The COVID-19 pandemic constitutes an arduous global health challenge, and the increasing number of fatalities calls for the speedy pursuit of a remedy. This review emphasizes the changing aspects of the COVID-19 disease, featuring the cytokine storm’s pathological processes. Furthermore, we briefly reviewed potential therapeutic agents that may modulate and alleviate cytokine storms. The literature exploration was made using PubMed, Embase, MEDLINE, Google scholar, and China National Knowledge Infrastructure databases to retrieve the most recent literature on the etiology, diagnostic markers, and the possible prophylactic and therapeutic options for the management of cytokine storm in patients hospitalized with COVID-19 disease. The causative agent, severe acute respiratory coronavirus-2 (SARS-CoV-2), continually threatens the efficiency of the immune system of the infected individuals. As the first responder, the innate immune system provides primary protection against COVID-19, affecting the disease’s progression, clinical outcome, and prognosis. Evidence suggests that the fatalities associated with COVID-19 are primarily due to hyper-inflammation and an aberrant immune function. Accordingly, the magnitude of the release of pro-inflammatory cytokines such as interleukin (IL)-1, (IL-6), and tumor necrosis alpha (TNF-α) significantly differentiate between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for diagnosis and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. The prophylaxis and the rapid treatment of cytokine storm by clinicians will significantly enhance the fight against the dreaded COVID-19 disease.

At present, there is no cure or vaccine for the devastating new highly infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected people globally. Herein, we identified potent phytocompounds from two antiviral plants Momordica charantia L. and Azadirachta indica used locally for the treatment of viral and parasitic infections. Structure-based virtual screening and molecular dynamics (MD) simulation have been employed to study their inhibitory potential against the main protease (M pro ) SARS-CoV-2. A total of 86 compounds from M. charantia L. and A. indica were identified. The top six phytocompounds; momordicine, deacetylnimninene, margolonone, momordiciode F2, nimbandiol, 17-hydroxyazadiradione were examined and when compared with three FDA reference drugs (remdesivir, hydroxychloroquine and ribavirin). The top six ranked compounds and FDA drugs were then subjected to MD simulation and pharmacokinetic studies. These phytocompounds showed strong and stable interactions with the active site amino acid residues of SARS-CoV-2 Mpro similar to the reference compound. Results obtained from this study showed that momordicine and momordiciode F2 exhibited good inhibition potential (best MMGBA-binding energies; −41.1 and −43.4 kcal/mol) against the M pro of SARS-CoV-2 when compared with FDA reference anti-viral drugs (Ribavirin, remdesivir and hydroxychloroquine). Per-residue analysis, root mean square deviation and solvent-accessible surface area revealed that compounds interacted with key amino acid residues at the active site of the enzyme and showed good system stability. The results obtained in this study show that these phytocompounds could emerge as promising therapeutic inhibitors for the M pro of SARS-CoV-2. However, urgent trials should be conducted to validate this outcome. Communicated by Ramaswamy H. Sarma

The results of this study support that flavonoids may modulate the expression of GLP-1 and its release via TGR5. This finding may underscore its anti-diabetic potency.

The effect of consumption of leaves of Solanum macrocarpon L. on the Prostate Specific Antigen (PSA) level, antioxidant status and hematological parameters in albino rats induced with Benign Prostate Hyperplasia (BPH) was studied. Twenty five animals divided into five experimental groups namely Normal Control group (NC-group), Benign Prostate Hyperplasia group (BPH-group), Finasteride-group, 5% Solanum macrocarpon-supplemented diet group (5% SMSD-group) and 10% SMSD-group were used in the study. The NC was not induced with BPH and fed a control diet (diet I). The BPH-group and Finasteride-group were induced with BPH but Finasteride-group was treated with finasteride and both were fed a control diet (diet I). Five percent SMSD-group and 10% SMSD-group were induced with BPH and fed with 5 and 10% S. macrocarpon-Supplemented Diet (SMSD), respectively. Benign prostate hyperplasia was induced in the animals by daily subcutaneous injections of Testosterone Propionate (TP) in olive oil for a period of 12 weeks and the animals were fed their respective diets throughout the duration. Parameters including Prostate Specific Antigen (PSA), hematological indices including hemoglobin and white blood cells in vivo antioxidant markers such as Superoxide Dismutase (SOD), Glutathione-S-Transferase (GST), glutathione (GSH) and catalase were determined. The histo-pathological changes of the prostate were also examined. The results showed that PSA levels decreased significantly (p<0.05) in groups fed with SMSD. Superoxide dismutase (SOD), Glutathione-S-Transferase (GST) and glutathione (GSH) levels increased significantly (p<0.05) while WBC were significantly decreased (p<0.05) in the groups fed SMSD. The histological studies showed a considerable improvement in the prostatic histo-architecture of the groups fed SMSD. These findings indicate that S. macrocarponsupplemented diets may prevent or suppress the development of BPH and be useful in its treatment and management.

Lasianthera africana P. Beauv. (Icacinaceae) is a traditional Nigerian medicinal plant used for treatment of ulcers, diarrhea, parasitic infections and diabetes. This study was aimed at characterizing the bioactive principles extractable from the flavonoid-rich fraction of L. africana leaves (LAFRF), and to evaluate its effects on renal and cardiac functions. Isolation, and purification of the LAFRF was achieved using standard methods. The in vitro antioxidant activity was evaluated on DPPH* and ferric reducing antioxidant potential (FRAP). The total flavonoids (281.05 AE 7.44 mg QE/g), were identified, structurally characterized and quantified using high resolution ultra-performance liquid chromatography, in tandem with quadrupole-time-of-flight electrospray ionization mass spectrometer (UPLC-PDA-QTOF-ESI-MS/MS). Fifty Wistar rats of both sexes (110-130 g), were distributed into 10 groups (n ¼ 5). Groups 1 and 2 served as the normal and CCl 4 controls respectively. Groups 3A-6B constituted the preventive and curative studies. The effects of the LAFRF at 3, 10, and 30 mg/kg body weight on urea and creatinine concentrations, lactate dehydrogenase (LDH), and creatine kinase (CK) activities of CCl 4 -intoxicated rats were assessed. The LAFRF displayed remarkable in vitro antioxidant property by scavenging the DPPH*, with an IC 50 of 5.40 AE 0.00 μg/ml which is more potent than the scavenging activity of the ascorbic acid (IC 50 of 7.18 AE 0.00 μg/ml), and also effectively reduced Fe 3þ to Fe 2þ when compared to gallic acid. The UPLC-PDA-QTOF-ESI-MS/MS fingerprint of the LAFRF indicated presence of quercetin (758983.6 mg/kg), rutin (17540.4 mg/kg), luteolin (126524.3 mg/kg), isorhamnetin (197949.0 mg/kg), and other non-phenolic compounds. The LAFRF significantly (p < 0.05) improved renal function, and normalized cardiac enzyme activities in vivo. The ability of the LAFRF to scavenge the DPPH and Fe 3þ radicals, improve renal and cardiac functions following CCl 4 intoxication shows its potential in the development of alternative therapy for combating oxidative stress-related complications.

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Context Bryophyllum pinnatum (Lam.) Oken (Crassulaceae) is used traditionally to treat many ailments. Objectives This study characterizes the constituents of B. pinnatum flavonoid-rich fraction (BPFRF) and investigates their antioxidant and anticholinesterase activity using in vitro and in silico approaches. Materials and methods Methanol extract of B. pinnatum leaves was partitioned to yield the ethyl acetate fraction. BPFRF was isolated from the ethyl acetate fraction and purified. The constituent flavonoids were structurally characterized using UPLC-PDA-MS 2 . Antioxidant activity (DPPH), Fe 2+ -induced lipid peroxidation (LP) and anticholinesterase activity (Ellman’s method) of the BPFRF and standards (ascorbic acid and rivastigmine) across a concentration range of 3.125–100 μg/mL were evaluated in vitro for 4 months. Molecular docking was performed to give insight into the binding potentials of BPFRF constituents against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Results UPLC-PDA-MS 2 analysis of BPFRF identified carlinoside, quercetin (most dominant), luteolin, isorhamnetin, luteolin-7-glucoside. Carlinoside was first reported in this plant. BPFRF significantly inhibited DPPH radical (IC 50 = 7.382 ± 0.79 µg/mL) and LP (IC 50 = 7.182 ± 0.60 µg/mL) better than quercetin and ascorbic acid. Also, BPFRF exhibited potent inhibition against AChE and BuChE with IC 50 values of 22.283 ± 0.27 µg/mL and 33.437 ± 1.46 µg/mL, respectively compared to quercetin and rivastigmine. Docking studies revealed that luteolin-7-glucoside, carlinoside and quercetin interact effectively with crucial amino acid residues of AChE and BuChE through hydrogen bonds. Discussion and conclusions BPFRF possesses an excellent natural source of cholinesterase inhibitor and antioxidant. The material could be further explored for the potential treatment of oxidative damage and cholinergic dysfunction in Alzheimer’s disease.

With increasing fatalities, the COVID-19 pandemic constitutes a formidable global health challenge. The causative agent, SARS-CoV-2 constantly tests the efficacy of the immune system of its victims. The protective ability of the innate immune system as the first responder largely determines the progression of disease and its clinical prognosis. Evidence suggests that mortalities associated with COVID-19 are largely due to hyperinflammation and a dysregulated immune response. Consequently, the degree of the release of pro-inflammatory cytokines such as IL1, IL-6, and TNF alpha remarkably distinguishes between mild and severe cases of COVID-19. The early prediction of a cytokine storm is made possible by several serum chemistry and hematological markers. The prompt use of these markers for laboratory tests, and the aggressive prevention and management of a cytokine release syndrome is critical in determining the level of morbidity and fatality associated with COVID-19. With respect to the SARS-CoV-2 and the host cell, this literature review focuses on the dynamics of the COVID-19 disease highlighting on the pathogenesis, and the markers of Cytokine Storm. It also proffers solutions by critically looking at the current and potential pharmacological agents that are or can be used to mitigate and manage cytokine storms.