Therapeutics to Treat Psychiatric and Neurological Disorders: A Promising Perspective from Algerian Traditional Medicine.

Ancient people sought out drugs in nature to prevent, cure, and treat their diseases, including mental illnesses. Plants were their primary source for meeting their healthcare needs. In Algeria, folk medicine remains a fundamental part of the local intangible knowledge. This study aims to conduct a comprehensive ethnomedicinal investigation and documentation of medicinal plants and the different plant formulations traditionally used in Algeria for the treatment of pain, psychiatric, and neurological disorders. It also intends to improve the current knowledge of Algerian folk medicine. Several scientific databases were used to accomplish this work. Based on this investigation, we identified 82 plant species belonging to 69 genera and spanning 38 distinct botanical families used as remedies to treat various psychological and neurological conditions. Their traditional uses and methods of preparation, along with their phytochemical composition, main bioactive constituents, and toxicity were noted. Therefore, this review provides a new resource of information on Algerian medicinal plants used in the treatment and management of neurological and psychological diseases, which can be useful not only for the documentation and conservation of traditional knowledge, but also for conducting future phytochemical and pharmacological studies.

Proposed Mechanism for the Antitrypanosomal Activity of Quercetin and Myricetin Isolated from Hypericum afrum Lam.: Phytochemistry, In Vitro Testing and Modeling Studies.

The in vitro activity of L. donovani (promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells) and T. brucei, from the fractions obtained from the hydroalcoholic extract of the aerial part of Hypericum afrum and the isolated compounds, has been evaluated. The chloroform, ethyl acetate and n-butanol extracts showed significant antitrypanosomal activity towards T. brucei, with IC50 values of 12.35, 13.53 and 12.93 µg/mL and with IC90 values of 14.94, 19.31 and 18.67 µg/mL, respectively. The phytochemical investigation of the fractions led to the isolation and identification of quercetin (1), myricitrin (2), biapigenin (3), myricetin (4), hyperoside (5), myricetin-3-O-ß-d-galactopyranoside (6) and myricetin-3'-O-ß-d-glucopyranoside (7). Myricetin-3'-O-ß-d-glucopyranoside (7) has been isolated for the first time from this genus. The chemical structures were elucidated by using comprehensive one- and two-dimensional nuclear magnetic resonance (1D and 2D NMR) spectroscopic data, as well as high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). These compounds have also been evaluated for their antiprotozoal activity. Quercetin (1) and myricetin (4) showed noteworthy activity against T. brucei, with IC50 and IC90 values of 7.52 and 5.71 µM, and 9.76 and 7.97 µM, respectively. The T. brucei hexokinase (TbHK1) enzyme was further explored as a potential target of quercetin and myricetin, using molecular modeling studies. This proposed mechanism assists in the exploration of new candidates for novel antitrypanosomal drugs.

Total Phenolic and Flavonoid Content and Biological Activities of Extracts and Isolated Compounds of Cytisus villosus Pourr.

The aim of this study was to evaluate the total phenolic and flavonoid content, and the in vitro antioxidant, anti-inflammatory, antibacterial, antifungal, antimalarial, cytotoxicity, and antiprotozoal activities of the Algerian plant Cytisus villosus Pourr. (Syn. Cytisus triflorus L'Hérit.). Additionally, the radioligand displacement affinity on opioid and cannabinoid receptors was assessed for the extracts and isolated pure compounds. The hydro alcoholic extract of the aerial part of C. villosus was partitioned with chloroform (CHCl3), ethyl acetate (EtOAc), and n-butanol (n-BuOH). The phenolic content of the C. villosus extracts was evaluated using a modified Folin-Ciocalteau method. The total flavonoid content was measured spectrometrically using the aluminum chloride colorimetric assay. The known flavonoids genistein (1), chrysin (2), chrysin-7-O-ß-d-glucopyranoside (3), and 2″-O-α-l-rhamnosylorientin (4) were isolated. The antioxidant activities of the extracts and isolated compounds were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DDPH) and cellular antioxidant activity (CAA) assays. The plant extracts showed moderate antioxidant activity. EtOAc and n-BuOH extracts showed moderate anti-inflammatory activity through the inhibition of induced nitric oxide synthase (iNOS) with IC50 values of 48 and 90 µg/mL, respectively. The isolated pure compounds 1 and 3 showed good inhibition of Inducible nitric oxide synthase (iNOS) with IC50 values of 9 and 20 µg/mL, respectively. Compounds 1 and 2 exhibited lower inhibition of Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB) with IC50 values of 28 and 38 µg/mL, respectively. Furthermore, the extracts and isolated pure compounds have been shown to exhibit low affinity for cannabinoid and opioid receptors. Finally, n-BuOH extract was a potent inhibitor of Trypanosoma brucei with IC50 value of 7.99 µg/mL and IC90 value of 12.61 µg/mL. The extracts and isolated compounds showed no antimicrobial, antimalarial nor antileishmanial activities. No cytotoxic effect was observed on cancer cell lines. The results highlight this species as a promising source of anti-inflammatory and antitrypanosomal agents.

Secondary metabolites from the aerial parts of Cytisus villosus Pourr.

Phytochemical investigation of the aerial parts of Cytisus villosus Pourr. resulted in the isolation and characterization of a new isoflavan, (3S, 4S)-2',4'-dihydroxy-3'-methoxy-6,7-methylenedioxyisoflavan- 4-ol (1), and a new monoterpene, (4R,6S)-4-hydroxy-2,2,6-trimethyl-9-oxabicyclo [4.2.1] non-1(8)-en-7-one (2), together with four known flavonoids: geinstein (3), chrysin (4), chrysin -7-O-ß-D-glucopyranoside (5) and 2″-O-α-L-rhamnosylorientin (6). The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D, 2D NMR (1H, 13C, COSY, TOCSY, HMBC and HSQC) and HRESIMS. The absolute configurations of 1 and 2 were established by the comparison of experimental and calculated electronic circular dichroism (ECD) spectra.

Inhibition of human monoamine oxidase A and B by flavonoids isolated from two Algerian medicinal plants.

BACKGROUND: Monoamine oxidases (MAOs) are outer mitochondrial membrane flavoenzymes. They catalyze the oxidative deamination of a variety of neurotransmitters. MAO-A and MAO-B may be considered as targets for inhibitors to treat neurodegenerative diseases and depression and for managing symptoms associated with Parkinson's and Alzheimer's diseases. PURPOSE: The objective was to evaluate the inhibitory effect of Hypericum afrum and Cytisus villosus against MAO-A and B and to isolate the compounds responsible for the MAO-inhibitory activity. METHODS: The inhibitory effect of extracts and purified constituents of H. afrum and C. villosus were investigated in vitro using recombinant human MAO-A and B, and through bioassay-guided fractionation of ethyl acetate fractions of areal parts of the two plants collected in northeastern Algeria. In addition, computational protein-ligand docking and molecular dynamics simulations were carried out to explain the MAO binding at the molecular level. RESULTS: The ethyl acetate (EtOAc) fractions of H. afrum and C. villosus showed the highest MAO inhibition activity against MAO A and B with IC50 values of 3.37 µg/ml and 13.50 µg/ml as well as 5.62 and 1.87 µg/ml, respectively. Bioassay-guided fractionation of the EtOAc fractions resulted in the purification and identification of the known flavonoids quercetin, myricetin, genistein and chrysin as the principal MAO-inhibitory constituents. Their structures were established by extensive 1 and 2D NMR studies and mass spectrometry. Quercetin, myricetin and chrysin showed potent inhibitory activity towards MAO-A with IC50 values of 1.52, 9.93 and 0.25 µM, respectively, while genistein more efficiently inhibited MAO-B (IC50 value: 0.65 µM). The kinetics of the inhibition and the study of dialysis dissociation of the complex of quercetin and myricetin and the isoenzyme MAO-A showed competitive and mixed inhibition, respectively. Both compounds showed reversible binding. Molecular docking experiments and molecular dynamics simulations allowed to estimate the binding poses and to identify the most important residues involved in the selective recognition of molecules in the MAOs enzymatic clefts. CONCLUSION: Quercetin and myricetin isolated from H. afrum together with genistein and chrysin isolated from C. villosus have been identified as potent MAO-A and -B inhibitors. H. afrum and C. villosus have properties indicative of potential neuroprotective ability and may be new candidates for selective MAO-A and B inhibitors.