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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of coronavirus disease 2019 (COVID-19). This virus has become a global pandemic with unprecedented mortality and morbidity along with attendant financial and economic crises. Furthermore, COVID-19 can easily be transmitted regardless of religion, race, sex, or status. Globally, high hospitalization rates of COVID-19 patients have been reported, and billions of dollars have been spent to contain the pandemic. Angiotensin-converting enzyme (ACE) 2 is a receptor of SARS-CoV-2, which has a significant role in the entry of the virus into the host cell. ACE2 is highly expressed in the type II alveolar cells of the lungs, upper esophagus, stratified epithelial cells, and other tissues in the body. The diminished expressions of ACE2 have been associated with hypertension, arteriosclerosis, heart failure, chronic kidney disease, and immune system dysregulation. Overall, the potential drug candidates that could serve as ACE2 activators or enhance the expression of ACE2 in a disease state, such as COVID-19, hold considerable promise in mitigating the COVID-19 pandemic. This study reviews the therapeutic potential and pharmacological benefits of the novel ACE2 in the management of COVID-19 using search engines, such as Google, Scopus, PubMed, and PubMed Central.

Sanah Malomile Nkadimeng,1 Christiaan ML Steinmann,2 Jacobus N Eloff1 1Phytomedicine Programme, Paraclinical Sciences Department, University of Pretoria, Onderstepoort, Pretoria, Gauteng, 0110, South Africa; 2Physiology Department, Sefako Makgatho Health Sciences University, Ga-Rankuwa, Gauteng, 0208, South AfricaCorrespondence: Sanah Malomile NkadimengPhytomedicine Programme, Paraclinical Sciences Department, University of Pretoria, P/Bag X04, Onderstepoort, Pretoria, Gauteng, 0110, South AfricaTel +27 12 529 8187Email sanah.nkadimeng@up.ac.zaPurpose: During a pathological inflammation, macrophages are activated to produce accumulation of inflammatory mediators such as induced-cyclooxygenase-2 (COX-2), 15-lipoxygenase (15-LOX) and pro-inflammatory cytokines. Pathological inflammation is a significant problem in many chronic diseases. As a result, more research into natural remedies with anti-inflammatory potential is crucial. Since ancient times, psilocybin-containing mushrooms, also known as magic mushrooms, were used for mind healing and also to advance the quality of life. However, not much is known about their anti-inflammatory potential. This study aimed at investigating the anti-inflammatory effects of four psilocybin-containing mushrooms (Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis and Psilocybe cubensis leucistic A+ strain) from genus Panaeolus and Psilocybe for the first time in vitro on 15-LOX activity and also on lipopolysaccharide (LPS)-induced inflammation in human U937 macrophage cells.Methods: Mushrooms were grown and extracted with boiling hot water. Effects of the four water extracts on 15-LOX activity were determined. Confluent human U937 cells were differentiated with phorbol 12-myristate 13-acetate and treated with the hot-water extracts (25 and 50 μg/mL) 2 hours before being stimulated with 1 μg/mL LPS over 24 hours. Quercetin was used as a positive control. Control cells were differentiated but not LPS-induced nor treated. Tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 concentrations were measured. Levels of COX-2 and mitochondrial activity were also determined.Results: The four water extracts had poor 15-LOX inhibition activity with IC50 > 250 μg/mL. Extracts were safe at the concentration studied and inhibited the LPS-induced production of pro-inflammatory mediators, TNF-α and IL-1β significantly and lowered IL-6 and COX-2 concentrations in treated human U937 macrophage cells. Water extracts also increased percentage viability of treated cells and levels of anti-inflammatory IL-10 non-significantly.Conclusion: The study suggested that the hot-water extracts of the four psilocybin-containing magic mushrooms have potential anti-inflammatory effects executed by down-regulating pro-inflammatory mediators.Keywords: Panaeolus cyanescens, Psilocybe natalensis, Psilocybe cubensis, Psilocybe cubensis A+ strain, pro-inflammatory cytokine, COX-2, 15-LOX

Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil and the atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases and disorders caused by chemicals such as sodium fluoride (NaF) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the renoprotective and antihypertensive effects of L- Arginine on NaF-induced nephrotoxicity. Thirty male Wistar rats (150 – 180 g) were used in this study. The rats were randomly divided into five groups of six rats each as Control, NaF (300 ppm), NaF + L- Arginine (100 mg/kg), NaF + L- Arginine (200 mg/kg), and NaF + Lisinopril (10 mg/kg), respectively; orally for eight days. Histopathological examination and immunohistochemistry of renal angiotensin converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defence system, and blood pressure parameters were determined. L- Arginine significantly (p hydrogen peroxide (H2O2), malondialdehyde (MDA) and protein carbonyl (PCO) and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L arginine. The results of this study suggest that L- Arginine normalized high blood pressure, reduced oxidative stress, reduced the expression of renal ACE and MCR, and improved nitric oxide production. Thus, L- Arginine holds promise as a potential therapy against hypertension and renal damage.

Ethnoveterinary medicine (EVM), although not documented well, still serves as an alternative or complementary medication for curing or preventing bacterial, fungal and helminth diseases, as well as other maladies such as ticks and tick-borne diseases in South Africa. The aim of this study was to document plant species used as EVM by the Mnisi community at Bushbuckridge in the province of Mpumalanga, and to evaluate their antimicrobial, antibiofilm and cytotoxic activities. The survey was carried out for two weeks from the end of January to the beginning of February 2018 at the local dipping tanks following the Rapid Rural Appraisal (RRA) approach. A total of 50 individuals were interviewed: 82% were local small scale farmers, 10% were herdsmen, 6% herbalists and 2% animal health technicians. Three plant species were selected for bioassays based on their frequency index and lack of information on their bioactivity in the literature. Traditional methods were used for plant extraction using water as described by the respondents. Acetone was used as an organic solvent to compare traditional and organic solvent methods of extract preparation. The extracts were tested for their antibacterial, antibiofilm, antifungal, and cytotoxic properties. Eleven plant species belonging to seven families were reported by the farmers for EVM use, and fresh plants from the wild were commonly used to prepare the remedies as decoctions, infusions, pastes and extracted sap. Elephantorrhiza obliqua acetone extract had the best antibacterial activity with a minimum inhibitory concentration (MIC) value of 0.09 mg/mL against Pseudomonas aeruginosa, while E. obliqua water extracts had the best antifungal activity with MIC values of 0.02 to 0.04 mg/mL against Aspergillus fumigatus. Schotia brachypetala acetone extracts inhibited Enterococcus faecalis biofilms by 113% and 135% at zero and 24 h of bacterial growth respectively, while E. obliqua acetone extracts had values of 64% and 83% at these time periods, indicating that they were good inhibitors of biofilm formation and also had the capacity to act against mature biofilms. Seven out of nine tested plant extracts (78%) were non-toxic to moderately cytotoxic while only two plant extracts were relatively toxic against Vero cells. Traditionally prepared remedies were generally more active against fungi and mycobacteria and less toxic than the organic solvent extracts. However, in vivo studies are necessary to support the traditional use of the remedies against diseases in livestock in terms of validating the efficacy but also assessing their potential toxicity.

Inflammation associated with sexually transmitted infection (STIs) often results from delayed diagnosis or treatment, and may result in life-threatening complications. The root or stem bark of plants selected in this study are used by traditional healers in the management of STIs and to treat the associated inflammation. This study evaluated the anti-inflammatory activities of 12 South African medicinal plants used traditionally in the treatment of STIs and the associated inflammation. Acetone extracts were tested for anti-inflammatory activity against 15-lipoxygenase (15-LOX), xanthine oxidase (XO) and inducible nitric oxide production in lipopolysaccharide (LPS) stimulated RAW 264.7 macrophage cells. The free radical and nitric oxide scavenging capacity was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and nitric oxide inhibition assays. The MTT assay was used to determine the cytotoxic effect of the extracts on RAW 264.7 macrophages and Vero cells. Preliminary phytochemical analysis was carried out using NMR spectroscopy, Gas Chromatography Mass Spectroscopy (GC–MS) analysis and the determination of total phenolic and flavonoid contents. The root bark extract of Lannea schweinfurthii had the highest inhibitory activity against 15-LOX (IC50 = 40 ± 3 μg/mL) while C. abbreviata best inhibited XO (IC50 = 46.8 ± 1.5 μg/mL). Extracts of Ficus abutilifolia, Faurea saligna and Zanthoxylum capense showed significant suppression of inducible nitric oxide production with IC50 values comparable to quercetin (IC50

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the etiological agent for the Coronavirus Disease 2019 (COVID‐19). The COVID‐19 pandemic has created unimaginable and unprecedented global health crisis. Since the outbreak of COVID‐19, millions of dollars have been spent, hospitalization overstretched with increasing morbidity and mortality. All these have resulted in unprecedented global economic catastrophe. Several drugs and vaccines are currently being evaluated, tested, and administered in the frantic efforts to stem the dire consequences of COVID‐19 with varying degrees of successes. Zinc possesses potential health benefits against COVID‐19 pandemic by improving immune response, minimizing infection and inflammation, preventing lung injury, inhibiting viral replication through the interference of the viral genome transcription, protein translation, attachment, and host infectivity. However, this review focuses on the various mechanisms of action of zinc and its supplementation as adjuvant for vaccines an effective therapeutic regimen in the management of the ravaging COVID‐19 pandemic. Practical applications The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the etiological agent for the Coronavirus Disease 2019 (COVID‐19), has brought unprecedented untold hardship to both developing and developed countries. The global race for vaccine development against COVID‐19 continues with success in sight with attendant increasing hospitalization, morbidity, and mortality. Available drugs with anti‐inflammatory actions have become alternative to stem the tide of COVID‐19 with attendant global financial crises. However, Zinc is known to modulate several physiological functions including intracellular signaling, enzyme function, gustation, and olfaction, as well as reproductive, skeletal, neuronal, and cardiovascular systems. Hence, achieving a significant therapeutic approach against COVID‐19 could imply the use of zinc as a supplement together with available drugs and vaccines waiting for emergency authorization to win the battle of COVID‐19. Together, it becomes innovative and creative to supplement zinc with currently available drugs and vaccines., Dietary supplementation of Zinc could, therefore, be of immense benefits during the COVID‐19 pandemic due to its array of biological and pharmacological properties which include anti‐inflammatory, antioxidant, antiflu, antimicrobial, wound healing, antiaging, and a signaling molecule. Drugs such as chloroquine, and flavonoids including quercetin and epigallocatechin‐gallate act as facilitators and enhance the entry of zinc into the cell, and are, therefore, known as zinc ionophores. Hence, combining Zn as part of drug regimen for COVID‐19 could offer significant therapeutic advantage for the successful management of global COVID‐19 crisis.

Background Owing to antibiotic resistance, alternative antimicrobials from medicinal plants are receiving attention as leads for anti-infective agents. This study aimed to investigate selected tree species and their constituents for activity against bacterial foodborne pathogens, particularly Salmonella serovars. Methods Antibacterial activity of ten plant species was determined by serial microdilution against bacteria implicated in causing gastrointestinal ailments. Active compounds were isolated from Loxostylis alata using bioassay-guided fractionation. Antioxidant activity was determined using free-radical scavenging assays. Cytotoxicity and genotoxicity of the extracts was ascertained on Vero cells, and using the Ames assay respectively. Results Extracts had low to moderate MIC values from 0.04 to 2.5 mg/mL. Protorhus longifolia and Loxostylis alata were most active and L. alata had the highest selectivity index value (2.51) against Salmonella Typhimurium, as well as high antioxidant activity. Cytotoxicity values ranged from 0.02 to 0.47 mg/mL, while tested extracts were not genotoxic. Bioactive compounds isolated from L. alata included delicaflavone and a polymethoxyflavone. Conclusions The Loxostylis alata leaf extract had strong activity against Salmonella serovars but isolated compounds were less active, indicating likely synergistic effects. Extracts of L. alata are promising candidates for development of antimicrobial preparations or food additives against microbial contamination.

Kigelia africana is used to manage inflammation among indigenous communities. We hypothesized that K. africana extracts contain phytoconstituents with good antioxidant and anti-inflammatory activities. The methanolic extract of K. africana fruits and Spathodea campanulata leaves (SPK04), K. africana aqueous fruit extract (KFM02), and K. africana acetone fruit extract (KFM05) were subjected to antioxidant and anti-inflammatory assays. Antioxidant activity was evaluated using the ABTS radical scavenging assay, and the MTT cell viability assay was used for cytotoxicity. The extracts were preincubated with enzymes and assayed for 15-LOX and COX-2 enzyme activity using an ELISA method. Nitric oxide (NO) inhibitory effect of the extracts was evaluated and measurement of proinflammatory cytokines (IL-1β, TNF-α, and IL-6) and the anti-inflammatory cytokine (IL-10) was done using ELISA kits. SPK04 had the highest antioxidant activity with a mean inhibition of 99.37 ± 0.56% and an IC50 of 4.28 µg/mL. SPK04 and KFM05 did not inhibit 15-LOX as their IC50 values were >1000 μg/mL. All extracts were safe on Vero cells at the highest concentration (200 µg/mL) tested. KFM02 was the best inhibitor of NO production and had the highest cell viability at both the lowest (50 µg/mL) and highest concentrations (200 µg/mL). SPK04 was the best COX-2 inhibitor while KFM05 expressed the strongest suppression effect for IL-β and IL-6. KFM02 did not inhibit IL-6 at the highest concentration (200 µg/mL). The order of suppression of TNF-α by the extracts differed across concentrations, KFM05 > SPK04 > KFM02 at 200 µg/mL, KFM02 > SPK04 > KFM05 at 100 µg/mL, and SPK04 > KFM02 > KFM05 at 50 µg/mL. All the tested extracts had no inhibitory effect against IL-10. SPK04, KFM05, and KFM02 had good antioxidant and anti-inflammatory activity and this supports their use as potential anti-inflammatory therapies. This study presents for the first time the antioxidant and anti-inflammatory activity of K. africana and S. campanulata polyherbal extract. It is also among the very few studies that have reported the inhibitory effect of cytokines IL-1β, TNF-α, IL-6, and IL-10 by K. africana.

Although orthodox medications are available for skin diseases, expensive dermatological services have necessitated the use of medicinal plants as a cheaper alternative. This study evaluated the pharmacological and phytochemical profiles of four medicinal plants (Drimia sanguinea, Elephantorrhiza elephantina, Helichrysum paronychioides, and Senecio longiflorus) used for treating skin diseases. Petroleum ether and 50% methanol extracts of the plants were screened for antimicrobial activity against six microbes: Bacillus cereus, Shigella flexneri, Candida glabrata, Candida krusei, Trichophyton rubrum and Trichophyton tonsurans using the micro-dilution technique. Antioxidant activity was conducted using 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging and &beta, carotene linoleic acid models. Cytotoxicity was determined against African green monkey Vero kidney cells based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay. Spectrophotometric and Gas Chromatography-Mass Spectrometry (GC-MS) methods were used to evaluate the phytochemical constituents. All the extracts demonstrated varying degrees of antimicrobial potencies. Shigella flexneri, Candida glabrata, Trichophyton rubrum and Trichophyton tonsurans were most susceptible at 0.10 mg/mL. In the DPPH test, EC50 values ranged from approximately 6&ndash, 93 &micro, g/mL and 65%&ndash, 85% antioxidant activity in the &beta, carotene linoleic acid antioxidant activity model. The phenolic and flavonoid contents ranged from 3.5&ndash, 64 mg GAE/g and 1.25&ndash, 28 mg CE/g DW, respectively. The LC50 values of the cytotoxicity assay ranged from 0.015&ndash, 5622 &micro, g/mL. GC-MS analysis revealed a rich pool (94&ndash, 198) of bioactive compounds including dotriacontane, benzothiazole, heptacosane, bumetrizole, phthalic acid, stigmasterol, hexanoic acid and eicosanoic acid, which were common to the four plants. The current findings provide some degree of scientific evidence supporting the use of these four plants in folk medicine. However, the plants with high cytotoxicity need to be used with caution.

Kigelia africana has been used in the management of human ailments since time immemorial. Ethnobotanists have documented the traditional uses of K. africana, which include treatment of skin disorders, cancer and gynecological complaints, among others. This has interested scientists, who have examined K. africana plant parts for their bioactivity. This review provides an insightful understanding on the ethnobotany, phytochemistry and pharmacology of K. africana. Web search engines Google and Google Scholar, as well as the databases of PubMed, Scopus, JSTOR, HINARI, SID, AJOL and Springer Link, were exhaustively searched using key words and phrases. Institutional reports and conference papers were also consulted. A total of 125 relevant international literature sources meeting the inclusion criteria were included. Kigelia africana has biologically active phytochemicals, many of which have been isolated. Whilst the fruits are most often cited in pharmacological studies, other plant parts are also used in herbal preparations. Commercially available products have been formulated from K. africana, though many have not been fully standardized. Despite many efforts by researchers to scientifically validate traditional uses of K. africana, many remain merely claims, thus the need to conduct more research, scientifically validate other traditional uses, isolate new bioactive phytochemicals and standardize K. africana products.