The Impacts of Anti-Inflammatory Agents on COVID-19 Cytokine Storm

The re-emergence of severe acute respiratory syndrome coronavirus 2 A(SARS-CoV-2) in Wuhan, China, has placed an unprecedented economic and health burden globally. The SARS-CoV-2 high mortality rate has brought great challenges to researchers, clinicians, and health workers in their bid to discover appropriate therapeutic interventions. The search for the ultimate remedy was initially centered on the use of antiviral agents targeting receptors and proteins involved in the pathophysiology of SARS-CoV-2. However, the upsurge of interest in repurposing anti-inflammatory agents was born out of the reported risks posed by a cytokine storm on COVID-19-induced fatality. A cytokine storm, as a result of the unregulated production of pro-inflammatory cytokines and other chemical mediators, triggers coagulopathy, viral sepsis, pneumonitis shock, and acute respiratory syndrome, which may lead directly to respiratory and organ failure and ultimately the death of the patient. The overwhelming evidence has shown that the early prediction of cytokine storm using serum chemistry and hematological markers and the use of appropriate anti-inflammatory agents will avert COVID-19 complications. These include the use of repurposed interferon (IFN) therapy and inhibitors of interleukin-1 (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and Janus kinase (JAKs) to nip the cytokine storm in the bud. This review critically used information retrieved from PubMed, China National Knowledge Infrastructure, Embase, Medline, and Google Scholar to elaborate on the mechanism and complications of COVID-19 cytokine storm, therapeutic interventions, and the way forward to discovering effective biocompatible drug targets

African and Holy Basil - a review of ethnobotany, phytochemistry, and toxicity of their essential oil: Current trends and prospects for antimicrobial/anti-parasitic pharmacology

The increased global health burden and mortality rate due to synthetic drug side effects and microbial resistance requires immediate attention for safer and better agents. This quest has fueled the search for phytotherapeutic alternatives, such as essential oils (EOs). Ocimum (Basil) essential oil has pleiotropic health-promoting potential in the treatment of a variety of diseases. This review focused on the ethnobotany, phytochemicals, antimicrobial properties, and toxicity of African and Holy Basil essential oils. African Basil EOs have been used to treat malaria, typhoid, yellow fever candidiasis, influenza, tooth gargle, sore eyes, and ear infections, among other things. Similarly, Holy Basil is used locally as a remedy for diseases such as colds, coughs, malaria, asthma, genitourinary infections, stomach acidity, diabetes, and influenza. This potency could be attributed to the abundance of phytochemicals in the plants, such as eugenol, linalool, and 1, 8-cineole. Experimental evidence has shown that the phytonutrients found primarily in their EOs have antimicrobial activity against many bacteria, fungi, viruses, and protozoans. This study discusses the multi-targeted approach of these compounds in eliminating microorganisms by distorting their cellular architecture, which leads to membrane permeability disruption, denaturation of key proteins for survival, damage to the microbial DNA and replication machinery, and ultimately cell lysis and organism death. Their antimicrobial pharmacology invariably positions them as a new, effective, and safer Phyto antimicrobial agent to reduce morbidity and mortality due to microbial resistance

Bioassay-guided identification of potential Alzheimer's disease therapeutic agents from Kaempferol-Enriched fraction of Aframomum melegueta seeds using in vitro and chemoinformatics approaches

Alzheimer's disease (AD) has become a major public health concern and the fifth major cause of death among the aging population globally. In this study, the total phenols and flavonoids contents (TPC and TFC) and in vitro antioxidant actions of the methanol extract and the various fractions of Aframomum melegueta were evaluated using 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, nitric oxide scavenging activity (NO), lipid peroxidation (TBARS) activity and ferric reducing power assay (FRAP). Furthermore, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the two most potent fractions were investigated, and the phytochemicals identified in the ethyl acetate fraction, which had the best antioxidant and cholinesterase inhibitory effects were subjected to chemoinformatics studies. The extract and its fraction had high amounts of TPC and TFC. The ethyl acetate fraction exerted the best DPPH, NO, TBARS, and FRAP inhibition with IC50 values of 5.06, 6.58, 2.12, and 88.73 µg/mL, respectively. Interestingly, n-hexane and ethyl acetate fractions inhibited AChE (IC5016.83 and 11.67 µg/mL) and BuChE (IC50 7.54 and 5.21 µg/mL) enzymatic activities more than the standard inhibitor, rivastigmine which had 11.99 and 11.40 µg/mL IC50 values, respectively. A total of 18 compounds were identified in ethyl acetate fraction, and kaempferol was the major component, with 40.01 µg/g (30%). More strikingly, the top-scoring compounds (catechin, and kaempferol) exhibited good binding affinity, and interacted favorably with amino acids residues around and within the active sites of AChE and BuChE and also obeyed drug-likeness rules, and did not show a tendency towards toxicity when placed side by side with rivastigmine which is immunogenic. Thus, A. melegueta seeds contain safe bioactive chemicals, which could be a veritable remedy for managing Alzheimer's and other neurodegenerative diseases.</p

Nephroprotective effects of Piper nigrum extracts against monosodium glutamate-induced renal toxicity in rats

Background: The toxicological effects of monosodium glutamate (MSG), widely used as a food additive, are a major public health challenge. This research aimed to investigate the nephroprotective effects of methanol and n-hexane extracts of Piper nigrum (MEPN and HEPN, respectively) against MSG-induced renal toxicity in rats. Materials and methods: The phytochemicals, vitamins, and in vitro antioxidant activities were determined using standard protocols. Acute toxicity was determined with thirty-two Swiss albino mice, while thirty male Wistar albino rats were used for the nephroprotective study. The rats were randomly distributed into 6 experimental groups (n = 5). Group 1 (baseline) was not induced or treated; groups 2–6 were given 2 g/kg body weight of MSG. Additionally, group 2 received normal saline; groups 3–6 were given 250 and 500 mg/kg body weight of MEPN and HEPN, respectively. MSG was administered alone for 21 days, after which MSG was concomitantly administered with the extracts for additional 28 days. After treatment, biochemical tests were done on the serum, and a histopathological examination was determined with the kidney. Results: Both extracts scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduced ferric ions to ferrous ions in the Ferric Reducing Antioxidant Power (FRAP) assay, with MEPN having higher efficacy. The extracts also ameliorated lipid peroxidation and increased the activities of superoxide dismutase and catalase, as well as the level of reduced glutathione. In addition, intervention with MEPN and HEPN provided nephroprotective effects by decreasing urea and creatinine levels and also improved the histo-architecture of the kidney. This efficacy could be due to the rich phytochemicals and antioxidant vitamins previously identified in the plant. Conclusions: These findings are critical in focusing attention on abolishing the use of MSG in our food sector and highlights the health benefits of incorporating P. nigrum into our food to avert food and drug toxicity

Bioassay-guided identification of potential Alzheimer’s disease therapeutic agents from Kaempferol-Enriched fraction of Aframomum melegueta seeds using in vitro and chemoinformatics approaches

Alzheimer's disease (AD) has become a major public health concern and the fifth major cause of death among the aging population globally. In this study, the total phenols and flavonoids contents (TPC and TFC) and in vitro antioxidant actions of the methanol extract and the various fractions of Aframomum melegueta were evaluated using 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, nitric oxide scavenging activity (NO), lipid peroxidation (TBARS) activity and ferric reducing power assay (FRAP). Furthermore, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the two most potent fractions were investigated, and the phytochemicals identified in the ethyl acetate fraction, which had the best antioxidant and cholinesterase inhibitory effects were subjected to chemoinformatics studies. The extract and its fraction had high amounts of TPC and TFC. The ethyl acetate fraction exerted the best DPPH, NO, TBARS, and FRAP inhibition with IC50 values of 5.06, 6.58, 2.12, and 88.73 µg/mL, respectively. Interestingly, n-hexane and ethyl acetate fractions inhibited AChE (IC5016.83 and 11.67 µg/mL) and BuChE (IC50 7.54 and 5.21 µg/mL) enzymatic activities more than the standard inhibitor, rivastigmine which had 11.99 and 11.40 µg/mL IC50 values, respectively. A total of 18 compounds were identified in ethyl acetate fraction, and kaempferol was the major component, with 40.01 µg/g (30%). More strikingly, the top-scoring compounds (catechin, and kaempferol) exhibited good binding affinity, and interacted favorably with amino acids residues around and within the active sites of AChE and BuChE and also obeyed drug-likeness rules, and did not show a tendency towards toxicity when placed side by side with rivastigmine which is immunogenic. Thus, A. melegueta seeds contain safe bioactive chemicals, which could be a veritable remedy for managing Alzheimer's and other neurodegenerative diseases

Bioassay-guided identification of potential Alzheimer's disease therapeutic agents from Kaempferol-Enriched fraction of Aframomum melegueta seeds using in vitro and chemoinformatics approaches

Alzheimer's disease (AD) has become a major public health concern and the fifth major cause of death among the aging population globally. In this study, the total phenols and flavonoids contents (TPC and TFC) and in vitro antioxidant actions of the methanol extract and the various fractions of Aframomum melegueta were evaluated using 2,2-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, nitric oxide scavenging activity (NO), lipid peroxidation (TBARS) activity and ferric reducing power assay (FRAP). Furthermore, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities of the two most potent fractions were investigated, and the phytochemicals identified in the ethyl acetate fraction, which had the best antioxidant and cholinesterase inhibitory effects were subjected to chemoinformatics studies. The extract and its fraction had high amounts of TPC and TFC. The ethyl acetate fraction exerted the best DPPH, NO, TBARS, and FRAP inhibition with IC50 values of 5.06, 6.58, 2.12, and 88.73 µg/mL, respectively. Interestingly, n-hexane and ethyl acetate fractions inhibited AChE (IC5016.83 and 11.67 µg/mL) and BuChE (IC50 7.54 and 5.21 µg/mL) enzymatic activities more than the standard inhibitor, rivastigmine which had 11.99 and 11.40 µg/mL IC50 values, respectively. A total of 18 compounds were identified in ethyl acetate fraction, and kaempferol was the major component, with 40.01 µg/g (30%). More strikingly, the top-scoring compounds (catechin, and kaempferol) exhibited good binding affinity, and interacted favorably with amino acids residues around and within the active sites of AChE and BuChE and also obeyed drug-likeness rules, and did not show a tendency towards toxicity when placed side by side with rivastigmine which is immunogenic. Thus, A. melegueta seeds contain safe bioactive chemicals, which could be a veritable remedy for managing Alzheimer's and other neurodegenerative diseases.</p

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves:In Silico and In Vitro Studies

The geometrical increase in diabetes mellitus (DM) and the undesirable side effects of synthetic drugs have intensified efforts to search for an effective and safe anti-diabetic therapy. This study aimed to identify the antioxidant and anti-diabetic agents in the ethanol extract of Leptadenia hastata (EELH). The phytochemicals, antioxidant vitamins, and minerals present in EELH were determined using standard procedures to achieve this aim. Gas chromatography coupled with mass spectroscopy and flame ionization detector (GC-MS/GC-FID) was employed to identify bioactive compounds. An e-pharmacophore model was generated from the extra precision, and energy-minimized docked position of standard inhibitor, acarbose onto human pancreatic amylase (HPA, PDB-6OCN). It was used to screen the GC-MS/GC-FID library of compounds. The top-scoring compounds were subjected to glide XP-docking and prime MM-GBSA calculation with the Schrodinger suite-v12.4. The Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction of the best-fit compounds was made using SwissADME and PROTOX-II webservers. Further validation of the docking results was performed with the in vitro analysis of the α-amylase and α-glucosidase inhibitory activities. EELH contains appreciable amounts of antioxidant and anti-diabetic phytoconstituents. The top-4 scoring compounds (rutin, epicatechin, kaempferol, and naringenin) from the EELH phytochemical library interacted with amino acid residues within and around the HPA active site. The ADMET prediction shows that epicatechin, kaempferol, and naringenin had favorable drug-likeness, pharmacokinetic properties, and a good safety profile. EELH demonstrated good inhibitory actions against α-amylase and α-glucosidase with 1C50 values of 14.14 and 4.22 µg/mL, respectively. Thus, L hastata phytoconstituents are promising novel candidates for developing an anti-diabetic drug.</p

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves:In Silico and In Vitro Studies

The geometrical increase in diabetes mellitus (DM) and the undesirable side effects of synthetic drugs have intensified efforts to search for an effective and safe anti-diabetic therapy. This study aimed to identify the antioxidant and anti-diabetic agents in the ethanol extract of Leptadenia hastata (EELH). The phytochemicals, antioxidant vitamins, and minerals present in EELH were determined using standard procedures to achieve this aim. Gas chromatography coupled with mass spectroscopy and flame ionization detector (GC-MS/GC-FID) was employed to identify bioactive compounds. An e-pharmacophore model was generated from the extra precision, and energy-minimized docked position of standard inhibitor, acarbose onto human pancreatic amylase (HPA, PDB-6OCN). It was used to screen the GC-MS/GC-FID library of compounds. The top-scoring compounds were subjected to glide XP-docking and prime MM-GBSA calculation with the Schrodinger suite-v12.4. The Adsorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) prediction of the best-fit compounds was made using SwissADME and PROTOX-II webservers. Further validation of the docking results was performed with the in vitro analysis of the α-amylase and α-glucosidase inhibitory activities. EELH contains appreciable amounts of antioxidant and anti-diabetic phytoconstituents. The top-4 scoring compounds (rutin, epicatechin, kaempferol, and naringenin) from the EELH phytochemical library interacted with amino acid residues within and around the HPA active site. The ADMET prediction shows that epicatechin, kaempferol, and naringenin had favorable drug-likeness, pharmacokinetic properties, and a good safety profile. EELH demonstrated good inhibitory actions against α-amylase and α-glucosidase with 1C50 values of 14.14 and 4.22 µg/mL, respectively. Thus, L hastata phytoconstituents are promising novel candidates for developing an anti-diabetic drug.</p

Exploring the potential of aqueous extracts of Artemisia annua ANAMED (A3) for developing new anti‐malarial agents: In vivo and silico computational approach

The emergence of resistance to current antimalarial drugs poses a significant challenge in the fight against malaria. This study aimed to investigate the in vivo antiplasmodial potential of the aqueous extract of fresh and dried leaves of A3 in Plasmodium berghei-infected (P. berghei) mice. A 4-day suppressive test was conducted, with infected BALB/c mice receiving artesunate and A3 extracts. The results showed that the tested doses of A3 attenuated the elevation of parasitemia induced by P. berghei, particularly at the dose of 400 mg/kg, and improved hematological indices. Computational techniques, including molecular docking, binding free energy calculations, and ADMET predictions, identified several bioactive compounds in A3 with promising inhibitory potential against lysyl-tRNA synthetases and Dihydrofolate reductase (DHFR), the crucial enzymes targeted by antimalarial drugs. In this paper, Friedelin, Bauerenol, Epifriedelanol, Alpha-Amyrenone, Stigmasterol, and beta-Amyrin acetate were top-ranked, having docking scores from −10.6 to −9.9 kcal/mol, compared with the −9.4 and −7.1 kcal/mol demonstrated by artesunate and chloroquine, respectively, as standard ligands. Also, it was shown that docking score from the Lysyl-tRNA protein target (4YCV) ranged from −9.5 to −7.8 kcal/mol in comparison to artesunate (8.1 kcal/mol) and chloroquine (5.6 kcal/mol). The results suggest that the identified compounds in A3 could serve as potential candidates for the development of new anti-malarial agents