Research Progress on Dihydroberberine in Regulating Glucose Metabolism Homeostasis

With the changes in lifestyle and the intensification of population aging, the global incidence of diabetes is increasing year by year. Finding safe and effective substances for blood glucose regulation has become a research hotspot in the field of medicine and pharmacy. As a hydrogenated derivative of berberine, dihydroberberine is an isoquinoline alkaloid with good biological activity. This article reviews the sources and physicochemical properties of dihydroberberine, focuses on its roles in improving insulin sensitivity, promoting glucose metabolism and utilization, and inhibiting excessive hepatic glucose production, and discusses its application value and future research directions, aiming to provide a reference for the in-depth research and application of dihydroberberine in the field of blood glucose management.

Keywords: Dihydroberberine; Blood glucose balance; Hypoglycemia; Insulin sensitivity

1. Introduction

Blood glucose balance is an important basis for maintaining normal physiological functions of the human body. Sustained abnormal elevation of blood glucose levels can lead to metabolic diseases such as diabetes, thereby causing various complications and seriously threatening human health. Dihydroberberine is a natural alkaloid derivative extracted from plants of the Berberidaceae family. Compared with berberine, it has higher bioavailability and better pharmacological activity. Recent studies have shown that dihydroberberine has good potential in regulating blood glucose balance and reducing blood glucose levels, but its specific functions and mechanisms need to be systematically organized. Based on existing research results, this article reviews the blood glucose regulatory effect of dihydroberberine, providing a theoretical basis for its further research and development.

2. Sources and Characteristics of Dihydroberberine

Dihydroberberine is a hydrogenated derivative of berberine, belonging to isoquinoline alkaloids. It mainly exists in the rhizomes of traditional medicinal plants of the Berberidaceae family, such as Coptis chinensis, Phellodendron, and Berberis, and is one of the important active ingredients for these plants to exert pharmacological effects. Compared with berberine, dihydroberberine has significantly enhanced lipid solubility due to the addition of hydrogen atoms in its chemical structure. This characteristic enables it to be absorbed more efficiently in organisms, facilitating its entry into cells to exert effects, thus showing significantly better bioavailability than berberine. As a naturally derived alkaloid derivative, dihydroberberine not only retains certain pharmacological activities but also has advantages in absorption and utilization, making it a research hotspot in the field of blood glucose regulation in recent years.

3. Common Inducing Factors of Blood Glucose Imbalance and Their Health Impacts

Blood glucose imbalance is mainly manifested as persistently high blood glucose levels, i.e., diabetes or pre-diabetic state, which is closely related to multiple factors that interact to affect blood glucose stability. An unreasonable dietary structure is one of the important inducing factors. Long-term intake of high-sugar, high-fat, and high-calorie foods causes the body to take in far more energy than it consumes. The excess energy is converted into fat for storage, while increasing the burden on insulin, gradually leading to decreased insulin sensitivity and difficulty in effectively regulating blood glucose. Lack of exercise is also a key factor. Exercise can promote the consumption and utilization of glucose and enhance insulin sensitivity. However, a long-term sedentary lifestyle and insufficient physical activity will reduce the body's responsiveness to insulin, slow down the rate of glucose metabolism, and increase the risk of blood glucose imbalance. Genetic factors cannot be ignored. If there are diabetic patients in the family, the probability of an individual developing diabetes will increase significantly, which is related to the metabolic regulation ability determined by genetic genes. In addition, factors such as obesity, aging, and long-term mental stress can also lead to blood glucose imbalance by affecting insulin secretion and the uptake and utilization of glucose by cells. Long-term high blood glucose can damage multiple organs of the body, such as damaging vascular endothelium, affecting kidney function, and impairing the nervous system, causing various complications and seriously reducing the quality of life.

4. Manifestations of Dihydroberberine's Blood Glucose Regulatory Effects

4.1 Improving Insulin Sensitivity

Insulin is a key hormone for regulating blood glucose. When cells' sensitivity to insulin decreases, even if there is sufficient insulin in the body, it cannot effectively promote glucose to enter cells, resulting in elevated blood glucose. Dihydroberberine can improve the responsiveness of cells to insulin, making cells more "cooperative" with the role of insulin, thereby improving the efficiency of glucose uptake and utilization, allowing glucose in the blood to smoothly enter cells for consumption, and achieving the goal of lowering blood glucose. In relevant studies, the insulin sensitivity indicators of experimental subjects supplemented with dihydroberberine were significantly improved.

4.2 Promoting Glucose Metabolism and Utilization

The metabolic utilization of glucose in the body mainly includes processes such as oxidative decomposition for energy supply and conversion into glycogen for storage. Dihydroberberine can accelerate the rate of these metabolic processes, promoting more glucose to be decomposed and utilized, and reducing the accumulation of glucose in the blood. At the same time, it can also promote the synthesis of glycogen in the liver and muscles, storing excess glucose to avoid a sharp increase in blood glucose after meals, which helps maintain blood glucose stability.

4.3 Inhibiting Excessive Hepatic Glucose Production

The liver is one of the important sources of glucose in the body. When blood glucose levels are low, the liver will decompose hepatic glycogen or generate glucose through gluconeogenesis to release into the blood, maintaining blood glucose stability. However, when blood glucose is high, if the liver continues to excessively produce glucose, it will aggravate blood glucose imbalance. Dihydroberberine can regulate the process of hepatic glucose production, reducing glucose release when blood glucose is high, thereby reducing the glucose content in the blood and playing an auxiliary role in lowering blood glucose.

5. Experimental and Clinical Research Evidence for the Hypoglycemic Effect of Dihydroberberine

5.1 Preclinical Pharmacodynamic Evaluation

In animal model studies, researchers observed the hypoglycemic effect of dihydroberberine by constructing diabetic models. After diabetic model animals were administered dihydroberberine, their fasting blood glucose levels and postprandial blood glucose levels were significantly lower than those of model animals not administered, and the area under the blood glucose curve was significantly reduced, indicating that it can effectively control blood glucose fluctuations. At the same time, the insulin resistance state of model animals was improved, the insulin levels in the blood gradually returned to normal, and the synthesis of glycogen in the liver and muscles increased, further confirming its regulatory effect on glucose metabolism.

5.2 Preliminary Evaluation of Clinical Efficacy

At present, human clinical studies on dihydroberberine are still in their infancy, but there have been some positive results. In a small-scale clinical trial on patients with type 2 diabetes, subjects supplemented with dihydroberberine on the basis of conventional treatment. After a period of time, their fasting blood glucose and glycosylated hemoglobin levels decreased more significantly than those in the control group receiving only conventional treatment, and insulin sensitivity indicators also improved. Another study on pre-diabetic populations showed that supplementation with dihydroberberine can delay the progression to diabetes, and blood glucose levels are effectively controlled. However, these studies have small sample sizes, and more large-scale, long-term clinical studies are needed to verify their efficacy and safety.

6. Application Value and Development Direction of Dihydroberberine

Based on existing research evidence, dihydroberberine has good application prospects in the field of blood glucose management. Due to its ability to improve insulin sensitivity, promote glucose metabolism, and inhibit excessive hepatic glucose production, it can be used as an ingredient for auxiliary blood glucose regulation, applied in the intervention of pre-diabetic populations, auxiliary treatment of patients with type 2 diabetes, and other aspects. Compared with some traditional hypoglycemic drugs, dihydroberberine is derived from natural plants, with high safety and relatively few side effects, suitable for long-term use, which gives it unique advantages in the research and development of health products and drugs. However, since its specific metabolic process and action duration in the body have not been fully clarified, more in-depth research is needed to clarify them. In addition, the synergistic effect of dihydroberberine with other hypoglycemic drugs or ingredients is also worthy of study to find more efficient blood glucose management schemes.

7. Summary and Outlook

As an alkaloid derivative with good bioavailability, dihydroberberine plays a positive role in regulating blood glucose balance and reducing blood glucose through improving insulin sensitivity, promoting glucose metabolism and utilization, and inhibiting excessive hepatic glucose production. Animal experiments and preliminary clinical studies provide certain evidence for its efficacy, showing its application potential in the field of blood glucose management. In the future, with the deepening of research, it is expected to clarify the specific action details and clinical application standards of dihydroberberine, providing a more solid scientific basis for its wide application in diabetes prevention and treatment. It is believed that through further research and development, dihydroberberine will bring new health options for people with blood glucose imbalance.

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