Studies On The Synthesis Of Geniposide Derivatives And Its Anti-inlfammatory And Immunomodulatory Activity

Chinese medicine gardenia is the dried ripe fruit of Rubiaceae Gardenia (Gardeniajasminoides Ellis), only contained the "Shen Nong’s Herbal Classic", as the product, itscold, sour and bitter taste, non-toxic, with a purging fire in addition totrouble, heatdiuretic, cooling blood detoxification effect, taken orally for fever, irritability, jaundice,red urine, discredited astringent pain, red eyes and throat, fire canker sores, outside therule sprain pain. Gardenia was called of yellow gardenia, Shan gardenia, Huangguoshu,red gardenia, is an evergreen shrub, has widely growing areas, mainly produced inZhejiang, Jiangxi, Hubei, Hunan and other places. In recent years, studies have shownthat the gardenia and active ingredient has a wide range of pharmacological effects in inthe digestive system, cardiovascular system, central nervous system and anti-tumor.Geniposide is an iridoid glucoside, it is the main active ingredient of gardenia, is anoteworthy high yield and easy to get natural products, experiments have shown that acertain dose of Geniposide has a protective effect on Acute Alcoholicliver injury, inaddition, it is relatively broad in the field of plant yield agents, biological testing andbiological agents carrier. However, Since it is difficult to isolate glycoside due to itshigh polarity, which greatly limits its application. In addition, studies have shown thathemiacetal structure of Geniposide is necessary for anti-tumor activity groups, and substituent of C-4is essential antioxidant activity, For the above reasons, thisexperiment is take Geniposide as the lead compound, structural transformation,designed and synthesized series geniposide derivatives and preliminary screening of itsactivity.The main contents were divided into some sections as follows:1. Synthesis of Geniposide derivativesStudies have shown that hemiacetal structure of Geniposide is necessary foranti-tumor activity groups, and substituent of C-4is essential antioxidant activity, so wetake Geniposide as the lead compound, make the hydroxyl of10-bit and2’,3’,4’,5’-bitof Geniposide acetylation and/or11-bit of Geniposide introduction of the differentlength of Saturated carbon chain and/or aromatic ammonia substituted, and makedouble bond of7,8-bit epoxidized. Structure of Geniposide derivatives were confirmedby1H-NMR,13C-NMR and TOF-HRMS spectra.2. The activity screening of the Geniposide derivatives on anti-inflammatory andimmunomodulatory in vitroThe experiment was designed to study the immunomodulatory activity ofGeniposide derivatives. Ten Sprague-Dawiey rats were fed for10~15days. Then therats were killed by bleeding of the Femoral artery. Immune cells (peritonealmacrophages) were obtained, then cultured in vitro with Geniposide derivatives. Theimmune index prostaglandin E2(PGE2) was detected by the method of enzyme linkedimmunosorbent assay, making a primary screening to these Selected derivatives onanti-inflammatory and immunomodulatory activity. We found that derivatives of1a,1j,2f,1f,1m,1i,2b showed greated inhibition of excessive generated of PGE2thanmaternal Geniposide, which showed good anti-inflammatory and immune activity. 3. Studies on the protective effect on acute liver injury in vivoOn the basis of the anti-inflammatory immune activity screening studies in vitro,we select derivatives1j and1f, which showed good anti-inflammatory and immuneactivity in vitro, to explore its hepatoprotective role on acute liver injury induced byD-galactosamine in mice. Experimental results show that Geniposide derivatives1j and1f can reduce the content of serum ALT, AST, increase the liver tissue SOD andGSH-Px level, lower the content of MDA and protein content, also can reduce the liverindex, and significantly improve the degree of liver tissue injury. Under an opticalmicroscope, the histopathological examination results show that the given1j and1f cansignificantly reduce the liver tissue degeneration and necrosis, and inflammatoryreaction. These findings suggest that: the1j and1f on D-GalN-induced acute liverinjury prevention; The mechanism of its hepatoprotective pharmacological remains tobe further experimental study.