| Semen Celosiae (Amaranthaceae)，the dry seed of Celosia argentea L，isrecorded in Chinese Pharmacopoeia. It tastes bitter. It has been utilized to removeliver-heat, improve eyesight, clear wind-heat. Modern pharmacological studiesconfirmed that the seeds could protect liver, anti-tumor, lower blood sugar levels,regulate dyslipidemia, so it owns important medicinal value and developmentprospects.BackgroundDyslipidemia, a chronic disease. patients with dyslipidemia showed an increase inconcentrations of cholesterol(TC), triglyceride (TG), low density lipoproteincholesterol (LDL-C) and decrease in high-density lipoprotein cholesterol (HDL-C)levels. Factors, such as lifestyle, diet, environment and inheritace, could lead to theoccurrence of the disease. dyslipidemia may induce atherosclerosis, coronary heartdisease, myocardial infarction and other cardiovascular and cerebrovascular diseases,which do harm to the health of humans badly, Therefore, diet therapy and lifestyle isthe first choice for the treatment of dyslipidemia. And the second choice is the drugstreatment. Clinically, the main lipid-regulating drugs are statins and fibrates, niacin,resins, inhibitors of cholesterol absorption. Statins are widely used to treat the patientswith hyperlipidemia, and it reduce total cholesterol and LDL-C(low densitylipoprotein cholesterol) largely, but studies have reported the injury to the liver, Somepatients do not tolerate it, even accompanying side effects such as rhabdomyolysistherefore, it is significant to find new drugs to make up deficiencies for existinglipid-regulating drugs.Our previous studies on the chemical composition of the seeds of Celosiaargentea L discover nine new pentacyclic triterpenoid saponins, which are celosins A,B, C, D, E, F, G, I and II. Experiments show that total saponins from Semen Celosiae(celosin I and celosin II) had antioxidant effects and protect from liver injury. Inaddition, Liang Lin indicates that total saponins from Semen Celosiae could reduceTC levels in the model of rat and rabbit. As a continued work, Syrian golden hamsters,whose lipid composition and lipoprotein metabolism is similar to humans, so theywere chosen to establish hyperlipidemia model, mimicing hyperlipidemia in human,to confirmed the lipid-regulating effect of CES, and further explore its mechanism by testing protein and gene expression levels of genes related to lipid metabolism.Meanwhile,We establish an analytical method for the determination of the twocompounds using HPLC-ELSD in order to screen resources of elite germplasm forfurther applications. These studies lay the foundation for the development andutilization of resources of Semen Celosiae and new drug development in the future.methods and results1. lipid-regulating effects of CES:(1) the establishment of hyperlipidemia model: theSyrian golden hamster was chosen to establish the model of hyperlipidemia byfeeding them the diet containing high fat, the blood was analysed for the TC, TG,HDL-C and LDL-C concentrations after two weeks, the results showed that:compared with the normal group, the model group elevated TC, TG and LDL-C by143%,263%and156%respectively (p <0.01), there is no significant change in thelevel of HDL-C between model group and normal group, so,these data suggest thatthe model of hyperlipidemia was successfully established.(2) regulation on serumlipids of CES: The animals were divided into normal group, model group, the Lipitorgroup (2.5mg/kg), CES (10mg/kg)group, CES (30mg/kg) group, CES (90mg/kg)group, two weeks after administration, the concentration of serum lipids were tested,the results show: all three CES groups can significantly reduce serum TC levels by12.8%(p <0.05),18.3%(p <0.01),37.8%(p <0.01) respectively in a dose-dependentmanner; Meanwhile, three CES groups lower TG levels by45.1%,42.5%,48.0%respectively (p <0.01); CES (30mg/kg) group significantly reduced LDL-C levels (p<0.01), CES (10mg/kg and30mg/kg)could also lower LDL-C, but it is notsignificant statistically.(3) regulation on lipids in liver of CES: The lipid levels inliver of the hamster was detected, the result show: CES (30mg/kg)group cansignificantly reduce TC and TG by25.1%and31.6%respectively(p <0.05); CES(90mg/kg)significantly decreased TC and TG by23.1%and39.2%(p <0.01), whileCES (10mg/kg) group could not significantly lower TC and TG; CES(90mg/kg)groupsignificantly decreased LDL-C levels (p <0.05) by37.8%(4) liver damageindicators: compared with model group, ALT, AST, ALP, A/G in Lipitor group wassignificantly elevated, indicating that Lipitor has the effects of the liver injury; CESin low, medium, high doses did not influence three ALT, AST, ALP, A/G,suggesting no damage to the liver (5) anti-inflammatory and antioxidant effects ofCES: liver tissue by detecting inflammatory cytokines IL-6, IL-10, IL-1β,TNF-α and antioxidant enzyme activity such as CAT, SOD, CAT, GSH, GSH-Px, MDA,T-AOC, the results show that inflammatory markers and antioxidant parameterswere not significantly different between the model group and the normal group, wespeculated hamsters in the model group did not produce a significant inflammatorymarkers and reactive oxidative species;(6) Oil Red staining of liver tissue: The resultsshow: compared with normal group, a lot of fat accumulated in the liver tissue ofmoded group, two weeks after CES administration, fat content is decreasd as thedosage increase;(7) Western blot and qRT-PCR detection: By using Western blot andqRT-PCR, the effect of CES on protein expression of HMGCoAR, LDLR,CYP7A1, CYP4A1, CPT1A, ABCG1and ABCG1investigated, the data demostratedthat CES can increase LDLR protein expression, decrease HMGCR expression,decrease PCSK9Mrna expression, these results indicated: CES possibly decreasePCSK9mRNA expression, therefore increase LDLR levels, lower LDL-Cconcentrations; CES decrease HMGCR protein expression, inhibit vivo synthesis ofcholesterol, lower TC concentration; CES increase LDLR protein expression,increased LDLR to eliminate LDL-C, lower LDL-C concentrations.CES caneffectively reduce TC and LDL-C concentrations in hamsters.2. estabilshing the method for the simultaneous determination celosinI, II contentby using HPLC-ELSD. Chromatographic conditions are as follows: agilent SB c18column; mobile phase: acetonitrile-0.1%acetic acid in water (32:68); speed:1ml/min;ELSD (gain:8; temperature:40℃; gas:3.5bar). two compounds in the0.20-1.00range show good linear relationship, linear equation are y=1.4597x+2.9165(celosinI) and y=1.4204x+2.8411(celosin II), r2reached0.999, the method is simple, goodprecision, accurate and reliable.3.21batches of seeds of Celosia argentea L. from different origin weredeterminated for the content of two saponins, significant differences exist in thecontent between different origin herbs. crude drug from Yongzhou(Hunan province),Zhuhai (Guangdong), Nanning(Guangxi) contain the highest contents of all. andherbs from Hebei (anguo), Xibeiwang(Beijing) and linshui(Henan) show the lowestlevels (P <0.01). in additon,The study found that the location has a significantinfluence on the content celosinI、 II from seeds of Celosia argentea L, herbs fromlower latitudes contain high levels of celosins I、II， and herbs from high latitudes isadverse. Light play a key role on the content of the two saponins, indicating that environmental factors as important factors that affect the quality of the seeds of herbs. |
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