Phytosterols in hull-less pumpkin seed oil, rich in ∆7-phytosterols, ameliorate benign prostatic hyperplasia by lowing 5α-reductase and regulating balance between cell proliferation and apoptosis in rats

Xin-Cong Kang; Tian Chen; Jia-Li Zhou; Peng-Yuan Shen; Si-Hui Dai; Chang-Qing Gao; Jia-Yin Zhang; Xing-Yao Xiong; Dong-Bo Liu

doi:10.29219/fnr.v65.7537

Phytosterols in hull-less pumpkin seed oil, rich in ∆⁷-phytosterols, ameliorate benign prostatic hyperplasia by lowing 5α-reductase and regulating balance between cell proliferation and apoptosis in rats

Food Nutr Res. 2021 Dec 2:65. doi: 10.29219/fnr.v65.7537. eCollection 2021.

Authors

Xin-Cong Kang^{1

2

3

4

5}, Tian Chen^{1

5}, Jia-Li Zhou¹, Peng-Yuan Shen¹, Si-Hui Dai¹, Chang-Qing Gao⁶, Jia-Yin Zhang^{1

2

3}, Xing-Yao Xiong^{1

2

7}, Dong-Bo Liu^{1

2

3

4}

Affiliations

¹ Horticulture College, Hunan Agricultural University, Changsha, Hunan, P. R. China.
² Hunan Provincial Key Laboratory of Crop Germplasm Innovation and Utilization, Hunan Agricultural University, Changsha, Hunan, P. R. China.
³ State Key Laboratory of Subhealth Intervention Technology, Changsha, Hunan, P. R. China.
⁴ Hunan Co-Innovation Center for Utilization of Botanical Functional Ingredients, Changsha, Hunan, P. R. China.
⁵ These authors contributed equally to this work.
⁶ Department of Laboratory Animals, Xiang Ya Hospital, Central South University, Changsha, Hunan, P. R. China.
⁷ Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.

Abstract

Background: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated.

Objective: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH.

Design: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting.

Results: The ∆⁷-phytosterols in TPS reached up to 87.64%. Among them, 24β-ethylcholesta-7,22,25-trienol, 24β-ethylcholesta-7,25(27)-dien-3-ol, and ∆⁷-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-β1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation.

Conclusion: TPS from hull-less pumpkin seed oil, with ∆⁷-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.

Keywords: 5α-reductase inhibitor; Curcurbita pepo; MAPK pathway; apoptosis; lower urinary tract symptoms; phytochemicals; proliferation.