Identification of anti-HIV biomarkers of Helichrysum species by NMR-based metabolomic analysis

Several species of the Helichrysum genus have been used ethnobotanically to treat conditions that we today know have been caused by viral infections. Since HIV is a modern disease with no ethnobotanical history, we commenced with a study on the antiHIV activity of several Helichrysum species. Drug discovery of small molecules from natural resources that is based on the integration of chemical and biological activity by means of metabolomical analyses, enables faster and a more cost-effective path to identify active compounds without the need for a long process of bioassay-guided fractionation. This study used metabolomics to identify anti-HIV compounds as biomarkers from 57 Helichrysum species in a combined study of the chemical and biological data of two previous studies. In the OPLS-DA and hierarchical cluster analyses, anti-HIV activity data was included as a secondary observation, which assisted in the correlation of the phytochemical composition and biological activity of the samples. Clear grouping revealed similarity in chemical composition and bioactivity of the samples. Based on the biological activity of polar extracts, there was a distinct phytochemical difference between active and non-active groups of extracts. This NMR-based metabolomic investigation showed that the chlorogenic acids, compounds with cinnamoyl functional groups, and quinic acid were the most prominent compounds in the Helichrysum species with anti-HIV activity. This study further revealed that the chlorogenic acid type compounds and quinic acid are biomarkers for anti-HIV activity.The National Research Foundation of South Africa.https://www.frontiersin.org/journals/pharmacologydm2022Plant Production and Soil Scienc

Santalum genus : phytochemical constituents, biological activities and health promoting-effects

Santalum genus belongs to the family of Santalaceae, widespread in India, Australia, Hawaii, Sri Lanka, and Indonesia, and valued as traditional medicine, rituals and modern bioactivities. Sandalwood is reported to possess a plethora of bioactive compounds such as essential oil and its components (α-santalol and β-santalol), phenolic compounds and fatty acids. These bioactives play important role in contributing towards biological activities and health-promoting effects in humans. Pre-clinical and clinical studies have shown the role of sandalwood extract as antioxidant, anti-inflammatory, antibacterial, antifungal, antiviral, neuroleptic, antihyperglycemic, antihyperlipidemic, and anticancer activities. Safety studies on sandalwood essential oil (EO) and its extracts have proven them as a safe ingredient to be utilized in health promotion. Phytoconstituents, bioactivities and traditional uses established sandalwood as one of the innovative materials for application in the pharma, food, and biomedical industry.https://www.degruyter.com/view/j/znaam2023Plant Production and Soil Scienc

A review on Tradescantia : phytochemical constituents, biological activities and health-promoting effects

Tradescantia is a genus of herbaceous and perennial plants belonging to the Commelinaceae family and organized into three infrageneric classifications and 12 sections. More than 80 species within the genus have been used for centuries for medicinal purposes. Phytochemical compounds (from various species of the genus) such as coumarins, alkaloids, saponins, flavonoids, phenolics, tannins, steroids and terpenoids have recently been characterized and described with antioxidant, cytotoxic, anti-inflammatory, anticancer or antimicrobial properties. The objective of this review is to describe the different aspects of the genus Tradescantia, including its botanical characteristics, traditional uses, phytochemical composition, biological activities, and safety aspects.https://www.imrpress.com/journal/FBLdm2022Plant Production and Soil Scienc

Metabolomic analysis on anti-HIV activity of selected Helichrysum species

Since the beginning of human civilization, medicinal plants have been used to treat a variety of infectious and non-infectious diseases. The therapeutic properties of phytochemicals have been recognized since ancient human history. The genus Helichrysum Mill. with its attractive flowers consist of an estimated 500‒600 species in the Asteraceae family. In South Africa and Namibia there are about 244‒250 species with tremendous morphological diversity. Several Helichrysum species are widely used by the indigenous population to treat various disorders such as wounds, infections, respiratory conditions, headaches, coughs, colds and fevers. Several of the Helichrysum species exhibit antiviral activity with the most relevant to this study being the discovery of anti-human immunodeficiency virus (anti-HIV) and anti-reverse transcriptase (anti-RT) activity of some species. Drug discovery and development, from the early stages of a promising compound to the final medication, is an intensive, expensive and incremental process. The ultimate goal is to identify a molecule with the desired effect in the human body and to establish its quality, safety and efficacy for treating patients. The ability to combine high-throughput analytical techniques like metabolomic and other experimental approaches with drug discovery will speed up the development of safer, more effective and better-targeted therapeutic agents. The rapidly emerging field of metabolomics and molecular docking analysis provides valuable information on drug activity, toxicity, customized drug treatments and can predict therapeutic outcomes. Extraction of the aerial parts of 32 Helichrysum species was done using polar [methanol (MeOH) 50%: distilled water (dH2O) 50%] and non-polar [hexane (Hex), dichloromethane (DCM) and acetone (Ace)] solvent systems. Anti-human immunodeficiency virus bioassays on the live HI virus revealed that polar extracts of H. mimetes and H. chrysargyrum at 2.5 μg/mL and 25 μg/mL, polar and non-polar extracts of H. infuscum at 25 μg/mL and polar and non-polar extracts of H. zeyheri, H. setosum, H. platypterum and H. kraussii at 2.5 and 25 μg/mL, had higher than 90% inhibitory activity. The polar extract of H. mimetes also exhibited reverse transcriptase (RT) inhibition as a possible indication of the mechanism of action. Proton nuclear magnetic resonance (1H NMR) spectra of the polar extracts exhibited the presence of aromatic compounds and carbohydrate moieties. Principal component analysis (PCA) of the polar extracts showed clustering related to the activity of the extracts with good predictability scores (Q2 > 0.5). However, orthogonal projections to latent structures discriminant analysis (OPLS-DA) predictability of the model was low based on the Q2 at approximately 0.25. Quinic acid (QA), isolated from H. mimetes showed promising anti-RT activity [50% inhibition concentration (IC50) = 53.82 μg/mL] which was comparable to the positive drug control, doxorubicin (IC50 = 40.31 μg/mL). The molecular docking study revealed the probable binding site and conformation of QA within cavity 4, with a docking score of -8.03. The docking score of doxorubicin within cavity 4 was -7.87. With this study, it was shown that metabolomic analysis as a tool to predict anti-HIV activity in Helichrysum species can be valuable to shorten the process. Moreover, the study of molecular docking revealed the mechanism action of quinic acid and doxorubicin against RT.Thesis (PhD)--University of Pretoria, 2019.Plant Production and Soil SciencePhDUnrestricte

Antiviral, antibacterial and cytotoxic activities of South African plants containing cardiac glycosides

South Africa has one of the richest and diverse floras in the world with over 30000 species of higher plants. There are approximately 3000 species of medicinal plants in South Africa. The discovery of active compounds in medicinal plants plays a strategic role in the phytochemical investigation of crude plant extracts. Secondary metabolites of medicinal plants are a major source of drugs for the treatment of various health disorders. Cardiac glycosides are one of the subgroups of steroids modified from terpenoids. The existence of cardiac glycosides in some plant species often indicates toxicity. Among the contagious elements, diseases caused by viruses are one of the major causes of death, disability, and social and economic disruption for millions of people. Viruses also cause many important plant diseases and are responsible for huge losses in crop production and quality in all parts of the world. According to literature, plants containing cardiac glycosides demonstrate potential for the discovery of more effective new drugs in the treatment of infection especially viral contagions. The main objectives of this study were to evaluate the antiviral (HSV-2 and PVYN), antibacterial and cytotoxic activities of South African plants containing cardiac glycosides. Furthermore, isolation and identification of compounds with an emphasis on cardiac glycosides was carried out. Eight plants known to contain cardiac glycoside compounds were selected. Leaves of Gomphocarpus fruticosus, Nerium oleander, Cotyledon orbiculata, the fruits and leaves of Strophanthus speciosus, the bulbs of Bowiea volubilis and Merwilla plumbea were selected to examine their antimicrobial activities, toxicity, antiviral and to isolate potential pure compounds. The ethanol extracts of all selected plants were screened for antibacterial activity against two Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and two Gram-negative (Escherichia coli and Klebsiella pneumonia) pathogens. Plant extracts showed promising antibacterial action against Gram-positive bacteria. The most active extract against both Gram-positive bacteria was C. orbiculata with the MIC value of 1.25 mg/ml. Cell toxicity was monitored by determining the effect of the ethanolic crude extracts on human embryonic kidney cell line (HEK 293) using the XTT method. All extracts exhibited high toxic effects with IC50 < 100 μg/ml on the tested cell line. The XTT assay was used to determine of the antiviral activity of crude ethanolic extracts on the kidney epithelial cells of African Green Monkey (Vero). The results revealed that the crude ethanolic extracts of all iv selected plants exhibited a cytotoxic effect on Vero cells at concentrations lower than their EC50. Consequently, the determination of antiviral activity of the selected plant extracts was not successful. Based on the chromatographic and bioassay results from the six plants selected for this study, the fruit extract of S. speciosus, belonging to the Apocynaceae family, was chosen for the isolation of compounds, particularly cardiac glycosides. All plant extracts were tested for antibacterial activity against E. coli (Gram-negative) and E. faecalis (Gram-positive) by using bioautography. The general TLC test showed more variety of compounds in the fruit extract of S. speciosus. The results of the bioassay showed promising activity of the fruit extract of S. speciosus and the bulb extract of B. volubilis against Gram-positive bacteria. The chromatographic investigation of the S. speciosus fruit extract led to the isolation of three pure compounds including a cardiac glycoside. The three compounds were identified based on NMR (1D and 2D) and HRMS. The isolated compounds were identified as: a triterpene (ursolic acid methyl ester), a sugar: myo-inositol methyl ester and an unidentified cardiac glycoside. According to literature, it is the first report of the isolation of ursolic acid methyl ester and myo-inositol-methyl ether from S. speciosus fruit extract. The isolated cardiac glycoside exhibited no inhibitory activity at 1.25 mg/ml (the highest concentration tested) against all four tested bacteria (S. aureus, E. faecalis, E. coli and K. pneumonia). The cytotoxicity and anti-HSV-2 screening of the isolated cardenolide demonstrated the highly toxic effect of this compound on the HEK 293 cell line with 4.62 μg/ml IC50 value and < 25 μg/ml IC50 of Vero cell line. No evidence could be found in the literature of the cytotoxic activity of cardiac glycoside compounds on the HEK 293 cell line. The ethanolic extracts of all plant extracts and isolated cardenolide were tested against the PVYN in vivo and in vitro. The results revealed that the high concentration (50 mg/ml) of M. plumbea, N. oleander, B. volubilis (fresh bulb), C. orbiculata and isolated cardenolide reduced the PVYN symptoms on tobacco plants in an in vivo experiment. In in vitro analysis, the high concentration (50 mg/ml) of S. speciosus (leaves & fruits), and especially M. plumbea (dry bulb) showed significant antiphytoviral activity. In vivo and in vitro results demonstrated that M. plumbea has potential antiphytoviral activity.Dissertation (MSc)--University of Pretoria, 2013.gm2014Plant ScienceUnrestricte

Plants containing cardiac glycosides showing antiphytoviral activity against Potato virus Y (PVYNTN) on tobacco plants

The tuber necrotic strain of Potato virus Y (PVYNTN) causes widespread disease and has severe negative effects on the growth and yields of plants, especially those of the Solanaceae family. The consequences of residual toxicity and non-biodegradation of synthetic chemicals and pollution of the environment has led to investigations into new non-toxic and biological treatments to control plant viral diseases. Ethanolic extracts of Bowiea volubilis (bulbs), Cotyledon orbiculata (leaves), Gomphocarpus fruticosus (leaves), Merwilla plumbea (dry and fresh bulbs), Nerium oleander (leaves), and the fruits and leaves of Strophanthus speciosus, were evaluated against PVYNTN in vivo and in vitro. At a concentration of 20 mg · ml−1, ethanolic extracts of Strophanthus speciosus (leaves) and fruits (50 mg · ml−1) significantly reduced the expression of PVYNTN symptoms on tobacco plants in vitro without affecting the normal growth and development of the plant. Similarly, at 50 mg · ml−1, N. oleander, C. orbiculata and B. volubilis (fresh bulbs) and S. speciousus leaves at 20 mg · ml−1 extracts showed significant differences in PVYNTN symptoms in the in vivo experiment. Strophanthus speciosus leaf and fruit extracts showed significant inhibition in the in vitro and in vivo assays and demonstrated that S. speciosus has potential to be used as an antiphytoviral treatment

Anti-HIV-1 activity of quinic acid isolated from Helichrysum mimetes using NMR-based metabolomics and computational analysis

Please read abstract in the article.The SWISS-SA collaboration (SA-JRP14), the University of Basel, the CSIR, the University of Pretoria and the National Research Foundation of South Africa (NRF).http://www.elsevier.com/locate/sajb2020-11-01hj2020Plant Production and Soil Scienc

Papaver Plants: Current Insights on Phytochemical and Nutritional Composition Along with Biotechnological Applications

The genus Papaver is highly esteemed in the pharmacy industry, in the culinary field, and as ornamental plants. These plants are also valued in traditional medicine. Among all Papaver species, Papaver somniferum L. (opium poppy) is the most important species in supplying phytochemicals for the formulation of drugs, mainly alkaloids like morphine, codeine, rhoeadine, thebaine, and papaverine. In addition, Papaver plants present other types of phytochemicals, which altogether are responsible for its biological activities. Therefore, this review covers the phytochemical composition of Papaver plants, including alkaloids, phenolic compounds, and essential oils. The traditional uses are reviewed along with their pharmacological activities. Moreover, safety aspects are reported to provide a deep overview of the pharmacology potential of this genus. An updated search was carried out in databases such as Google Scholar, ScienceDirect, and PubMed to retrieve the information. Overall, this genus is a rich source of alkaloids of different types and also contains interesting phenolic compounds, such as anthocyanins, flavonols, and the characteristic indole derivatives nudicaulins. Among other pharmacological properties, numerous preclinical studies have been published about the analgesic, anticancer, antimicrobial, antioxidant, and antidiabetic activities of Papaver plants. Although it highlights the significant impact of this genus for the treatment of a variety of diseases and conditions, as a future prospect, characterization works accompanying preclinical studies are required along with clinical and toxicology studies to establish a correlation between the scientific and traditional knowledge