Obesity is a risk factor that leads to the development of other diseases such as dyslipidemia and diabetes. These three metabolic disorders can occur simultaneously, hence, the treatment requires many drugs. Antioxidant compounds have been reported to have activities against obesity, dyslipidemia and diabetes via several mechanisms. This review aims to discuss the antioxidant compounds that have activity against obesity, dyslipidemia and diabetes together with their molecular signaling mechanism. The literature discussed in this review was obtained from the PUBMED database. Based on the collection of literature obtained, antioxidant compounds having activity against the three disorders (obesity, dyslipidemia and diabetes) were identified. The activity is supported by various molecular signaling pathways that are influenced by these antioxidant compounds, further study of which would be useful in predicting drug targets for a more optimal effect. This review provides insights on utilizing one of these antioxidant compounds as opposed to several drugs. It is hoped that in the future, the number of drugs in treating obesity, dyslipidemia and diabetes altogether can be minimized consequently reducing the risk of side effects.

Type 2 diabetes mellitus (T2DM) is the world’s most common metabolic disease. The development of T2DM is mainly caused by a combination of two factors: the failure of insulin secretion by the pancreatic β-cells and the inability of insulin-sensitive tissues to respond to insulin (insulin resistance); therefore, the disease is indicated by a chronic increase in blood glucose. T2DM patients can be treated with mono- or combined therapy using oral antidiabetic drugs and insulin-replaced agents; however, the medication often leads to various discomforts, such as abdominal pain, diarrhea or constipation, nausea and vomiting, and hypersensitivity reactions. A biguanide drug, metformin, has been used as a first-line drug to reduce blood sugar levels. Sulfonylureas work by blocking the ATP-sensitive potassium channel, directly inducing the release of insulin from pancreatic β-cells and thus decreasing blood glucose concentrations. However, the risk of the failure of sulfonylurea as a monotherapy agent is greater than that of metformin or rosiglitazone (a thiazolidinedione drug). Sulfonylureas are used as the first-line drug of choice for DM patients who cannot tolerate metformin therapy. Other antidiabetic drugs, thiazolidinediones, work by activating the peroxisome proliferator-activated receptor gamma (PPARγ), decreasing the IR level, and increasing the response of β-cells towards the glucose level. However, thiazolidines may increase the risk of cardiovascular disease, weight gain, water retention, and edema. This review article aims to discuss case reports on the use of metformin, sulfonylureas, and thiazolidinediones in DM patients. The literature search was conducted on the PubMed database using the keywords ‘metformin OR sulfonylureas OR thiazolidinediones AND case reports’, filtered to ‘free full text’, ‘case reports’, and ‘10 years publication date’. In some patients, metformin may affect sleep quality and, in rare cases, leads to the occurrence of lactate acidosis; thus, patients taking this drug should be monitored for their kidney status, plasma pH, and plasma metformin level. Sulfonylureas and TZDs may cause a higher risk of hypoglycemia and weight gain or edema due to fluid retention. TZDs may be associated with risks of cardiovascular events in patients with concomitant T2DM and chronic obstructive pulmonary disease. Therefore, patients taking these drugs should be closely monitored for adverse effects.

Type 2 diabetes mellitus (T2DM) is a chronic disease with high-cost treatment. This study aimed to analyze the cost-effectiveness of T2DM treatment in hospitalized patients with complications of kidney and peripheral vascular disease (PVD) in Indonesia by focusing on patients of Health Social Security Agency (BPJS Kesehatan). An observational study was applied by collecting data retrospectively from patients’ medical record at the biggest public hospital in West Java Province, Indonesia. Two perspectives of payer and healthcare provider were applied to estimate the treatment cost. We considered following inclusion criteria: (i) Hospitalized T2DM patients without complication, with complications of kidney and PVD during 2014–2017; (ii) member of BPJS Kesehatan; (iii) >18 years old patients; and (iv) patients with complete medical record data. The results showed that the majority patients were female (56.72%), 45–64 years old (69.40%), and had a length of stay at 4–10 days (54.48%). The greatest contributions in the total treatment cost were found to be hospital room, medical services and medicines for the treatment of T2DM without complications, with complications of kidney and PVD, respectively. From the perspective of payer, the incremental cost-effectiveness ratios (ICERs) of T2DM treatment with complications of kidney and PVD would be IDR 215,723 and IDR 234,591 per 1 mg/dL blood glucose reduction, respectively. From the perspective of healthcare provider, the ICERs of T2DM treatment with complications of kidney and PVD would be IDR 166,289 and IDR 681,853 per 1 mg/dL blood glucose reduction in both perspectives (1 US$ = IDR 13,451). In a comparison with T2DM without complication, reducing 1 mg/dL blood glucose in T2DM treatment with complication of PVD would require higher cost than in T2DM treatment with complication of kidney from both perspectives.

Bouea macrophylla Griffith (B. macrophylla) is one of the many herbal plants found in Asia, and its fruit is plum mango. This plant is rich in secondary metabolites, including flavonoids, tannins, polyphenolic compounds, and many others. Due to its bioactive components, plum mango has powerful antioxidants that have therapeutic benefits for many common ailments, including cardiovascular disease, diabetes, and cancer. This review describes the evolution of plum mango’s phytochemical properties and pharmacological activities including in vitro and in vivo studies. The pharmacological activities of B. macrophylla Griffith reviewed in this article are antioxidant, anticancer, antihyperglycemic, antimicrobial, and antiphotoaging. Each of these pharmacological activities described and studied the possible cellular and molecular mechanisms of action. Interestingly, plum mango seeds show good pharmacological activity where the seed is the part of the plant that is a waste product. This can be an advantage because of its economic value as a herbal medicine. Overall, the findings described in this review aim to allow this plant to be explored and utilized more widely, especially as a new drug discovery.

In Indonesia, plants have been indigenously used to treat various diseases and as cosmetics. It is always challenging to explore the molecular interactions of phenolic compounds towards the levels of constituents that contribute to the biological activities of plants. This study aimed to select a plant of the Zingiberaceae family with the highest phenolics and flavonoids, the strongest radical scavenging activity, and the best interaction towards tyrosinase in terms of docking score and binding mode. Initially, the total phenolics and radical scavenging capacity of Zingiberaceae plants, namely, Hedychium coronarium, Curcuma zedoaria, Curcuma heyneana, and Alpinia galanga, were determined using the Folin–Ciocâlteu method and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The main phytoconstituents of plants with the highest phenolic levels were docked to the binding site of tyrosinase. Three anti-melanogenesis agents commonly used in cosmetics, namely, arbutin, hydroquinone, and kojic acid, were used as the standard. Our study revealed that all the tested plants contain polyphenolic compounds in the range of 17.92 (C. zedoaria rhizome extract) to 252.36 (A. galanga rhizome extract) mg GAE/g and have radical scavenging capacity, with IC₅₀ values in the range of 66.67 (A. galanga rhizome extract) to 320.0 (C. heyneana rhizome extract) μg/mL. A molecular docking simulation demonstrated that four constituents, i.e., kaempferol, galangin, ethyl p-methoxycinnamate, and 6-gingerol, could occupy the binding site of tyrosinase with prominent affinity and interact with essential residues of the enzyme. This study confirms that Alpinia galanga possesses the potential to be further developed as a cosmetic with a radical scavenging and tyrosinase inhibitory activity. However, it may be interesting to carry out further studies of how the plant extract affects the melanogenesis signaling pathway.

Introduction: Tyrosinase is considered an important target of melanin biosynthesis inhibitors. Curcuma longa L. has been used in the Javanese traditional whitening cosmetics. This work aimed to explore the effect of C. longa extracts on mushroom tyrosinase activity and the cytotoxicity of the extract towards murine skin cancer B16F10 cells. Methods: C. longa rhizomes were cold-extracted using ethanol 70% and yielded 15.3% w/w of extract (ECL). The presence of curcuminoids in ECL was determined by reversed-phase high-performance liquid chromatography (RP-HPLC). ECL was assessed for its inhibitory effects on mushroom tyrosinase activity using L-DOPA as substrate and kojic acid as the positive control drug. The cytotoxicity of ECL and curcumin was studied in B16F10 cells. Results: Triplet peaks of RP-HPLC chromatogram revealed that curcuminoids were available in ECL. The level of bisdemethoxycurcumin was 6.3306% (tR = 12.646 minutes), demethoxycurcumin was 3.1414% (tR = 13.675 minutes), and curcumin was 8.3754% (tR = 14.802 minutes). ECL had a weak inhibitory activity towards mushroom tyrosinase with IC50 = 564.8 µg/mL, while the IC50 = of kojic acid was 55.70 µg/mL. Both ECL and kojic acid had moderate toxicity to B16F10 cells (IC50 survival growth rates were 98.06 µg/mL and 65.54 µg/ mL, respectively). Curcumin was highly toxic to B16F10 cells (IC50 = 14.42 µg/mL). Conclusion: Taken together, ECL might be able to prevent melanogenesis via the inhibition of tyrosinase activity, and interestingly, it could inhibit the growth of murine skin cancer B16F10 cells. However, further studies are needed to verify its antimelanogenesis and anticancer properties.