Emberton M, Marberger M, de la Rosette J. Understanding patient and physician perceptions of benign prostatic hyperplasia in Europe: the prostate research on Behaviour and Education (PROBE) Survey. Int J Clin Pract. 2008;62(1):18–26.

    Article  CAS  PubMed  Google Scholar 

  19. Ückert S, Kedia GT, Tsikas D, Simon A, Bannowsky A, Kuczyk MA. Emerging drugs to target lower urinary tract symptomatology (LUTS)/benign prostatic hyperplasia (BPH): focus on the prostate. World J Urol. 2020;38(6):1423–35.

    Article  PubMed  Google Scholar 

  20. Dunn MW, Kazer MW. Prostate cancer overview. In: Seminars in oncology nursing: 2011: Elsevier; 2011: 241–50.

  21. Silva J, Silva CM, Cruz F. Current medical treatment of lower urinary tract symptoms/BPH: do we have a standard? Curr Opin Urol. 2014;24(1):21–8.

    Article  PubMed  Google Scholar 

  22. Van Asseldonk B, Barkin J, Elterman DS. Medical therapy for benign prostatic hyperplasia: a review. Can J Urol. 2015;22(Suppl 1):7–17.

    PubMed  Google Scholar 

  23. Saka SA, Yusuf AA, Campus S. Drug therapy problem in elderly outpatients with benign prostatic hyperplasia. West Afr J Pharm. 2021;32(1):33–44.

    Google Scholar 

  24. Eleazu C, Eleazu K, Kalu W. Management of benign prostatic hyperplasia: could dietary polyphenols be an alternative to existing therapies? Front Pharmacol. 2017;8:234.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Cicero AFG, Allkanjari O, Busetto GM, Cai T, Larganà G, Magri V, Perletti G, Robustelli Della Cuna FS, Russo GI, Stamatiou K et al. Nutraceutical treatment and prevention of benign prostatic hyperplasia and prostate cancer. Archivio italiano di urologia andrologia: organo ufficiale [di] Societa italiana di ecografia urologica e nefrologica 2019, 91(3).

  26. Curtis Nickel J, Shoskes D, Roehrborn CG, Moyad M. Nutraceuticals in prostate disease: the urologist’s role. Rev Urol. 2008;10(3):192–206.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Talwana H, Serem A, Ndabikunze B, Nandi J, Tumuhimbise R, Kaweesi T, Chumo C, Palapala VA. Production Status and Prospects of Cocoyam (Colocasia esculenta L. Schott.) in East Africa. 2009.

  28. Otekunrin OA, Sawicka B, Adeyonu AG, Otekunrin OA, Rachoń L. Cocoyam [Colocasia esculenta (L.) Schott]: exploring the production, Health and Trade Potentials in Sub-Saharan Africa. Sustainability. 2021;13(8):4483.

    Article  Google Scholar 

  29. Prajapati R, Kalariya M, Umbarkar R, Parmar S, Sheth N. Colocasia esculenta: a potent indigenous plant. Int J Nutr Pharmacol Neurol Dis. 2011;1(2):90.

    Article  CAS  Google Scholar 

  30. Mitsunari K, Miyata Y, Matsuo T, Mukae Y, Otsubo A, Harada J, Kondo T, Matsuda T, Ohba K, Sakai H. Pharmacological Effects and potential clinical usefulness of polyphenols in Benign Prostatic Hyperplasia. Molecules. 2021;26(2):450.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Keerthy S, Joshi KH. The pharmacological importance of Colocasia esculenta Linn: a review. J Pharmacognosy Phytochemistry. 2019;8(6):1945–8.

    CAS  Google Scholar 

  32. Brown AC, Reitzenstein JE, Liu J, Jadus MR. The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells in vitro. Phytother Res. 2005;19(9):767–71.

    Article  PubMed  Google Scholar 

  33. Kalariya M, Prajapati R, Parmar SK, Sheth N. Effect of hydroalcoholic extract of leaves of Colocasia esculenta on marble-burying behavior in mice: implications for obsessive-compulsive disorder. Pharm Biol. 2015;53(8):1239–42.

    Article  PubMed  Google Scholar 

  34. Islam MH, Mostafa MN, Rahmatullah M. Antihyperglycemic activity of methanolic extracts of corms of Colocasia esculenta var esculenta. Eur J Pharm Med Res. 2018;5(3):129–32.

    Google Scholar 

  35. Tripathi AK, Kohli S. Phytochemical screening and evaluation of antidiabetic activity of Colocasia esculenta (L) leaves on STZ induced diabetic rats. Adv Pharmacol Toxicol. 2013;14(2):1.

    Google Scholar 

  36. Eleazu CO, Okafor PN, Ifeoma I. Biochemical basis of the use of cocoyam (Colocassia esculenta L.) in the dietary management of diabetes and its complications in streptozotocin induced diabetes in rats. Asian Pac J Trop Disease. 2014;4:705–S711.

    Article  Google Scholar 

  37. Shithi S, Mohammed R. Antihyperglycemic and antinociceptive activities of methanolic extract of Colocasia esculenta (L.) Schott stems: a preliminary study. American-Eurasian J Sustainable Agric. 2013;7(4):314–9.

    Google Scholar 

  38. Eleazu C. Characterization of the natural products in cocoyam (Colocasia esculenta) using GC–MS. Pharm Biol. 2016;54(12):2880–5.

    Article  CAS  PubMed  Google Scholar 

  39. Nyonseu Nzebang DC, Ngaha Njila MI, Bend EF, Oundoum Oundoum PC, Koloko BL, Bogning Zangueu C, Belle Ekedi P, Sameza M, Massoma Lembè D. Evaluation of the toxicity of Colocasia esculenta (Aracaceae): preliminary study of leaves infected by Phytophthora colocasiae on wistar albinos rats. Biomed pharmacotherapy = Biomedecine pharmacotherapie. 2018;99:1009–13.

    Article  Google Scholar 

  40. Eleazu K, Maduabuchi Aja P, Eleazu CO. Cocoyam (Colocasia esculenta) modulates some parameters of testosterone propionate-induced rat model of benign prostatic hyperplasia. Drug Chem Toxicol 2021:1–11.

  41. Stowell LI, Sharman LE, Hamel K. An enzyme-linked immunosorbent assay (ELISA) for prostate-specific antigen. Forensic Sci Int. 1991;50(1):125–38.

    Article  CAS  PubMed  Google Scholar 

  42. Feldman AT, Wolfe D. Tissue processing and hematoxylin and eosin staining. Methods in molecular biology (Clifton NJ). 2014;1180:31–43.

    Article  CAS  Google Scholar 

  43. Omotoso Abayomi E, Kenneth E, Mkparu K. Chemometric profiling of methanolic leaf extract of Cnidoscolus aconitifolius (Euphorbiaceae) using UV-VIS, FTIR and GC-MS techniques. J Med Plants Res. 2014;2(1):6–12.

    Google Scholar 

  44. Eleazu CO. Characterization of the natural products in cocoyam (Colocasia esculenta) using GC–MS. Pharm Biol. 2016;54(12):2880–5.

    Article  CAS  PubMed  Google Scholar 

  45. Kalu W, Okafor P, Ijeh I, Eleazu C. Effect of kolaviron, a biflavanoid complex from Garcinia kola on some biochemical parameters in experimentally induced benign prostatic hyperplasic rats. Biomed Pharmacother. 2016;83:1436–43.

    Article  CAS  PubMed  Google Scholar 

  46. Eleazu CO, Iroaganachi M, Eleazu K. Ameliorative potentials of cocoyam (Colocasia esculenta L.) and unripe plantain (Musa paradisiaca L.) on the relative tissue weights of streptozotocin-induced diabetic rats. Journal of diabetes research 2013, 2013.

  47. Azubuike NC, Onwukwe OS, Onyemelukwe AO, Maduakor UC, Ifeorah IM, Okwuosa CN, Achukwu PU. Impact of Colocasia esculenta extract and fractions on high-fat diet-induced changes in body weight, adipose tissue and liver of rats. Pak J Pharm Sci 2018.

  48. Van ROIJENJH, OOMS MP, WEBER RF, BRINKMANN AO, GROOTEGOED JA, VREEBURG JT. Comparison of the response of rat testis and accessory sex organs to treatment with testosterone and the synthetic androgen methyltrienolone (R1881). J Androl. 1997;18(1):51–61.

    Google Scholar 

  49. Princewill-Ogbonna IL, Ihedioha S, Ijeoma SN. Hematological and liver/Kidney histology of rats feed with cocoyam (Colocasia esculenta L). Contemp J Empir Res. 2016;2(3):271–87.

    Google Scholar 

Download references

Acknowledgements

We acknowledge contributions of laboratory technicians at Ebonyi state University and Mbarara University of science and technology including Mr. Mutekanga Emanuel, Mr Mukundane Victor and Mr Rujumba Bright. The DAAD staff exchange fellowship for sub-Saharan Africa that provided Dr Patrick M. Aja an opportunity to visit Mbarara University during this project. We also acknowledge technical support from Mr Joseph Oloro and support in terms of infrastructure of specific universities including Mbarara and Ebonyi state University and Kampala International University.

Funding

There was no funding of any of the authors for this project.

Author information

Authors and Affiliations

  1. Department of Biochemistry, Faculty of Medicine, Mbarara University of Science and Technology, Mbarara, Uganda

    Deusdedit Tusubira, Patrick M. Aja, Jonasi Munezero & Nathim Namale

  2. Department of Biochemistry, Faculty of Sciences, Ebonyi State University, Abakaliki, Nigeria

    Patrick M. Aja & Peter C. Agu

  3. Department of Medical Biochemistry, Kampala International University, Kampala, Uganda

    Patrick M. Aja & Josiah E. Ifie

  4. Medical Laboratory Science, Mbarara University of science and Technology, Mbarara, Uganda

    Frank Ssedyabane

  5. Faculty of Medicine, Department of Pharmacy, Mbarara University of Science and Technology, Mbarara, Uganda

    Clement O. Ajayi

  6. Department of Biochemistry, Soroti University, Soroti, Uganda

    Joash Okoboi

Authors
  1. Deusdedit Tusubira
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Patrick M. Aja
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jonasi Munezero
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frank Ssedyabane
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nathim Namale
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Josiah E. Ifie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peter C. Agu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Clement O. Ajayi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joash Okoboi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DT, PMA conceived the idea., DT, PMA, JM, FS, NN, JEI, COA, and JO designed experiments, carried out laboratory work, analyzed data, PMA wrote the first draft of the manuscript, all members revised and contributed to the final version of manuscript.

Corresponding author

Correspondence to Deusdedit Tusubira.

Ethics declarations

Ethics approval and consent to participate

This study was done under the supervision and approval by the Office of Research, Innovation and Institutional Ethics Committee of Ebonyi state university, Nigeria (EBSU/BCH/ET/21/001). All procedures for animal studies were carried out and reported based on the Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines and legislations consistent with the National Institute of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 80-23, revised in 1996) [33] as well as National guidelines for the use of laboratory animals for research and teaching based on the principles of 3Rs, reduce refine or replace.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tusubira, D., Aja, P.M., Munezero, J. et al. Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia. BMC Complement Med Ther 23, 187 (2023). https://doi.org/10.1186/s12906-023-04018-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12906-023-04018-4

Keywords

BMC Complementary Medicine and Therapies

ISSN: 2662-7671

Contact us