May 2020 – “Pao Pereira Extract Suppresses Benign Prostatic Hyperplasia by Inhibiting Inflammation-Associated NFκB Signaling”

by Yu Dong, Jiakuan Liu, Zesheng Xue, Jingya Sun, Zhengnan Huang, Yifeng Jing, Bangmin Han, Bing Shen, Jun Yan and Ruimin Huang BMC Complement Med Ther 20, 150 (2020). https://doi.org/10.1186/s12906-020-02943-2

Pao pereira extract reduces inflammation in BPH by inhibiting NFKappaB signaling.

Pao pereira (Pau pereira) is incredibly effective for chronic inflammation of the prostate commonly known as BPH or Benign Prostatic Hyperplasia. BPH is an enlargement of the prostate caused by inflammation that is common among older men. The enlarged prostate gives rise to serious urinary problems and quality of life issues. A new study from Dr. Jun Yan’s group at Nanjing University in China shows that Pao pereira (Pau pereira) inhibits the control center that is activated in prostate inflammation. In BPH, this master switch, called NFKappaB, is turned on which triggers expression of pro-inflammatory cytokines and genes involved in extracellular matrix remodeling. These cytokines trigger proliferation of prostate cells and further enlargement of the gland. The Pao pereira (Pau pereira) extract turns the switch off so NFKappaB signaling is quieted and the levels of cytokines and remodelers are diminished. Not only does the extract resolve the inflammatory response in BPH it also reduces viability of the two major cell types in the prostate: epithelial and stromal cells. The chronic inflammation associated with BPH damages and destabilizes the DNA in the cells which renders them susceptible to apoptosis induced by the Pao pereira (Pau pereira) extract.  Apoptosis, or programmed cell death, is triggered in both epithelial and stromal cells in the BPH tissue. Induction of apoptosis is the precise mechanism of action of the Pao extract in cancer cells which, as Dr. Beljanksi showed, contain destabilized DNA. Malins’ work revealed that cells in the BPH prostate suffer similar DNA damage even though the cells are not cancerous, but rather chronically inflamed or precancerous. The new study from Dr. Yan’s group shows that DNA damage in BPH is sufficient to result in apoptosis in the presence of the Pao pereira (Pau pereira) extract.

There is more!

A previous paper from the Nanjing group showed that Pao pereira (Pau pereira) addresses the androgen imbalance that promotes BPH as men age (read the previous study from the Nanjing group here). The extract inhibits the enzyme that converts testosterone to dihydrotestosterone which triggers prostate enlargement. The Pao extract reduces the size of BPH prostates, lowers the levels of androgen receptor, and lowers PSA–the well-known marker for prostate inflammation. The Pao extract does all of this just as well Finasteride, but without the negative side effects associated with this drug.

Pao pereira (Pau pereira) is indeed incredibly effective for BPH.

Abstract

Background

Our previous study revealed the extract from the bark of an Amazonian tree Pao pereira (Pau pereira) can suppress benign prostatic hyperplasia (BPH) in a rat model. Herein, we examined its inhibitory effects on human BPH cells and dissect its molecular mechanism.

Methods

We applied the Pao extract to human BPH epithelial BPH-1 and prostate myofibroblast WPMY-1 cells. Cell viability, apoptosis and immunoblotting were performed, followed by gene expression profiling and gene set enrichment analysis (GSEA) to detect the differentially expressed genes and signaling pathway induced by Pao extract. Human ex vivo BPH explant organ culture was also used to examine the effects of Pao extract on human BPH tissues.

Results

Pao extract treatment inhibited viability and induced apoptosis in human BPH-1 and WPMY-1 cells. Gene expression profiling and the following validation indicated that the expression levels of pro-apoptotic genes (eg. PCDC4, CHOP and FBXO32) were induced by Pao extract in both two cell lines. GSEA further revealed that Pao extract treatment was negatively associated with the activation of NFκB signaling. Pao extract suppressed the transcriptional activity of NFκB and down-regulated its target genes involved in inflammation (CXCL5, CXCL6 and CXCL12) and extracellular matrix (ECM) remodeling (HAS2, TNC and MMP13) in both cultured cells and human ex vivo BPH explants.

Conclusion

In both BPH epithelial and stromal cells, Pao extract induces apoptosis by upregulating the pro-apoptotic genes and inhibiting the inflammation-associated NFκB signaling via reducing phosphorylation of NFκB subunit RelA. Our data suggest that Pao extract may be a promising phytotherapeutic agent for BPH.

Research Publication Data

Figure 1 shows Pao pereira (Pau pereira) inhibited the proliferation and induced apoptosis in BPH-1 and WPMY-1 cells. Image a shows changes of BPH-1 and WPMY-1 cells upon Pao extract treated for 48 h. Image b shows the effects of Pao pereira (Pau pereira) on cell viability by the SRB assay. Figure 2 shows Pao pereira (Pau pereira) induced apoptosis in BPH-1 and WPMY-1 cells. Image a shows the flow cytometry analysis on BPH-1 and WPMY-1 cells treated with Pao pereira (Pau pereira) using an Annexin V-FITC/PI double staining kit. Image b shows the cell death rates in BPH-1 and WPMY-1 cells treated with Pao pereira (Pau pereira). Annexin V-positive cells were defined as apoptotic cells. Image c is the effects of Pao pereira (Pau pereira) on the apoptosis-related proteins by Western blotting assay. Data are presented as mean ± SD; * p < 0.05, ** p < 0.01, and *** p < 0.001 Figure 3 shows Pao pereira (Pau pereira) inhibited NFκB signaling pathway in human BPH tissues. Image a is a schematic diagram of the ex vivo BPH explant culture process. BPH explants were treated with 0, 250, 500 μg/ml Pao pereira (Pau pereira) for 48 h. Image b is the phosphorylation of RelA and protein expression levels of pro-apoptotic and inflammation-associated genes survival-associated proteins (PDCD4 and DDIT3/CHOP) were analyzed by Western blotting in BPH explants with Pao pereira (Pau pereira) treatment. Image c is the mRNA expression levels of target genes from NFκB signaling pathway, pro-apoptotic and inflammation-associated genes in BPH explants with Pao pereira (Pau pereira) treatment by qRT-PCR. * p < 0.05, ** p < 0.01, *** p < 0.001, and ns p ≥ 0.05