What Is the Benefit of Luo Han Guo Extract Mogroside V?

Luohanguo is a traditional Chinese medicinal plant native to the tropical and subtropical mountainous regions of Guangxi, Guangdong, Hunan, and Jiangxi. It has been used medicinally for over 300 years in Guangxi. Luohanguo is rich in vitamins C and E, fructose, essential amino acids, trace elements, and other nutrients, as well as flavonoids, polysaccharides, glycosides, and polyphenols. Traditional medicine believes that Luohanguo can moisten the lungs to relieve coughs, cool the blood, and moisten the intestines to promote bowel movements. Modern pharmacological studies have confirmed that Luohanguo has pharmacological effects such as relieving coughs and phlegm, regulating the movement of the digestive tract, enhancing the body's immune system, anti-oxidation, protecting the liver, and inhibiting the cariogenicity of Streptococcus mutans. The main active ingredient is the intensely sweet non-sugar substance triterpenoid mogroside, of which mogroside V is the most abundant. Due to its high sweetness, low calories, light color, good water solubility and stability, safety in consumption, and so on, China approved the product as a food additive in 1996. It can be used as a sweetener to partially or completely replace sucrose and is widely used in various types of food, especially as a substitute for sugar for people with obesity and diabetes. This article provides a brief overview of the physical and chemical properties, physiological functions and applications of monk fruit sweeteners in foods, with the aim of providing a basis for the comprehensive utilization and development of monk fruit sweetener resources.

1 Chemical structure and physical and chemical properties of Mogroside V

Mogroside V, also known as Luo-han-kuo extract Mogroside V. In the 1970s, scholars began to study Mogroside V. In 1975, Lee first reported that the fruit of the Luo Han Guo contains triterpene glycosides. In 1983, Japanese scholar Takemoto Tsunematsu and others isolated and identified seven types of Luo Han Guo glycosides from Luo Han Guo purchased in Macau. Kasai also obtained four types of Luo Han Guo glycosides from Luo Han Guo produced in Xishuangbanna, Yunnan. In 1996 Wang Xuefen et al. [1] isolated a series of cucurbitane-type tetracyclic triterpenoid acids from the liposoluble fraction of the root of Luo Han Guo in 1996.

Qi Yiping et al. [2] pointed out in their research that Mogroside V is a triterpene glucoside, its aglycone is a triterpene alcohol, and two glucoside side chains consisting of less than four glucose units are linked to the aglycone by β-glycosidic bonds. The main linkages between the glucose side chains are β-1.6 and β-1.2 glycosidic bonds. Luohanguo saponins are cucurbitane-type compounds. 26 types of cucurbitane-type triterpene saponins have been isolated and identified, which have the same aglycone Luohanguo alcohol (see Figure 1). The main difference lies in the number of sugar moieties and the different connection modes. At the same time, the C11-OH or 7-H of some individual saponins is oxidized to =O. The basic structure is shown in Figure 1. Recently, studies on the roots and unripe fruits of Luo Han Guo have isolated and identified 12 types of cucurbitane-type saponins, two of which have slightly different chemical structures compared to the structures of typical cucurbitane-type triterpenoid aglycones (see Figure 2) [3].

Mogroside is one of the main active ingredients in Luohanguo. The total content in the dried fruit is 3.775-3.858% [4]. It is a light yellow powder that is easily soluble in water and diluted ethanol. It is stable in a neutral aqueous solution at 100°C, and remains undamaged when heated in air at 120°C for a long time. It is also non-fermentable, not prone to mould, and unaffected by pH when used (pH between 2-10).

2 Physiological functions of Mogroside

2.1 Expectorant and antitussive effects

Luohanguo has significant antitussive and expectorant activities, and its main active ingredient is the glycoside V. Chen Yao et al. [5] used an ammonia-induced cough test and a phenol red-stimulated tracheal secretion test to observe the effects of Luohanguo glycoside on cough and tracheal secretions in mice. The results showed that an oral dose of Luohanguo glycoside greater than 15 g/kg can significantly reduce the number of coughs in mice and increase the amount of tracheal secretions, suggesting that it has a significant antitussive and expectorant effect. Li Jian et al. [6] used the guinea pig citric acid cough induction method, capsaicin cough induction method and mechanical stimulation cough induction method to observe the effect of Luo Han Guo water extract on the number of coughs and cough latency in animals. The results showed that Luo Han Guo water extract can significantly reduce the number of coughs caused by citric acid or capsaicin in guinea pigs and prolong the cough latency, and suppress the number of coughs caused by mechanical stimulation in guinea pigs. At present, there is no research on the specific mechanism of Luo Han Guo sweet saponin expectorant and antitussive effects, and further exploration is needed.

2.2 Anti-inflammatory and antibacterial

Studies have shown that in a lipopolysaccharide-activated mouse macrophage model, Luo Han Guo extract significantly inhibits the protein and mRNA expression of inducible nitric oxide synthase and cyclooxygenase-2, and has anti-inflammatory activity [7].

Recently, Shi et al. [8] demonstrated that Mogroside V has an inhibitory effect on respiratory tract inflammation in a study using a mouse model of acute lung injury induced by LPS. Zhao Yan [9] studied the effects of Luo han guo concentrated juice and Mogroside on the growth, acid production and adhesion, and compared it with sucrose, fructose, glucose and xylitol to explore its effect as a natural high-potency sweetener in preventing tooth decay. The results showed that the growth rate and adhesion of Streptococcus mutans in culture medium containing Luo Han Guo concentrated juice were significantly lower than those in sucrose (P<0.05), but the acid production was higher; in the culture medium containing Mogroside, there was almost no growth and reproduction, and the difference with xylitol was not significant (P>0.05), indicating that monk fruit water extract and monk fruit sweetener have strong antibacterial activity.

Chen Yao et al. [10] used xylene and carrageenan to induce inflammation in experiments to to observe the anti-inflammatory effect of Luo Han Guo saponin, and the results showed that Luo Han Guo saponin had no significant effect on the inflammation model caused by xylene and carrageenan. Di et al. [11] used a mouse ear swelling model to study the effect of Luo Han Guo saponin and found that it down-regulates COX-2 and IL-6 and up-regulates the expression of certain inflammatory protective genes, such as PARP1, BCL211, TRP53, MAPK9 and PPARδ gene expression to suppress inflammation induced by 12-O-tetradecanoylphorbol-13-acetate. Further research is needed to understand the anti-inflammatory effects of monascus saponins and their related mechanisms.

2.3 Scavenging free radicals and antioxidant effects

Mangiferin has antioxidant properties. Qi Xiangyang et al. [12] found that MG can inhibit lipid peroxidation in rat liver tissue and has a protective effect on Fe2+ and H2O2-induced peroxidation damage to liver tissue. It can reduce the occurrence of red blood cell hemolysis. MG-V has a comparable effect to MG in scavenging hydroxyl radicals, but a better effect than MG in scavenging O2-·. This indicates that MG has antioxidant biological activity, and further suggests that MG-V is the main antioxidant active ingredient in the extract. Nong Yiqing [13] found that Mogroside extract (total Mogroside ≥ 98%, MogrosideV content 65.20%) has a certain scavenging effect on both hydroxyl free radicals and superoxide anion free radicals. With an increase in the concentration of Mogroside, the scavenging effect gradually increases, showing a certain dose-effect relationship.

Zhao Yan et al. [14] showed that both the water extract and the sweetener of the monk fruit significantly increased the serum GSH-Px and SOD activities (P<0.05) and significantly reduced the serum MDA content (P<0.05), indicating that both Luo Han Guo water extract and Mogroside have strong antioxidant effects, and the mechanism may be related to the inhibition of lipid peroxidation. Xu et al. [15] used the mouse insulinoma NIT-1 cell line as the experimental subject studied the inhibitory effect of Luo Han Guo saponin on palmitic acid-induced intracellular oxidative stress. The results showed that compared with the palmitic acid-induced group, the Luo Han Guo saponin co-culture group significantly reduced the intracellular ROS concentration and restored the expression levels of GLUT-2 and pyruvate kinase mRNA, but Luo Han Guo saponin was unable to reduce palmitic acid-induced apoptosis. In vitro experiments also confirmed that Mogroside V has strong antioxidant activity and the ability to scavenge active oxygen free radicals. It can be seen that Mogroside V may exert its antioxidant effect by reducing intracellular ROS and regulating the expression of glucose metabolism-related genes.

2.4 Hypoglycemic

Literature reports that Mogroside extract significantly reduces the activity of heme oxygenase-1, manganese superoxide dismutase and glutathione peroxidase in a diabetic model, inhibits the expression of heme oxygenase-1 and manganese superoxide dismutase mR-NA, increases serum HDL-C levels, upregulates the expression of heme oxygenase-1 and manganese superoxide dismutase mRNA, activates liver antioxidant enzymes, reduces urinary albumin and urine volume in diabetic rats, and alleviates some symptoms of diabetic kidney disease [16-18]. Yuji et al. [19] further confirmed in vitro that Luo Han Guo total saponins, and the monomeric components Luo Han Guo saponins III, V, IV and Simonin have the activity of inhibiting maltase in the small intestine. He Chaowen et al. [20] studied the pharmacodynamics of fresh Luo Han Guo saponin in regulating blood glucose and found that fresh Luo Han Guo saponin has a significant inhibitory effect on postprandial blood glucose generation in normal mice. the main reason for regulating and lowering blood glucose is by inhibiting the conversion of food glucose and increasing insulin levels; compared with dried Luo Han Guo saponin, the effect of increasing postprandial insulin levels is more significant in fresh Luo Han Guo saponin than in dried Luo Han Guo saponin, while the inhibitory effect of dried Luo Han Guo saponin on α-glucosidase activity is stronger than that of fresh Luo Han Guo saponin.

Xu Qing et al. [21] also found through research that a one-time oral dose of 30% Mogroside 200mg/kg had no significant effect on blood glucose levels or liver enzyme activity in healthy adults, indicating that MogrosideV is a safe sweetener that does not affect blood glucose levels in normal people. In addition, Luo Han Guo saponin has a significant hypoglycemic effect on mice with diabetes induced by alloxan, and can prevent and treat the abnormal increase in serum triglycerides and serum cholesterol in diabetic mice. It can also increase the content of high-density lipoprotein cholesterol in the serum, normalize the blood lipid level of the body, and prevent lipid metabolic disorders caused by diabetes. The mechanism of lowering blood sugar may be related to improving the antioxidant and free radical scavenging capacity of diabetic mice, improving blood lipid levels, thereby reducing the damage of alloxan to pancreatic β cells or improving the function of damaged cells [22]. Further research is needed to investigate the mechanism of its anti-diabetic effects in vivo and in vitro.

2.5 Hepatoprotective effect

Xiao Gang et al. [23] found in an experimental study on the protective effect of Mogroside on experimental liver damage in mice that Mogroside can reduce the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of mice with immune liver damage, can increase the activity of superoxide dismutase (SOD) in the homogenate of mouse liver tissue, and lowered malondialdehyde (MDA) levels, significantly reducing the degree of pathological changes in liver tissue, indicating that Mogroside have a protective effect on acute and immune liver damage in mice. Chen et al. [24] studied the effect of monk fruit sweeteners Mogroside on liver fibrosis in rats caused by complex factors, and found that compared with the model control group, different doses of Mogroside can dose-dependently reduce ALT activity and TC and TG levels in rat serum (P<0.05 or P<0.01); and can reduce MDA and Hyp levels in liver tissue (P<0.05 or P<0.01), suggesting that Luo Han Guo sweet saponin has a protective effect on rats with liver fibrosis caused by a complex factor. Song Kaijuan et al. [25] used methods such as CCK8, RT-PCR and ELISA to investigate the effects of Luo Han Guo sweet saponin on the activation and apoptosis of human hepatic stellate cells LX-2, which are key cells in the development of liver fibrosis. The results showed that Luo Han Guo sweeteners can inhibit the activation of hepatic stellate cells by inhibiting the expression of TGF-β1 and type I collagen proteins and TGF-β1 and α-SMA mRNAs, and can also promote the apoptosis of hepatic stellate cells, thereby exerting an anti-hepatic fibrosis effect.

2.6 Anti-cancer effect

Japanese scholar Takashi Kimijima [26] conducted a two-stage carcinogenicity test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter in a test of the anticancer effect of Mogroside. it was found that loganin V has an anticancer effect, and this delayed carcinogenic effect is even stronger than that of stevioside. Takasaki et al. [27] found that loganin has an inhibitory effect on the early Epstein-Barr virus antigen induced by the tumor promoter TPA. MogrosideV and 11-oxo-luohanguo V have a strong inhibitory effect on the two-stage carcinogenesis of mouse skin induced by peroxynitrite ion as initiator and TPA as promoter. In a mouse liver cancer model induced by dicyclanil, Sayaka et al. [28] found that Luo Han Guo extract inhibited the expression of Cyp1a1, thereby inhibiting the production of liver cancer.

2.7 Boosts immunity

Mogrosides have immunomodulatory properties. Research has found that Mogroside IV extract can increase the percentage of peripheral blood acidic α-naphthyl acetate-positive lymphocytes and the rate of spleen-specific rosette-forming cells, and improve the phagocytic function of macrophages and the proliferative effect of T cells in cyclophosphamide immunosuppressed mice [29]. Chen Weijun et al. [30] studied the effect of Luo Han Guo saponin extract on the cellular immune function of mice with diabetes induced by tetrazine, and found that it can increase the number of CD4+ T lymphocytes, restore the decreased CD4+/CD8+ ratio, resulting in a shift in the expression of pro-inflammatory Th1 cytokines, IFN-γ, and TNF-α, towards the beneficial Th2 pattern, thereby improving the cellular immune imbalance in diabetic mice. Given that MG has pharmacological activities that protect and regulate immune function, further research on its mechanism of action in improving immune function in the body will be beneficial for maintaining human health.

2.8 Other effects

Mogroside can significantly reduce the total cholesterol and triglyceride levels in the serum of animal models with hyperlipidemia, as well as significantly increase the high-density lipoprotein cholesterol level, and has a positive effect on regulating blood lipid metabolism [31]. Chen Zhuang et al. [32] found that Luo Han Guo sweeteners have a delaying effect on aging in mice with D-galactose aging model. Liu Ting et al. [33] found that Mogroside V also has a significant antagonistic effect on the bronchospasm caused by histamine. Chen Yao et al. [10 used a mouse constipation model to observe the laxative effect of Mogroside and found that Luo Han Guo sweeteners Mogroside can increase the ink propulsion rate of constipated mice, reduce the time of the first bowel movement, and increase the number and weight of bowel movements. Ding Xiushi [34] believes that Mogroside have a certain effect in the fields of anti-exercise fatigue and anti-exercise immunodeficiency.

3 Application

Mogroside is widely used in the food industry. The FDA approved the use of Mogroside in food in 1995, and China also approved the use of this product as a food additive at the 17th meeting of the National Food Additive Standardization Technical Committee in July 1996. Currently, countries that allow the use of Luo Han Guo Extract as a food additive include Japan, South Korea, Thailand, Singapore, the United Kingdom and other countries. Japan began importing large quantities of monk fruit from China in the 1990s. In addition to using it as a natural sweetener, Japanese manufacturers have also used Luo Han Guo Extract to develop a variety of health foods, such as anti-allergy granules, diet foods, sugar-lowering foods, etc.; it is also used as a sweetener in food processing to replace aspartame, sodium saccharin, etc., and is used in the production of foods such as syrup, instant drinks, chewable tablets, effervescent tablets, etc.

China is the origin and only place of cultivation of Luo Han Guo, which is rich in renewable resources. The Ministry of Health has included it in the list of the first varieties that are both food and medicine. At the same time, it is widely used in the food and health food industries because of its high sweetness, low caloric value, good water solubility and thermal stability, non-toxicity, food safety and lack of odor. Monk fruit sweetener can be added to various foods as a sweetener to partially or completely replace sucrose. When making candy, if 0.012% Mogroside is added to the starch jelly, it can produce candies with good flavor and texture. Luo Han Guo Extract can replace sucrose to produce biscuits with a very good structure and texture. It is refreshing in the mouth and does not feel dry when chewed. In Japan, 0.005% monk fruit sweetener is added to the solution used to make pickles, and the amount of salt used for pickling can be reduced by 50%. The pickled vegetables are crisp and refreshing. A low-sugar type of solid drink made from Luo Han Guo Extract and pueraria root extract is clear and transparent when mixed, with a light fragrance. It has the effect of quenching thirst, diuresis, refreshing, lowering blood pressure and promoting digestion. Mogroside V can also be combined with green tea, osmanthus, mung beans, pearls and other nutritious ingredients to make health drinks with different characteristics. Adding monk fruit sweetener to dairy products can promote the health of children, the elderly and patients. The UK has developed a cube of sugar pressed with 0.015% monk fruit sweetener as an auxiliary material of soluble starch for drinking when making coffee, and Japan uses monk fruit sweetener to make throat lozenges [35].

4 Outlook

At present, the Luohanguo food processing industry is mainly manifested in the production of Luohanguo extracts such as Mogroside V and Luohanguo extracts, the baking and sale of raw Luohanguo fruit, and the use of Luohanguo extracts to produce some more traditional Luohanguo-flavored pastes, sugars, blocks, instant drinks, teas, and other low-end convenience foods. The industrial structure is simple, and the product range is simple. In recent years, studies have been conducted on the physiological functions of Mogroside V, including their ability to scavenge free radicals and fight oxidation, regulate blood sugar, modulate the immune system, and resist fatigue and hypoxia. As a result, their functional properties have attracted increasing attention.

In the future, the focus of food development should be on increasing the technological added value of Luo Han Guo products. Using the functional properties of Mogroside V, anti-diabetic foods, anti-caries foods for children, anti-aging foods, constipation-preventing foods, lipid-lowering and weight-loss foods, and foods with a low glycemic index can be developed. The application of Luo Han Guo can be developed from traditional foods to new functional health foods. At the same time, since there is no domestic standard for Mogroside, manufacturers produce according to their own standards, and the technology and craftsmanship vary, resulting in uneven product quality of monk fruit sweeteners, which severely restricts the development of China's monk fruit industry. A sound quality standard for monk fruit extract should be established as soon as possible, quality certification should be standardized, product supervision should be strengthened, and the standardization of the monk fruit industry should be promoted. With the continuous deepening of basic research and product research and development of monk fruit, as well as people's increasing awareness of their own health, monk fruit sweetener will have very broad application prospects and market potential in the fields of pharmaceuticals, cosmetics and health food.

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