One of the oldest known disorders is diabetes mellitus (DM) in humans. It is assumed that DM due to the inherent stresses of modern lifestyles and the increasing prevalence of diabetes is becoming a major public health problem affecting millions of people worldwide. According to the World Health Organization (WHO), by 2025, 300 million people will have diabetes. Diabetes mellitus is a pathological disease, and as a result causes severe metabolic imbalances and abnormal changes in many tissues, especially in the pancreas, where an important role in etiology is played by oxidative stress. High oxidative stress because of persistent and chronic high blood sugar is tested in diabetic and experimental animal models, thus destroying the activity of the antioxidant defense system and thereby producing free radicals [1–3]. In diabetes mellitus, changes in the defense mechanisms of endogenous free radical scavenging may lead to ineffective inhibition of oxygen-reactive species, leading to oxidative damage and tissue damage. Tissue damage has been suggested and streptozotocin acts as a diabetic agent due to its ability to destroy pancreatic β-cells, possibly by the mechanism of free radicals [4, 5].
The pancreas is the synthesis, storage and secretion site of insulin. In the pancreatic islets, there is a complex signaling cascade for the secretion of glucose-stimulating insulin that includes ATP-sensitive potassium channels (KATP). In the presence of glucose, an increase in the intracellular ATP/ADP ratio causes the KATP channels to close, resulting in the plasma membrane depolarization, extracellular calcium influx, and exocytosis activation. The cell plasma membrane islet has KATP channels, although most KATP channels are located on secretory granule membranes. The KATP channels of pancreas have four sulfonylurea-regulating receptor subunits (SUR1) and four potassium pore-formation subunits (Kir6.2) . One of the chronic autoimmune diseases is type 1 diabetes (T1D) in which insulin-producing beta-cells in the pancreas are destroyed, resulting in chronic high blood sugar. Pancreatic exocrine abnormalities have been described in recent decades in terms of anatomy and function. It is not clear whether exogenous changes of in T1D are relevant to identical genetic, immunological, and environmental events that lead to the destruction of beta-cells and are secondary to functional β cell loss. Therefore, insulin acts as a trophic agent for the exocrine compartment .
The main goal of caring for diabetic patients is to minimize the risk of microvascular and macrovascular complications by returning blood pressure, and lipid and glycemic profiles to normal. The particular aim for glycemic control is to reach glycated hemoglobin (HbA1c) to a normal range because good glycemic control is important to decrease the long-term microvascular complication risk in both type 1 and 2 diabetes . HbA1c can be measured at any time of the day, regardless of the duration of the fast or the content of the previous meal. It can also be analyzed using a portable device with a small blood sample . Glycated hemoglobin (HbA1c) analysis in blood enables evidence of a person's average blood glucose level over the past two to three months, which is the red blood cell (RBC) half-life .
There is ample evidence that β-cell regeneration and function in the adult pancreas are mediated partly by pancreatic and duodenal homeobox 1 (Pdx1), and that changes in expression are associated with the alterations in the expression of target genes, including insulin 1 (Ins1) . Pdx1 is an important transcription factor needed for pancreatic development and maintains the distinctive function of β-cells, especially the regulation of normal glucose-insulin secretion [11, 12]. The first transcription factor produced in the growing pancreas is Pdx1, and lack of this factor causes pancreatic agenesis because of the inability to generate a variety of duct, exocrine or endocrine cells. Conditional elimination of Pdx1 from β cell formation by insulin Cre lines leads to hyperglycemia [13, 14]. Previous studies have shown that Pdx1 plays a major role in diabetes and that reducing the expression of Pdx1 exacerbates diabetes [15, 16].
Scrophularia striata, known as “Teshnedari” from the Scrophulariaceae family, is one of the most important herbal medicines that is widely used in western Iran. This herb is an annual or perennial plant that has a zygomorphic flower and 5 petals flower, and the calyx has lobes and its fruit is a capsule with many seeds. It has been reported that Scrophularia striata has some medicinal effects including analgesic, antimicrobial, nephrotic, nitric oxide suppressant, antitumor, hepatic protection and anti-inflammatory effects [17–20]. Due to the medicinal effects of Scrophularia striata plants and their side effects, they have not been studied thus far. In this study, using an animal model, the effects of this plant were investigated in preventing diabetes-induced damage to the pancreas and its functions.