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Metabolic syndrome (METS) is a complex disorder that predisposes an affected person to an increased risk of diabetes and cardiovascular disease. Bitter Asteraceae plants contain several compounds active against METS that can be used as an alternative preventive therapy. Our previous work showed that a natural chicory extract (NCRAE) containing chicoric acid (CRA) and chlorogenic acid (CGA) in a molar ratio of 70/30 exhibited an antioxidant, insulin sensitization and anti-hyperglycemic effect. The present study was designed to evaluate the preventive effects of an NCRAE-like extract against METS in a complementary natural pharmacotherapeutic approach. An original Asteraceae infused drink containing the NCRAE CRA/CGA molecular ratio equivalent was prepared from dandelion (Taraxacum officinale L.) and burdock (Arctium lappa L.). The anti-METS effect of this drink was evaluated on the fructose-rat model for 8 weeks. Body weight, blood biochemistry, hepatic glucose-6-phosphatase, arterial blood pressure glucose and insulin tolerance were evaluated after 8 weeks. Our results show that daily oral intake of the Asteraceae infused drink led to a reduction of body weight gain, hyperglycemia, hypertriglyceridemia, insulin resistance and hypertension. Moreover, rat-by-rat analysis of the insulinemia measures revealed two types of responders. One sub-group of subjects demonstrated normal insulinemia and the other subgroup demonstrated hyperinsulinemia. This hyperinsulinemia, associated with the inhibition of the glucose-6-phosphatase activity in the liver tissue, may suggest an insulin release caused by CGA. The present study suggests that this original infusion of dandelion leaves and burdock roots may be used as an adjuvant therapy to prevent metabolic syndrome.

The aim of our study was to identify novel molecules able to induce an adaptative response against oxidative stress during the first stages of metabolic syndrome. A cellular survival in vitro test against H2O2-based test was applied after pretreatment with various natural bitter Asteraceae extracts. This screening revealed potent protection from burdock leaf extract. Using chromatography and LC-MS—RMN, we then isolated and identified an original sesquiterpene lactone bioactive molecule: the Xanthatin-13-(pyrrolidine-2-carboxylic acid) (XPc). A real-time RT-qPCR experiment was carried out on three essential genes involved in oxidative stress protection: GPx, SOD, and G6PD. In presence of XPc, an over-expression of the G6PD gene was recorded, whereas no modification of the two others genes could be observed. A biochemical docking approach demonstrated that XPc had a high probability to directly interact with G6PD at different positions. One of the most probable docking sites corresponds precisely to the binding site of AG1, known to stabilize the G6PD dimeric form and enhance its activity. In conclusion, this novel sesquiterpene lactone XPc might be a promising prophylactic bioactive agent against oxidative stress and inflammation in chronic diseases such as metabolic syndrome or type 2 diabetes.

Plant bioactive extracts represent a major resource for identifying drugs and adjuvant therapy for type 2 diabetes. To promote early screening of plants’ antidiabetic potential, we designed a four in vitro tests strategy to anticipate in vivo bioactivity. Two antidiabetic plants were studied: Ocimum gratissimum L. (Oc) leaf extract and Musanga cecropoides R. Br. ex Tedlie (Mu) stem bark extract. Chemical compositions were analyzed by LCMS and HPLC. Antidiabetic properties were measured based on (1) INS-1 cells for insulin secretion, (2) L6 myoblast cells for insulin sensitization (Glut-4 translocation), (3) L6 myoblast cells for protection against hydrogen peroxide (H2O2) oxidative stress (cell mortality), and (4) liver microsomial fraction for glucose-6-phosphastase activity (G6P). Oc extract increased insulin secretion and insulin sensitivity, whereas it decreased oxidative stress-induced cell mortality and G6P activity. Mu extract decreased insulin secretion and had no effect on insulin sensitivity or G6P activity, but it increased oxidative stress-induced cell mortality. Results were compared with NCRAE, an antidiabetic plant extract used as reference, previously characterized and reported with increased insulin secretion and insulin sensitivity, protection against oxidative stress, and decreased G6P activity. The proposed set of four in vitro tests combined with chemical analysis provided insight into the interest in rapid early screening of plant extract antidiabetic potential to anticipate pharmaco-toxicological in vivo effects.

The inhibition of recombinant CpLIP2 lipase/acyltransferase from Candida parapsiolosis was considered a key model for novel antifungal drug discovery and a potential therapeutic target for candidiasis. Lipases have identified recently as potent virulence factors in C. parapsilosis and some other yeasts. The inhibition effects of orlistat and four flavonols (galangin, kaempferol, quercetin and myricetin) characterized by an increasing degree of hydroxylation in B-ring, were investigated using ethyl oleate hydrolysis as the model reaction. Orlistat and kaempferol (14 µM) strongly inhibited CpLIP2 catalytic activity within 1 min of pre-incubation, by 90% and 80%, respectively. The relative potency of flavonols as inhibitors was: kaempferol > quercetin > myricetin > galangin. The results suggested that orlistat bound to the catalytic site while kaempferol interacted with W294 on the protein lid. A static mechanism of interactions between flavonols and CpLIP2 lipase was confirmed by fluorescence quenching analyses, indicating that the interactions were mainly driven by hydrophobic bonds and electrostatic forces. From the Lehrer equation, fractions of tryptophan accessibility to the quencher were evaluated, and a relationship with the calculated number of binding sites was suggested.