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Aconiti Lateralis Radix Preparata, the Dried Root of Aconitum carmichaelii Debx., Improves Benign Prostatic Hyperplasia via Suppressing 5-Alpha Reductase and Inducing Prostate Cell Apoptosis.

ABSTRACT: Benign prostatic hyperplasia (BPH) is a common disease in elderly men which can be characterized by an abnormal enlargement of the prostate associated with lower urinary symptoms. Current medications available for BPH treatment display several adverse effects; thus, the search for effective treatments with less side effects is still ongoing. In this study, we investigated the effect of Aconiti Lateralis Radix Preparata (dried root of Aconitum carmichaelii Debx.; AL), which is an herb used to treat extremely cold symptoms in traditional Korean medicine, on BPH using a testosterone propionate- (TP-) induced BPH rat model. Eight-week inguinal injection of TP induced BPH in rats, the prostate of which was displaying an abnormal proliferation. The pathological proliferation of the prostate was ameliorated by AL treatment of 4 weeks. Pathohistological changes in the prostate including epithelial thickness and lumen area were restored in AL-treated rats. Furthermore, 5?-reductase (5AR) and androgen receptor (AR), the two main factors in the pathogenesis of BPH, were decreased. In addition, the ratio of BAX and Bcl-2, an indicator of apoptosis, was increased by AL as well. Similar results were observed in AL-treated LNCaP prostate cancer cells. AL treatment suppressed the expression of the 5AR-AR axis and increased the ratio of BAX and Bcl-2. Apoptosis in the testis is considered a crucial side effect of finasteride, a 5AR inhibitor used to treat BPH. Our results showed that AL treatment did not display such effects, while finasteride treatment resulted in loss of spermatogenic cells within the prostate. Overall, these results suggest AL as a potentially safe nature-derived therapeutic agent for BPH treatment.

SUBMITTER: Park J

PROVIDER: S-EPMC6701400 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Aconiti Lateralis Radix Preparata, the Dried Root of <i>Aconitum carmichaelii</i> Debx., Improves Benign Prostatic Hyperplasia via Suppressing 5-Alpha Reductase and Inducing Prostate Cell Apoptosis.

Park Jinbong J Youn Dong-Hyun DH Um Jae-Young JY

Evidence-based complementary and alternative medicine : eCAM 20190731

Benign prostatic hyperplasia (BPH) is a common disease in elderly men which can be characterized by an abnormal enlargement of the prostate associated with lower urinary symptoms. Current medications available for BPH treatment display several adverse effects; thus, the search for effective treatments with less side effects is still ongoing. In this study, we investigated the effect of Aconiti Lateralis Radix Preparata (dried root of <i>Aconitum carmichaelii</i> Debx.; AL), which is an herb used ...[more]

PMID: 31467577

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Project description:Fuzi-Gancao herb couple is one of the commonly used herb couples involved in the traditional Chinese medicine formulations, with radix aconiti lateralis (Fuzi in Chinese) and radix glycyrrhizae (Gancao in Chinese) as a ratio of 1:1. Alkaloids and flavonoids were considered as the main active ingredients of Fuzi-Gancao herb couple. However, no analytical methods have been reported to quantitatively analyze these activity ingredients in Fuzi-Gancao herb couple simultaneously.To develop a simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds, namely, aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconitine (BAC), benzoylmesaconitine (BMA), benzoylhypaconitine (BHA), liquiritin, isoliquiritin, and licochalcone A (LCA) in Fuzi-Gancao herb couple.The chromatographic separation was achieved using a reversed phase C18 column and a mobile phase consisted of water (0.1% formic acid in water, v/v) and acetonitrile. The detection was achieved in multiple reaction monitoring modes. The optimal mass transition ion pairs (m/z) for quantitation were 646.3/586.5 for AC, 632.4/572.5 for MA, 616.3/556.4 for HA, 604.5/572.5 for BAC, 590.4/540.4 for BMA, 574.1/542.5 for BHA, 419.4/257.1 for liquiritin, 419.4/257.1 for isoliquiritin, and 339.2/121.1 for LCA.Good linearity was observed in validated concentration range for each analyte (r > 0.9992), and the intra- and inter-day precisions were <3.12% and 3.65%, respectively. The recovery ranged from 85.36% to 110.14%.The results demonstrated that the method developed was reliable, rapid, and specific. Moreover, this method was successfully applied to control the quality of Fuzi-Gancao herb couple.A simple, rapid, and sensitive UHPLC-MS/MS method for simultaneous quantitation of six alkaloid and three flavonoid compounds in Fuzi-Gancao herb couple has been developed. Abbreviations used: UHPLC-ESI-MS/MS: Ultra High Performance Liquid Chromatography-electrospray ionization-mass spectrometry; RSD: Relative standard deviations; LOD: Limit of detection; LOQ: Limit of quantification; MRM: Multiple reaction monitor; TCMs: Traditional Chinese medicines.

Project description:Radix Aconiti Lateralis Preparata (fuzi) is the processed product of Aconitum carmichaelii Debeaux tuber, and has great potential anti-myocardial infarction effects, including improving myocardial damage and energy metabolism in rats. However, the effects of Radix Aconiti Lateralis Preparata extracts in a rat model of myocardial infarction have not yet been fully illustrated. Herein, Radix Aconiti Lateral Preparata was used to prepare Radix Aconiti Lateralis Preparata extract (RAE), fuzi polysaccharides (FPS), and fuzi total alkaloid (FTA). Then, we aimed to compare the effects of RAE, FPS, and FTA in MI rats and further explore their influence on small molecules in the heart. We reported that Radix Aconiti Lateralis Preparata extract (RAE) and fuzi total alkaloid (FTA) significantly improved left ventricular function and structure, and reduced myocardial damage and infarct size in rats with myocardial infarction by the left anterior descending artery ligation. In contrast, fuzi polysaccharides (FPS) was less effective than RAE and FTA, indicating that alkaloids might play a major role in the treatment of myocardial infarction. Moreover, via matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), we further showed that RAE and FTA containing alkaloids as the main common components regulated myocardial energy metabolism-related molecules and phospholipids levels and distribution patterns against myocardial infarction. In particular, it was FTA, not RAE, that could also regulate potassium ions and glutamine to play a cardioprotective role in myocardial infarction, which revealed that an appropriate dose of alkaloids generated more obvious cardiotonic effects. These findings together suggested that Radix Aconiti Lateralis Preparata extracts containing an appropriate dose of alkaloids as its main pharmacological active components exerted protective effects against myocardial infarction by improving myocardial energy metabolism abnormalities and changing phospholipids levels and distribution patterns to stabilize the cardiomyocyte membrane structure. Thus, RAE and FTA extracted from Radix Aconiti Lateralis Preparata are potential candidates for the treatment of myocardial infarction.

Project description:BackgroundMale lower urinary tract symptoms (LUTS) occur in more than half of men above 50 years of age. LUTS were traditionally attributed to benign prostatic hyperplasia (BPH) and therefore the clinical terminology often uses LUTS and BPH interchangeably. More recently, LUTS were also linked to fibrogenic and inflammatory processes. We tested whether osteopontin (OPN), a proinflammatory and profibrotic molecule, is increased in symptomatic BPH. We also tested whether prostate epithelial and stromal cells secrete OPN in response to proinflammatory stimuli and identified downstream targets of OPN in prostate stromal cells.MethodsImmunohistochemistry was performed on prostate sections obtained from the transition zone of patients who underwent surgery (Holmium laser enucleation of the prostate) to relieve LUTS (surgical BPH, S-BPH) or patients who underwent radical prostatectomy to remove low-grade prostate cancer (incidental BPH, I-BPH). Images of stained tissue sections were captured with a Nuance Multispectral Imaging System and histoscore, as a measure of OPN staining intensity, was determined with inForm software. OPN protein abundance was determined by Western blot analysis. The ability of prostate cells to secrete osteopontin in response to IL-1β and TGF-β1 was determined in stromal (BHPrS-1) and epithelial (NHPrE-1 and BHPrE-1) cells by enzyme-linked immunosorbent assay. Quantitative polymerase chain reaction was used to measure gene expression changes in these cells in response to OPN.ResultsOPN immunostaining and protein levels were more abundant in S-BPH than I-BPH. Staining was distributed across all cell types with the highest levels in epithelial cells. Multiple OPN protein variants were identified in immortalized prostate stromal and epithelial cells. TGF-β1 stimulated OPN secretion by NHPrE-1 cells and both IL-1β and TGF-β1 stimulated OPN secretion by BHPrS-1 cells. Interestingly, recombinant OPN increased the mRNA expression of CXCL1, CXCL2, CXCL8, PTGS2, and IL6 in BHPrS-1, but not in epithelial cell lines.ConclusionsOPN is more abundant in prostates of men with S-BPH compared to men with I-BPH. OPN secretion is stimulated by proinflammatory cytokines, and OPN acts directly on stromal cells to drive the synthesis of proinflammatory mRNAs. Pharmacological manipulation of prostatic OPN may have the potential to reduce LUTS by inhibiting both inflammatory and fibrotic pathways.

Dataset Information

Aconiti Lateralis Radix Preparata, the Dried Root of Aconitum carmichaelii Debx., Improves Benign Prostatic Hyperplasia via Suppressing 5-Alpha Reductase and Inducing Prostate Cell Apoptosis.

Publications

Aconiti Lateralis Radix Preparata, the Dried Root of <i>Aconitum carmichaelii</i> Debx., Improves Benign Prostatic Hyperplasia via Suppressing 5-Alpha Reductase and Inducing Prostate Cell Apoptosis.

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