Extraction And Biological Activity Mechanistic Study Of Polyphenolic Compounds From Litchi Seed

Litchi(Litchi chinensis Sonn.),a plant of the genus litchi in the family Sapindaceae,is one of the most common fruit crops in daily life and is known as the"queen of fruits".Its whole body is full of treasures,but except for the litchi flesh,its seeds are almost abandoned.It is estimated that total global production of litchi is～2.7 million tons which can generate as much as～0.54 million tons of seeds per year.Litchi seeds are often discarded,and how to turn it into treasures is a challenge facing the food industry.Traditional Chinese medicine believes that litchi seed can dispel wind and cold,and have analgesia effect,therefore relieving orchitis,neuralgia,testicular swelling,hernia,abdominal pain,etc.Current research has found that litchi seeds are rich in polyphenolic compounds,such as rutin,gallic acid,catechin,epicatechin and oligomeric procyanidins,which have shown obvious anti-inflammatory,antioxidant,lipid-lowering,hypoglycemic and anti-tumor effects.Hypertension is one of the most common cardiovascular diseases in clinic,known as the"invisible killer",and is a chronic lifelong disease,which affects more than 1 billion people worldwide in varying degrees.Hypertension can cause a variety of complications and is the second largest cause of chronic kidney disease.Renal injury is one of the most frequent and serious complications.The occurrence of early renal injury in hypertension is related to a variety of factors,and the specific mechanism is not completely clear.Previous studies found that litchi seed extract(LSE)could improve dyslipidemia,hyperglycemia and oxidative stress caused by type 2 diabetes.However,there are few studies on whether LSE can alleviate hypertension and hypertension induced renal injury.In this experiment,we carried out the study on the effect of LSE on hypertension and its renal injury,and made in-depth exploration from the aspects of pathology and mechanism of action.In the first part of this study,the litchi seed was extracted with 75%ethanol by heating reflux,purified with D101 macroporous resin,and analyzed by UPLC-Q/TOF-MS.It was identified that LSE contained 13 polyphenols and 1 fatty acid,including 8 procyanidins.First,the possible mechanism by which LSE alleviates hypertension-induced renal injury is predicted by network pharmacology.The results of network pharmacology prediction showed that the target genes of LSE for relieving hypertension and renal injury included IL-6,TNF-a,AKT,STAT3 and NOS3;TNF signaling pathway,IL-6 mediated signaling pathway,NF kappa B signaling pathway,removal of superoxide radials,negative regulation of blood pressure were the main signal pathways.Spontaneously hypertensive rats(SHR)were given LSE(60 mg/kg)by gavage every day.After 10 weeks treatment,LSE significantly reduced systolic blood pressure(SBP),thickness of thoracic aorta wall,and serum ET-1 and AngⅡlevels.Renal pathology,creatinine,urea nitrogen and creatinine clearance showed that LSE could alleviate hypertension induced renal injury.LSE mainly inhibited IL-6/TNF-a/NF-κB p65 signaling pathway to relieve nephritis damage and activated HO-1/Nrf2 signaling pathway to relieve renal oxidative damage.The experimental results were consistent with the predictions of network pharmacology.In addition,LSE also regulated the disordered gut microbiota of SHR rats,increased the relative abundance of Lactobacillus and the production of short chain fatty acids.Our research showed that the polyphenol extract of litchi seed could reduce hypertension and alleviate hypertension-induced renal injury.Colorectal cancer(CRC),the digestive tract malignant tumor,which can be included by factors such as genetics,diet,and obesity.Its diagnostic rate and mortality rank the third and second in the world,respectively.Numerous epidemiology shows that hypertension is positively correlated with CRC incidence.Compared with people with normal blood pressure,people with high blood pressure have a 15 percent higher risk of CRC.Procyanidins are the main polyphenol compounds in litchi seed,and research has found that have obvious anti-tumor activity.However,there is a comparative paucity of information on if and how LPC inhibits colon cancer pulmonary metastasis.In this study,LPC significantly inhibited CT26colon cancer cells proliferation and metastasis in vivo and in vitro.Transcriptome analysis showed that LPC could significantly regulate T cell related signaling pathways.LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8~+cytotoxic T lymphocytes infiltration and decreasing the number of macrophages.In addition,the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006,Ruminococcus,and their metabolites like acetic acid,propionic acid and butyric acid in CT26 lung metastasis mice.In germ-free mice,the therapeutic effect of LPC on colon cancer metastasis and regulation of T cells were weakened with the clearance of gut microbiota.Taken together,LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response.In this study,the litchi seed extract was studied to prove the relieving effect of LSE on hypertension and hypertension induced renal injury,and the inhibitory effect of procyanidins in litchi seed extract on lung metastasis of colon cancer,and its mechanism was explored on this basis.We hoped that the above research results will provide experimental basis and guidance for litchi seed in the field of medical care against hypertension and its complications and colon cancer.At the same time,it enriches the public’s understanding of litchi seed,realizes the effective use of all parts of litchi,lays a theoretical and practical foundation for the development of high-value-added products,and has important economic significance for improving the additional economic value of litchi seed and turning waste into treasure.