Alzheimer's disease (AD) is a severe neurodegenerative disorder of different brain regions accompanied by distresses and affecting more than 25 million people in the world. This progressive brain deterioration affects the central nervous system and has negative impacts on a patient's daily activities such as memory impairment. The most important challenge concerning AD is the development of new drugs for long-term treatment or prevention, with lesser side effects and greater efficiency as cholinesterases inhibitors and the ability to remove amyloid-beta(Aβ) deposits and other related AD neuropathologies. Natural sources provide promising alternatives to synthetic cholinesterase inhibitors and many have been reported for alkaloids while neglecting other classes with potential cholinesterase inhibition. This review summarizes information about the therapeutic potential of small natural molecules from medicinal herbs, belonging to terpenoids, coumarins, and phenolic compounds, and others, which have gained special attention due to their specific modes of action and their advantages of low toxicity and high efficiency in the treatment of AD. Some show superior drug-like features in comparison to synthetic cholinesterase inhibitors. We expect that the listed phytoconstituents in this review will serve as promising tools and chemical scaffolds for the discovery of new potent therapeutic leads for the amelioration and treatment of Alzheimer's disease.

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Rationale Imperatorin, a naturally occurring furanocoumarin, inactivates gamma-aminobutyric acid transaminase and inhibits acetylcholinesterase activity. Objectives The purpose of our experiment was to examine the influence of imperatorin on cognitive impairment and oxidative stress in the brain induced by scopolamine in male Swiss mice. Methods In the present studies, we used scopolamine-invoke memory deficit measured in passive avoidance (PA) paradigm as an animal model of Alzheimer disease (AD). Results Our finding revealed that imperatorin administered acutely at the doses of 5 and 10 mg/kg prior to the injection of scopolamine (1 mg/kg) improved memory acquisition and consolidation impaired by scopolamine. Furthermore, repeatable (7 days, twice daily) administration of the highest dose of imperatorin (10 mg/kg) significantly attenuated the effects of scopolamine on memory acquisition, whereas the doses of 5 and 10 mg/kg of this furanocoumarin were effective when memory consolidation was measured. Imperatorin, administered with scopolamine, increased antioxidant enzymes activity and decreased concentration of malondiamide, an indicator of lipid peroxidation level. Conclusions These results demonstrate that imperatorin may offer protection against scopolamine-induced memory impairments and possesses antioxidant properties, thus after further preclinical and clinical studies this compound may provide an interesting approach in pharmacotherapy, as well as prophylactics of AD.

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The aim of the present study was to assess the effect of quercetin and imperatorin administered separately and in combination on apoptosis and autophagy induction in human cervical carcinoma HeLa cells and laryngeal carcinoma Hep-2 cells cultured in vitro. Conducted MTT measurements proved that quercetin and imperatorin displayed a strong antiproliferative activity manifested in markedly reduction of HeLa and Hep-2 cells viability as a result of treatment with 50 μM of each compound. Further cell staining assays revealed that concentration mentioned above generated the highest percentage of apoptotic cells especially in the case of application of both drugs for 48 h. Simultaneous quercetin and imperatorin administration induced apoptosis remarkably stronger than treatment with single drugs. Experiments at the molecular level confirmed these results accompanied with the decreased Hsp27 and Hsp72 expression and, in addition, with increased caspases activity. Autophagy was not observed and no significant changes in the expression of beclin-1 were noticed. Additionally, experiments were performed on the above-mentioned cell lines with blocked Hsp27 and Hsp72 expression. In these cells, no significant changes in the sensitivity to apoptosis induction upon quercetin and imperatorin treatment were observed. The present study has provided evidence supporting the potential of the combination of quercetin and imperatorin drugs as a novel tool to be used in anticancer therapy. Our results have also demonstrated that blocking of the Hsp27 and Hsp72 gene expression is not enough to sensitize cancer cells to programmed cell death induction in HeLa and Hep-2 cells.

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The purpose of the reported experiments was to examine the effects of imperatorin [9-[(3-methylbut-2-en-1-yl)oxy]-7H-furo[3,2-g]chromen-7-one] on anxiety and memory-related responses induced by nicotine in mice and their relation to the level of nicotine-induced oxidative stress in brain as well as in the hippocampus and the prefrontal cortex. Male Swiss mice were tested for anxiety in the elevated plus maze test (EPM), and for cognition using passive avoidance (PA) procedures. Imperatorin, purified by high-speed counter-current chromatography from methanol extract of fruits of Angelica officinalis, acutely administered at the doses of 10 and 20mg/kg impaired the anxiogenic effect of nicotine (0.1mg/kg, s.c.). Furthermore, acute injections of subthreshold dose of imperatorin (1mg/kg, i.p.) improved processes of memory acquisition when co-administered with nicotine used at non-active dose of 0.05 mg/kg, s.c. Additionally, repeated administration of imperatorin (1mg/kg, i.p., twice daily, for 6 days) improved different stages of memory processes (both acquisition and consolidation) when injected in combination with non-active dose of nicotine (0.05 mg/kg, s.c.) in the PA task. Oxidative stress was assessed by determination of antioxidant enzymes (glutathione peroxidases (GPx), superoxide dismutase (SOD), glutathione reductase (GR)) activities as well as of malondialdehyde (MDA) concentration in the whole brain, the hippocampus and the prefrontal cortex after repeated administration of imperatorin (1mg/kg, 6 days) and single nicotine injection (0.05 mg/kgs.c.) on the seventh day. The results of our research suggest strong behavioural interaction between imperatorin and nicotine at the level of anxiety- and cognitive-like processes. Furthermore, imperatorin inhibited nicotine-induced changes in examined indicators of oxidative stress, especially in the hippocampus and the cortex.

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Natural polyphenols are valuable compounds possessing scavenging properties towards radical oxygen species, and complexing properties towards proteins. These abilities make polyphenols interesting for the treatment of various diseases like inflammation or cancer, but also for anti-ageing purposes in cosmetic formulations, or for nutraceutical applications. Unfortunately, these properties are also responsible for a lack in long-term stability, making these natural compounds very sensitive to light and heat. Moreover, polyphenols often present a poor biodisponibility mainly due to low water solubility. Lastly, many of these molecules possess a very astringent and bitter taste, which limits their use in food or in oral medications. To circumvent these drawbacks, delivery systems have been developed, and among them, encapsulation would appear to be a promising approach. Many encapsulation methods are described in the literature, among which some have been successfully applied to plant polyphenols. In this review, after a general presentation of the large chemical family of plant polyphenols and of their main chemical and biological properties, encapsulation processes applied to polyphenols are classified into physical, physico-chemical, chemical methods, and other connected stabilization methods. After a brief description of each encapsulation process, their applications to polyphenol encapsulation for pharmaceutical, food or cosmetological purposes are presented.

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