Increase in insulin sensitivity by the association of chicoric acid and chlorogenic acid contained in a natural chicoric acid extract (NCRAE) of chicory (Cichorium intybus L.) for an antidiabetic effect, Journal of Ethnopharmacology, https://doi.org/10. 1016/j.jep.2017.12.035 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ABSTRACT Ethnopharmacological relevance Chicory (Cichorium intybus L.) is an indigenous vegetable widely cultivated in Europe,America and Asia. In ancient times, the leaves, flowers, seeds, and roots have been used as a wealth of health benefits including its tonic effects, the ability to ease digestive problems and to detoxify liver. In Indian traditional therapy, chicory was known to possess antidiabetic effect. In the traditional medicine of Bulgaria and Italy, chicory was used as hypoglycemic decoctions. Aims of the studiesWe wanted to obtain the complete chemical composition of the natural chicoric acid extract (NCRAE), a chicory root extract rich in chicoric acid, which previously showed its glucose tolerance effect in normal rats. To investigate if the whole NCRAE is required to be effective, we performed a comparative in vivo experiment on STZ diabetic rats treated either with NCRAE or a mixture composed of the two major compounds of NCRAE. Materials and Methods1 K. Ferrare and L.P.R. Bidel contributed equally to this study. ResultsThe LC-MS analysis confirmed the high abundance of chicoric acid (64.2%) in NCRAE and a second part of NCRAE is composed of caffeoylquinic acids (CQAs) at 19.6% with among them the chlorogenic acid. This result has permitted us to prepare a mixture of synthetic Lchicoric acid (70%) and synthetic chlorogenic acid (30%): the solution is designated SCCAM.Our results showed that both NCRAE and SCCAM are able to improve a glucose tolerance in STZ diabetic rats after a subchronic administration of seven days. Alone NCRAE allows to significantly decrease the basal hyperglycemia after six days of treatment. In vivo experiments on streptozotocin Chicoric acid 72.4 % Caffeoyl-quinic acids 19.6 % NCRAE contained a mixture of CRA, CGA and others caffeoyl derivatives that confer this antidiabetic -NCRAE induced a antidiabetic effect, -SCCAM induced an glucose
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.
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