Alpha-Mangostin for Diabetes Mellitus Therapy

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Diabetes Mellitus (DM) is a metabolic disorder that affects about 6% of the world’s population. DM is characterized by a prolonged hyperglycemic condition due to lack of insulin secretion and insulin sensitivity. DM is divided into DM type-1 and DM type-2. Type 1 DM is an autoimmune disease that causes the immune system to attack pancreatic cells, thereby impairing a person’s ability to produce insulin. Type 2 DM is a metabolic disorder characterized by insulin resistance, decreased sensitivity of cells to insulin, and a relative lack of insulin due to damage to β cells in Langerhans islets in the pancreas. Decreased cell sensitivity to insulin is a special condition causing type 2 DM. A progressive decrease in insulin secretion is generally the result of a decrease in tissue sensitivity to insulin.

Beside prolonged hyperglycemic condition, one of the factors causing DM is obesity due to increased levels of fat in the body caused by hyperlipidemia and increased levels of cholesterol in the blood. Elevated blood cholesterol levels can be followed by a free fatty acid generating superoxide production augmented by the mitochondria and the risk of exposure to higher cell by reactive oxygen species (ROS). Superoxide production will cause an increase in nitric oxide (NO) caused by enzyme induction. This condition leads to the production reactive nitrogen species (RNS) which will oxidize sulfhydryl protein groups, especially amino acid nitrates such as tyrosine and increase lipid peroxidation and damage DNA damaging cells.

Hyperlipidemia in people with obesity can increase oxidative stress in the body leading to several complications. People with obesity also experience high levels of cholesterol in the body (hypercholesterolemia) caused by excessive accumulation of fat in the body. One of the negative effects of obesity is insulin resistance, the inability of insulin to produce normal biological functions and cause lower tissue sensitivity to insulin. Cellular resistance to cellular action of insulin is developed in people with obesity, characterized by the reduced ability of insulin to support the intake of glucose in fat and muscle to produce hyperglycemic conditions. The condition of hyperglycemia leads directly to an increase in ROS and RNS levels. ROS and RNS can directly oxidize and destroy DNA, protein, and lipids. High levels of ROS and RNS can also indirectly damage the micromolecules, which cause oxidative stress. Oxidative stress occurs when there is an imbalance between the amount of highly reactive molecules (ROS and RNS) with existing antioxidants.

Antioxidants are substances that can prevent the negative effects of free radicals by providing electrons to make it possible to suppress damage to lipids, cell membranes, blood vessels, DNA, damages caused by reactive compounds, such as ROS and RNS. To reduce the occurrence of free radical effects, additional exogenous antioxidants, such as vitamin E, vitamin C and other antioxidants obtained from consuming various types of fruits and vegetables that contain high antioxidants are needed. One type of antioxidant that still provides an opportunity to overcome free radicals is alpha – mangostin. The alpha – mangostin compound is a pigment in Garcinia mangostana which is able to make a hydrogen donor and stabilize free radicals. In addition to neutralizing free radicals, antioxidants are expected to reduce oxidative stress, especially in various cells affected by prolonged hyperglycemic conditions, such as hepatocyte cells in the liver and kidney tubular cells.

Indonesia has a high amount of biodiversity containing a variety of natural potentials that can be utilized for the treatment of various diseases. One of Indonesia’s native flora which currently has great potential to be developed as a raw material for medicine is mangosteen. Mangosteen peel contains an active compound known as xanthones. Xanthone compounds also play an important role as a powerful antioxidant compared to vitamin C and vitamin E in preventing free radicals and cell damage, as well as inhibiting the process of cell degeneration. Xanthone compounds contained in mangosteen peel, especially alpha – mangostin compounds, has been shown to repair damaged pancreatic islets of Langerhans so that insulin can be produced optimally. Research conducted by Husen et al . (2019) revealed the effect of alpha – mangostin on glucose levels, cholesterol levels, and the diameter of the islets of Langerhans from STZ induced diabetic rats. The research is the base of the herbal medicine development for antidiabetic therapy.

Author: Saikhu Akhman Husen

Journal Title: The Effect of Alpha-mangostin in Glucose Level, Cholesterol Level, and Diameter of the Islets of Langerhans of STZ-induced Diabetic Mice

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