A secondary approach with conventional medicines and supplements to recuperate current COVID-19 status.

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.

Neferine improves oxidative stress and apoptosis in benign prostate hyperplasia via Nrf2-ARE pathway.

BACKGROUND: Progression of Benign Prostate hyperplasia (BPH) is vulnerable to oxidative stress (OS) and prostatic enlargement among the aging males through apoptosis deregulation. Our present study aimed to investigate the effect of neferine (NF) in the regulation of oxidative stress and apoptosis in human BPH-1 cells. METHODS: BPH epithelial cell line BPH-1 was treated with NF for 24 and 48 h. To measure oxidative stress (OS) we investigated MDA, SOD, and GST expression along with Nrf2 and its downstream gene and protein expression. Cell proliferation and apoptosis regulation was assayed with respective methods. RESULTS: Investigation revealed NF remarkably activate Nrf2 and its downstream proteins HO-1 and NQO1 at 48 h more substantially. Nrf2/Keap1 relative gene and protein expression indicated that NF might trigger Nrf2 upregulation by decreasing Keap1 expression. Both NF concentrations (3 µM and 9 µM) were able to deplete ROS and lipid peroxidation, concurrently, up-regulated SOD and GST. NF reduced cell proliferation significantly along with the regulation of apoptotic proteins Bax, Bcl2, Cyt-C, Caspase 9, and Caspase 3 at the same time (48 h). CONCLUSION: This study is the first to manifest that NF may potentially regulate BPH by counterbalancing between OS and apoptosis through the activation of Nrf2-ARE pathway.

One month of the novel coronavirus 2019 outbreak: Is it still a threat?

The novel coronavirus 2019 disease (COVID-19) is now in an outbreak not only in China but also around the world, suspected to be originated from a wet market in Wuhan, Hubei province, China. The flare-up of COVID-19, it has already been infected 78,811 people with 2462 fatalities in 1 month window. The most alarming issue is the virus can transmit from host to host and still asymptomatic. Currently, 24 counties with 505 confirmed cases have been reported. Presently, there is no specific treatment or vaccine but physicians are battling with the use of antibiotics, steroid, anti-viral and anti-HIV drugs and some of the infected cases are testified improved. WHO and China National health Commission are cooperatively striving to come up with elucidation but it will take a minimum of 3 to 4 months at least to undergo a phase-1 trial. However, the soaring rates of spreading each day has become much stable which might even improve within the next few weeks in China but not for some other countries. Healthy peoples are instructed to avoid public gathering, always wearing the mask and frequently wash hands. Currently, China has able to hold up more than 97.7% infection within China but a scientific breakthrough is crucial before it's too late.

Effects of isocorynoxeine, from Uncaria, on lower urinary tract dysfunction caused by benign prostatic hyperplasia via antagonism of α1A-adrenoceptors.

Medical therapy of lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) targets smooth muscle contraction in the prostate, for which α1A-adrenoceptor (α1A-AR) antagonists have been considered to be the primary therapeutic method. We investigated the effects and underlying mechanisms of isocorynoxeine (ICN), one of indole alkaloids from Uncaria, on the treatment of LUTS secondary to BPH via α1A-ARs in mice. The effect of ICN on prostatic contractility was studied via myographic measurements in the prostates of rabbits. The effects of ICN on bladder function, serum-hormone levels, bladder histology, and prostate histology were determined in testosterone propionate-induced prostatic hyperplasic wild-type (WT) and α1A-AR knockout (α1A-KO) mice. The cytotoxicity of ICN in cultured human prostatic stromal cells (WPMY-1) was assessed by the following: a cell-counting kit, measuring the relaxant effect on WPMY-1 by a collagen gel contraction assay, intracellular Ca2+ mobilization indicated by Fluo-4, cytoskeletal organization by phalloidin staining, and expressions of α1A-AR-mediated key messengers by western blot analyses. ICN non-competitively antagonized the contractions of prostates induced by α1A-AR agonists. ICN treatment improved bladder functions in prostatic hyperplasic WT mice, whereas it failed to ameliorate bladder functions in prostatic hyperplasic α1A-KO mice. In WPMY-1, ICN relaxed cell contractions on collagen gels, disrupted F-actin organization, inhibited α1A-AR agonist-stimulated Ca2+ mobilization, and antagonized α1A-ARs via the RhoA/ROCK2/MLC signaling pathway. Our results suggest that ICN may be a promising therapeutic drug for targeting α1A-ARs in the treatment of BPH/LUTS.

Endothelium-independent vasodilator effect of isocorynoxeine in vitro isolated from the hook of Uncaria rhynchophylla (Miquel).

This study was designed to investigate the vasorelaxant effects and underlying mechanism of isocorynoxeine (ICN), one of the indole alkaloids from Uncaria hooks, on isolated mesenteric arteries in vitro. The myograph system was applied for isometric tension recording in the vascular rings. ICN relaxed both endothelium-intact and endothelium-denuded rat vascular rings precontracted with phenylephrine or KCl in a dose-dependent manner. Propranolol, tetraethylammonium, BaCl2, and glibenclamide had no influence on the vasodilator effect of ICN on phenylephrine-primed vascular rings, while 4-aminopyridine decreased the maximum relaxation. Furthermore, ICN produced a significant drop in maximum response in the PE log concentration-response curve without shifting to the right. In the Ca2+-free Kreb's-Henseleit buffer, ICN inhibited the contraction in vascular rings evoked by PE, but not by KCl. The phasic contractions of segments in the Ca2+-free Kreb's-Henseleit buffer induced by CaCl2 were restrained by ICN, while contractions elicited by caffeine displayed no differences. Furthermore, the phasic vasodilation of ICN was significantly lower than controls when pretreated with nifedipine and heparin. Both BAYK8644- and PE-evoked responses were significantly inhibited in the presence of 100 µM of ICN in human vascular smooth muscle cells loaded with the fluorescent Ca2+ indicator Fluo-4-AM. All these results suggest that ICN act in an endothelium-independent manner on the mesenteric artery. Its mechanisms of vasorelaxant action were produced by the inhibition of L-type calcium channel-mediated external Ca2+ influx and α1A-adrenoceptor-mediated intracellular Ca2+ release in vascular smooth muscle cells, and the participation of the Kv channel.