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A suggested scheme of the effect of CC on related receptors and coactivators in the pathogenesis of BPH.: Testosterone is converted into dihydrotestosterone (DHT) by the action of 5α-reductase (5AR). While DHT binds to the androgen receptor (AR), steroid receptor coactivator 1 (SRC1), a classical type I AR co-regulator, is recruited to the DHT-AR bind. On the other hand, aromatase converts testosterone into estradiol, which also forms a bind with the estrogen receptor α (ERα). The DHT-AR-SRC1 complex and estradiol-ERα bind enter the nucleus and acts as transcription factors, resulting in proliferation of the prostate cells. During the described pathogenesis of benign prostatic hyperplasia (BPH), Cinnamomi Cortex (CC) inhibits 5AR, AR, SRC1 and ERα, suggesting its possibility for BPH treatment.
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Cinnamomi cortex (dried bark of Cinnamomum verum) is an important drug in Traditional Korean Medicine used to improve blood circulation and Yang Qi. Benign prostatic hyperplasia (BPH) is a common chronic disease in aging men. This study was conducted to determine the effect of Cinnamomi cortex water extract (CC) on BPH. BPH was induced by a pre-4-w...
Citations
... Herbs and medicinal plants including willow herb, pumpkin seed, maritime pine bark, rye pollen, tomato, Pygeum africanum bark and saw palmetto fruit are particularly useful in the management of BPH largely due to their reduced side effects and high phytochemical content. A number of these beneficial plants contain active ingredients including phytosterols, β-sitosterol and lectins (Choi et al., 2016;Csikós et al., 2021;Fagelman & Lowe, 2002), also present in the Juglans regia (Delaviz, Mohammadi, Ghalamfarsa, Mohammadi, & Farhadi, 2017;Mollica et al., 2017). ...
Benign prostatic hyperplasia (BPH) and prostatic cancer are aging-associated urological conditions in men. While significant advances have been made in relation to treatment, poor response, treatment resistance and adverse side-effects limit currently available therapies. The possible antiproliferative and/or ameliorative potentials of Juglans regia have been reported, however, there is a dearth of scientific information on its effect on BPH or prostatic cancer. In this study, in-vivo and in-vitro studies were used to assess the possible benefits of fresh walnut fruits extract in BPH or prostate cancer. High-performance liquid chromatography coupled with electro spray ionization and quadrupole-time-of-flight mass spectrometry (HPLC-ESI-Q-TOF) was used to assess the chemical profile of the plant extract. The anti-proliferative activity of Juglans regia extract was tested against normal and cancerous human prostate cell line by using the iCELLigence real-time and label-free cell analysis system. The ameliorative potential of fresh fruits Juglans regia extract was assessed by administering the extract at 50 and 100 mg/kg body weight to rats with testosterone induced BPH. Analysis of phytochemicals in Juglans regia revealed a high concentration of phenolic acids and flavonoids, Juglans regia also showing time- and dose-dependent anti-proliferative activity against prostate cancer cells, and reversed biochemical and histomorphological changes induced by testosterone-induced BPH.
... Prostate enlargement otherwise known as benign prostatic hyperplasia (BPH) occurs in 50% of men aged over 50 years (Berry et al., 1984). It is an increase in the prostate size that is unconnected with cancerous features but described as proliferation of the smooth muscles and epithelial cells (Choi et al., 2016). Some of the clinical symptoms include frequent urination, troubled urine emptying, weak stream, and inability to control bladder (Berry et al., 1984). ...
... Along with the decrease in serum T levels, the activities of 5-AR and AR are increased. After conversion of T to DTH by 5-AR, DTH binds to AR. Androgen/AR signaling influences the development of BPH by both the autocrine and paracrine pathways, including promoting the growth of prostate epithelial and stromal cells, in addition to EMT (Choi et al., 2016;Wen et al., 2015;Thomson et al., 2008). In this study, E 2 and DTH serum levels and the E 2 /T ratio were significantly increased in adult rats with BPH, while treatment with KCF reversed this phenomenon. ...
Background:
Benign prostatic hyperplasia (BPH) is a common disease in older men worldwide. However, there is currently no effective treatment for BPH. Bushen Tongluo Formula (Kidney-supplementing and collaterals-unblocking formula [KCF]) is a traditional Chinese medicine formula commonly used to ameliorate the symptoms of BPH, although the specific molecular mechanisms remain unclear.
Purpose:
We aimed to discover the effects and potential mechanisms of KCF against BPH.
Methods:
Sixty male SD rats were randomly assigned to one of six group (n = 10): control, low-dosage KCF, medium-dosage KCF, high-dosage KCF, BPH model, and finasteride. A rat model of BPH was established by surgical castration followed by subcutaneous injection of testosterone propionate (TP) for 4 weeks. After treatment, the prostate index, histopathological staining, serum levels of estradiol (E2) and dihydrotestosterone (DHT), protein/mRNA levels of E-cadherin, TGF-β1, caspase-3, Ki67, and vimentin, abundances of serum metabolites, and the proliferation, cell cycle, and apoptosis of BPH-1 cells were documented.
Results:
KCF treatment for 4 weeks reduced the prostate volume and prostate index, alleviated histopathological changes to the prostate of rats with TP-induced BPH, decreased serum levels of E2 and DHT, reduced protein/mRNA levels of TGF-β1 and vimentin, and increased E-cadherin levels. Moreover, KCF-spiked serum inhibited proliferation of BPH-1 cells, blocked the cell cycle, and promoted apoptosis. KCF was also found to regulate the contents of three metabolites (D-maltose, citric acid, and fumaric acid).
Conclusion:
The present study was the first to report that KCF exhibited therapeutic effects against BPH by regulating energy metabolism and inhibiting epithelial-mesenchymal transition in prostate tissues. Hence, KCF presents a viable treatment option for BPH.
... The prostate weights of the finasteride and HT080 groups were significantly reduced in comparison with the BPH group, demonstrating the ability of HT080 in inhibiting the BPH. It has been reported in animals that C. verum bark, which is similar in major components to C. cassia bark, and ellagic acid, the major component of R. laevigata fruit, are effective in suppressing BPH [31,32]. It is predicted that both C. cassia and R. laevigata contributed to the inhibitory effects of HT080 on BPH. ...
Benign prostatic hyperplasia (BPH) is the most common condition in elderly men that is characterized by an increase in the size of the prostate gland. Cinnamomum cassia and Rosa laevigata have been reported to treat the symptoms associated with BPH. The aim of this study was to evaluate the effects of HT080, an herbal extract of C. cassia and R. laevigata, on a testosterone propionate (TP)-induced BPH rat model. The rats received a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks to induce BPH. Rats were divided into four groups: group 1 (sham), group 2 (BPH, TP alone), group 3 (Fina, TP + finasteride 1 mg/kg/day), and group 4 (HT080, TP + HT080 200 mg/kg/day). At the end of the experiment, all rats were sacrificed, and their prostate glands were removed, weighed, and subjected to histopathological examination and western blot analyses. Serum testosterone and dihydrotestosterone (DHT) levels were determined. In addition, serum alanine and aspartate aminotransferase levels were measured to evaluate the toxicity in the liver. The Hershberger bioassay was also conducted to investigate the effects of HT080 on androgenic and antiandrogenic activities. In the BPH model, the prostate weight, prostate index, prostate epithelial thickness, and serum testosterone and DHT levels in the HT080 group were significantly reduced compared to the BPH group. Histological studies showed that HT080 reduced prostatic hyperplasia. The protein expression of androgen receptor from the HT080 group was significantly reduced in comparison with the BPH group (p < 0.05). HT080 also induced apoptosis by regulating Bcl-2 and Bax expression. In addition, HT080 showed no toxicity in the liver and did not exhibit androgenic and antiandrogenic activities. Our finding revealed that HT080 can be a potential candidate for the treatment of BPH by regulating androgen receptor signaling and apoptosis.
... Androgens promote the proliferation of epithelial cells or stromal cells within the PG in autocrine or paracrine manners. This action leads to an imbalance of the proliferation and apoptosis of PG cells, which is considered to be an important cause of BPH [16]. In the PG, testosterone is converted to dihydrotestosterone (DHT) by the enzyme steroid 5-alpha reductase 2 (SRD5A2), which is a potent androgen because of its high binding ability to androgen receptors (ARs) [17]. ...
Benign prostatic hyperplasia (BPH) is a chronic disease that affects the quality of life of older males. Sinomenine hydrochloride (SIN) is the major bioactive alkaloid isolated from the roots of the traditional Chinese medicinal plant Sinomenium acutum Rehderett Wilson. We wondered if the SIN administration exerted a regulatory effect on BPH and its potential mechanism of action. Mice with testosterone propionate-induced BPH subjected to bilateral orchiectomy were employed for in vivo experiments. A human BPH cell line (BPH-1) was employed for in vitro experiments. SIN administration inhibited the proliferation of BPH-1 cells (p < 0.05) by regulating the expression of androgen-related proteins (steroid 5-alpha reductase 2 (SRD5A2), androgen receptors, prostate-specific antigen), apoptosis-related proteins (B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)) and proliferation-related proteins (proliferating cell nuclear antigen (PCNA), mammalian target of rapamycin, inducible nitric oxide synthase) in vitro. SIN administration decreased the prostate-gland weight coefficient (p < 0.05) and improved the histological status of mice suffering from BPH. The regulatory effects of SIN administration on SRD5A2, an apoptosis-related protein (Bcl-2), and proliferation-related proteins (PCNA, matrix metalloproteinase-2) were consistent with in vitro data. SIN exerted a therapeutic effect against BPH probably related to lowering the SRD5A2 level and regulating the balance between the proliferation and apoptosis of cells. Our results provide an important theoretical basis for the development of plant medicines for BPH therapy.
... Serenoa repens, also known as saw palmetto, is widely used as an herbal medicine for the treatment of BPH (Vela-Navarrete et al., 2005). In addition, studies on other natural products are being actively conducted (Choi et al., 2016;Cordaro et al., 2017;Song et al., 2020;Mitsunari et al., 2021). In this study, we investigated whether GUWE could relieve BPH. ...
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Background
Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources.
Purpose
In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis.
Methods
To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells.
Results
In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity.
Conclusion
These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.
... Phytotherapeutics have recently received much attention as an efficient and safe treatment strategy for BPH patients, and many plants have shown anti-BPH effects [12]. Several traditional medicine prescriptions or herbs have been reported for their successful impact on BPH, such as Saw palmetto and Rubus coreanus [13], Zi-Shen Pill (ZSP), which consists of different medicinal plants [14], Curcuma longa [15], Scutellaria baicalensis [16], Yukmijihwang-tang [17], curcumin [18] and Cinnamomi cortex [19]. Marjoram (Origanum majorana L.) is a herb with fragrant leaves that is commonly used in flavoring and culinary applications [20,21]. ...
Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat's body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms.
... The antibodies used in this study were shown in Supplementary Table 1. BPH was induced by subcutaneous injection of TP (5 mg/kg) dissolved in corn oil containing 5% ethanol for 8 weeks, as described previously [36]. In detail, the rats (n = 24) were randomly divided into two groups, either the vehicle group (n = 6) that were subcutaneously injected with corn oil containing 5% ethanol, or the TP group (n = 18) that were subcutaneously injected with TP. ...
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Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.
... In the USA and Europe,~50% of patients with BPH use phytotherapeutic drugs alone or with pharmacologic drugs to treat BPH [15,16]. Phytotherapeutic supplements, including Serenoa repens, Pygeum africanum, Cinnamomi cortex, Asteris Radix et Rhizoma, and Pao Pereira Extract have been evaluated as complementary treatments for the management of BPH in preclinical and clinical trials [17][18][19][20][21]. Thus, phytotherapeutic supplements may alternatively be an essential approach in the treatment of BPH as well as BPH-induced ED. ...
Benign prostatic hyperplasia (BPH) is one of the most prevalent conditions among aged men. The use of 5α-reductase inhibitors (5-ARIs) to treat BPH was linked to erectile dysfunction (ED). Many medicinal plants and secondary metabolites are used in the management of ED. Onion (Allium cepa L.) is an economically affordable vegetable with vital phytochemicals and biological functions. The study aimed to identify the beneficial effects of onion juice on dutasteride (a 5-ARI)-induced ED. Rats were divided into two groups (n = 5 per group): control and dutasteride-treated rats (0.5 mg/kg/day). Dutasteride was administered in drinking water for 12 weeks. Experiments were performed at the end of the 12th week. In vivo erectile responses were measured before and after intracavernosal injection of onion. Relaxant responses to onion juice were examined in the corpus cavernosum (CC). Acetylcholine (ACh)-, electrical field stimulation (EFS)-, sodium nitroprusside (SNP)-induced relaxation responses in CC tissues were evaluated in the absence and presence of onion juice. Total intracavernosal pressure (ICP) and ICP/ mean arterial pressure were significantly reduced in dutasteride-treated rats (1881.14 ± 249.72 mmHg, P < 0.001;0.26 ± 0.03, P < 0.01) as compared to control rats (4542.60 ± 429.19 mmHg, 0.51 ± 0.05), which was normalized after the intracavernous administration of onion (3288.60 ± 185.45 mmHg, 0.58 ± 0.04). Onion markedly induced relaxant responses in control (72.5 ± 4.7) and dutasteride-treated (66.5 ± 2.7) groups after precontraction with phenylephrine. Relaxation responses to onion were partially inhibited after precontraction with KCl (32.5 ± 3.1, P < 0.001). The relaxant responses to ACh (14.9 ± 4.2, P < 0.01) were diminished in dutasteride-treated CC) compared to control CC (59.8 ± 3.4), which was enhanced after the incubation with onion (36.6 ± 4.8). There were no differences in relaxation response to SNP among all groups. However, relaxation response to SNP was reduced in dutasteride-treated CC at 1 μM (P < 0.05) and 10 μM dosages (P < 0.001), which was partially increased after the incubation with onion at 10 μM dosage (P < 0.01). The presence of onion did not change the reduction in EFS-caused relaxation in the dutasteride-treated group. The current data suggest that red onion juice has a restorative effect on erectile function and endothelium-dependent relaxation response following the treatment of dutasteride.
... Prostate enlargement otherwise known as benign prostatic hyperplasia (BPH) occurs in 50% of men aged over 50 years (Berry et al., 1984). It is an increase in the prostate size that is unconnected with cancerous features but described as proliferation of the smooth muscles and epithelial cells (Choi et al., 2016). Some of the clinical symptoms include frequent urination, troubled urine emptying, weak stream, and inability to control bladder (Berry et al., 1984). ...
Background and Purpose: Men of age 40 years and above are at risk of non-cancerous enlargement of the prostate gland also known as benign prostatic hyperplasia (BPH). Adverse drug reactions and treatment relapse limit the effectiveness of orthodox pharmacotherapies. This study evaluated the effect of Cassia fistula hydroalcoholic extract on BPH. Methods: BPH was induced in Wistar rats by subcutaneous injection of 10 mg/kg/day of testosterone propionate (TP) for 7 days. The rats were randomly allotted to five groups: corn oil only; finasteride (FS) 5 mg/kg/day; and C. fistula extract at doses of 100, 200, and 400 mg/kg/day. A sixth group in which BPH was not induced received only the vehicle. At the end of 28 consecutive days of treatment, prostate and testicular weights and indices were evaluated. The in vitro antioxidant capacity of the extract was evaluated using the DPPH free radical scavenging method. Results: The extract showed a very strong free radical scavenging activity with IC50 value of 1.58 µg/mL (IC50 of gallic acid = 0.63 µg/mL) due to the presence of secondary metabolites. The results also showed significant (P?0.0001) reduction in the prostate weight, prostatic index, testes weight, and testes index of C. fistula extract-treated rats when compared with the untreated BPH group. Conclusion: These results suggest that C. fistula extract possesses potentials as a remedy for the treatment of BPH.
