What Is the Benefit of Anthocyanin in Black Rice?

Black rice is an ancient and rare rice resource in China. Compared with ordinary white rice, black rice is not only rich in dietary fiber, vegetable protein, a variety of essential amino acids, vitamins and minerals such as iron, copper and zinc, but also contains the functional ingredient anthocyanin. Black rice anthocyanin is a natural flavonoid compound extracted from the bran of black rice. Because of its strong antioxidant activity and ability to scavenge free radicals, it has shown potential in promoting human health. Therefore, the physicochemical properties and functional effects of black rice anthocyanin have attracted widespread attention from scientific researchers. This article mainly reviews the pharmacological effects and functions of black rice anthocyanin in terms of antioxidant, anti-inflammatory, hypolipidemic, anti-diabetic complications, anti-cancer and anti-aging, revealing its application prospects in the fields of functional foods and medicine, and providing a reference for the application of black rice anthocyanin in the health industry.

1 Composition of black rice anthocyanin

Black rice anthocyanin is an extract from the bran of black rice. It mainly exists in the form of glycosides in plants. The anthocyanin component is relatively simple, and the main components of black rice anthocyanin are cornflower blue-3-O-glucoside, cornflower blue-3,5-diglucoside, cornflower blue-3-rhamnoside, geranium-3,5-diglucoside, paeoniflorin-3-glucoside, paeoniflorin-3-arabinoside, and malvinidin-3-galactoside. Of these, cyanidin-3-O-glucoside accounts for more than 95% of the total anthocyanin content [1]. Some studies have shown that the use of methanol solution with hydrochloric acid can effectively avoid the problem of anthocyanin hydrolysis, and the extracted anthocyanin cyanidin-3-O-glucoside accounts for 57.3% to 74.5% of the total content of the sample [2].

2 Pharmacological effects of black rice anthocyanin

2.1 Antioxidant effect

Shi Juan et al. [3] used gavage to feed mice, setting up low, medium and high dose groups (50, 100, 200 mg/kg), feeding the corresponding concentrations of crude black rice anthocyanin. After 30 days, it was found that the spleen and thymus index of the mice increased, and the activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) in the liver, kidney, heart and serum were significantly increased. SOD), total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activity significantly increased, malondialdehyde (MDA) content decreased, and the scavenging capacity of oxygen free radicals significantly improved. Li Wen et al. [4] compared the antioxidant activity of black rice anthocyanin, American ginseng saponin, Ganoderma lucidum polysaccharide and stilbene glycoside monomers, and the results showed that the antioxidant activity of black rice anthocyanin was superior to that of American ginseng saponin, Ganoderma lucidum polysaccharide and stilbene glycoside. Liang Yinku et al. [5] found in an in vitro antioxidant experiment that the inhibition rate of black rice anthocyanin on hydroxyl radicals and superoxide anions and the total antioxidant activity increased with its concentration.

2.2 Lipid-lowering effect

Many scholars have found that black rice anthocyanins have the effect of regulating blood lipids. Zhang Mingwei et al. [6] found that giving black rice anthocyanins to hyperlipidemic rats can lower the blood lipid levels of hyperlipidemic rats, improve the oxidative stress state in the body, and found that anthocyanins in black rice bran and unsaturated fatty acids are the main substance basis for their antioxidant and hypolipidemic effects. Xu Huilong [7] found that black rice anthocyanins can significantly reduce serum total cholesterol (TCHO), triglycerides (TG), arteriosclerosis index (AS), and apolipoprotein B (ApoB) levels, increase high density liptein cholesterol (H-DLC), and apolipoprotein AI (ApoA-I) levels, and is positively correlated with the dose, indicating that black rice bran can significantly improve lipid metabolism abnormalities in hyperlipidemic rats and has the effect of regulating lipid metabolism disorders caused by a high-fat diet.

WANG et al. [8] constructed a high cholesterol model mouse by feeding it a high fat high cholesterol diet, and treated it daily with black rice anthocyanin. The results showed that supplementing black rice anthocyanin can effectively alleviate the increase in body weight, liver weight, perirenal fat mass and epididymal fat mass in mice. Zhuo Xueming et al. [9] fed high cholesterol mice black rice anthocyanin for 15 weeks, the anti-blood lipid effect of Anthocyanin was studied by measuring the levels of total cholesterol (TCHO), low-density lipoprotein cholesterol (LDL-C), high-density lipteincholesterol (H-DLC) and triglyceride (TG). The results showed that black rice anthocyanins have a blood lipid-regulating effect. Liu et al. [10] established a high cholesterol model by feeding a high cholesterol diet, and fed black rice anthocyanins for 12 weeks. The results showed that black rice anthocyanins can reduce the absorption of cholesterol in the intestine and promote the reverse transport of cholesterol in the intestine by regulating the expression levels of related genes. In addition, a black rice diet can also repair intestinal tissue damaged by a high-cholesterol diet and increase the proportion of beneficial intestinal bacteria.

2.3 Anti-diabetic and its complications

2.3.1 Hypoglycemic effect

In 2019, the number of people with diabetes in China was about 116 million. According to statistics, China has become the country with the largest number of diabetes patients in the world [11]. Therefore, the treatment of diabetes has gradually entered people's field of vision, and improving diabetes symptoms through diet is more in line with people's needs in their daily lives. Cyanidin-3-O-glucoside is an important active monomer in black rice anthocyanin.

Zheng Hongxing et al. [12] found that cyanidin-3-O-glucoside in black rice anthocyanin can lower blood glucose in diabetic rats. By administering streptozotocin to induce diabetes in rats and then administering cyanidin-3-O-glucoside for 8 weeks, significantly reduced blood glucose in diabetic rats and improved the “three highs and one low” in diabetic rats. Its hypoglycemic effect was not significantly different from that of metformin, the first-line drug in the clinic. Li Chengling et al. [13] constructed a diabetic rat model by intraperitoneally injecting mice with alloxan, and divided the mice into groups to give black rice extract black rice polyphenols by gavage for 4 weeks. It was found that black rice extract had an inhibitory effect on the trend of elevated blood glucose in mice with diabetes induced by tetraoxypyrimidine. Bhuyan et al. [14] found that the cornflowerin-3-O-glucoside in black rice extract can effectively bind to fructose-6-phosphate transaminase, producing a significant hypoglycemic effect.

2.3.2 Anti-diabetic osteoporosis effect

Diabetic osteoporosis (DOP) is one of the complications of diabetes mellitus, which is mainly manifested as a decrease in bone mass and destruction of bone microstructure, increased bone fragility, increased risk of fracture, high disability and mortality rate [15]. Qi Shanshan et al. [16] established a diabetic rat model by streptozotocin injection, and found that black rice anthocyanin extract given by gavage for 8 weeks increased bone density and reduced serum bone turnover markers in diabetic rats. In the high-dose group, bone microstructure and the number of osteoclasts returned to normal, At the same time, black rice anthocyanin extract can inhibit the adipogenesis of diabetic rats' bone marrow. The osteogenic specific transcription factor (RUNX2) in the bone tissue of rats in the treatment group was significantly increased. Other natural products such as eucommia total flavonoids and lycopene also have a beneficial effect on diabetes-induced osteoporosis, and their mechanism of action is consistent with black rice anthocyanin [17]. The above results show that black rice anthocyanins and similar anthocyanin extracts can improve bone loss caused by diabetes and have an anti-diabetic effect on osteoporosis. The main mechanism is to inhibit bone turnover, inhibit bone marrow adipogenesis, and upregulate RUNX2 expression.

2.3.3 Anti-diabetic nephropathy

Diabetic nephropathy (DN) is a serious complication of diabetes. About 30% of diabetic patients have serious symptoms such as nephropathy and proteinuria, which eventually develop into diabetic nephropathy. It is one of the main causes of death in diabetic patients, and 53% of DN patients die of kidney failure [18]. Diabetic nephropathy, as a chronic disease that endangers human health, has become an important public health and social issue. Qi Shanshan et al. [19] found that the main active ingredient of black rice anthocyanin, cyanidin-3-O-glucoside, can repair the renal dysfunction caused by diabetic nephropathy, protect renal tubular cells from damage, inhibit the aggregation of extracellular matrix in glomerular cells and renal fibrosis, At the same time, the study also compared the efficacy of black rice cyanidin-3-O-glucoside with the first-line clinical drug lisinopril in the treatment of diabetic nephropathy, and found that there was no significant difference between black rice cyanidin-3-O-glucoside and lisinopril in the treatment of diabetic nephropathy. The mechanism by which black rice anthocyanin can prevent diabetic nephropathy is similar to that of other natural products such as notoginseng saponins, which is achieved through anti-oxidation, anti-inflammation and inhibition of renal fibrosis.

2.3.4 Anti-diabetic retinopathy

Diabetic retinopathy (DR) is a fundus lesion with specific changes and is one of the important complications of diabetic microvascular disease. Under a high sugar state, the body produces oxidative stress through processes such as glucose autoxidation, polyol pathway and protein glycation, inducing the overexpression of peroxides, disrupting the antioxidant mechanism, triggering degeneration of retinal cells, and causing retinal damage. Qi Shanshan et al. [20] constructed a diabetic rat model by intraperitoneal injection of streptozotocin, and then administered 200 mg/(kg·d) black rice anthocyanin extract to the diabetic rats by gavage. After 8 weeks of administration, the retinal tissue structure and its morphometric parameters, superoxide dismutase activity, and malondialdehyde content were observed by histopathological methods.

The study found that Compared with the model group, the retinal structure and morphology of rats in the black rice anthocyanin administration group improved significantly. The internal limiting membrane of the retina was better connected, and the cells in the inner and outer nuclear layers were arranged neatly. The total thickness of the retina, the thickness of the inner nuclear layer, and the thickness of the outer nuclear layer were all significantly thicker than those in the model group. The number of ganglion cells per unit distance was significantly higher than that in the model group, suggesting that black rice anthocyanins have the effect of improving the structure of the retina in diabetic rats and improving diabetic retinopathy. At the same time, this study found that black rice anthocyanins can improve lipid oxidation in diabetic rats.

2.4 Anti-inflammatory effect

Zhao et al. [21] found that treatment with black rice anthocyanin extract and rosmarinic acid in mice with dextran sodium sulfate-induced colitis showed a strong inhibitory effect on the disease activity index of colitis, nitric oxide (NO) content, serum interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) expression showed a strong inhibitory effect. Among them, black rice anthocyanin extract had a stronger inhibitory effect on the repair of intestinal tissue in colitis mice, the content of NO in the intestine, the level of serum IL-6 and the expression of IL-6 and inducible nitric oxide synthase (iNOS mRNA) than rosemary acid. The results show that black rice anthocyanin extract can be used as a functional food or nutritional product for the treatment of inflammatory bowel disease in humans.

Wu et al. [22] constructed a model of obese mice by feeding mice a high-fat diet and treated them with black rice anthocyanin. They found that the black rice anthocyanin treatment group had significantly lower levels of TNF-α, IL-6, nuclear factor kappa-B ( NF-κB) and inducible nitric oxide synthase (iNOS) genes were significantly reduced, indicating that black rice anthocyanins can reduce liver inflammation caused by a high-fat diet. Tancharoen et al. [23] used 5-fluorouracil to induce oral mucositis in rats, and found that black rice anthocyanin had a good anti-inflammatory effect on 5-fluorouracil-induced oral mucositis by inhibiting the activation of the NF-κB signaling pathway after one month of treatment.

2.5 Inhibit tumor cell proliferation

Experimental studies in animal models of disease have shown that long-term dietary black rice products or black rice extracts can prevent and treat certain types of cancer by inhibiting tumor cell phosphorylation or upstream signaling pathways. Teng et al. [24] constructed a tumor model mouse by subcutaneously injecting mouse breast cancer cells, and injected 50 μL of black rice anthocyanin solution (20 mg/mL) into the tumor. Anthocyanin from black rice was found to significantly inhibit tumor growth by inhibiting the transformation of epithelial cells into mesenchymal cells, thereby enhancing local hyperthermia and metastasis. Anthocyanin from black rice also has good photothermal stability and photothermal conversion efficiency, which can increase the temperature of anthocyanin from black rice to an effect sufficient to induce tumor cell death.

Jiang Weiwei et al. [25] found that black rice anthocyanin can inhibit the proliferation of human prostate cancer cells (PC-3), and the mechanism of action may be through upregulating the levels of reactive oxygen species (ROS) and NO, which leads to mitochondrial damage, the release of cytochrome C into the cytoplasm, and the phosphorylation of p38 and JNK. This activates the JNK and p38 signal transduction pathways, thereby inducing apoptosis in PC-3 cells. Overexpression of human epidermal growth factor receptor-2 (HER-2) leads to fast cell proliferation and metastasis in breast cancer patients. Luo Liping et al. [26] found that black rice anthocyanin can inhibit the growth and proliferation of HER-2-positive breast cancer cells and promote apoptosis by downregulating the phosphorylation level of HER-2. Liu Chunyuan et al. [27] found that black rice anthocyanins can inhibit the proliferation of colon cancer cells (SW480), block the progression of the cell cycle, and promote apoptosis of colon cancer cells.

2.6 Anti-aging effect

Although aging is inevitable, it is possible to slow it down through a reasonable diet and balanced nutrition. Li et al. [28] found that black rice anthocyanins can be used as a source of dietary antioxidants. Experiments were carried out on wild fruit flies, and black rice anthocyanins were added to the flies' food. It was eventually found that supplementing black rice anthocyanins can regulate glutathione metabolism, neuroactive ligand-receptor interactions, as well as the forkhead transcription factor (FOXO) signaling pathway and the mammalian target of rapamycin (mTOR) signaling pathway to extend the lifespan of fruit flies and improve motor function damage. Lu et al. [29] showed that black rice anthocyanins have an anti-aging effect, and that the mechanism is closely related to the fact that black rice anthocyanins can enhance the antioxidant activity of the brain, liver and kidney, increase the activity of aging-related enzymes, and alter gene expression.

2.7 Inhibit cerebral infarction and memory loss caused by cerebral ischemia

Wattanathorn et al. [30] induced metabolic syndrome in rats by feeding them a high-fat diet. The model rats were fed a combined extract of black rice anthocyanin and fennel for 21 days. The results showed that black rice anthocyanin can reduce the levels of MDA, IL-6 and NF-κB, increase the activity of antioxidant enzymes in the frontal cortex and the expression of nitric oxide synthase, while increasing the diameter of the vascular lumen and reducing the thickness of the intima and media of the common carotid artery. Studies have shown that black rice anthocyanins have a beneficial effect on cerebral infarction. Hwang et al. [31] established a cerebral ischemia model in mice by performing a sham operation and treated the model mice with black rice anthocyanin by gavage for 21 days. the death of hippocampal neurons was significantly reduced, and the proliferation of reactive astrocytes was significantly inhibited. In the Morris water maze test, black rice anthocyanins significantly improved the memory impairment induced by arterial occlusion. The above results indicate that supplementing black rice anthocyanins has a significant inhibitory effect on cerebral ischemia.

2.8 Osteoporosis caused by low anti-estrogen levels

Postmenopausal osteoporosis (PO) is commonly characterized by reduced bone mass, destruction of bone microstructure, and decreased bone density, which causes inconvenience in the lives of postmenopausal women [32]. Lee et al. [33] induced a rat osteoporosis model by removing the rat's ovaries and gave the rats black rice extract daily by gavage. It was found that black rice extract can prevent bone loss induced by ovariectomy, which has great potential for the treatment of postmenopausal osteoporosis by regulating bone metabolism and alleviating postmenopausal osteoporosis. Shimizu et al. [34] found that bilberry extract rich in anthocyanins also has a therapeutic effect on osteoporosis in ovariectomized rats. After 8 weeks of administration of bilberry extract, the bone volume fraction (BV/TV), bone mineral density (BMD), trabecular thickness ( Tb.Th) and trabecular number (trabecular number, Tb.N) levels increased, and trabecular separation (trabecular separation, Tb.Sp) levels decreased, indicating that bilberry anthocyanin-rich extract can alleviate osteoporosis, and its effect is similar to that of black rice anthocyanin.

2.9 Anti-liver damage

Lu Hongchao et al. [35] established a mouse model of alcoholic liver injury by administering 50% alcohol to mice by gavage for 11 days. The treatment group was treated with black rice anthocyanin by gavage. The results showed that the SOD and GSH activities in the mouse liver were increased, and the MDA content was significantly reduced, indicating that black rice anthocyanin can improve alcoholic liver injury by scavenging free radicals in the body and preventing lipid peroxidation. Wang Zhibo et al. [36] established a rat model of acute liver injury by intraperitoneally injecting carbon tetrachloride, and found that black rice anthocyanin could effectively alleviate carbon tetrachloride-induced liver injury by gavage once a day for 7 days. Jiang et al. [37] found that daily intake of cyanidin-3-O-β-glucoside can prevent the progression of carbon tetrachloride-induced liver fibrosis in mice by inhibiting the activation of hepatic stellate cells, which provides a basis for the clinical prevention of liver fibrosis.

2.10 Other effects

In addition to the above-mentioned functional effects, black rice anthocyanins also have other pharmacological effects. Sunarti et al. [38] found that goat milk supplemented with black rice extract can reduce insulin resistance by improving blood lipid levels and inhibiting the expression of retinol-binding protein in diabetic rats. Ona Kevin et al. [39] found that anthocyanin extracts from black rice can alleviate acute lead poisoning, providing a new approach for the treatment of acute lead poisoning.

3 Summary and outlook

Currently, the public's demand for food safety and nutrition is constantly increasing. Black rice anthocyanins have the effects of anti-oxidation, anti-inflammation, lipid-lowering, anti-aging, and anti-cancer, and are a dietary supplement for health science. In addition, black rice anthocyanins have a preventive and therapeutic effect on chronic diseases such as diabetes, cardiovascular disease, and osteoporosis, as well as other non-communicable diseases. Black rice anthocyanins play an important role in disease prevention and nutritional intervention for chronic diseases. China is rich in black rice resources, and black rice anthocyanins have good application prospects in the food, functional food and pharmaceutical industries.

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