Benign prostatic hyperplasia (BPH) affects aging men worldwide, with the frequent clinical symptoms such as lower urinary tract symptoms (LUTS) including difficulty emptying the bladder, urgency, nocturia, dysuria and frequency bother the aging men’ life quality as well as health adversely [1]. Beyond its primary clinical manifestations, BPH exhibits a striking association with metabolic disorders, such as obesity, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), and hypertension [2]. Dysregulation of metabolism elevates the circulating concentrations of pro-inflammatory cytokines and promotes systemic oxidative stress, which in turn drives immune cell infiltration, ultimately leads to significant prostatic enlargement and exacerbation of LUTS [3,4]. Conventional surgical methods for patients with BPH usually resulted in complications such as pseudo urinary incontinence after surgery [5]. Moreover, the incidence rate of BPH increases with age as the morbidity of BPH increased from 70 % in 60–69 years aging men to 90 % in men aged more than 80 [1,6]. With the development of population aging, the number of patients with BPH is increasing year by year, so it is urgent to explore the exact pathogenesis and effective treatment of BPH.

As one of urological disorders, BPH is most widespread among elderly men [7]. Risk in men aged 50–70 is 50–70 % for BPH and 17 % as well as BPH and prostate cancer can coexist in 20 % of men with BPH [8]. BPH was associated with increased risk of complications such as pyelonephritis, prostatitis, and hospitalization in acute cystitis in men [9]. BPH correlated with high levels of co-morbid diseases, such as diabetes mellitus, renal and cardiovascular disorders, which have negative impacts on human quality of life [10]. Diabetes mellitus, especially type 2 diabetes (T2DM) is risk factor of cardiovascular disorders and diabetic kidney disease [[11], [12], [13]]. And the disease burden from T2DM was markedly higher in males and escalated with increasing age [14]. Moreover, T2DM is one of risk factors of BPH [15]. In another study, researchers demonstrated that the risk of LUTS mediated by BPH as well as BPH development in patients with diabetes increased significantly compared with control group [16]. Metabolic syndrome (MetS) involved in obesity, hypertension, hyperlipidemia and hyperglycemia was associated with BPH-LUTS [17]. Obesity and type 2 diabetes were also confirmed as risk factor of BPH [15] as well as men with diabetes have BPH more commonly compared with those with normal glucose [18]. EMT has been confirmed in previous studies that it plays an important role in tumor progression and metastasis [[19], [20], [21]]. Recent reports demonstrated that EMT in prostate cells contributed to BPH development and progress [22,23]. HG tends to induce EMT in renal tubular epithelial [24], tumor and BPH cells [25]. Inhibiting EMT is beneficial to attenuate diabetic nephropathy [26]. Ghrelin is preferred to correlate with obesity and diabetes and contribute to MetS [27]. Furthermore, our previous study indicated that Ghrelin might promote BPH progress through regulating gut microbiota [28] which may associate with predisposing obesity-prone individuals to diabetes [29].Therefore, block ghrelin signaling system may be a promising target for MetS which is involved in BPH development. MBOAT4 contributes to Ghrelin activating to acetylated Ghrelin formation, the latter functions with its receptor of GHS-R.

Arctigenin, one of the major active ingredients of Arctium lappa L (A lappa) and may serve as a potential therapeutic compound against multiple human diseases such as acute inflammation and various chronic diseases, cancers and immune disorders due to its potent anti-inflammatory, anti-oxidative stress, anti-fibrosis, anti-ER stress, anti-steatosis and pro-apoptosis [30]. Arctigenin attenuates diabetic kidney disease [31] as well as mitigates insulin resistance in T2DM mice [32]. Arctigenin is a mitochondrial complex I inhibitor and has been reported to promote necroptotic cell death via ROS-mediated mitochondrial damage in prostate cancer [33] which is correlated with immune dysfunction [22,34] and other disease [35]. According to other researchers, Arctigenin represses EMT in peritoneal mesothelial cells and human lung cancer cells [36,37]. The role of Arctigenin in BPH and its mechanism of action remain to be investigated.

In the present study, we proposed to explore the therapeutic effect of Arctigenin on BPH accompanied with T2DM and the molecular mechanism was also investigated for further. Clinical samples of patients with BPH or both BPH and T2DM were collected and measured to observe EMT related markers and Ghrelin/MBOAT4/GHS-R in our study. The role of Arctigenin in cell proliferation, migration and vascular-like networks formation of epithelial and stromal cells as well as BPH cells with/without HG culture were explored. T2DM mice with BPH were also involved in our study. Results of our study would serve as theoretical and experimental support for BPH therapy exploration.