Exploring the potentials of some compounds from
            <i>Garcinia kola</i>
            seeds towards identification of novel PDE‐5 inhibitors in erectile dysfunction therapy

Ojo, Oluwafemi Adeleke; Ojo, Adebola Busola; Maimako, Rotdelmwa Filibus; Rotimi, Damilare; Iyobhebhe, Matthew; Alejolowo, Omokolade Oluwaseyi; Nwonuma, Charles Obiora; Elebiyo, Tobiloba Christiana

doi:10.1111/and.14092

Cited by 15 publications

(7 citation statements)

References 29 publications

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“…These processes include the molecular docking of catechin, garcinal, garcinoic acid, d-tocotrienol, and sildenafil to receptor PDE5 via Auto Dock Vina. 53 Similar results were observed by Temkitthawon et al, 80 when they investigated the chemical constituents of the tubers of Eulophia macrobulbon and found phenanthrenes as a new class of PDE5 inhibitors. 80 Clerodendrumcole brookianum Walph has ethno-medicinal importance for the treatment of hypertension and reported to show activity against anti-hypertensive drug targets rho-associated coiled-coil protein kinase (ROCK), angiotensin-converting enzyme, and PDE5.…”

Section: Natural Pde5 Inhibitorssupporting

confidence: 76%

“…When NO binds with guanylyl cyclase, it undergoes a conformational change, allowing it to catalytically produce 3'-5'-cyclic guanosine monophosphate from guanosine 5'-triphsophate ( Figure 2 ). 7,53 The intracellular trigger for penile erection is cGMP, which activates PKG. PKG reduces intracellular calcium levels, causing arterial and trabecular smooth muscle to relax, resulting in arterial dilation, venous constriction, and penile erection stiffness.…”

Section: Pde5 and Erectile Dysfunctionmentioning

confidence: 99%

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A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

Saikia

Hazarika

Mishra

2022

Journal of Pharmacology and Pharmacotherapeutics

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Phosphodiesterase type 5 (PDE5) is a cyclic GMP (cGMP) specific protein. It hydrolyzes the phosphodiesterase linkage and catalyzes the conversion of cGMP to 5’ GMP, which controls different physiological activities of the body. PDE5 is associated with biomedical conditions like neurological disorders, pulmonary arterial hypertension, cardiomyopathy, cancer, erectile dysfunction, and lower urinary tract syndrome. Inhibition of PDE5 has now been proven pharmaceutically effective in a variety of therapeutic conditions. Avanafil, tadalafil, sildenafil, and vardenafil are the most commonly used PDE5 inhibitors (PDE5i) today which are often used for the management of erectile dysfunction, lower urinary tract syndromes, malignancy, and pulmonary arterial hypertension. However, these synthetic PDE5i come with a slew of negative effects. Some of the most common side effects include mild headaches, flushing, dyspepsia, altered color vision, back discomfort, priapism, melanoma, hypotension and dizziness, non-arteritic anterior ischemic optic neuropathy (NAION), and hearing loss. In light of the potential negative effects of this class of medications, there is a lot of room for new, selective PDE5 inhibitors to be discovered. We have found 25 plant botanical compounds effectively inhibiting PDE5 which might be useful in treating a variety of disorders with minimal or no adverse effects.

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Section: Natural Pde5 Inhibitorssupporting

confidence: 76%

Section: Pde5 and Erectile Dysfunctionmentioning

confidence: 99%

A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

Saikia

Hazarika

Mishra

2022

Journal of Pharmacology and Pharmacotherapeutics

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“…It is therefore uncertain whether G. kola derived vitamin E derivatives have the capability to produce comparable pharmacological effect as α-tocopherol or their efficiency is significantly diminished as in the case of remaining α-tocopherol derivatives. Additionally, δ-tocotrienol, garcinoic acid and garcinal have displayed similar affinity towards PDE-5 as Viagra®, however, these results were only thus far observed in an in silico model (Ojo et al 2021 ). Vitamin E have largely failed in clinical trials to provide therapeutic benefits in various human diseases (such as cardiovascular disorders, hypertension, diabetes, and cancer) (Robinson et al 2006 ; Steinhubl 2008 ).…”

Section: Discussionmentioning

confidence: 95%

“…GA was also found to improve heart function in myocardial infarction rats by increasing levels of pro-angiogenic factors, including hypoxia-inducible factor 1-alpha (HIF-1α), VEGF-A, and basic fibroblast growth factor (bFGF) (Hu et al 2020 ). Very recently, garcinoic acid, together with related structures garcinal and tocotrienol, have showed phosphodiesterase-5 (PDE-5) inhibitory activity in molecular docking study (Ojo et al 2021 ). Their activity was comparable to sildenafil (Viagra®), suggesting that these compounds may be useful in treatment of erectile disfunction.…”

Section: Resultsmentioning

confidence: 99%

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant

et al. 2023

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Garcinia kola Heckel (Clusiaceae) is a tree indigenous to West and Central Africa. All plant parts, but especially the seeds, are of value in local folklore medicine. Garcinia kola is used in treatment of numerous diseases, including gastric disorders, bronchial diseases, fever, malaria and is used to induce a stimulating and aphrodisiac effect. The plant is now attracting considerable interest as a possible source of pharmaceutically important drugs. Several different classes of compounds such as biflavonoids, benzophenones, benzofurans, benzopyran, vitamin E derivatives, xanthones, and phytosterols, have been isolated from G. kola, of which many appears to be found only in this species, such as garcinianin (found in seeds and roots), kolanone (fruit pulp, seeds, roots), gakolanone (stem bark), garcinoic acid, garcinal (both in seeds), garcifuran A and B, and garcipyran (all in roots). They showed a wide range of pharmacological activities (e.g. analgesic, anticancer, antidiabetic, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective and neuroprotective effects), though this has only been confirmed in animal models. Kolaviron is the most studied compound and is perceived by many studies as the active principle of G. kola. However, its research is associated with significant flaws (e.g. too high doses tested, inappropriate positive control). Garcinol has been tested under better conditions and is perhaps showing more promising results and should attract deeper research interest (especially in the area of anticancer, antimicrobial, and neuroprotective activity). Human clinical trials and mechanism-of-action studies must be carried out to verify whether any of the compounds present in G. kola may be used as a lead in the drug development.

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“…The NO-cGMP pathway serves as the principal mechanism for penile erection in primates, including humans. Sexual arousal activates neurological pathways, triggering the release of NO directly into the corpus cavernosum of the penis from both neurons and endothelial cells [11,41]. The biological stimulus responsible for initiating penile erection is cGMP, which then activates protein kinase G (PKG), responsible for the reduction of intracellular calcium levels.…”

Section: Erectile Dysfunction (Ed)mentioning

confidence: 99%

Exploring the Multifaceted Potential of Sildenafil in Medicine

Pușcașu,

Zanfirescu,

Negreș

et al. 2023

Medicina

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Phosphodiesterase type 5 (PDE5) is pivotal in cellular signalling, regulating cyclic guanosine monophosphate (cGMP) levels crucial for smooth muscle relaxation and vasodilation. By targeting cGMP for degradation, PDE5 inhibits sustained vasodilation. PDE5 operates in diverse anatomical regions, with its upregulation linked to various pathologies, including cancer and neurodegenerative diseases. Sildenafil, a selective PDE5 inhibitor, is prescribed for erectile dysfunction and pulmonary arterial hypertension. However, considering the extensive roles of PDE5, sildenafil might be useful in other pathologies. This review aims to comprehensively explore sildenafil’s therapeutic potential across medicine, addressing a gap in the current literature. Recognising sildenafil’s broader potential may unveil new treatment avenues, optimising existing approaches and broadening its clinical application.

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Exploring the potentials of some compounds from Garcinia kola seeds towards identification of novel PDE‐5 inhibitors in erectile dysfunction therapy

Cited by 15 publications

References 29 publications

A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

A Review on the Pharmacological Importance of PDE5 and Its Inhibition to Manage Biomedical Conditions

Garcinia kola: a critical review on chemistry and pharmacology of an important West African medicinal plant

Exploring the Multifaceted Potential of Sildenafil in Medicine

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