Botanical Formulation HX109 Ameliorates TP-Induced Benign Prostate Hyperplasia in Rat Model and Inhibits Androgen Receptor Signaling by Upregulating Ca2+/CaMKKβ and ATF3 in LNCaP Cells

Abstract

Benign prostatic hyperplasia (BPH) is a common disease in the elderly male population throughout the world. Among other factors, androgen dysregulation has been known to play major roles in its pathogenesis. HX109 is a botanical formulation prepared from a mixture of Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera, which have traditionally been used—usually along with other plants—to treat urinary diseases. An ethanol extract was prepared from a mixture of these three plants, and its quality was controlled through cell-based bioassays and by quantification of several marker compounds by high-performance liquid chromatography (HPLC). In the testosterone propionate (TP)-induced prostate hyperplasia rat model, oral administration of HX109 ameliorated prostate enlargement and histological changes induced by TP. In LNCaP cells, a human prostate epithelial cell line, HX109 repressed AR-mediated cell proliferation and the induction of androgen receptor (AR) target genes at the transcriptional level without affecting the translocation or expression of AR. Such effects of HX109 on AR signaling were mediated through the control of activating transcriptional factor 3 (ATF3) expression, phosphorylation of calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ), and increases in intracellular calcium, as evidenced by data from experiments involving ATF3-specific siRNA, CaMKKβ inhibitor, and calcium chelator, respectively. Taken together, our data suggest that HX109 might be used as a starting point for developing therapeutic agents for the treatment of BPH.

Botanical preparation HX109 inhibits macrophage-mediated activation of prostate epithelial cells through the CCL4-STAT3 pathway: implication for the mechanism underlying HX109 suppression of prostate hyperplasia

“…in the context of bioactivities. In our previous report, we described the development of cell-based bioassays for HX109, using human PSA as a biomarker whenever different batches of the extract were prepared [22].…”

“…Lipopolysaccharides from Escherichia coli O111:B4 (Sigma-Aldrich, MA) were used at 100 ng/ml for macrophage activation. HX109 was prepared, and its batch-to-batch consistency was controlled as previously described [22]. Briefly, combination of three plants-Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera-was extracted in 25% EtOH at 20 C for 8 h, followed by filtration, concentration, and lyophilization.…”

“…HX109 is an ethanol extract prepared from three plants: Taraxacum officinale, Cuscuta australis, and Nelumbo nucifera. We previously reported on the development of standardization and quality control methods for HX109 by using HPLC and MS analyses, and the capability of this botanical extract inhibiting BPH in in vivo studies, probably by suppressing AR signaling through the upregulation of Ca2þ/CAMKKβ and ATF expression [22]. AR has been known to play an important role in this cell-to-cell communication [23].…”

Effects of larval extracts from identified Protaetia brevitarsis seulensis against benign prostatic hyperplasia induced by testosterone in rats

“…The development of BPH usually occurs after 40 years of age and its prevalence gradually increases with increasing age (Shin et al., 2012a ). Its prevalence is nearly 50% in men over the age of 50 and reaches 80% in men over the age of 90 (Lim et al., 2018 ). BPH is featured as a hyperplasia of the stromal and epithelial cells of the prostate, thereby increased prostate size and caused lower urinary tract symptoms such as dysuresia (Jeon et al., 2017 ).…”

HX109 Herbal Extract Promotes Hair Growth by Regulating Cell Cycle in Hair Follicle Dermal Papilla Cells

“…연자육 추출물은 항스테 로이드 및 항산화 효능, 안드로겐 신호전달 조절 효능을 갖는다고 알 려져 있다 (Gupta et al, 1996;Rai et al, 2006;Wethangkaboworn & Munglue, 2014). 이와 같이 각 생약은 안드로겐 호르몬 기능과 연 관이 있는 비뇨기계 질환에 긍정적인 효능을 보이며, 이 생약들의 혼 합추출물인 HX109는 특히 남성호르몬에 직접적으로 작용하는 기 존의 탈모치료제와는 다르게 간접적으로 호르몬 신호전달경로를 조 절하는 효능이 있는 것으로 밝혀진 바 있다 (Lim et al, 2018). 이는 HX109가 기존의 치료제 대비 부작용은 적으면서 유사한 수준의 효 능을 나타낼 가능성을 시사한다 (Lim et al, 2018) 상세한 분석 방법 및 성분 분석 결과는 본 연구진이 수행한 선행연구 에서 확인할 수 있다 (Lim et al, 2018).…”