Monk Fruit Extract Mogroside, Is It Safe?

Siraitia grosvenorii (Swingle) C. Jeffery, also known as Luohan Guo, is a traditional Chinese medicine that is endemic to southern China. It is mainly produced in the tropical and subtropical mountainous areas of Guangxi, Guangdong, Hunan, Hainan, Jiangxi, and Guizhou provinces, and belongs to the gourd family of vine-like deciduous plants. To date, the history of Luohanguo being eaten and used medicinally in folk medicine goes back more than 300 years. For nearly half a century, it has been cultivated on a large scale in Guangxi and exported to Europe and the United States. Since the 1970s, each edition of the Chinese Pharmacopoeia has included Luohanguo as a traditional Chinese medicine. It is cool in nature, sweet in taste, and enters the lung and large intestine channels. It has the effects of clearing heat and cooling the blood, generating body fluid to relieve coughing, loosening the bowels to detoxify, rejuvenating the skin and benefiting the complexion, and moistening the lungs to resolve phlegm. Modern pharmacological studies have also shown that Luo Han Guo extract can regulate blood sugar and fat metabolism, and has various biological activities on respiratory, digestive and immune functions [1-2].

Many scholars have studied the chemical composition of Luo Han Guo extract [3-6], and have found compounds such as sterols, mogrosides, flavonoids and tetracyclic triterpenoid acids. Mogrosides are the main sweetening components, including 13 types of triterpenoid glycosides (mainly mogrosides IV, V and III) (mogroside V is the sweetening component with the highest content in the fruit). Mogroside is a light yellow powder with good water solubility and no precipitation. It is safe and non-toxic. Its sweetness is about 300 times that of sucrose. It is a low-calorie, non-nutritive, non-fermentable sweetener that will not be destroyed by continuous heating at 100-120°C for 25 hours. Therefore, it can be used as a relatively ideal natural sweetener for food industry production.

Currently, it has long been sold on the international market, in Europe and the United States, Southeast Asia, Hong Kong and Macao. In the United States in particular, it has been approved by the Food and Drug Administration (FDA) as a natural sweetener. In China, it is also widely used in the food industry for pharmaceuticals, beverages and elderly healthcare products [3-5]. As humans gain a deeper understanding of the impact of lifestyle and diet on physical health, especially the understanding of diseases such as diabetes, obesity, and hypertension caused by excessive sugar and calorie intake, there is a need not only for long-term drug treatment and dietary care for patients, but also for more attention to improving the quality of life through improving the taste of food (especially sweeteners). This article provides a review of pharmacological activity research and related toxicological research on Mogroside.

1 Pharmacological effects of Mogroside

1.1 Effect on blood glucose

In recent years, many scholars have conducted research on the effect of Mogroside on blood glucose. It has been reported that after a single oral dose of 30% Mogroside at a dose of 200 mg/kg was given to healthy adults, the results showed that 30% Mogroside had no significant effect on blood glucose levels and liver enzyme activity in healthy people [7-9]. Some scholars have also studied the effect of Mogroside on blood glucose through animal experiments. For example, Qi Xiangyang et al. [10] gave normal mice and diabetic mice 0.5, 1.0, and 3.0 g/kg doses of Luo Han Guo extract (containing Mogroside) by continuous gavage for 30 days. It was found that there was no effect on the blood glucose of normal mice; the middle and low dose groups had a hypoglycemic effect on diabetic mice, i.e. at 0.5 g/kg, blood glucose decreased from (15.45± 5.76) mmol/L to (11.84±4.24) mmol/L, and at 1.0 g/kg, blood glucose decreased from (15.52+ 5.70) mmol/L to (15.08±4.64) mmol/L; while in the high dose group (3.0 g/kg), the blood glucose of mice increased from (15.54±5.77) mmol/L to (20.35±4.36) mmol/L. This indicates that the dosage of 0.5–1.0 g/kg of Luo Han Guo extract has the effect of lowering the fasting blood glucose of diabetic mice, and the hypoglycemic effect is dose-dependent.

1.2 Cough suppressant and expectorant effects

Wang Ting et al. [11] gavaged mice with Mogroside with a purity of 98% at doses of 80, 160, and 320 mg/kg, and Mogroside with a purity of 50% given at doses of 4.0 g/kg and 8.0 g/kg by gavage also significantly reduced the number of coughs in mice induced by concentrated ammonia water. It was confirmed that the purity and dose of Mogroside directly affect the cough-relief effect in mice. Chen Yao et al. [12] found that Mogroside can also increase the phenol red excretion of the trachea in mice, promote the movement of frog esophageal ciliated cells, and significantly increase the amount of sputum excreted, proving that Mogroside has the property of improving respiratory function.

1.3 Antioxidant and liver protection

Mogroside Ⅴ is the main saponin component of Luo Han Guo and also the most active antioxidant ingredient [13]. Xiao Gang et al. [14] found in their experimental study of 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, It can increase the activity of superoxide dismutase (SOD) in mouse liver tissue homogenates, reduce the content of malondialdehyde (MDA), and significantly reduce the degree of pathological changes in liver tissue, indicating that Mogroside has a protective effect on acute and immune liver damage in mice.

Zhao Yan et al. [15] studied the in vivo antioxidant effects of water extract of Luo Han Guo and its sweeteners. They gave 2% aqueous solution of water extract of Luo Han Guo and 0.08% solution of Luo Han Guo sweeteners to high-fat model mice for 60 days (the amount of water extract of Luo Han Guo and Luo Han Guo sweeteners added to the drinking water of the mice was the median of the amount added to the food). the results showed that both Mogroside and Mogroside water extract significantly increased the activity of glutathione peroxidase (GSH-PX) and SOD in the serum of high-fat model mice, and significantly reduced the content of MDA in the serum. This indicates that Mogroside and Mogroside water extract have a strong antioxidant effect.

1.4 Immune regulation

In a study of the immune regulation effects of mogroside on mice, Wang Qin et al. [16] found that after 80% mogroside was administered at doses of 0.75 g/kg and 1.5 g/kg to normal mice and mice with the immunosuppressive model of cyclophosphamide via continuous gavage for 10 days, Mogroside had no significant effect on the phagocytic function of normal mouse macrophages and lymphocyte proliferation, but significantly improved the function of cyclophosphamide immunosuppressed mouse macrophages and lymphocyte proliferation[17 -18]. Zhang Liqin et al. [13] used 80% Luo Han Guo saponin extract at doses of 150 mg/kg and 300 mg/kg to continuously gavage mice with type 1 diabetes induced by alloxan for 30 days. It was found that Luo Han Guo saponin extract can affect the mouse spleen lymphocyte subsets and the expression of cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-4 expression, thereby improving the immune imbalance in diabetic mice.

1.5 Anti-cancer effect

Japanese scholar Takao Kijima [19] used 7,12-dimethylbenz[a]anthracene (DMBA) as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter in a two-stage carcinogenesis experiment on mouse skin in a test of Mogroside's anticancer effect. The results showed that Mogroside V had an anticancer effect, and this delayed carcinogenic effect was even stronger than that of stevioside.

1.6 Regulating blood lipid metabolism

Zhao Yan et al. [20] used a 0.08% solution of mogroside to continuously gavage a mouse model with a high-lipidemia immune complex rosette rate (I-CR) for 60 days. It was found that the total cholesterol (TC) and total triglyceride (TG) levels in the serum of hyperlipidemic mice were reduced, while the high-density lipoprotein cholesterol (HDL-C) level was significantly increased. This indicates that Mogroside has the function of regulating blood lipid metabolism.

1.7 Anti-caries effect

Zhao Yan [21] conducted an experimental study on the anti-caries properties of Mogroside and Luo Han Guo concentrated juice. Luo Han Guo concentrated juice, Mogroside, sucrose, fructose, glucose and xylitol were added to the basic culture medium to give a final sugar concentration of 20 g/L. under aseptic conditions, the Streptococcus mutans bacterial solution was inoculated at a rate of 2% (by volume) into each culture medium, and the Streptococcus mutans bacterial solution was inoculated at a rate of 10% into each culture medium. Streptococcus mutans was inoculated at a rate of 10% into a culture medium containing 20 g/L of Luo Han Guo concentrated juice, 20 g/L of Mogroside and 20 g/L of sucrose. After mixing, it was found that the growth rate and adhesion of Streptococcus mutans in the culture medium containing Luo Han Guo concentrated juice were significantly lower than those in the sucrose culture medium, but the acid production was higher. and almost no growth in the culture medium containing mogroside. The results show that mogroside is a low-caries substitute for sucrose and can be used as a health-conscious high-intensity sweetener.

2 Toxicity studies

2.1 Acute toxicity test

Su Xiaojian et al. [9] used 81.6% Mogroside to treat Kunming mice by gavage at a dose of 0.2 mL/10 g once. The LD50 was >10 g/kg. After one week of observation, the mice were normal in activity, diet, bowel movements, and body weight, and there were no deaths. This proves that Mogroside is non-toxic. Li Xiaohong et al. in this laboratory used the maximum tolerated dose (MTD) method. Luo Han Guo sweet glycosides (total glycosides greater than or equal to 80%, Mogroside V greater than or equal to 30%) were administered to Kunming mice and SD rats at a maximum tolerated dose of 15 g/kg by gavage once. The animals were observed for 2 weeks. There were no deaths or adverse reactions in the rats or no deaths or adverse reactions were observed in either rats or mice, which also proves that mogroside has no adverse reactions.

2.2 Ames test

The histidine-deficient Salmonella typhimurium (TA97, TA98, TA100, TA102) strains were used. the mutagenicity of Mogroside was tested under conditions with and without an in vitro activation system (+S9) simultaneously. The results showed that the spontaneous revertant numbers of the strains in each dose group were all within the normal range, indicating that Mogroside has no direct or indirect mutagenic effect on the test strains [9, 22-23].

2.3 30-day feeding trial in dogs

Domestic dogs were given a one-time dose of Mogroside 10 mL/kg (3.0 g/kg) by gavage for 28 consecutive days. The general condition of the dogs was observed during administration. On the 29th day, the dogs were killed and their organs were removed for pathological examination. The results showed that there was no significant effect on the hematological indicators, liver and kidney function, blood glucose, urine glucose, heart, liver, spleen, lung, kidney morphology showed no significant effect [9, 24-28], confirming that Mogroside has no adverse reactions.

3 Outlook

Mogroside is a unique product in China. It has been eaten and drunk in folk history since ancient times. Due to its various characteristics such as food safety, low calories, high sweetness, non-diabetic and non-caries-causing, it is expected to become an alternative to the artificial sweetener aspartame. and will also become an ideal food sweetener for patients with obesity, hyperglycemia, and hyperlipidemia. It also has broad development and application prospects in the development of functional food additives, and is a sweet-tasting plant with great potential.

With the improvement of living standards, more than 80% of pregnant women with diabetes have gestational diabetes, and less than 20% have diabetes combined with pregnancy. The incidence of gestational diabetes has been reported to range from 1% to 14% in countries around the world, and the incidence in China is 1% to 5%, with a significant upward trend in recent years. Pregnancy can cause insulin resistance in pregnant women, as well as symptoms such as pre-eclampsia, premature rupture of membranes, and premature birth. The risk of fetal abnormalities is 3 to 5 times higher than normal. At present, there is no radical cure, and it is a major hazard to both mother and child, so it must be taken seriously.

Although in recent years many scholars have studied the composition and pharmacological effects of Mogroside [29-31], whether it has potential genotoxicity, especially whether it has an effect on maternal blood glucose, insulin levels and embryonic development in pregnant women after consuming foods containing Mogroside, and whether it is suitable for long-term consumption by all populations, can only be thoroughly discussed through extensive clinical studies and animal model experiments for gestational diabetes. can be thoroughly discussed. In particular, animal experiments on the genotoxicity and embryotoxicity of Mogroside are indispensable in order to provide richer experimental data and theoretical basis for clinical application and food production.

References

[1] Si Jianyong, Chen Dihua. Research on the chemical composition of the root of the Guangxi specialty plant Luohanguo [J]. Journal of Pharmacy, 1999, 34 (12): 918-920.

[2] Zhu Hua, Chen Xiaobo, Liang Changxiang, et al. Overview of research on Luohanguo [J]. Chinese Medicine Information Journal, 2008, 15 (Suppl. 1): 100-102.

[3] Liao Riquan, Li Jun, Huang Xishan, et al. Research on the chemical composition of Luo Han Guo [J]. Acta Botanica Boreali-Occidentalia Sinica, 2008, 28(6): 1250-1254.

[4] Li Wende, Jian Jiangbo. Development and application of the functional sweet plant Luo Han Guo [J]. China Food Additives, 2007 (6): 120-121.

[5] Li Jun. Luo Han Guo sweet glycoside [J]. China Food Chemicals, 1997 (2): 39-41.

[6] Ju Wei, Cheng Yuyan, Zhang Jian. Overview of research on Luo Han Guo [J]. Guangxi Light Industry, 2001 (4): 4-6.

[7] Xu Qing, Liang Ronggan, Su Xiaojian, et al. Effect of Mogroside on blood glucose and liver enzyme activity in normal people [J]. Food Science, 2007, 28 (6): 315-317.

[8] Zhang Hong, Li Xiaohong. Research progress on the pharmacological effects and toxicity of Luo Han Guo [J]. Chinese Agricultural Science Bulletin, 2011, 27(5): 430-433.

[9] Su Xiaojian, Xu Qing, Liang Ronggan, et al. Research on the toxic effects of Mogroside [J]. Food Science, 2005, 26(3): 221-224.

[10] Qi Xiangyang, Chen Weijun, Song Yunfei, et al. Hypoglycemic effect of Mogroside extract in diabetic mice [J]. Chinese Journal of Public Health, 2003, 19(10): 1226-1227.

[11] Wang Ting, Huang Zhijiang, Jiang Yimin, et al. Research on the biological activity of mogroside [J]. Chinese Herbal Medicine, 1999, 30 (12): 914-916.

[12] Chen Yao, Fan Xiaobing, Wang Yongxiang, et al. Research on the antitussive and expectorant effects of mogroside [J]. Chinese Food Additives, 2006 (1): 41-43.

[13] Zhang Liqin, Qi Xiangyang, Chen Weijun, et al. Effects of Mogroside extract on blood glucose, blood lipids and antioxidant activity in diabetic mice [J]. Chinese Pharmacological Bulletin, 2006, 22 (2): 237-240.

[14] Xiao Gang, Wang Qin. Protective effect of mogroside on experimental liver injury in mice [J]. Research in Chinese Medicine, 2008, 19 (3): 163-165.

[15] Zhao Yan, Liu Guoyan, Shi Xianming. In vivo antioxidant effects of water extract of Luo Han Guo and its glycosides [J]. Food Research and Development, 2012, 33 (2): 174-176.

[16] Wang Qin, Wang Kun, Dai Shengming, et al. Regulation of Luo Han Guo glycosides on mouse cellular immune function [J]. Traditional Chinese Medicine, 2001, 24(11): 811-812.

[17] Li J, Huang Y, Liao RQ, et al. Effect of Siraitia grosvenori polysaccharide on immune function in mice [J]. Chinese Pharmacological Bulletin, 2008, 24(9): 1237-1240.

[18] Qi XY, Chen WJ, Liu LG, et al. Effect of a Siraitia grosvenori extract containing mogrosides on the cellular immune system of type Ⅰdiabetes mellitus mice [J]. Mol Nutr Food Res, 2006, 50(8): 732-738.

[19] K. Kijima. Anticancer effect of the sweet substance in Luo Han Guo [J]. Foreign Medicine. Traditional Chinese Medicine Supplement, 2003, 25(3): 174.

[20] Y. Zhao, G. Liu, X. M. Shi. Effects of Luo Han Guo concentrated juice and Luo Han Guo glycosides on blood lipid metabolism in mice [J]. Chinese Journal of Food Science, 2008, 8(1): 9-12.

[21] Zhao Yan. Experimental study on the cariostatic properties of Luo Han Guo concentrate and Luo Han Guo glycoside [J]. Food Research and Development, 2010, 31(2): 87-90.

[22] Marone PA, Borzelleca JF, Merkel D, et al. Twenty eight-day dietary toxicity study of Luo Han fruit concentrate in Hsd: SD rats [J]. Food Chem Toxicol, 2008, 46(3): 910-919.

[23] Jin M, Muguruma M, Moto M, et al. Thirteen-week repeated dose toxicity of Siraitia grosvenori extract in Wistar Hannover (GALAS) rats [J]. Food Chem Toxicol, 2007, 45(7): 1231-1237.

[24] Hao Guixia. The scavenging effect of Siraitia grosvenori extract on free radicals [J]. Jiangxi Chemical Industry, 2005 (4): 89-90.

[26] Chen WJ, Wang J, Qi XY, et al. The antioxidant activities of natural sweeteners, mogrosides, from fruits of Siraitia grosvenori [J]. Int J Food Sci Nutr, 2007, 58(7): 548-556.

[27] Konoshima T, Takasaki M. Cancer-chemopreventive effects of natural sweeteners and related compounds [J]. Pure Appl Chem, 2002, 74(7): 1309-1316.

[28] Takasaki M, Konoshima T, Murata Y, et al. Anticarcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori [J]. Cancer Lett, 2003, 198(1): 37-42.

[29] Zhou X, Song J. Research on the pharmacological effects of Luo Han Guo and Luo Han Guo extract [J]. Chinese Medicine, 2004, 22 (9): 1723-1724.

[30] Liao RQ, Li J, Huang XS, et al. Study on the chemical constituents of Luo Han Guo [J]. Journal of Northwest Plant Protection, 2008, 28 (6): 1250-1254.

[31] Xu Q, Su XJ, Liang RG, et al. Subchronic 90-day oral (gavage) toxicity study of a Luo Han Guo mogroside extract in dogs [J]. Food Chem Toxicol, 2006, 44(12): 2106-2109.