Siraitia grosvenorii is a perennial herbaceous vine of the genus Siraitia grosvenorii, CucurbitaceaeSiraitia grosvenorii (swing) the dried fruit of C. Jeffrey ex Lu et Z. y. Zhang, mainly produced in Guilin, Guangxi [1]. Traditional Chinese medicine believes that arhat fruit is sweet in taste and cool in nature. It belongs to the lung and large intestine meridian, and has the effects of moistening the lung, relieving cough, generating saliva, quenching thirst, and moistening the intestine. Siraitia grosvenorii has a history of folk medicine for more than 300 years. It is the first batch of dual-use traditional Chinese medicine approved by the former Ministry of health and the administration of traditional Chinese medicine. It has therapeutic effects on pulmonary tuberculosis, hypertension, gastritis, asthma, whooping cough, acute and chronic tracheitis, constipation, etc. Momordica grosvenoril and its derivative Momordica grosvenorin, which are unique components in Momordica grosvenorii, are a class of cucurbitane type triterpene glycosides [1-2], among which Momordica grosvenorin is a cucurbitane type triterpene glycoside, and its aglycone is Momordica grosvenorin [3].
Momordica grosvenorin is one of the most studied chemical constituents of Momordica grosvenorin. At present, cucurbitane type triterpenoids extracted, isolated and identified from Siraitia grosvenorii fruits include siraitol, siraitoside iia1, siraitoside IIE, siraitoside III, siraitoside IIIE, Mogroside IV, Mogroside IVA, Mogroside ive, siraitoside V, siraitoside VI, 11 oxygen siraitol, 11 oxygen siraitoside V, etc. [4-5]. In recent years, the pharmacological effects of Momordica grosvenoril and its derivative Momordica grosvenorin have attracted extensive attention of researchers. In this paper, the research of Momordica grosvenoril and its derivative Momordica grosvenorin in liver protection, neuroprotection, anti-inflammatory effect, anti-tumor effect, treatment of diabetes and its complications were reviewed.
1 hepatoprotective effect
Metabolic related fatty liver disease is a common chronic liver disease, including simple steatosis, nonalcoholic steatohepatitis, liver fibrosis and cirrhosis. Huangyanjing et al. [6] found in the cell model of metabolic related fatty liver disease that Momordica grosvenoril can inhibit the expression of sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase by activating the adenylate activated protein kinase (AMPK) signaling pathway, inhibit the synthesis of fatty acids, and thus promote lipid metabolism, which proved that Momordica grosvenoril has a therapeutic effect on metabolic related fatty liver disease in vitro. In the metabolism related fatty liver disease model in vivo and in vitro, Momordica grosvenorin V can regulate SREBP-1c, peroxygenase activated proliferative receptor gamma (ppar- γ), peroxygenase activated proliferative receptor alpha (ppar- α) by activating AMPK to improve hepatic lipogenesis and metabolic imbalance, thereby alleviating hepatic steatosis caused by hyperlipidemia [7].
Liver fibrosis is a necessary stage for the development of chronic liver disease to cirrhosis. Momordica grosvenorii saponin ive can significantly reverse liver fibrosis and improve liver function through mitogen activated protein kinase (MAPK) and toll like receptor 4 (TLR4) / hypoxia inducible factor-1 α (HIF-1 α) signaling pathway in vivo and in vitro [8].
Sepsis liver injury is one of the manifestations of sepsis multiple organ dysfunction syndrome. Zhouhaiyin et al [9] found that Momordica grosvenorin VI could reduce the level of hepatic oxidative stress, improve liver tissue damage in septic mice, and then improve liver function in mice. The activation of peroxisome proliferator activated receptor gamma coactivator 1 α (PGC-1 α) played a key role in it.
In conclusion, Momordica grosvenoril and its derivative Momordica grosvenorin can protect liver by promoting lipid metabolism, anti-inflammatory and anti-oxidation, as shown in Table 1.
2 neuroprotection
Alzheimer's disease is a neurodegenerative disease with severe cognitive and memory impairment. Studies have shown that Momordica grosvenoril can alleviate the neuroinflammatory response induced by β amyloid 1-42 (a β 1-42) by downregulating the nuclear factor - κ B (nf- κ b) signaling pathway, and can significantly alleviate the memory impairment caused by a β 1-42, inhibit the excessive activation of microglia induced by a β 1-42, and prevent the neural apoptosis in the hippocampus caused by a β 1-42[10]. .
Schizophrenia is a serious mental disease, which will have a significant impact on the quality of life of patients and their caregivers. Studies have found that Momordica grosvenorin V can restore the neural structure of mice damaged by dezocycline treatment, and significantly improve the schizophrenic like behavior caused by dezocycline. At the same time, the gut microbiota metabolite of Momordica grosvenorin V, 11 oxygen momorditol, can also reduce the neurotoxicity of dezocycline by regulating the protein kinase B (Akt) / target of rapamycin (mTOR) pathway [12].
Parkinson's disease is the most common neurodegenerative movement disorder. Momordica grosvenorin V effectively alleviates rotenone induced neurotoxicity through the endogenous mitochondrial pathway associated with reactive oxygen species. Momordica grosvenorin V can reduce the overproduction of reactive oxygen species in cells, improve the protein expression of silent information regulatory protein 3 and mitochondrial superoxide dismutase, restore mitochondrial membrane potential, reduce apoptosis, and increase the oxygen consumption rate of cells and the generation of adenosine triphosphate [13].
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3 anti inflammatory effect
Some scholars found that Momordica grosvenorin V could significantly inhibit the expression of prostaglandin E2 and cyclooxygenase-2 in lipopolysaccharide stimulated macrophages, significantly reduce the expression of phosphorylated nuclear factor kappa B inhibitory protein (I κ b- α), increase I κ b- α, and reduce the expression of human nuclear transcription factor peptide (nf- κ B p65) and CCAAT enhancer binding protein δ (c/ebp δ). . This indicates that Momordica grosvenorin V exerts anti-inflammatory effects by blocking Akt mediated activation of nf- κ B and c/ebp δ, reactive oxygen species generation, and expression of activator protein-1 (AP-1) / heme oxygenase-1 (HO-1) [14].
Acute pancreatitis is one of the common acute abdominal diseases in clinic, which may cause multiple organ dysfunction syndrome with high mortality. According to the literature, Momordica grosvenorii saponin IIE significantly reduces the levels of serum lipase and serum amylase in mice with acute pancreatitis by inhibiting interleukin-9 (IL-9) / interleukin-9 receptor (il-9r) / calcium overload / cathepsin b/ trypsinogen and inhibiting il-9/ il-9r/ calcium overload / autophagy / trypsinogen, which has a certain therapeutic effect on acute pancreatitis [15].
Ulcerative colitis is a chronic non-specific inflammatory bowel disease. Patients often have bloody stool and diarrhea. Studies have found that Momordica grosvenoril can inhibit inflammatory cell infiltration through AMPK and nf- κ bsignaling pathway, attenuate the abnormal expression of nod like receptor heat protein domain related protein 3 (NLRP3), and significantly reduce the pathological damage of ulcerative colitis in mice [16].
It can be seen that Momordica grosvenoril and its derivatives can inhibit different types of inflammatory responses through multiple targets in vitro and in vivo, as shown in Table 3.
4 anti tumor effect
Fuyuxia et al [17] found that Momordica grosvenoril can significantly inhibit the proliferation of human prostate cancer cells (DU145), human liver cancer cells (HepG2), human non-small cell lung cancer cells (A549), well differentiated nasopharyngeal carcinoma cells (CNE1), poorly differentiated nasopharyngeal carcinoma cells (CNE2), and the most obvious inhibitory effect on CNE1 cells, with an IC50 of (81.48 ± 4.73) μ mol/l. The mechanism is that Momordica grosvenoril inhibits the expression of anti apoptotic genes such as survivin and b-lymphoma-2, and promotes the expression of Caspase-3 and Bcl-2.The expression of Pro apoptotic genes such as cl-2-related X protein (Bax).
Lung cancer is one of the most common cancers and the main cause of cancer death worldwide. Liucan et al [18] found that momorditol upregulated the expression of cyclindependent protein kinase inhibitor 1a (p21) protein in A549 cells, resulting in G1 arrest of cells; . Studies have shown that Momordica grosvenoril reduced the tumor volume and mass of lung cancer bearing nude mice, significantly inhibited the proliferation and migration of lung cancer cells A549 and sk-mes-1 cells, and promoted the apoptosis of cancer cells [3]. This is because Momordica grosvenoril activated AMPK to induce excessive autophagy and autophagy dependent apoptosis, and upregulated p53 led to cell cycle arrest and apoptosis.
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Leukemia is a common hematological malignancy. . And Momordica grosvenoril up-regulated the expression of p21, making the leukemia cell cycle arrest in g0/g1 phase [20].
. In the pancreatic cancer model in vitro and in vivo, Momordica grosvenorin V exerts the activity of inhibiting the growth of tumor cells by promoting the apoptosis and cell cycle arrest of pancreatic cancer cells. Momordica grosvenorin V can also inhibit tumor growth by inhibiting angiogenesis in vivo, and can improve the survival time of mice. Its mechanism of action is related to STAT3 pathway [21].
In summary, Momordica grosvenoril and its derivatives have therapeutic effects on a variety of tumors by promoting apoptosis, promoting autophagy, and anti epithelial mesenchymal transition, as shown in Table 4.
5 treatment of diabetes and its complications
Renal podocyte injury caused by diabetes will lead to the increase of protein content in urine of diabetic patients, thus accelerating the development of diabetic nephropathy. Momordica grosvenorii saponin IIIE can activate ampk/ SIRT1 pathway, inhibit high concentration glucose induced kidney foot apoptosis by up regulating Bcl-2, down regulating Bax, cleaved Caspase-3, cleaved caspase-9, and at the same time Momordica grosvenorii saponin IIIE can also down regulate NLRP3, ASC type amino acid transporter (ASC), caspase-1, tumor necrosis factor - α (tnf- α), leukocytes interleukin-1 β (IL-1 β) receptor and interleukin-6 (IL-6) inhibit the inflammatory response and oxidative stress induced by high concentrations of glucose [22].
Diabetic cardiomyopathy is a myocardial lesion caused by sustained hyperglycemia that impairs cardiac structure and function. It is the most common complication of diabetes. Some studies have pointed out that Momordica grosvenorii saponin IIE can reduce the levels of lactate dehydrogenase 2 (ldh2), creatine phosphokinase isoenzyme (CKMB) and creatine kinase (CK) while reducing the blood glucose and lipid levels in rats fed a high-fat and high sugar diet, improve cardiac function, and improve diabetic cardiomyopathy in rats to a certain extent. Momordica grosvenorii saponin IIE can also inhibit the secretion of interleukin 1 (IL-1), IL-6 and tnf- α, improve myocardial morphology and reduce myocardial apoptosis[23].
The pathogenesis of gestational diabetes mellitus is complex, which poses a serious threat to the safety of mothers and infants. Studies have found that Momordica grosvenorii saponin IIIE can significantly alleviate hyperglycemia and insulin resistance in gestational diabetic mice through ampk/ histone deacetylase 4 (HDAC4) / glucose-6-phosphatase (G6Pase) pathway, and improve fetal development and maternal health [24].
In general, Momordica grosvenoril and its derivatives exert anti hyperglycemia, anti inflammation, anti oxidative stress, anti apoptosis and other effects, and play a protective role against diabetes and its complications, as shown in Table 5.
6 others
The differentiation of preadipocytes into adipocytes is an important part of fat regulation. Harada et al [25] found that Momordica grosvenoril inhibited the lipid accumulation of preadipocytes by attenuating the expression of cyclic adenosine monophosphate effector element binding protein (CREB) and promoting the phosphorylation of AMPK protein, thereby inhibiting the differentiation of preadipocytes into adipocytes.
Pulmonary fibrosis is a fibrotic interstitial lung disease with a chronic course and progressive and fatal characteristics. In vitro, the researchers used murine primary fibroblasts and mle-12 cells as the objects, and used transforming growth factor beta 1 (tgf- β 1) to model pulmonary fibrosis; In vivo, c57bl/6 and ICR mice were used to model pulmonary fibrosis with bleomycin. .
7 conclusion
Momordica grosvenorii, as a traditional Chinese medicine in China, is also a famous genuine medicinal material in Guangxi, with rich drug sources. Traditional Chinese medicine believes that Siraitia grosvenorii has the effects of clearing heat and moistening the lungs, benefiting the pharynx and opening the voice, and smoothing the intestine and defecating. Momordica grosvenoril and its derivatives as the main active substances in Momordica grosvenorii have become a research hotspot in recent years [27]. With the deepening of research, new progress has been made in liver protection, neuroprotection, anti-inflammatory, anti-tumor, treatment of diabetes and its complications, but there are still many problems worthy of study: in terms of the mechanism of action, most of the research focuses on AMPK, mapksignaling pathway and related pathways such as oxidative stress, inflammation, apoptosis, and less on other mechanisms. In terms of pharmacological effects, the research of Momordica grosvenoril and its derivatives mainly stays in cell and animal experiments, and the reports of clinical studies are relatively rare. Because the research on Biopharmaceutics is far from enough, the metabolic pathways of Momordica grosvenoril and its derivatives in vivo still need further study and discussion.
In conclusion, the triterpenoids extracted from Siraitia grosvenoril and its derivative Siraitia grosvenorin have been proved to be pharmacologically active in a large number of experimental studies. It is suggested that these findings should be verified through preclinical studies in humans, and they are expected to better serve clinical applications in the future.
References (omitted)
Source: Wei Dong, Yang Linjie, Yang Yudan, Lu Liang. Research progress on pharmacological effects of Momordica grosvenoril and its derivatives [j]. modern medicine and clinic, 2022, 37 (11): 2659-2664