Green Synthesized Silver Nanoparticles as Silver Lining in Antimicrobial Resistance: A Review.

Unprincipled use of antibiotics has led to antimicrobial resistance (AMR) against mostly available compounds, and has now become a major cause of concern for the scientific community. However, in the past decade, green synthesized silver nanoparticles (AgNPs) have received greater attention for the development of newer therapies as antimicrobials by virtue of their unique physico- chemical properties. Unlike traditional antibiotics, AgNPs exert their action by acting on multiple mechanisms, which make them potential candidates against AMR. Green synthesis of AgNPs using various medicinal plants has demonstrated a broader spectrum of action against several microbes in a number of attempts. The present paper provides an insight into the scientific studies that have elucidated the positive role of plant extracts/phytochemicals during the green synthesis of AgNPs and their future perspectives. The studies conducted so far seem promising; still, a few factors like the precise mechanism of action of AgNPs, their synergistic interaction with biomolecules, and industrial scalability, need to be explored further till effective drug development using green synthesized AgNPs in healthcare systems against AMR is established.

Demystifying therapeutic potential of medicinal plants against chikungunya virus.

Viral infections are posing a great threat to humanity for the last few years. Among these, Chikungunya which is a mosquito-borne viral infection has produced enormous epidemics around the world after been rebounded. Although this infection shows a low mortality rate, patients suffer from fever, arthralgia, and maculopapular rashes, which reduce the quality of life for several weeks to years. The currently available treatments only provide symptomatic relief based on analgesics, antipyretics, and anti-inflammatory drugs which are nonspecific without satisfactory results. Medicinal plants are a widely accepted source of new molecules for the treatment of infectious diseases including viral infections. The scientific reports, primarily focusing on the anti-chikungunya activity of plant extracts, natural origin pure compounds, and their synthetic analog published from 2011 to 2021, were selected from PubMed, Google Scholar, and Scopus by using related keywords like anti-chikungunya plants, natural antivirals for Chikungunya. The present review decodes scientific reports on medicinal plants against chikungunya virus (CHIKV) infection and demystifies the potential phytoconstituents which reveals that the screening of flavonoids containing plants and phytochemicals showing efficacy against other arbovirus infections, may prove as a potential lead for drug development against CHIKV. The present article also outlines pathogenesis, clinical aspects, molecular virology, and diagnostic approaches of CHIKV infection.

Lipid profile as an indicator of COVID-19 severity: A systematic review and meta-analysis.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic. Studies reported dyslipidemia in patients with COVID-19. Herein, we conducted a systematic review and meta-analysis of published articles to evaluate the association of the lipid profile with the severity and mortality in COVID-19 patients. METHODS: PubMed/Medline, Europe PMC, and Google Scholar were searched for studies published between January 1, 2020 and January 13, 2021. Random or Fixed effects models were used to calculate the mean difference (MD) and 95% confidence intervals (CIs). Statistical heterogeneity was assessed using Cochran's Q test and I2 statistics. RESULTS: This meta-analysis included 19 studies. Of which, 12 studies were categorized by severity, 04 studies by mortality, and 03 studies by both severity and mortality. Our findings revealed significantly decreased levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in the severe group when compared with the non-severe group in a random effect model. Similarly, random effect model results demonstrated significantly lower levels of HDL-C and LDL-C in the non-survivor group when compared with the survivor group. The level of TC was also found to be decreased in the non-survivor group when compared to the survivor group in a fixed-effect model. CONCLUSION: In conclusion, the lipid profile is associated with both the severity and mortality in COVID-19 patients. Hence, the lipid profile may be used for assessing the severity and prognosis of COVID-19. PROSPERO REGISTRATION NUMBER: CRD42021216316.

Skin photo-protection with phytochemicals against photo-oxidative stress, photo-carcinogenesis, signal transduction pathways and extracellular matrix remodeling-An overview.

Excessive exposure of skin to UV radiation triggers the generation of oxidative stress, inflammation, immunosuppression, apoptosis, matrix-metalloproteases production, and DNA mutations leading to the onset of photo ageing and photo-carcinogenesis. At the molecular level, these changes occur via activation of several protein kinases as well as transcription pathways, formation of reactive oxygen species, and release of cytokines, interleukins and prostaglandins together. Current therapies available on the market only provide limited solutions and exhibit several side effects. The present paper provides insight into scientific studies that have elucidated the positive role of phytochemicals in counteracting the UV-induced depletion of antioxidant enzymes, increased lipid peroxidation, inflammation, DNA mutations, increased senescence, dysfunctional apoptosis and immune suppression. The contribution of phytochemicals to the downregulation of expression of oxidative-stress sensitive transcription factors (Nrf2, NF-Kb, AP-1 and p53) and protein kinases (MSK, ERK, JNK, p38 MAPK, p90RSK2 and CaMKs) involved in inflammation, apoptosis, immune suppression, extracellular matrix remodelling, senescence, photo ageing and photo-carcinogenesis, is also discussed. Conclusively, several phytochemicals hold potential for the development of a viable solution against UV irradiation-mediated photo ageing, photo-carcinogenesis and related manifestations.

Amantadine exerts anxiolytic like effect in mice: Evidences for the involvement of nitrergic and GABAergic signaling pathways.

Amantadine is a glutamatergic antagonist that works by inhibiting the NMDA receptor. Besides the inhibition of NMDA receptors amantadine also stabilizes the glutamatergic system and protects the neurons against the NMDA toxicity. Amantadine treatment also reduces the production of NO and metabolism of GABA. Therefore amantadine modulates glutamate, GABA and NO which are known to be implicated in the pathogenesis of anxiety and related behavior. The present study was designed to investigate the anxiolytic like effect of amantadine in mice. Nitrergic and GABAergic signaling influence in the anxiolytic like effect of amantadine was also studied. Amantadine (25, 50 and 75 mg/kg, i.p.) was administered and the anxiety related behavior was determined using light and dark box (LDB) and elevated plus maze (EPM) methods. Further, the effect of various treatments on the whole brain glutamate, nitrite and GABA levels were also determined. The results obtained demonstrated that the amantadine (50 mg/kg, i.p.) exerted anxiolytic like effect in mice and reduced the levels of glutamate, nitrite and GABA in the brain of mice as compared to control. Further, the influence of NO and GABA in the anxiolytic like effect of the amantadine was also determined. The results obtained demonstrated that NO donor counteracted while NO inhibitor potentiated the anxiolytic like effect of amantadine in mice. Also the combined treatment of amantadine (25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) did not affect the anxiety related behavior, brain GABA and nitrite level of mice but reduced the levels the brain glutamate levels significantly as compared to amantadine (25 mg/kg, i.p.) and diazepam (1 mg/kg, i.p.) treated mice. Thus, amantadine exerted anxiolytic like effect in mice and the anxiolytic like effect of amantadine was modulated by nitrergic and GABAergic signaling pathway.

Lithium potentiated, pyridoxine abolished and fluoxetine attenuated the anxiolytic effect of diazepam in mice.

In the present study, the anxiolytic effect of diazepam (1 and 2 mg/kg, i.p.) was determined alone and in combination with lithium (50 mg/kg, i.p.), pyridoxine (90 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) using elevated plus maze (EPM) and light/dark box (LDB) tests in experimental mice. The effect of various treatments on the brain GABA levels and glutamic acid decarboxylase (GAD) expression were also determined. The results obtained suggested that the diazepam (2 mg/kg, i.p.) exerted anxiolytic effect and significantly increased the brain GABA levels and GAD expression as compared to control group. Fluoxetine (10 mg/kg, i.p.) exerted anxiogenic effects, but did not affect the brain GABA levels and GAD activity significantly as compared to control. Pretreatments of pyridoxine (90 mg/kg, i.p.) abolished; lithium (50 mg/kg, i.p.) potentiated while fluoxetine (10 mg/kg, i.p.) attenuated the anxiolytic and neurochemical effects of diazepam (1 and 2 mg/kg, i.p.) treatment in mice. Therefore, the combined treatment of lithium and diazepam might be a promising treatment for anxiety.

Nitrergic signaling modulation by ascorbic acid treatment is responsible for anxiolysis in mouse model of anxiety.

The present study was designed to investigate the effect of ascorbic acid (AA) treatment on the anxiety related behavioral and neurochemical alterations. AA (50, 100 and 200 mg/kg, i.p.) was administered to the mice and anxiety related behavior and levels of glutamate and nitrite in the brain of mice were determined. The results obtained revealed that the administration of AA (100 mg/kg, i.p.) significantly reduced the anxiety related behavior and the levels of nitrite in the brain of mice. Nitrergic interactions were further determined by the pretreatment of mice with nitric oxide (NO) modulator and AA treatment followed by behavioral and neurochemical measurements. The results obtained suggested that NO inhibition potentiated the anxiolytic like activity of AA in mice. It was also observed that the glutamate and nitrite level in the brain of mice were significantly reduced by the NO inhibitor pretreatment. Thus, the present study demonstrated the possible nitrergic pathways modulation in the anxiolytic like activity of AA in mice.

NO-sGC-cGMP signaling influence the anxiolytic like effect of lithium in mice in light and dark box and elevated plus maze.

Glutamate is an excitatory neurotransmitter implicated in the pathogenesis of psychiatric disorders. Glutamate results in the activation of an enzyme called glycogen synthase kinase-3 (GSK-3) acting through N-methyl-d-aspartate (NMDA) receptors. Impaired expression of GSK-3 affects behavior and neurochemicals level in the brain responsible for the pathogenesis of mood disorders. It has been reported that lithium acts as an inhibitor of GSK-3 and inhibit the enzyme GSK-3 in an uncompetitive manner. In the present study, anxiolytic like effect of lithium in mice is investigated through light and dark box (LDB) and elevated plus maze (EPM). Lithium (50, 100 and 200 mg/kg, i.p.) was administered to the mice to determine the anxiety related behavior. Results obtained suggests that the administration of lithium (100 mg/kg, i.p.) reversed the anxiety related behavior of mice and decreased the levels of glutamate and nitrite as compared to control. Glutamate acting through the NMDA receptor has been found to regulate the expression of enzyme neuronal nitric oxide synthase (nNOS), which is responsible for the release of nitric oxide (NO), suggesting a possible link between NO and GSK-3 also. Therefore, to determine the possible interaction with NO, sub-effective dose of lithium was administered in combination with NO donor i.e. l-Arginine (50 mg/kg, i.p.), NOS and soluble guanylate cyclase (sGC) inhibitor i.e. methylene blue (1 mg/kg, i.p.) and phosphodiesterase inhibitor i.e. sildenafil (1 mg/kg, i.p.). The results obtained demonstrated that the anxiolytic like effect of lithium was abolished by the pretreatment with NO donor and potentiated by the pretreatment with NOS inhibitor. Therefore, it is suggested that NO signaling pathway influence the anxiolytic like activity of lithium in mice, further suggesting the link between the GSK-3 and NO signaling in the regulation of anxiety related behavior.

Anxiolytic-like effect of pyridoxine in mice by elevated plus maze and light and dark box: Evidence for the involvement of GABAergic and NO-sGC-cGMP pathway.

Present study was carried out to investigate the 'anxiolytic-like' effect of pyridoxine in mice. Pyridoxine (90, 180 and 360 mg/kg) was administered by intraperitoneal (i.p.) route to the experimental mice and anxiety-related behavior was evaluated by light and dark box (LDB) and elevated plus maze (EPM) models. Glutamate, GABA and nitrite levels were also determined in the isolated whole brain of mice. It was observed that pyridoxine (180 mg/kg, i.p.) exerted 'anxiolytic-like' effect in mice in EPM and LDB models. Also, there was a significant increase in the levels of GABA whereas; the levels of glutamate and nitrite were decreased as compared to the control group. Administration of pentamethylene tetrazole (PTZ; 20 mg/kg, i.p.) exerted anxiogenic effects in mice, but the combination of PTZ and pyridoxine (180 mg/kg, i.p.) abolished the 'anxiolytic-like' effect of pyridoxine, thereby, suggesting the possible role of GABA in the 'anxiolytic-like' effect of pyridoxine in mice. Further, the influence of NO-sGC-cGMP pathway was investigated by administering the sub-effective dose of pyridoxine in combination with sub-threshold doses of NO modulators i.e. l­arginine (50 mg/kg, i.p.; NO donor); methylene blue (1 mg/kg, i.p.; NO and soluble guanylate cyclase inhibitor) and sildenafil (1 mg/kg, i.p.; phosphodiesterase inhibitor and cGMP modulator). It was observed that the 'anxiolytic-like' effect of pyridoxine in mice was counteracted by the NO donor and potentiated by the NO inhibitors. Thus, the present study confirmed the involvement of GABAergic and NO-sGC-cGMP pathway in the 'anxiolytic-like' effect of pyridoxine in mice.

Antioxidant potential of Lactuca sativa.

The present study is based on the evaluation of antioxidant potential of a well known plant Lactuca sativa. Methanolic leaf extract was investigated for in vitro inhibition of oxidative damage induced by UV-radiations to the salmonella typhi bacteria and in vivo effect on the production of body enzymes i.e. catalase and superoxide dismutase. The lipid peroxidation masurement was also done in terms of thiobarbituric acid reactive substances (TBARS) in blood and brain of male albino wistar rats. The plant extract has shown significant antioxidant potential both in vitro and in vivo.