Taraxacum mongolicum total triterpenoids and taraxasterol ameliorate benign prostatic hyperplasia by inhibiting androgen levels, inflammatory responses, and epithelial-mesenchymal transition via the TGFβ1/Smad signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Taraxacum mongolicum Hand.-Mazz. is a well-known plant used both medicinally and as food, commonly used in traditional Chinese medicine prescriptions to alleviate benign prostatic hyperplasia (BPH). However, the material basis and molecular mechanisms of T. mongolicum alone in improving BPH remain unclear. In recent years, triterpenoids have been considered to be a key chemical constituents for T. mongolicum to exert its biological activity.

AIM OF THE STUDY: To explore the therapeutic efficacy and underlying mechanism of total triterpenoids from T. mongolicum (TTM) and its active constituents against BPH.

MATERIALS AND METHODS: The chemical components of TTM were determined using UPLC-QTOF-MS analysis. We established a testosterone propionate (TP)-induced rat model of BPH to assess the potential of TTM in vivo. Subsequently, network pharmacology was combined with experimental results from a TGFβ1-stimulated BPH-1 cell model to reveal the molecular mechanism of TTM. The main active ingredient (taraxasterol, TAR) of TTM was screened by evaluating its antiproliferative ability against BPH-1 and WPMY cells. Eventually, RNA-sequencing, RT-qPCR, immunofluorescence, and Western blotting were employed to elucidate the potential molecular targets and signalling pathways of TAR in BPH rats.

RESULTS: TTM was mainly composed of ten pentacyclic triterpenoids and one phytosterol, including TAR, lupeol, β-amyrin, taraxerol, and their acetates. TTM ameliorated TP-induced BPH by decreasing androgen levels and repressing inflammatory responses and oxidative stress. Furthermore, TTM inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition via impeding the TGFβ1/Smad signalling pathway in BPH-1 cells based on the network pharmacology. Among the main chemical components of TTM, TAR exerted the strongest antiproliferative activity in vitro, and inhibited the growth of BPH-1 and WPMY-1 cells in a concentration dependent manner. Importantly, TAR also reduced androgen levels and inflammatory responses to balance proliferation and apoptosis in BPH rats. Transcriptomic analysis showed that TAR attenuated collagen deposition in BPH by inhibiting ECM-receptor interaction pathway. In addition, TAR notably suppressed EMT and the TGFβ1/Smad signalling in BPH rats, as evidenced by reduced the protein levels of collagen I, a-SMA, Snail, TGFβ1, p-Smad2/Smad2, and p-Smad3/Smad3, alongside an increase in E-cadherin expression.

CONCLUSIONS: TTM or TAR could effectively improve TP-induced BPH by suppressing androgen levels, inflammatory response, and EMT via the TGFβ1/Smad signalling pathway. These findings may present new therapeutic approachs for BPH in clinical settings. Notably, this study is the first to systematically elucidate the therapeutic mechanism of triterpenoids from T. mongolicum in treating BPH.