Study on the process of extracting iridoid compounds from Dolichandrone spathacea and synthesizing some derivatives to produce hypoglycemic preparations

According to the World Health Organization and the Diabetes Federation, Vietnam is one of the countries with the fastest growing rate of diabetes in the world. Currently, the trend of diabetes control is shifting from western medicine treatment to combining western medicine with the use of natural herbs, both to improve the effectiveness of lowering and stabilizing blood sugar and help reduce the side effects of the drug. Contributing to research in this field, Assoc. Prof. Dr. Tran Thi Phuong Thao and a research team of Institute of Chemistry conducted a project: Research on the process of extracting irinoid compounds from Dolichandrone spathacea and synthesizing a number of derivatives to create a blood sugar-lowering product, code: VAST04.03/19-20.

The objective of the research is to develop a process for extracting irinoid compounds from Dolichandrone spathacea with high efficiency, to provide a conversion process to create derivatives of the extracted irinoids, and to create an irinoid containing product with good hypoglycemic effect.

Dolichandrone spathacea is a species of mangrove with the scientific name of Dolichandrone spathacea (L.f) K. Schum. of the Bignoniaceafamily: The tree grows in many parts of the world, including Vietnam. In terms of chemical composition, compounds isolated from Dolichandrone spathacea mainly belong to the iridoid group. In the southern region of our country, especially in the Mekong Delta, the species of Dolichandrone spathacea is very common. The tree grows on the mud, against tidal canals and scads, and along estuaries, often in the form of shrubs and sometimes also found near the beach. It is usually a tree, sometimes it only bears leaves for a short time (in the dry season), sometimes the tree has leaves and flowers all year round. Dolichandrone spathacea tree has many uses such as a laxative for the liver, an antidote, for treating allergies, as an antiseptic. The flowers and young fruit of the Dolichandrone spathaceatree are edible.

Fruit, leaves and flowers of Dolicandrone spathacea

Iridoids are secondary compounds found in many plants and some animals. They are monoterpenes biosynthesized from isoprene and are often intermediates in alkaloid biosynthesis.Chemically, iridoids usually have a cyclopentane ring connected to an oxygen-containing hexavalent heterocyclic ring. Iridoid compounds often have many interesting activities such as hypoglycemic, analgesic, anti-inflammatory, antispasmodic, anti-inflammatory, antiviral, laxative. Especially, in recent years, the hypoglycemic activity of iridoids has been studied by scientists around the world.

The iridoids have potent hypoglycemic activity. Therefore, the research team conducted an exploration of the α-glucosidase enzyme inhibitory activity of two iridoids QN1 and QN2.The results showed that these two compounds were able to inhibit the enzyme α-glucosidase better than acarbose with IC50 of 191.50 and 175.52 μM, respectively (acarbose control 278.80 μM). The group's studies have shown that the class of iridoid substances accounts for a large amount of the plant in both bark, branches and leaves of Dolicandrone spathacea. On the basis of research on the laboratory scale iridoid extraction process, acetone solvent was selected as the extraction solvent for the preparation process of 100g/batch scale. Acetone has the ability to selectively extract iridoids, less toxic, and easy to remove during extraction.

Some iridoid compounds isolated from water hyacinth plant

Process of making Dolicandrone spathacea with the scale of 100g inoculants/batch

The results of the evaluation of α-glucosidase enzyme inhibitory activities of 14 iridoid derivatives showed that there were 5 compounds with the highest activity in the order of QN3 ˃ QN2 ˃ QN5 ˃ QN4 ˃ QN1 (corresponding to the following values IC50 0.05; 7.24; 8.65; 20.84 and 24.89 μM, acarbose control IC50 285.0 μM).Compound QN3 (nemoroside) exhibited the most potent α-glucosidase inhibitory activity, 5,700 times stronger than the control. Molecular docking studies gave quite similar results, in which the order of binding to 3W37: QN2 ˃ QN3 ˃ QN1 ˃ QN19 ˃ QN5 and binding to 3AJ7: QN5 ˃ QN2 ˃ QN3 ˃ QN15 ˃ QN1 = QN19. Lipinski's five rules show that QN3 is the most promising compound for oral application, while QN1, QN2 and QN5 are the most suitable substances for the physiological environment of the body in this study. The obtained results show that there is a similarity between the theoretical calculation and the experiment, the structure-activity correlation of iridoid derivatives on the mechanism of action on the carbohydrate hydrolyzed proteins 3W37 and 3AJ7 has been studied.

Molecular docking between QN3, QN5 and QN12 with 3W37 protein

The new contributions of the project are:
- For the first time, the chemical composition of the fruit has been studied
- 03 substances were isolated for the first time from this species and 05 new semi-synthetic iridoid derivatives
- For the first time, the study evaluated the inhibitory activity of α-glucosidase enzyme of derivatives and iridoids isolated from water hyacinth.
- For the first time studying theoretical calculations on molecular docking models of 15 iridoids to determine the structure-activity correlation.
The subject is rated Excellent.

Translated by Phuong Ha
Link to Vietnamese version

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