Study on the Benefit of Mogroside

Siraitiae Fructus (罗汉果) is a dual-purpose medicinal and edible plant in the Cucurbitaceae family. It was first recorded in the 1930 publication “Drug Production Identification” edited by modern pharmacologist Chen Renshan, and is one of the authentic medicinal herbs of Guangxi[1]. Siraitiae Fructus has a long history of use and is effective in moistening the lungs and clearing away heat. It is mostly used in the form of dried fruit, which enters the lung and large intestine meridians. It is cool in nature and sweet in taste[2]. Luohan fruit extract is mainly composed of triterpenoid saponins, flavonoids, polysaccharides, protein amino acids, volatile components, etc. Its main active ingredient is mogroside, which accounts for about 3.8% of the Luohan fruit. It is a triterpene glucoside substance belonging to the cucurbitane type of compound [3−4], including mogroside III, mogroside IV, mogroside V, mogroside VI, etc. The general formula is shown in Figure 1, of which mogroside V is the main sweetening component. In addition to mogroside, monk fruit bitter glycoside also belongs to monk fruit glycoside.  Luohanguo sweet glycoside and Luohanguo bitter glycoside have the same aglycone, but the total number of glucose residues connected at the 3rd and 24th positions of the aglycone is different. Luohanguo bitter glycoside is connected to 1 to 3 glucose residues, while mogroside is connected to 4 to 6 glucose residues, and is a strong sweetener [5].

Existing studies have found that Mogroside has various effects, such as regulating blood sugar [6], lowering blood lipids [7], resisting oxidative stress [8], relieving fatigue [9], protecting and nourishing the liver and preventing liver fibrosis [10], anti-inflammatory [11], improving lung function [12], protecting nerves [13], anti-cancer [14], promoting reproduction [15–16] and other effects. At present, the application of Mogroside is mostly focused on sweeteners. Although the application prospects of Mogrosides are broad, there are problems such as insufficient product development, low extraction purity, and incomplete exploration of pharmacological mechanisms. This study reviewed literature from recent years, summarized functional and application research on Mogroside at home and abroad, and explored them according to their functions and applications. The aim is to deepen the understanding of monk fruit, so as to provide new ideas for further exploration of the functional activity of Mogroside and provide reference materials for its in-depth development and application.

1 Functional activity of mogrosides

1.1 Regulating blood sugar and lowering lipids

Research has found that mogrosides have an anti-hyperglycemic effect, and the mechanism may be related to intestinal flora [6, 17]. Mogrosides can inhibit the activity of α-glucosidase, thereby exerting an anti-hyperglycemic effect. Some scholars have found that the IC50 of Mogroside extract from dried Luohanguo for inhibiting α-glucosidase is 2.40 mg/mL in the range of 0.04–10 mg/mL, Mogroside extract from fresh Luo Han Guo has an IC50 of 11.51 mg/mL for α-glucosidase inhibition in the range of 0.63-80 mg/mL, and has a certain degree of α-glucosidase inhibitory activity [18]. Huang Panling et al. [19] found that Luo Han Guo glycoside can inhibit α-glucosidase activity at 200.00 mg/kg and 100.00 mg/kg, and that there is a significant difference (P<0.05) in the inhibition of α-glucosidase activity compared to diabetic model mice. The decrease in α-glucosidase activity helps slow down the rate of carbohydrate breakdown, regulate glucose metabolism, and thus inhibit the rapid rise in postprandial blood glucose, which has an anti-hyperglycemic effect. The inhibitory activity of mogroside against α-glucosidase provides new ideas for the development of α-glucosidase inhibitors and offers a solution to the problems of existing α-glucosidase inhibitors, such as their side effects and poor efficacy.

In recent years, with the increasing number of obese people, obesity-related diseases have also received increasing public attention. In terms of obesity, Liu et al. [7] showed that Mogroside-rich extracts have lipid-lowering effects, and that the exertion of these effects is related to AMPK signal activation. It can be inferred that Mogroside, which is present in high concentrations in the extract, exerts lipid-lowering effects. Another study found that a glycoside in Mogroside inhibits fat production. In-depth research on the mechanism found that it mainly works by activating the AMPK signal transduction pathway and reducing the activation of the cAMP response element binding protein during early cell differentiation [20]. In a mouse protection experiment with a high-fat diet, it was also found that mogroside V can activate AMPK thereby achieving a protective effect on mice fed a high-fat diet [21]; it can be inferred that the lipid-lowering function of mogroside is closely related to the activation of the AMPK signaling pathway, which can inhibit fat production by activating the AMPK signaling pathway. This also suggests that mogroside can be used for the development of functional foods for lipid-lowering and weight-loss applications, better meeting the needs of the times for fat-reducing products.

1.2 Antioxidant stress

Oxidative stress is caused by an imbalance of free radicals in the body on the one hand and the accumulation of reactive oxygen species (ROS) in the body on the other. With in-depth research on the functions of mogrosides, scholars have found that mogrosides have potential free radical scavenging activity. When the concentration of mogrosides reaches 80 μmol/L, the DPPH free radical scavenging rate can reach 17.23%. At a concentration of 16.8 μmol/L, its superoxide anion radical scavenging rate can reach 16.48% [22]. Xia Xing et al. [8] further demonstrated in an experiment using H2O2 to induce oxidative stress in PC12 cells that mogroside can exert its antioxidant stress effect by regulating the free radical balance. H2O2, as a reactive oxygen species, can induce cells to form highly active free radicals, causing oxidative stress and cell damage. After intervention with mogroside ≥80% purity, the superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity of H2O2-treated PC12 cells were significantly increased (P<0.001).

Xu et al. [23] also found that Mogroside can exert its antioxidant stress effect by reducing intracellular reactive oxygen species. The 1 mmol/L Mogroside treatment group significantly reduced the intracellular ROS concentration (P<0.05) compared to the blank group, while the cells intervened by palmitic acid, after the intracellular reactive oxygen species level increased, were treated with 1 mmol/L Mogroside, can inhibit the increase in the level of active oxygen (P<0.05). In summary, Mogroside can exert an anti-oxidative stress effect by scavenging free radicals and also by scavenging accumulated active oxygen in the body.

It is currently known that HSP70 is often highly induced in stressed cells and has a stress-protective effect. When Mogroside acts on the gastric tissue of rats that have been exhausted by exercise, it can increase HSP70 mRNA expression and HSP70 protein expression levels. The low, medium and high-dose groups (100, 200, 400 mg/kg) had higher HSP70 mRNA expression levels than the resting group and exercise group (P<0.01, P<0.05), and the HSP70 protein expression levels were significantly higher than the exercise group (P<0.05) [24], which can play a role in stress protection. Therefore, Mogroside exerts its stress protection effect by regulating heat shock proteins, which can also be used as an entry point for the development of Mogroside antioxidant stress products. However, there is currently a lack of support from clinical trial data, and the corresponding mechanism exploration still needs to be further investigated.

At present, it has been found that various mogroside compounds such as mogroside V, mogroside IIA2, mogroside VI, mogroside III, 11-oxo-mogroside V, and mogroside IV all have antioxidant activity [25]. Oxidative stress is an important factor in aging. The antioxidant activity of various Mogrosides provides favorable conditions for the development and utilization of Mogrosides in anti-aging products.

1.3 Anti-fatigue

Under the influence of many factors such as the accelerated pace of society, the term “fatigue” has slowly entered the public eye. Existing studies have shown that Mogroside has functional activity against fatigue. For example, in mice that have been subjected to exhaustive exercise and in normobaric hypoxia tolerance experiments, Mogroside was found to significantly increase the body's glycogen reserves (P<0.001) and significantly enhance lactate dehydrogenase activity (P<0.05), thereby accelerating lactic acid metabolism and ultimately enhancing the mice's resistance to fatigue and hypoxia [9].

The most direct manifestation of fatigue is a decrease in exercise tolerance. In terms of the anti-fatigue activity of Mogroside, both Mogroside and Mogroside extract can prolong the exhaustion swimming time of mice, and can also significantly reduce the blood lactate (P<0.001) and blood urea nitrogen levels (P<0.001) of mice, and increase the liver and muscle glycogen reserves and post-exercise lactate dehydrogenase activity. Mogroside has the strongest effect on extending the duration of swimming in mice, suggesting that it is an important substance for exerting anti-fatigue activity [26]. When the body exercises heavily, it produces a large number of free radicals, which in turn trigger oxidative stress and are one of the causes of exercise fatigue. Mogrosides have strong free radical scavenging and lipid peroxidation inhibition effects. Therefore, supplementing with mogrosides during exercise can relieve exercise fatigue.

1.4 Liver protection, liver care and anti-liver fibrosis

There are many causes of liver damage, which can be divided into acute and chronic liver damage. In a study on Mogroside's intervention in liver damage, Mogroside VI was found to alleviate acute liver damage caused by sepsis in mice by enhancing PGC-1α-mediated mitochondrial biosynthesis. The experiment found that the PGC-1α expression level in the 100 mg/kg MogrosideⅥ treatment group was significantly higher than that in the model group mice (P<0.05), suggesting that MogrosideⅥ may improve liver damage by enhancing liver mitochondrial biosynthesis [10]. Some scholars applied Mogroside to rats with CCl4-induced chronic liver injury model and gave Mogroside at three doses (0.8, 0.4, and 0.2 g/kg, respectively). The results showed that the serum ALT and AST levels in the three dose groups were significantly reduced (P<0.05), liver pathological damage was also alleviated, and the expression of TGF-β 1 was inhibited, suggesting that blocking the expression of TGF-β 1 may be one of the mechanisms by which Mogroside protects against liver damage [27].

At present, there are a large number of liver cancer patients in China each year, and there is a lot of social and economic pressure. The number of deaths accounts for about 51% of the total number of deaths from liver cancer worldwide. Liver fibrosis is the pathological basis of many liver diseases[28], and research on liver fibrosis has received widespread attention. Although there is currently no effective clinical drug treatment for liver fibrosis, some studies have shown that mogroside can reduce the degree of liver fibrosis in mice[29]. Mogroside has a certain inhibitory effect on the development of liver fibrosis. Research on mogroside has found that it can inhibit collagen production, promote the degradation of the extracellular matrix, and induce apoptosis of the hepatic stellate cell line HSC-T6 to exert anti-fibrosis effects [30–31]. Hepatic stellate cells play an important role in the process of liver fibrosis. The above findings suggest that the anti-fibrosis mechanism of mogroside is related to the promotion of apoptosis of hepatic stellate cells. Song Kaijuan et al. [32] further verified the correctness of this hypothesis. Mogroside can inhibit the activation of hepatic stellate cells on the one hand and promote the apoptosis of hepatic stellate cells on the other hand, thereby achieving the effect of anti-fibrosis. In summary, Mogroside's anti-hepatic fibrosis effect may be related to promoting the apoptosis of hepatic stellate cells.

1.5 Anti-inflammatory

Mogroside has anti-inflammatory biological activity and has a good effect on a variety of inflammations. In a study of mice with ulcerative colitis model, mogroside was found to prevent intestinal epithelial barrier dysfunction through the AMPK-mediated signaling pathway and inhibit the production of inflammatory mediators in cells [11]. In terms of intervention therapy for neuritis, some scholars have revealed the mechanism of mogroside on LPS-induced neuroinflammation and neuronal damage. Mogroside may exert a protective effect by inhibiting TLR4-MyD88 and activating the AMPK/AKT-Nrf2 signaling pathway, indicating that mogroside has anti-neuroinflammatory function [33].

In terms of pancreatitis, Mogroside can reduce the level of interleukin 9 (IL-9) in mice with a pancreatitis model by downregulating the IL-9/IL-9 receptor pathway, thereby improving the symptoms of pancreatitis in mice, thus exerting its anti-pancreatitis effect [34]. Scholars have found that Mogroside-containing extracts can significantly reduce epidermal hyperplasia and inflammatory cell infiltration in atopic dermatitis skin lesions and reduce the severity score of dermatitis when intervening in a mouse model of atopic dermatitis allergic inflammation, suggesting that Mogroside has a certain therapeutic effect on atopic dermatitis and has the potential to be used as a treatment for atopic dermatitis [35]. In summary, mogroside has a certain therapeutic effect on a variety of inflammatory responses, but there are still gaps in the exploration of its corresponding mechanisms, and more high-quality studies are needed for further exploration.

1.6 Improve lung function

As a medicinal herb with similar properties to food, Luo Han Guo enters the lung meridian and has the property of benefiting the pharynx and opening the voice. It can be used to develop health foods that improve lung function. For example, when mogroside is used in an ovalbumin (OVA)-induced asthma mouse model, it reduces airway hyperresponsiveness, decreases the number of inflammatory cells, and alleviates the inflammatory infiltration in the mouse lungs, providing good asthma-alleviating effects [12]. Some scholars have found that the expectorant effect of Luo Han Guo is the result of the combined action of multiple ingredients, but Mogroside contributes the most to the expectorant effect [36]. Research has found that Mogroside V and berberine can have a synergistic effect on cough suppression and expectorant action. The specific combination ratio can be 1:1 or 1:2 [37]. The above research suggests that when Mogroside is used, it not only has the effect of improving lung function by relieving asthma, expectorating and relieving cough, but also should be combined with a variety of drugs to maximize its efficacy.

1.7 Protecting the nerves

Neuron damage is one of the causative factors of many diseases, and Mogroside's neuroprotective function is important for the treatment of these diseases. For example, studies have shown that mitochondrial dysfunction and oxidative stress play a major role in the pathogenesis of Parkinson's disease. Mogroside can alleviate mitochondrial dysfunction by upregulating Sirtuin3, thereby reducing damage to neurons and exerting a protective effect, which is beneficial to the treatment and rehabilitation of Parkinson's disease [13]. In terms of research on Mogroside's ability to protect neurons from damage, scholars have found that Mogroside has a protective effect on neurons damaged by MK-801. The bioactive components of Mogroside and its metabolites can prevent neuronal damage by promoting neurite growth, inhibiting apoptosis and calcium ion release, and have certain potential for the treatment of schizophrenia [38]. In summary, Mogroside has a certain therapeutic effect on neurological diseases, especially in the treatment of some diseases caused by nerve damage. Its mechanism may be related to the protection of neuronal function.

1.8 Anti-cancer

Cancer is a type of disease that seriously threatens human health, so the exploration, research and application development of anti-cancer drugs is very necessary. At present, the bioactive component of Luo Han Guo, Luo Han Guo Glucoside, has been reported to have anti-cancer effects. High blood sugar can promote the invasion and migration of two lung cancer cell lines, A549 and H1299, and promote epithelial-mesenchymal transition (EMT). Therefore, in the treatment of lung cancer, not only should it be anti-cancer, but also pay attention to changes in blood sugar in patients. Luo Han Guo Glucoside not only has the property of regulating blood sugar, but also has anti-cancer properties.

Experiments have shown that it can inhibit the migration of lung cancer cells, upregulate E-Cadherin expression, and downregulate N-Cadherin, Vimentin, and Snail expression to reverse the EMT process. It has the effect of inhibiting the migration and invasion of lung cancer cells induced by high blood sugar and protecting the lungs from cancer [14]. In studies of colorectal and laryngeal cancer, loganin has shown a certain inhibitory activity against colorectal and laryngeal cancer, and its inhibitory activity also showed a dose-dependent effect, suggesting that mogroside can be used as a phytochemical supplement for the treatment of colorectal and laryngeal cancers [39]; the natural sweet compound mogroside can inhibit the proliferation and survival of pancreatic cancer cells by targeting multiple biological targets [40], suggesting that mogroside can help in the treatment of pancreatic cancer and provide new ideas for the development of anti-cancer drugs.

Mogroside intervention when TPA induces skin cancer in mice, and then showed a strong inhibitory effect on cancer, the results showed that the number of papillomas per mouse decreased by more than 50% within 20 weeks [41]. In addition, mogroside can also be used in the treatment of ovarian cancer [42]. Through network pharmacology and molecular docking, combined with previous results, it was determined that mogroside can treat ovarian cancer through core targets including Jun, IL2, HSP90AA1, AR, PRKCB, VEGFA, TLR9, TLR7, STAT3, and PRKCA, providing a basis for mogroside to fight ovarian cancer. From the above, it can be seen that mogroside has shown a good inhibitory effect on cancer, which suggests that mogroside may be a good starting point for the development of anti-cancer drugs, but there is currently a lack of corresponding clinical trials to further verify this.

1.9    Promoting reproduction

Mogroside not only has the effect of anti-apoptosis, but also has the effect of promoting oocyte development [15−16]. In a study on pig oocytes, LPS was used to induce meiotic defects in pig oocytes, and mogroside was then selected for intervention. The results showed that mogroside reduced the level of reactive oxygen species (ROS) in oocytes exposed to LPS (P<0.005), and the percentage of positive oocytes decreased, and the fluorescence intensity of m6A was significantly increased (P<0.05), suggesting that Mogroside can protect oocytes from LPS-induced meiotic defects by reducing oxidative stress and maintaining m6A levels [43]. Sui et al. [44] further demonstrated that Mogroside can alleviate oocyte meiotic defects, and also shows that Mogroside has a certain role in reducing damage and promoting development during oocyte meiosis maturation and subsequent embryonic development. Some scholars have also found that Mogroside may also effectively improve the ovarian microenvironment by upregulating the expression of LDHA, HK2 and PKM2 in cells, enhancing lactic acid and energy production, thereby inducing follicle development and ovulation in rats [45]. Moreover, Mogroside also has the effect of promoting the proliferation and differentiation of osteoblasts [46]. The above studies have shown that Mogroside has a good effect on promoting reproduction, providing a feasible basis for the development of new applications.

2 Application of Mogroside in food

2.1 Sweetener

Mogroside is one of the active ingredients of the mogroside glycoside family. Mogroside V has good biological activity, making it a non-sugar, high-intensity sweetener on the market [47]. Scholars have found that mogroside can be synthesized by means of biosynthesis, and its sweetness intensity can reach 250 times that of sucrose [48]. In the development and utilization of Mogroside sweeteners, in addition to considering the sweetness factor, off-flavor is also a factor that needs to be considered in the development and commercialization of new products. The off-flavor can be optimized by using the central composite design method for transglycosylation of Mogroside extracts, and experimental parameters such as concentration, temperature, reaction time, enzyme activity and pH can be combined for processing [49].

In terms of improving the taste, research has shown that the beer yeast Dekkera bruxellensis can be used to extract the sweetener Mogroside, as this species of beer yeast can selectively hydrolyze the glycosidic bond of Mogroside V, which can produce a stronger sweetness and optimal taste than other Mogrosides after conversion [50]. Today, the application of Mogroside sweeteners is diverse, such as Mogroside sugar substitutes suitable for consumption by diabetics [51]. Mogroside is selected for free combination, and the resulting sugar substitute has low calories and a good taste. Mogroside is also combined with other substances to make new flavorings, which are used in many fields such as beverages and candy, and have achieved good results. Wang Jun et al. [52] used Mogroside to replace traditional white sugar and mixed it with milk, purple sweet potatoes, etc., to make a mellow and rich sugar-free drink. Coca-Cola also uses Mogroside as a sweetener in beverages to prepare drinks with a better taste and stronger sweetness [53]. Scholars still need to explore the purity and extraction methods of the Mogroside sweetener in order to develop a better, purer and more refined Mogroside sweetener that can be better applied to people's lives.

2.2 Anti-aging products

Mogroside is a natural antioxidant with development potential. After studying Mogroside extracts, it was found that Mogroside has a certain antagonistic effect on ethanol-induced liver injury cells in vitro. Mogroside can maintain cell membrane integrity, enhance the antioxidant activity of cells, inhibit lipid peroxidation, and reduce oxidative stress [54], which can inhibit cell aging caused by oxidative damage to a certain extent.

Qin Si et al. [55] found that Mogroside, when applied to products, has a scavenging effect on ROS in cell tissues and can inhibit the PI3K/AKT1 signaling pathway to exert an antioxidant effect. Moreover, studies on the activity of Mogroside have shown that Mogroside can also reduce H2O2-induced oxidative stress and enhance the endogenous antioxidant activity of skin fibroblasts. Compared with the oxidative damage model group, cell viability increased after treatment with 60 μg/mL and 90 μg/mL Mogroside (P<0.001), which protected cells from H2O2-induced damage and has value as an anti-aging cosmetic ingredient [56].

Among Mogroside's antioxidant and anti-aging products, an oral liquid made from one of Mogroside's glycosides [57] has a mellow taste, retains the flavor of Luohanguo, is full of fruitiness, and can effectively prevent oxidative damage to organs caused by free radicals, demonstrating the potential of Mogroside for use in anti-aging products. As can be seen above, the development and use of Mogroside anti-aging products mostly focuses on reducing oxidative damage and anti-oxidation, which is an extension of Mogroside's anti-oxidative stress function.

2.3 Sports nutrition supplements

Certain fatigue symptoms may occur after exercise, and effective sports nutrition supplements can relieve the fatigue caused by exercise. Through research on fatigued mice [26], scholars have found that Mogroside, as the main active substance in Luo Han Guo extract, has anti-fatigue properties. Applying it to sports nutrition supplements and developing anti-fatigue products, such as adding Mogroside to fitness products [58], not only has a certain effect of post-exercise nutritional supplementation, but also can alleviate post-exercise fatigue and reduce the feeling of fatigue after exercise by using its anti-fatigue functional activity. Song Wei et al. [59] invented an anti-fatigue and lung-clearing beverage, which contains mogrosides and red dates, etc., and is rich in nutrients. It can also synergistically exert an anti-fatigue effect with wolfberries, and has broad market application prospects.

2.4 Anti-inflammatory agent

For chronic inflammation, if western medicine is used for intervention and treatment, it is often necessary to use antibiotics and hormone drugs such as hydrocortisone and dexamethasone for a long time. This will cause certain damage to the body over time. At present, the abuse of antibiotics in China is relatively serious, and there is a real need for an anti-inflammatory drug with few side effects and good results. Mogroside has a significant preventive effect on inflammatory lesions [60]. It has the potential to prevent airway inflammation and also has a certain protective effect against acute lung injury [61]. Its mechanism of action may be through activation of AMPK, which in turn downregulates the TLR4/MAPK/NF-κB signaling pathway [62].

Some scholars have confirmed through transcriptomics and proteomics that mogroside has a certain effect on lung inflammation in mice [63]. The study found that mogroside plays an important role in relieving allergic pneumonia [64], further verifying the anti-inflammatory effect of mogroside. Qin Si et al. [65] found that Mogroside has anti-inflammatory activity. When applied to anti-inflammatory foods, health products or drugs, Mogroside can inhibit the activation of the MAPK-NF-κB and PI3K/AKT1 signal pathways to exert its anti-inflammatory effect. It has few toxic side effects and has broad market prospects. The above research provides a basis for the clinical use of Luo Han Guo as an anti-inflammatory agent. However, in-depth research on its mechanism of action and the conduct of clinical trials with multiple samples are still required for practical application.

2.5 Throat-soothing products

Luo Han Guo is known to have the effect of soothing the throat, and its main active ingredient, Mogroside, also has the effects of relieving phlegm, relieving coughs, and clearing the throat. A candy was made by mixing 50% maltose syrup, 30% Mogroside extract, 5% milk powder starch mixture, 10% peppermint, 0.5% calcium, and 0.3% sodium alginate [66]. Research on its efficacy found that this candy not only has the effect of relieving the throat, but also has a good taste, is well received, and has a certain health effect. The above shows that mogroside not only can exert its effect as a sweetener, but also has the effect of expectorant, antitussive and throat-soothing, providing a basis for the development of health products such as throat-soothing products. In the future, in addition to focusing on the efficacy, the development of other Mogroside throat-soothing products should also comprehensively consider factors such as palatability, efficacy, and safety.

2.6 Intestinal flora regulator

When applied to intestinal flora regulators, mogroside, as a potential prebiotic, can benefit human health through interactions with the intestinal microbiota. The minimum inhibitory concentration of mogroside for 50 μL suspensions of Escherichia coli and Staphylococcus aureus is 12.5%, and mogroside also has inhibitory effects on Bacillus subtilis, Salmonella, Aspergillus niger, Aspergillus niger and Saccharomyces cerevisiae [67].

In addition, Mogroside can regulate the composition of the intestinal microbiota and the synthesis of short-chain fatty acids, thereby regulating obesity while regulating the intestinal flora [68]. It can be used in products that exert a fat-reducing effect by regulating the intestinal flora. Other scholars have found that Mogroside-rich extracts can improve the intestinal flora of obese mice [69], further evidence that Mogroside can also be used as a fat-reducing product when used as an intestinal flora regulator. In summary, Mogroside can inhibit a variety of bacteria and regulate obesity and other conditions in the body by regulating the intestinal flora.

2.7 Novel drug carriers

At present, many scholars have begun to explore the development and utilization of new Mogroside carriers. For example, Wang Xingli et al. [70] found that mogrosides can increase the solubility of poorly soluble drugs, providing new ideas for the construction of new carriers. Their research also found that if the drug solubilization multiple is used as the evaluation index, a solid dispersion dosage ratio of 1:20 has a better effect. Another scholar used the solvent evaporation method to prepare solid dispersion particles of silymarin (SLY)/Mogroside V (MOG-V). Compared with pure silymarin, the solubility of this new solid dispersion particles was increased by 1931 times, and pharmacokinetics showed a significant increase in oral absorption [71]. From the above, it can be seen that Mogroside can be used as a new drug carrier, and the development of Mogroside as a new drug carrier will help to develop more diverse, multifunctional, and multi-featured mogroside products.

3 Conclusion

Mogroside is the main active substance in Luo Han Guo. Existing research has shown that Mogroside has a wide range of functions, such as regulating blood sugar, lowering blood fat, resisting oxidative stress, anti-fatigue, protecting the liver, anti-liver fibrosis, anti-inflammatory, improving lung function, protecting nerves, anti-cancer, and promoting reproduction.

Researchers have developed health foods and medicines such as sweeteners, anti-aging products, sports nutrition supplements, anti-inflammatory agents, throat-soothing products, and intestinal flora regulators based on Mogroside's various functions. They have also developed a new drug carrier by combining the property of mogroside to increase the solubility of poorly soluble drugs. At present, most of the research on Mogroside is animal experiments or cell experiments, lacking data from clinical studies with multiple samples and corresponding mechanism exploration, as well as evidence from evidence-based medicine. The raw materials used in activity tests are mostly crude Luo Han Guo, with varying degrees of purity and unclear content, which is not conducive to the large-scale and standardized development of the Mogroside industry. With the forward development of science and technology, Mogroside, as a high-quality raw material, has great potential for application in other fields. Therefore, it is necessary to conduct systematic research on the functions of Mogroside and explore and expand its applications. It is necessary to conduct in-depth research on the purification process of Mogroside, the content of various components, biological activity and mechanism of action, in order to form a Mogroside industry chain with solid theory, safe closed loop, diverse products and stable effects, and create more social and economic value.

Reference:

［ 1 ］ LI H X, FAN W F, ZHENG Y L, et al. Herbal textual research of Siraitia grosvenorii[J]. Lishizhen Medicine and Materia MedicaResearch，2020，31（6）：1376−1379.

［ 2 ］HUANG X H, NIE T J, BAN Z D, et al. Technical specification for standardized production  of cutting  seedlings  of Siraitia  grosvenorii[J].  South China Fruits，2022，51（3）：182−185.

［ 3 ］LI C F, CHEN   L, WU X R. Regio-selective glycosylation of mogroside  ⅢE by gly-   cosyltransferase[J].  Journal  of  China  Pharmaceutical  University， 2019，50（2）：222−229.

［ 4 ］JIANG J L, LIANG J, YANG Y Y, et al. Research progress on pharmaco- logical and toxicological effects of mogroside[J]. Modern  Preven- tive Medicine，2020，47（ 12）：2246−2248, 2262.

［ 5 ］WANG L, LIU J L, LU F L, et al. Improve the taste of bitter   mogroside by  enzymatic  glycosylation  method[J].  Guihaia，2015， 35（6）：782−785.

［ 6 ］ZHANG Y, ZHOU G, PENG Y, et al. Anti-hyperglycemic and   anti-hyperlipidemic effects of a  special fraction of Luohanguo  ex-   tract on obese T2DM rats [J]. Journal of Ethnopharmacology，2020， 247：112273.

［ 7 ］LIU H, QI X, YU K, et al. AMPK activation is involved in hy- poglycemic and hypolipidemic activities of mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on high-fat diet/streptozo- tocin-induced diabetic mice[J]. Food & Function，2019，10（ 1）：151− 162.

［ 8 ］XIA X, ZHONG Z G, XIAO Y M. Protective effect of mogroside on H2O2  induced oxidative stress in PC12 cell[J]. Lishizhen Medicine and Materia Medica Research，2013，24（4）：818−820.

［ 9 ］XIA X, ZHONG Z G, LIN C Y, et al. Anti-fatigue and hypoxia tolerance effect of mogrosides in mice[J]. Chinese Journal of Experimental Tra- ditional Medical Formulae，2012，18（ 17）：198−201.

［ 10 ］ZHOU H Y, LONG C X, LUO L, et al. Ef-   fect of mogroside VI on acute liver injury induced by sepsis in mice   and related mechanisms[J]. Chinese Journal of Contemporary Pedi-   atrics，2020，22（ 11）：1233−1239.

［ 11 ］ LIANG H, CHENG R, WANG J, et al. Mogrol, an aglycone of mogrosides, attenuates ulcerative colitis by promoting AMPK ac- tivation[J].  Phytomedicine:International  Journal  of  Phytotherapy and Phytopharmacology，2021，81：153427.

［ 12 ］ SONG  J  L, QIAN B, PAN C, et al. Protective activity of mogroside V against ovalbumin-induced experimental allergic asth-ma  in  Kunming  mice[J].  Journal  of  Food  Biochemistry，2019， 43（9）：e12973.

［ 13 ］ LUO  H, PENG  C, XU X,  et al. The protective effects of mogroside V against neuronal damages by attenuating mitochondri- al dysfunction via upregulating Sirtuin3[J]. Molecular Neurobiolo- gy，2022，59（4）：2068−2084.

［ 14 ］ CHEN J, JIAO D, LI Y, et al. Mogroside V inhibits  hyperglycemia-induced  lung  cancer  cells  metastasis  through  reversing   EMT and damaging cytoskeleton[J]. Current Cancer Drug Targets， 2019，19（ 11）：885−895.

［ 15 ］ XIA X, ZHONG Z G, XIAO Y M, et al. Protective ef-   fect of mogroside against H2O2  induced apoptosis in PC12 cell[J].   Chinese Journal of Hospital Pharmacy，2013，33（ 10）：786−789.

［ 16 ］NIE J, YAN K, SUI L, et al. Mogroside V improves porcine oocyte in vitro maturation and subsequent embryonic development [J]. Theriogenology，2020，141：35−40.

［ 17 ］ZHANG Y, PENG Y, ZHAO L, et al. Regulating the gut microbiota and SCFAs in the faeces of T2DM rats should be one of antidiabetic  mechanisms  of  mogrosides   in   the   fruits   of  Siraitia   grosvenorii[J]. Journal of Ethnopharmacology，2021，274：114033. 

 ［ 18 ］ HE C W,   YAO M C, XIA X, et al. Rregulation effect of fresh mangosteen  saponins on blood sugar[J]. Modern Food Science and Technology， 2012，28（4）：382−386.

［ 19 ］HUANG P L, XIAO Y M, LI B C, et al. Mogroside improves glycemic controlin diabetic mice[J]. Food Research and Development，2022，43 （5）：8−13.

［ 20 ］ HARADA N, ISHIHARA M, HORIUCHI H, et al. Mogrol derived  from  Siraitia  grosvenorii  mogrosides  suppresses  3T3-L1 adipocyte differentiation by reducing cAMP-response element-bind- ing protein phosphorylation and increasing AMP-activated protein kinase phosphorylation[J]. Plos One，2016，11（9）：e0162252.

［ 21 ］ LI L, ZHENG W, WANG C, et al. Mogroside V protects against hepatic steatosis in mice on a high-fat diet and LO2 cells treated with free fatty acids via AMPK activation[J]. Evidence-based Complementary and Alternative Medicine，2020，2020：7826874.   

［ 22 ］HUANG S X, ZHOU X L, MOU J F, et al. Spectral features, α-glucosidase inhibitory activities, antioxi- dant activities and quantitative determination of mogroside   ⅡA of Siraitia grosvenorii[J]. Journal of Guangxi Normal University(Nat- ural Science Edition)，2019，37（3）：132−141.

［ 23 ］ XU Q, CHEN S Y, DENG L D, et al. Antioxidant effect of mogrosides  against  oxidative  stress  induced  by  palmitic  acid  in mouse insulinoma NIT-1 cells[J]. Brazilian Journal of Medical and Biological Research，2013，46（ 11）：949−955.

［ 24 ］MO W B, BU K, HUANG L L, et al. Ef-   fects of mogroside on expression of HSP70  mRNA and protein in   gastric tissue of exhaustive rats [J]. Chinese Journal of Experimental Traditional Medical Formulae，2015，21（7）：103−106.

［ 25 ］ ZOU J, CHEN   Q P, LIU H S, et al. Antioxidant activities of mogrosides from Sira-   tia grosvenorii fruits[J]. Journal of Nuclear Agricultural Sciences， 2016，30（ 10）：1982−1988.

［ 26 ］ HE C W, XIA X, ZHU X Y, et al. The anti-fatigue activity of fresh tissue culture seedling gros- venor momordica fruit[J]. Food Science and Technology，2012，37 （8）：75−78.

［ 27 ］XIAO G, WANG Q.  Experi-   ment study on the hepatoprotective effect of mogrosides[J]. Chi-   nese Journal of Experimental Traditional Medical Formulae，2013， 19（2）：196−200.

［ 28 ］ZHOU  Z   W,  LI  S,  LIU  X   H,  et  al.  Research  advances  in   monomers of Chinese herbs in treatment of liver fibrosis by regulat-   ing oxidative stress [J]. Journal of Clinical Hepatology，2021，37（9）： 2198−2202.

［ 29 ］ CAO F, ZHANG Y, LI W, et al. Mogroside IVE attenuates experimental  liver  fibrosis  in  mice  and  inhibits  HSC  activation through downregulating TLR4-mediated pathways[J]. International Immunopharmacology，2018，55：183−192.

［ 30 ］ LONG Y, WANG W, TIAN H, et al. Experimental study of sieroside serum interfering with hepatic stellate cell cycle and apoptosis[J]. Chinese Traditional Patent Medicine，2015，37（7）：1576−1579.

［ 31 ］WANG Q, WANG W, LONG Y, et al. Effects of mogrosides on proliferation  of hepatic  stellate  cell-T6  and  hepatofibrosis-related gene[J]. Chinese Traditional and Herbal Drugs，2013，44（3）：331− 334.

［ 32 ］SONG K J, LIAO C X, LIU Y P, et al. Effect of activation and apoptosis of mogroside  on  hepatic  stellate  cell[J].  Chinese  Traditional  Patent Medicine，2014，36（3）：481−484.

［ 33 ］ LIU  Y,  ZHANG  B,  LIU  J,  et  al.  Mogroside  V  alleviates   lipopolysaccharide-induced   neuroinflammation   via   inhibition   of  TLR4-MyD88 and activation of AKT/AMPK-Nrf2 signaling  pathway[J]. Evidence-Based Complementary and Alternative Medicine， 2021，2021：5521519.

［ 34 ］XIAO J, HUANG K, LIN H, et al. Mogroside IIE inhibits di-   gestive enzymes via suppression of interleukin 9/interleukin 9 recep-   tor signalling in acute pancreatitis[J]. Frontiers in Pharmacology， 2020，11：859.

［ 35 ］ SUNG  Y  Y,  YUK  H  J,  YANG  W  K,  et  al.  Siraitia   grosvenorii residual extract attenuates atopic dermatitis by  regulat-   ing immune dysfunction and skin barrier abnormality[J]. Nutrients， 2020，12（ 12）：3638.

［ 36 ］WANG Q, XIAO X Q, DONG W, et al. Spectrum-effect relationship on expectorant efficacy of Sir- aitia grosvenorii[J]. Guihaia，2017，37（5）：606−609.

［ 37 ］ WU Y, JIANG R W, ZHAO B. Study on the relieving cough and eliminating phlegm effects of stemoninine combined with  mogro- side V on mice[J]. China Pharmacy，2017，28（ 13）：1755−1757.

［ 38 ］ JU P, DING W,  CHEN J,  et  al. The protective effects of mogroside V and its metabolite 11-oxo-mogrol of intestinal  micro- biota against MK801-induced neuronal damages[J]. Psychopharma- cology (Berl)，2020，237（4）：1011−1026.

［ 39 ］ LIU  C,  DAI L, LIU Y,  et  al. Antiproliferative  activity  of triterpene glycoside nutrient from monk fruit in colorectal cancer and throat cancer [J]. Nutrients，2016，8（6）：360.

［ 40 ］ LIU C, DAI L H, DOU D Q, et al. A natural food sweetener   with anti-pancreatic cancer properties[J]. Oncogenesis，2016，5（4）： e217.

［ 41 ］ TAKASAKI M, KONOSHIMA T, MURATA Y, et al. Anti- carcinogenic activity of natural sweeteners, cucurbitane glycosides, from Momordica grosvenori[J]. Cancer Letters，2003，198（ 1）：37− 42.

［ 42 ］ LI Y, CHEN Y, WEI M, et al. Preclinical in silico evidence indicates the pharmacological targets and mechanisms of mogroside V inpatients with ovarian cancer and coronavirus disease 2019[J]. Frontiers in Endocrinology，2022，13：845404.

［ 43 ］ YAN K, CUI K, NIE J, et al. Mogroside V protects porcine oocytes from lipopolysaccharide-induced meiotic defects[J]. Fron- tiers in Cell and Developmental Biology，2021，9：639691.

［ 44 ］ SUI L, YAN K, ZHANG H, et al. Mogroside V alleviates oocyte meiotic defects and quality deterioration in benzo(a) pyrene- exposed mice[J]. Frontiers in Pharmacology，2021，12：722779.

［ 45 ］ HUANG L, LIANG A, LI T, et al. Mogroside V improves follicular development and ovulation in young-adult PCOS rats  in- duced by letrozole and high-fat diet through promoting glycolysis [J]. Frontiers in endocrinology，2022，13：838204.

［ 46 ］YAO S H, WEI H C, QIN J G, et al. Mogro-   side V stimulatesosteoblast proliferation and differentiation by pro-   moting LncRNA TUG1 expression[J]. Chinese Journal of Tissue   Engineering Research，2020，24（26）：4129−4134.

［ 47 ］ SUN Z M, LÜ B, FENG Y J. Synthetic biology for the synthesis of mogroside V-a review[J]. Chinese Journal of Biotechnology，2020，36（ 10）：2017− 2028.

［ 48 ］ITKIN M, DAVIDOVICH R R, COHEN S, et al. The biosyn- thetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii[J]. Proceedings of the National Acade- my of Sciences，2016，113（47）：7619−E7628.

［ 49 ］ MUNOZ L A, AZCARATE S, LEBRON A R, et al. High- yield synthesis of transglycosylated mogrosides improves the flavor profile of monk fruit extract sweeteners [J]. Journal of Agricultural and Food Chemistry，2021，69（3）：1011−1019.

［ 50 ］WANG R, CHEN Y C, LAI Y J, et al. Dekkera bruxellensis,   a beer yeast that specifically bioconverts mogroside extracts into the   intense natural sweetener siamenoside I[J]. Food Chemistry，2019， 276：43−49.

［ 51 ］ZHAO X N. A sweet glycosides of mogroside suitable for diabetics and its prepara- tion method: China, 201910751148.1[P]. 2019-11-22.

［ 52 ］WANG J, ZHAO Y Q, XU J W, et al. A sugar-free drink and its preparation method: China, 201911014834.7[P]. 2020-01-07.

［ 53 ］ IN- DRA P, JIMA. Sweetness and taste improvement of stevioside or mogroside sweeteners: China, 201780031217.0[P]. 2019-01-15. ］

［ 54 ］ ZHU H L, LIU H S, QI X Y, et al. Protective effect of mogroside extract on ethanol-induced L-02 hepatocytes damage[J]. Journal of Chinese Institute of Food Science and Technology，2015，15（ 1）：13− 18.

［ 55 ］TAN  S, LIU J  Q, ZOU L Y. Application of mogroside IIE in preparation  of antioxidant  food,  health  food  or  medicine:  China, 202010471884.4[P]. 2020-10-02.

［ 56 ］ MO Q, FU H, ZHAO D, et al. Protective effects of mogro- side V on oxidative stress induced by H2O2  in skin fibroblasts[J]. Drug Design, Development and Therapy，2021，15：4901−4909.

［ 57 ］ LI W, HUANG H X. A  11-O-rosanol oxime ether derivative and  antioxi- dant  anti-aging  oral  liquid:  China,  202010482662.2[P].  2021-06- 22.

［ 58 ］ LI S, CHEN Q, GUO Y C. A levocarnitine jelly supplement for  exer- cise  and  fitness  population   and  its  preparation   method:  China, 202111592428.6[P]. 2022-04-29.

［ 59 ］ SONG W, QI T T, SONG G X.   An  anti-fatigue  lung  clearing  drink:  China,  201611138577.4[P].   2017-04-26.

［ 60 ］LI Y, ZOU L, LI T, et al. Mogroside V inhibits LPS-induced COX-2 expression/ROS production and overexpression of HO-1 by blocking  phosphorylation  of AKT1  in  RAW264.7  cells[J].  Acta Biochim Biophys Sin (Shanghai)，2019，51（4）：365−374.

［ 61 ］ SHI D, ZHENG M, WANG Y, et al. Protective effects and mechanisms of mogroside V on LPS-induced acute lung injury in mice[J]. Pharmaceutical Biology，2014，52（6）：729−734.

［ 62 ］TAO L, CAO F, XU G, et al. Mogroside IIIE attenuates LPS- induced acute lung injury in mice partly through regulation of the TLR4/MAPK/NF-κB  axis  via  AMPK  activation[J].  Phytotherapy Research，2017，31（7）：1097−1106.

［ 63 ］ DOU T, WANG J, LIU Y, et al. A combined transcriptomic and  proteomic  approach  to  reveal  the  effect  of mogroside  V  on OVA-induced pulmonary inflammation in mice[J]. Frontiers in Im- munology，2022，13：800143.

［ 64 ］LIU Y, WANG J, DOU T, et al. The liver metabolic features   of mogroside V compared to Siraitia grosvenorii fruit extract in  al-   lergic   pneumonia    mice[J].   Molecular    Immunology，2022，145： 80−87.

［ 65 ］TAN S, LIU J Q, PAN S J, et al. Application of mogroside IIE in   the preparation of anti-inflammatory food, health care products or   drugs: China, 202010471878.9[P]. 2020-10-02.

［ 66 ］ YAN J W, JIANG X K. Optimization of extraction technology of mogro- side and development of natural throat healthy candy[J]. Journal of Northeast Agricultural Sciences，2019，44（5）：116−122.

［ 67 ］REN X R, LI L H. Extraction of saponin from siraitia grosvenorii flower and its antibacterial activ- ity[J]. The Food Industry，2015，36（6）：4−7.

［ 68 ］ XIAO R, LIAO W, LUO G, et al. Modulation of gut micro-   biota composition and short-chain fatty acid synthesis by mogroside   V  in  an  in  vitro  iincubation  system[J].  Acs  Omega，2021，6（39）： 25486−25496.

［ 69 ］ WANG S, CUI K, LIU J, et al. Mogroside-rich extract from Siraitia grosvenorii fruits ameliorates high-fat diet-induced obesity associated with the modulation of gut microbiota in mice[J]. Fron- tiers in Nutrition，2022，9：870394.

［ 70 ］WANG X L,   WANG S, ZHANG L, et al. Solubilization effects of novel carrier   mogroside  V  on  paclitaxel[J].  Herald  of  Medicine，2019，38（6）： 770−774.

［ 71 ］LUO Y, GONG C, WEI M, et al. Evaluation of mogroside V as a promising carrier in drug delivery: Improving the bioavailabili-  ty and liver distribution of silybin[J]. Aaps Pharmscitech，2020，21 （4）：123.