Ginkgo biloba extract possess several promising biological activities; currently, it is clinically employed in the management of several diseases. This research work aimed to extrapolate the antioxidant and anti-inflammatory effects of Ginkgo biloba (Gb) in methotrexate (MTX)-induced liver toxicity model. These effects were analyzed using different in vivo experimental approaches and by bioinformatics analysis. Male SD rats were grouped as follows: saline; MTX; Gb (pretreated for seven days with 60, 120, and 180 mg/kg daily dose before MTX treatment); silymarin (followed by MTX treatment); Gb 180 mg/kg daily only; and silymarin only. Histopathological results revealed that MTX induced marked hepatic injury, associated with a substantial surge in various hepatic enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and serum alkaline phosphatase (ALP). Furthermore, MTX caused the triggering of oxidative distress associated with a depressed antioxidant system. All these injury markers contributed to a significant release of apoptotic (caspase-3 and c-Jun N-terminal kinases (JNK)) and tumor necrosis factor (TNF-α)-like inflammatory mediators. Treatment with Gb counteracts MTX-mediated apoptosis and inflammation dose-dependently along with modulating the innate antioxidative mechanisms such as glutathione (GSH) and glutathione S-transferase (GST). These results were further supplemented by in silico study to analyze drug-receptor interactions (for several Gb constituents and target proteins) stabilized by a low energy value and with a good number of hydrogen bonds. These findings demonstrated that Gb could ameliorate MTX-induced elevated liver reactive oxygen species (ROS) and inflammation, possibly by JNK and TNF-α modulation.

Purpose: Melatonin and celecoxib are antioxidants and anti-inflammatory agents that exert protective effects in different experimental models. In this study, the neuroprotective effects of melatonin and celecoxib were demonstrated against ethanol-induced neuronal injury by in silico, morphological, and biochemical approaches. Methods: For the in silico study, 3-D structures were constructed and docking analysis performed. For in vivo studies, rats were treated with ethanol, melatonin, and celecoxib. Brain samples were collected for biochemical and morphological analysis. Results: Homology modeling was performed to build 3-D structures for IL1β), TNFα, TLR4, and inducible nitric oxide synthase. Structural refinement was achieved via molecular dynamic simulation and processed for docking and postdocking analysis. Further in vivo experiments showed that ethanol induced marked neuronal injury characterized by downregulated glutathione, glutathione S-transferase, and upregulated inducible nitric oxide synthase. Additionally, ethanol increased the expression of TNFα and IL1β. Finally, neuronal apoptosis was demonstrated in ethanol-intoxicated animals using caspase 3 and activated JNK staining. On the other hand, melatonin and celecoxib treatment ameliorated the biochemical and immunohistochemical alterations induced by ethanol. Conclusion: These results demonstrated that ethanol induced neurodegeneration by activating inflammatory and apoptotic proteins in rat brain, while melatonin and celecoxib may protect rat brain by downregulating inflammatory and apoptotic markers.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection can trigger the adaptive and innate immune responses, leading to uncontrolled inflammatory reactions and associated local and systematic tissue damage, along with thromboembolic disorders that may increase the risk of acute ischemic stroke (AIS) in COVID-19 patients. The neuropilin (NRP-1) which is a co-receptor for the vascular endothelial growth factor (VEGF), integrins, and plexins, is involved in the pathogenesis of AIS. NRP-1 is also regarded as a co-receptor for the entry of SARS-CoV-2 and facilitates its entry into the brain through the olfactory epithelium. NRP-1 is regarded as a cofactor for binding of SARS-CoV-2 with angiotensin-converting enzyme 2 (ACE2), since the absence of ACE2 reduces SARS-CoV-2 infectivity even in presence of NRP-1. Therefore, the aim of the present study was to clarify the potential role of NRP-1 in COVID-19 patients with AIS. SARS-CoV-2 may transmit to the brain through NRP-1 in the olfactory epithelium of the nasal cavity, leading to different neurological disorders, and therefore about 45% of COVID-19 patients had neurological manifestations. NRP-1 has the potential capability to attenuate neuroinflammation, blood–brain barrier (BBB) permeability, cerebral endothelial dysfunction (ED), and neuronal dysfunction that are uncommon in COVID-19 with neurological involvement, including AIS. Similarly, high NRP-1 serum level is linked with ED, oxidative stress, and the risk of pulmonary thrombosis in patients with severe COVID-19, suggesting a compensatory mechanism to overcome immuno-inflammatory disorders. In conclusion, NRP-1 has an important role in the pathogenesis of COVID-19 and AIS, and could be the potential biomarker linking the development of AIS in COVID-19. The present findings cannot provide a final conclusion, and thus in silico, experimental, in vitro, in vivo, preclinical, and clinical studies are recommended to confirm the potential role of NRP-1 in COVID-19, and to elucidate the pharmacological role of NRP-1 receptor agonists and antagonists in COVID-19.

Alzheimer’s disease is an emerging health disorder associated with cognitive decline and memory loss. In this study, six curcumin analogs (1a–1f) were synthesized and screened for in vitro cholinesterase inhibitory potential. On the basis of promising results, they were further investigated for in vivo analysis using elevated plus maze (EPM), Y-maze, and novel object recognition (NOR) behavioral models. The binding mode of the synthesized compounds with the active sites of cholinesterases, and the involvement of the cholinergic system in brain hippocampus was determined. The synthesized curcumin analog 1d (p < 0.001, n = 6), and 1c (p < 0.01, n = 6) showed promising results by decreasing retention time in EPM, significantly increasing % SAP in Y-maze, while significantly (p < 0.001) enhancing the % discrimination index (DI) and the time exploring the novel objects in NORT mice behavioral models. A molecular docking study using MOE software was used for validation of the inhibition of cholinesterase(s). It has been indicated from the current research work that the synthesized curcumin analogs enhanced memory functions in mice models and could be used as valuable therapeutic molecules against neurodegenerative disorders. To determine their exact mechanism of action, further studies are suggested.

Enterococcus species are an emerging group of bacterial pathogens that have a significant role in hospital-associated infections and are associated with higher mortality and morbidity rates. Among these pathogens, Enterococcus mundtii is one of the causative agents of multiple hospital associated infections. Currently, no commercially available licensed vaccine is present, and multi-drug resistant strains of the pathogen are prominent. Due to several limitations of experimental vaccinology, computational vaccine designing proved to be helpful in vaccine designing against several bacterial pathogens. Herein, we designed a multi-epitope-based vaccine against E. mundtii using in silico approaches. After an in-depth analysis of the core genome, three probable antigenic proteins (lytic polysaccharide monooxygenase, siderophore ABC transporter substrate-binding protein, and lytic polysaccharide monooxygenase) were shortlisted for epitope prediction. Among predicted epitopes, ten epitopes—GPADGRIAS, TTINHGGAQA, SERTALSVTT, GDGGNGGGEV, GIKEPDLEK, KQADDRIEA, QAIGGDTSN, EPLDEQTASR, AQWEPQSIEA, QPLKFSDFEL—were selected for multi-epitope vaccine construct designing. The screened B- and T-cell epitopes were joined with each other via specific linkers and linked to the cholera toxin B subunit as an adjuvant to enhance vaccine immune protection efficacy. The designed vaccine construct induced cellular and humoral immune responses. Blind docking with immune cell receptors, followed by molecular dynamic simulation results confirms the good binding potency and stability of the vaccine in providing protection against the pathogen.

Crocus sativus, a medicinally important herbaceous plant, has been traditionally used to cure coughs, colds, insomnia, cramps, asthma, and pain. Moreover, the therapeutic applications of saffron include its immunomodulatory and anticancer properties. The current experimental analysis was performed to explore the potential nutraceutical efficacy of corm, leaf, petal, and stigma of saffron ethanolic extracts as analgesic, anti-inflammatory, anticoagulant, and antidepressant using hot plate, carrageenan-induced paw edema, capillary tube and forced swim test, respectively in mice. The results indicated that among all the extracts, stigma ethanolic extract (SEE) represented maximum latency activity (72.85%) and edema inhibition (77.33%) followed by petal ethanolic extract (PEE) with latency activity and edema inhibition of 64.06 and 70.50%, respectively. Corm ethanolic extract (CEE) and leaf ethanolic extract (LEE) displayed mild analgesic activity of 22.40% and 29.07%, respectively. Additionally, LEE (53.29%) and CEE (47.47%) exhibited mild to moderate response against inflammation. The coagulation time of SEE (101.66 s) was almost equivalent to the standard drug, aspirin (101.66 s), suggesting a strong anticoagulant effect followed by PEE (86.5 s). LEE (66.83 s) represented moderate inhibitory effect on coagulation activity while CEE (42.83 s) showed neutral effect. Additionally, PEE and SEE also expressed itself as potential antidepressants with immobility time ≤76.66 s, while CEE (96.50 s) and LEE (106.83 s) indicated moderate to mild antidepressant efficacy. Based on the in vivo activities, saffron extract, particularly SEE and PEE, can be used as a potential nutraceutical and therapeutic agent due to its significant pharmacological activities.