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Background The absolute number of new stroke patients is annually increasing and there still remains only a few Food and Drug Administration (FDA) approved treatments with significant limitations available to patients. Tanshinone IIA (Tan IIA) is a promising potential therapeutic for ischemic stroke that has shown success in pre-clinical rodent studies but lead to inconsistent efficacy results in human patients. The physical properties of Tan-IIA, including short half-life and low solubility, suggests that Poly (lactic-co-glycolic acid) (PLGA) nanoparticle-assisted delivery may lead to improve bioavailability and therapeutic efficacy. The objective of this study was to develop Tan IIA-loaded nanoparticles (Tan IIA-NPs) and to evaluate their therapeutic effects on cerebral pathological changes and consequent motor function deficits in a pig ischemic stroke model. Results Tan IIA-NP treated neural stem cells showed a reduction in SOD activity in in vitro assays demonstrating antioxidative effects. Ischemic stroke pigs treated with Tan IIA-NPs showed reduced hemispheric swelling when compared to vehicle only treated pigs (7.85 ± 1.41 vs. 16.83 ± 0.62%), consequent midline shift (MLS) (1.72 ± 0.07 vs. 2.91 ± 0.36 mm), and ischemic lesion volumes (9.54 ± 5.06 vs. 12.01 ± 0.17 cm3) when compared to vehicle-only treated pigs. Treatment also lead to lower reductions in diffusivity (−37.30 ± 3.67 vs. −46.33 ± 0.73%) and white matter integrity (−19.66 ± 5.58 vs. −30.11 ± 1.19%) as well as reduced hemorrhage (0.85 ± 0.15 vs 2.91 ± 0.84 cm3) 24 h post-ischemic stroke. In addition, Tan IIA-NPs led to a reduced percentage of circulating band neutrophils at 12 (7.75 ± 1.93 vs. 14.00 ± 1.73%) and 24 (4.25 ± 0.48 vs 5.75 ± 0.85%) hours post-stroke suggesting a mitigated inflammatory response. Moreover, spatiotemporal gait deficits including cadence, cycle time, step time, swing percent of cycle, stride length, and changes in relative mean pressure were less severe post-stroke in Tan IIA-NP treated pigs relative to control pigs. Conclusion The findings of this proof of concept study strongly suggest that administration of Tan IIA-NPs in the acute phase post-stroke mitigates neural injury likely through limiting free radical formation, thus leading to less severe gait deficits in a translational pig ischemic stroke model. With stroke as one of the leading causes of functional disability in the United States, and gait deficits being a major component, these promising results suggest that acute Tan IIA-NP administration may improve functional outcomes and the quality of life of many future stroke patients., Highlights • Tanshinone IIA loaded nanoparticles demonstrate antioxidative capabilities in neural stem cell cultures. • Tanshinone IIA loaded nanoparticles leads to reduced lesion volume, midline shift, and white matter damage post-stroke. • Tanshinone IIA loaded nanoparticle treatment leads to marked improvements in spatiotemporal and kinetic gait parameters.

Transmissible Covid-19, caused by novel corona virus since last of 2019 has outspread widely until now. Where, India was the second most affected country and 3rd in mortality rate. In world ancient history, medicinal plants were played a crucial role to cure several diseases. In present study, we show some novel natural medicinal plant metabolites as the potential inhibitors against papain-like protease (PLpro), main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), transmembrane proteinase Serine 2 (TMPRSS2) and angiotensin converting enzyme-2 (ACE-2) of Covid-19. Plant metabolites were having been proven to inhibit SARS-CoVs, which also actively walkable against Covid-19., Graphical abstract Image 1

Graphical abstract, The 2019 novel coronavirus (2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)) has witnessed a rapid and global proliferation since its early identification in patients with severe pneumonia in Wuhan, China. As of 27th May 2020, 2019-nCoV cases have risen to >5 million, with confirmed deaths of 350,000. However, Coronavirus disease (COVID-19) diagnostic and treatment measures are yet to be fully unraveled, given the novelty of this particular coronavirus. Hence, no drug or vaccine has been adapted for treatment, and the accuracy of the current diagnostic tests is debatable. Therefore, existing antiviral agents used for severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) were repurposed for COVID-19, taking their biological features into consideration. This study provides a concise review of the current and emerging detection and supervision technologies for SARS-CoV-2, which is the viral etiology of COVID19, and their performance characteristics, with emphasis on the novel Nano-based diagnostic tests (protein corona sensor array and magnetic levitation) and treatment measures (treatment protocols based on nano-silver colloids) for COVID-19.

Background : The corona virus disease 2019 (COVID-19) pandemic has highlighted the fact that there are few effective anti-viral agents for treating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Although the very recent development of vaccines is an extremely important breakthrough it remains unclear how long-lived such vaccines will be. The development of new agents therefore remains an important goal. Purpose : Given the multifaceted pathology of COVID-19, a combinatorial formulation may provide an effective treatment. BEN815, a natural nutraceutical composed of extracts from guava leaves (Psidium guajava L), green tea leaves (Camellia sinensis), and rose petals (Rosa hybrida), had previously shown to have a therapeutic effect on allergic rhinitis. We investigated whether BEN815 possesses anti-inflammatory, antiviral and antioxidant activities, since the combination of these effects could be useful for the treatment of COVID-19. Study design : We examined the anti-inflammatory effects of BEN815 and its principal active components quercetin and epigallocatechin gallate (EGCG) in lipopolysaccharide (LPS)-induced RAW264.7 cells and in an LPS-challenged mouse model of endotoxemia. We also assessed the antioxidant activity, and antiviral effect of BEN815, quercetin, and EGCG in SARS-CoV-2-infected Vero cells. Methods : The principal active ingredients in BEN815 were determined using HPLC. Changes in the levels of LPS-induced pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α were measured by ELISA. Changes in the expression levels of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) were analyzed using western blotting. Antioxidant assay was performed using DPPH and ABTS assay. SARS-CoV-2 replication was measured by immunofluorescence staining. Results : BEN815 significantly suppressed the induction of IL-6 and TNF-α as well as COX-2 and iNOS in LPS-induced RAW264.7 cells. In addition, BEN815 protected against LPS-challenged endotoxic shock in mice. Two major ingredients of BEN815, quercetin and EGCG, reduced the induction of IL-6 and TNF-α as well as COX-2 and iNOS synthase in LPS-induced RAW264.7 cells. BEN815, quercetin, and EGCG were also found to have antioxidant effects. Importantly, BEN815 and EGCG could inhibit SARS-CoV-2 replications in Vero cells. Conclusion : BEN815 is an anti-inflammatory, antiviral, and antioxidant natural agent that can be used to prevent and improve inflammation-related diseases, COVID-19., Graphical abstract Image, graphical abstract

Graphical abstract, Owing to the efficacy in reducing pain and inflammation, non-steroidal anti-inflammatory drugs (NSAIDs) are amongst the most popularly used medicines confirming their position in the WHO’s Model List of Essential Medicines. With escalating musculoskeletal complications, as evident from 2016 Global Burden of Disease data, NSAID usage is evidently unavoidable. Apart from analgesic, anti-inflammatory and antipyretic efficacies, NSAIDs are further documented to offer protection against diverse critical disorders including cancer and heart attacks. However, data from multiple placebo-controlled trials and meta-analyses studies alarmingly signify the adverse effects of NSAIDs in gastrointestinal, cardiovascular, hepatic, renal, cerebral and pulmonary complications. Although extensive research has elucidated the mechanisms underlying the clinical hazards of NSAIDs, no review has extensively collated the outcomes on various multiorgan toxicities of these drugs together. In this regard, the present review provides a comprehensive insight of the existing knowledge and recent developments on NSAID-induced organ damage. It precisely encompasses the current understanding of structure, classification and mode of action of NSAIDs while reiterating on the emerging instances of NSAID drug repurposing along with pharmacophore modification aimed at safer usage of NSAIDs where toxic effects are tamed without compromising the clinical benefits. The review does not intend to vilify these ‘wonder drugs’; rather provides a careful understanding of their side-effects which would be beneficial in evaluating the risk–benefit threshold while rationally using NSAIDs at safer dose and duration.

Graphical abstract, Highlights • Tacrolimus (TAC), an immunosuppressant drug has been demonstrated to augment free radical production. • It increased serum creatinine, BUN and oxidative deterioration of cellular tissues in CD-1 mice. • TAC-induced nephrotoxicity altered the mitochondrial antioxidant defense, expression of PCNA, Bcl2. • TAC-induced changes are ameliorated by pretreatment of Ocimum basilicum L (OB). • OB can be considered as a potential source of antioxidants, phenols, alkaloids with potent nephroprotective activity., Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC50) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P

The search for safe antimalarial compounds acting against asexual symptom-responsible stages and sexual transmission-responsible forms of Plasmodium species is one of the major challenges in malaria elimination programs. So far, among current drugs approved for human use, only primaquine has transmission-blocking activity. The discovery of small molecules targeting different Plasmodium falciparum life stages remains a priority in antimalarial drug research. In this context, several independent studies have recently reported antiplasmodial and transmission-blocking activities of commonly used stains, dyes and fluorescent probes against P. falciparum including chloroquine-resistant isolates. Herein we have studied the antimalarial activities of dyes with different scaffold and we report that the triarylmethane dye (TRAM) Brilliant green inhibits the growth of asexual stages (IC50 ≤ 2 μM) and has exflagellation-blocking activity (IC50 ≤ 800 nM) against P. falciparum reference strains (3D7, 7G8) and chloroquine-resistant clinical isolate (Q206). In a second step we have investigated the antiplasmodial activities of two polysulfonated triarylmethane food dyes. Green S (E142) is weakly active against P. falciparum asexual stage (IC50 ≃ 17 μM) whereas Patent Blue V (E131) is inactive in both antimalarial assays. By applying liquid chromatography techniques for the culture supernatant analysis after cell washings and lysis, we report the detection of Brilliant green in erythrocytes, the selective uptake of Green S (E142) by infected erythrocytes, whereas Patent Blue V (E131) could not be detected within non-infected and 3D7-infected erythrocytes. Overall, our results suggest that two polysulfonated food dyes might display different affinity with transporters or channels on infected RBC membrane., Graphical abstract Image 1, Highlights • Dyes are tested against P. falciparum 3D7, 7G8 lines, CQ-resistant field isolate Q206. • Brilliant green is active against asexual and sexual stages of Plasmodium falciparum. • Food dye Green S (E142) is weakly active against Plasmodium falciparum asexual forms. • Food dye Green S (E142) is found in the cellular content of infected erythrocytes. • Polysulfonated triarylmethane possibly interact with plasmodial surface anion channel.

undergoes complex metabolic and morphological changes during its lifecycle in order to adapt and survive inside the mammalian host and the tsetse fly vector. Oneof these adaptations to different environments is reflected by the expression of variousnucleoside transporters. As protozoan parasites are unable to synthesise the purine ring