Diabetes mellitus (DM) is a metabolic disorder that causes hyperglycemia conditions and leads to various chronic complications that causes death. The prevalence of diabetes is predicted to continue to increase, and with the high toxicity levels of current diabetes drugs, the exploration of natural compounds as alternative diabetes treatment has been widely carried out, one of which is berberine. Berberine and several other alkaloid compounds, including some of its derivatives, have shown many bioactivities, such as neuraminidase and hepatoprotective activity. Berberine also exhibits antidiabetic activity. As an antidiabetic compound, berberine is known to reduce blood glucose levels, increase insulin secretion, and weaken glucose tolerance and insulin resistance by activating the AMPK pathway. Apart from being an antidiabetic compound, berberine also exhibits various other activities such as being anti-adipogenic, anti-hyperlipidemic, anti-inflammatory, and antioxidant. Many studies have been conducted on berberine, but its exact mechanism still needs to be clarified and requires further investigation. This review will discuss berberine and its mechanism as a natural compound with various activities, mainly as an antidiabetic.

Diabetes mellitus is a group of metabolic disorders characterized by hyperglycemia caused by resistance to insulin action, inadequate insulin secretion, or excessive glucagon production. Numerous studies have linked diabetes mellitus and oxidative stress. People with diabetes usually exhibit high oxidative stress due to persistent and chronic hyperglycemia, which impairs the activity of the antioxidant defense system and promotes the formation of free radicals. Recently, several studies have focused on exploring natural antioxidants to improve diabetes mellitus. Fibraurea tinctoria has long been known as the native Borneo used in traditional medicine to treat diabetes. Taxonomically, this plant is part of the Menispermaceae family, widely known for producing various alkaloids. Among them are protoberberine alkaloids such as berberine. Berberine is an isoquinoline alkaloid with many pharmacological activities. Berberine is receiving considerable interest because of its antidiabetic and antioxidant activities, which are based on many biochemical pathways. Therefore, this review explores the pharmacological effects of Fibraurea tinctoria and its active constituent, berberine, against oxidative stress and diabetes, emphasizing its mechanistic aspects. This review also summarizes the pharmacokinetics and toxicity of berberine and in silico studies of berberine in several diseases and its protein targets.

Melanogenesis is a biochemical process that regulates skin pigmentation, which is crucial role in protecting against ultraviolet radiation. It is also associated with hyperpigmentation conditions such as melasma and age spots, which negatively impact aesthetics and self-confidence. Tyrosinase (TYR), a key enzyme in the melanogenesis pathway, catalyzes the biosynthesis of melanin in the skin. Inhibition of tyrosinase particularly by blocking its active site and preventing the binding of natural substrates such as tyrosine, can reduce melanin production, making it a promising therapeutic target for treating hyperpigmentation. Peptides have emerged as promising therapeutics to regulate melanogenesis by minimizing the side effects associated with conventional skin whitening therapeutics. This review is designed to offer a comprehensive analysis of current strategies in peptide design aimed at optimizing anti-melanogenic activity, by focusing on the role of molecular weight, polarity, and cyclization strategies in enhancing peptide efficacy and stability. It was found that optimal peptide size was within the range of 400– 600 Da. The balance between hydrophilic and hydrophobic properties in peptides is crucial for effective TYR inhibition, as higher hydrophilicity enhances affinity for the TYR active site and stronger catalytic inhibition, while hydrophobicity can contribute through alternative mechanisms. Cyclization of peptides enhances their structural stability, serum resistance, and binding affinity while reducing toxicity. This process increases resistance to enzymatic degradation and improves target specificity by limiting conformational flexibility. Additionally, the rigidity and internal hydrogen bonding of cyclic peptides can aid in membrane permeability, making them more effective for therapeutic use. Peptide optimizations through size modification, polarity change, and cyclization strategies have been shown to be promising as reliable and safe agents for melanin inhibition. Future studies exploring specific amino acid in peptide chains are required to improve efficacy and potential clinical applications of these anti-melanogenic peptides as a hyperpigmentation treatment.

The mutation rate of mitochondrial DNA (mtDNA) is 17 times higher than nuclear DNA, and these mutations can cause mitochondrial disease in 1 of 10.000 people. The T10609C mutation was identified in type 2 diabetes mellitus (T2DM) patients and the C10676G mutation in cataract patients, with both mutations occurring in the ND4L gene of mtDNA that encodes ND4L protein. ND4L protein, a subunit of complex I in the respiratory complex, has been shown to play a role in the proton translocation process. The purpose of this study was to investigate the effect of both mutations on the proton translocation mechanism. Mutation mapping showed changes in amino acids M47T (T10609C) and C69W (C10676G). The 100 ns molecular dynamics (MD) simulations performed on native and mutants of ND4L-ND6 subunits. It is revealed that the native model had a similar proton translocation pathway to that of complex I from other organisms. Interestingly, the mutant M47T and C69W showed the interruption of the translocation pathway by a hydrogen bond formation between Glu34 and Tyr157. It is observed that the mutations were restricting the passage of water molecules through the transmembrane region. These results could help to develop the computational assay for the validation of a specific genetic biomarker for T2DM and cataracts.

Background and purpose: The increase in diabetes cases has become a major concern in the healthcare sector, necessitating the development of efficient and minimal diagnostic methods. This study aims to provide a comprehensive examination of electrochemical biosensors for detecting diabetes mellitus biomarkers, with a special focus on the utilization of carbon-based electrodes. Review approach: A detailed analysis of electrochemical biosensors incorporating various carbon electrodes, including screen-printed carbon electrodes, glassy carbon electrodes, and carbon paste electrodes, is presented. The advantages of carbon-based electrodes in biosensor design are highlighted. The review covers the detection of several key diabetes biomarkers, such as glucose, glycated hemoglobin (HbA1c), glycated human serum albumin (GHSA), insulin, and novel biomarkers. Key results: Recent developments in electrochemical biosensor technology over the last decade are summarized, emphasizing their potential in clinical applications, particularly in point-of-care settings. The utilization of carbon-based electrodes in biosensors is shown to offer significant advantages, including enhanced sensitivity, selectivity, and cost-effectiveness. Conclusion: This review underscores the importance of carbon-based electrodes in the design of electrochemical biosensors and raises awareness for the detection of novel biomarkers for more specific and personalized diabetes mellitus cases. The advancements in this field highlight the potential of these biosensors in future clinical applications, especially in point-of-care diagnostics.

Diabetes is a chronic disease with a high mortality rate worldwide and can cause other diseases such as kidney damage, narrowing of blood vessels, and heart disease. The concomitant use of drugs such as metformin, sulfonylurea, miglitol, and acarbose may cause side effects with long-term administration. Therefore, natural ingredients are the best choice, considering that their long-term side effects are not significant. One of the compounds that can be used as a candidate antidiabetic is mangostin; however, information on the molecular mechanism needs to be further analyzed through molecular docking, simulating molecular dynamics, and testing the in silico antidiabetic potential. This study focused on modeling the protein structure, molecular docking, and molecular dynamics simulations and analyses. This process produces RMSD values, free energies, and intermolecular hydrogen bonding. Based on the analysis results, all molecular dynamics simulations can occur under physiological conditions, and γ-mangostin is the best among the test compounds.