Kitul, a food plant with antidiabetic-like effects: Reduction of intracellular reactive species in glucose-stimulated RIN-5F pancreatic ß-cells and mitigation of pro-inflammatory mediators in activated RAW 264.7 macrophages.

Kitul (Caryota urens L.) inflorescences are broadly used for sweet sap production in Asian countries and Kitul food products are known as being suitable for diabetic patients. Considering the strong ability to inhibit α-glucosidase, we hypothesize that kitul antidiabetic properties might also involve the modulation of inflammatory pathways and hyperglycaemia-induced oxidative damage. Hence, the effects of an inflorescence's methanol extract were investigated in glucose-stimulated pancreatic cells (RIN-5F) and LPS-stimulated RAW 264.7 macrophages. The extract reduced the overproduction of intracellular reactive species in pancreatic cells and also NO, L-citrulline and IL-6 levels in LPS-stimulated RAW 264.7 macrophages. Inhibition of 5-lipoxygenase (IC50 = 166.1 µg/mL) through an uncompetitive manner was also recorded upon treatment with C. urens inflorescences extract. The phenolic profile of the inflorescences was characterized by HPLC-DAD, six hydroxycinnamic acids being identified and quantified. Overall, our data provide additional evidence on the pleiotropic mechanisms of Kitul inflorescences as an antidiabetic agent.

Valorisation of kitul, an overlooked food plant: Phenolic profiling of fruits and inflorescences and assessment of their effects on diabetes-related targets.

Caryota urens L. has long been valued as a traditional food, the edible fruits being eaten raw and the inflorescences commonly used on sweet sap and flour production. In the current work, the phenolic profile of methanol extracts obtained from the inflorescences and fruits was unveiled for the first time, nine caffeic acid derivatives being identified and quantified. Since kitul products have been reported for their antidiabetic properties, extracts radical scavenging activity and α-amylase, α-glucosidase and aldose reductase inhibitory activity were assessed. The inflorescences' extract was particularly active against yeast α-glucosidase (IC50 = 1.53 µg/mL), acting through a non-competitive inhibitory mechanism. This activity was also observed in enzyme-enriched homogenates obtained from human Caco-2 cells (IC50 = 64.75 µg/mL). Additionally, the extract obtained from the inflorescences showed no cytotoxicity on HepG2, AGS and Caco-2 cell lines. Our data suggest that C. urens inflorescences can support the development of new functional foods with α-glucosidase inhibitory activity.

Gustavia gracillima Miers. flowers effects on enzymatic targets underlying metabolic disorders and characterization of its polyphenolic content by HPLC-DAD-ESI/MSn.

Notwithstanding Gustavia gracillima Miers widespread distribution in neotropical regions, its chemical profile and biological properties remain uninvestigated. A methanol extract obtained from the flowers was characterized through HPLC-DAD-ESI/MSn, nine ellagic acid derivatives and twelve kaempferol 3-O-glycosides being identified and quantitated for the first time at the species and genus. Preliminary cytotoxicity screening did not reveal noticeable effects upon gastrointestinal representative cell lines (AGS, Caco-2 and Hep G2), which further prompted us to evaluate the impact in a series of targets involved in metabolic disorders and associated complications. Despite of the moderate inhibition towards 5-lipoxygense activity, G. gracillima methanol extract displayed significant effects on carbohydrates-hydrolysing enzymes. In contrast with the antidiabetic reference drug acarbose, the extract was able to selectively inhibit yeast α-glucosidase activity (IC50 = 4.72 µg/mL), with negligible inhibitory effects upon α-amylase. Kinetic studies pointed to a model of mixed inhibition with a great binding activity, characterized by an inhibitory constant of 2.91 µg/mL. The notable inhibitory activity was also confirmed in α-glucosidase homogenates isolated from human intestinal cells (IC50 = 34.03 µg/mL). Moreover, the extract obtained from the flowers of G. gracillima displayed significant aldose reductase inhibition (IC50 = 61.88 µg/mL), as well as O2- and NO scavenging properties. A moderate inhibitory effect was also recorded against pancreatic lipase (IC50 = 362.17 µg/mL) through a mixed inhibition mode. Recorded data supports the potential incorporation of G. gracillima flowers on antidiabetic herbal formulations and/or supplements, with not only straight action on carbohydrates digestion, but also direct interference with targets involved on subsequent diabetes events, such as triglycerides metabolism, inflammation and radical-mediated stress.

Medicinal plants utilized in Thai Traditional Medicine for diabetes treatment: Ethnobotanical surveys, scientific evidence and phytochemicals.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus remains the most lethal metabolic disease of contemporaneous times and despite the therapeutic arsenal currently available, research on new antidiabetic agents remains a priority. In recent years, the revitalization of Thai Traditional Medicine (TTM) became a clear priority for the Thai government, and many efforts have been undertaken to accelerate research on herbal medicines and their use in medical services in various hospitals. Additionally, and particularly in rural areas, treatment of diabetes and associated symptomatology frequently relies on herbal preparations recommended by practitioners of TTM. In the current work, medicinal plants used in Thailand for treating diabetes, as well as their hypoglycaemic pharmacological evidences and potential therapeutic use for diabetes-related complications were reviewed. MATERIALS AND METHODS: Ethnopharmacological information on the plant materials used in TTM for diabetes treatment was collected through literature search in a range of scientific databases using the search terms: diabetes, folk medicine, Thailand medicinal plants, traditional medicine. Information regarding scientific evidence on the antidiabetic effects of surveyed species was obtained considering not only the most common taxonomic designation, but also taxonomic synonyms, and including the keywords 'diabetes' and 'hypoglycaemic effect'. RESULTS: A total of 183 species known to be used for diabetes management in TTM were reviewed, with 30% of them still lacking experimental evidences to support claims regarding the mechanisms and phytochemicals underlying their antidiabetic properties. Moreover, a total of 46 bioactives displaying effective antidiabetic effects have been isolated from 24 species, their underlying mechanism(s) of action being fully or partially disclosed. CONCLUSIONS: We deliver the most extensive survey dealing with the ethnomedicinal knowledge of Thai medicinal plants utilized on diabetes management. We are certain that the current review will spark further research on Thai plants for the development of new standardized phytomedicines through drug discovery programmes.

Phenolic Profiling and Biological Potential of Ficus curtipes Corner Leaves and Stem Bark: 5-Lipoxygenase Inhibition and Interference with NO Levels in LPS-Stimulated RAW 264.7 Macrophages.

The economic value of fig trees has been globally acknowledged due to their utilization in the food industry, being also frequently used in traditional medicine. While ubiquitously distributed in Southeast Asia, Ficus curtipes Corner remains uninvestigated concerning its biological properties and chemical profile. HPLC-DAD-ESI/MSn characterization of methanol extracts obtained from the stem bark and leaves allowed the identification and quantitation of 21 phenolic compounds for the first time; the stem bark was predominantly rich in flavan-3-ols and apigenin derivatives, while solely apigenin-di-glycosides have been identified and quantitated on the leaf extract. Both extracts inhibited 5-lipoxygenase (5-LOX) activity in a concentration-dependent manner, the one obtained from the stem bark being significantly more active (IC50 = 10.75 µg/mL). The effect of both extracts on lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages was evaluated, and while the stem bark extract did not lead to a noticeable interference on nitric oxide (NO) levels, the extract obtained from the leaves notably decreased NO and L-citrulline levels at concentrations ranging from 250 to 500 µg/mL. Herein, F. curtipes is valorized due to its modulatory effects on inflammatory mediators and also as a source of bioactive phenols, which may fuel further studies on the development of nutraceuticals.