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Multiple sclerosis (MS) is the most prevalent chronic autoimmune inflammatory- demyelinating disorder of the central nervous system (CNS). It usually begins in young adulthood, mainly between the second and fourth decades of life. Usually, the clinical course is characterized by the involvement of multiple CNS functional systems and by different, often overlapping phenotypes. In the last decades, remarkable results have been achieved in the treatment of MS, particularly in the relapsing- remitting (RRMS) form, thus improving the long-term outcome for many patients. As deeper knowledge of MS pathogenesis and respective molecular targets keeps growing, nowadays, several lines of disease-modifying treatments (DMT) are available, an impressive change compared to the relative poverty of options available in the past. Current MS management by DMTs is aimed at reducing relapse frequency, ameliorating symptoms, and preventing clinical disability and progression. Notwithstanding the relevant increase in pharmacological options for the management of RRMS, research is now increasingly pointing to identify new molecules with high efficacy, particularly in progressive forms. Hence, future efforts should be concentrated on achieving a more extensive, if not exhaustive, understanding of the pathogenetic mechanisms underlying this phase of the disease in order to characterize novel molecules for therapeutic intervention. The purpose of this review is to provide a compact overview of the numerous currently approved treatments and future innovative approaches, including neuroprotective treatments as anti-LINGO-1 monoclonal antibody and cell therapies, for effective and safe management of MS, potentially leading to a cure for this disease., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Benign prostatic hypertrophy (BPH) is a common condition in elderly men that impairs quality of life and leads to a number of medical complications. The use of phytotherapeutic compounds in patients with relatively moderate BPH symptoms has been growing steadily. In the present study, acute toxicity of lyophilised aqueous extracts of Cistus incanus L. and Cistus monspeliensis L., collected in Sicily, was evaluated on the shrimp (Artemia salina L.) lethality assay, an alternative test to determine the toxicity of natural products. The cytotoxic and growth inhibitory effects were studied on normal human prostate cells (PZ-HPV-7 and PNT1A) and on a lung fibroblast cell line (V79-4). Cell proliferation was evaluated by MTT and SRB assays. Cytotoxicity was measured using the Trypan blue exclusion assay. Cistus extract treatment on prostate cell lines resulted in an almost identical growth inhibitory response and in a significant decrease in an cell viability. These findings indicate the biologically relevant effect of polyphenolic compounds present in Cistus extracts, and suggest that these substances may prove beneficial in BPH treatment.

A simple high-performance liquid chromatography method using a diode array detector (DAD) is developed for the simultaneous analysis of five major catechins: (+)-catechin (C), (-)-epicatechin (EC), (-)-gallocatechin (GCT), (-)-epigallocatechin (EGC), (-)-epigallocatechin gallate (EGCG), and the phenolic plant metabolites gallic acid (GA) and rutin (RT) in lyophilized extracts of Cistus species. The optimal analytical conditions are investigated to obtain the best resolution and the highest UV sensitivity for the quantitative detection of catechins. The optimized conditions (acetonitrile-phosphate buffer 50 mM, pH 2.5, gradient elution system on a C18 reversed-phase column with a flow rate of 1 mL/min and UV absorbance at 210 nm) allowed a specific and repeatable separation of the studied analytes to be achieved. All compounds are successfully separated within 32 min. Calibration curves are linear in the 2-50 microg/mL range for GCT, C, and EGCG and in the 5-50 microg/mL range for GA, EGC, EC, and RT. The limit of detection values ranged from 0.24 to 0.74 microg/mL. The limit of quantitation limit values ranged from 0.77 to 1.94 microg/mL. The validated method is applied to the determination of the specific phytochemical markers GA, GCT, C, and RT in Cistus incanus and Cistus monspeliensis lyophilised extracts. The recovery values ranged between 78.7% and 98.2%. The described HPLC method appears suitable for the differentiation and determination of the most common catechins together with the glycoside rutin and the phenolic compound gallic acid and can be considered an effective and alternative procedure for the analyses of this important class of natural compounds.

The lyophilized aqueous extracts from Cistus incanus L. (CI) and Cistus monspeliensis L. (CM) collected in Sicily were studied in order to evaluate their myorelaxant activity by using isolated smooth muscle of rat ileum and rat aorta. Both CI and CM extracts concentration-dependently inhibited the contractile response to acetylcholine (ACh), phenylephrine (PE) and to 100 mM KCl. The concentration-contraction curves to ACh in ileum and to PE in aorta, were displaced to the right by Cistus extracts in a non-competitive manner, with a depression of the maximum contractile response. The EC50 (microg/ml) of CM and CI were: ileum/KCl, CM 457+/-99, CI 681+/-80; ileum/ACh 100 microM, CM 297+/-66, CI 335+/-41; aorta/KCl, CM 360+/-21, CI 843+/-36; and aorta/PE 10 microM, CM 287+/-33, CI 451+/-58. The two extracts resulted almost equi-active in ileum, whereas CM was more active than CI in aorta. These data indicate that Cistus extracts act as spasmolytic on intestinal and vascular smooth muscle. The antagonism they exert on ACh-, PE- and KCl-evoked contractions seems to be functional, because it is not specifically directed toward any particular receptor; furthermore, a calcium-antagonist activity seems unlikely, since the extracts are capable of completely block the contractile response to agonists.

The genus Cistus includes many typical species of Mediterranean flora; Cistus species are used as antidiarrhetics, as general remedies for treatment of various skin diseases in folk medicine and as anti-inflammatory agents. These species contain flavonoids that are considered to be chain-breaking antioxidants. In this work, we have investigated the effects of crude aqueous extracts from Cistus incanus and Cistus monspeliensis on DNA cleavage and their free-radical scavenging capacity. In addition, their effect on lipid peroxidation in rat liver microsomes was evaluated. These extracts showed a protective effect on DNA cleavage and a dose-dependent free-radical scavenging capacity; Cistus monspeliensis was more active than Cistus incanus; these results were confirmed by a significant inhibition of lipid peroxidation in rat liver microsomes. The experimental evidence, therefore, suggests that because of their antioxidant activity these extracts may offer excellent photoprotection for skin and may be useful in the treatment of human diseases where oxidative stress plays a key role.

The antiulcer activity of a short-boiled aqueous extract from aerial parts of Cistus incanus was studied in rats against gastric lesions induced by necrotizing agents (1N HCl and absolute ethanol), indomethacin, serotonin and reserpine. The extract, containing bioflavonoids, was orally administered in the range from 0.25 to 0.50 g kg-1. It was found to have significant dose-related protective effects in all these experimental models, and was more effective against reserpine- and serotonin-induced mucosal congestion and haemorrhagic ulcers. These data suggest that the active constituents of the crude extract could be responsible for its protective effect by maintaining an efficient gastric mucosal microvascular supply.

In this study the pharmacological evaluation of MED-15, a non-acidic prodrug of tolmetin, is described. After oral administration the new compound shows a marked anti-inflammatory activity similar to that of tolmetin, but with minor ulcerogenic action and lower acute toxicity.

The effects of sodium valproate (150 mg/kg) and carbamazepine (300 mg/kg), alone and in combination, on the content of glutathione (GSH) were investigated in the rat cerebral cortex. No modification was found either 4, 12 or 16 hours after treatment, suggesting that sodium valproate and carbamazepine do not affect the cortical GSH metabolism in rats.

In the present study we have assayed the effect of divicine in G6PD-deficient red blood cells in the presence of deferoxamine (iron-chelating drug) and NaN3 (inhibitor of catalase). The effect of divicine has been compared to oxidative stress by H2O2; haemolysis is regarded as an index of cellular toxicity. In addition, we have tested antioxidant enzymatic systems. No significant change in antioxidant enzymatic systems was found in RBCs from subjects with G6PD deficiency when compared to the control group, either in oxidative haemolysis by divicine or by H2O2; a significant decrease in oxidative haemolysis by H2O2 was observed in the presence of deferoxamine, whereas no change was found in oxidative haemolysis by divicine. The replacement of incubation medium by homologous plasma or the supplementation with bovine serum albumin resulted in a marked decrease of percentage of haemolysis by divicine.

In the outline of the investigations concerning the analgesic and antiinflammatory activity of new fused heterocyclic compounds containing the pyrimidine ring, a series of 6H-thiazolo[3',2': 1,2]-5-oxopyrimido[5,4-b]indole derivatives was synthesized. Pharmacological results are reported and discussed.

As a part of a study on analgesic and antiinflammatory active condensed heterocyclic compounds containing the pyrimidinic ring, a number of 6H-1,3,4-thiadiazolo [3',2':1,2]-5-oxopyrimido [5,4-b]indole and 1-phenyl-6H-1,2,4-triazolo [1',5':1,2]-5-oxopyrimido [5,4-b] indole were synthesized and tested. The results of pharmacological assays are reported and discussed.

The authors evaluated the vegetative growth and alkaloid content of the Papaver somniferum L. var. album D.C. capsules cultivated in Assoro (Enna) Sicily, in relation to the geographical position, environmental conditions and soil type. Gas chromatography revealed low alkaloid opiate producing capacity which makes cultivation for therapeutic and toxicologic purposes uneconomic. On the contrary, the elevated production of capsules containing numerous seeds justifies its cultivation for extraction of oil for the food industry and paint production. The results suggest that the cultivation of Papaver somniferum studied is used for baking traditional cakes and bread.