Diabetes mellitus (DM) is a fast-growing health problem that causes significant economic burden worldwide, especially the adult-onset or type 2 diabetes mellitus (T2DM) (Arokiasamy et al., 2021). It was reported that the global prevalence of diabetes among adults has reached alarming levels all over the world; it was nearly 9.4% in the year 2019, which indicated approximately 462 million adults had DM worldwide, and this number would increase to 700 million in 2045 (Alp et al., 2023).

The increased incidence of known risk factors for T2DM, such as physical inactivity, obesity, and unhealthy diet, increased the morbidity and mortality of the world population (Arokiasamy et al., 2021).

In the early stages of T2DM, oxidative stress, together with other factors, upregulated the activation of AMP-activated protein kinase (AMPK) and enhanced pancreatic beta cell survival and function. However, in chronic cases, chronic oxidative stress conditions can be the result of the continuous production of reactive oxygen species that chronically activate AMPK and result in damage to pancreatic beta cells with repressed insulin release (Fu et al., 2013). Therefore, reducing inflammation and oxidative stress can be one of the main therapeutic objectives for managing T2DM (Vivó-Barrachina et al., 2022). Seeds and nuts can be useful sources for the aforementioned therapeutic targets for T2DM. Their bioactive components have high nutraceutical and medicinal value (Shalaby et al., 2015; El-Deen et al., 2018; El-Deen et al., 2019; El-Deen et al., 2024). They proved to be beneficial in controlling body weight, blood glucose levels, and blood pressure, along with reduction of coronary heart disease and levels of blood cholesterol and triacylglycerol (Sater et al., 2016; Shalaby et al., 2016; El-Deen et al., 2018; Jugran et al., 2021).

Apricot (Prunus armeniaca L.) is a fruit that belongs to the genus Prunus of the Rosaceae family. The fruits contain a kernel enclosed in a stone seed. The kernel can be a food by-product for its high content of dietary protein (14%–45%), oil (28%–66.7%), and phytochemicals such as phenolic compounds, carotene, phytosterols, and tocopherol (Mohamed et al., 2021). Apricot kernel contains caffeic acid and gallic acid, which are used in anti-asthmatic, antiseptic, sedative, emetic, and laxative medicinal preparations. It can also be beneficial in the treatment of various diseases such as cardiovascular disease and breast cancer (Akhone et al., 2022; Hamid et al., 2022). They can also be used in developing a source of antioxidant biocompounds and some hypoglycemic agents like anthocyanin (Akbari et al., 2022).

Caffeine (1,3,7-trimethylxanthine) is present in different sources, mainly coffee, tea, and soft drinks (Heckman et al., 2010). Coffee contains several bioactive compounds that are well known for being antioxidants (Cämmerer and Kroh, 2006; Neves et al., 2018). Antioxidants have been shown to reduce diabetes complications by improving cell function in animal models, suggesting that enhancing antioxidant defense mechanisms in pancreatic islets may be a valuable pharmacologic approach to managing diabetes. Several studies have demonstrated that a higher consumption of coffee is associated with a lower risk of developing T2DM (Huxley et al., 2009; Muley et al., 2012; Bidel and Tuomilehto, 2013).

Our hypothesis is that apricot kernel can reduce the blood glucose concentration in type 2 diabetic patients and may also reduce complications resulting from chronic uncontrolled diabetes because it contains antioxidants and some hypoglycemic agents. So, the aim of this work was to study the effect of apricot kernel with or without caffeine on blood glucose concentration and lipid and antioxidant profiles in diabetic rats.

In this study, T2DM was induced in male albino rats fed with a high-fat diet for 3 weeks, followed by a low dose of streptozotocin (Nath et al., 2017). Low streptozotocin doses partially damage pancreatic beta cells and cause the breakage of DNA strands (Szkudelski, 2001). The alkylation of DNA is followed by cell death, and then consequently, an increase in blood sugar levels. Both a high-fat diet and streptozotocin mimic the human syndrome T2DM (Rais et al., 2022). Apricot kernel oil contains some biologically active substances, such as β-carotene, phenolic compounds, campesterol, stigmasterol, sitosterol, and provitamin A (Fratianni et al., 2018). The presence of tocopherols, vitamin C, saponins, oleic acid, and amygdalin in apricot kernel boosts its antioxidant activity and anti-lipemic capacity (Dawod and Ahmed, 2021). Specifically, 100 mg/kg of amygdalin can increase gene expression of glutathione peroxidase and superoxide dismutase in the hepatic tissue of mice (Dawod and Ahmed, 2021).

The reduction of blood glucose levels is the primary therapeutic goal for controlling diabetes (Ceriello et al., 2022). In the present study, the blood glucose level of diabetic rats was significantly decreased when treated with apricot kernels, and this effect was synergized when the kernel was combined with caffeine. The reduction of blood glucose may be either due to the increased level of plasma insulin in diabetic rats, which may influence the stimulation of pancreatic insulin secretion from beta cells in islets of Langerhans, or due to the enhanced transport of blood glucose to peripheral tissue. The mass loss and functionality of pancreatic beta cells have been the major concerns in the pathogenesis of T2DM (Dawood et al., 2023). Functional improvement by increasing the expression of genes linked to beta cell function and insulin biogenesis is one of the mechanisms of the apricot kernel in boosting insulin secretion (Anwar et al., 2018) and improving insulin sensitivity, which is an important therapeutic approach to treating T2DM (Blahova et al., 2021). It could also improve glucose tolerance, augment energy expenditure, and reduce adiposity (Szkudelski, 2001); apricot kernels can be considered a hypoglycemic agent, protecting beta cells, improving their function ability, and acting as hepatoprotective agents (Peng et al., 2023).

Hyperglycemia is accompanied by dyslipidemia, characterized by an increase in TC, LDL, and TG and a fall in HDL. This altered serum lipid profile was reversed to normal after treatment with metformin, as mentioned by Mullugeta et al. (2012). In this study, there was an increase in plasma TG, TC, and LDL-C fractions along with a decreased HDL-C level in the diabetic control group. The HDL-C levels in diabetic and non-diabetic rats fed with apricot kernels were found to be higher compared to the diabetic control group, an indication of a beneficial effect of the apricot kernels, while TG, TC, and LDL levels were decreased in both diabetic and non-diabetic rats fed with apricot kernels. Similarly, consumption of apricot kernels daily had a positive effect on lowering plasma TC and LDL-C in patients with dyslipidemia without a significant effect on plasma cholesterol levels (Zibaeenezhad et al., 2017; Kopčeková et al., 2021; Kopčeková et al., 2022). Furthermore, it reduced hepatic lipid synthesis by decreasing the activity of lipogenic enzymes and increasing hepatic lipolytic enzymes, consequently lowering plasma TG (Sun et al., 2020; Dinda and Dinda, 2022; Kopčeková et al., 2022). The possible mechanism of the anti-hyperlipidemic effect of caffeine might include the changed activity of cholesterol biosynthesis enzymes and/or the changed level of lipolysis, which are under the control of insulin, as mentioned by Zhang et al. (2013). It is reported that caffeine treatment could decrease the capacity of LDL to carry free cholesterol to various tissues without affecting the capacity of HDL to carry cholesterol back to the liver in rats (Ontawong et al., 2019). In addition, apricot kernel treatment can correct hyperlipidemia in rats, as reported by Kutlu et al. (2009). Our results indicated that the lipid-lowering effect could be an indirect consequence of amelioration of insulin resistance or a direct hypolipidemic effect mediated through other mechanisms.

Apricot mostly contains phytochemicals that reduce the risk of free radicals, which cause oxidative damage in living cells and common degenerative disorders such as cancer and cardiovascular diseases; the major anti-inflammatory compounds are acetylcholinesterase (Vahedi-Mazdabadi et al., 2020). Cyclooxygenase, interleukin 6, prostaglandin, Toll-like receptors, and tumor necrosis factor alpha (Huang et al., 2011). The antioxidant potential of apricot has been repeatedly investigated through different in vitro systems by measuring its ability to reduce free radicals and comparing it with standard reference compounds (Arora et al., 2017). Tissue MDA content, the final product of lipid breakdown caused by oxidative stress, is an important indicator of free radical-induced lipid peroxidation (Tsikas, 2017). In our study, there was a significant decrease in MDA in diabetic rats treated with apricot and caffeine, which indicates the positive effect of apricot kernels as an antioxidant. MDA is one of the final products of polyunsaturated fatty acid peroxidation in the cells (Tsikas, 2017). An increase in free radicals causes overproduction of MDA. Therefore, it is commonly known as a marker of oxidative stress and the antioxidant status in patients (Demirci-Cekic et al., 2022). There was a significant increase in GPx in diabetic rats treated with apricot and caffeine, which are the most important selenoenzymes due to their role in a diverse range of biological functions, including the detoxification of H₂O₂ and hydroperoxides (Lima-Cabello et al., 2023). The catalase activity was significantly increased in diabetic rats treated with apricot and caffeine. Measurements of catalase activity function as a good evaluating tool for assessing the liver’s capacity to attenuate the inclination toward oxidative stress (Sousa et al., 2020).

Caffeine had a similar effect to kernel on blood glucose level, HDL-C, HbA1c, and GPX; conversely, the kernel has a better effect on other parameters such as lipid profile and insulin. Caffeine did not exceed kernel in any tested parameter; however, the addition of caffeine to kernel improved its effect in all tested parameters.

In the study of Ramli et al. (2021), caffiene was shown to reduce the risk of metabolic syndrome. It was found to reduce waist circumference, triglyceride levels, low-density lipoprotein-cholesterol levels, and blood pressure. In a systematic review of the effect of caffeine therapy on cardiometabolic markers in rat models of the metabolic syndrome, out of 228 studies retrieved from the search, caffeine was found to favorably reduce obesity and insulin resistance in the rat model of the metabolic syndrome (Alhadi et al., 2023). In the current study, caffeine had a similar effect to kernel on blood glucose level, HDL-C, HbA1c, and GPX; conversely, kernel has a better effect on another parameter, although caffeine yielded no better result than kernel in any parameter. The addition of caffeine to kernel improved its effect on all tested parameters. The study of caffeine and kernel needs more advanced and deeper research.

In conclusion, apricot kernel helped reduce blood glucose levels and lipid content and increase plasma insulin, in addition to its antioxidant effect. The addition of caffeine augments its beneficial properties. The apricot kernel has excellent therapeutic properties and can be considered a potential ingredient in many drugs and food supplements due to its cost effective and ecofriendly nature. Moreover, further work is necessary to elucidate in detail the mechanism of action of the apricot kernel at the cellular and molecular levels.