Withania frutescens (L.) Pauquy, a valuable Mediterranean shrub containing bioactive withanolides.

The bushy plant Withania frutescens (L.) Pauquy is well distributed in the West-Mediterranean area, notably in the south of Spain, Algeria and Morocco where is it is used traditionally for the treatment of various human diseases, including diabetes. Unlike the two major species W. somnifera and W. coagulans extensively studied, the genomically close species W. frutescens has been much less investigated. Nevertheless, this shrub species displays a comparable phytochemical profile and marked antioxidant and anti-inflammatory properties, at the origin of reported pharmacological effects and its traditional uses. Here we have analyzed the diversity of biological effects reported with leaves and root extracts of W. frutescens. Hydroalcoholic extracts prepared from the aerial parts of the plant have revealed antihyperglycemic and cell-protective activities along with antimicrobial and anticorrosive effects. The extracts contained diverse polyphenolic compounds and a few alkaloids (calystegines) but most of the observed effects have been attributed to the presence of withanolides which are modified C28 ergostane-type steroids. Our analysis focused in part on specific withanolides found in W. frutescens, in particular an unusual 3-O-sulfated withanolide considered as a potential pro-drug of the major active compound withaferin A (WA) and a lead compound for the development of a potential drug candidate. The mechanism of action of this sulfated WA analogue is discussed. Altogether, our unprecedented extensive analysis of W. frutescens highlighted the pharmacological potential of this atypical medicinal plant. By analogy with the major cultivated Withania species, the market potential of little-known plant is underlined.

Ethnobotanical Uses and Pharmacological Activities of Moroccan Ephedra Species.

Ephedra species are among the most popular herbs used in traditional medicine for a long time. The ancient Chinese medical book "Treatise on Febrile Diseases" refers to the classic traditional Chinese medicine prescription Ge Gen decoction, which consists of seven herbs, including an Ephedra species. Ephedra species are utilized all over the world to treat symptoms of the common cold and coughs, and to combat major human diseases, such as asthma, cancers, diabetes, cardiovascular and digestive disorders, and microbial infections. This study aimed at identifying specific Ephedra species used traditionally in Morocco for therapeutic purposes. The plant parts, their preparation process, and the treated pathologies were identified and analyzed. The results revealed five ethnobotanically important species of Ephedra: Ephedra alata Decne, Ephedra altissima Desf., Ephedra distachya L., Ephedra fragilis Desf., and Ephedra nebrodensis Tineo. These species are used traditionally in Morocco for treating people with diabetes, cancer, rheumatism, cold and asthma, hypertension, influenza virus infection, and respiratory ailments. In addition, they are occasionally used as calefacient agents, to regulate weight, or for capillary care. Few studies have underlined the antibacterial and antioxidant activities of some of these Moroccan Ephedra species, but little information is available regarding the natural products at the origin of the bioactivities. Further phytochemical investigations and clinical data are encouraged to better support the use of these plants.

Tetraclinis articulata (Vahl) Mast.: Volatile constituents, antioxidant, antidiabetic and wound healing activities of its essential oil.

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome known to contribute to impaired wound healing. This condition can be further worsened by excessive melanin production, elastin degradation, and chronic infections at the wound site, potentially leading to melasma and diabetic dermopathy. The purpose of this study was to investigate the phytochemical profile and inhibitory effects of Tetraclinis articulata essential oil (TAEO) on target enzymes involved in diabetes pathogenesis and chronic wound remodeling, namely α-amylase, α-glucosidase, tyrosinase, and elastase, as well as its in vitro antibacterial activity. Gas chromatography and mass spectrometry (GC-MS) analysis of TAEO led to the identification of 46 volatile compounds, representing 96.61 % of TAEO. The major metabolites were bornyl acetate (29.48 %), α-pinene (8.96 %), germacrene D (7.70 %), and d-limonene (5.90 %). TAEO exhibited limited scavenging activity against DPPH free radicals, whereas the FRAP and ABTS assays indicated a relatively higher antioxidant activity. Remarkably, TAEO disclosed a promising in vitro antidiabetic activity against α-glucosidase with an IC50 value of 178 ± 1.6 µg/mL, which is comparable to the standard inhibitor acarbose (IC50 = 143 ± 1.1 µg/mL). In silico, molecular docking analysis against α-glucosidase identified 15 compounds that interacted with the enzyme's active site, whereas skin permeability and sensitization assessments indicated that 26 out of the 44 identified volatile compounds were predicted to be free from any skin sensitivity risk. On the other hand, moderate inhibitory activity was recorded against α-amylase, tyrosinase, and elastase. Notably, TAEO at 5 % significantly suppressed biofilm formation by P. aeruginosa, S. aureus, and E. faecalis, common skin pathogens associated with wound infections, and reduced their swarming motility. Our findings suggest that TAEO may hold the potential as a natural remedy for type 2 diabetes and its associated co-morbidities, especially chronic wounds.

Carvacrol and Thymol Content Affects the Antioxidant and Antibacterial Activity of Origanum compactum and Thymus zygis Essential Oils.

Essential oils are of great interest due to their potent pharmaceutical and biological activities. In this study, essential oils extracted from Origanum compactum and Thymus zygis originating from the Middle Atlas of Morocco were investigated. Their chemical compositions were analyzed using gas chromatography and mass spectrometry, while the assessment of the trapping power of the radical (DPPH: 1,1-diphenyl-2-picrylhydrazyl) and the reducing antioxidant potential of ferric ions (FRAP: Ferric Reducing Antioxidant Power) were performed in order to evaluate the antioxidant activity. Their antibacterial potency was tested against six bacterial strains through the disk diffusion method. The chromatography analyses of the extracted essential oils highlighted the presence of two main components, namely carvacrol at 75.70% in O. compactum and thymol at 40.67% in T. zygis. The antioxidant activity tests showed that both essential oils demonstrated a significant antioxidant activity comparable to the positive control (e.g., ascorbic acid). The antibacterial activity results showed a strong antimicrobial effect for both essential oils, compared to synthetic antibiotics. This study affirms the presence of bioactive components with interesting antioxidant and antibacterial activities in the essential oils extracted from Origanum compactum and Thymus zygis, which could find several applications in the food and pharmaceutical industries through the substitution of synthetic antioxidants and antibiotics.

Tanacetum species: Bridging empirical knowledge, phytochemistry, nutritional value, health benefits and clinical evidence.

Introduction: The Tanacetum genus consists of 160 accepted flowering species thriving throughout temperate regions, mainly in the Mediterranean Basin, Northern America, and southwestern and eastern Asia. Tanacetum species bear a long-standing record of use in the folk medicine of indigenous tribes and communities worldwide, along with multitudinous applications in traditional cuisines, cosmeceuticals, and agricultural fields. Methods: Up-to-date data related to traditional uses, phytochemistry, biological activities, toxicity and clinical trials of the genus Tanacetum were systematically reviewed from several online scientific engines, including PubMed, Web of Science, Scopus, SciFinder, Wiley Online, Science Direct, and Cochrane library. Results and discussion: Over the past three decades, 241 metabolites have been isolated from nearly twenty species, including phenolic acids, flavonoids, coumarins, fatty acids and alkanes, aldehydes, volatile compounds, and naphthoquinones. Some unique metabolites have also been identified, such as the ceramides tanacetamide (A-D) from T. artemisioides, pyrethrins from T. cinerariifolium, and sesquiterpene lactones from several species. However, these secondary metabolites are still poorly studied despite in vitro clues highlighting their colossal pharmacological properties, especially as hypotensive, neuroprotective, anticancer, and antimicrobial agents. Scientific studies have validated some traditional claims of the plant, such as antidiabetic, anticancer, anthelmintic, insecticide, antioxidant, and hepatoprotective activities, as well as against festering wounds, skin ulcers, urinary tract infections, and sexually transmitted diseases. Other ethnomedicinal uses for arthritis, gout, rheumatism, anemia, and as a litholytic, antivenom and diaphoretic have not yet been supported and would constitute the subject of further research.

Phytochemical Profile, Antioxidant, Antimicrobial, and Antidiabetic Activities of Ajuga iva (L.).

In Morocco, many applications in ethnomedicine on Ajuga iva (L.) have been recognized as able to treat various pathologies such as diabetes, stress, and microbial infections. The objective of this work is to carry out phytochemical, biological, and pharmacological investigations on the extracts of Ajuga iva leaves in order to confirm its therapeutic effects. The phytochemical screening carried out on the different extracts of Ajuga iva showed its richness in primary (lipids and proteins) and secondary metabolites (flavonoids, tannins, reducing compounds, oses, and holoside. The best contents of polyphenols, flavonoids, and tannins evaluated by spectrophotometric methods were found in the hydroethanolic extract (69.850 ± 2.783 mg EAG/g DE, 17.127 ± 0.474 mg EQ/g DE, 5.566 ± 0.000 mg EQC/g DE), respectively. Analysis of the chemical composition of the aqueous extract by LC/UV/MS revealed 32 polyphenolic compounds including ferulic acid (19.06%), quercetin (10.19%), coumaric acid (9.63%), and apigenin-7-(2-O-apiosylglucoside) (6.8%). The antioxidant activity of Ajuga iva extracts was evaluated by three methods (DPPH*, FRAP, CAT). The hydroethanolic extract recorded the strongest reducing power: DPPH* (IC50 = 59.92 ± 0.7 µg/mL), FRAP (EC50 = 196.85 ± 1.54 (µg/mL), and CAT (199.21 ± 0.37 mg EAG/gE). A strong correlation between phenolic compounds and antioxidant activities was confirmed by the determination of Pearson's coefficient. The antimicrobial activity of Ajuga iva studied by the microtiter method revealed potent antifungal and antibacterial qualities against Candida parapsilosis and Staphylococcus aureus BLACT. An in vivo oral glucose tolerance test (OGTT) using normal rats revealed that the antihyperglycemic action of the aqueous extract significantly reduced postprandial hyperglycaemia at (30 min, p < 0.01) and area under the curve (AUC glucose), p < 0.01. Similarly, the aqueous extract, tested on pancreatic α-amylase enzyme activity in vitro and in vivo significantly inhibited pancreatic α-amylase activity with IC50 = 1.52 ± 0.03 mg/mL. In conclusion, the extract from Ajuga iva could be a good source of bioactive molecules, which exhibit potent antioxidant and antimicrobial activity, as well as strong antidiabetic activity, for applications in the pharmaceutical industry.

Cubeb (Piper cubeba L.f.): A comprehensive review of its botany, phytochemistry, traditional uses, and pharmacological properties.

Piper cubeba L.f. (Piperaceae), known as cubeb, is a popular traditional herbal medicine used for the treatment of many diseases, especially digestive and respiratory disorders. The plant is rich in essential oil, found mainly in fruits, and this makes it economically important. Many traditional utilizations have been also validated from the plant and its isolated compounds owing to their antioxidant, antibacterial, anti-inflammatory and anticancer effects. These biological activities are attributed to the phytochemicals (phenolic compounds, lignans and alkaloids) and the essential oil of the plant. The present work aims to provide an up-to-date review on the traditional uses, phytochemistry and pharmacology of the plant and discusses the future perspectives to promote its valorization for nutritional- and health-promoting effects.

HPLC-PDA/ESI-MS Analysis of Phenolic Compounds and Bioactivities of the Ethanolic Extract from Flowers of Moroccan Anacyclus clavatus.

In this work, polyphenols were extracted from Anacylus clavatus flowers using a hydroethanolic solvent, and the obtained extract was studied for its total phenol and flavonoid contents and evaluated for its antioxidant and antibacterial capacities. The contents of total phenols and flavonoids were measured by employing gallic acid and quercetin as references, respectively, and the phenolic composition analysis was conducted using high-performance liquid chromatography combined with a photodiode array and electrospray ionization mass spectrometry (HPLC-PDA/ESI-MS). The antioxidant capacity of the extracts was tested using a potassium ferric reducing antioxidant power (PFRAP) assay, and the antibacterial activity assay was carried out against Gram-negative bacteria (Escherichia coli and Salmonella typhimirium) and Gram-positive bacteria (Staphyloccocus aureus and Listeria monocytogenes) using the broth microdilution assay. The phenolic and flavonoid contents of the extracts equaled 9.53 ± 0.48 mg GAE/g dm and 1.31 ± 0.06 mg QE/g dm, respectively. The chromatographic analysis of the phenolic profile detected 26 phenolic compounds belonging to phenolic acids, flavones and flavonols, and with the caffeoylquinic acid derivatives being the major phenolic compounds present in 12 isomers. Only one organic compound, viz. citric acid, was found. The extracts exhibited interesting antioxidant activity. Bacteriostatic activity towards Escherichia coli and bactericidal activity against Salmonella typhimirium, Staphyloccocus aureus and Listeria monocytogenes were determined. This study revealed that Anacyclus clavatus flower extracts contain phenolic compounds with interesting bioactivities.

Antifungal and Cytotoxic Activity of Diterpenes and Bisnorsesquiterpenoides from the Latex of Euphorbia resinifera Berg.

Euphorbia resinifera latex has been extensively utilized in traditional medicine due to its range of bioactivities. Chromatographic separations on silica gel of ethanol extract of E. resinifera latex led to the development of a new procedure for isolating resiniferatoxin (4) via dried E. resinifera latex and the identification of nine compounds. Among these, catechol (7), protocatechuic acid (8) and 3,4-dihydroxyphenylacetic acid (9), known phenolic compounds, were identified for the first time in E. resinifera latex. Herein we investigated the effects of major compounds of the latex of E. resinifera on the yeast Saccharomyces cerevisiae, on the growth of Aspergillus carbonarius, a widespread fungal contaminant, and on the breast cancer cell line MCF7 as well as on MCF10A normal breast cells. 12-deoxyphorbol-13-isobutyrate-20-acetate (2) had an inhibiting effect on the growth of A. carbonarius, and 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) showed a negative effect on yeast cell growth and also a cytotoxic effect on breast cancer cell line MCF7, but not on MCF10A cells. Deglucosyl euphorbioside A (5) and euphorbioside A (6) showed a discoloration effect that was possibly related to mitochondrial functionality in yeast, and also cytotoxicity only on the cancer cell line that was tested. Interestingly, treatment of MCF7 cells with 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) and deglucosyl euphorbioside A (5) not only led to a specific cytotoxic effect but also to the increase in the level of intracellular ROS.

Exploring the Use of Iris Species: Antioxidant Properties, Phytochemistry, Medicinal and Industrial Applications.

The genus Iris from the Iridaceae family consists of more than 262 recognized species. It is an ornamental and medicinal plant widely distributed in the Northern Hemisphere. Iris species convey a long history as valuable traditional drugs with a wide variety of applications in various cultures, having been recorded since medieval times. Currently, Iris spp. still find application in numerous fields, including cosmetics, pharmaceutics and the food industry. Moreover, many of their empirical uses have been validated by in vitro and in vivo studies, showing that Iris spp. exhibit potent antioxidant, anticancer, anti-inflammatory, hepatoprotective, neuroprotective and anti-microbial properties. Phytochemicals investigations have revealed that the plant extracts are rich in phenolic compounds, especially flavonoids and phenolic acids. As such, they constitute a promising lead for seeking new drugs with high susceptibilities towards various health issues, particularly oxidative-stress-related diseases such as cancers, neurodegenerative diseases, cardiovascular diseases, diabetes, etc. Herein, we present a literature review of the genus Iris intending to determine the plant's chemical profile and establish a coherent overview of the biological applications of the plant extracts with reference to their traditional uses.

N-(1-Allyl-3-chloro-4-eth-oxy-1H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

In the title compound, C19H20ClN3O3S, the benzene ring is inclined to the indazole ring system by 51.23 (8)°. In the crystal, mol-ecules are linked by pairs of N-H⋯O hydrogen bonds, forming inversion dimers which stack in columns parallel to [011]. The atoms in the allyl group are disordered over two sets of sites with an occupancy ratio of 0.624 (8):0.376 (8).

N-(2-Allyl-4-eth-oxy-2H-indazol-5-yl)-4-methyl-benzene-sulfonamide.

The indazole ring system of the title compound, C19H21N3O3S, is almost planar (r.m.s. deviation = 0.0192 Å) and forms dihedral angles of 77.99 (15) and 83.9 (3)° with the benzene ring and allyl group, respectively. In the crystal, centrosymmetrically related mol-ecules are connected by pairs of N-H⋯O hydrogen bonds into dimers, which are further linked by C-H⋯O hydrogen bonds, forming columns parallel to the b axis.

Synthesis and antitumor activity of some substituted indazole derivatives.

Some new N-[6-indazolyl]arylsulfonamides and N-[alkoxy-6-indazolyl]arylsulfonamides were prepared by the reduction of 2-alkyl-6-nitroindazoles with SnCl2 in different alcohols, followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. The newly synthesized compounds were evaluated for their antiproliferative and apoptotic activities against two human tumor cell lines: A2780 (ovarian carcinoma) and A549 (lung adenocarcinoma). Preliminary in vitro pharmacological studies revealed that N-(2-allyl-2H-indazol-6-yl)-4-methoxybenzenesulfonamide 4 and N-[7-ethoxy-2-(4-methyl-benzyl)-2H-indazol-6-yl]-4-methyl-benzenesulfonamide 9 exhibited significant antiproliferative activity against the A2780 and A549 cell lines with IC50 values in the range from 4.21 to 18.6 µM, and also that they trigger apoptosis in a dose-dependent manner. Furthermore, both active compounds were able to cause an arrest of cells in the G2/M phase of the cell cycle, typical but not exclusive of tubulin interacting agents, although only infrequent interactions with the microtubule network were observed by immunofluorescence microscopy, while docking analysis showed a possible different behavior between the two active compounds.

N-(3-Chloro-1H-indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.

In the title compound, C14H12ClN3O3S, the fused five- and six-membered rings are folded slightly along the common edge, forming a dihedral angle of 3.2 (1)°. The mean plane through the indazole system makes a dihedral angle of 30.75 (7)° with the distant benzene ring. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules, forming a two-dimensional network parallel to (001).

N-(1H-Indazol-5-yl)-4-meth-oxy-benzene-sulfonamide.

In the title compound, C14H13N3O3S, the fused ring system is almost planar, the largest deviation from the mean plane being 0.023 (2) Å, and makes a dihedral angle of 47.92 (10)° with the benzene ring of the benzene-sulfonamide moiety. In the crystal, mol-ecules are connected through N-H⋯O hydrogen bonds and weak C-H⋯O contacts, forming a two-dimensional network which is parallel to (010).