Preclinical prediction of phytochemicals identified from cannabis as novel inhibitors of TEX 11, DHCR24, and CatSper 1 in fertility drug design

Taiwo, Odunayo Anthonia; Dosumu, Oluwatosin Adebisi; Oni, E.O.; Akomolafe, Victoria Omoyemi; Elazab, Sara T.; Qusti, Safaa; Alshammari, Eida M.; Batiha, Gaber El‐Saber; Ojo, Oluwafemi Adeleke

doi:10.1016/j.imu.2021.100747

Cited by 5 publications

(4 citation statements)

References 16 publications

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“…Validation of the feasibility of binding affinity of a ligand in complex with a receptor is crucial, hence the need to consider the stability of the complex through post docking analysis [37] . The binding free energy of the docked complexes were visualized and calculated via Prime MM-GBSA.…”

Section: Discussionmentioning

confidence: 99%

Pre-puberty cannabichromene exposure modulates reproductive function via alteration of spermatogenesis, steroidogenesis, and eNOS pathway metabolites

Taiwo

Dosumu

James³

et al. 2023

Toxicology Reports

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Section: Discussionmentioning

confidence: 99%

Pre-puberty cannabichromene exposure modulates reproductive function via alteration of spermatogenesis, steroidogenesis, and eNOS pathway metabolites

Taiwo

Dosumu

James³

et al. 2023

Toxicology Reports

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“…The results indicated the inhibitory potential of ascorbic acid to target the induced apoptosis of sperm DNA. In another study [17], a computational approach was used to compare the effectiveness of reported bioactive chemicals in plant hemp towards three proteins associated with male fertility (i.e., 24-dehydrocholesterol reductase (DHCR24), cation channel sperm associated 1 (CatSper 1), and testis expressed protein 11 (TEX 11)) with clomiphene, a particular estrogen-receptor stipulated for the medical management of infertility. A large number of compounds showed commendable binding affinity, according to the analyses of protein modeling, docking simulations, ADME toxicity, induced-fit docking simulation, as well as linking free energy over ligand-protein complexes.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study

Jahangeer,

Mustafa,

Munir

et al. 2023

Molecules

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Infertility is a well-recognized multifactorial problem affecting the majority of people who struggle with infertility issues. In recent times, among infertility cases, the male factor has acquired importance, and now it contributes to approximately half of the infertility cases because of different abnormalities. In the current study, we used natural phytochemicals as potential drug-lead compounds to target different receptor proteins that are involved in the onset of male infertility. A set of 210 plant phytochemicals were docked counter to active site residues of sex hormone-binding globulin, a disintegrin and metalloproteinase 17, and DNase I as receptor proteins. On the basis of binding scores and molecular dynamics simulation, the phytochemicals tricin, quercetin, malvidin, rhamnetin, isorhamnetin, gallic acid, kaempferol, esculin, robinetin, and okanin were found to be the potential drug candidates to treat male infertility. Molecular dynamics simulation showed tricin as a strong inhibitor of all selected receptor proteins because the ligand–protein complexes remained stabilized during the entire simulation time of 100 ns. Further, an in vivo study was designed to evaluate the effect of tricin in male rats with nicotine-induced infertility. It was explored that a high dose of tricin significantly reduced the levels of alanine transaminase, aspartate transaminase, urea, creatinine, cholesterol, triglyceride, and low-density lipoprotein and raised the level of high-density lipoprotein in intoxicated male rats. A high dose of tricin also increased the reproductive hormones (i.e., testosterone, luteinizing hormone, follicle-stimulating hormone, and prolactin) and reduced the level of DHEA-SO4. The phytochemical (tricin, 10 mg/kg body weight) also showed significant improvement in the histo-architecture after nicotine intoxication in rats. From the current study, it is concluded that the phytochemical tricin could serve as a potential drug candidate to cure male infertility.

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“…Several other chemicals have been shown in single studies to potentially inhibit DHCR24 but have not yet been reproduced. These include studies on the phytochemicals in Cannabis sativa [104] and the chemical genkwadaphnin, extracted from the flower buds of Daphne genkwa [105]. The synthetic gamma secretase modulator E2012 also inhibited DHCR24 and led to development of cataract in rats, with increased desmosterol and decreases cholesterol in lens, liver, and plasma [106].…”

Section: Other Dhcr24 Inhibitorsmentioning

confidence: 99%

Chemical Inhibition of Sterol Biosynthesis

Peeples,

Mirnics,

Korade

2024

Biomolecules

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Cholesterol is an essential molecule of life, and its synthesis can be inhibited by both genetic and nongenetic mechanisms. Hundreds of chemicals that we are exposed to in our daily lives can alter sterol biosynthesis. These also encompass various classes of FDA-approved medications, including (but not limited to) commonly used antipsychotic, antidepressant, antifungal, and cardiovascular medications. These medications can interfere with various enzymes of the post-lanosterol biosynthetic pathway, giving rise to complex biochemical changes throughout the body. The consequences of these short- and long-term homeostatic disruptions are mostly unknown. We performed a comprehensive review of the literature and built a catalogue of chemical agents capable of inhibiting post-lanosterol biosynthesis. This process identified significant gaps in existing knowledge, which fall into two main areas: mechanisms by which sterol biosynthesis is altered and consequences that arise from the inhibitions of the different steps in the sterol biosynthesis pathway. The outcome of our review also reinforced that sterol inhibition is an often-overlooked mechanism that can result in adverse consequences and that there is a need to develop new safety guidelines for the use of (novel and already approved) medications with sterol biosynthesis inhibiting side effects, especially during pregnancy.

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Preclinical prediction of phytochemicals identified from cannabis as novel inhibitors of TEX 11, DHCR24, and CatSper 1 in fertility drug design

Cited by 5 publications

References 16 publications

Pre-puberty cannabichromene exposure modulates reproductive function via alteration of spermatogenesis, steroidogenesis, and eNOS pathway metabolites

Pre-puberty cannabichromene exposure modulates reproductive function via alteration of spermatogenesis, steroidogenesis, and eNOS pathway metabolites

Exploring the Potential of Plant Bioactive Compounds against Male Infertility: An In Silico and In Vivo Study

Chemical Inhibition of Sterol Biosynthesis

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