Ethnopharmacological relevance Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. Aim of the study This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. Materials and methods Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3β). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. Results Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3β inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. Conclusions The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.

Tacripyrines (1-14) have been designed by combining an ACNE inhibitor (tacrine) with a calcium antagonist such as nimodipine and are targeted to develop a multitarget therapeutic strategy to confront AD. Tacripyrines are selective and potent ACNE inhibitors in the nanomolar range. The mixed type inhibition of hAChE activity of compound 11 (IC50 105 +/- 15 nM) is associated to a 30.7 +/- 8.6% inhibition of the proaggregating action of ACNE on the A beta and a moderate inhibition of A beta self-aggregation (34.9 +/- 5.4%). Molecular modeling indicates that binding of compound 11 to the ACNE PAS mainly involves the (R)-11 enantiomer, which also agrees with the noncompetitive inhibition mechanism exhibited by p-methoxytacripyrine 11. Tacripyrines are neuroprotective agents, show moderate Ca2+ channel blocking effect, and cross the blood-brain barrier, emerging as lead candidates for treating AD.. - MEC [AP20020576]; Fundacion Tedfilo Hernando [BF12003-02722, SAF2006-08764-C02-01, SAF-2006-08540, SAF2006-1249, CTQ2005-09365]; CAM [S/SAL-0275-2006]; ISCIII ; Red RENEVAS [RD06/0026/1002]; CSIC-GRICES [2007PT-13]. - J.M.C. thanks Dr. MSUPa/SUP. Luz de la Puente (Analytical Technologies Department, Lilly SA), and Dr. Ma. Angeles Martinez-Grau (Lilly SA) for the resolution of compound 11. J.M.C. and also R.L. thank MEC for a fellowship (AP20020576) and B.L. thanks CSIC for a I3P Training Contract. The present work has been supported by Fundacion Tedfilo Hernando, MEC grants BF12003-02722; SAF2006-08764-C02-01, SAF-2006-08540, SAF2006-1249, and CTQ2005-09365, CAM (S/SAL-0275-2006), ISCIII [Red RENEVAS (RD06/0026/1002)], CSIC-GRICES project (2007PT-13), and Fundacidn La Caixa (Barcelona, Spain).