Revive Herbal Capsule: A Review on the Mechanism of Action, Constituent Herbs and Phytochemicals

Revive capsule, also called Kedi Revive capsule is a polyherbal formulation manufactured by Kedi healthcare company limited in Hong Kong, China. The drug is widely used around the globe, especially in Africa and Asia for the treatment of erectile dysfunction or enhancement of libido in men. Each capsule contains 400 mg of the constituent herbs including 80 mg of herb Epimedii, 80mg of Radix ginseng, 40 mg of Cordyceps militaris, 80mg of Tribulus terrestris, 80mg of Radix polygoni multiflori, and 40 mg of Eucommia ulmoides, with its effects exerted four hours after administration via the oral route. The adult man dosage is two capsules (800 mg) to be taken once daily for at least 28 days (before significant improvements may be observed when used to treat erectile dysfunction). Phytochemical analysis of the drug reported the presence of flavonoids, cardiac glycosides, tannins, polyphenols, alkaloids and quinones. Due to its speculated use in the treatment of erectile dysfunction or enhancement of libido, it may be referred to as an herbal phosphodiesterase type-5 inhibitor, that acts by selectively inhibiting the enzyme phosphodiesterase type-5, and thus enhancing increased arterial blood flow into the penis, which results in penile erection; however, the mechanism of action of this drug may be attributed to the contained phytochemicals. Additionally, due to its increased use, it is highly recommended that further studies be conducted on this drug to ascertain its effects on some biochemical components and vital organs of the body.

Penile Hemodynamic Response to Phosphodiesterase Type V Inhibitors after Cavernosal Sparing Inflatable Penile Prosthesis Implantation: A Prospective Randomized Open-Blinded End-Point (PROBE) Study

Forceful corporal dilatation amidst penile prosthesis implantation may injure cavernosal arteries compromising penile vasculature. In this study, we aimed to compare the conventional and cavernosal sparing techniques regarding cavernosal artery preservation. Overall, 33 patients underwent inflatable penile prosthesis implantation with Coloplast Titan Touch® three-piece inflatable penile implants. 16 patients had conventional implantations with serial vigorous dilatations, while 17 patients were implanted with the cavernosal sparing technique, consisting of a single minimal corporal dilatation after an intraoperative intracavernosal injection (ICI) of Alprostadil. Postoperatively, a penile duplex Doppler ultrasound study was performed. Whenever a cavernosal artery was spared and thus successfully probed, its hemodynamics were studied before and after an oral administration of a phosphodiesterase type 5 inhibitor (PDE5i). A cavernosal artery was successfully probed in 16/17 (94%) of patients in the cavernosal sparing group compared to 5/16 (31%) of patients in the conventional group with a significant statistical difference ( P = 0.001 ). This demonstrated that the cavernosal sparing technique was superior to the conventional approach in preserving the cavernosal artery (odds ratio 35.2, 95% IC 3.5–344.2; P = 0.0022 ). Whenever a cavernosal artery could be probed, its hemodynamic responsiveness was also preserved. This trial is registered with NCT03733860.

Sildenafil Counteracts the In Vitro Activation of CXCL-9, CXCL-10 and CXCL-11/CXCR3 Axis Induced by Reactive Oxygen Species in Scleroderma Fibroblasts

Oxidative stress plays a key role in systemic sclerosis (SSc) pathogenesis, and an altered redox homeostasis might be responsible for abnormal inflammatory status, fibrosis and tissue damage extension. In this study, we explored the effect of the phosphodiesterase type 5 inhibitor sildenafil in modulating the activation of the CXCL-9, -10, -11/CXCR3 axis, which is fundamental in the perpetuation of inflammation in different autoimmune diseases, in the cell culture of SSc human dermal fibroblasts exposed to a pro-oxidant environment. We observed that sildenafil significantly reduced gene expression and release of CXCL-9, -10 and -11, inhibited the CXCR3 action and suppressed the activation of STAT1-, JNK- and p38MAPK pathways. This in vitro study on dermal fibroblasts supports clinical studies to consider the efficacy of sildenafil in preventing tissue damage and fibrosis in SSc by targeting central biomarkers of disease progression, vascular injuries and fibrosis and reducing the pro-inflammatory activation induced by oxidative stress.

Sildenafil Alleviates Murine Experimental Autoimmune Encephalomyelitis by Triggering Autophagy in the Spinal Cord

Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice via modulation of apoptotic pathways, but other signaling pathways were not previously covered. Therefore, the aim of the present study was to further investigate the effects of Sildenafil treatment on autophagy and nitrosative stress signaling pathways in EAE. 24 female C57BL/6 mice were divided into the following groups: (A) Control - received only water; (B) EAE - EAE untreated mice; (C) SILD - EAE mice treated with 25mg/kg of Sildenafil s.c. The results showed that EAE mice presented a pro-nitrosative profile characterized by high tissue nitrite levels, lowered levels of p-eNOS and high levels of iNOS. Furthermore, decreased levels of LC3, beclin-1 and ATG5, suggests impaired autophagy, and decreased levels of AMPK in the spinal cord were also detected in EAE mice. Surprisingly, treatment with Sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK. In conclusion, we propose that Sildenafil alleviates EAE by activating autophagy via the eNOS-NO-AMPK-mTOR-LC3-beclin1-ATG5 and eNOS-NO-AMPK-mTOR-CREB-BDNF pathways in the spinal cord.

Tadalafil ameliorates bladder overactivity by restoring insulin-activated detrusor relaxation via the bladder mucosal IRS/PI3K/AKT/eNOS pathway in fructose-fed rats

The pathophysiologies of metabolic syndrome (MS) and overactive bladder (OAB) might overlap. Using fructose-fed rats (FFRs) as a rodent model of MS we investigated the effects of tadalafil (a phosphodiesterase type 5 inhibitor) on the dysregulated insulin signalling in the bladder mucosa and bladder overactivity. Micturition behaviour was evaluated. Concentration–response curves on detrusor relaxation to insulin stimulation were examined. Expression and phosphorylation of proteins in the insulin signalling pathway were evaluated by Western blotting. Levels of detrusor cGMP and urinary nitrite and nitrate (NOx) were measured. We observed FFRs exhibited metabolic traits of MS, bladder overactivity, and impaired insulin-activated detrusor relaxation in organ bath study. A high-fructose diet also impeded insulin signalling, reflected by overexpression of IRS1/pIRS1Ser307 and pIRS2Ser731 and downregulation of PI3K/pPI3KTyr508, AKT/pAKTSer473, and eNOS/peNOSSer1177 in the bladder mucosa, alongside decreased urinary NOx and detrusor cGMP levels. Tadalafil treatment restored the reduced level of mucosal peNOS, urinary NOx, and detrusor cGMP, improved the insulin-activated detrusor relaxation, and ameliorated bladder overactivity in FFRs. These results suggest tadalafil may ameliorate MS-associated bladder overactivity by restoring insulin-activated detrusor relaxation via molecular mechanisms that are associated with preservation of IR/IRS/PI3K/AKT/eNOS pathway in the bladder mucosa and cGMP production in the bladder detrusor.