Erythrina subumbrans (Hassk) Merr. (Fabaceae) Inhibits Insulin Resistance in the Adipose Tissue of High Fructose-Induced Wistar Rats.

Background: The twigs and roots of Erythrina subumbrans (Hassk). Merr. Was reported to possess antidiabetic activity by reducing the activity of α-glucosidase and α-amylase. TNF-α is a pro-inflammatory cytokine in obesity and diabetes mellitus (DM). It inhibits the action of insulin, causing insulin resistance. Adiponectin is an anti-inflammatory peptide synthesized in white adipose tissue (WAT) and its high levels are linked with a decreased risk of DM. However, information about the effect of Erythrina subumbrans (Hassk). Merr. on insulin resistance are still lacking. Purpose: To obtain the effects of the ethanol extract of E. subumbrans (Hassk) Merr. leaves (EES) in improving insulin resistance conditions. Methods: The leaves were collected at Ciamis, West Java, Indonesia, and were extracted using ethanol 96%. The effects of EES were studied in fructose-induced adult male Wistar rats by performing the insulin tolerance test (ITT) and assessing blood glucose, TNF-α, adiponectin, and FFA levels. The number of WAT and BAT of the adipose tissues was also studied. The total phenols and flavonoids in EES were determined by the spectrophotometric method and the presence of quercetin in EES was analyzed using the LC-MS method. Results: EES significantly reduced % weight gain, TNF-α levels, and increased adiponectin levels in fructose-induced Wistar rats. EES significantly reduced the FFA levels of fructose-induced Wistar rats and significantly affected the formation of BAT similar to that of metformin. All rats in EES and metformin groups improved insulin resistance as proven by higher ITT values (3.01 ± 0.91 for EES 100 mg/kg BW; 3.01 ± 1.22 for EES 200 mg/kg BW; 5.86 ± 3.13 for EES 400 mg/kg BW; and 6.44 ± 2.58 for metformin) compared with the fructose-induced group without treatment (ITT = 2.62 ± 1.38). EES contains polyphenol compounds (2.7638 ± 0.0430 mg GAE/g extract), flavonoids (1.9626 ± 0.0152 mg QE/g extract), and quercetin 0.246 µg/mL at m/z 301.4744. Conclusion: Erythrina subumbrans (Hassk). Merr. extract may have the potential to be further explored for its activity in improving insulin resistance conditions. However, further studies are needed to confirm its role in alleviating metabolic disorders.

Pharmacology activity, toxicity, and clinical trials of Erythrina genus plants (Fabaceae): an evidence-based review.

The concept of using plants to alleviate diseases is always challenging. In West Java, Indonesia, a local plant, named dadap serep has been traditionally used to reduce blood glucose, fever, and edema, by pounding the leaves and applying them on the inflamed skin, or boiled and consumed as herbal tea. This plant belongs to the Erythrina genus, which covers approximately 120 species. The scope of this review (1943-2023) is related to the Global Development Goals, in particular Goal 3: Good Health and Wellbeing, by focusing on the pharmacology activity, toxicity, and clinical trials of Erythrina genus plants and their metabolites, e.g., pterocarpans, alkaloids, and flavonoids. Articles were searched on PubMed and ScienceDirect databases, using "Erythrina" AND "pharmacology activity" keywords, and only original articles written in English and open access were included. In vitro and in vivo studies reveal promising results, particularly for antibacterial and anticancer activities. The toxicity and clinical studies of Erythrina genus plants are limitedly reported. Considering that extensive caution should be taken when prescribing botanical drugs for patients parallelly taking a narrow therapeutic window drug, it is confirmed that no interactions of the Erythrina genus were recorded, indicating the safety of the studied plants. We, therefore, concluded that Erythrina genus plants are promising to be further explored for their effects in various signaling pathways as future plant-based drug candidates.

Review of the Case Reports on Metformin, Sulfonylurea, and Thiazolidinedione Therapies in Type 2 Diabetes Mellitus Patients.

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 ß-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 ß-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 ß-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.

Antidiabetic Activity of Combination of Binahong (Anredera cordifolia Ten. Steenis), Cherry (Muntingia calabura L.) and Brotowali (Tinospora crispa L.) Extracts.

Background: Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia. Diabetes mellitus is a silent killer because sufferers are often not aware of it when it is realized, complications have occurred. Treatment for this disease must be done for life to control blood sugar in the body; however, oral antidiabetic drugs often produce unwanted side effects such as bloating, diarrhea, and stomach cramps. One of the treatments for diabetes is to find sources of treatment using natural ingredients that are relatively safe, including using plants as medicines. Based on several studies, Binahong leaves (Anredera cordifolia Ten. Steenis), brotowali (Tinospora crispa L.), and cherry (Muntingia calabura L.) are medicinal plants that can be used to reduce blood sugar levels. This study aims to test the antidiabetic activity using in vivo and in vitro testing methods of extracts of binahong leaves, cherry leaves, brotowali stems and their combinations. Methods: In vivo method uses animal modeling of insulin deficiency, whereas in vitro method with alpha glycosidase inhibition activity assay. The administration of extracts was repeated every day for 14 days and blood glucose levels were measured on the 0, 7th, and 14th days. Then surgery was performed on the pancreas and calculated the area of the islets of Langerhans, and the number of alpha and beta cells in the pancreas. The inhibitory activity of the alpha-glucosidase enzyme with the IC50 value of each extract and its combination was determined, with acarbose used as a standard. Result: The combination of binahong leaves (Anredera cordifolia Ten.Steenis) and cherry leaves (Muntingia calabura L.) and the combination of brotowali stems (Tinospora crispa (L.) and binahong leaves showed in vivo antidiabetic activity with insulin deficiency method. The combination of these extracts was able to reduce blood sugar levels until the observation on day 14. In in vitro testing by inhibiting alpha-glucosidase enzymes, binahong leaves extract, brotowali stems, and cherry leaves were able to inhibit alpha-glucosidase enzymes at IC50 of 35.07 ± 2.35; 29.42 ± 1.40; and 26.63 ± 1.15, respectively. Conclusion: The best combination of extracts by in vitro and in vivo methods was shown in the combination of binahong leaf and brotowal stem extract binahong leaves, brotowali stems (2:1).