What Is Monk Fruit?

Siraitia grosvenorii, known by its Latin name Siraitiagrosvenorii, is a perennial vine in the family Cucurbitaceae. It is a traditional Chinese medicine, and the main cultivation is concentrated in Yongfu and Lingui counties in Guangxi[1]. The “Zhongyao Zhi” (A Compendium of Chinese Materia Medica) records that Luo Han Guo is sweet and cool in nature, and has the effects of clearing away heat and detoxifying, moistening the bowels and relieving constipation, and moistening the lungs and relieving coughing. It is clinically used to treat a variety of diseases, such as acute and chronic bronchitis, tonsillitis, pulmonary tuberculosis, and hypertension[2]. As a medicinal and edible agricultural by-product, Monk Fruit is rich in a variety of nutrients, such as essential amino acids, VC, VE, trace elements, etc., and also contains bioactive ingredients such as flavonoids, saponins, polysaccharides, and polyphenols[3]. As research progresses, Luo Han Guo is being used more and more in the food industry. This article reviews the current research status of the bioactive components, pharmacological effects and product processing of Luo Han Guo, with the aim of providing a reference for further research and development of the utilization of Luo Han Guo resources.

1 Bioactive components of Luo Han Guo

The main bioactive components of Luo Han Guo are cucurbitane triterpenoids, flavonoids, protein amino acids, polysaccharides and other components.

1.1 Cucurbitane triterpenoids

The main bioactive component of Luo Han Guo, cucurbitane triterpenoids, accounts for 3.75% to 3.85% of the total content in the dried fruit of Luo Han Guo[4]. As early as 1975, American scholar Lee extracted triterpenoids from Luo Han Guo[5]. To date, 12 triterpenoid compounds (cucurbitane glycosides) have been found in Luo Han Guo, namely: Siamenside I, grosmomoside I, grosmomoside III, ogroside IIE, mogroside III, mogroside III E, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroside VI, mogroside A, mogroside II, mogroside III, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroester, mogroside A, mogroside II, mogroside III, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroester, mogroside A, mogroside II, mogroside III, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroester, mogroside A, mogroside II, mogroside III, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroester, mogroside A, mogroside II, mogroside III, mogroside IV, mogroside V, 11-oxo-mogroside V, mogroester, mogroside A, mogroside II, mogros As a natural sweetener, the health and safety of the triterpene compound monacolin K has been widely used in foods.

1.2 Flavonoids

Flavonoids are present in Luo Han Guo in the form of glycosides, and the main components are mainly kaempferol and quercetin. There have been relatively few reports on flavonoids in Luo Han Guo, and they are generally only mentioned when analyzing Luo Han Guo glycosides[8]. In 1994, Si Jianyong and others were the first to isolate two flavonoid glycosides from fresh Luo Han Guo[9]. Chen Quanbin et al. used RP-HPLC to determine that the total flavonoid content in Luo Han Guo was 5 mg to 10 mg per fruit, accounting for 1.42% of the total content [10]. Flavonoids have antibacterial, anti-inflammatory, antiviral and anti-tumor effects.

1.3 Polysaccharides

Polysaccharides are commonly found in the tissues of plants, animals and microorganisms in nature, and have a variety of important physiological functions. Initially, Xu Weikun et al. measured the total sugar content in the dried fruit of Monk Fruit to be between 25% and 38%, and the reducing sugar content to be between 16% and 33%. The fructose content of the reducing sugars was 10% to 18%, and the glucose content of the reducing sugars was 6% to 15% [11]. Li Jun et al. isolated and purified Monk Fruit polysaccharides and analyzed the components, which were found to contain xylose, glucose, rhamnose, galactose, arabinose and glucuronic acid[12]. Li Qi et al. found that most of the Luo Han Guo polysaccharides and total sugars are present in the pulp of the fruit, while the seeds contain very little [13].

1.4 Proteins and amino acids

Xu Weikun et al. measured the protein and amino acid content of dried Monk Fruit and found that the protein content was 7.1% to 7.8%, and 18 amino acids were broken down in the hydrolysate, including 8 essential amino acids and 10 non-essential amino acids, with glutamic acid and aspartic acid being the most abundant [14].

1.5 Other ingredients

Monk Fruit contains a non-triterpene glycoside sweetener, D-mannitol, which is used clinically as a sweetener substitute for diabetics [15]. Wang Haibo et al. extracted nine fatty acids from Monk Fruit seeds, including 47.2% linoleic acid and 24.53% linolenic acid [16]. In addition, Luo Han Guo also contains a variety of trace elements and macroelements needed by the human body, among which calcium, magnesium and potassium are the macroelements with higher content, while the trace elements with higher content are silicon and selenium [17].

2 Pharmacological effects of Luo Han Guo

2.1 Cough suppressant and expectorant

It has been reported that Mogroside Ⅴ can significantly reduce the stimulation of the mouse respiratory system by ammonia, reduce the number of coughs, and increase the excretion of phenol red in the mouse trachea, indicating that Mogroside V has a certain effect of relieving cough and phlegm [18]. Wang Qin et al. showed that the expectorant effect of Luo Han Guo is not due to a single component, but rather the result of the combined action of multiple components. When used in combination with other cough suppressants, it has a synergistic effect [19]. Lv Jinyan et al. screened 13 components of Luo Han Guo with cough suppressant and expectorant effects through the TCMSP database analysis platform, and proved that most of these 13 active components are Luo Han Guo glycosides. A network model of Luo Han Guo's cough suppressant and phlegm-resolving effect was also constructed, providing a basis for further exploring Luo Han Guo's cough suppressant and phlegm-resolving effect [20].

2.2 Hypoglycemic, hypolipidemic and treatment of diabetes

Studies have shown that Luo Han Guo has a very significant hypoglycemic effect, and the main active substances are Mogroside, Luo Han Guo flavonoids and Luo Han Guo polysaccharides. Foreign scholars have found that Mogroside can lower insulin levels, thereby reducing fasting blood glucose and serum insulin levels in diabetic mice [21]. A study by Li Dan et al. showed that the flavonoids in Luo Han Guo can effectively improve diabetes, significantly lower blood sugar, inhibit α-glucosidase, protect the pancreas, etc. A diet containing higher levels of flavonoids can reduce the incidence of diabetes [22]. Huang Fei measured the lipid-lowering activity of Luo Han Guo polysaccharide. The results showed that Luo Han Guo polysaccharide has a certain metabolic effect on blood triglycerides and cholesterol, that is, Luo Han Guo polysaccharide has the effect of lowering blood sugar and blood lipids[23].

2.3 Scavenging free radicals and anti-oxidation

Free radicals exist in the body in a free form. The removal of excess free radicals in the body is beneficial to the prevention and treatment of diseases. Therefore, the current global research hotspot is to find safe and efficient natural antioxidants[24]. It has been reported that mogroside can increase the activity of SOD and GSH-PX in the body and reduce the content of MDA in the serum, indicating that mogroside has the ability to scavenge free radicals and resist lipid peroxidation [25]. The antioxidant effect of mogroside is reflected in its large number of phenolic hydroxyl groups, which can scavenge active oxygen and free radicals [26].

2.4 Anti-bacterial, anti-inflammatory, liver-protecting and enzyme-inhibiting

Mogroside has a certain anti-bacterial and anti-inflammatory effect. Research has confirmed that Mogroside can protect the liver, lower enzymes, prevent liver fat accumulation, inhibit lipid peroxidation, improve inflammation, and treat non-alcoholic fatty liver disease [27]. Di et al. used a mouse ear swelling model and found that Mogroside exerts an anti-inflammatory effect by inhibiting the expression of key inflammatory genes, enhancing protective inflammatory genes, and inhibiting cellular inflammatory responses [28]. Liang Shuo et al. studied the antibacterial properties of Luo Han Guo extract and confirmed that it can inhibit the activity of Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Aspergillus niger and Aspergillus oryzae, i.e. Luo Han Guo has antibacterial properties, which provides a reliable theoretical basis for the development of natural antibacterial preservatives [29].

2.5 Regulating the body's immune system

Li Jun et al. pointed out that Luo Han Guo polysaccharide can significantly increase the weight of normal mouse immune organs, improve the phagocytic capacity of mouse peritoneal macrophages, promote the formation of serum hemolysin, increase the conversion rate of lymphocytes and the index of immune organs, so Luo Han Guo polysaccharide has a significant immune enhancing effect on the body [30]. Chen Weijun et al. found that mogroside can regulate the antigen expression of splenic lymphocytes in type 1 diabetic mice, thereby playing a certain therapeutic role in type 1 diabetes [31].

2.6 Anti-cancer and tumor inhibition

Mogroside is the precursor of mogroside, which can inhibit the proliferation of tumor cells, induce apoptosis of tumor cells, and block the cell cycle, thereby achieving an anti-tumor effect [32]. Another study pointed out that mogroside can reduce the density of microvessels and the formation of tumor blood vessels, and can also arrest the growth cycle of pancreatic cancer cells and promote the death of pancreatic cancer cells, thereby inhibiting tumor growth [33]. S.M. pointed out that Luo Han Guo extract can inhibit the expression of the Cyplal gene, thereby preventing the production of reactive oxygen species (ROS) and inhibiting the occurrence of liver cancer [34].

2.7 Other pharmacological effects

Monk Fruit extract has been shown to have some effect in combating fatigue. Yu Cong et al. analyzed the metabolic status and fatigue resistance of rats trained in swimming with weights by administering Monk Fruit extract. The results showed that Monk Fruit extract can increase the testosterone levels of rats trained in swimming with weights and enhance material metabolism, thereby increasing the rats' resistance to exercise and fatigue [35]. Ju Peijun et al. found that Mogroside V can effectively improve the schizoid behavior of mice with hypofunction of glutamate and regulate the damage of PPI [36]. In addition, it was found that MogrosideIII E can inhibit myocardial fibrosis and prevent and treat myocardial fibrosis [37].

3  Research status of the processing and application of Monk Fruit products

Luo Han Guo is known as the “Oriental Divine Fruit”. It is full of treasures, and everything from the outside peel to the inside flesh to the seeds has high medicinal value. At present, in the development and utilization of Luo Han Guo products, the main substance being studied is the sweetener mogroside. As a natural sweetener, it is hundreds of times sweeter than sucrose, but has very few calories, only 1/50 of sucrose. This makes Luo Han Guo the most popular sugar substitute for people with diabetes, hypertension, obesity, etc. As early as 1995, Mogroside was approved for use as a food additive by the FDA and China; subsequent approvals were also granted in Singapore, Japan, Thailand, South Korea and many other countries.

3.1 Application of Luo Han Guo in food

The main applications of Monk Fruit in food are as follows: firstly, it can be directly sold as dried fruit; secondly, it can be made into Luo Han Guo powder or extracted as a natural sweetener and added to various types of food. For example, Wang Shupei and others combined Luo Han Guo extract with Wuyi cinnamon tea to develop a Monk Fruit tea with an excellent taste[38]. Zhang Ruirui et al. combined Luo Han Guo, lemon and kumquat to obtain a sweet and sour Luo Han Guo compound beverage [39]. Wang Chen et al. found that the application of Luo Han Guo's sweeteners has been studied, and Mogroside is now available as a “sugar packet” for customers to choose to add to drinks such as coffee, milk tea and soy milk [40].

3.2 Application of Luo Han Guo in health products

Due to its high sweetness and calorie-free characteristics, Luo Han Guo is widely used in health foods, such as the development of functional products with weight loss effects. He Weiping and others developed a low glycemic index nutritional powder using Luo Han Guo as the raw material, which has opened up food items for diabetic patients and obese people[41]. In addition, He Yi and others developed a Monk Fruit chewable tablet with Luo Han Guo as the main ingredient, adding starch and microcrystalline cellulose. This chewable tablet is uniform in color, has a refreshing sweet and sour taste, and has a certain antibacterial effect, which is a nemesis of chronic pharyngitis[42]. Yu Xin and others developed a natural health drink that is beneficial for people with diabetes by mixing Monk Fruit, Hedyotis diffusa Willd. and citric acid in a certain ratio [43].

3.3 Luo Han Guo in medicine

Luo Han Guo is often used in combination with other Chinese medicines that have the effect of relieving coughs and phlegm, such as Compound Luo Han Guo Cough Syrup [44], Qingfei Luo Han Guo Syrup [45], and Compound Luo Han Guo Cough Tablets [46]. In addition, Luo Han Guo has also been developed into Luo Han Guo effervescent tablets [47] and Luo Han Guo throat tablets [48] because of its efficacy in soothing the throat and moistening the throat.

4 Summary

Since the 21st century, people's health awareness has continued to improve. As a leader in “medicinal and edible plants”, Luo Han Guo can not only be used as a daily dietary ingredient, but also has important nutritional and health benefits. The processing and production of Luo Han Guo in China mainly involves making dried Luo Han Guo fruit, Luo Han Guo mixed drinks, and extracting Mogroside as a food additive. At present, dried fruit is still the main form of Monk Fruit product on the market, so Monk Fruit products are relatively simple. There are also problems with the in-depth processing of Monk Fruit to extract sweeteners, such as low utilization, high cost, and easy loss of effective ingredients. Therefore, research and development of new Monk Fruit products is an important guarantee for the long-term development of the Monk Fruit industry. In order to better exploit the nutritional benefits and economic value of Monk Fruit, its application has shifted from the traditional food industry to new types of functional health foods. To this end, we should establish a more comprehensive industrial system, intensify deep processing, open up foreign markets, and explore new ways of comprehensive utilization of Monk Fruit.

References:

[ 1] Chen Dihua, Si Jianyong, Chang Qi, et al. Research and application of natural sweetener Luohanguo [J]. Natural Product Research and Development, 1992 (1): 72-77.

[2] Lin Yanxiang, Liang Jingyu. Chemical research on Luohanguo [J]. Strait Pharmacy, 1997, 9 (2): 1-3.

[3] LIU C, RONG YH, WANG ZB, et al. Extraction of polyphenols from Luo Han Guo by flash extraction [J]. Food Science, 2010, 31(22): 50-53.

[4] LI DP, ZHANG HR. Research and application of Luo Han Guo, a specialty plant in Guangxi [J]. Guangxi Botany, 2000(3): 270-276.

[5] LEE CH. Intense sweetener from Lo HanKuo (Momordicagrosveno- rii) [J]. Experimentia, 1975 (31): 533.

[6] XIAO G, WANG Q. Research progress of Luo Han Guo [J]. Shanghai Journal of Traditional Chinese Medicine, 2006, 40 (11): 71-73.

[7] LARRY W, GREENLY D C. A doctor's guide to sweeteners [J]. Journal of Chiropractic Medicine, 2003, 2(2): 80-86.

[8] SU X, DENG Y, TAO M, et al. Nutritional and health-care functions of Luo Han Guo and progress in its development and application [J]. Anhui Agricultural Science Bulletin, 2019, v. 25; No. 360, No. 361 (Z1): 32-34.

[9] Si Jianyong, Chen Dihua, Chang Qi, et al. Separation and structural determination of flavonoid glycosides in fresh Luo Han Guo [J]. Acta Pharmaceutica Sinica, 1994, 29 (2): 158-160.

[10] Chen Quanbin, Yang Ruiyun, Yixianghui. Determination of total flavonoid content in fresh Luohanguo fruit and sweeteners by RP-HPLC [J]. Food Science, 2003, 24 (5): 133-135.

[11] Xu Weikun, Meng Lishan. Analysis of the sugar content of Luo Han Guo [J]. Guangxi Agricultural Science, 1980 (3): 29.

[12] Li Jun, Chen Haiyan. Separation, purification and analysis of Luo Han Guo polysaccharides [J]. Chemical World, 2005 (5): 277-280.

[13] Li Qi, Xiao Cong. Determination of the content of fructose components in Luo Han Guo [C]. Proceedings of the 9th Chinese Medicine Identification Conference of the Chinese Society of Traditional Chinese Medicine, 2008: 563-567.

[14] Xu Weikun, Meng Lishan. Determination of the content of Luo Han Guo protein [J]. Guangxi Botany, 1986, (4): 295-296.

[15] C. A. M. HOUGH. Developments in sweeteners—1 applied science publishers [M]. London, 2005: 72.

[16] WANG Haibo, LI Changbao, WU Xuehui, et al. Optimization of the seed oil extraction process of Luo Han Guo using the response surface methodology and analysis of the fatty acid composition [J]. Chinese Journal of Cereals, Oils and Foodstuffs, 2013, 28(7): 46-49.

[ 17] Zhou Xinxin. Chemical composition and development and application of Luo Han Guo [J]. Chinese Medicine, 2003(9): 1482-1483.

[18] Liu Ting, Wang Xuhua, Li Chun, et al. Study on the antitussive, expectorant and antispasmodic effects of Luohanguo saponin V [J]. Chinese Journal of Pharmacy, 2007, 42 (20): 1534-1536, 1590.

[19] Wang Q, Xiao XQ, Dong W, et al. Research on the spectrum-effect relationship of the expectorant effect of Luohanguo [J]. Guangxi Plant, 2017, 37(5): 606-609.

[20] Lv JY, Huang JY, Yuan CY, et al. Research on the active ingredient targets of Luo Han Guo for cough and phlegm relief based on network pharmacology. Journal of Natural Sciences of Hunan Normal University, 2019, 42(1): 40-48.

[21] Liu HS, Qi XY, Yu K, et al. AMPK activation is involved in the hypoglycemic and hypolipidemic activities of mogroside-rich extract from siraitiagrosvenorii (Swingle) fruits on high-fat diet/streptozotocin-induced diabetic mice [J]. Food & Function, 2019, 10(1): 151-162.

[22] Li D, Peng C, Xie XF. Research progress on the treatment of diabetes and its complications with flavonoids [J]. Chinese Journal of Experimental Pharmacology, 2014, 20(11): 239-242.

[23] Huang F. Research on active ingredients of hawthorn leaves and monk fruit polysaccharides [D]. Nanning: Guangxi University, 2000.

[24] Jiang Jialuo, Liang Jie, Yang Yaya, et al. Research progress on the pharmacological and toxicological effects of loganin [J]. Modern Preventive Medicine, 2020, 47(12): 2246-2248, 2262.

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

[26] Shao Pei, Zhuang Hu, Jian Shunhua, et al. Research progress on the extraction, purification and bioactivity of Luo Han Guo flavonoids [J]. Food and Machinery, 2019, 35 (12): 221-225.

[27] Li Meifeng. Research on the efficacy and mechanism of Luo Han Guo water extract and Luo Han Guo glycoside V in the treatment of non-alcoholic fatty liver disease [D]. Guangzhou: Guangdong Pharmaceutical University, 2017.

[28] DI R, HUANG MT, HO CT, et al. Anti-inflammatory activities of mogrosides from Momordica grosvenori in murine macrophages in- terferon-α production by Pichia pastoris with an ethanol on- line measurement based DO-stat glycerol feeding strategy [J]. Chem Tech-nol Biot, 2014 (89): 10-16.

[29] Liang Shuo, Yang Zhiping, Fei Zhenhong, et al. Study on the antibacterial properties of Luo Han Guo [J]. Food Industry, 2016, 37 (7): 207-209.

[30] Li Jun, Huang Yan, Liao Riquan, et al. Effects of Luo Han Guo polysaccharide on immune function in mice [J]. Chinese Journal of Pharmacology, 2008, 24(9): 1237-1240.

[31] Chen Weijun, Song Fangfang, Liu Liegang, et al. Effects of Luo Han Guo saponin extract on cellular immune function in mice with type 1 diabetes [J]. Journal of Nutrition, 2006, 28 (3): 221-225.

[32] Fu Yuxia, Wang Lei, Li Dianpeng. Research on the antitumor activity and mechanism of Luo Han Guo alcohol [J]. Guangxi plants, 2016, 36 (11): 1369-1375.

[33] Liu C, Dai LH, Dou DQ, et al. A natural food sweetener with anti- pancreatic cancer properties [J]. Oncogenesis, 2016, 5: 217.

[34] SAYAKAM, MEILANJ, YASUAKID, et al. Suppressive effect of Siraitiagrosvenori extract on dicyclanil-promoted hepatocellular proliferativelesions in male mice [J]. J Toxicol Sci, 2009, 34(1): 109-118.

[35] Yu Cong, Wang Jie. Effects of Luo Han Guo extract on material metabolism and anti-exercise fatigue ability in rats trained with weight-bearing swimming [J]. Chinese Journal of Gerontology, 2016, 36(1): 12-13.

[36] Tao LJ, Yang JY, Cao FY, et al. Mogroside IIIE, a novel anti-fibrotic compound, reduces pulmonary fibrosis through Toll-Like receptor 4 pathways [J]. Journal of Pharmacology and Experimental Therapeutics, 2017, 361(2): 268-279.

[37] Ju Peijun, Ding Wenhua, Li Xiaobo, et al. Effects of monomeric morroniside on the schizophrenia-like behavior induced by dizoxanpium in mice [J]. Journal of Clinical Psychiatry, 2015 (4): 231-233.

[38] Wang Shupei, Shi Changrong, Wu Yucai, et al. Preparation of Luo Han Guo compound Wuyi cinnamon herbal tea beverage [J]. Subtropical Agriculture Research, 2016, 12(2): 113-119.

[39] Zhang Ruirui, Wang Jingjing, Lin Jiason, et al. Development of Luo Han Guo compound beverage [J]. Food Research and Development, 2020, 41(4): 136-140.

[40] Wang Chen, Zhang Sicong, Wang Jian, et al. Research progress and development suggestions for the application of Mogroside [J]. Modern Food, 2020(14): 61-65.

[41] He Weiping, Zhu Xiaoyun, Liu Lijun, et al. Research on the hypoglycemic index (GI) food and pharmacology of Luo Han Guo [J]. Guangxi Light Industry, 2011 (7): 1-3.

[42] He Yi, Liu Hanfei, Lin Bing, et al. Optimization of the preparation process and antibacterial activity of Luo Han Guo chewing tablets [J]. Food Research and Development, 2020, 41 (5): 138-144.

[43] Yu Xin, Chen Yuejiao, Qiu Liyong, et al. Research on the health care drink of Hedyotis diffusa Willd. and Luo Han Guo [J]. Food Science, 2002 (6): 42-45.

[44] Qin Qiaofeng, Lan Xiaoqing, Wen Qingwei, et al. Determination of Luo Han Guo saponin V in Compound Luo Han Guo Cough Suppressant by HPLC-ELSD [J]. Chinese Journal of Modern Applied Pharmacy, 2014, 31(7): 850-852.

[45] Wei Qizhi, Zhou Zhi, Liu Yankuai, et al. Pharmacodynamic study of Luo Han Guo syrup for clearing the lungs [J]. Chinese Journal of Experimental Formulae, 2004, 10(2): 51-53.

[46] Song Zhi-zhao, Wen Zhi-yun, Li Xing-yu, et al. Study on the extraction process of compound Luo Han Guo cough suppressant tablets [J]. Chinese patent medicine, 2009, 31 (11): 1773-1774.

[47] Chen Bo, Chen Wei, Zhang Yu-mei, et al. Study on the preparation process of Luo Han Guo effervescent tablets [J]. Chinese Medicine, 2015, 28(4): 101-103.

[48] Jin Chunhua, Jiang Xiulian, Hong Tie, et al. Pharmacological study of Luo Han Guo throat tablets. Chinese Materia Medica, 1997, 20(11): 574-577.