The relationship between free radicals and acute or chronic inflammation has been well established. We have previously reported the significant antioxidant activity of the natural azulene derivatives chamazulene and guaiazulene. Furthermore, some synthetic azulene analogues have been found to possess anti-inflammatory activity. In this investigation we report the synthesis of five 3-alkyl or 3-(hydroxy)alkylazulene-1-carboxylic acids and esters, from tropolone, via the corresponding furanone. The synthesised compounds were tested for their effect on the peroxidation of rat hepatic microsomal membrane lipids, applying the 2-thiobarbituric acid test. Their anti-inflammatory activity was evaluated in vitro by the offered inhibition of soybean lipoxygenase. All the tested molecules were found to inhibit lipid peroxidation by 100% at 1 mM. They were also found to considerably inhibit lipoxygenase activity. The above results are discussed in relation to the structure and physicochemical properties of the examined azulene derivatives.

Oxidative stress and hyperlipidemia are important factors for the initiation and progression of various cell degenerative pathological conditions, including cardiovascular and neurological diseases. A series of cinnamic acid-derived acids, such as ferulic acid, sinapic acid, 3,4-dimethoxycinnamic acid, p-coumaric acid, and (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid, were esterified or amidated with various moieties, bearing different biological activities, and evaluated. The antioxidant and radical scavenging abilities of the compounds via inhibition of rat hepatic microsomal membrane lipid peroxidation, as well as their interaction with the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), were assessed. Further, their hypolipidemic activity in vivo was tested. The majority of the obtained compounds demonstrated considerable radical scavenging and antioxidant action, with a parallel decrease in Triton-induced hyperlipidemia in rats. The (E)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)acrylic acid derivative with morpholine and 4-methylpiperidine (compounds 4 and 13, respectively) significantly decreased triglycerides and total cholesterol in the plasma of hyperlipidemic rats, with an antioxidant capacity similar to that of the antioxidant Trolox. The compounds were designed to exhibit antioxidant and hypolipidemic pharmacological actions, and this succeeded for the majority of them. Thus, such agents may be of interest in conditions and diseases implicating oxidative stress and dyslipidemia.

A series of thiomorpholine and cinnamyl alcohol derivatives, conjugated with cinnamic acid-containing moieties, such as ferulic acid, sinapic acid and 3,4-dimethoxycinnamic acid, were synthesized and tested for their antioxidant, anti-inflammatory and hypolipidemic properties. An indomethacin ester with 2,6-di-tert-butyl-4-(hydroxymethyl)phenol was also prepared for reasons of comparison. The majority of the compounds demonstrated considerable antioxidant capacity and radical scavenging activity, reaching up to levels similar to the well-known antioxidant trolox. Some of them had an increased anti-inflammatory effect on the reduction of carrageenan-induced rat paw edema (range 17–72% at 150 μmol/kg), having comparable activity to the NSAIDs (non-steroidal anti-inflammatory drugs) used as reference. They had moderate activity in soybean lipoxygenase inhibition. All the tested compounds exhibited a significant decrease in lipidemic indices in Triton-induced hyperlipidemia in rats, whilst the most active triglycerides and total cholesterol decreased by 72.5% and 76%, respectively, at 150 μmol/kg (i.p.), slightly better than that of simvastatin, a well-known hypocholesterolemic drug, but with negligible triglyceride-lowering effect. Since our designed compounds seem to exhibit multiple pharmacological activities, they may be of use in occasions involving inflammation, oxidative stress, lipidemic deregulation and degenerative conditions.

Vitamins are micronutrients necessary for the normal function of the body. Although each vitamin has different physicochemical properties and a specific role in maintaining life, they may also possess a common characteristic, i.e., antioxidant activity. Oxidative stress can harm all the main biological structures leading to protein, DNA and lipid oxidation, with concomitant impairment of the cell. It has been established that oxidative stress is implicated in several pathological conditions such as atherosclerosis, diabetes, obesity, inflammation and metabolic syndrome. In this review we investigate the influence of oxidative stress on the above conditions, examine the interrelation between oxidative stress and inflammation and point out the importance of vitamins in these processes, especially in oxidative load manipulation and metabolic abnormalities.

Multiple sclerosis (MS) is a complex neurodegenerative disease. Although its pathogenesis is rather vague in some aspects, it is well known to be an inflammatory process characterized by inflammatory cytokine release and oxidative burden, resulting in demyelination and reduced remyelination and axonal survival together with microglial activation. Antioxidant compounds are gaining interest towards the manipulation of MS, since they offer, in most of the cases, many benefits, due to their pleiotropical activity, that mainly derives from the oxidative stress decrease. This review analyzes research articles, of the last decade, which describe biological in vitro, in vivo and clinical evaluation of various categories of the most therapeutically applied natural antioxidant compounds, and some of their derivatives, with anti-MS activity. It also summarizes some of the main characteristics of MS and the role the reactive oxygen and nitrogen species may have in its progression, as well as their relation with the other mechanistic aspects of the disease, in order for the multi-targeting potential of those antioxidants to be defined and the source of origination of such activity explained. Antioxidant compounds with specific characteristics are expected to affect positively some aspects of the disease, and their potential may render them as effective candidates for neurological impairment reduction in combination with the MS treatment regimen. However, more studies are needed in order such antioxidants to be established as recommended treatment to MS patients.