Abstract
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.
Highlights
Type 2 diabetes (T2D) is a metabolic disorder characterized by uncontrolled chronically high glucose levels
We showed that NCRAE was able to increase insulin secretion of INS-1 cells, increase the insulin sensitization of L6 myoblast cells [8], protect the L6 cells against an oxidative H2O2 stress, and decrease the glucose-6-phosphatase (G6Pase) activity in rat liver microsomes [10]
We showed that the in vivo antidiabetic property of NCRAE on streptozotocin rats was correlated with a set of four in vitro tests and showed its ability to increase insulin secretion in INS-1 cells, to increase the insulin sensitization of L6 myoblast cells, to protect L6 cells against oxidative H2O2 stress, and to decrease the glucose-6-phosphatase (G6Pase) activity on rat liver microsomes
Summary
Type 2 diabetes (T2D) is a metabolic disorder characterized by uncontrolled chronically high glucose levels. It is admitted that chronic oxidative stress and low grade chronic inflammation are associated with the insulin resistance of insulin-sensitive tissues, e.g., skeletal muscles, liver, and adipose tissue [1]. To treat T2D, oral pharmacological antidiabetic allopathic drugs are prescribed in order to reduce hyperglycemia These drugs include insulin secretagogue agents (sulfonylureas, glinides), insulin-sensitizing agents (metformin), and glucose absorption inhibitors such as α-glucosidase inhibitors (acarbose, miglitol). These drug molecules are used effectively, none of them are simultaneously targeting oxidative stress/chronic inflammation and insulin resistance
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