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Protective effect of the hydroethanolic extract of camelthorn (Alhagi maurorum) on benign prostatic hyperplasia induced by testosterone in rats

BMC Complementary Medicine and Therapies volume 25, Article number: 136 (2025) Cite this article

Abstract

Background

One of the Iranian medicinal plants is Alhagi maurorum, which belongs to the Fabaceae family. The plant is used to treat different conditions, such as aphthous ulcers, cardiac pains, hemorrhoids, kidney stones, dysuria, etc. Given that A. maurorum is characterized by its richness in flavonoids and phenolic compounds, and it is used to treat urinary tract disorders, this study aimed to investigate the protective effects of its hydroethanolic extract in a rat model of benign prostatic hyperplasia (BPH).

Methods

After preparing the hydroethanolic extract, phytochemical analysis, including GC–MS, was conducted. Adult male Wistar rats (n:35) were randomly divided into five groups (n:7): A sham surgery was conducted on the first group, while the other four groups underwent castration through the scrotal route. Seven days after the surgery, benign prostatic hyperplasia (BPH) was induced in all groups except the first one, using a subcutaneous injection of testosterone propionate at a dosage of 10 mg/kg/day. The treatment duration lasted 28 days, during which the animals received oral treatments as follows: 1. Sham control: normal saline, 2. Positive control (BPH group): normal saline, 3. Comparative control: finasteride at 5 mg/kg/day, 4. T1 group: A. maurorum extract at 200 mg/kg/day, and 5. T2 group: A. maurorum extract at 400 mg/kg/day. At the end of the experiment, following an overnight fast and after administering anesthesia with ketamine and xylazine, blood was collected through cardiac puncture, and sera were harvested for hormone assay. Finally after euthanizing the rats, the ventral prostatic lobes were dissected for biochemical, histopathological, and gene expression analyses.

Results

GC–MS analysis showed the presence of nine components. A. maurorum extract and/or Finasteride led to a significant reduction of the prostate weight and prostatic index, serum, and prostatic levels of testosterone. These compounds led to the downregulation of 5-α reductase and androgen receptor genes expression, boosted total antioxidant capacity, and declined prostatic malondialdehyde levels. Intervention using the extract, comparable to Finasteride, led to BPH-induced histopathological enhancements in the prostate.

Conclusion

Treatment using A. maurorum extract resulted in significant protection of the prostate against BPH, which is attributable to its antioxidant and androgen-modulating characteristics.

Graphical Abstract

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Introduction

One may describe benign prostatic hyperplasia (BPH) as the prostate enlargement resulting from non-cancerous agents. It is typically associated with the failure of the urinary tract characterized by complications in the urination frequency, inability to fully empty the bladder, a history of urinary/bladder infections, or clinical symptoms of the men in their fifth decade of life, in particular about the age of 80 [1, 2].

BPH development results from the overgrowth of the fibromuscular cells and glandular epithelial cells found within the stroma, which results in prostate gland enlargement and uncontrolled hyperplasia [3].

The BPH pathophysiology has not been fully understood in spite of numerous scientific investigations. As a multifactorial disorder, benign prostatic hyperplasia includes inflammatory mediators and genes, endocrine imbalance, oxidative stress augmentation, and apoptosis [4, 5].

As soon as testosterone, secreted by the Leydig cells of the testes, reaches the prostate, it is transformed by the 5α-reductase enzyme into dihydrotestosterone (DHT). Dihydrotestosterone shows a higher affinity to bind to the androgen receptor (AR) found in prostate cells and compared to testosterone, results in increased signaling of the androgen receptor tenfold [6]. In fact, the androgens, in particular DHT and AR, play crucial roles in the regular function and development of prostate gland throughout life. This is because they make it possible for the glandular cells to survive and proliferate [7]. Benign prostatic hyperplasia may lead to higher AR expression levels in both prostatic epithelial and stromal cells in comparison with the normal tissues [8, 9]. The effect of pre-existing 5α-reductase deficiency can exemplify the critical importance of the presence of androgens in the prostate gland. Based on the observations, the affected males show significantly smaller prostates in comparison with the unaffected men of the same age [10]. Given the role played by the same enzyme, and thereby, the generation of dihydrotestosterone in a prostate gland suffering from hyperplasia, the use of 5α-reductase inhibitors (5-ARIs, for instance, finasteride) has long been approved for the purpose of treating the same disorder [11]. One may administer Alpha-1 blockers, e.g., tamsulosin, in order to relax the smooth muscles found in the prostatic urethra, which leads to the promotion of better urine flow. Also, one may use a combination of 5-ARIs and alpha-blockers [12]. However, due to the adverse effects of these agents, e.g., dizziness, headache, gynecomastia, declined libido, and erectile or ejaculatory dysfunctions, their use is faced with restrictions [13,14,15]. It is noteworthy that such medications may require several months to take effect [10], and this may be wearisome for a number of patients and may affect their compliance.

With regard to the same issue, finding agents characterized by lower side effects with the capability of addressing multiple BPH pathogenesis pathways is critical.

As mentioned before, a close relationship is found between prostatic hyperplasia development and oxidative stress [4, 16]. A number of investigations have indicated the key function of reactive oxygen species (ROS) in the BPH pathophysiology. Applying a variety of antioxidants, e.g., diosmin, berberine, etc., alleviates the augmentation of oxidative stress caused by BPH induction significantly [17, 18].

As a medicinal plant, Alhagi maurorum Medik., which is also called camelthorn, belongs to the Fabaceae family. The plant is widely distributed across Central Asia, the Middle East, Africa, and Europe [19, 20]. Traditionally, the species of the plant are used for their medicinal characteristics, such as diuretic, anti-urolithiasis, diaphoretic, expectorant, anti-ulcerogenic, and aphrodisiac effects. [21]. In addition, the plant is regarded to be effective in the treatment process of a variety of ailments, including rheumatism, liver diseases, urinary tract disorders, gastrointestinal complications, and bilharziasis [22]. Besides its conventional use in traditional medicine, modern pharmacological investigations have indicated that the plant is effective in the treatment of diabetes, gastric ulcers, and urolithiasis resulting from sulfonamides. In addition, it shows protective features against the agents harmful to the kidneys, heart, and liver. Given its anti-nociceptive, antipyretic, and anti-inflammatory effects, the plant is an invaluable medicine [23].

It's important to note that this medicinal plant has been used in many animal models to study urinary tract disorders. It has shown protective effects in conditions such as urolithiasis induced by sulfadimidine in rabbits [24], as well as nephrotoxicity induced by gentamicin [25] and norfloxacin [26] in rats. Also, the A. maurorum extract has shown a strong protective effect against the LNCaP cell line in vitro. LNCaP cells are androgen-sensitive human prostate adenocarcinoma cells. The results indicated that this extract significantly inhibited the proliferation of this cell line with an IC50 of 43.9 µg/mL [27]. Therefore, it is reasonable to assess this extract on prostatic hyperplasia in vivo, using a rat model of BPH. According to a number of investigations, A. maurorum is a rich source of phenolic and flavonoid compounds characterized by a high antioxidant capacity [28,29,30].

All in all, this investigation is targeted at analyzing the potential protective effect of the hydroethanolic extract of A. maurorum in a BPH rat model. This evaluation is concentrated on biochemical, histopathological, and oxidative stress status parameters.

Methods

Plant material

From the Camelthorn plants (A. maurorum Medik.) grown in Songhor, located in Kermanshah, Iran, the aerial parts were collected in August 2022. Sampling was conducted on desert public land in this region, as the medicinal plant is a native wild species, so no permission was necessary. Dr Kanani, who is a botanist working at the Botany Department of the Medicinal Plants and Drug Research Institute situated at Shahid Beheshti University in Iran, authenticated the species and genus of the concerned plant. Also, a voucher sample featuring the plate number MPH-3199 was deposited at the herbarium of the Research Institute.

Extract preparation

After washing the aerial parts of A. maurorum Medik. gently and thoroughly, they were dried in the shade and were then ground so as to acquire a fine powder. Using the cold maceration technique with 70% ethanol, the hydroethanolic extract was prepared. Using a 1:10 (w/v) ratio, a volume of 1000 mL of 70% ethanol was mixed with 100 g of the ground plant material, which was kept for 48–72 h in the dark at room temperature. A Waterman filter (No. 1) paper was used to filter the macerate. Then, a rotary evaporator was used to concentrate the obtained liquid, which was then dried at 40 °C in an oven [31]. Finally, the powder was stored at a temperature of − 20 °C until it was ready to use. At the time of administration, it was dissolved in distilled water.

Phytochemical analysis

To determine the total phenolic content of the extract of A. maurorum, which was described in terms of gallic acid [32], the Folin-Ciocalteu reagent technique was employed, while the total flavonoid content was determined as rutin [33]. Furthermore, the antioxidant activity of the plant was determined by employing the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and reducing power assay (RPA). The results, described as IC50, indicate the concentration of a compound leading to an inhibition of 50% in the radical capacity [34]. The A. maurorum extract was analyzed via gas chromatography-mass spectrometry (GC–MS) by employing an Agilent 6890N gas chromatograph featuring an Agilent 5975 Mass Selective Detector and an HP-5 column.

Animals

In the present research, 35 adult male Wistar rats weighing between 220 and 260 g and at the age of 12 weeks were procured from Animal Lab, Kermanshah University of Medical Sciences located in Kermanshah, Iran. The animals were kept within polypropylene cages in the animal house by following the standards laboratory conditions, e.g., a relative humidity ranging between 40 and 60%, a 12-h light/12-h dark cycle, and a temperature ranging between 22 and 25 ◦C. The animals had free access to standard food pellets and water. The mentioned procedures followed in the present investigation were confirmed by the Ethical Committee of Experimental Animals of Razi University with the No. IR.RAZI.REC.1401.022 ethical code. The present investigation was conducted by observing the criteria expressed in the as-published guidelines for the Care and Use of Laboratory Animals that were issued by the National Institute of Health (NIH).

Study design and tissue sampling

After the acclimatization of the rats to the new conditions and the laboratory environment for a duration of seven days, they were randomly split into five groups (n:7): 1. Sham control: the animals undergoing sham surgery and receiving normal saline daily via oral gavage. 2. Positive control (BPH group): these animals were castrated and received a testosterone propionate dosage of 10 mg/kg/day (procured from Aburaihan Pharmaceutical Co., Iran) [35] via SC injections so as to induce benign prostatic hyperplasia in them. In addition, they received normal saline via oral gavage on a daily basis. 3. Comparative control (Finasteride group): these animals that underwent BPH induction, received finasteride (Sigma, Germany) at a dosage of 5 mg/kg/day [36] through the oral gavage. 4 and 5. i.e., Treatment-1 and Treatment-2 (the groups of Alhagi 200 and 400): the animals developing benign prostatic hyperplasia received the extract of A. maurorum at dosages of 200 and 400 mg/kg/day [25, 37] respectively via the oral gavage. Administration of all medications commenced 7 days post-surgery, whether sham or castration, and continued for 28 consecutive days. All rats were reweighed and anesthetized using xylazine (8 mg/kg) and ketamine (80 mg/kg) after an overnight fast [18]. Using the cardiac puncture, a 5 mL sample of their blood was collected from their hearts, which was then left to coagulate at room temperature. Its serum was then separated through centrifugation (3000 RPM). After separating the serum, its samples were kept at a temperature of −80 ºC to conduct more analyses. Then, after euthanizing the rats through deepening anesthesia with xylazine (30 mg/kg) and ketamine (300 mg/kg) [38], the ventral prostatic lobes of them were dissected and then weighed [39]. Then by dividing the weight of the prostate gland of every single animal by its body weight, one could determine the Prostatic Index (PI). Then, the inhibition percentage for the Prostatic Index was determined by employing the formula presented here: 100—[(T-SC)/(PC-SC) * 100], in which PC, T, and SC stand for the values of the positive control, treatment groups (comparative control, Treatment-1, and Treatment-2), and the sham control, respectively [40]. While half of the animals’ prostates were kept in formalin for the purpose of histopathological analyses, the other half was kept at a temperature of −80 °C for oxidative stress indices, Real-Time PCR, and biochemical tests.

Histopathological evaluation

For the purpose of histopathological evaluations, suitable samples were taken from the tissues of the prostate, which were then fixed in a solution containing 10% neutral buffered formalin, embedded in paraffin, and then sectioned at a 5-μm thickness, and then stained using hematoxylin–eosin for the purpose of light microscopic examinations. The lesions were described and scored on the basis of the grading criteria presented earlier by Mostafa et al. (2019) [41]. In summary, the histopathological lesions were evaluated by considering these parameters in the ventral lobe of prostate tissues: acinar epithelial hyperplasia with polyp formation, acinar epithelial hypertrophy congestion in blood vessels, and focal interstitial hemorrhage. Each lesion was scored in accordance with the scale that follows: 0: none, 1: mild, 2: moderate, and 3: severe. Also for every single sample, the final score was determined as the sum of those scores. In addition, the epithelial thickness of the prostate was determined in five randomly selected fields (× 200) of every single animal (n = 7 per group) by employing the Image J software (ver. 1.47).

Preparing prostatic tissue homogenate

By employing a manual homogenizer, the part remaining from the prostatic tissue underwent homogenization in phosphate buffer saline (PBS), which was centrifuged for 15 min at 3000 rpm. Then, the supernatant was collected for the purpose of further analysis. First, the total protein found in the supernatant was measured by employing a commercial Bradford kit (purchased from Navand Salamat Co., Urmia, Iran). Then, in accordance with the total protein content, other indices were standardized.

Tissue and serum level of testosterone

By following the guidelines provided by the enzyme-linked immunosorbent assay (ELISA) kit (manufactured by Monobind Inc. USA) featuring a 0.0576 ng/mL sensitivity, the prostatic tissue and serum levels of testosterone were determined.

Analysis of oxidative stress indices

By determining the total antioxidant capacity (TAC) and malondialdehyde (MDA) levels, the prostatic oxidative stress was evaluated. Also, by following the guidelines presented by the lipid peroxidation assay kit (purchased from Navand Salamat Co, Urmia, Iran), the malondialdehyde levels were determined. At 532 nm, the readings were recorded, which were expressed as nmol/mg protein. In addition, the levels of total antioxidant capacity were measured by colorimetric assay at 593 nm by employing the Zantox commercial kit (purchased from Kavosh Arian Azma Co, Birjand, Iran) in accordance with the manufacturer’s guidelines. The obtained results were presented as µmol/mg protein.

Gene expression analysis

The total RNA content was extracted by employing the RNX-Plus Solution Kit from an Iranian company, Sinaclone. The quantity and quality of the extracted RNA were assessed by using a UV/Visible Spectrophotometer manufactured by Jenway, Malaysia. Also, given the extracted RNA concentration and the maximum capacity provided by the cDNA synthesis kit from Sinaclone, the obtained RNA was immediately used for the cDNA synthesis. In addition, the quantitative real-time PCR was carried out using a Rotor-Gene Q real-time thermal cycler purchased from Qiagen Co. in Germany and the SYBR Green Master Mix from Ampliqon in Denmark. It is noteworthy that the PCR reactions for mRNA expression involved a denaturing cycle at 95 °C for a period of ten minutes, followed by 38–42 cycles of annealing at a temperature of 90 °C for 15 s and extension at a temperature of 72 °C for 20 s. The gene sequences have been presented in Table 1, and β-actin was utilized as a housekeeping gene.

Table 1 Primers sequences for the RT-PCR
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Statistical analyses

The data were reported as Mean ± SD. Upon the completion of testing for normal distribution, a one-way analysis of variance (ANOVA) was used to compare the quantitative data. In order to determine the differences observed between groups, the post-hoc Tukey test was conducted. The Mann–Whitney U tests were carried out to analyze the histopathological base scoring data and in order to test significant differences between the groups. The complete statistical analyses were carried out by employing SPSS (version 22) and GraphPad Prism 10. Differences characterized by P-value < 0.05 were considered to be statistically significant.

Results

Phytochemical parameters and GC–MS analysis of A. maurorum

The total flavonoid content, which is reported in mg rutin, and the content of phenolic materials, which is reported in mg gallic acid, were 90.99 ± 10.87 mg/g and 56.31 ± 6.01 mg/g, respectively. The calculated IC50 for the antioxidant capacity was 122.68 ± 0.15 ppm. According to the GC–MS analysis conducted on the extract of A. maurorum, nine main bioactive compounds were present in the extract (Table 2). Based on the results of the GC–MS spectra, the most abundant compounds were 10-Octadecenoic acid, methyl ester, and 12,15-Octadecadienoic acid, methyl ester. Also, the least abundant compounds were Oxiraneoctanoic acid, 3-octyl-, and Trimethyl-tetradecane methyl ester.

Table 2 Phytochemical components found in the extract of A. maurorum Medik. determined by employing gas chromatography-mass spectrometry
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The total body and prostate weight, prostatic index (PI) and the inhibition percentage

As Table 3 illustrates, the induction of benign prostatic hyperplasia using testosterone (positive control group) led to decreased body weight of the animals compared to that in the sham control group (p < 0.0001) after 28 days. Nonetheless, the same parameter increased significantly (p < 0.05) by administering finasteride and also high (400) and low (200) dosages of the A. maurorum extract compared to the BPH group.

Table 3 The contribution of the A. maurorum to the body weight, prostate weight, and prostate enlargement indices in rats with benign prostatic hyperplasia. The obtained results have been presented as mean ± SD
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The prostatic index and prostate weight declined in the BPH group in comparison with those of the sham control group (p < 0.0001), and the same parameters increased significantly in the Alhagi 200, Alhagi 400, and Finasteride groups compared to the BPH group (p < 0.0001).

Also the maximum inhibition percentage for the prostatic index was associated with the Alhagi 400 group, followed by the Finasteride group and Alhagi 200 group.

Histopathology of the prostatic tissue

According to the histopathological examinations, the rats’ prostates in the control group typically showed three distinctive lobes, i.e., lateral lobe, ventral lobe, and dorsal lobe. No morphological changes were observed in the acinar size and shape or in the lining epithelium belonging to the acini of prostatic tissues. Also, the lining epithelium was characterized by columnar to cuboidal epithelial cells featuring a regular size in the single-layer arrangement (Fig. 1A).

Fig. 1
figure 1

H&E staining carried out for the tissues of rats’ prostates in the sham control and BPH groups. The sections prepared from the prostates of the sham control group indicated a normal histoarchitecture for their prostate glands characterized by regular size acini lined featuring a simple columnar to cuboidal epithelium (A). The prostate sections obtained from the untreated BPH animals indicated that the thickness of the hyperplastic glandular epithelium increased significantly (square) (B), irregular acinar shape featuring papillary projections into the lumen (square) (C), and enlarged glands, which are filled by large amounts of red secretions, accompanied by severe interstitial edema and vascular congestion (arrowhead) (D)

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By contrast, the testosterone injection led to mild, moderate, and severe tissue changes in the experimental groups. The prostate sections of the BPH control group indicated abnormal acini of the prostate characterized by significant hyperplasia and hypertrophy in the lining epithelium along with a number of intraluminal papillary folds that extended toward the lumen. The epithelium is multilayered, extremely cylindrical, and characterized by irregularly aligned ovoid/round nuclei. In addition, in the BPH group, the prostate tissues showed severe interstitial edema, vascular congestion, and widening of the glandular luminal area. No evidence of interacinar fibrosis was found in the ventral lobe of the animals belonging to the BPH group (Fig. 1B-D).

Nonetheless, in the treated groups, the pattern of lesions shows similarity to the patterns witnessed in the BPH control group; however, treatments using finasteride and A. maurorum hydroalcoholic extracts led to a noticeable decrease in the severity and extent of pathological lesions in prostatic tissues. In detail, the treated group showed mild interstitial edema and vascular congestion, a significant decrease in the thickness of the glandular epithelium, and mild epithelial hypertrophy and hyperplasia without the formation of polyps (Fig. 2A-C). Based on the semi-quantitative analysis of such changes in histopathology, one may observe the most therapeutic contributions in the group treated using A. maurorum at a dosage of 400 mg/kg, followed by finasteride and A. maurorum 200 mg/kg (Table 4).

Fig. 2
figure 2

H&E staining conducted for the animals belonging to the groups treated using finasteride and A. maurorum extracts. The sections prepared from the BPH rats’ prostates treated using finasteride (5 mg/kg) (A), A. maurorum (200 mg/kg) (B), and A. maurorum (400 mg/kg) (C) indicated a significant decline in the hypertrophy and hyperplasia of the glandular epithelium (square) and also mild interstitial edema and vascular congestion (arrowhead)

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Table 4 Histopathological scores of prostates in different groups
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In addition, the epithelial hyperplasia development was assessed by measuring the thickness of glandular epithelium belonging to the ventral prostates in various groups. As Fig. 3 illustrates, the BPH group showed the maximum average values of epithelial thickness. It is noteworthy that the treatment using finasteride and A. maurorum extracts led to a significant decrease in the thickness of the epithelial layer in comparison with that in the BPH group (p < 0.0001). A comparison between the treated groups indicated that the A. maurorum 400 mg/kg showed the minimum average values of epithelial thickness. However, a significant difference was only observed between low and high doses of A. maurorum extracts (p < 0.0036). Also, as the figure shows, in all treatment groups, the average values of this parameter are higher than those of the sham control group (p < 0.0001).

Fig. 3
figure 3

The mean ± SD values for ventral prostate epithelial thicknesses in various groups are displayed. Statistical significances are indicated at p ≤ 0.05, with p-values shown above the columns

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Prostatic and serum levels of testosterone

According to Fig. 4, the prostatic and serum testosterone levels were higher in the animals with BPH compared to the sham control (p < 0.0001). The treatments of the rats suffering from hyperplasia using finasteride and A. maurorum at high and low dosages resulted in a significant decline of such parameters compared to the BPH group (p < 0.0001). Furthermore, it is noteworthy that at a dosage of 400 mg/kg, the extract was more effective in decreasing the prostatic and serum hormone level in comparison with A. maurorum at a dosage of 200 mg/kg, but this difference was statistically significant, only about the serum testosterone level (p < 0.05). In all treatment groups (Alhagi 200, Alhagi 400, and Finasteride), the level of both parameters is the same as those parameters in the sham control group (p > 0.05); however, the level of serum testosterone in the sham control group is lower than its level in the Alhagi 200 group (p = 0.0026).

Fig. 4
figure 4

The testosterone levels in serum (A) and prostate (B) in various groups are provided as Mean ± SD. The level of statistical significance is p ≤ 0.05, and the p-values have been presented above the columns

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Oxidative stress parameters in prostate tissue

Figure 5 clearly shows that the BPH induction (in the positive control group) led to increased MDA concentration (p < 0.0001) and thereby reduced TAC level (p = 0.0008) compared to the sham control group. Furthermore, the concentration of MDA in the Alhagi 400 and Finasteride groups is lower compared to that in the BPH group (p < 0.0001). In addition, the Alhagi 200 group indicated a noticeable difference at p = 0.0018 in comparison with the BPH group.

Fig. 5
figure 5

The values associated with the MDA (A) and TAC (B) prostatic levels for various groups are shown as Mean ± SD. The level of statistical significance is p ≤ 0.05, and the p-values have been presented above the columns

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In all treatment groups (Finasteride, Alhagi 200, and Alhagi 400), the TAC concentration increased in comparison with the positive control (BPH group) at the p = 0.0016, p = 0.0112, and p = 0.0004 levels, respectively. In all treatment groups (Alhagi 200, Alhagi 400, and Finasteride), the levels of both parameters are nearly the same as those levels in the sham control group (p > 0.05).

5-Alpha reductase and androgen receptor gene expression in prostate

Figure 6 evidently illustrates that the expression of androgen receptor and 5-alpha reductase genes in prostatic cells showed a significant increase following the BPH induction compared to the sham control group (p < 0.0001). The 5-alpha reductase gene expression declined significantly in the Alhagi 400 and Finasteride groups compared to the BPH group (p = 0.0199 and p < 0.0001, respectively). In addition, the level of androgen receptor gene expression declined for the prostates of the animals in the Alhagi 400 and Finasteride groups (p = 0.0328 and p = 0.0069, respectively) compared to the BPH group. Although these two indices declined in animals treated with Alhagi 200 in comparison to BPH group, but these differences were not significant (p > 0.05). Also both parameters in the Alhagi 400 and Finasteride groups had the same levels as those levels in the sham control group (p > 0.05).

Fig. 6
figure 6

The 5-alpha reductase (A) and androgen receptor (B) genes expression levels in various groups after a 28-day treatment. The target genes underwent normalization to β-actin as the housekeeping control gene. The experiments were completely conducted in triplicate (n = 3), and the relevant data have been presented as means ± SD. Also the considered significance level was p ≤ 0.05, and the p-values have been presented above the columns

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Discussion

The enlargement of the prostate gland as a result of the proliferation of epithelial and stromal elements that leads to benign prostatic hyperplasia is among the most common urological diseases among aging men. One may typically manage such a condition via different techniques, such as surgical procedures and pharmacological therapy [45]. Now, medicinal plants characterized by richness in secondary metabolites are utilized in order to alleviate and treat a variety of complications, e.g., BPH [36, 46, 47].

As a medicinal herb rich in flavonoids and phenolic compounds, e.g., quercetin and kaempferol, Alhagi maurorum may effectively treat urinary tract disorders, e.g. nephrotoxicity, chronic kidney disease, and urolithiasis [24, 26, 48, 49]. Such an issue motivated us to determine the effect of the hydroalcoholic extract obtained from camelthorn on the rat model with the BPH induced via testosterone.

According to our results, the animals in the positive control group showed prominent signs of benign prostatic hyperplasia, which included increased testosterone levels in both the prostate and serum, higher prostatic index and weight, evident histopathological changes, and higher levels of gene expressions for the androgen receptor and 5-alpha reductase in the prostate. Such findings are in agreement with those obtained in the earlier studies conducted on the benign prostatic hyperplasia subject [18, 46, 47, 50, 51]. The extract of A. maurorum could positively alter these parameters, and for nearly all of the evaluated parameters, its impact was comparable to the effect of finasteride. Benign prostatic hyperplasia results from the progressive growth of the cells found in the prostate, which results in uncontrolled enlargement and hyperplasia [3]. As a result, the increased prostate weight may serve as a symptom of benign prostatic hyperplasia [50, 52]. Given that the weight of the prostate may increase in line with the body weight, the prostate index (the prostate weight divided by the body weight) serves as the main indicator. The present investigation showed an increase in the prostate index (PI) and the prostate weight of the positive control group. In addition, according to the histopathology of the same group of rats, the acinar epithelial hypertrophy and hyperplasia confirm the prostate enlargement and the BPH induction. The use of the A. maurorum extract reduced the increase in prostatic index, weight, and histopathological changes. The higher dose of the same medicinal herb indicated the effects comparable to those of the finasteride.

The present investigation showed that the testosterone level in both prostate and serum in the BPH group was higher when compared to the sham control group. As said before, the androgens, such as testosterone and, in particular, DHT and also the androgen receptor, have a critical role in the normal function, development, and growth of the prostate gland. The higher testosterone levels, higher expression of the androgen receptor and 5-alpha reductase genes in the BPH group serve as key factors affecting the prostate weight gain, index, and histopathological changes in the BPH group. This is attributable to the fact that testosterone is converted into DHT by the activity of the 5-alpha reductase enzyme. The increased activity and concentration of the enzyme along with its expression results in elevated levels of dihydrotestosterone. This leads to logical prostatic hypertrophy, and hyperplasia, followed by prostate enlargement, and its increased index and weight. These parameters were reduced after the treatment using finasteride and A. maurorum. Also, the histopathological changes and the prostatic weight gain and index were improved as well. It is noteworthy that a few hours after castration in the animals, both the DHT and testosterone levels decrease over time. Nonetheless, the decreased concentration of DHT in the prostate is more significant, and it declines to 3% of its normal levels after 72 h. However, the testosterone level in the serum indicates a sharper decline and declines to 4% of its normal levels after 3 h. Such a difference can be attributed to the fact that, contrary to its role in the serum, DHT serves as the main androgen in the prostate gland, and the prostate gland shows a higher 5-α reductase activity even in comparison with that in seminal vesicles [53]. As a result, given the time course of our investigation and by considering the castration of the animals, one may consider it logical to hypothesize that the testosterone level assayed in the rats’ prostate or serum in the Finasteride, treatments, and BPH groups was the testosterone propionate to the exogenous administration. According to the obtained results, the testosterone level in the sham control group which was not subject to castration surgery, was in the normal range contrary to the BPH group.

Another finding of the study was that we witnessed the effect of antioxidant characteristics of the Alhagi extract on the prostate tissue for the increased TAC levels and decreased MDA levels. The overproduction of the reactive oxygen species and thereby the augmentation of the oxidative stress are effective in cancer development and the pathogenesis of prostatic hyperplasia [54]. Also, it is shown that the DNA damage, oxidative stress, and chromosomal aberrations were significantly higher in pre-operative BPH subjects in comparison with the controls [55].

The present investigation evaluated the total antioxidant capacity (TAC) and malondialdehyde (MDA) as two indicators of oxidative stress in prostate gland tissue. As the primary and final product of the peroxidation of lipids, MDA is a long-lived and highly reactive agent that causes irreversible damage to the proteins and nucleic acids. Thus, MDA has been investigated as a sign of oxidative stress [56, 57].

According to the obtained results, benign prostatic hyperplasia led to increased MDA levels and decreased TAC in the tissues of the prostate gland. Nonetheless, both TAC and MDA levels returned to their normal levels following the administration of A. maurorum and Finasteride.

It is noteworthy that the higher MDA levels in the prostate can be attributed to the increased generation of oxygen free radicals. This may result in reduced concentration of the antioxidants due to their higher consumption rates. The decreased TAC level in the prostate gland indicates that the reactive oxygen species generated due to benign prostatic hyperplasia have a higher chance of damaging the prostate cells’ components. In general, the A. maurorum herb utilized in the present investigation can inhibit the oxidative stress resulting from benign prostatic hyperplasia in prostate tissues. Such a protective effect is potentially caused by the high antioxidant capacity of the herb as shown by the DPPH, and its rich content of flavonoids, phenols, and the other compounds isolated from the extract of the herb in the present investigation. Such compounds help prevent the excessive generation of reactive oxygen species (ROS) and decrease oxidative stress. Regarding the same issue, earlier investigations have indicated the antioxidant activity of the bioactive metabolites isolated from the hydroethanolic extract of A. maurorum via the GC–MS analysis in this evaluation [58,59,60,61,62].

Conclusion

By employing histopathological and biochemical analyses and molecular PCR, our investigation strongly supports the effectiveness of the extract of A. maurorum used as an adjuvant treatment for benign prostatic hyperplasia in a dose-dependent mode. Such a finding was approved by decreased prostatic index and weight and testosterone levels, downregulation of androgen receptor and 5-alpha reductase, lowered MDA levels, increased TAC levels, and regression of stromal and epithelial hypertrophy and hyperplasia in experimental BPH animals. According to these results, these protective effects are ascribable to reduced oxidative stress in the prostate gland. Nonetheless, more pharmacological, clinical, and biochemical studies are required to completely understand the other molecular mechanisms by which A. maurorum mediates such effects.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

5-ARIs:

5α-Reductase inhibitors

ANOVA:

Analysis of variance

AR:

Androgen receptor

BPH:

Benign prostatic hyperplasia

BW:

Body weight

cDNA:

Complementary deoxyribonucleic acid

DHT:

Dihydrotestosterone

DPPH:

1,1-Diphenyl-2-picrylhydrazyl

GC–MS:

Gas chromatography-mass spectrometry

MDA:

Malondialdehyde

NIH:

National Institute of Health

P.O.:

Orally

PCR:

Polymerase chain reaction

PI:

Prostatic index

PW:

Prostate weight

RNA:

Ribonucleic acid

ROS:

Reactive oxygen species

RPA:

Reducing power assay

RT:

Retention time

S.C.:

Subcutaneously

SD:

Standard deviation

TAC:

Total antioxidant capacity

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Acknowledgements

The authors would like to thank the authorities of the Faculty of Veterinary Medicine, Razi University, for their cooperation.

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Authors and Affiliations

  1. Department of Basic Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah-Sheikh-E- Tousi Blvd, Kermanshah, 6715685414, Iran

    Fatemeh Hoseinpour, Mohammad Mohsen Salari Asl, Farshad Zare & Iman Ahmadi Zanjani

  2. Department of Pathobiology, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran

    Mohammad Hashemnia

  3. Department of Clinical Sciences, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran

    Hadi Cheraghi

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Contributions

All authors have made a significant contribution to the work and have approved the final version of the manuscript. F.H: Conceptualization, Methodology, Supervision, Project administration, Formal analysis, Writing—original draft; and Writing—review & editing. M.H: Methodology, Histopathological assessments, Formal analysis. H.Ch: Methodology, Gene expression management, Formal analysis. M.M.S.A., F.Z. and I.A.Z: Resources, Investigation, Data curation.

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Correspondence to Fatemeh Hoseinpour.

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Ethics approval: All procedures followed in the present investigation were confirmed by the Ethical Committee of Experimental Animals of Razi University with the No. IR.RAZI.REC.1401.022 ethical code.

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Hoseinpour, F., Hashemnia, M., Cheraghi, H. et al. Protective effect of the hydroethanolic extract of camelthorn (Alhagi maurorum) on benign prostatic hyperplasia induced by testosterone in rats. BMC Complement Med Ther 25, 136 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12906-025-04862-6

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  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12906-025-04862-6

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BMC Complementary Medicine and Therapies

ISSN: 2662-7671

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