Secondary Metabolites Isolated from Artemisia afra and Artemisia annua and Their Anti-Malarial, Anti-Inflammatory and Immunomodulating Properties-Pharmacokinetics and Pharmacodynamics: A Review.

There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components.

Cytotoxic, Antioxidant, and Antidiabetic Activities versus UPLC-ESI-QTOF-MS Chemical-Profile Analysis of Ipomoea aquatica Fractions.

Ipomoea aquatica is a common green leafy vegetable that has numerous uses in traditional medicine. This study focused on the determination of the cytotoxic, antiradical, and antidiabetic properties of various fractions of the I. aquatica methanolic extract, as well as on the tentative identification of some bioactive compounds in the same fractions. The cytotoxicity was determined by the brine shrimp lethal test. The antioxidant activities of the I. aquatica fractions were investigated through 3 assays. The antidiabetic activity (in vitro) was measured by α-glucosidase and α-amylase inhibition assays. Phytochemical qualitative analyses demonstrated the presence of alkaloids, terpenoids, phenols, and flavonoids in the ethyl acetate-methanol and methanol fractions. The total phenolic and total flavonoid contents were found to be highest in the ethyl acetate-MeOH fractions. The evaluation of the cytotoxicity showed that the hexane-dichloromethane fraction is the most toxic, while the others are moderately toxic. The antioxidant activity assays showed that the ethyl acetate-MeOH fractions are the most potent, while the α-glucosidase and α-amylase assays revealed that the hexane-dichloromethane fraction might contain a potent antidiabetic agent. Some bioactive substances in the MeOH fractions, such as salicylic acid glucoside, 1-O-sinapoyl-ß-D-glucose derivative, and dihydroferulic acid derivative, were tentatively identified. To the best of our knowledge, this is the first report to detect and identify these compounds in this species. Based on the results of this study, it may be concluded that I. aquatica is a potent antioxidant agent and could be a good candidate as a natural antioxidant in food and therapeutics.

Four Pistacia atlantica subspecies (atlantica, cabulica, kurdica and mutica): A review of their botany, ethnobotany, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia atlantica (wild pistachio) belongs to the Anacardiaceae family, and growing from the Mediterranean basin to central Asia, especially in Iran, Turkey, Iraq and Saudi Arabia where it is extensively used in traditional medicine for a wide range of ailments related to relieving upper abdominal discomfort and pain, dyspepsia and peptic ulcer. OBJECTIVE: Despite the diverse biological activities of P. atlantica, there is no current review summarizing medicinal properties of its subspecies, including cabulica, kurdica and mutica. Thus, this paper aims to explore the current understanding of the chemical, pharmacological, and biochemical properties of the extracts and the main active constituents found in each subspecies of this plant. METHODS: Peer-reviewed articles, using "Pistacia atlantica" as search term (″all fields″), were retrieved from Scifinder, Pubmed, Science direct, Wiley, Springer, ACS, Scielo, Web of Science and other web search instruments (Google Scholar, Yahoo search). Papers published until July 2020 are considered. In addition, various books were consulted that contained botanical and ethnopharmacological information. The information provided in this review is based on peer-reviewed papers in English and French. RESULTS: Phytochemical studies have shown the presence of numerous valuable compounds, including volatile compounds, flavonoids, phenolic compounds, fatty acids, tocopherols and phytosterols. P. atlantica contains also minerals and trace elements, like iron, lead, copper, potassium, sodium and calcium; fatty acids, like oleic, linoleic, and palmitic acid; fat-soluble vitamins, such as α, ß, γ and δ tocopherols; phytosterols, like betasitosterol, stigmasterol, campesterol and Δ5-avenasterol. Crude extracts and isolated compounds from P. atlantica show a wide range of pharmacological properties, such as antimicrobial, antifungal, anti-inflammatory, analgesic, antinociceptive, wound healing, anticancer, cytotoxic, anticholinesterase, antidiabetic, hepatoprotective, urease inhibition, antihypertension, nipple fissure healing, antileishmanial and antiplasmodial activities. However, there are no reports summarizing the P. atlantica bioactivity, its therapeutic value, and the roles played by each of the numerous phytoconstituents. CONCLUSION: Many traditional uses of P. atlantica and its subspecies have now been confirmed by pharmacologic research. Systematic phytochemical investigation of the P. atlantica subspecies and the pharmacological properties, especially the mechanisms of action and toxicology, to illustrate their ethnomedicinal use, to explore the therapeutic potential and support further health-care product development, will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of P. atlantica subspecies should be carried out in future for the safety approval of therapeutic applications.

Defining a standardized methodology for the determination of the antioxidant capacity: case study of Pistacia atlantica leaves.

Antioxidant activity can be measured by a variety of methods, that include hydrogen atom transfer (HAT) and single electron transfer (ET) methods. Most of these techniques are spectrophotometric, and thus incapable of quantifying or indicting individual antioxidant compounds. Nowadays, the integration of chromatographic and chemometric approaches allows a high-throughput identification and activity prediction of herbal products. The ethyl acetate fraction from the aqueous-acetone extract of Pistacia atlantica leaves is frequently used for the isolation of antioxidants. In this study it is investigated for its antioxidant properties in order to define a potential methodology for the determination of the antioxidant capacity of herbal extracts (which need to be confirmed by future studies). The seven free radical assays evaluated can be divided into two groups depending on the oxidizing reagent. Three methods use stable, non-biological radicals, i.e. the diphenyl-1-picrylhydrazyl (DPPH) assay, the azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and the N,N-dimethyl-p-phenylenediamine (DMPD) assay, which have no direct physiological importance. Four methods work with biological radical producers, including superoxide anion (O2˙-), hydroxyl (˙OH), nitric oxide (NO˙) and peroxyl (ROO˙) are produced metabolically in living organisms, and thus direct information on an extract's protective action is obtained. Furthermore, the reducing power method by potassium ferricyanide (RPC), and the iron (ferrous) ion chelating activity also have been investigated. The antioxidant activities of the samples were measured according to the different methods and modelled as a function of the HPLC fingerprints using the partial least squares (PLS) technique. The regression coefficients of the models were studied to indicate the peaks potentially responsible for the antioxidant activity. From the combined results of the different PLS models, we recommend using the DPPH, RPC and ROO˙ assays, to evaluate the overall antioxidant capacity; in the case study of P. atlantica leaves.

Antioxidant activity of Vitis vinifera, Punica granatum, Citrus aurantium and Opuntia ficus indica fruits cultivated in Algeria.

Four edible fruits from Vitis vinifera, Punica granatum, Citrus aurantium and Opuntia ficus indica from Algeria were analyzed in order to determine the total polyphenol, total flavonoid and flavonol contents using classical spectrophotometric methods. The antioxidant activity was established by three different single-electron-transfer-based assays (ABTS radical cation, FRAP, and DPPH assays) and one hydrogen-atom-transfer based assay (ORAC). Among the four fruits tested, the Vitis vinifera hydroalcoholic extract showed the highest antioxidant capacity with all methods. The results indicated that the antioxidant activity and the total phenolic content of the selected plants are significantly different (p < 0.001).

Polyphenolic contents, antioxidant activities and UPLC-ESI-MS analysis of Haplophyllum tuberculatum A. Juss leaves extracts.

The aim of this study is to determine the phytochemical profile, the total polyphenolic contents and the antioxidant activities of Haplophyllum tuberculatum leaves extracts. The most active extracts were analyzed by ultra-high performance liquid chromatography coupled to electrospray ionization mass spectrometry. Antioxidant activities were screened by the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) test and measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ß-carotene bleaching inhibition assays. Phytochemical screening of the extracts revealed the presence of various secondary metabolites. The ethyl acetate extract was the richest extract in phenolics and flavonoids with 262mg gallic acid equivalents/g and 99.1mg quercetin equivalent/g of dry weight, respectively. The same extract showed an important scavenging effect on DPPH, ABTS and ß-carotene/linoleic acid with IC50 of 0.020mg/mL, 0.029mg/mL and 0.022mg/mL, respectively. The correlations between the antioxidant capacities and the polyphenolic content were ranging between 0.889 and 0.256 and occasionally found to be significant. The UPLC-ESI-MS analysis showed the presence of polyphenolic and alkaloid compounds. Arabelline, majidine, dictamine and a qudsine derivative are found for the first time in H. tuberculatum. The results indicate that polyphenolic and alkaloid compounds may be major contributors to the antioxidant activity of these extracts.

Identification of some Bioactive Metabolites in a Fractionated Methanol Extract from Ipomoea aquatica (Aerial Parts) through TLC, HPLC, UPLC-ESI-QTOF-MS and LC-SPE-NMR Fingerprints Analyses.

INTRODUCTION: The plant species Ipomoea aquatica contains various bioactive constituents, e.g. phenols and flavonoids, which have several medical uses. All previous studies were executed in Asia; however, no reports are available from Africa, and the secondary metabolites of this plant species from Africa are still unknown. OBJECTIVE: The present study aims finding suitable conditions to identify the bioactive compounds from different fractions. METHODOLOGY: Chromatographic fingerprint profiles of different fractions were developed using high-performance liquid chromatography (HPLC) and then these conditions were transferred to thin-layer chromatography (TLC). Subsequently, the chemical structure of some bioactive compounds was elucidated using ultra-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry (UPLC-QTOF-MS) and liquid chromatography-solid phase extraction-nuclear magnetic resonance (LC-SPE-NMR) spectroscopy. RESULTS: The HPLC fingerprints, developed on two coupled Chromolith RP-18e columns, using a gradient mobile phase (methanol/water/trifluoroacetic acid, 5:95:0.05, v/v/v), showed more peaks than the TLC profile. The TLC fingerprint allows the identification of the types of chemical constituents, e.g. flavonoids. Two flavonoids (nicotiflorin and ramnazin-3-O-rutinoside) and two phenolic compounds (dihydroxybenzoic acid pentoside and di-pentoside) were tentatively identified by QTOF-MS, while NMR confirmed the structure of rutin and nicotiflorin. CONCLUSION: The HPLC and TLC results showed that HPLC fingerprints give more and better separated peaks, but TLC helped in determining the class of the active compounds in some fractions. Bioactive constituents were identified as well using MS and NMR analyses. Two flavonoids and two phenolic compounds were tentatively identified in this species for the first time, to the best of our knowledge. Copyright © 2017 John Wiley & Sons, Ltd.

Potentially antidiabetic and antihypertensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting.

The objective of this paper is to evaluate the variations in the ability of Pistacia atlantica leaves to inhibit enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and to hypertension (angiotensin converting enzyme-I (ACE-I)), depending on harvesting month, gender and growing region, as well as to identify the peaks in chromatographic fingerprints that potentially correspond to components with enzymatic inhibitory activities. In this study, LC fingerprints of P. atlantica leave extracts were developed. Peaks which were probably responsible for the anti-amylase, anti-glucosidase and anti-ACE-I activities were assigned. For the latter purpose, the relevant information was extracted, linking the chromatographic fingerprints with the activities using a linear multivariate calibration technique, i.e., Partial Least Squares (PLS) regression. Prior to the construction of the models, the fingerprints are aligned using a warping method, called Correlation Optimized Warping (COW). Besides COW, different other data pretreatment methods were applied and compared. Our findings revealed that the influence of the growing region and gender on the α-amylase, α-glucosidase and ACE-I inhibitory activities of P. atlantica leaves was less important than the harvest time. Thirteen common peaks were selected from the chromatograms and used as a dataset to model the biological activities. The peaks potentially responsible for the biological activity of the samples were indicated by studying the regression coefficients of the models. Seven peaks corresponding to possibly anti-amylase compounds were found, while 6 peaks were considered important for inhibiting the α-glucosidase activity. Furthermore, the regression coefficients of the hypertension model indicated eight peaks as being important for inhibiting the ACE-I activity. The contributions of individual phenolic compounds of P. atlantica leaves to the α-amylase, α-glucosidase and ACE-I inhibitory activities were also identified. This investigation showed that the extract of P. atlantica leaves provides a rational basis for the isolation and development of antidiabetic and antihypertensive agents.

Seasonal, gender and regional variations in total phenolic, flavonoid, and condensed tannins contents and in antioxidant properties from Pistacia atlantica ssp. leaves.

CONTEXT: The widespread use of Pistacia atlantica Desf. ssp. (Anacardiaceae) in traditional medicine can be partly attributed to the content of its secondary metabolites, in particular, the phenolic compounds. OBJECTIVE: The effects of harvest period, growing region and gender on the phenolic compounds, flavonoids and condensed tannins contents were studied, as well as on the antioxidant activities of P. atlantica leaves in order to provide a scientific basis for optimal collection. MATERIALS AND METHODS: Leaves were collected monthly from April to October 2010 in two Algerian sites. The powdered leaves were used for preparing the ethyl acetate extract. Contents of total phenolics (TPC), flavonoids (FC) and condensed tannins (CTC) were determined spectrophotometrically. Antioxidant activity was evaluated through radical scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (250 µM) and the reducing power capacity (RPC) determination by K3Fe(CN)6 (1%). RESULTS: The TPC was found to vary from 79 ± 13 to 259 ± 8 mg gallic acid equivalents/g of dry weight (DW) during the study period. The RSA and RPC varied between 262 ± 18 and 675 ± 21 mg Ascorbic Acid Equivalent (AAE)/g DW, and from 259 ± 16 to 983 ± 20 mg AAE/g DW, respectively. A seasonal pattern was observed consisting of a decrease in TPC content and RPC from spring to autumn. The FC, CTC and RSA did not show a seasonal pattern. DISCUSSION AND CONCLUSION: Our findings showed that secondary metabolite content and antioxidant activities of P. atlantica leaves were more influenced by harvest time and growing region than by gender.