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Anti-liver Fibrosis Effect And Mechanism Of Tibetan Medicine

Posted on:2019-03-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:X FengFull Text:PDF
GTID:1314330545996062Subject:Chinese medicine pharmacy
Abstract/Summary:PDF Full Text Request
Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even death at the end stage.Herpetospermum caudigerum Wall(BLGZ)is a traditional Tibetan medicine,which has been used to ameliorate liver injuries in the folk.Two new poly hydroxy polyacetylenes,herpecaudenes A and B(1 and 2),were isolated from the ethanol extract of seeds of Herpetospermum caudigerum,an important Tibetan medicine.The structures of them were elucidated on the basis of extensive spectroscopic methods including UV,IR,HRESIMS,1H and 13C NMR,HMBC,HSQC,and 1H-1H COSY.The present study was designed to investigate the beneficial effects of Herpetospermum caudigerum Wallagainst carbon tetrachloride(CCl4)hepatotoxicity in rats,and explore the underlying mechanisms.In our results,animals were treated with either CCl4 and/or BLGZ for six consecutive weeks.The levels of inflammatory cytokines in serum and liver,hepatotoxicity markers in serum and histopathological evaluation were determined.HCWsignificantly inhibited the CCl4-incuded overproduction of inflammatory cytokines including tumor necrosis factor α(TNF-α),cytokines interleukin-1β(IL-1β),and interleukin-6(IL-6)in serum and liver.Animals treated with BLGZexhibited lower levels of alanine transaminase(ALT)and aspartate transaminase(AST).BLGZ administration alleviated CCl4 induced hepatic fibrosis as manifested in histopathological records.It depleted the accumulation of inflammatory cytokines,and decreased the production of p-NF-κBp65 and p-IκBα.In addition,BLGZ also significantly reversed CCl4-induced alteration of TGF-β and p-samd-3 in liver tissue.This study,NMR-based metabolomics analysis combined with biochemical assays and element analysis was used to demonstrate the protection of BLGZ against CCl4-induced liver injury in rats and to seek the underlying mechanisms.The results showed that BLGZcould significantly reduce the elevated levels of fibrosis markers such as hyaluronidase,laminin,Type III procollagen and Type IV collagen in the serum,improve the activities of the antioxidant enzymes,and effectively reverse the abnormal levels of elements in liver fibrosis rats.Orthogonal partial least squares-discriminant analysis and correlation networks analysis revealed that BLGZ could heal liver fibrosis through ameliorating oxidative stress,repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms.In conclusion,this integrated metabolomics approach provides new insights into the protective mechanism of BLGZ in the CCl4-induced liver fibrosis rats.
Keywords/Search Tags:Tibetan medicine, Herpetospermum caudigerum Wall., hepatic fibrosis, Western blot, Metabolomics
PDF Full Text Request
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