Diabetes Mellitus (DM) is a pathology caused by the inability to metabolize glucose. There are two forms of the disease, differentiated by the age at which metabolic disorders appear: type 1 DM (which occurs from childhood due to genetic causes) and type 2 DM. The latter is the most predominant, accounting for 90–95% of cases, and originates mainly due to age or following an unhealthy lifestyle. Specifically, type 2 DM is a multifactorial disease where stress and inflammation lead to interference in cellular glucose uptake, an increase in monosaccharide demand, and the breakdown of fatty acids, among other metabolic defects (1). Oxidation substances produced in the mitochondria due to stress or environmental factors, such as age or a sedentary lifestyle, lead to damage in the pancreatic β-cells. Thus, either through a reduction in insulin secretion or abnormalities in insulin receptor signaling, the body triggers resistance to this hormone (2). On the other hand, the aforementioned inflammation affects not only the pancreas but also gives rise to other complications in common organs affected by this disease, such as nephropathies, neuropathies, retinopathies, and vascular damage.
The treatment of type 2 DM consists of following a healthy lifestyle, avoiding obesogenic factors, and regularly practicing sports to reduce the accumulation of glucose in the blood. In cases of necessity, fundamentally in patients with type 1 DM or who are insulin-dependent, the administration of exogenous insulin is required (2). Antidiabetic drugs can also be used to achieve an optimal glycemic index; however, the long-term therapeutic effect of these medications in type 2 diabetes has not yet been defined, nor has their ability to prevent complications regarding the cardiovascular system or reduce side effects such as weight gain or reduced bone mass. For example, one of the most widely used is metformin, which causes gastrointestinal problems and is contraindicated in cases of renal, hepatic, and respiratory failure (3).
Various medicinal plants allow for a mild but significant treatment of DM complications without exhibiting as much toxicity or side effects as those mentioned above with pharmaceutical drugs, while also reducing frequency and dosage; this makes them an alternative for the treatment of the disease. Furthermore, another advantage of medicinal plants over drugs is that more than one plant can be included to treat other pathologies such as obesity, dyslipidemia, or hypertension through various metabolic pathways, whereas a medication usually contains only one active ingredient.
Among these medicinal extracts, plants of the genus Berberis stand out, having attracted attention for both their hypoglycemic and hypolipidemic capabilities. These two actions are due to berberine, a compound derived from the isoquinoline alkaloid (4). In addition to these properties, many studies have attributed other therapeutic properties to it, such as antioxidant, anti-inflammatory, and antiarrhythmic activities, or improvements in the treatment of diabetic nephropathy, neuropathy, and cardiomyopathy. On the other hand, it is also believed to be effective in treating other chronic diseases besides DM, such as hypertension, hyperlipidemia, cancer, or depression.
The hypoglycemic activity of berberine is due to the stimulation of glycolysis by increasing glucokinase activity through signaling pathways, the increase in insulin secretion, and the suppression of hepatic gluconeogenesis and adipogenesis. It is known that treatment with berberine increases the phosphorylation of protein kinase B, which produces an increase in AMPK activation; this, in turn, increases the translocation of the GLUT-4 transporter in the cell’s plasma membrane, thereby improving insulin sensitivity and resistance. On the other hand, berberine was shown to increase insulin secretion in islet cells through elevated levels of GLP-1 (glucagon-like peptide-1). GLP-1 receptors are important components involved in islet cell survival. GLP-1 activation of adenylate cyclase increases cyclic AMP levels, leading to increases in intracellular Ca2+ and stimulating the migration and exocytosis of insulin granules (4). We can also mention the role of berberine in reducing intestinal glucose absorption due to the inhibition of α-glucosidase, an enzyme responsible for digesting carbohydrates by reducing them to monosaccharides. Finally, another hypoglycemic activity of berberine consists of modulating the gut microbiota. Due to berberine’s antimicrobial effect, it could displace viruses, bacteria, fungi, and even parasitic worms. The genera Firmicutes and Bacteroidetes are types of intestinal bacteria responsible for modulating metabolic homeostasis. With a high-fat and unhealthy diet, the Firmicutes genus is increased while Bacteroidetes is reduced, a ratio associated with a higher risk of suffering from obesity, diabetes, and hypercholesterolemia. Thus, it has been observed that using berberine modulates this ratio toward a higher content of Bacteroidetes, which help control weight and reduce blood glucose and lipid levels (4).
The growing number of people with DM is driving the search for more options beyond pharmaceuticals to treat this disease, especially in Asian countries where prevalence is higher. Numerous clinical studies have demonstrated the efficacy of berberine’s hypoglycemic effect as well as its safety when used alone or with other drugs such as metformin. Results in patients with type 2 DM treated with berberine or metformin showed that levels of HbA1c (glycated hemoglobin), triglycerides, and LDL-C decreased in both groups, with a significant difference between before and after treatment (5). Furthermore, the hypoglycemic effect of berberine was similar to that of metformin, with berberine doses ranging between 200 and 500 mg, 2 or 3 times a day. Overall, berberine is safe in the treatment of patients with type 2 DM and, due to its low toxicity, could be used in diabetic patients with chronic hepatitis, renal failure, or respiratory problems where the use of medications like metformin is contraindicated.
- American Diabetes Association (2011). Diagnosis and classification of diabetes mellitus. Diabetes care, 34 Suppl 1(Suppl 1), S62–S69. https://doi.org/10.2337/dc11-S062
- Guthrie, Richard A.; Guthrie, Diana W. (2004). Pathophysiology of Diabetes Mellitus. Critical Care Nursing Quarterly, 27(2), 113–125. doi:10.1097/00002727-200404000-00003
- Crespo Herrera, Sonia. (2009). Metformina, a 50 años de su uso: Eficacia, tolerancia, seguridad y nuevas indicaciones. Revista Científica Ciencia Médica, 12(2), 23-25. Retrieved November 03, 2021, from http://www.scielo.org.bo/scielo.php?script=sci_arttext&pid=S1817-74332009000200009&lng=es&tlng=es.https://pubmed.ncbi.nlm.nih.gov/15137354/
- Chang, Wenguang; Chen, Li; Hatch, Grant M. (2014). Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies. Biochemistry and Cell Biology, (), 1–8. doi:10.1139/bcb-2014-0107
- Pang B, Zhao LH, Zhou Q, Zhao TY, Wang H, Gu CJ, Tong XL. (2015). Application of berberine on treating type 2 diabetes mellitus. Int J Endocrinol. 2015;2015:905749. doi: 10.1155/2015/905749. Epub 2015 Mar 11. PMID: 25861268; PMCID: PMC4377488.