Francesco Menichini

In vivo anti-inflammatory and in vitro antioxidant activities of Mediterranean dietary plants.

Five hydroalcoholic extracts of edible plants from Calabria region (Italy) used in local traditional medicine for the treatment of inflammatory diseases were evaluated for their in vivo topical anti-inflammatory activity (inhibition of croton oil-induced ear oedema in mice) and in vitro antioxidant and antiradical properties (inhibition of linoleic acid oxidation and bovine brain liposomes peroxidation, DPPH radical scavenging). All the extracts showed an anti-inflammatory effect: 300 microg/cm(2) provoked oedema reductions ranging from 21 to 27%. All the extracts exerted also radical scavenging and/or antioxidant properties, the most active plant being Mentha aquatica L. (Lamiaceae) which contained the highest amount of phenolics (337 mg/g) and of flavonoids (15.75 mg/g). Moreover, the content and the composition of sterols were assessed by GC-MS in the examined plants Borago officinalis L. (Boraginaceae) contained the highest number of sterols.

Biological and Pharmacological Activities of Iridoids: Recent Developments

Iridoids represent a large group of cyclopenta[c]pyran monoterpenoids that occur wide-spread in nature, mainly in dicotyledonous plant families like Apocynaceae, Scrophulariaceae, Diervillaceae, Lamiaceae, Loganiaceae and Rubiaceae. Recently, more extensive studies revealed that iridoids exhibit a wide range of bioactivity, such as neuroprotective, antinflammatory and immunomodulator, hepatoprotective and cardioprotective effects. Anticancer, antioxidant, antimicrobic, hypoglycaemic, hypolipidemic, choleretic, antispasmodic and purgative properties were also reported. The aim of the present review is to discuss the recent developments on biological and pharmacological activities of iridoids, supporting the new therapeutic possibilities for the use of these compounds.

Estrogenic and antiproliferative activities of isoliquiritigenin in MCF7 breast cancer cells

Licorice root contains chemically diverse compounds that exhibit estrogenic effects in vitro and in vivo. The chalcone isoliquiritigenin (ISL) is a component of licorice extract exhibiting either antitumorigenic activity or estrogen receptor (ER) alpha-dependent growth promoting effects on breast cancer cells. In order to contribute to a better understanding of this apparent paradox, we synthesized and ascertained the estrogenic properties of ISL using, as model systems, the hormone-sensitive MCF7 breast cancer cells and the steroid-independent HeLa cells. Transfection experiments reveal that ISL is able to transactivate the endogenous ER alpha in MCF7 cells and this is supported by the capability to induce down-regulation of ER alpha protein levels and up-regulation of pS2 mRNA. Moreover, by using chimeric proteins consisting of the hormone binding domains of ER alpha and ER beta fused to the Gal4 DNA binding domain, we have determined that ISL is an estrogenic agonist of both ER isoforms. As a biological counterpart, low and intermediate ISL concentrations that induce substantial transcriptional activity stimulate the proliferation of MCF7 cells. However, high levels of ISL become cytotoxic even in steroid-receptor negative HeLa cells. Thus, the activity of ISL and the balance between risk or chemopreventive factor for estrogen-dependent breast cancer may depend on dietary intake.

Natural Products and their Derivatives as Cholinesterase Inhibitors in the Treatment of Neurodegenerative Disorders: An Update

Alzheimers disease (AD) is the most common form of neurodegenerative disorders. If more effective therapies than the ones currently available are not developed that either prevent AD or other neurodegenerative or block progression of the diseases in its very early stages, the economic and societal cost of caring for AD patients will be devastating. Besides the neuropathologic hallmarks of the diseases, namely neurofibrillary tangles and AD neuritic plaques, the disease is characterized neurochemically by a consistent deficit in cholinergic neurotransmission, particularly affecting cholinergic neurons in basal forebrain. AD and other forms of dementia could be treated by the use of agents which restore the level of acetylcholine through inhibition of both two major forms of cholinesterase: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Moreover, the inhibition of AChE holds a key role not only to enhance cholinergic transmission in the brain but also to reduce the aggregation of beta-amyloid and the formation of the neurotoxic fibrils in AD. Following this view, in recent years, an increased interest has emerged directed to finding drugs able to inhibit both of these events. This review summarizes and highlights recent advances in current knowledge on natural products as cholinesterase inhibitors and how these compounds have also served as the starting points for semi-synthetic analogs with improved properties.

Antioxidant activity of methanolic extract of Hypericum triquetrifolium Turra aerial part

The antioxidant activity of the methanol extract of Hypericum triquetrifolium Turra (Hypericaceae) aerial part and of flavonoids isolated therein, I3,II8-biapigenin, quercetin-3-O-galactoside, kaempferol-3-O-glycoside, (-)-epicatechin and hypericin, was evaluated. The IC(50) resulted between 0.062 and 1 mg/ml.

In vitro inhibitory activities of plants used in Lebanon traditional medicine against angiotensin converting enzyme (ACE) and digestive enzymes related to diabetes

AIM OF THE STUDY In recent years the use of medicinal plants has been growing worldwide and this is particularly true in Lebanon. In the present investigation we report the inhibitory activity against digestive enzymes related to diabetes and angiotensin converting enzyme (ACE) of extracts of nine plant species collected in Lebanon, where they have a traditional use against diabetes. MATERIALS AND METHODS In order to evaluate if the extraction procedure could influence the activity we decided to perform different extractions with methanol, n-hexane and chloroform of Calamintha origanifolia, Satureja thymbra, Prangos asperula, Sideritis perfoliata, Asperula glomerata, Hyssopus officinalis, Erythraea centaurium, Marrubium radiatum and Salvia acetabulosa and test each of them. RESULTS AND CONCLUSIONS Marrubium radiatum and Salvia acetabulosa methanol extracts exerted the highest activity against alpha-amylase (IC(50) 61.1 and 91.2 microg/ml, respectively) and alpha-glucosidase (IC(50) 68.8 and 76.9 microg/ml, respectively). The same extracts exhibited a strong inhibitory activity against ACE with IC(50) of 72.7 and 52.7 microg/ml, respectively. The results support the traditional use of some the species examined.

Phytochemical Analysis and in vitro Antiviral Activities of the Essential Oils of Seven Lebanon Species

The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS‐CoV and HSV‐1 replication in vitro by visually scoring of the virus‐induced cytopathogenic effect post‐infection. L. nobilis oil exerted an interesting activity against SARS‐CoV with an IC50 value of 120 μg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of β‐ocimene, 1,8‐cineole, α‐pinene, and β‐pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which α‐pinene and β‐myrcene were the major constituents, revealed antiviral activity against HSV‐1 with an IC50 value of 200 μg/ml and a SI of 5.

Oldenlandia diffusa extracts exert antiproliferative and apoptotic effects on human breast cancer cells through ERα/Sp1-mediated p53 activation†‡

Breast cancer is the most frequent tumor and a major cause of death among women. Estrogens play a crucial role in breast tumor growth, which is the rationale for the use of hormonal antiestrogen therapies. Unfortunately, not all therapeutic modalities are efficacious and it is imperative to develop new effective antitumoral drugs. Oldenlandia diffusa (OD) is a well‐known medicinal plant used to prevent and treat many disorders, especially cancers. The aim of this study was to investigate the effects of OD extracts on breast cancer cell proliferation. We observed that OD extracts strongly inhibited anchorage‐dependent and ‐independent cell growth and induced apoptosis in estrogen receptor alpha (ERα)‐positive breast cancer cells, whereas proliferation and apoptotic responses of MCF‐10A normal breast epithelial cells were unaffected. Mechanistically, OD extracts enhance the tumor suppressor p53 expression as a result of an increased binding of ERα/Sp1 complex to the p53 promoter region. Finally, we isolated ursolic and oleanolic acids as the bioactive compounds able to upregulate p53 expression and inhibit breast cancer cell growth. These acids were greatly effective in reducing tamoxifen‐resistant growth of a derivative MCF‐7 breast cancer cell line resistant to the antiestrogen treatment. Our results evidence how OD, and its bioactive compounds, exert antiproliferative and apoptotic effects selectively in ERα‐positive breast cancer cells, highlighting the potential use of these herbal extracts as breast cancer preventive and/or therapeutic agents. J. Cell. Physiol. 227: 3363–3372, 2012.

Acetylcholinesterase and butyrylcholinesterase inhibition of ethanolic extract and monoterpenes from Pimpinella anisoides V Brig. (Apiaceae)

Ethanolic extract from the fruits of Pimpinella anisoides, an aromatic plant and a spice, exhibited activity against AChE and BChE, with IC(50) values of 227.5 and 362.1 microg/ml, respectively. The most abundant constituents of the extract were trans-anethole, (+)-limonene and (+)-sabinene. trans-Anethole exhibited the highest activity against AChE and BChE with IC(50) values of 134.7 and 209.6 microg/ml, respectively. The bicyclic monoterpene (+)-sabinene exhibited a promising activity against AChE (IC(50) of 176.5 microg/ml) and BChE (IC(50) of 218.6 microg/ml).

Salvia leriifolia Benth (Lamiaceae) extract demonstrates in vitro antioxidant properties and cholinesterase inhibitory activity

The object of the present study was to investigate the in vitro antioxidant properties and cholinesterase inhibitory activity of Salvia leriifolia Benth extracts and fractions. The functional role of herbs and spices and their constituents is a hot topic in food-related plant research. Salvia species have been used since ancient times in folk medicine for cognitive brain function and have been subjected to extensive research. Thus, we hypothesize that S leriifolia, because of its functional properties, would be a good candidate to use as a nutraceutical product for improving memory in the elderly or patients affected by Alzheimer disease (ad). To test this hypothesis, we examined the cholinesterase inhibitory activity using the modified colorimetric Ellmans method against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The n-hexane exhibited the highest activity, with inhibitory concentration 50% (IC(50)) values of 0.59 and 0.21 mg/mL, for AChE and BChE, respectively. This extract was fractionated, and 9 of these fractions (A-I) were obtained and tested. Fraction G, characterized by the presence of sesquiterpenes as major components, was the most active against AChE (IC(50) = 0.05 mg/mL). Because oxidative stress is a critical event in the pathogenesis of AD, we decided to screen the antioxidant activity (AA) using 2,2-diphenyl-1-picrylhydrazyl test, β-carotene bleaching test, and bovine brain peroxidation (thiobarbituric acid) assay. The ethyl acetate extract showed the highest activity, with IC(50) values of 2 and 33 μg/mL on β-carotene bleaching test and thiobarbituric acid test, respectively. These results suggest potential health benefits of S leriifolia extracts. However, this finding requires additional investigation in vivo.