The global prevalence of diabetes mellitus in adults increased by 463 million (6.20%) in 2020 (International Diabetes Federation, 2019). In addition, diabetes mellitus was responsible for 6.70 million deaths in 2021. This means there is 1 death every 5 seconds. It increases the risk of diseases such as heart attack, stroke, blindness, nephropathy, and gangrene (World Health Organization, 2016). More than 80 million people are estimated to have diabetes mellitus in Southeast Asia and the Asia-Pacific countries. In Indonesia, the prevalence of diabetes mellitus increased by 2% from 2013 to 2018 (Ministry of Health of Indonesia, 2018). In Surabaya, a large city in Indonesia and the capital of East Java Province, diabetes mellitus is the disease with the fourth highest mortality rate (Ministry of Health of Indonesia, 2017). It contributes to the development of cardiovascular disease risk, and obesity is the major contributing factor to cardiovascular disease and diabetes mellitus. An increased leptin concentration in patients with obesity reduces the response of pancreatic β-cell, resulting in increased insulin secretion and likely leading to hyperinsulinemia. Leptin regulates BG concentrations by increasing insulin sensitivity of liver and muscle cells in normal conditions (Majewska et al., 2016).
Generally, the leptin: adiponectin ratio is significantly associated with the incidence of diabetes mellitus among teenagers with obesity (Maahs et al., 2009). Leptin and adiponectin are produced in the adipose tissue and are involved in regulating insulin sensitivity and inflammation (Safai et al., 2015). Adiponectin has antidiabetic functions, strengthens insulin signaling pathways, reduces glucose production in the liver, increases fatty acid oxidation, improves mitochondrial function, and regulates glucose metabolism in the liver and muscles (López-Jaramillo et al., 2014; Chakraborti, 2015). Synthetic drugs are used to decrease blood glucose concentrations in patients with diabetes mellitus; however, these drugs have many side effects on human health. Traditional medicine using medicinal plants is an alternative for disease prevention and treatment. One of the plants with medicinal potential is Tithonia diversifolia, which is traditionally used to prevent stomach pain, bloating, diarrhea, and inflammation. T. diversifolia leaves, roots, stems, fruits, and seeds are sources of chemicals. For example, T. diversifolia leaves contain active substances (phytochemicals), such as alkaloids, saponins, saponin glycosides, tannins, balsam, and volatile oils (John-Dewole and Oni, 2013). T. diversifolia also has antidiabetic potential; it is commonly known as the insulin plant among Indonesians. A critical component in the pathogenesis of diabetes is insulin.
Insulin, an important hormone produced by pancreatic β-cells, regulates glucose homeostasis in various tissues. The mechanism of action of insulin includes inhibiting gluconeogenesis, stimulating glycogen synthesis, and activating lipogenesis in the liver (Hirako, 2016). In muscle and fat tissues, insulin induces glucose uptake through the insulin receptor (IR) activation pathway. The IR substrate is activated through the activation of phosphoinositide 3-kinase and phosphoinositide-dependent kinase-1 for protein synthesis, cell development, transcription, and glycogen synthesis. Insulin also plays a role in regulating cell growth and proliferation (Samarghandian et al., 2017).
The study, conducted by Muniroh, et al (2002) aims to evaluate the effect of Tithonia diversifolia extract (TDE) on leptin, adiponectin, and insulin receptor (IR) concentrations in diabetic, streptozotocin-induced rats. It is revealed that giving T. diversifolia leaf extract can reduce leptin and CD14 macrophages and increase adiponectin concentration and insulin receptors.
Twenty-four Wistar rats were divided into control and treatment groups (n=6 per group). The control group received normal saline, and the treatment groups received 0.25% sodium carboxymethyl cellulose, TDE at 100 mg/kg body weight (bw), and catechin at 10 mg/kg bw for 7 days. On day 8, the rats were sacrificed, blood samples were obtained, and leptin, adiponectin, and insulin concentrations were measured using avidinhorseradish peroxidase sandwich-enzyme-linked immunosorbent assay. A calorimetric method was used to measure blood glucose (BG) and total serum cholesterol concentrations. The pancreas and kidneys were collected for the measurement of renal IR and macrophage cluster of differentiation CD14 levels using immunohistochemical staining. Acute type 2 diabetes mellitus (T2DM) with elevated BG and total serum cholesterol concentrations was observed in the treatment groups administered streptozotocin. The study demonstrated that T. diversifolia leaf extract decreases leptin and BG concentrations by increasing IR expression and reduces pancreatic tissue necrosis by suppressing macrophage CD14 concentrations in rats with STZ-induced diabetes.
Author: Lailatul Muniroh, S.KM., M.Kes.
Journal: Effect of Tithonia diversifolia Leaf Extract on Leptin, Adiponectin, and Insulin Receptor Levels in Diabetic Rats
