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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

Purpose: Anacardium occidentale commonly known as Cashew is a plant that is widely used in African traditional medicine. It is endowed with phytochemical constituents that are responsible for its medicinal properties., Methods: Twenty-five male Wistar rats were grouped as follows: Control (Group A), Group B (L-NAME 40 mg/kg), Group C (100 mg/kg Anacardium occidentale extract plus 40 mg/kg L-NAME), Group D (200 mg/kg extract plus 40 mg/kg L-NAME) and Group E (10 mg/kg of Lisinopril plus 40 mg/kg L-NAME). The animals were treated with oral administration of either the extracts or Lisnopril daily for 4 weeks. Neuro-behavioural tests such as the Morris Water Maze and Hanging Wire Grip tests were carried out to evaluate memory/spatial learning and muscular strength, respectively. Makers of oxidative stress, antioxidant enzymes and immunohistochemical staining of Glial Fibrillary Acidic Protein and Ionised Calcium Binding Adaptor molecule 1 were assessed., Results: L-NAME administration caused significant increases in biomarkers of oxidative stress, decreased antioxidant status, acetylcholinesterase activity, altered neuro-behavioural changes, astrocytosis, and microgliosis. However, Anacardium occidentale reversed exaggerated oxidative stress biomarkers and improved neuro-behavioural changes., Conclusions: Combining all, Anacardium occidentale enhanced brain antioxidant defence status, improved memory and muscular strength, thus, suggesting the neuroprotective properties of Anacardium occidentale .

Purpose The persistent and alarming rates of increase in cardiovascular and renal diseases caused by chemicals such as cobalt chloride (CoCl 2 ) in mammalian tissues have led to the use of various drugs for the treatment of these diseases. This study aims at evaluating the nephron-protective action of Naringin (NAR), a metal-chelating antioxidant against CoCl 2 -induced hypertension and nephrotoxicity. Methods Forty-two male Wistar rats were randomly distributed to seven rats of six groups and classified into Group A (Control), Group B (300 part per million; ppm CoCl 2 ), Group C (300 ppm CoCl 2 + 80 mg/kg NAR), Group D (300 ppm CoCl 2 + 160 mg/kg NAR), Group E (80 mg/kg NAR), and Group F (160 mg/kg NAR). NAR and CoCl 2 were administered via oral gavage for seven days. Biomarkers of renal damage, oxidative stress, antioxidant status, blood pressure parameters, immunohistochemistry of renal angiotensin-converting enzyme and podocin were determined. Results Cobalt chloride intoxication precipitated hypertension, renal damage, and oxidative stress. Immunohistochemistry revealed higher expression of angiotensin-converting enzyme (ACE) and podocin in rats administered only CoCl 2 . Conclusion Taken together, the antioxidant and metal-chelating action of Naringin administration against cobalt chloride-induced renal damage and hypertension could be through abrogation of angiotensin-converting enzyme and podocin signalling pathway.

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 atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against 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 follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ethnopharmacological Relevance: Global interest in phytogenic feed additives as alternatives to antibiotics in feed has been spurred by the banning of antibiotic growth promoters by several countries. Suitable plant extracts for development of phytogenic feed additives should have therapeutic value and should also be safe., Aim of Study: The aim of this study was to evaluate the antibacterial, antioxidant and anti-lipoxygenase activities as well as cytotoxicity of selected plant species used in poultry ethnomedicine in Zimbabwe., Methods: Antibacterial activity was determined against three ATCC strains (Staphylococcus aureus, Escherichia coli, Salmonella Enteritidis) and two clinical strains isolated from chickens (Escherichia coli and Salmonella Gallinarum) using a two-fold serial microdilution assay. Qualitative antibacterial bioautography was also carried out using the ATCC strains. Antioxidant activities of crude acetone and methanol extracts were determined using free radical scavenging assays whilst anti-lipoxygenase activity was evaluated using a ferrous oxidation-xylenol orange (FOX) assay. Cytotoxicity was evaluated using a tetrazolium-based colorimetric assay (MTT assay) on Vero monkey kidney cells., Results: Erythrina abyssinica had the best antibacterial activity against both ATCC strains and clinical strains with minimum inhibitory concentration (MIC) values ranging from 0.02 to 0.156 mg/ml. Aloe greatheadii, Adenia gummifera (leaves), Senna singueana and Aloe chabaudii had moderate activity against the poultry pathogens. Bioautography showed that all ten plant species have antibacterial activity against the tested microorganisms with E. abyssinica and S. singueana having prominent bands of inhibition against both Gram-negative and Gram-positive bacteria. The acetone extract of S. singueana and the methanol extract of Euphorbia matabelensis had the most powerful antioxidant activities with mean IC 50 values of 1.43 μg/ml and 1.31 μg/ml respectively in the ABTS assay which were comparable with those of the positive controls (ascorbic acid and trolox). Bobgunnia madagascariensis, A. chabaudii, E. abyssinica and Tridactyle bicaudata extracts had reasonable antioxidant activity. The S. singueana extract had the most potent anti-lipoxygenase activity with a mean IC 50 value of 1.72 μg/ml. The cytotoxicity results showed that only the acetone extracts of A. greatheadii and S. singueana were relatively safe at concentrations that were active against the tested microorganisms (selective index >1). Regarding anti-lipoxygenase activity, extracts of B. madagascariensis, S. singueana, T. bicaudata and E. matabelensis were more active than toxic (selective index >5) indicating anti-inflammatory potential., Conclusions: This study showed that S. singueana had a cocktail of therapeutic activity and supports further investigation of this plant species for development of phytogenic poultry feed additives. Other plant species with noteworthy biological activities include B. madagascariensis, E. abyssinica, A. greatheadii, T. bicaudata and E. matabelensis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Launaea taraxacifolia has been traditionally used for the management of conditions such as cardiovascular, respiratory, and metabolic diseases. High blood pressure was established by oral administration of L-Nitro Arginine Methyl Ester (L-NAME) a non-selective inhibitor of endothelial nitric oxide synthase (eNOS). The antihypertensive action of the methanol leaf extract of L. taraxacifolia was examined. Fifty male Wistar rats were divided into 5 groups of 10 animals per group: Group A (Distilled water), Group B (Hypertensive rats; 40mg/kg L-NAME), Group C (Hypertensive rats plus 100mg/kg extract), Group D (Hypertensive rats plus 200 mg/kg extract) and Group E (Hypertensive rats plus 10mg/kg of Lisinopril). The treatments were orally administered for five weeks. Haemodynamic parameters, urinalysis, indices of oxidative stress and immunohistochemistry were determined. Findings from this study showed that blood pressure parameters, urinary sodium and indices of oxidative stress increased significantly while In-vivo antioxidant defence systems decreased significantly in hypertensive rats. Immunohistochemistry revealed significant increases in expressions of mineralocorticoid receptor, angiotensin converting enzyme activity and kidney injury molecule-1 in kidney of hypertensive rats. Treatment with Launeae taraxacifolia normalized blood pressure parameters, urinary sodium, oxidative stress indices, antioxidant defence system, and serum nitric oxide bioavailability.

Bacterial secondary metabolites play a major role in the alleviation of diseases; however, the cytotoxicity of other metabolites cannot be ignored as such metabolites could be detrimental to human cells. Three Staphylococci strains Staphylococcus aureus , staphylococcus epidermidis and staphylococcus saprophyticus were used in the experiments. These strains are well known to cause hospital and community-acquired infections. Secondary metabolites from S. aureus isolated from milk of cows with clinical features of mastitis (swollen udders and the production of watery clotted milk), S. saprophyticus (ATCC 35552), and S. epidermidis (ATCC 51625) were exposed to a minimal medium then screened using Gas Chromatography High-Resolution Time-of-flight Mass Spectrometry (GC-HRTOF-MS) and identified with Nuclear Magnetic Resonance (NMR). From S. epidermidis , two compounds were isolated: oleamide and methyl palmitate; three from S. aureus, including fluoranthene, 3-methyl-2-phenyl-1H-pyrrole, and cyclo(L-Leu-L-Propyl); while S. saprophyticus yielded succinic acid, 1,2,6-hexantriol, veratramine, and 4-methyl-pentyl-amine. The secondary metabolites were tested for cytotoxicity using the Vero cell line. Fluoranthene exhibited toxicity with an LC 50 of 0.0167 mg/mL to Vero cells, while the other metabolites did not. Methyl palmitate was the least toxic of all of the metabolites. The results imply that none of the compounds, except fluoranthene, pose any danger to human cells.

Ethnopharmacological Relevance: Cissampelos mucronata A. Rich., a perennial climber belonging to the family Menispermaceae, has been used traditionally to treat parasites and tuberculosis-related symptoms. Co-infection of helminth parasites and tuberculosis-causing pathogens heightens the risk of developing active tuberculosis., Aim of the Study: The aim was to isolate and characterize antimycobacterial compounds from Cissampelos mucronata and to investigate their antibiofilm and anthelmintic efficacy as well as cytotoxicity., Materials and Methods: The acetone extract of C. mucronata leaves and stems was fractionated by vacuum liquid chromatography using hexane, ethyl acetate, acetone and methanol:chloroform (3:7). Separation of the active ethyl acetate fraction by column and preparative thin layer chromatography led to the isolation and identification of five compounds using NMR and LC-MS, as well as GC-MS for non-polar compounds. The anthelmintic, antimycobacterial, antibiofilm, antioxidant and anti-inflammatory effects as well as cytotoxicity of the fractions and compounds were determined., Results: The ethyl acetate fraction had the best antimycobacterial activity (MIC = 0.015-0.08 mg/ml). The fractions were relatively non-toxic to Vero cells (0.03-0.79 mg/ml) and had good anti-inflammatory and antibiofilm effects. Five compounds were identified as stigmasterol, hentriacontane, simiarenol, nonacosene and carbonic acid. Nonacosene had moderate anthelmintic effects but poor antimycobacterial activity (MIC = 0.375 mg/ml). Nonacosene and hentriacontane had good biofilm inhibitory effect (90-100%)., Conclusions: This study reveals that C. mucronata is a potential source of promising compounds with a range of useful bioactivities that support its use in traditional medicine. Development of plant-based remedies may assist in reducing the impact of co-infections with helminth parasites and tuberculosis-causing mycobacteria., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Sodium fluoride (NaF) is one of the neglected environmental pollutants. It is ubiquitously found in the soil, water, and environment. Interestingly, fluoride has been extensively utilized for prevention of dental caries and tartar formation, and may be added to mouthwash, mouth rinse, and toothpastes. This study is aimed at mitigating fluoride-induced hypertension and nephrotoxicity with clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist. For this study, forty male Wistar rats were used and randomly grouped into ten rats per group, control, sodium fluoride (NaF; 300 ppm) only, NaF plus clofibrate (250 mg/kg) and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. The administration of NaF was by drinking water ad libitum, while clofibrate and lisinopril were administered by oral gavage. Administration of NaF induced hypertension, and was accompanied with exaggerated oxidative stress; depletion of antioxidant defence system; reduced nitric oxide production; increased systolic, diastolic and mean arterial pressure; activation of angiotensin-converting enzyme activity and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB); and testicular apoptosis. Treatment of rats with clofibrate reduced oxidative stress, improved antioxidant status, lowered high blood pressure through the inhibition of angiotensin-converting enzyme activity, mineralocorticoid receptor over-activation, and abrogated testicular apoptosis. Taken together, clofibrate could offer exceptional therapeutic benefit in mitigating toxicity associated with sodium fluoride., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Leonotis leonurus (L.) R.Br. (Lamiaceae) is a perennial shrub native to South Africa used to treat various diseases including digestive tract problems, intestinal worms and constipation., Aim of the Study: The aim was to isolate and characterise nematicidal compounds from leaves of L. leonurus., Materials and Methods: Bioassay-guided fractionation was carried out using the free-living nematode Caenorhabditis elegans as a model organism. Structural elucidation of the purified compound was carried out using NMR spectroscopic analyses and UPLC-QTOF-MS. The fractions and the isolated compound were tested for nematicidal activity on motility of plant-parasitic Meloidogyne incognita juveniles (J2s) and J2 hatch inhibition. Further screening was done to determine the minimum inhibitory concentration (MIC) of the fractions against bacterial phytopathogens and cytotoxicity against Vero kidney cells., Results: Leoleorin C isolated from L. leonurus had moderate activity against C. elegans juveniles (34%) but was not active against J2 motility and J2 hatch of M. incognita. Thus, activity against the free-living C. elegans did not correspond with efficacy against plant-parasitic nematodes. Leoleorin C was not active against the tested bacterial phytopathogens, but some activity was observed in the bioautography assay against Clavibacter michiganensis subsp. michiganensis, the organism causing bacterial canker in tomatoes. The plant extract, fractions and leolorin C were relatively non-toxic to Vero cells with LC 50 values greater than 0.01 mg/mL., Conclusion: The crude extract of L. leonurus and fractions may be useful in developing complementary treatments for controlling nematodes and phytopathogens. This study does not support the use of free-living nematodes as a model to isolate anti-parasitic compounds from plants., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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., (Copyright: © Oyagbemi, et al.)

Ethnopharmacological Relevance: Combretum species are used traditionally for the treatment of diarrhoea, hookworm, fever, inflammation, pain and infectious diseases. Infections are commonly caused by the intake of food contaminated with foodborne pathogens. These are a significant concern in the food industry owing to their ability to form biofilms and cause food spoilage, despite the availability of modern food preservation techniques. Combretum elaeagnoides Klotzsch (Combretaceae) is used in southern African traditional medicine against infections and diarrhoea., Aim of the Study: This study evaluated the antimicrobial ability of C. elaeagnoides leaf fractions and the isolated compound quercetin-3-O-rhamnoside against a panel of foodborne pathogens, and biofilms formed by them. The samples were also assessed for their antioxidant activity and cytotoxicity., Materials and Methods: Fractions prepared from the methanol extract of the leaves, and a bioactive compound (quercetin-3-O-rhamnoside) isolated from the ethyl acetate fraction were investigated for activity against nine reference and clinical strains of foodborne pathogens. The microdilution method was used to determine the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the fractions and compound. The inhibition of biofilm formation and the crystal violet staining assays were used to determine the antibiofilm efficacy. The DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay and the 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) electron reduction assay were used to determine the antioxidant potential of the fractions and compound. The cytotoxicity was assessed using the 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay against Vero African monkey kidney cells., Results: The fractions were active against all tested organisms, with MIC values ranging from 0.03 to 1.25 mg/mL. The best MBC was 0.63 mg/mL. All the fractions and the purified compound inhibited biofilm formation of Staphylococcus aureus and Salmonella Typhimurium, with percentage inhibition values greater than 50% at 1 mg/mL. The compound had very promising antibiofilm activity against Escherichia coli 1 (ATCC 25922) with percentage inhibition of >150%. The compound and fractions had good radical scavenging potential against the DPPH and ABTS radicals. Quercetin-3-O-rhamnoside and the fractions were relatively non-cytotoxic., Conclusion: The ability of the fractions and compound to reduce and inhibit biofilm biomass and their promising antioxidant potential provide motivation to further investigate the use of plants to protect food products from contamination, as well as to treat infections characterized by bacterial biofilms., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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.

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., (© 2021 Wiley Periodicals LLC.)

Prevalence of major depression in people with chronic heart failure is higher than in normal populations. Depression in heart failure has become a major issue. Psilocybin-containing mushrooms commonly known as magic mushrooms, have been used since ancient times for their mind healing properties. Their safety in cardiovascular disease conditions is not fully known and may pose as a risk for users suffering from these illnesses. Study investigates the effects and safety of Psilocybe cubensis and Panaeolus cyanescens magic mushrooms use from genus Psilocybe and Panaeolus respectively, in a pathological hypertrophy conditions in which endothelin-1 disorder is a contributor to pathogenesis. We examined the effects of the mushrooms extracts on endothelin-1-induced hypertrophy and tumor necrosis factor-α (TNF- α)-induced cell injury in H9C2 cardiomyocytes. Mushrooms were oven dried and extracted with cold and boiling-hot water. H9C2 cardiomyocytes were induced with endothelin-1 prior to treatment with extracts over 48 h. Cell injury was stimulated with TNF-α. Results proposed that the water extracts of Panaeolus cyanescens and Psilocybe cubensis did not aggravate the pathological hypertrophy induced by endothelin-1 and also protected against the TNF-α-induced injury and cell death in concentrations used. Results support medicinal safe use of mushrooms under controlled conditions and cautioned use of higher concentrations.

Hypertension is the most common cardiovascular disease that affects approximately 26% of adult population, worldwide. Rutin is one of the important flavonoids that is consumed in the daily diet, and found in many food items, vegetables, and beverages. Uninephrectomy (UNX) of the left kidney was performed, followed by induction of hypertension. The rats were randomly divided into four groups of 10 rats: group 1-Sham-operated rats; group 2-UNX rats, group 3-UNX-L-NAME (40 mg/kg) plus rutin (100 mg/kg bwt), and groups 4-UNX-L-NAME plus lisinopril (10 mg/kg bwt), orally for 3 weeks. Results revealed significant heightening of arterial pressure and oxidative stress indices, while hypertensive rats treated with rutin had lower expressions of angiotensin converting enzyme (ACE) and mineralocorticoid receptor in uninephrectomized rats. Together, rutin as a novel antihypertensive flavonoid could provide an unimaginable benefits for the management of hypertension through inhibition of angiotensin converting enzyme and mineralocorticoid receptor. PRACTICAL APPLICATIONS: Hypertension has been reported to be the most common cardiovascular disease, affecting approximately 26% of the adult population worldwide with predicted prevalence to increase by 60% by 2025. Recent advances in phytomedicine have shown flavonoids to be very helpful in the treatment of many diseases. Flavonoids have been used in the treatment and management of cardiovascular diseases, obesity and hypertension. The study revealed that rutin, a known flavonoid inhibited angiotensin converting enzyme (ACE), angiotensin 2 type 1 receptor (ATR1), and mineralocorticoid receptor (MCR), comparable to the classic ACE inhibitor, Lisinopril, indicating the novel antihypertensive property of rutin. Therefore, flavonoids such as rutin found in fruits and vegetables could, therefore, serve as an antihypertensive drug regimen. Combining all, functional foods rich in flavonoids could be used as potential therapeutic candidates for managing uninephrectomized hypertensive patients., (© 2020 Wiley Periodicals LLC.)

Psilocybin-containing mushrooms, commonly known as magic mushrooms, have been used since ancient and recent times for depression and to improve quality of life. However, their anti-inflammatory properties are not known. The study aims at investing cytotoxicity; antioxidant; and, for the first time, anti-inflammatory effects of Psilocybe natalensis , a psilocybin-containing mushroom that grows in South Africa, on lipopolysaccharide-induced RAW 264.7 macrophages. Macrophage cells were stimulated with lipopolysaccharide and treated with different concentrations of Psilocybe natalensis mushroom extracted with boiling hot water, cold water and ethanol over 24 h. Quercetin and N-nitro-L-arginine methyl ester were used as positive controls. Effects of extracts on the lipopolysaccharide-induced nitric oxide, prostaglandin E 2 , and cytokine activities were investigated. Phytochemical analysis, and the antioxidant and cytotoxicity of extracts, were determined. Results showed that the three extracts inhibited the lipopolysaccharide-induced nitric oxide, prostaglandin E 2 , and interleukin 1β cytokine production significantly in a dose-dependent manner close to that of the positive controls. A study proposed that ethanol and water extracts of Psilocybe natalensis mushroom were safe at concentrations used, and have antioxidant and anti-inflammatory effects. Phytochemical analysis confirmed the presence of natural antioxidant and anti-inflammatory compounds in the mushroom extracts.

Hypertension is a condition with chronic elevation of blood pressure and a common preventable risk factor for cardiovascular disease with attendant global morbidity and mortality. The present study investigated the novel antihypertensive and neuroprotective effect of Naringenin on L-N G -Nitro arginine methyl ester (L-NAME) induced hypertension together with possible molecular mechanism of action. Rats were divided into four groups. Rats in Group A were normotensive. The hypertensive group (Group B) received 40 mg/kg) of L-NAME alone while Groups C and D were concurrently administered Naringenin (50 mg/kg) or Lisinopril (10 mg/Kg) together with L-NAME orally for 3 weeks. Blood pressure parameters, markers of oxidative stress and renal damage were measured. The immunohistochemistry of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme were also determined. Results indicated significant increases in malondialdehyde, advanced oxidation protein products, protein carbonyl contents and decrease in serum nitric oxide bioavailability in hypertensive rats. Furthermore, there were significant increases in serum myeloperoxidase, urinary creatinine, albumin and blood urea nitrogen in hypertensive rats in comparison to hypertensive rats treated with either Naringenin or Lisinopril. Immunohistochemistry reveal significant expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme in hypertensive rats. However, co-treatment with either Naringenin or Lisinopril mitigated both renal and neuronal oxidative stress, normalized blood pressure and lowered the expressions of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme. Collectively, Naringenin offered a novel antihypertensive and neuroprotective effect through down regulation of kidney injury molecule 1, mineralocorticoid receptor and angiotensin converting enzyme., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

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-1 β , 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 IC 50 of 4.28  µ g/mL. SPK04 and KFM05 did not inhibit 15-LOX as their IC 50 values were >1000  μ g/mL. All extracts were safe on Vero cells at the highest concentration (200  µ g/mL) tested. KFM02 was the best inhibitor of NO production and had the highest cell viability at both the lowest (50  µ g/mL) and highest concentrations (200  µ g/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  µ g/mL). The order of suppression of TNF- α by the extracts differed across concentrations, KFM05 > SPK04 > KFM02 at 200  µ g/mL, KFM02 > SPK04 > KFM05 at 100  µ g/mL, and SPK04 > KFM02 > KFM05 at 50  µ g/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-1 β , TNF- α , IL-6, and IL-10 by K. africana ., Competing Interests: The authors report no conflicts of interest in this work., (Copyright © 2020 Alice Nabatanzi et al.)

Fluoride is an environmental contaminant that is ubiquitously present in air, water, and soil. It is commonly added in minute quantity to drinking water, toothpaste, and mouth rinses to prevent tooth decay. Epidemiological findings have demonstrated that exposure to fluoride induced neurodevelopmental toxicity, developmental neurotoxicity, and motor disorders. The neuroprotective effect of clofibrate, a peroxisome proliferator-activated receptor alpha agonist, was investigated in the present study. Forty male Wistar rats were used for this study and randomly grouped into 10 rats per group as control, sodium fluoride (NaF) alone (300 ppm), NaF plus clofibrate (250 mg/kg), and NaF plus lisinopril (10 mg/kg), respectively, for 7 days. NaF was administered in drinking water while clofibrate and lisinopril were administered by oral gavage. Markers of neuronal inflammation and oxidative stress, acetylcholinesterase activity, and neurobehavioral (hanging wire and open field) tests were performed. Immunohistochemistry was performed on brain tissues, and they were probed with glial fibrillary acidic protein, ionized calcium-binding adaptor molecule 1, and cerebellar Ca 2+ -binding protein calbindin-D28k. The results showed that NaF significantly increased of oxidative stress and neuroinflammation and inhibited AChE activity. Immunostaining showed reactive astrocytes, microgliosis, loss of dendritic spines, and arborization in Purkinje cells in rats administered only NaF. Neurobehavioral results showed that cotreatment of NaF with clofibrate improved muscular strength and locomotion, reduced anxiety, and significantly reduced astrocytic count. Overall, cotreatment of NaF with either clofibrate or lisinopril showed neuroprotective effects by mitigating neuronal inflammation and oxidative and motor incoordination. Hence, clofibrate could be seen as a novel drug candidate against neurodegeneration and motor disorders., (© 2019 Wiley Periodicals, Inc.)

Ethnopharmacological Relevance: Hypoxis hemerocallidea (commonly known as African Potato) is popular in African traditional medicine. It is used in the management of diverse ailments including burns, wounds and skin-related diseases., Aim of the Study: The current study investigated the antimicrobial effects of Hypoxis hemerocallidea against six microorganisms associated with skin diseases. In addition, the antioxidant activity, phytochemical profiles and cytotoxicity of the bulb extracts were evaluated., Materials and Methods: The antimicrobial activity of 50% methanol (MeOH) and petroleum ether (PE) extracts of Hypoxis hemerocallidea bulbs was tested against two bacterial and four fungal strains implicated in causing opportunistic skin-related diseases. Antioxidant potential of the extract was investigated via the 2,2-diphenyl-1-picryhydrazyl (DPPH) free radical scavenging assay and β-carotene linoleic acid model. Phytochemical profiling of the 50% MeOH extract of Hypoxis hemerocallidea was done using spectrophotometric assay and Gas Chromatography-Mass Spectrometry (GC-MS). The extracts were also evaluated for cytotoxicity against African green monkey Vero kidney cell lines based on the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay., Results: Both 50% MeOH and PE extracts showed considerable inhibitory effects against all six microorganisms. The extracts were potent against Shigella flexneri and Trichophyton tonsurans with minimum inhibitory concentration (MIC) values less than 1 mg/ml. However, there was relatively poor antifungal activity against the other fungal strains. In the DPPH assay, the MeOH extract of the bulb had an EC 50 of 29.8 μg/ml while 76.91% antioxidant activity was observed in the β-carotene-linoleic acid model. The extract contained total phenolics (41 mg GAE/g) and flavonoids (10 mg CE/g). The GC-MS analysis of Hypoxis hemerocallidea bulb revealed 29 and 160 bioactive compounds for 50% MeOH and PE extracts, respectively. Based on the cytotoxicity, Hypoxis hemerocallidea had LC 50 value of 210.9 ± 18.4 and 95.5 ± 13.3 μg/ml for PE and MeOH extracts, respectively., Conclusions: The bulb extracts of Hypoxis hemerocallidea exhibited good antimicrobial and antioxidant activities, which could be attributed to the presence of phenolics, flavonoids and the other bioactive compounds identified through GC-MS, making it a potentially effective cosmetic plant. These findings also account for the multi-pharmacological use of Hypoxis hemerocallidea in traditional medicine, especially related to skin diseases. The plant extracts can be considered as safe based on their LC 50 values (< 20 μg/ml). However, other form of cytotoxicity studies need to be carried out on Hypoxis hemerocallidea, as well as in vivo tests, to confirm its safety and efficacy as a treatment for skin-related diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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 β-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, EC 50 values ranged from approximately 6-93 µg/mL and 65%-85% antioxidant activity in the β-carotene linoleic acid antioxidant activity model. The phenolic and flavonoid contents ranged from 3.5-64 mg GAE/g and 1.25-28 mg CE/g DW, respectively. The LC 50 values of the cytotoxicity assay ranged from 0.015-5622 µg/mL. GC-MS analysis revealed a rich pool (94-198) 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.