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Oxidative stress is a key factor that activates several transcription factors and mediators involved in the inflammatory pathways responsible for the pathogenesis of many chronic diseases. Targeting the expression of these mediators represents a promising approach to preventing these diseases. Cassinopsis ilicifolia leaf infusion is traditionally used for treating conditions such as inflammation and pain relief. Thus, the present study assessed the antioxidant and anti-inflammatory activities of the hydroethanolic leaf extract of C. ilicifolia using in vitro and cell-based assays. As a result, C. ilicifolia extract exhibited the highest DPPH• and ABTS•+ radical scavenging potential. At the same time, it weakly scavenged the Fe3+-TPTZ radical up to 200 µg/mL, thus suggesting a different antioxidant mechanism triggered during each assay. Additionally, C. ilicifolia extract inhibited NO production and 15-LOX activity with IC50 values of 21.10 µg/mL and 40.28 µg/mL, respectively. Further, C. ilicifolia extract was found to strongly inhibit ROS production in LPS-activated RAW 264.7 cells, and the study of its mechanism of action showed that it exerts its anti-inflammatory effect by downregulating the expression of inflammatory mediators such as IL-1β, TNF-α, and COX-2. Overall, C. ilicifolia extract showed consistent potency in all assays, and the analysis of its phytochemical profile led to the identification of 30 compounds, among which the most abundant were secologanic acid (1), chlorogenic acid (3CQA) (2), monotropein (3), chlorogenic acid (5CQA) (4), geniposidic acid (5), rutin (6), quercetin 3-galactoside (7), astragalin-7-rhamnoside (8), and minecoside (9) that are possibly responsible for its anti-inflammatory and antioxidant activities. Therefore, our findings suggested the potential use of C. ilicifolia as an alternative source for developing plant-based products against oxidative stress and inflammation-related conditions.

Abstract The emergence of drug-resistant Mycobacterium tuberculosis strains is a threat to global health necessitating the discovery of novel chemotherapeutic agents. Natural products drug discovery, which previously led to the discovery of rifamycins, is a valuable approach in this endeavor. Against this backdrop, we set out to investigate the in vitro antimycobacterial properties of medicinal plants from Ghana and South Africa, evaluating 36 extracts and their 252 corresponding solid phase extraction (SPE) generated fractions primarily against the non-pathogenic Mycobacterium smegmatis and Mycobacterium aurum species. The most potent fraction was further evaluated in vitro against infectious M. tuberculosis strain. Crinum asiaticum (bulb) (Amaryllidaceae) emerged as the most potent plant species with specific fractions showing exceptional, near equipotent activity against the non-pathogenic Mycobacterium species (0.39 µg/ml ≤ MIC ≤ 25 µg/ml) with one fraction being moderately active (MIC = 32.6 µg/ml) against M. tuberculosis. Metabolomic analysis led to the identification of eight compounds predicted to be active against M. smegmatis and M. aurum. In conclusion, from our comprehensive study, we generated data which provided an insight into the antimycobacterial properties of Ghanaian and South African plants. Future work will be focused on the isolation and evaluation of the compounds predicted to be active.

This study determines the phytochemical contents of selected medicinal plant extracts quantitatively using spectrophotometry and to evaluate their safety on mammalian cells in vitro using tetrazolium-based colorimetric cytotoxicity assay. Twenty-two ethanolic plant extracts were assessed, and the result showed that Psidium guajava had the highest concentration of alkaloids (219.06±11.50mg/g dry-weight (dw)). In contrast, Acacia nilotica leaf extract with 191.60±9.07mg/gdw had the highest level of flavonoids. Vernonia amygdalina and Moringa oleifera contained more steroids than the other plant extracts while condensed tannin was highest in Carya illinoinensis (21.72 ± 0.84 mg/g dw). Coffea arabica, Acacia nilotica leaf, Vernonia amygdalina, Carya illinoinensis and Psidium guajava had more saponins than the other plant extracts. Regarding cytotoxicity evaluation, Allium cepa and Tulbaghia violacea with concentration killing 50% of cells (LC50) values of 0.5182±0.40 and 0.4909 ± 0.034 mg/ml, respectively, were the safest of all the plant extracts. Acacia nilotica pod and Camelia japonica leaf extracts were the most cytotoxic with LC50 values of 0.0101 ± 0.016 and 0.0151 ± 0.005 mg/ml, respectively, which are well below the recommended toxic cut-off point (0.03mg/ml). The best selectivity index (SI) value of 1.061 was obtained with Aloe ferox against S. aureus, which is a Gram-positive bacterium.

Background:Sarcocephalus pobeguinii (Hua ex Pobég) is used in folk medicine to treat oxidative-stress related diseases, thereby warranting the investigation of its anticancer and anti-inflammatory properties. In our previous study, the leaf extract of S. pobeguinii induced significant cytotoxic effect against several cancerous cells with high selectivity indexes towards non-cancerous cells.Aim: The current study aims to isolate natural compounds from S. pobeguinii, and to evaluate their cytotoxicity, selectivity and anti-inflammatory effects as well as searching for potential target proteins of bioactive compounds.Methods: Natural compounds were isolated from leaf, fruit and bark extracts of S. pobeguinii and their chemical structures were elucidated using appropriate spectroscopic methods. The antiproliferative effect of isolated compounds was determined on four human cancerous cells (MCF-7, HepG2, Caco-2 and A549 cells) and non-cancerous Vero cells. Additionally, the anti-inflammatory activity of these compounds was determined by evaluating the nitric oxide (NO) production inhibitory potential and the 15-lipoxygenase (15-LOX) inhibitory activity. Furthermore, molecular docking studies were carried out on six putative target proteins found in common signaling pathways of inflammation and cancer.Results: Hederagenin (2), quinovic acid 3-O-[α-D-quinovopyranoside] (6) and quinovic acid 3-O-[β-D-quinovopyranoside] (9) exhibited significant cytotoxic effect against all cancerous cells, and they induced apoptosis in MCF-7 cells by increasing caspase-3/-7 activity. (6) showed the highest efficacy against all cancerous cells with poor selectivity (except for A549 cells) towards non-cancerous Vero cells; while (2) showed the highest selectivity warranting its potential safety as a chemotherapeutic agent. Moreover, (6) and (9) significantly inhibited NO production in LPS-stimulated RAW 264.7 cells which could mainly be attributed to their high cytotoxic effect. Besides, the mixture nauclealatifoline G and naucleofficine D (1), hederagenin (2) and chletric acid (3) were active against 15-LOX as compared to quercetin. Docking results showed that JAK2 and COX-2, with the highest binding scores, are the potential molecular targets involved in the antiproliferative and anti-inflammatory effects of bioactive compounds.Conclusion: Overall, hederagenin (2), which selectively killed cancer cells with additional anti-inflammatory effect, is the most prominent lead compound which may be further investigated as a drug candidate to tackle cancer progression.

Secondary metabolites were isolated using chromatographic techniques after being extracted sequentially from the roots of Artemisia afra using organic solvents such as ethanol, ethyl acetate, dichloromethane, and n-hexane. The isolated compounds were evaluated for anti-fungal, anti-bacterial, and cytotoxicity activities. Spectroscopic techniques, including Nuclear Magnetic Resonance (NMR), Fourier transform infrared (FTIR), and liquid chromatography–mass spectrometry (LC-MS), were used to elucidate the structures of the isolated compounds. The phytochemical investigation of A. afra led to the isolation of eight (A–H) compounds which were identified as 3β-taraxerol (A), 3β-taraxerol acetate (B), dodecyl-p-coumarate (C), ferulic acid (D), scopoletin (E), sitosterol-3-O-β-D-glucopyranoside (F), 3,5-di-O-feruloylquinic acid (G) and Isofraxidin-7-O-β-D-glucopyranoside (H) based on spectroscopic data. Compounds A, B, C, F, G, and H are known but were isolated for the first time from the roots of A. afra. The isolated compounds and extracts from A. afra exhibited good anti-fungal and anti-bacterial activity with dichloromethane and ethyl acetate crude extracts (0.078 mg/mL) and compound E (62.5 µg/mL) showed good activities against Escherichia coli. Compounds C and F also showed good activity against Enterococcus faecalis with minimum inhibitory concentration (MIC) values of 62.5 and 31.25 µg/mL, respectively. Extracts and compounds (A–H) exhibited anti-fungal and anti-bacterial properties and showed no toxicity when tested on Vero monkey kidney (Vero) cells.

Abstract Background This study evaluated the in vitro antioxidant activity and comparison of anti-inflammatory and cytotoxic activity of Harpagopytum zeyheri with diclofenac. Methods In vitro assays were conducted using water, ethanol, and ethyl acetate extracts of H.zeyheri. The antioxidant activity was evaluated using the 2,2′-diphenyl-1-picrylhydrazy (DPPH) and 2,2′- azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. The anti-inflammatory activity was determined by measuring the inhibition of nitric oxide (NO) on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages as well as cytokine (TNF-α and IL-10) expression on LPS-induced U937 human macrophages. For cytotoxicity, cell viability was determined using the 3-(4, 5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results The ethyl acetate extract had the lowest IC50 values in the DPPH (5.91 μg/ml) and ABTS (20.5 μg/ml) assay compared to other extracts. Furthermore, the ethyl acetate extracts effectively inhibited NO and TNF-α and proved to be comparable to diclofenac at some concentrations. All extracts of H. zeyheri displayed dose-dependent activity and were associated with low levels of human-IL-10 expression compared to quercetin. Furthermore, all extracts displayed low toxicity relative to diclofenac. Conclusions These findings show that H. zeyheri has significant antioxidant activity. Additionally, similarities exist in the inflammatory activity of H. zeyheri to diclofenac at some concentrations as well as low toxicity in comparison to diclofenac.

Every year, the number of studies that evaluate the pharmacological effects, (clinical) efficacy or the toxicity of medicinal plant extracts is constantly increasing, but the reporting quality remains unsatisfactory. One of the main reasons is that there is a lack of detailed reporting standards for guidance. In response to this long-standing challenge, a core group of nine experts with proficiency in phytochemical analysis, including editors-in-chief of leading specialist journals, and based in different research settings globally, developed the Consensus based reporting guidelines for Phytochemical Characterisation of Medicinal Plant extracts (ConPhyMP) through a multi-staged development process. This incorporated a) a global survey among medicinal plant researchers, b) a core group, who reviewed and developed the guidelines through a Delphi process, and c) an advisory group of 20 experts, including editors of leading journals and scientific societies in medicinal plants research, who provided feedback and sanctioned the final guidelines. The ConPhyMP guidelines comprise two tables with accompanying explanatory figures. The first table provides recommendations for reporting the starting material and its initial processing, and the second table presents recommendations for conducting and reporting the analytical methods for defining the chemical profile based on the type of extracts used in the research. The group hopes that the ConPhyMP will support authors as well as peer reviewers and editors assessing these studies for publication and assist the production of evidence-based guidance of studies utilising medicinal plant extracts.

Background: Research on medicinal plants and extracts derived from them differs from studies performed with single compounds. Extracts obtained from plants, algae, fungi, lichens or animals pose some unique challenges: they are multicomponent mixtures of active, partially active and inactive substances, and the activity is often not exerted on a single target. Their composition varies depending on the method of preparation and the plant materials used. This complexity and variability impact the reproducibility and interpretation of pharmacological, toxicological and clinical research.Objectives: This project develops best practice guidelines to ensure reproducibility and accurate interpretations of studies using medicinal plant extracts. The focus is on herbal extracts used in pharmacological, toxicological, and clinical/intervention research. Specifically, the consensus-based statement focuses on defining requirements for: 1) Describing the plant material/herbal substances, herbal extracts and herbal medicinal products used in these studies, and 2) Conducting and reporting the phytochemical analysis of the plant extracts used in these studies in a reproducible and transparent way.The process and methods: We developed the guidelines through the following process: 1) The distinction between the three main types of extracts (extract types A, B, and C), initially conceptualised by the lead author (MH), led the development of the project as such; 2) A survey among researchers of medicinal plants to gather global perspectives, opportunities, and overarching challenges faced in characterising medicinal plant extracts under different laboratory infrastructures. The survey responses were central to developing the guidelines and were reviewed by the core group; 3) A core group of 9 experts met monthly to develop the guidelines through a Delphi process; and. 4) The final draft guidelines, endorsed by the core group, were also distributed for feedback and approval to an extended advisory group of 20 experts, including many journal editors.Outcome: The primary outcome is the “Consensus statement on the Phytochemical Characterisation of Medicinal Plant extracts“ (ConPhyMP) which defines the best practice for reporting the starting plant materials and the chemical methods recommended for defining the chemical compositions of the plant extracts used in such studies. The checklist is intended to be an orientation for authors in medicinal plant research as well as peer reviewers and editors assessing such research for publication.

Black locust (Robinia pseudoacacia L.), an invasive tree in Europe, commonly known for its negative impact on biodiversity, is a rich source of phenolic compounds recognized in traditional medicine. Since the metabolite profile depends on the environment and climate, this study aimed to provide the first LC-MS phytochemical screening of the black locust from the Istria region (Croatia). The compounds were extracted from leaves and flowers with 70% ethanol and 80% methanol. Total phenolics (TP) and flavonoids (TF), as well as antioxidant capacity (AC) measured by ABTS (17.49–146.41 mg TE/g DW), DPPH (24.67–118.49 mg TE/g DW), and FRAP (7.38–77.53 mg TE/g DW) assays, were higher in leaf than in flower extracts. Higher TP and total non-flavonoid (TNF) values were displayed in ethanolic than in methanolic extracts. In total, 64 compounds were identified, of which flavonols (20) and hydroxycinnamic acid derivatives (15) were the most represented. Flavanols such as catechin dominated in leaf extracts, followed by flavonols, with kaempferol glucuronyl rhamnosyl hexosides as the main compound, respectively. Flower extracts had the highest share of flavones, followed by ellagitannins, with luteolin dirhamnosyl hexosides and vescalagin, respectively, being predominant. The extracts had good quorum sensing, biofilm formation prevention, and eradicating capacity. The results provided new insights into the phytochemical properties of R. pseudoacacia as the first step toward its potential pharmaceutical use.

Abstract 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.

Abstract Background Some viruses play a key role in the disturbance of the digestive system. The common viruses which cause infectious diarrhoea (gastroenteritis) include astrovirus, caliciviruses, coronavirus and torovirus which are single-stranded RNA viruses. Influenza A virus (H1N1) also causes diarrhoea in addition to being associated with respiratory symptoms. In preliminary studies, Newtonia hildebrandtii and N. buchananii leaf extracts had good antibacterial activity against some bacteria implicated in causing diarrhoea. The aim of this study was to evaluate the anti-influenza activity of two Newtonia species extracts and the isolated compound (myricitrin). Methods N. hildebrandtii and N. buchananii acetone, and MeOH: DCM (methanol-dichloromethane) leaf and stem extracts, and an antibacterial compound myricetin-3-o-rhamnoside (myricitrin), isolated from N. buchananii, were evaluated for their antiviral efficacy against influenza A virus (IAV) PR8/34/H1N1 as a model organism. The MTT and hemagglutination assays were used to assess the extracts and compound interference with cell viability and viral surface HA glycoprotein. The quantitative real-time PCR was performed to assess the viral load. Results Plant extracts of N. hildebrandtii and N. buchananii were effective against IAV. The extracts in combination with H1N1 showed highly significant antiviral activity (P

Bovine mastitis in dairy livestock production is a serious economic problem causing milk production losses and increased management costs. Staphylococcus aureus and non-aureus staphylococcus (NAS) are important causes of bovine mastitis. Antimicrobial resistance can limit the control of mastitis pathogens. Antibacterial and cytotoxic activities of acetone and ethanol extracts of nine South African plants were determined against reference and drug-resistant staphylococci isolated from clinical cases of bovine mastitis. The nine plants, namely, Antidesma venosum, Elaeodendron croceum, Erythrina caffra, Indigofera frutescens, Pleurostylia capensis, Searsia lancea, Searsia leptodictya, Trichilia emetica, and Ziziphus mucronata, were chosen for research material. The antibacterial activity of extracts was determined using a serial microdilution method, while a tetrazolium-based assay was used to determine their cytotoxicity against Vero cells. The values of antibacterial minimum inhibitory concentration (MIC) obtained were promising, with MIC ranging between 0.01 and 1.41 mg/mL. Generally, acetone extracts of most plants had better activity than their ethanol counterparts. The S. aureus strains were more susceptible to all the extracts than the NAS strains. The plant extracts’ half-maximal toxicity (LC50) was higher than 0.02 mg/mL, which is the recommended cytotoxic cut-off concentration. The ethanol extract of E. caffra, which showed better MIC values than its acetone extract, had the highest mean selectivity index (SI) of 8.30. Among the plants tested, S. lancea exhibited the most potent antibacterial activity, suggesting its potential usefulness as a broad-spectrum antibacterial agent against staphylococci associated with bovine mastitis, at relatively non-cytotoxic concentrations. Therefore, it is recommended for further investigation.

Antimicrobial resistant poultry pathogens are responsible for treatment failure and economic losses, and can also be a source of resistant zoonotic infections representing a risk to human health. In 2006 the European Union banned the use of antibiotics as growth promoters in farm animals and other regions are likely to follow suit. Alternative products and strategies are sought to help maintain animal gut health to reduce the prevalence of pathogens in the food chain. The minimum inhibitory concentration (MIC) of organic and aqueous leaf extracts of Alchornea laxiflora, Ficus exasperata, Morinda lucida, Jatropha gossypiifolia, Ocimum gratissimum, and Acalypha wilkesiana were tested against bacterial poultry pathogens including Staphylococcus aureus, Enterococcus faecalis, Salmonella spp., Escherichia coli, Campylobacter spp., and fungal species (Aspergillus fumigatus, Aspergillus flavus, and Candida albicans) using a 2-fold serial microdilution method. Activity of extracts against biofilms of the pathogens was done using a modified crystal violet staining in vitro assay. The safety of extracts was determined against Vero and Caco-2 cells using a tetrazolium-based in vitro assay. Acetone and cold water extracts of M. lucida had the best activity against three bacteria (MIC = 0.05–0.07 mg/ml) and two fungal (MIC = 0.03–0.15 mg/ml) organisms, respectively. The E. coli isolate and A. flavus were the most susceptible bacteria and fungi, respectively. Caco-2 cells generally displayed higher selectivity index (SI) values compared to Vero cells and average SI values against Vero and Caco-2 cells for both bacteria and fungi ranged from 0.01 to 4.48 and 0.005 to 16.41, respectively. All plant extracts had good anti-biofilm activity (>50%) against at least one organism. The disruption of established biofilm growth by the plant samples proved to be more difficult to achieve than efficacy against planktonic forms of bacteria. This study shows that some of the plant species are potential candidates as alternative feed additives in poultry production. In the future, a poultry feed trial to evaluate their in vivo efficacy as herbal feed additives will be conducted.

Abstract Background Antibiotics are commonly added to livestock feeds in sub-therapeutic doses as growth promoters and for prophylaxis against pathogenic microbes, especially those implicated in diarrhoea. While this practice has improved livestock production, it is a major cause of antimicrobial resistance in microbes affecting livestock and humans. This has led to the banning of prophylactic antibiotic use in animals in many countries. To compensate for this, alternatives have been sought from natural sources such as plants. While many studies have reported the antimicrobial activity of medicinal plants with potential for use as phytogenic/botanical feed additives, little information exists on their mode of action. This study is based on our earlier work and describes ultrastructural damage induced by acetone crude leaf extracts of Syzygium legatii and Eugenia zeyheri (Myrtaceae) active against diarrhoeagenic E. coli of swine origin using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescent microscopy (FM). Gas chromatography/mass spectrometry (GC-MS) was used to investigate the chemical composition of plant extracts. Results The extracts damaged the internal and external anatomy of the cytoplasmic membrane and inner structure at a concentration of 0.04 mg/mL. Extracts also led to an increased influx of propidium iodide into treated bacterial cells suggesting compromised cellular integrity and cellular damage. Non-polar compounds such as α-amyrin, friedelan-3-one, lupeol, and β-sitosterol were abundant in the extracts. Conclusions The extracts of S. legatii and E. zeyheri caused ultrastructural damage to E. coli cells characterized by altered external and internal morphology. These observations may assist in elucidating the mode of action of the extracts.

Abstract Background Urinary tract infections (UTIs) caused by opportunistic pathogens are among the leading health challenges globally. Most available treatment options are failing as a result of antibiotic resistance and adverse effects. Natural sources such as plants may serve as promising alternatives. Methods Compounds were isolated from the South African weed Chromolaena odorata through column chromatography. Purified compounds were tested for antimicrobial activity using the p-iodonitrotetrazolium chloride (INT) colorimetric method, against uropathogenic Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Aspergillus fumigatus and Cryptococcus neoformans. Anti-biofilm, anti-adhesion and metabolic inhibition activities were investigated against selected strains. Safety of the compounds was determined against Vero monkey kidney, C3A human liver and colon (Caco2) cells. Results Four compounds identified as pectolinaringenin (1), (±)-4′,5,7-trimethoxy flavanone (2), 5-hydroxy-3,7,4′-trimethoxyflavone (3) and 3,5,7-trihydroxy-4′-methoxyflavone) (4) were isolated. Minimum inhibitory concentration (MIC) varied between 0.016 and 0.25 mg/mL. Compounds 2 and 3 showed promising antimicrobial activity against E. coli, S. aureus, K. pneumoniae, A. fumigatus and C. neoformans with MIC between 0.016 and 0.125 mg/mL, comparable to gentamicin, ciprofloxacin and amphotericin B used as positive controls. Compounds 2 and 3 showed good anti-biofilm and metabolic inhibition activities against E. coli and S. aureus but weak anti-adhesion activity against the organisms. Low toxicity with selectivity indexes between 1 and 12.625 were recorded with the compounds, indicating that the compounds were rather toxic to the microbial strains and not to the human and animal cells. Conclusion Pharmacological activities displayed by compounds 2 and 3 isolated from C. odorata and low toxicity recorded credits it as a potential lead for the development of useful prophylactic treatments and anti-infective drugs against UTIs. Although known compounds, this is the first time these compounds have been isolated from the South African weed C. odorata and tested for antimicrobial, anti-biofilm, metabolic inhibition and anti-adhesion activities.

Tuberculosis (TB) is a disease of global importance that affects millions of people. Approximately a quarter of the world’s population is currently infected with M. tuberculosis, and about 10% of those infected will develop into active disease, particularly immune compromised individuals. Helminthiasis is of global health importance, affecting over 2 billion people mostly in resource-poor countries. Co-infection with tuberculosis (TB) and helminths (worms) is an emerging global public health concern with both affecting about one-third of the global population. Chronic infection with helminths can result in impaired immune responses to TB as well as enhancing failure to TB therapy and BCG vaccination. Antimycobacterial and anthelmintic activities of the acetone extract and fractions of Psychotria capensis were evaluated, including their in vitro safety. In addition, the anti-inflammatory and immunomodulatory effect of the fractions and crude extract of P. capensis were assessed. Antimycobacterial activity of the extract and fractions was tested against four non-tuberculous mycobacteria (Mycobacterium smegmatis, M. fortuitum, M. aurum, M. bovis BCG) and pathogenic M. tuberculosis H37Rv while the Egg Hatch Assay (EHA) was used for the anthelmintic test on eggs of Haemonchus contortus. Cytotoxicity was determined against Vero kidney cells while in vitro immune modulation via cytokine production was determined on activated macrophages. The minimum inhibitory concentration (MIC) values of the Psychotria capensis acetone extract and fractions ranged from 39 to 1,250 μg/ml with the crude extract and hexane fraction having the best MIC values (both 39 μg/ml). In the EHA, the inhibitory concentration (IC50) ranged from 160 to 630 μg/ml with the hexane fraction having the best activity. The hexane and chloroform fractions were relatively non-toxic with LC50 values of 290 and 248 μg/ml respectively, while the acetone crude extract (64 μg/ml) and n-butanol fraction (71 μg/ml) were moderately toxic. The SI values (LC50/MIC) ranged from 0.1 to 7.4 with the hexane fraction having the highest value against M. smegmatis (7.4). The hexane fraction had the best dual anthelmintic and antimycobacterial activity. This fraction had the best NO inhibitory activity and was the least cytotoxic, indicating that its activity was not due to general metabolic toxicity, with 96.54% cell viability. Pro-inflammatory cytokines such as IL-12p70 were upregulated while IL-10 expression was inhibited by the extracts. Compounds were detected using GC-MS analysis, and in both the crude acetone extract and the hexane fraction was the diterpene neophytadiene, which has anti-inflammatory and antimicrobial activity. Finding alternative or complementary approaches to dealing with TB infections by, amongst other things, reducing the incidence of helminth infestations may lessen the burden of TB, contributing to slowing the spread of multi-drug resistance.

There has been burgeoning interest in plant-based feed additives following restrictions placed on the use of antibiotic feed additives in many countries. Phytogenic feed additives are recommended to have a range of useful properties to support the growth and development of poultry to a similar level as that obtained by supplementing feed with antibiotics. The aim of this study was to evaluate the antibacterial, anti-lipoxygenase and antioxidant activity, and in vitro safety of fractions and isolated compounds from leaves of Senna singueana. Antibacterial activities of the fractions and isolated compounds were determined against a panel of bacteria using a two-fold serial microdilution assay and qualitative bioautography assays. Anti-lipoxygenase activity was evaluated using the ferrous oxidation-xylenol orange (FOX) method. Antioxidant activity was assessed qualitatively and quantitatively using radical scavenging assays. Dichloromethane and ethyl acetate fractions from solvent-solvent partitioning had the best antibacterial activity with MIC values ranging from 156 to 313 μg/ml. Fractions obtained from column chromatography had significant to weak antibacterial activity with MIC values ranging from 50 to 1,250 μg/ml. Bioautography showed clear bands of bacterial inhibition, indicating the presence of a number of active compounds in several fractions. The ethyl acetate fraction and all the tested column fractions had potent anti-lipoxygenase activity with IC50 values of ≤2.5 μg/ml which were lower than that of quercetin (positive control), indicating anti-inflammatory potential. The ethyl acetate fraction and several column fractions had powerful antioxidant activity with IC50 values of ≤5 μg/ml in the ABTS assay. Cytotoxicity values against Vero kidney cells ranged from LC50 = 40.0–989.3 μg/ml. Bioassay-guided fractionation led to the isolation and identification of a known bioactive compound, luteolin. S. singueana is a promising candidate for the development of poultry phytogenic feed additives.

Despite the medicinal uses of Phragmanthera capitata, Globimetula dinklagei and Tapinanthus bangwensis against memory loss, convulsions and pain, their efficacy against brain-dysfunction diseases and inflammation models has not yet been studied. Therefore, this study aims to investigate the anti-inflammatory and acetylcholinesterase (AChE) inhibitory potentials of their crude extracts and isolated natural compounds by combining in vitro and in silico experiments. Crude extracts and isolated compounds were tested in vitro for their AChE inhibitory activity by using Ellman’s method. Additionally, their anti-inflammatory activity was determined by evaluating the nitric oxide (NO) production inhibitory activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells and the 15-lipoxygenase (15-LOX) inhibitory activity by using the ferrous oxidation xylenol orange assay. Furthermore, the in silico efficacy of natural compounds was investigated against ten putative target enzymes relevant in Alzheimer’s disease (AD) pathogenesis and inflammation. It was found that the crude extracts had weak to moderate inhibitory potential against AChE, with the extract of T. bangwensis being the most active (50% inhibitory concentration (IC50) = 48.97 µg/mL). Six natural compounds, namely, 3-O-β-D-glucopyranosyl-28-hydroxy-α-amyrin (2), apigenin- 8-C-β-D-glucopyranoside (3), globimetulin B (5), globimetulin C (6), bangwaursene B (8) and 3β-acetoxy-11,12-epoxytaraxerol (9), were identified for the first time as having anti-AChE potential, among which (9) had the highest efficacy with an IC50 of 13.89 µM. Among the anti-AChE compounds, (5) was also efficient against NO production and 15-LOX, and the data are in agreement with the docking score. In summary, compounds (5) and (9) are the most prominent lead compounds that should be further tested experimentally against molecular targets of AD and inflammation.

Abstract Background Influenza A virus (IAV) is still a major health threat. The clinical manifestations of this infection are related to immune dysregulation, which causes morbidity and mortality. The usage of traditional medication with immunomodulatory properties against influenza infection has been increased recently. Our previous study showed antiviral activity of quercetin-3-O-α-L-rhamnopyranoside (Q3R) isolated from Rapanea melanophloeos (RM) (L.) Mez (family Myrsinaceae) against H1N1 (A/PR/8/34) infection. This study aimed to confirm the wider range of immunomodulatory effect of Q3R on selective pro- and anti-inflammatory cytokines against IAV in vitro, to evaluate the effect of Q3R on apoptosis pathway in combination with H1N1, also to assess the physical interaction of Q3R with virus glycoproteins and RhoA protein using computational docking. Methods MDCK cells were exposed to Q3R and 100CCID50/100 μl of H1N1 in combined treatments (co-, pre- and post-penetration treatments). The treatments were tested for the cytokines evaluation at RNA and protein levels by qPCR and ELISA, respectively. In another set of treatment, apoptosis was examined by detecting RhoA GTPase protein and caspase-3 activity. Molecular docking was used as a tool for evaluation of the potential anti-influenza activity of Q3R. Results The expressions of cytokines in both genome and protein levels were significantly affected by Q3R treatment. It was shown that Q3R was much more effective against influenza when it was applied in co-penetration treatment. Q3R in combination with H1N1 increased caspase-3 activity while decreasing RhoA activation. The molecular docking results showed strong binding ability of Q3R with M2 transmembrane, Neuraminidase of 2009 pandemic H1N1, N1 and H1 of PR/8/1934 and Human RhoA proteins, with docking energy of − 10.81, − 10.47, − 9.52, − 9.24 and − 8.78 Kcal/mol, respectively. Conclusions Quercetin-3-O-α-L-rhamnopyranoside from RM was significantly effective against influenza infection by immunomodulatory properties, affecting the apoptosis pathway and binding ability to viral receptors M2 transmembrane and Neuraminidase of 2009 pandemic H1N1 and human RhoA cellular protein. Further research will focus on detecting the detailed specific mechanism of Q3R in virus-host interactions.

Several cancers are induced by microbial infections or chronic inflammation. Ptaeroxylon obliquum is traditionally used to treat various infections characterized by inflammation. The in vitro antiproliferative and antioxidant activity of P. obliquum leaf extracts, fractions and isolated compounds were determined. Antiproliferative activity was assessed against normal Vero cells, and several cancerous human cells, including human breast cancer (MCF-7), hepatocarcinoma (HepG2), lung adenocarcinoma (A549) and human cervical cancer cells (HeLa) using a colorimetric tetrazolium bromide assay. Radical scavenging activity was tested using the 2,2-diphenyl-1-instrpicrylhydrazyl (DPPH) and 2,2’-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays. Obliquumol, O-methylalloptaeroxylin and a mixture of lupeol and β-amyrin were isolated from the chloroform fraction using silica gel open column chromatography. Acetone extracts were toxic to HepG2 cells with IC50 values from 8 to 200 µg/mL but were less toxic to other cells with selectivity index as high as 14. Aqueous extracts and fractions were non-toxic at concentrations tested against all the cell lines (IC50 > 100 µg/mL). Isolated compounds had IC50 values ranging from 52 to 539 µg/mL and 189 to 247 µg/mL against HepG2 and HeLa cells, respectively. Light microscopy showing changes in HepG2 and HeLa cell morphology supported the cytotoxicity of the acetone extracts. Water extracts scavenged ABTS and DPPH radicals with IC50 values as low as 29.06 µg/mL and 43.4 µg/mL. P. obliquum extracts may be useful as sources of anticancer therapy, as they have selective cytotoxicity against cancer cell lines.

Selenium (Se) is an essential trace nutrient for humans and animals owing to its role in redox regulation, thyroid hormone control factors, immunity, inflammatory reactions, brain activities, and carbohydrate regulation. It is also important to support muscle development, as well as for reproductive and cardiovascular well-being. Furthermore, sulfur is known to be a healing element, due to the remarkable function of specialized and secondary S-containing compounds. The scope of the current study was to determine the impact of Se and S enrichment on the secondary metabolite accumulation and antibacterial and NO inhibition activities in green and red leaf lettuce (V1 and V2, respectively). The plants were grown in a hydroponic system supplied with different S concentrations (S0: 0, S1: 1 mM and S2: 1.5 mM K2SO4) via the nutrient solution and foliar-applied varying levels of Se (0, 0.2 and 2.6 µM). Electrospray ionization–quadrupole time-of-flight mass spectrometry (ESI-QTOF/MS) combined with ultra-performance liquid chromatography (UPLC) was used to identify the secondary metabolites in green and red lettuce. The results indicated that extracts of the biofortified lettuce were not cytotoxic to Vero kidney cells at the highest concentration tested of 1 mg/mL. The ESI/MS of the tentatively identified metabolites showed that the response values of 5-O-caffeoylquinic acid, cyanidin 3-O-galactoside, quercetin 3-O-(6′′-acetyl-glucoside) and quercetin 3-O-malonylglucoside were induced synergistically under higher Se and S levels in red lettuce plants. The acetone extract of red lettuce had antibacterial activity against Pseudomonas aeruginosa, with a minimum inhibitory concentration (MIC) of 0.156 and 0.625 μg/mL under S2/Se1 and S2/Se2 treatments, respectively. As with antibacterial activity, the acetone extract of green (V1) lettuce treated with adequate (S1) and higher S (S2) under Se-limiting conditions showed the ability to inhibit nitric oxide (NO) release from macrophages. NO production by macrophages was inhibited by 50% at respective concentrations of 106.1 ± 2.4 and 101.0 ± 0.6 μg/mL with no toxic effect on the cells, in response to S1 and S2, respectively, under Se-deficient conditions (Se0). Furthermore, the red cultivar (V2) exhibited the same effect as the green cultivar (V1) regarding NO inhibition, with IC50 = 113.0 ± 4.2 μg/mL, in response to S1/Se2 treatments. Collectively, the promising NO inhibitory effect and antibacterial activity of red lettuce under the above-mentioned conditions might be attributed to the production of flavonoid glycosides and phenylpropanoic acid esters under the same condition. To the best of our knowledge, this is the first report to show the novel approach of the NO inhibitory effect of Se and S enrichment in food crops, as an indicator for the potential of Se and S as natural anti-inflammatory agents.

No abstract available.

Abstract Background Many studies have revealed that bioactive compounds for different indications are not extracted from plants with water, the only extractant practically available to rural communities. We compared the acaricidal activity of acetone extracts of 13 species used traditionally to protect cattle against ticks. We also investigated if the extraction of biologically active compounds against Rhipicephalus (Boophilus) decoloratus ticks could be enhanced by adding a liquid soap that is locally available to smallholder farmers. Methods A total of 13 plant species selected based on reported traditional use in Zimbabwe, were dried and finely ground before extraction with water, or water plus a surfactant, or acetone. The adapted Shaw Larval Immersion Test (SLIT) method was used to determine the activity of acetone and crude water extracts with or without liquid soap against the tick larvae. The activity of four fractions of crude acetone extracts (extracted using solvents of different polarity), of the most active plant species, Maerua edulis (tuber and leaf) was also compared to identify the most active fraction. Results Aqueous plant extracts were not toxic to ticks, but the addition of 1% liquid soap as a surfactant increased mortality of the R. (B) decoloratus larvae significantly. With the Maerua edulis tuber extract, the efficacy of the 1% liquid soap was comparable to that of the amitraz based commercial synthetic acaricide. The use of acetone as an extractant, also increased the mortality of the tick larvae in all the plant species. With M. edulis (tuber and leaf), Monadenium lugardae and Kleinia sp. acetone extracts, the activity was comparable to that of the positive control (a commercially available amitraz-based synthetic acaricide). The non-polar fractions of the acetone extract of leaf and tuber of M. edulis caused up to 100% mortality. This indicates that non-polar to intermediate polarity compounds are responsible for the acaricidal activity. Conclusion Organic solvents such as acetone extracted active compounds but water did not. By adding commonly available dishwashing soap to water active compounds were extracted leading to a high acaricidal activity of the plant extracts. In some cases, it was as active as non-polar extracts and a synthetic commercial acaricide (positive control). This approach makes it possible for the smallholder farmers and traditional healers to extract biologically active compounds from plants by using water.

Abstract Background Antimicrobial resistance (AMR) remains an important global health issue but the gap between AMR and development of new antimicrobials is increasing. Plant extracts may have good activity per se or may be sources of effective antimicrobial compounds which can act against planktonic and/or biofilms of pathogens. We determined the antimicrobial efficacy and cytotoxicity of some under-investigated plants from the Myrtaceae family endemic to South Africa. The ability of the plant extracts to inhibit or destroy pre-formed bacterial biofilms was also determined. Methods Based on previous preliminary in vitro screening and on chemotaxonomy, nine species from the Myrtaceae family were selected. The antimicrobial activity of the crude acetone leaf extracts was determined against six common nosocomial pathogens, namely: Gram-positive bacteria (Bacillus cereus, Enterococcus faecalis, Staphylococcus aureus), Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium) using a two-fold serial microdilution assay with p-iodonitrotetrazolium violet as growth indicator. The number of antimicrobial compounds present in extracts was determined by bioautography. Cytotoxicity of extracts was determined against Vero kidney cells using a colorimetric tetrazolium-based assay. The total antibacterial activity (TAA) in ml/g and selectivity index (LC50/MIC) of the plant extracts were calculated. A modified crystal violet assay was used to determine the antibiofilm activity of the extracts. Results Syzygium legatii, Syzygium masukuense, and Syzygium species A had the best activities against Gram-negative and Gram-positive bacteria (MIC) values ranging from 0.04–0.08 mg/ml. Eugenia erythrophylla had the best MIC (0.02 mg/ml) against Bacillus cereus. Many extracts had relatively low cytotoxicity (LC50 > 20 μg/ml) leading to reasonable selectivity indices. Three leaf extracts (Syzygium masukuense, Syzygium species A, and Eugenia natalitia) were moderately cytotoxic (20 μg/ml

Abstract Background Diarrhoea, a global economically important disease burden affecting swine and, especially piglets, is commonly caused by infection with entero-toxigenic E. coli (ETEC). Adherence of ETEC to porcine intestinal epithelial cells following infection, is necessary for its pathogenesis. While antimicrobials are commonly given as therapy or as feed additives for prophylaxis against microbial infections, the concern over increased levels of antimicrobial resistance necessitate the search for safe and effective alternatives in livestock feed. Attention is shifting to natural products including plants as suitable alternatives to antimicrobials. The activity of acetone crude leaf extracts of nine under-explored South African endemic plants from the Myrtaceae family with good antimicrobial activity were tested against pathogenic E. coli of porcine origin using a microplate serial dilution method. Bioautography, also with p-iodonitrotetrazolium violet as growth indicator was used to view the number of bioactive compounds in each extract. In vitro toxicity of extracts was determined against Caco-2 cells using the 3-(4,5-dimethythiazolyl-2)-2,5-diphenyltetrazolium bromide reduction assay. The antimicrobial susceptibility of E. coli isolates was tested on a panel of antimicrobials using the Kirby-Bauer agar diffusion method while the anti-adherence mechanism was evaluated using a Caco-2 cell enterocyte anti-adhesion model. Results The MIC of the extracts ranged from 0.07–0.14 mg/mL with S. legatii having the best mean MIC (0.05 mg/mL). Bioautography revealed at least two active bands in each plant extract. The 50% lethal concentration (LC50) values ranged between 0.03–0.66 mg/mL. Eugenia zeyheri least cytotoxic (LC50 = 0.66 mg/ml) while E. natalitia had the highest cytotoxicity (LC50 = 0.03 mg/mL). All the bacteria were completely resistant to doxycycline and colistin sulphate and many of the plant extracts significantly reduced adhesion of E. coli to Caco-2 cells. Conclusions The extracts of the plants had good antibacterial activity as well as a protective role on intestinal epithelial cells against enterotoxigenic E. coli bacterial adhesion. This supports the potential use of these species in limiting infection causes by E. coli. Some of these plants or extracts may be useful as phytogenic feed additives but it has to be investigated by animal feed trials.

Abstract Background Tuberculosis is a deadly disease caused by Mycobacterium species. The use of medicinal plants is an ancient global practice for the treatment and prevention of diverse ailments including tuberculosis. The aim of this study was to isolate and characterize antimycobacterial compounds by bioassay-guided fractionation of the acetone leaf extract of Oxyanthus speciosus. Methods A two-fold serial microdilution method was used to determine the minimum inhibitory concentration (MIC) against mycobacteria. Cytotoxicity and nitric oxide inhibitory activity of the isolated compounds was determined to evaluate in vitro safety and potential anti-inflammatory activity. Intracellular efficacy of the crude extract against Mycobacterium-infected macrophages was also determined. Results Two compounds were isolated and identified as lutein (1) and rotundic acid (2). These had good antimycobacterial activity against the four mycobacteria tested with MIC values ranging from 0.013 to 0.1 mg/mL. Rotundic acid had some cytotoxicity against C3A human liver cells. Lutein was not cytotoxic at the highest tested concentration (200 μg/mL) and inhibited nitric oxide production in RAW 264.7 macrophages by 94% at a concentration of 25 μg/mL. The acetone crude extract (120 μg/mL) of O. speciosus had intracellular antimycobacterial activity, reducing colony forming units by more than 90%, displaying bactericidal efficacy in a dose and time-dependent manner. Conclusion This study provides good proof of the presence of synergism between different compounds in extracts and fractions. It is also the first report of the antimycobacterial activity of lutein and rotundic acid isolated from Oxyanthus speciosus. The promising activity of the crude extract of O. speciosus both in vitro and intracellularly in an in vitro macrophage model suggests its potential for development as an anti- tuberculosis (TB) herbal medicine.

The emergence of viral pneumonia caused by a novel coronavirus (CoV), known as the 2019 novel coronavirus (2019-nCoV), resulted in a contagious acute respiratory infectious disease in December 2019 in Wuhan, Hubei Province, China. Its alarmingly quick transmission to many countries across the world and a considerable percentage of morbidity and mortality made the World Health Organization recognize it as a pandemic on March 11, 2020. The perceived risk of infection has led many research groups to study COVID-19 from different aspects. In this literature review, the phylogenetics and taxonomy of COVID-19 coronavirus, epidemiology, and respiratory viruses similar to COVID-19 and their mode of action are documented in an approach to understand the behavior of the current virus. Moreover, we suggest targeting the receptors of SARS-CoV and SARS-CoV-2 such as ACE2 and other proteins including 3CLpro and PLpro for improving antiviral activity and immune response against COVID-19 disease. Additionally, since phytochemicals play an essential role in complementary therapies for viral infections, we summarized different bioactive natural products against the mentioned respiratory viruses with a focus on influenza A, SARS-CoV, MERS, and COVID-19.Based on current literature, 130 compounds have antiviral potential, and of these, 94 metabolites demonstrated bioactivity against coronaviruses. Interestingly, these are classified in different groups of natural products, including alkaloids, flavonoids, terpenoids, and others. Most of these compounds comprise flavonoid skeletons. Based on our survey, xanthoangelol E (88), isolated from Angelica keiskei (Miq.) Koidz showed inhibitory activity against SARS-CoV PLpro with the best IC50 value of 1.2 μM. Additionally, hispidulin (3), quercetin (6), rutin (8), saikosaponin D (36), glycyrrhizin (47), and hesperetin (55) had remarkable antiviral potential against different viral infections. Among these compounds, quercetin (6) exhibited antiviral activities against influenza A, SARS-CoV, and COVID-19 and this seems to be a highly promising compound. In addition, our report discusses the obstacles and future perspectives to highlight the importance of developing screening programs to investigate potential natural medicines against COVID-19.

Cryopreservation and storage of semen for artificial insemination (AI) result in excessive accumulation of reactive oxygen species (ROS). This leads to a shortened life span and reduced motility of spermatozoa post-thawing, with consequent impairment of their function. However, certain levels of ROS are essential to facilitate the capacitation of spermatozoa required for successful fertilisation. Tannins, as well-known antioxidant compounds, may act as ROS binders/acceptors/scavengers to inhibit the damaging effects of ROS. This review comprises an analysis of the semen cryopreservation protocol and health functions of tannins, as well as the effects of ROS on fresh and cryopreserved semen’s longevity and fertilisation. Additionally, we surveyed available evidence of the effects of tannin extract feed supplementation on male fertility. We furthermore interrogated existing theories on tannin use as a potential additive to semen extenders, its relationship with semen quality, and to what degree existing theories have been investigated to develop testable new hypotheses. Emphasis was placed on the effects of tannins on ROS, their involvement in regulating sperm structure and function during cryopreservation, and on post-thaw sperm motility, capacitation, and fertilising ability. The diverse effects of tannins on the reproductive system as a result of their potential metal ion chelation, protein precipitation, and biological antioxidant abilities have been identified. The current data are the first to support the further investigation of the incorporation of tannin-rich plant extracts into semen extenders to enhance the post-thaw survival, motility, and fertilising ability of cryopreserved spermatozoa.

Abstract Background Croton species (Euphorbiaceae) are distributed in different parts of the world, and are used in traditional medicine to treat various ailments including cancer, inflammation, parasitic infections and oxidative stress related diseases. The present study aimed to evaluate the antioxidant, anti-inflammatory and cytotoxic properties of different extracts from three Croton species. Methods Acetone, ethanol and water leaf extracts from C. gratissimus, C. pseudopulchellus, and C. sylvaticus were tested for their free radical scavenging activity. Anti-inflammatory activity was determined via the nitric oxide (NO) inhibitory assay on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages, and the 15-lipoxygenase inhibitory assay using the ferrous oxidation-xylenol orange assay. The cytotoxicity of the extracts was determined on four cancerous cell lines (A549, Caco-2, HeLa, MCF-7), and a non-cancerous African green monkey (Vero) kidney cells using the tetrazolium-based colorimetric (MTT) assay. The potential mechanism of action of the active extracts was explored by quantifying the caspase-3/− 7 activity with the Caspase-Glo® 3/7 assay kit (Promega). Results The acetone and ethanol leaf extracts of C. pseudopulchellus and C. sylvaticus were highly cytotoxic to the non-cancerous cells with LC50 varying between 7.86 and 48.19 μg/mL. In contrast, the acetone and ethanol extracts of C. gratissimus were less cytotoxic to non-cancerous cells and more selective with LC50 varying between 152.30 and 462.88 μg/mL, and selectivity index (SI) ranging between 1.56 and 11.64. Regarding the anti-inflammatory activity, the acetone leaf extract of C. pseudopulchellus had the highest NO inhibitory potency with an IC50 of 34.64 μg/mL, while the ethanol leaf extract of the same plant was very active against 15-lipoxygenase with an IC50 of 0.57 μg/mL. A linear correlation (r

Abstract Background The constant emergence of antibiotic resistant species and the adverse side effects of synthetic drugs are threatening the efficacy of the drugs that are currently in use. This study was aimed at investigating the possible antibacterial interactions, anti-inflammatory and cytotoxic effects of selected medicinal plants based on their traditional usage. Methods The acetone extracts of four plant species were assessed independently and in combination for antibacterial activity using microdilution assay and the sum of the fractional inhibitory concentration (FIC) was calculated. The ability of Dombeya rotundifolia and Schkuhria pinnata extracts to inhibit the production of reactive oxygen species (ROS) in LPS induced RAW 264.7 macrophage cells was evaluated using Dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay to determine anti-inflammatory potential and the toxicity on African green monkey kidney (Vero) cells was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results The antibacterial efficacies of the different combinations of Schkuhria pinnata (A), Commelina africana (B), Dombeya rotundifolia (C) and Elephantorrhiza elephantina (D) plants varied from combination to combination. Synergistic effects were only exhibited against P. aeruginosa, while the antagonistic effects were only observed against E. coli. Both S. pinnata and D. rotundifolia demonstrated anti-inflammatory potential by inhibiting the production of ROS in a dose dependant manner. The cytotoxicity of the plants (LC50 values) ranged from

Abstract Background Influenza infection is a major public health threat. The role of influenza A virus-induced inflammatory response in severe cases of this disease is widely recognized. Drug resistance and side effects of chemical treatments have been observed, resulting in increased interest in alternative use of herbal medications for prophylaxis against this infection. The South African medicinal plant, Rapanea melanophloeos (RM) (L.) Mez of the family Myrsinaceae was selected owing to its traditional use for the treatment of several diseases such as respiratory ailments and also previous preliminary studies of anti-influenza activity of its methanolic extract. The aim of this study was to investigate the immunomodulatory properties of a glycoside flavone isolated from RM against influenza A virus. Methods The non-cytotoxic concentration of the quercetin-3-O-α-L-rhamnopyranoside (Q3R) was determined by MTT assay and tested for activity against influenza A virus (IAV) in simultaneous, pre-penetration and post-penetration combination treatments over 1 h incubation on MDCK cells. The virus titer and viral load targeting NP and M2 viral genes were determined using HA and qPCR, respectively. TNF-α and IL-27 as pro- and anti-inflammatory cytokines were measured at RNA and protein levels by qPCR and ELISA, respectively. Results Quercetin-3-O-α-L-rhamnopyranoside at 150 μg/ml decreased the viral titer by 6 logs (p

Abstract Background Influenza infection remains a major health threat for animals and humans which crucially requires effective antiviral remedies. The usage of herbal medications as readily available alternatives for their compatibility with the body and fewer side effects compared to synthetic chemical treatments has become popular globally. The aim of this study was to investigate and screen in vitro anti-influenza activity of extracts of five South African medicinal plants, namely Tabernaemontana ventricosa, Cussonia spicata, Rapanea melanophloeos, Pittosporum viridiflorum and Clerodendrum glabrum, species which are used traditionally for the treatment of several diseases such as inflammatory and respiratory diseases. Methods Methanol, ethanol (100% and 30%), acetone, hot and cold water extracts of the powdered plants leaves were obtained by standard methods. The cytotoxicity was determined by the MTT colorimetric assay on MDCK cells. The concentrations below CC50 values were tested for antiviral activity against influenza A virus (IAV) in different combination treatments. The effect of extracts on viral surface glycoproteins and viral titer were tested by HI and HA virological assays, respectively. Results Based on the applied methods, the most effective results against IAV were obtained from Rapanea melanophloeos methanol leaf extract (EC50 = 113.3 μg/ml) and Pittosporum viridiflorum methanol, 100% and 30% ethanol and acetone leaf extracts (EC50 values = 3.6, 3.4, 19.2, 82.3 μg/ml, respectively) in all types of combined treatments especially in pre- and post-penetration combined treatments with highly significant effects against viral titer (P ≤ 0.01). Conclusion The outcomes offer for the first time a scientific basis for the use of extracts of Rapanea melanophloeos and Pittosporum viridiflorum against IAV. It is worth focusing on the isolation and identification of effective active compounds and elucidating the mechanism of action from these species. However, Tabernaemontana ventricosa, Cussonia spicata and Clerodendrum glabrum leaf extracts were ineffective in vitro in this study.

A series of 2-arylbenzo[b]furan–appended 4-aminoquinazoline hybrids were prepared and evaluated for cytotoxicity in vitro against the human lung cancer (A549), colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A) and cervical cancer (HeLa) cell lines. Compounds 10d and 10j exhibited significant cytotoxicity against the C3A and Caco-2 cell lines and induced apoptosis in these cell lines. Likewise, compounds 10d and 10e exhibited significant inhibitory activity towards epidermal growth factor receptor-tyrosine kinase phosphorylation (IC50 values of 29.3 nM and 31.1 nM, respectively) against Gefitinib (IC50 = 33.1 nM). Molecular docking of compounds 10 into EGFR-TK active site suggests that they bind to the region of EGFR like Gefitinib does.

Selenium (Se)-enriched vegetables are promising dietary sources of Se, which provides beneficial biological effects in humans. In this study, we investigated the effects of foliar application of Se on hydroponically grown multi-leaf green (V1) and red (V2) lettuce plants. Three selenate (SeIV) amendment levels were evaluated for their influence on plant growth, elemental composition and radical scavenging capacity. Lettuce heads biofortified with 0.598 mg Se plant−1 accumulated 19.6–23.6 and 14.9–17.6 μg Se g−1 DM in the multi-leaf green (V1) and red (V2) lettuce plants, respectively. The accumulated Se levels can contribute significantly to the recommended dietary allowance of 70 µg day−1 for adult men and 60 µg day−1 for adult women. Accordingly, both V1 and V2 lettuce cultivars grown under the Se3 foliar application condition can cover the daily requirement for adult men by approximately 100% and 85% to 100%, respectively, by consuming 75–90 g or 100 g fresh weight from V1 or V2, respectively. The ABTS radical scavenging potential of green lettuce was induced at Se2 and Se3 foliar application levels, where the IC50 was 1.124 ± 0.09 μg mL−1 at Se0 and improved to 0.795 ± 0.03 and 0.697 ± 0.01 μg mL−1, respectively. There was no cytotoxicity against Vero kidney cells among all treated lettuce plants at the highest concentration tested of 1 mg/mL. Finally, a further focused investigation of the metabolic profile of lettuce plants under varied Se levels needs to be investigated in future studies.

Abstract Background Tuberculosis is a world-wide problem affecting humans and animals. There is increasing development of resistance of the pathogens to current antimycobacterial agents. Many authors have investigated activities of extracts and isolated compounds from plants. The traditional uses of plants have frequently been the criterion to select plants investigated. In this contribution, we investigate whether plant extracts with very good activity against Escherichia coli may also be active against mycobacteria. Methods The antimycobacterial activity of eight South African tree leaf extracts with high activity against Escherichia coli were determined in vitro against Mycobacterium smegmatis, M. fortuitum and M. aurum, using a serial microdilution method. The cellular cytotoxicity was also determined by the MTT assay using Vero monkey kidney cells. The selectivity index was determined by dividing the cytotoxicity of extracts by MIC. Results The antimycobacterial activity of the extracts ranged from 0.02 to 2.5 mg/ml. Mycobacterium smegmatis was more sensitive to the extracts (Average MIC = 0.96 mg/ml) and Mycobacterium aurum was comparatively resistant (Average MIC = 2.04 mg/ml). The extracts of Cremaspora triflora had strong antimycobacterial activity with a MIC of 0.05 mg/ml that compared reasonably well with that of streptomycin (0.01 mg/ml) and rifampicin (0.03 mg/ml), p > 0.05. Cremaspora triflora had the best selectivity index of 2.87 against Mycobacterium fortuitum. Conclusion The high activity of C. triflora extracts against the fast-growing mycobacteria and good cellular safety is promising. It may be interesting to investigate extracts against pathogenic M. tuberculosis, M. bovis and M. avium cultures and to isolate active antimycobacterial compounds.

Hot water and hydroethanolic (70:30) extracts were prepared from 15 plant species, which were investigated to discover eco-friendly and less expensive tick control methods as an alternative to synthetic acaricides. A contact bioassay was used to determine the acaricidal activity of these extracts against the cattle tick, Rhipicephalus turanicus (Acari: Ixodidae) at a concentration of 20% (200 mg/mL). The hydroethanolic extracts had better activity than the hot water extracts against R. turanicus. The hydroethanolic extract from Tabernaemontana elegans (leaves) had the best mortality (87.0%). This was followed by Calpurnia aurea (stems) with a mortality of 75.0%, Schkuhria pinnata (whole plant) with a mortality of 67.0% and Aloe rupestris (leaves) with a mortality of 66.6%. The toxicity of the plant extracts was also investigated and it was found that most of the hydroethanolic and hot water extracts were either safe or very safe on human Vero kidney and liver HepG2 cells. From this study, it was evident that botanicals have the potential to be developed as environmentally benign natural acaricides against R. turanicus.

Tuberculosis (TB), a disease caused by microorganisms of the Mycobacterium tuberculosis complex, infects almost one-third of the world’s population. The TB epidemic has been further exacerbated by the emergence of multi, extensively, and totally-drug-resistant (MDR, XDR, and TDRTB) strains. An effective immune response plays a crucial role in determining the establishment of TB infection. Therefore, the modulation of the immune system has been considered as a vital approach for the treatment or control of various immune-related diseases such as TB. In this study, the antimycobacterial, immunomodulatory, and apoptosis-inducing effects of six Rubiaceae species were evaluated. A twofold serial dilution method was used to determine the minimum inhibitory concentration values of the plant extracts. The effect of the extracts on the activity of 15-lipoxygenase was investigated. The levels of six different cytokines, IL-2, IL-4, IL-5, IL-10, IFN-γ, and TNF-α, were measured in LPS-activated U937 cell line while the apoptosis-inducing effect of the extracts was evaluated using an annexin V/PI assay using a flow cytometer. The results obtained revealed that all the six extracts tested had antimycobacterial activity against M. tuberculosis H37Rv, M. tuberculosis ATCC 25177, and Mycobacterium bovis ATCC 27299 strains, with MIC values ranging from 39 to 312 μg/mL. The extracts of Cremaspora triflora and Cephalanthus natalensis were the most active against M. tuberculosis (MIC = 39 μg/mL), followed by Pavetta lanceolata and Psychotria zombamontana against M. bovis (MIC = 78 μg/mL). The extracts of P. zombamontana and Psychotria capensis had remarkable IC50 values of 4.32 and 5.8 μg/mL, respectively, better than that of quercetin. The selected extracts promoted Th1/Th2 balances in an in vitro model at the tested concentration which may suggest the therapeutic value of the plant in diseases where inflammation is a significant factor such as TB. The addition of the crude extracts of C. triflora, P. capensis, and P. zombamontana at the tested concentrations to the cell culture medium induced apoptosis in a time- and dose-dependent manner. This interesting preliminary result generated from this study encourages further investigations of these extracts owing to the LOX-inhibitory effect, immunomodulatory, and apoptotic-inducing properties in addition to their antimycobacterial properties.

Plants of the genus Euphorbia are widely distributed across temperate, tropical and subtropical regions of South America, Asia and Africa with established Ayurvedic, Chinese and Malay ethnomedical records. The present review reports the isolation, occurrence, phytochemistry, biological properties, therapeutic potential and structure–activity relationship of Euphorbia flavonoids for the period covering 2000–2020, while identifying potential areas for future studies aimed at development of new therapeutic agents from these plants. The findings suggest that the extracts and isolated flavonoids possess anticancer, antiproliferative, antimalarial, antibacterial, anti-venom, anti-inflammatory, anti-hepatitis and antioxidant properties and have different mechanisms of action against cancer cells. Of the investigated species, over 80 different types of flavonoids have been isolated to date. Most of the isolated flavonoids were flavonols and comprised simple O-substitution patterns, C-methylation and prenylation. Others had a glycoside, glycosidic linkages and a carbohydrate attached at either C-3 or C-7, and were designated as d-glucose, l-rhamnose or glucorhamnose. The structure–activity relationship studies showed that methylation of the hydroxyl groups on C-3 or C-7 reduces the activities while glycosylation loses the activity and that the parent skeletal structure is essential in retaining the activity. These constituents can therefore offer potential alternative scaffolds towards development of new Euphorbia-based therapeutic agents.

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.

South Africa has a long history and strong belief in traditional herbal medicines. Using ethnobotanical knowledge as a lead, a large number of South African medicinal plants have been discovered to possess a wide spectrum of pharmacological properties. In this review, bioprospecting of endophytes is highlighted by following the advantages of the ethnomedicinal approach together with identifying unique medicinal plants where biological activity may be due to endophytes. This review focuses on the current status of South African medicinal plants to motivate the research community to harness the benefits of ethnobotanical knowledge to investigate the presence of endophytic microbes from the most potent South African medicinal plants. The potential chemical diversity and subsequent putative medicinal value of endophytes is deserving of further research. A timely and comprehensive review of literature on recently isolated endophytes and their metabolites was conducted. Worldwide literature from the last 2 years demonstrating the importance of ethnobotanical knowledge as a useful approach to discover endophytic microbes was documented. Information was obtained from scientific databases such as Pubmed, Scopus, Scirus, Google Scholar, Dictionary of Natural Products, Chemical Abstracts Services, official websites, and scientific databases on ethnomedicines. Primary sources such as books, reports, dissertations, and thesises were accessed where available. Recently published information on isolated endophytes with promising bioactivity and their bioactive natural products worldwide (2015-2017) was summarized. The potential value of South African medicinal plants as sources of endophytes is discussed. The insights provided through this study indicate that medicinal plants in South Africa are highly under-investigated sources of potentially useful endophytic microbes. New approaches may be used by medicinal plant scientists for further exploration of natural products from endophytic fungi and bacteria in southern Africa.

BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 (μg/L. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 (μg/L) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 μg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 μM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 (μg/L for (1), 34.15 (μg/L for (2) and 45.66 (μg/L for (3), compared to galantamine (IC50 of 8.22 ( g/mL) used as positive control CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production

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, EC50 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 LC50 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.

Peptides are important biomolecules which facilitate the understanding of complex biological processes, which in turn could be serendipitous biological targets for future drugs. They are classified as a unique therapeutic niche and will play an important role as fascinating agents in the pharmaceutical landscape. Until now, more than 40 cyclic peptide drugs are currently in the market, and approximately one new cyclopeptide drug enters the market annually on average. Interestingly, the majority of clinically approved cyclic peptides are derived from natural sources, such as peptide antibiotics and human peptide hormones. In this report, the importance of cyclic peptides is discussed, and their role in drug discovery as interesting therapeutic biomolecules will be highlighted. Recently isolated naturally occurring cyclic peptides from microorganisms, sponges, and other sources with a wide range of pharmacological properties are reviewed herein.

A series of indole-aminoquinazolines was prepared via amination of the 2-aryl-4-chloroquinazolines with the 7-amino-2-aryl-5-bromoindoles. It was then evaluated for cytotoxicity in vitro against human lung cancer (A549), epithelial colorectal adenocarcinoma (Caco-2), hepatocellular carcinoma (C3A), breast adenocarcinoma (MCF-7), and cervical cancer (HeLa) cells. A combination on the quinazoline and indole moieties of a 2-phenyl and 2-(4-fluorophenyl) rings in compound 4b; 2-(4-fluorophenyl) and 3-chlorophenyl rings in compound 4f; or the two 2-(4-fluorophenyl) rings in compound 4g, resulted in significant and moderate activity against the Caco-2 and C3A cell lines. The indole-aminoquinazoline hybrids compounds 4f and 4g induced apoptosis in Caco-2 and C3A cells, and were also found to exhibit moderate (IC50 = 52.5 nM) and significant (IC50 = 40.7 nM) inhibitory activity towards epidermal growth factor receptor (EGFR) against gefitinib (IC50 = 38.9 nM). Molecular docking suggests that 4a–h could bind to the ATP region of EGFR like erlotinib.