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Protective Effect And Mechanisms Of Steamed Platycodon Grandiflorum And Platycodin D On Alcohol Oracetaminophen-induced Liver Injury

Posted on:2017-01-23Degree:MasterType:Thesis
Country:ChinaCandidate:Y LiuFull Text:PDF
GTID:2284330503966307Subject:Pharmacy
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Platycodon grandiflorum A.DC is a species of perennial flowering plant of the family Campanulaceae. Platycodi Radix(PR), the dried root of Platycodon grandiflorum has been used as a traditional medicine in China. As a traditional medicine, PR can effectively treat cough, abscess and excessive phlegm with bitter, acrid, flat. The principal bioactive constituents of this herb are triterpenoid saponins, which exhibit a variety of pharmacological activities such as anti-tumor, hepatoprotective, anti-diabetes and antiobesity effects. Characteristics of edible and officinal, is often be used as the raw material of health care products and a vegetarian. The resources and cultivation of Platycodin grandiflorum are very abundant in our country. It is great significance to further study the mechanism ofPR and develop its health care products and drugs.Processing methods existed since ancient times recorded in the Master Lei’s Discourse on Drug Processing at the earliest. In this experiment, we observed that PR sent out a special aroma after high temperature and high pressure steamed with browning reaction. In addition, showed that steamed PR contains 23 kinds of saponins and lobetyolin, including platycodin D and d-platycodin D analyzed by high performance liquid chromatography(HPLC) method and the modern spectral technology LC–MS.ALD is becoming the most common alcohol-related disease and causes substantial morbidity and mortality in China recently. Generally, ALD can lead to steatosis, steatohepatitis, fibrosis, and ultimately cirrhosis because liver is the main place to degrade alcohol metabolism. It also showed that the crude extract and saponin constituents had a wide range of protective effect on acute alcohol-induced oxidative stress injury. Therefore, the current study was performed to investigate whether steamed PRhad protective effect on acute alcohol-induced liver injury in mice. Results indicated that steamed PR pretreatment could be effective in preventing alcohol-induced dramatic increase in mice serum aminotransferase, preventing lipid peroxidation and fatty degeneration, significantly attenuating the oxidative stress injury and preserving the defense capability on acute liver injury.Platycodin D(PD) is the major triterpene saponin in the root of Platycodon grandiflorum. This study also investigated the preventive action of PD on acute alcohol liver injury in mice. The results indicated that PD pretreatment significantly decreased the levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST) triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(L-DLC) in serum and malondialdehyde(MDA) in liver. PD was also found to increase the activities of catalase(CAT), superoxide dismutase(SOD), and glutathione peroxidase(GSH-Px) in the live. In addition, PD markedly decreased the levels of proinflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and IL-6, which was caused by alcohol exposure. In contrast, histopathological examinations revealed that PD pretreatment noticeably prevented alcohol-induced hepatocyte apoptosis and steatosis. Collectively, the present study clearly suggested that the protective effect exhibited by PD on alcohol-induced liver oxidative injury may occur via the alleviation of oxidative stress and inflammatory response.The liver is not only the main place of alcohol metabolism, but also the target of drug metabolism and drug damage. Acetaminophen(APAP) is a widely used analgesic and antipyretic that is safe and effective, when it is taken at therapeutic doses. However, an acute or cumulative overdose of APAP can cause severe liver injury and liver failure. Excessive dosecan cause the body’s mitochondria oxidative stress injury and damage. Finally, we performed a study to assess the protective potential of platycodin D on APAP-induced liver injury in mice. Pretreatment with PD for 7 days significantly decreased acetaminophen-induced ALT, AST, MDA levels, as well as glutathione(GSH) depletion. PD depressed the increase of pro-inflammatory factors, such as TNF-α, NF-κB and IL-6, respectively. Furthermore, PD-treated mice reduced hepatocyte necrosis, apoptosis, intrahepatic hemorrhage and DNA fragment.Collectively, steamed PR tasted good after high temperature and high pressure, and 23 kinds of saponins and lobetyolin including platycodin D and d-platycodin D were identified. In addition, steamed PR and PD can effectively prevent alcohol and acetaminophen induced acute liver injury in mice, closely associated with increase antioxidant capacity, reduce inflammation and inhibiting hepatocyte apoptosis.
Keywords/Search Tags:Platycodon grandiflorum, Steamed, Platycodin D, Alcohol, Acetaminophen, Acute liver injury
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