Chinese Skullcap (Scutellaria baicalensis Georgi) inhibits inflammation and proliferation on benign prostatic hyperplasia in rats
Graphical abstract
Introduction
Benign prostatic hyperplasia (BPH) is defined as the enlargement of prostate owing to non-malignant abnormal growth of the gland. BPH is one of the frequently diagnosed disease in men aged over 50 years (Keoghane, 1998). Abnormal growth of the prostate raises to the bladder outlet obstruction, resulting in obstructive lower urinary tract symptoms (LUTS) (Rule et al., 2005). The aetiology of BPH is multifactorial, and previous studies have suggested to many elements, including age-dependent alterations in hormone ratio, tissue remodelling, engagement of various growth factors and disturbance of metabolic balance (Hammarsten et al., 1998, Lucia and Lambert, 2008, Untergasser et al., 2005). Recurrent tissue damage owing to chronic inflammation leads to compensated cellular proliferation, which results in hyperplasia (Chughtai et al., 2011, Sciarra et al., 2007). This event also induces disproportion between cell proliferation and apoptosis and leads to the occurrence of BPH (Zhang et al., 2006). Previous study identified that the apoptotic extent of prostate epithelium cells was higher in the normal tissue than in the hyperplastic prostate, whereas there was a significant augment in the proliferative cell proportions in the BPH tissue (Kyprianou et al., 1996).
Current therapy options for BPH include invasive surgical strategy, microwave thermotherapy, and pharmacological treatment. Although transurethral resection of prostate has remained gold standard of care for BPH, this operation still carries significant risks. Therefore, the medications for management of BPH are being developed for management of BPH (Bruskewitz, 1992). The most frequently used drugs are 5Ī±-reductase inhibitors and alpha-1 blockers. The 5Ī±-reductase inhibitors reduce conversion of testosterone to DHT, the most potent agonist of the AR. Alpha-1 blockers restrain the binding of adrenergic ligands on cognate receptors and suppress contraction of urinary bladder (Monda and Oesterling, 1993). Although these drugs have proven useful in the reducing BPH symptoms, considerable studies point to undesirable and serious adverse effects (Carruthers, 1994, Trost et al., 2013). 5Ī±-reductase inhibitor Finasteride causes severe allergic reactions, such as difficulty in breathing, rash, depression, erectile dysfunction, and reduction in semen volume. Adverse effects sometimes continue even after the drug taking is stopped (Hirshburg et al., 2016, Tacklind et al., 2010). As these synthetic agents pose several risks, effective remedies for BPH are being considered.
Chinese Skullcap (Scutellaria baicalensis Georgi) is member of the 50 fundamental herbs of Traditional Chinese Medicine, where its roots is called huang qin (Wong, 1976). It has been considered powerful medical herb for dysuria, pyrexia, atherosclerosis, allergies and inflammation (Horvath et al., 2005). Especially, Chinese Skullcap is a very well-known anti-inflammatory agent in East Asia countries. Chinese Skullcap root is prescribed as an important ingredient of a multi-herb formulation including Sho-saiko-to (Zhao et al., 2016). The bioactive compounds such as baicalin, wogonoside, baicalein and wogonin have been extracted from the root of Chinese Skullcap (Table 1). The dominant ingredients of Scutellaria baicalensis are Wogonin, Baicalein and Baicalin (Li-Weber, 2009). Numerous research shows that Chinese Skullcap root extract (SRE) and active compounds of skullcap modulate pro-inflammatory activity by inhibiting the expression of nitric oxide, PGE2 cytokine and NF-ĪŗB (Chou et al., 2003, Kim et al., 2009, Lee et al., 2015). Ye et al. also identified anticancer effect of SRE in prostate cancer cells. SRE treatment on prostatic cells induced direct elimination of COX-2 activity and cell cycle-related protein expression (Ye et al., 2007). But, even though many studies have demonstrated the pharmacological functions of Skullcap, neither the anti-BPH effect nor the understanding molecular mechanism could be considered. With the potential involvement of inflammation in aetiology of androgen-induced BPH, we sought to assess whether SRE is available as anti-BPH treatment. In this paper, we attempted to explain the effects of SRE and the detailed in vivo biological efficacy and demonstrated the underlying molecular mechanisms in rat with testosterone-induced BPH.
Section snippets
Chinese Skullcap extracts
The dehydrated roots of Chinese Skullcap were obtained from Nanumherb Co. Ltd. (Kyungpook, Republic of Korea) and a voucher specimen (No.161105) has been deposited at our laboratory. They were extracted with 30% ethylalcohol in water at 60āÆĀ°C for 4āÆh. The obtained preparation was purified from filter paper, and organic solvent was dematerialized using vacuous rotary evaporator (EYELA, Tokyo, Japan). The enriched sample was lyophilized, and the output was found to be 22.45% w/w.
Animals
All operations
Effects of SRE on prostate weight in BPH-induced rat model
Animals injected with TP for 4 weeks and the ventral prostate (VP) and dorsolateral prostate (DLP) were dissected. BPH-induced rats showed a notable increase in prostate size and weight, and prostate weight/body weight index. Fig. 1A shows representative prostate tissues of each group. BPH group showed a swollen volume and physiology of blood supply of VP as against the control group. BPH group also remarkably mounted up prostate weight in comparison with the control group. However,
Discussion
BPH is the most common male urologic disorder and the incidence has been reported to be 50% in men aged 50ā60 years and 90% in those over 80 years old (Elkahwaji, 2012). It is distinguished by the non-malignant enlargement and uncontrolled proliferation of prostate tissue, which lead to physical compression of the urethra and cause LUTS (Patel and Parsons, 2014). Although the pathogenesis of BPH remains in doubt, androgenic hormone, several growth factors, and inflammatory process are regarded
Conclusion
In conclusion, our study demonstrates that SRE significantly suppresses symptoms of BPH in TP-induced BPH rat model by inhibiting androgenic hormone-related markers and expression of pro-inflammation and anti-apoptosis factors.
Funding
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2016R1C1B2011827).
Additional information
Competing financial interests: The authors declare no competing financial interests.
Author contributions
B.R.J., K.S.C and H.J.A. conceived and designed the experiments. B.R.J. and H.J.K. performed the experiments and B.R.J. analyzed the data with K.S.C. and H.J.A.
H.J.A. contributed reagents, materials, and analysis tools. B.R.J. and H.J.A. wrote the paper. All authors read and approved the final manuscript.
Conflicts of interest
The authors declare no competing interests.
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