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Study On The Antitumor And Reducing Toxicity Of Rhizoma Paridis Saponins Combined With Curcumin

Posted on:2017-03-17Degree:MasterType:Thesis
Country:ChinaCandidate:J LiFull Text:PDF
GTID:2334330512480568Subject:Medicinal Chemistry
Abstract/Summary:PDF Full Text Request
Rhizoma Paridis saponins(RPS)are famous for the treatment of various cancers in modern clinical uses.Curcumin is a widely used spice and coloring agent in food and possesses anticarcinogenic pharmacological activities.The toxicity assessment of long-term use of them has been investigated.RPS can induced liver and lung injury while curcumin induced slight liver injury.However,the mechanism has not yet been investigated.In order to explain this phenomenon,oxidative stress,pro-inflammatory factors and detoxified enzymes were detected.As a result,RPS generated the over-expression of reactive oxygen species(ROS)and pro-inflammatory cytokines,and decreased the levels of antioxidant and detoxified enzymes.Meanwhile,as the self-protection of rats,RPS treatment activated the transcription of Nrf2 and elevated the expression HO-1 to reduce tissues damage.Curcumin generated slight over-expression of ROS and pro-inflammatory cytokines.Meanwhile,as the self-protection of rats,curcumin also treatment activated the transcription of Nrf2 and elevated the expression of HO-1 to reduce tissues damage.After 30 days' recovery,abnormalities in liver and lungs disappeared.Our work provides useful data for further research the minimizes the dangers of toxic herbal product use and it's necessary for intermittent administration of drug in our daily life.In our previous research,RPS-treatment caused a liver injury.However,it was alleviated through co-treatment with curcumin.In order to explain this result,we also detected oxidative stress,pro-inflammatory factors and detoxified enzymes.We find that the curcumin alleviated that RPS induced the enhancement of ROS and 8-hydroxy-2-deoxyguanosine(8-OHdG),down-regulation separation of thioredoxin(Trx)and thioredoxin-interacting protein(TXNIP)and up-regulation inflammation(COX-2,IL-10,and NF-?B),but enhancement of HO-1,GST and Nrf2.Our work provided useful data for further research and new drug exploration of RPS and curcumin.Based on previous research,RPS not only inhibited the liver tumor growth in H22 hepatocarcinoma mice and human hepatoma xenografts in nude mice,but also effectively attenuated hepatotoxicity in DEN induced pulmonary adenoma generation.However,the mechanism of them has not yet been investigated.In the present study,we use western blot,PCR technology to detect mechanism of anti-hepatotoxicity and anti-pulmonary metastasis.As a result,RPS alleviated levels of liver injury through inhibiting liver tissues of 8-OHdG up-regulating expression of phase ? and phase ? enzyme in DEN-induced rats.RPS effectively attenuated hepatotoxic and inhibited pulmonary adenoma through down-regulating expression of MMP-9 and upregulating level of TIMP-2 in DEN-induced rats.In conclusion,RPS would be a potent anticancer agent used in the prospective application.Previous studies have shown that RPS,curcumin and RC has been used in the treatment of pulmonary adenocarcinoma disease.We set up a mouse model of diethylnitrosamine(DEN)induced lung cancer to evaluate the antitumor effect of RPS,curcumin and RPS combined with curcumin(RC).After 27 weeks treatment,mice were sacrificed in order to perform histopathological examinations,oxidative stress assays,PCR and WB technology to detect mechanism of anti-lung cancer.As a result,DEN induced lung cancer formation.RPS,curcumin and RC inhibited lung cancer through significantly decreasing molecule target of EGFR,Her2,ALK and TGF,down-regulating expression of signaling pathways of Ras-pERK and PI3K-pAkt,inhibiting proliferation,inflammation and aberrant expression,enhancing apoptosis and differentiation.
Keywords/Search Tags:RPS, Curcumin, hepatotoxicity, pulmonary metastasis, lung cancer, oxidative stress, inflammatory
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