Piceatannol Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Modulation of Nrf2/HO-1/NFκB Axis

Eid, Basma G.; Abdel-Naim, Ashraf B.

doi:10.3389/fphar.2020.614897

Cited by 24 publications

(16 citation statements)

References 53 publications

(63 reference statements)

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“…These data are in agreement with the well‐known capacity of polyphenols intake in upregulating these markers in the liver and plasma (Lenquiste et al., 2015; Zhu et al., 2012). Moreover, studies reported that piceatannol could upregulate the GSH content in keratinocytes (Maruki‐Uchida et al., 2013) and to avoid the GSH depletion and catalase exhaustion promoted by testosterone in the prostate (Eid & Abdel‐Naim, 2020). A possible reason for these effects is the presence of catechol in piceatannol and (+)‐catechin.…”

Section: Discussionmentioning

confidence: 99%

Systemic antioxidant and anti‐inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression

Baseggio

Kido

Viganó

et al. 2021

Journal of Food Biochemistry

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We evaluated the impact of yellow passion fruit (Passiflora edulis sp.) bagasse extract (PFBE) administration in systemic oxidative and inflammatory parameters in vivo, considering prostate cancer progression in transgenic mice (TRAMP). Piceatannol, scirpusin‐B, dicaffeoylquinic acid, citric acid, and (+)‐catechin were identified in PFBE, and the extract showed high in vitro antioxidant capacity. Some alterations in systemic parameters were verified during prostate cancer progression, as the increase in ALT and MDA levels, and SOD and GPx activities in the plasma. In the liver, higher MDA, TNF‐α, and NF‐κB levels, and GR and GPx activities were verified. Compared to their respective controls, the short‐ and long‐term PFBE administration reduced MDA levels in the liver and plasma. The long‐term treatment increased the catalase activity in the plasma, while the short‐term treatment increased the hepatic SOD and catalase activities. Still, a reduction in hepatic TNF‐α and NF‐κB levels was verified after long‐term treatment. Practical applications Prostate cancer progression is associated with changes in systemic redox status and inflammation markers. Moreover, the intake of polyphenols with antioxidant properties, besides delaying prostate carcinogenesis, may improve the systemic antioxidant defenses and inflammatory response. In vitro studies pointed to a promising antioxidant and anti‐inflammatory potential of yellow passion fruit bagasse. However, in vivo studies are scarce. Our results provided information about in vivo impacts of PFBE oral consumption on antioxidant defense and inflammation, indicating its potential as an adjuvant during the initial steps of prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Systemic antioxidant and anti‐inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression

Baseggio

Kido

Viganó

et al. 2021

Journal of Food Biochemistry

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“…The Nrf2/HO-1 pathway has been widely studied with regard to its role in combating inflammation and fibrosis [ 66 ]. In BPH, Nrf2 and its target genes have been found to be deficient and insufficient for antioxidant response [ 67 ]. Nrf2 regulates the expression of key protective elements in BPH [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

et al. 2022

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Benign prostatic hyperplasia (BPH) is a widespread androgenic illness influencing elderly men. It is distinguished by prostatic epithelial and stromal muscle cell proliferation. Inflammation, oxidative stress, and apoptosis have all been interrelated to the development of BPH. Marjoram (Origanum majorana L.) is a herb with reported antiproliferative, proapoptotic, and antioxidative properties, which have not yet been studied in relation to BPH. Consequently, in this work, an ethanolic extract of O. majorana was prepared in two doses (250 and 500 mg/kg/day) to be injected into castrated rats after induction of a testosterone-BPH model. Testosterone propionate (TP) was subcutaneously injected (0.5 mg/kg/day) for one week after castration to induce BPH. Forty adult Wistar male rats were randomly allocated into five groups: control, BPH model, high and low O. majorana doses (250, 500 mg/kg/day), and finasteride (FN) (0.8 mg/kg/day) as a positive control. Treatment was continued with drugs/normal saline for 28 days. Rat’s body and prostate were weighed, prostate index (PI) and % of prostate growth inhibition were calculated, serum dihydrotestosterone (DHT), prostatic content of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and malondialdehyde (MDA), DN damage, histopathological changes, immune expression of proliferating cell nuclear antigen (PCNA), caspase-3, α-SMA, and TGF-β1 were assessed. In addition, molecular quantitative PCR and ELISA analyses were performed to identify the expression of mRNAs and related proteins of both caspase-3 and TGF-β1 in prostate tissue from O. majorana-treated and untreated groups. Rats with BPH had significantly higher prostate weights and PI, higher DHT, DNA damage (8-hydroxyguanine, 8-OH-dG), and MDA levels with prominent PCNA, α-SMA, and TGF-β expression, but lower SOD, CAT, and TAC activity and caspase-3 expression. O. majorana (250 and 500 mg/kg/day)-treated groups revealed a decrease in prostate weights and PI, lower levels of DHT, suppressed oxidative stress, reduced tissue proliferation and fibrosis, and restored antioxidant and proapoptotic activity. Additionally, quantitative PCR and ELISA analysis showed that treatment with O. majorana significantly upregulated the expression of caspase-3 and downregulated the expression of TGF-β in prostate tissues of BPH rats. The data were confirmed by the immunohistological reactivity of these targeted markers in the prostate tissues. These effects were more significant with O. majorana 500 mg/mL/rat. In conclusion, the current study indicates the efficient use of O. majorana in the treatment of testosterone-induced BPH through its antiproliferative, proapoptotic, and antioxidative mechanisms.

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“…Additionally, it is known that oxidative stress can aggravate the inflammatory responses via activation of NF-κB [53,54]. According to recent studies, Nrf2 regulates the expression of key protective enzymes through the antioxidant response element (ARE) in prostate cancer, and a number of its target genes are down-regulated in human prostate cancer and BPH [55]. Our results show that um-PEA/Baic treatment led to a considerable improvement in Nrf2, as well as increased HO-1 and MnSOD expression levels, suggesting the involvement of the Nrf2 antioxidant pathway in the mechanism of protection of PEA/Baic compared to the action of um-PEA, which showed only anti-inflammatory effects.…”

Section: Discussionmentioning

confidence: 99%

Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia

et al. 2021

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Benign prostatic hyperplasia (BPH) is the most common benign tumor in males. Androgen/androgen receptor (AR) signaling plays a key role in the development of BPH; its alterations cause an imbalance between prostate cell growth and apoptosis. Furthermore, chronic inflammation and oxidative stress, which are common conditions in BPH, contribute to disrupting the homeostasis between cell proliferation and cell death. With this background in mind, we investigated the effect of ultramicronized palmitoylethanolamide (um-PEA), baicalein (Baic) and co-ultramicronized um-PEA/Baic in a fixed ratio of 10:1 in an experimental model of BPH. BPH was induced in rats by daily administration of testosterone propionate (3 mg/kg) for 14 days. Baic (1 mg/kg), um-PEA (9 mg/kg) and um-PEA/Baic (10 mg/kg) were administered orally every day for 14 days. This protocol led to alterations in prostate morphology and increased levels of dihydrotestosterone (DHT) and of androgen receptor and 5α-reductase expression. Moreover, testosterone injections induced a significant increase in markers of inflammation, apoptosis and oxidative stress. Our results show that um-PEA/Baic is capable of decreasing prostate weight and DHT production in BPH-induced rats, as well as being able to modulate apoptotic and inflammatory pathways and oxidative stress. These effects were most likely related to the synergy between the anti-inflammatory properties of um-PEA and the antioxidant effects of Baic. These results support the view that um-PEA/Baic should be further studied as a potent candidate for the management of BPH.

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Piceatannol Attenuates Testosterone-Induced Benign Prostatic Hyperplasia in Rats by Modulation of Nrf2/HO-1/NFκB Axis

Cited by 24 publications

References 53 publications

Systemic antioxidant and anti‐inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression

Systemic antioxidant and anti‐inflammatory effects of yellow passion fruit bagasse extract during prostate cancer progression

Origanum majorana L. Extract Attenuated Benign Prostatic Hyperplasia in Rat Model: Effect on Oxidative Stress, Apoptosis, and Proliferation

Palmitoylethanolamide/Baicalein Regulates the Androgen Receptor Signaling and NF-κB/Nrf2 Pathways in Benign Prostatic Hyperplasia

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