1. Introduction
Dyslipidemia is one of the major risk factors of cardiovascular disease (CVD) and chronic non-communicable diseases (NCDs) and is characterized by an increase in one or more abnormal serum lipid concentrations of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C), which contribute to raising morbidity and mortality rates globally. This affects both health and economic status and raises worldwide healthcare costs [
1,
2]. Dyslipidemia is divided into primary and secondary types. Primary dyslipidemia is genetic and secondary dyslipidemia is acquired, as it is caused by obesity or diabetes [
3]. Dyslipidemia can damage blood vessels by triggering oxidative stress, inflammation, and immune dysregulation [
4,
5]. The use of herbalism and bioactive compounds from plants has increased worldwide because of their beneficial impacts on cardiovascular diseases, dyslipidemia, and diabetes. Moreover, the side effects associated with medicinal plants are fewer than those associated with chemical medications [
6]. Therefore, many people prefer to improve their lipid profile through dietary interventions or at least by integrating dietary changes with medication treatment. The use of plant-based medicines is not related to their positive effects on cholesterol, but to the fact that dietary supplements are perceived (erroneously) to be safer for consumers. The breakthrough in the use of dietary supplements for the prevention of diseases related to high cholesterol levels is related to the discovery of fermented red rice. Specifically, rice upon fermentation by
Monascus purpureus allows for the production of monacolin, which is structurally equivalent to lovastatin. However, equally to other statins, monacolin K displayed anaphylaxis, hepatotoxicity, central nervous system complaints, rhabdomyolysis effects, and a high possibility of developing diabetes mellitus. This is the motivation because the search for new therapeutic plants for the control of cholesterol levels is important today, as is finding a new anti-cholesterolemic agent that can prevent high levels of cholesterol with mechanisms different from states [
7].
Barley (
Hordeum vulgare L.) is an ancient plant of the Poaceae family and an essential cereal crop that is increasing worldwide due to high demand, covering about 9.4% of the world cereal production area [
8]. Due to its nutritional value and the high amounts of biologically active compounds that are present in barley, there is a growing interest in its use as a component in food products, among all cereals. Barley grains contain the highest amount of β-glucans and other bioactive compounds with beneficial effects, such as phenolic compounds, vitamin C, tocols, and sterols [
9,
10]. The phytochemicals present in barley exhibit a high anti-oxidative ability, immunostimulant potentials, and anti-inflammatory effects. In addition, it has been proven previously that they can suppress LDL cholesterol while raising HDL cholesterol levels [
11]. The germination approach improves the nutritional value and increases the bioactive components in grains [
12].
Additionally, germination softens the granular structure, improves the digestibility of grains and seeds, and reduces anti-nutritional components [
12,
13]. Furthermore, [
12] reported that germinated barley (GB) improves the lipid profile in rats with steatohepatitis by feeding them a high-fat diet. However, limited reports were completed regarding the potential use of germinated barley in reducing lipid release after feeding rats with HFD.
Ajwa date (AD,
Phoenix dactylifera L.) is one of the most abundant and popular dates and is cultivated in Al Madinah, western Saudi Arabia. Ajwa date has high nutritional and great medicinal value [
14]. Fresh dates contain high amounts of antioxidants, carotenoids, anthocyanins, phenolics, and free and bound phenolic compounds among fruit varieties. Moreover, it contains very high levels of phenolics due to its exposure to high temperatures and a hot climate [
15]. According to traditional and alternative medicine, AD dates provide several health benefits, including anticholesteremic, anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, and anticancer effects [
16]. A previous study has shown the therapeutic potential of AD in rats treated with isoproterenol to induce myocardial infarction. This study reported that the oral administration of Ajwa extract improved blood lipid profile, inflammation, and cardio-protectiveness, alongside having strong antioxidants [
17].
Based on the therapeutic effects of AD and GB, we hypothesized that the mixture of GB and AD would enhance the lipid profile and liver enzymes after feeding rats with HFD. Thus, the present study was designed firstly to determine the germination’s effect on barley’s phytochemical contents. Secondly, this study aimed to investigate the effect of the Ajwa date (AD) and germinated barley (GB) on the lipid profile in rats fed a high-fat diet (HFD).
4. Discussion
Recently, with the increase in ultra-processed foods, diets are enriched with different types of fats, resulting in hyperlipidemia (HYL), obesity, and cardiovascular diseases. Significant increases in TC, TG, VLDL, and LDL and decreases in HDL are the main categories for hyperlipidemia. Consequently, ameliorating HYL is substantial for avoiding and remedying cerebrovascular and cardiovascular syndromes and dropping social stress. In the current study, the authors described the potential of AD and GB in reducing the lipid profile due to their antihyperlipidemic and antioxidant effects. The mixture of AD and GB can effectively reduce lipid profile (TC, TG, VLDL, and LDL) in rats and increase HDL fed with HFD, as demonstrated in the present study.
The chemical composition of the barley before and after germination was analyzed to measure the effectiveness of germination on the barley with a high percentage of protein, vitamin C, and lower contents of fats for GB. This diversity of components between the seed and germinated barley may lead to the production of some amino acids during protein biosynthesis [
34]. Moreover, decreased percentages of fat in the germinated barley may lead to the breakdown of lipids into simpler compounds during the germination process [
35], and improve the beta oxidation of fats to provide more energy for cellular activity [
36]. A decrease in the beta-glucan fiber content of barley after germination was also observed in these results. These results agree with the results of [
9], which showed that germination causes an increase in the activity of beta-glucan enzymes, which are the primary enzymes responsible for breaking down the endosperm cell walls during germination, and thus reduce the beta-glucan content, and this decrease is inversely proportional to the increase in germination time.
The content of phenolic substances in barley increased with a statistically significant increase after germination compared to normal barley. This result is consistent with the results obtained by [
37,
38]. One of the main advantages of germination is that the antioxidant properties of grain can be enhanced by increasing the content of phenols, and this increase depends on the type of grain grown and the germination conditions. It was found from previous studies that using a mixture of organic solvent and water at a rate ranging between 50 and 70% allows for the extraction of most of the phenolic components from plant samples [
39,
40]. It also showed that the total polyphenol content of Ajwa dates ranges from 245 to 455.8 mg/100 g.
The amount of extracted phenols is greatly affected by the extraction solvent used, its concentration, and the degree of maturity of the dates, as the phenols content decreases significantly with the dates’ ripening progression. This is consistent with the researcher’s conclusion. Epidemiological studies have shown that the consumption of foods high in phenols is associated with reduced cardiovascular disease, inflammation, and cancer-related mortality [
41]. Moreover, the mixture of AD and GB (ABM) decreased the liver indices and enzymes, especially ALT, compared to the rats induced with the hyperlipidemia group (PC). We supposed that this improvement in lipid profile is a response to rats fed a HFD, which could be attributed to the potent antioxidant ability of AD and GB, as shown in
Table 2. Moreover, based on the chemical composition of GB, higher contents of carbohydrates and vitamin C are higher in GB than in barley seed (
Table 1).
Geminated seeds or sprout seeds present more active phytochemicals or carotenoids than seeds, demonstrating many health-promoting abilities, including reducing TC, anti-obesity, anti-oxidants, and inflammatory abilities [
42,
43]. Moreover, this research indicated that the mixture of GB and AD was related to reducing lipid accumulation in rats fed a HFD, as reported previously by [
44,
45] in hepatocytes and adipocytes. The anti-hyperlipidemic ability of barley sprouts might be associated with their high contents of saponarin, which considerably suppressed TC and TG gathering, and was accredited by decreases in TAG synthesis-related transcriptomics. Flavonoids and polyphenols in germinated barley and AD comprise several hydroxyl groups (-OH) which exert their antioxidant abilities [
46] by binding to oxidative markers, as mentioned in our data. Moreover, many previous studies have shown the therapeutic roles of geminated barely as an anti-obesity functional food [
47,
48]. Moreover, the mixture of barley sprout and Indian gooseberry significantly reduced the serum lipid profile and weights of rats fed a HFD [
47]. Several studies have indicated that AD has antihyperlipidemic action due to its anti-obesity qualities [
39].
In human studies, AD seed effectively reduced TC, LDL, and TG by 19.4, 22.5, and 25.78% in the treated group compared to the placebo group [
49]. This machinery of the anti-obesity qualities of GB can promote lipolysis and inhibit lipid synthesis due to its contents of saponarin and ellagic acid [
47].
Liver enzymes are responsible for the normal function of hepatocytes, and the increase in ALT and AST might be associated with liver injury [
50]. In the current study, rats fed a HFD displayed increased ALT and AST levels, indicating liver injury. This research indicates that feeding the rats a high-fat diet (HFD) during the experiment period led to possible damage or inflammation in the liver cells, which caused the aminotransferase enzymes (ALT, AST) to rise above the standard levels, which was evident in the results of the groups (ABM 30 and 40%).
A mixture of AD and GB at a ratio of 20, 30, and 40% restored the ALT enzyme to a level near that of the NC group. Unexpectedly, there was an increase in AST values recorded in ABM at a ratio of 20, 30, and 40%. This elevation of the AST enzyme may be due to the low beta-glucan content recorded in GB, since beta-glucan supplementation reduced liver damage and oxidative stress, which is represented by the significant lowering of AST [
51]. This later study supposed that the increasing of AST might be related to the liver damages in rats. Thus, further research would be conducted to illustrate this topic and support the increasing levels of AST. The authors did not examine any histological features for a more in-depth discovering of the hepatocytes status.
Nevertheless, ALT is a more specific indicator of liver inflammation than AST [
52], as AST may also be elevated in diseases affecting other organs, such as the heart or muscles [
53].
Treating rats induced with hepatic steatosis with GB prevented the weakening of hepatocyte function and diminished inflammation [
11]. β-glucans are recognized for their glucoregulatory actions, promoting hepatic health from the damages caused by HFD [
54]. Moreover, [
55] reported that GB has a hepatoprotective agent against heavy metals in rats. Epidemiological studies have shown that the consumption of foods high in phenols is associated with reduced cardiovascular disease, inflammation, and cancer-related mortality [
12,
42]. The TG was lower in all rats co-treated with AD and GB. Similar to our results, AD significantly reduced TC and glucose, indicating a protective agent against obesity in animal studies [
56,
57]. The dietary fiber of β-glucans can increase the abundance of probiotics, which can accelerate the secretion of unconjugated bile acids and thus help to regulate the level of TC in the blood short-chain fatty acids (SCFAs) resulting from the fermentation of food fibers inhibiting the activity of enzymes that synthesize TC within the body, thus reducing blood TC levels [
24].
The synergistic effects of AD and GB in reducing the lipid profile and exhibiting anti-hyperlipidemic effects may be due to their effect on TC and TG, involving avoiding their absorption by blocking the intestinal barriers related to enzymes that are responsible for the transportation of both molecules through the intestinal cavity [
25,
27]. Moreover, many phenolic compounds have different pharmacological properties on dyslipidemia or oxidative and inflammatory stress, as well as on risk factors for cardiovascular diseases. Based on the presented data, we suggested that the mixture of AD and GB may produce a higher effective strategy in promoting lipolysis and inhibiting lipogenesis.