Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome

Ahlem, Clarence N.; Auci, Dominick L.; Nicoletti, Ferdinando; Pieters, Raymond; Kennedy, Michael R.; Page, Theodore; Reading, Christopher L.; Enioutina, Elena Y.; Frincke, James M.

doi:10.1016/j.jsbmb.2011.04.010

Cited by 11 publications

(8 citation statements)

References 64 publications

(88 reference statements)

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“…β AET is found naturally in picomolar concentrations in human plasma [14], but is virtually absent in rodents without exogenous DHEA administration. β AET is not orally bioavailable, and plasma concentrations in humans cannot be appreciably augmented by DHEA supplementation due to DHEA's unfavorable absorption and metabolism characteristics [15]. HE3286 has anti-inflammatory activity in rodent disease models [16, 17].…”

Section: Introductionmentioning

confidence: 99%

“…HE3286 has anti-inflammatory activity in rodent disease models [16, 17]. Both β AET and HE3286 display many of the desirable anti-inflammatory activities reported for DHEA [18], suggesting that some aspects of DHEA's activity stem from polyhydroxylated metabolites that are readily formed in rodents [15]. HE3286 has no known intrinsic neuropharmacological activity or toxicity [13].…”

Section: Introductionmentioning

confidence: 99%

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17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
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17α-Ethynyl-androst-5-ene-3β,7β,17β-triol (HE3286) is a synthetic androstenetriol in Phase II clinical development for the treatment of inflammatory diseases. HE3286 was evaluated for blood-brain barrier (BBB) permeability in mice, and efficacy in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease (PD). We found that HE3286 freely penetrated the BBB. HE3286 treatment significantly improved motor function compared to vehicle in the rotarod test (mean 58.2 sec versus 90.9 sec, P < 0.0001), and reduced inflammatory mediator gene expression in the brain (inducible nitric oxide synthase, 20%, P = 0.002; tumor necrosis factor α, 40%, P = 0.038, and interleukin-1β, 33%, P = 0.02) measured by reverse-transcriptase polymerase chain reaction. Brain tissue histopathology and immunohistochemistry showed that HE3286 treatment increased the numbers of tyrosine hydroxylase-positive cells by 17% compared to vehicle (P = 0.003), and decreased the numbers of damaged neurons by 38% relative to vehicle (P = 0.029). L-3,4-dihydroxyphenylalanine (L-DOPA) efficacy was not enhanced by concurrent administration of HE3286. HE3286 administration prior to MPTP did not enhance efficacy. Our data suggest a potential role for HE3286 in PD treatment, and provides incentive for further investigation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
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“…Furthermore, the initial levels of these steroids positively correlated with a decline of somatic and psychosomatic symptoms as did the overall scores of the N-5 neurotic questionnaire (Figure 1a,b, Tables 2, 3 and 5). The ∆ 5 C19 steroids, and especially their 7α/β-7-oxo-and 16α-hydroxy-metabolites, are widely known as anti-glucocorticoid and immunoprotective substances [6,[28][29][30]. These results demonstrate that at least the activity of the ZR is augmented after intervention, and that its activity at the beginning of the treatment predicts the improvement in somatic and psychosomatic components of the N-5 neurotic questionnaire.…”

Section: Anti-glucocorticoid Immunoprotective Steroidsmentioning

confidence: 84%

“…The most important finding from the viewpoint of patients' welfare is that immunoprotective (stimulate immune response but suppress autoimmunity) ∆ 5 C19 steroids such as DHEA, androstenediol, 7α-hydroxy-DHEA, 7-oxo-DHEA, and 5-androstene-3β,7α,17β-triol [6,[28][29][30][31][32] (see Table 6) showed a significant increase after intervention (Table 1). Furthermore, the initial levels of these steroids positively correlated with a decline of somatic and psychosomatic symptoms as did the overall scores of the N-5 neurotic questionnaire (Figure 1a,b, Tables 2, 3 and 5).…”

Section: Anti-glucocorticoid Immunoprotective Steroidsmentioning

confidence: 99%

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Honců

Hill

Bičı́ková

et al. 2019

IJMS

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Spa treatment can effectively reestablish mood balance in patients with psychiatric disorders. In light of the adrenal gland’s role as a crossroad of psychosomatic medicine, this study evaluated changes in 88 circulating steroids and their relationships with a consolidation of somatic, psychosomatic and psychiatric components from a modified N-5 neurotic questionnaire in 46 postmenopausal 50+ women with anxiety-depressive complaints. The patients underwent a standardized one-month intervention therapy with physical activity and an optimized daily regimen in a spa in the Czech Republic. All participants were on medication with selective serotonin reuptake inhibitors. An increase of adrenal steroidogenesis after intervention indicated a reinstatement of the hypothalamic-pituitary-adrenal axis. The increases of many of these steroids were likely beneficial to patients, including immunoprotective adrenal androgens and their metabolites, neuroactive steroids that stimulate mental activity but protect from excitotoxicity, steroids that suppress pain perception and fear, steroids that consolidate insulin secretion, and steroids that improve xenobiotic clearance. The positive associations between the initial values of neurotic symptoms and their declines after the intervention, as well as between initial adrenal activity and the decline of neurotic symptoms, indicate that neurotic impairment may be alleviated by such therapy provided that the initial adrenal activity is not seriously disrupted.

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“…A aplicação intravenosa de androstenodiol melhorou a sobrevivência de animal no modelo de sepse e o mesmo efeito foi observado com o uso de DHEA subcutâneo (Schmitz, Lendemans et al 2014). O metabólito androstenetriol (βAET) apresentou efeitos inibidores na produção de NO por células RAW264-7 após estimulação com LPS, além de redução do infiltrado celular em animais após estímulo com carragenina (Ahlem, Auci et al 2011). Além disso, Babickova et.…”

Section: Avaliação Da Toxicidade E Perfil Lipídico Após Uso Do Dhea Iunclassified

Estudo do potencial imunomodulador de Dehidroepiandrosterona (DHEA) na inflamação intestinal experimental

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Primeiramente agradeço a Deus por ser o meu rochedo, minha fortaleza, meu escudo e o meu alto refúgio. Agradeço por me abençoar com seu Espírito para superar todos os obstáculos dessa trajetória me fortalecendo para finalizar este trabalho. À Profa. Dra. Cristina Ribeiro de Barros Cardoso que por meio dos seus conhecimentos me orientou com paciência e compreensão. Agradeço por confiar este projeto aos meus cuidados e por auxiliar no meu crescimento científico, profissional e pessoal. Ao Prof. Dr. Auro Nomizo, por enriquecer este trabalho com suas ideias dotadas de sabedoria, pela amizade, conselhos e por acreditar no meu potencial. Ao Prof. Dr. Javier Lazo Chica pelos ensinamentos e por colaborar neste trabalho. Aos demais colaboradores desse projeto: Paulo, Viviani e Angélica, que dedicaram seus esforços e tempo para ajudar nos longos experimentos. Sem o apoio de vocês, a finalização deste trabalho seria muito mais difícil. O meu muito obrigada de coração! Aos secretários da pós-graduação, Henrique e Rosana pela atenção, carinho e dedicação de sempre nos serviços burocráticos. A todos os professores da pós-graduação em Biociências Aplicadas à Farmácia, pela competência nas disciplinas e pelo compartilhamento de experiências que ajudaram no meu crescimento profissional. Às técnicas do Laboratório de Imunoendocrinologia e Regulação (LIR), Viviani e Lelis, pela dedicação, competência profissional, carinho e disposição em ajudar. Muito obrigada! Aos amigos do Laboratório de Imunoendocrinologia e Regulação (LIR), em especial ao Paulo, que sempre demonstrou amizade sincera, dando conselhos, me apoiando nos momentos difíceis e acreditando em minha capacidade. Ainda, agradeço aos amigos Giuliano, Patrícia, Carol e Angélica pelo companheirismo, momentos de auxílio e até descontração, é certo que a presença de vocês tornou o fardo mais leve. A FAPESP pela concessão da bolsa de doutorado (Processo N° 2012/17265-4) pelo suporte financeiro (Processo N° 2010/20162-7) e do NAP-DIN, que foram essenciais para o desenvolvimento deste trabalho. A minha mãe Hilda, meu pai Hiron e irmão Claudiney, por serem exemplos de humildade, solidariedade e companheirismo. Obrigada por me ensinarem o verdadeiro sentido da vida, por entenderem minhas escolhas, apoiarem as minhas decisões e compreenderem a minha ausência. ❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄❄ Agradecimentos Ao meu querido e amado Rosan, por sempre me escutar, estando ao meu lado nos momentos mais difíceis, por compreender minha ausência com paciência e por todo carinho. Muito obrigada por fazer parte da minha vida! As minhas queridas amigas, Beatriz Coutinho e Jane Freitas por sempre me apoiarem, pela amizade sincera e pelos inúmeros conselhos. A amizade verdadeira é aquela que nem o tempo e a distância conseguem enfraquecer. Obrigada por sempre estarem presentes na minha vida mesmo que distantes. Aos amigos do Espaço Ophelia Camassutti. Muito obrigada a todos vocês pelos momentos de descontração e por me ensinarem a nunca desistir de um sonho. A todos...

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Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome

Cited by 11 publications

References 64 publications

17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
Self Cite
7
2
6
0
View full text Add to dashboard Cite

17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
Self Cite
7
2
6
0
View full text Add to dashboard Cite

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Estudo do potencial imunomodulador de Dehidroepiandrosterona (DHEA) na inflamação intestinal experimental

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Pharmacology and immune modulating properties of 5-androstene-3β,7β,17β-triol, a DHEA metabolite in the human metabolome

Cited by 11 publications

References 64 publications

17α-Ethynyl-androst-5-ene-3β,7β,17Nicoletti1, Philippens2, Fagone3 et al. 2012Parkinson's DiseaseSelf Cite7260View full textAdd to dashboardCite

17α-Ethynyl-androst-5-ene-3β,7β,17Nicoletti1, Philippens2, Fagone3 et al. 2012Parkinson's DiseaseSelf Cite7260View full textAdd to dashboardCite

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

Estudo do potencial imunomodulador de Dehidroepiandrosterona (DHEA) na inflamação intestinal experimental

Contact Info

Product

Resources

About

17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
Self Cite
7
2
6
0
View full text Add to dashboard Cite

17α-Ethynyl-androst-5-ene-3β,7β,17
Nicoletti
¹
,
Philippens
²
,
Fagone
³

et al. 2012
Parkinson's Disease
Self Cite
7
2
6
0
View full text Add to dashboard Cite