curcumin and Prostatic-Hyperplasia

The prostate is an androgen-sensitive organ that needs proper androgen/androgen receptor (AR) signals for normal development. The progression of prostate diseases, including benign prostate hyperplasia (BPH) and prostate cancer (PCa), also needs proper androgen/AR signals. Tissue recombination studies report that stromal, but not epithelial, AR plays more critical roles via the mesenchymal-epithelial interactions to influence the early process of prostate development. However, in BPH and PCa, much more attention has been focused on epithelial AR roles. However, accumulating evidence indicates that stromal AR is also irreplaceable and plays critical roles in prostate disease progression. Herein, we summarize the roles of stromal AR in the development of normal prostate, BPH, and PCa, with evidence from the recent results of in vitro cell line studies, tissue recombination experiments, and AR knockout animal models. Current evidence suggests that stromal AR may play positive roles to promote BPH and PCa progression, and targeting stromal AR selectively with AR degradation enhancer, ASC-J9, may allow development of better therapies with fewer adverse effects to battle BPH and PCa.

Topics: Animals; Curcumin; Humans; Male; Neoplasm Proteins; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction

Benign prostatic hyperplasia (BPH) is the main prevalent disorder in men over forty years, usually revealing itself with lower urinary tract symptoms. Despite the existence of different treatments, the incidence of BPH is increasing, so further studies for better management are a necessity. This research was designed to assay the effectiveness of nano-micellar curcumin on biomedical indicators of patients with BPH.. The present research was a double-blind, randomized, and placebo-controlled trial that enrolled fifty-two patients with BPH between June 2021 and December 2021. Participants were randomized to receive 160 mg/d nano-micellar curcumin (n = 26) or placebo (n = 26) as soft gel during 3 months. Primary end point was changes in International Prostate Symptoms Score (IPSS). Data gathering was occurred using a standard inquiry form and measuring other biomedical parameters based on routine laboratory techniques. To compare the distribution of demographics and covariates, independent t-test and Chi-square were used.. Nano-micellar curcumin had significant effect on IPSS (p value: 0.010), low effect on high-sensitive C-reactive protein (hs-CRP) (p value: 0.032), and low to intermediate effect on malondialdehyde (MDA) (p value: 0.014) level as secondary end points after the intervention. The effect of nano-micellar curcumin on other parameters was negligible.. Overall, this trial indicated 3-month intake of nano-micellar curcumin had considerable effects on IPSS as the most common clinical symptom and also two biomedical parameters including serum hs-CRP and MDA.. http://www.irct.ir : IRCT20170430033730N3.

Topics: C-Reactive Protein; Curcumin; Humans; Lower Urinary Tract Symptoms; Male; Micelles; Prostate; Prostatic Hyperplasia; Treatment Outcome

The aim of this registry evaluation study was to compare, in symptomatic BPH patients, two management plans based on a currently validated standard treatment [defined as the best standard management (BSM)] including or not curcumin (administered as Meriva®) as a further complementary adjuvant element. Signs and symptoms were evaluated using the International Prostate Symptom Score (IPSS). SUBJECTS, METHODS: The study was carried out on a total of 61 subjects. 33 subjects (mean age 58.6;5.3) completed the survey with at least 24 weeks of treatment with Meriva® in association with the BSM. The BSM-alone control group consisted of 28 volunteers of similar age (58.4 years;3.4) and severity of the condition. The range of inclusion age was 55-65. No other clinical or metabolic problems were present. Meriva® was administered at the dosage of 2 tablets/day (2 x 500 mg of Meriva®/day, corresponding to 2 x 100 mg curcumin/day) with a compliance values > 95% as evaluated by the number of tablets used according to medical recommendation. No other drugs or food supplement were used during the study.. All IPSS scores, with the exception of the stream weakness score in the BSM group, were improved (p<0.05 vs. inclusion) in both groups. The overall results in the Meriva® group were significantly better than in the BSM-only group (p<0.05). No side effects were recorded. The quality of life improved in both groups, but was significantly better in the Meriva® group (p<0.01). There was also a significantly more important decrease in clinical and subclinical episodes of urinary infections and urinary block in the Meriva® group (p<0.01).. In patients with BPH, the addition of Meriva® to the standard treatment contributed to the reduction of signs and symptoms of the disease without causing any significant additional side effect. This pilot experience suggests a potential novel clinical application of curcumin, and further studies aimed at selecting the most appropriate dosages and length of treatment as well as the possibility to including longer treatments will, undoubtedly, validate and optimize the role of Meriva® in the management of BPH.

Topics: Aged; Curcumin; Drug Delivery Systems; Humans; Lecithins; Male; Middle Aged; Pilot Projects; Prostate; Prostatic Hyperplasia; Quality of Life; Surveys and Questionnaires; Urination Disorders

Benign prostatic hyperplasia (BPH) is a progressive urological disease occurring in middle-aged and elderly men, which can be characterized by the non-malignant overgrowth of stromal and epithelial cells in the transition zone of the prostate. Previous studies have demonstrated that lycopene can inhibit proliferation, while curcumin can strongly inhibit inflammation. This study aims to determine the inhibitory effect of the combination of lycopene and curcumin on BPH.. To induce BPH models in vitro and in vivo, the BPH-1 cell line and Sprague Dawley (SD) rats were used, respectively. Rats were divided into six groups and treated daily with a vehicle, lycopene (12.5 mg/kg), curcumin (2.4 mg/kg), a combination of lycopene and curcumin (12.5 mg/kg + 2.4 mg/kg) or finasteride (5 mg/kg). Histologic sections were examined via hematoxylin and eosin (H&E) staining and immunohistochemistry. Hormone and inflammatory indicators were detected via ELISA. Network pharmacology analysis was used to fully predict the therapeutic mechanism of the combination of lycopene and curcumin on BPH.. Combination treatment significantly attenuated prostate hyperplasia, alleviated BPH pathological features and decreased the expression of Ki-67 in rats. The upregulation of the expression of testosterone, dihydrotestosterone (DHT), 5α-reductase, estradiol (E2) and prostate-specific antigen (PSA) in BPH rats was significantly blocked by the combination treatment. The expression levels of inflammatory factors including interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α were strongly inhibited by the combination treatment. From the network pharmacology analysis, it was found that the main targets for inhibiting BPH are AKT1, TNF, EGFR, STAT3 and PTGS2, which are enriched in pathways in cancer.. The lycopene and curcumin combination is a potential and more effective agent to prevent or treat BPH.

Topics: Animals; Cell Proliferation; Curcumin; Humans; Inflammation; Lycopene; Male; Plant Extracts; Propionates; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Testosterone; Testosterone Propionate

Curcuma longa L is traditionally used as an anti-inflammatory remedy in Chinese traditional medicine. Curcuma oil (CO), a lipophilic fraction from Curcuma longa L. has been reported to have anti-proliferative, anti-inflammatory and anti-oxidant activities. However, CO has never been investigated for its possible therapeutic effects on benign prostatic hyperplasia (BPH).. The study is thus to determine the therapeutic effects of curcuma oil on BPH and also the possible mechanism (s) of action.. A BPH-1 cell line and Sprague Dawley (SD) rats were used to establish BPH models in vitro and in vivo, respectively. Rats were treated by CO (2.4, 7.2 mg/kg/i.g.) and finasteride (5 mg/kg/i.g.), respectively. Histological changes were examined by hematoxylin and eosin (H&E) staining. Protein expression was analyzed for 5α-reductase (5AR), dihydrotestosterone (DHT), interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by ELISA. Ki-67, Caspase-8,-9 and -3 expressions were evaluated via immunohistochemistry (IHC).. CO effectively induced apoptosis in BPH-1 cells. BPH was successfully established by administration of testosterone propionate (TP) in rats, which upregulated both 5α-reductase expression and DHT production. Importantly, TP establishment significantly stimulated the phosphorylation of p65, one subunit of NF-κB, thus led to activation of the NF-κB signaling pathway in prostatic tissues of rats. In turn, the activation of NF-κB pathway induced concomitant upregulation of proinflammatory factors IL-1β, IL-6, TNF-α, and COX-2 and significant increase of the Bcl2/Bax expression ratio for enhanced cell survival, contributing to the initiation and progression of BPH in rats. Notably, CO therapy significantly decreased prostate weight and hyperplasia in BPH-induced animals. Also CO was found to suppress the expression of 5α-reductase and thus the production of DHT, which is essential for the amelioration of BPH. More importantly, CO was shown to suppress the activation of NF-κB pathway through decreasing the expression of phosphorylated p65 and consequently reduced the inflammatory responses and cell survival in prostatic tissues, leading to the inhibition of BPH development in rats.. Curcuma oil is very effective for ameliorating BPH in rats. The underlying mechanisms involve in reduced inflammatory responses and cell survival through suppression of the NF-κB signaling pathway by CO in prostatic tissues.

Topics: Animals; Cell Line; Cell Survival; Curcuma; Disease Models, Animal; Disease Progression; Humans; Inflammation; Male; NF-kappa B; Plant Oils; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Signal Transduction

Topics: Animals; Curcumin; Disease Models, Animal; Humans; Male; Prostatic Hyperplasia; Rats; Testosterone

In this Open Controlled Trial we administered an innovative formulation of food supplement with curcumin (Killox®) to test its efficacy, safety and compatibility with other drugs, in the therapy of post-surgery complications of transurethral resection of prostate (TURP) and transurethral resection of bladder (TURB), and in the prevention of late complications. Furthermore, Killox® effects were verified in subjects with benign prostatic hyperplasia (BPH).. Killox® was administered to 40 TURP patients for 20 days, to 10 TURB patients for 10 days and to 30 BPH patients for 60 days. The study was an open controlled trial, approved by the internal Review Board, with a completely independent set of retrospective observations.. In the subjects who underwent surgery the treatment warded off postoperative and late complications, whereas among controls, without anti-inflammatory therapy after surgery until one week later, 21 (52.5%) out of 40 TURP subjects and 4 (40%) out of 10 TURB subjects were still found with symptoms of inflammation and urinary burning, and they had to be treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for seven days. Moreover among controls 2 in TURP group presented an urethral stricture, and no one in TURB group. Killox® patients did not report any adverse effect and the therapy was well tolerated, instead among 21 control subjects, who were treated with NSAIDs, 7 reported nausea and epigastric pain. Also in BPH patients the product was effective in a satisfying manner, shortening the duration of irritation symptoms. Noteworthy, Killox® administration did not modify the efficacy of the other treatments. The effect of Killox® was found statistically significant vs controls.. The therapeutic activity and safety of Killox® in urology allow physicians to administer a new efficient product in substitution of NSAIDs.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Chemistry, Pharmaceutical; Chitosan; Curcumin; Dietary Supplements; Drug Administration Schedule; Humans; Male; Middle Aged; Postoperative Complications; Postoperative Period; Prostatic Hyperplasia; Transurethral Resection of Prostate

Benign prostatic hyperplasia (BPH) is one of the common male diseases, which is provoked by dihydrotestosterone (DHT) and androgen signals. Several studies showed that curcumin has various effects of prevention and treatment to diseases. We investigated whether curcumin may repress the development of BPH in male Wistar rats.. Seven weeks male Wistar rats were and divided into 4 groups (normal group, BPH group, finasteride group, curcumin group; n = 8 for each group). In order to induce BPH in rats, rats were castrated and testosterone was injected subcutaneously everyday (s.c., 20 mg/kg). Rats in the curcumin group were treated 50 mg/kg, administered orally for 4 weeks. After 4 weeks, all rats were sacrificed and their prostate and serum were analyzed.. Compared to the finasteride group as positive group, the curcumin group showed similarly protective effect on BPH in histopathologic morphology, prostate volume. Results of immunohistochemistry and western-blot showed decreased expressions of VEGF, TGF-ß1, and IGF1 were also decreased in the curcumin group.. These results suggested that curcumin inhibited the development of BPH and might a useful herbal treatment or functional food for BPH.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Blood Glucose; Blotting, Western; Body Weight; Curcumin; Disease Models, Animal; Immunohistochemistry; Insulin-Like Growth Factor I; Male; Prostate; Prostatic Hyperplasia; Rats; Rats, Wistar; Testosterone; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9(®), led to the reduction of prostate size, which could be used in future therapy.

Topics: Androgen-Binding Protein; Animals; Cell Proliferation; Cells, Cultured; Curcumin; Disease Models, Animal; Epithelial Cells; Epithelial-Mesenchymal Transition; Fibroblasts; Gene Expression; Granulocyte-Macrophage Colony-Stimulating Factor; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocytes, Smooth Muscle; Organ Size; Prolactin; Prostate; Prostatic Hyperplasia; Proteolysis; Receptors, Androgen; STAT3 Transcription Factor; Stromal Cells

Early studies suggested macrophages might play roles in inflammation-associated benign prostatic hyperplasia (BPH) development, yet the underlying mechanisms remain unclear. Here we first showed that CD68(+) macrophages were identified in both epithelium and the stromal area of human BPH tissues. We then established an in vitro co-culture model with prostate epithelial and macrophage cell lines to study the potential impacts of infiltrating macrophages in the BPH development and found that co-culturing prostate epithelial cells with macrophages promoted migration of macrophages. In a three-dimensional culture system, the sphere diameter of BPH-1 prostate cells was significantly increased during coculture with THP-1 macrophage cells. Mechanism dissection suggested that expression levels of epithelial-mesenchymal transition (EMT) markers, such as N-cadherin, Snail, and TGF-β2, were increased, and administration of anti-TGF-β2 neutralizing antibody during co-culture suppressed the EMT and THP-1-mediated growth of BPH-1 cells, suggesting THP-1 might go through EMT to influence the BPH development and progression. Importantly, we found that modulation of androgen receptor (AR) in BPH-1 and mPrE cells significantly increased THP-1 and RAW264.7 cell migration, respectively, and enhanced expression levels of EMT markers, suggesting that AR in prostate epithelial cells might play a role in promoting macrophage-mediated EMT in prostate epithelial cells. Silencing AR function via an AR degradation enhancer, ASC-J9, decreased the macrophage migration to BPH-1 cells and suppressed EMT marker expression. Together, these results provide the first evidence to demonstrate that prostate epithelial AR function is important for macrophage-mediated EMT and proliferation of prostate epithelial cells, which represents a previously unrecognized role of AR in the cross-talk between macrophages and prostate epithelial cells. These results may provide new insights for a new therapeutic approach to battle BPH via targeting AR and AR-mediated inflammatory signaling pathways.

Topics: Androgen Receptor Antagonists; Animals; Cell Line; Cell Movement; Coculture Techniques; Curcumin; Epithelial Cells; Epithelial-Mesenchymal Transition; Gene Expression; Humans; Macrophages; Male; Mice; Molecular Targeted Therapy; Prostate; Prostatic Hyperplasia; Proteolysis; Receptors, Androgen; Spheroids, Cellular; Transforming Growth Factor beta2