Unscrewing the DHT-Blocking Properties of Allium cepa Extract: Virtual Screening of Active Compounds Against 5-Alpha Reductase and Evaluation of ADME/T Properties of Compounds

Androgenetic alopecia (AGA) occurs in genetically prone men and women and is defined by pattern-related, non-scarring hair follicle shrinkage. It is estimated that up to 80% of men and 50% of women will be affected by AGA at some stage in their lives. The underlying pathophysiology may be traced back to the enzyme 5-alpha-reductase, which is responsible for the conversion of testosterone to dihydrotestosterone (DHT), a more powerful androgen, and its accumulation in hair follicles leads to hair loss. The therapeutic approach for treating AGA mainly relies on the inhibition of 5-alpha- reductase. Allium cepa (onion) extract is in trend as a natural remedy for the treatment of AGA. The study aims at in-silico and ADME/T analysis of active compounds present in onion extract against 5-alpha-reductase to evaluate and visualize protein-ligand interaction.

Study on effect of extract from Tibetan medicine Urtica hyperborean on anti-prostatic hyperplasia / 中国中药杂志

In this study,mouse models of benign prostatic hyperplasia induced by subcutaneous injection of testosterone propionate was used to investigate the therapeutic effect and mechanism of Urtica hyperborean( UW) extracts on prostate hyperplasia in mice. The effects of UW extracts on prostate index,serum epidermal growth factor( EGF) and dihydrotestosterone( DHT) in model mice were observed,and the EGF and anti-apoptotic factor( Bcl-2) mRNA expression levels were detected as well as pathological changes in prostate tissue. The results showed that the ethyl acetate extraction and alcohol soluble fraction of the UW could significantly reduce the prostate index,reduce the serum DHT and EGF levels( P<0. 01),and significantly decrease the EGF and Bcl-2 mRNA expression( P<0. 01),significantly improved the morphological structure of prostate tissue. The above results confirmed that ethyl acetate extract and alcohol-soluble parts of UW have a good preventive effect on mice prostatic hyperplasia model,and its mechanism may be to reduce androgen levels by regulating polypeptide growth factors and/or inhibiting cell hyperproliferation and promoting apoptosis. This study laid the foundation for the further research on UW.

Effect of dihydrotestosterone on mouse embryonic stem cells exposed to H(2)O(2)-induced oxidative stress

Oxidative stresses induced by reactive oxygen species (ROS) have been shown to be involved in several physiological and pathophysiological processes, such as cell proliferation and differentiation. Steroid hormones can protect cells against apoptosis or induce cell proliferation by several mechanisms. Among androgenic hormones, dihydrotestosterone (DHT) is generated by a 5alpha- reduction of testosterone. Unlike testosterone, DHT cannot be aromatized to estradiol, therefore DHT is considered a pure androgenic steroid. This study was conducted to examine the effect of DHT (10(-7) M) on H(2)O(2) (10(-3) M) -induced injuries in mouse embryonic stem (ES) cells. H(2)O(2) induced ROS generation and increased lipid peroxide formation and DNA fragmentation. These effects of H(2)O(2) were inhibited by pretreatment with DHT. H(2)O(2) also increased the phosphorylation of p38 MAPK, SAPK/JNK and nuclear factor kappa B (NF-kappaB), but DHT blocked these effects. Moreover, H(2)O(2) decreased DNA synthesis and the levels of cell cycle regulatory proteins [cyclin D1, cyclin E, cyclin-dependent kinase (CDK) 2, and CDK 4]. These effects of H(2)O(2) were inhibited by pretreatment with DHT. In conclusion, DHT may partially prevent H(2)O(2)-induced cell injury through inhibition of ROS and ROS-induced activation of p38 MAPK, SAPK/JNK and NF-kappaB in mouse ES cells.

Cytotoxic Effect of 5, 7-DHT on the Endogenous Glial Cells in the Dorsal Raphe Nucleus of the Rat / 대한해부학회지

This study was designed to clarify the cytotoxic effects of 5, 7-dihydroxytryptamine (5, 7-DHT) on the serotonergic neurons in the dorsal raphe nucleus, and to investigate the glial reaction during the neurodegenerative changes by light and electron microscopy. Adult male rats (Sprague-Dawley strain) weighing from 250 g to 350 g each were used as experimental animal. 5, 7-DHT (200 mg dissolved in 0.9% NaCl) was injected into the lateral ventricle of the rat brain with the Hamiton syringe fixed on stereotaxic apparatus. The control rats were given with the similar volume of 0.9% NaCl. The rats were sacrified on the 1st, 3rd, 5th, 10th and 20th day after the injection of 5, 7-DHT. The results were as follows : Glial reactions induced by 5, 7-DHT were also observed in DRN. In early experimental stage, microglial reactions prevailed, whereas astroglial reactions were prevailing in later stage. In addition, microglial cells phagocytosed and removed the degenerated cells. However, astrocytes in DRN did not show phagocytotic activities such as microglial cells. Based on the results, author thought that 5, 7-DHT act as a specific neurotoxin to serotonergic neurons in DRN, and induces severe neurodegenerative changes. The glial reactions in DRN are activated during the neurodegerative changes, and show characteristic patterns of glial reactions.

Cytotoxic Effect of 5, 7-DHT on the Serotonergic Neurons in the Dorsal Raphe Nucleus of the Rat / 대한해부학회지

This study was designed to clarify the cytotoxic effects of 5, 7-dihydroxytryptamine (5, 7-DHT) on the serotonergic neurons in the dorsal raphe nucleus, and to investigate the glial reaction during the neurodegenerative changes by light and electron microscopy. Adult male rats (Sprague-Dawley strain) weighing from 250 g to 350 g each were used as experimental animal. 5, 7-DHT (200 microgram dissolved in 0.9% NaCl) was injected into the lateral ventricle of the rat brain with the Hamiton syringe fixed on stereotaxic apparatus. The control rats were given with the similar volume of 0.9% NaCl. The rats were sacrified on the 1st, 3rd, 5th, 10th and 20th day after the injection of 5, 7-DHT. The results were as follows : The cytotoxicity of 5, 7-DHT resulted in severe neurodegenerations of the serotonergic neurons. Most degenerated cells mainly showed necrotic findings, but a few of them exhibited apoptotic features. That is, in early stage of this experiment, the degenerated cells showed edematic changes of cytoplasm, but their nuclei were relatively seen intact. In late stage, the cells showed dark degenerative changes both in their cytoplasm and nuclei. Thereafter the cells were autolysed or phagocytosed by neighboring glial cells. Based on the results, author thought that 5, 7-DHT act as a specific neurotoxin to serotonergic neurons in DRN, and induces severe neurodegenerative changes. The glial reactions in DRN are activated during the neurodegerative changes, and show characteristic patterns of glial reactions.