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ObjectiveTo study the effect-enhancing and toxicity-reducing activities of astragalus polysaccharide injection （APS） on U14 cervical cancer in model mice receiving X-ray treatment. MethodU14 mouse cervical cancer cells were cultured in vitro and injected into the right forelimb armpit of Kunming mice for constructing a subcutaneous tumor-bearing model of cervical cancer. The tumor-bearing mice were randomly divided into the model group， X-ray intervention（IR， 6 Gy） group， APS （10 mL·kg-1·d-1） group， and IR + APS group. Following the observation of the state， body mass， and food intake of mice in each group， the volume of the tumor was measured. The tumor cell cycle and apoptosis were determined by flow cytometry. The protein and mRNA expression levels of apoptosis-related proteins p53， B-cell lymphoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and cleaved cysteine-dependent aspartate-directed protease-3 （Caspase-3） in tumor tissues were assayed by Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultThe comparison with the model group showed that mice in the IR group had poor mental status and reduced mobility. The IR group and IR + APS group exhibited reduced food intake and body mass since the 8th d （P<0.05， P<0.01） and narrowed tumor volume since the 9th d （P<0.01）. In the IR group， the proportion of cells in the G1 phase was increased， while the proportion of those in the S phase was decreased （P<0.01）. In the IR + APS group， the proportion of cells in the G1 phase rose， whereas the proportion of those in the G2 and S phases cells declined （P<0.05， P<0.01）. The apoptotic rates in both the IR group and IR + APS group were elevated significantly （P<0.01）. Compared with the model group， the IR group and IR + APS group displayed up-regulated cleaved Caspase-3 and Bax protein and mRNA expression in tumor tissues， but down-regulated Bcl-2 and p53 protein and mRNA expression （P<0.05， P<0.01）. Compared with the IR group， the mice in the IR + APS group had better mobility and hair， normal body mass， and increased food intake （P<0.05）. The tumor volume in the IR + APS group was reduced （P<0.05）. The proportion of cells in the G2 phase was reduced， but the proportion of those in the S phase was raised （P<0.05）. The apoptosis rate was increased （P<0.05）. The apoptosis-related protein Bax protein expression in the tumor tissue was up-regulated， while the protein expression levels of Bcl-2 and p53 were down-regulated （P<0.05， P<0.01）. ConclusionAPS maintains the life state of U14 cervical cancer model mice treated with X-ray and promotes tumor cell apoptosis， thus enhancing the efficiency and reducing toxicity.
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On the basis of the previous work of the research group, the orthogonal design method was further used to optimize the processing technology for reducing toxicity of fried Tripterygium wilfordii in Lysimachia christinae Decoction. A total of 9 processed products of T.wilfordii in L.christinae decoction were prepared by four factors and three levels orthogonal design table. The contents of triptolide in T.wilfordii were determined by high performance liquid chromatography(HPLC) before and after processing: 4.27, 3.92, 3.57, 2.75, 2.42, 2.66, 3.51, 1.87, 1.75, 2.03 μg·g~(-1). On this basis, the above processed products were orally given to mice for 28 days. 12 hours after the last administration, food fasting except water was provided, and 24 hours later, the eyeballs were taken for blood and liver tissue. Serum biochemical indexes, liver lipid peroxidation and antioxidant related indexes were detected by kit method. Twenty-eight days after oral administration of raw T.wilfordii, the levels of serum alanine aminotransferase(AST), alanine aminotransferase(ALT), alkaline phosphatase(ALP) and liver malondialdehyde(MDA) in mice increased by 91%(P<0.01), 46%(P<0.05), 73%(P<0.01) and 99%(P<0.01), while the liver antioxidant indexes such as superoxide dismutase(SOD), glutathione(GSH), glutathione peroxidase(GPX) and glutathione-S transferase(GST) significantly decreased(P<0.01). After administration of the processed products, the above indexes were significantly reversed(P<0.01 or P<0.05). Especially, the processing conditions of A_3B_2C_1D_3 had the best detoxification effect on T.wilfordii, which decreased the high levels of AST, ALT, ALP and MDA by 49%(P<0.01), 32%(P<0.01), 42%(P<0.01), and 17%(P<0.05). Therefore, the best processing conditions for T.wilfordii in L.christinae decoction were A_3B_2C_1D_3, namely "15% mass fraction of L.christinae, 1 h moistening time, 160 ℃ frying temperature, and 9 min frying time".
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Animals , Mice , Antioxidants , Liver , Primulaceae , Technology , TripterygiumABSTRACT
Polygalae Radix， a traditional Chinese medicine， has the functions of improving intelligence， calming nerves， relieving cough and eliminating phlegm. Its processing methods are various， but the purpose of processing is to reduce toxicity and increase efficiency. In this paper， the methods of ancient processing， such as cleansing， cutting， processing with excipient and processing without excipient， were summarized， the processing methods of Polygalae Radix in the different versions of Chinese Pharmacopoeia and the local processing specifications were summarized， in order to compare the differences and research progress of different processing methods. On this basis， taking the modern research of processed products of Polygalae Radix as the breakthrough point， this paper reviewed the modern research on processed products of Polygalae Radix from the aspects of processing technology， chemical composition changes and pharmacodynamics changes before and after processing， and the mechanism of reducing toxicity and increasing efficiency. Based on the research status of processing of Polygalae Radix， some existing problems were analyzed in this paper， including not many ancient processing methods used in modern times， lack of standardized research on processing technology， few studies on the ingredients introduced by excipients， etc. The author thinks that it is necessary to strengthen the research on the ancient processing of Polygalae Radix combined with processing methods with local characteristics. While discussing the processing technology， combining with the composition and efficacy， we should carry out in-depth research on the processing mechanism of different processing products of Polygalae Radix， so as to provide scientific basis for the rationality of processing of Polygalae Radix and ensure the clinical safety of medication.
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OBJECTIVE：To compare the content changes of active/toxic ingredient genkwanin in ethanol extract from Wikstroemia indica before and after processing with “sweat soaking method ”and the effects of processing method on its anti-oxidation ability. METHODS ：HPLC method was adopted to determine the content of genkwanin in W. indica before and after processing with “sweat soaking method ”. The separation was performed on Diamonsil C 18 column with 0.2％ phosphoric acid solution-methanol as mobile phase （gradient elution ）at the flow rate of 1 mL/min. The column temperature was 30 ℃ and detection wavelength was set at 346 nm. The sample size was 20 µL. SD rats were randomly divided into blank group ，W. indica raw product ethanol extract group （317.52 mg/kg，called“raw-product group ”as short ）and W. indica processed product ethanol extract group （317.52 mg/kg，called“processed-product group ”as short ），with 6 rats in each group. Blank group was given constant volume of 1.0％CMC-Na solution intragastrically ，and administration groups were given relevant medicine suspension intragastrically；all of them were given 20 mL/kg，once a day ，for consecutive 14 days. The contents of serum oxidant stress indexes（MDA，CAT，SOD）in rats were determined by ELISA. RESULTS ：The linear range of genkwanin were 0.147-27.360 μg （r＝0.999 9）；RSDs of precision ，reproducibility and stability tests were all lower than 3％ ；average recoveries were 98.64％-98.92％（RSD＜1％，n＝3）. Before and after processing with “sweat soaking method ”，average contents of genkwanin in W. indica were 0.377 6 and 0.234 0 mg/g. Compared with blank group ，the serum content of SOD in raw-product group was increased significantly ，while CAT content was decreased significantly （P＜0.05 or P＜0.01）；the serum content of MDA was decreased significantly in processed-product group ，while SOD content was increased significantly （P＜0.05 or P＜0.01）. MDA content of processed-product group was significantly lower than that of raw-product group ，while SOD content was significantly higher than raw-product group （P＜0.05）. CONCLUSIONS ：After proce ssing with “sweat soaking method ”，the content of genkwanin in W. indica is decreased ，and antioxidant activity is increased .“Sweat soaking method ”processes certain function of “reducing toxicity and increasing efficiency ”.
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Objective:To campare the hepatotoxicity on BRL and nephrotoxicity on NRK caused by dichloromethane site of Genkwa Flos before and after being processed with vinegar. Method:BRL of normal hepatocytes and NRK of normal renal cells in rats were selected as the subjects.Thiazolyl blue tetrazolium bromide method(MTT) was adopted to evaluate the effect of dichloromethane sites of raw and vinegar-processed products on cell activity of NRK and BRL.The levels or contents of aspartate aminotransferase(AST),alanine aminotransferase(ALT),alkaline phosphatase(ALP),glutathione(GSH),lactate dehydrogenase(LDH),blood urea nitrogen(BUN) were determined in cell culture supernatant and splitting supernatant for evaluation of their oxidative damage effect. Result:Compared with the blank group,dichloromethane site of raw products could obviously inhibit the cell activity of NRK and BRL,and increase the levels of AST,ALT,ALP and LDH(PPPPConclusion:Processing with vinegar can attenuate the hepatotoxicity and nephrotoxicity on NRK and BRL caused by dichloromethane site of Genkwa Flos,it can improve hepatic and renal function and antioxidant capacity.
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"Guiding herbs" is one of the characteristics of the special way of taking Chinese materia medica (CMM). However, some people have misunderstanding or lack of basic knowledge about how to choose the guiding herbs and its effect, leading to the poor clinical effect or even toxic effects because of improper decoction. This study attempts to analyze the action of the common guiding herbs in the Chinese Pharmacopoeia (2015 edition) from the perspective of reducing toxicity and increasing efficacy, returning drug to its channels, and put forward exploratory thinking on how to choose the guiding herbs to provide scientific evidence for promoting the rational use of drugs in clinic.
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Radiotherapy is one of the main means of clinical treatment for cancer, although the continuous updating and development of technology and equipment, adverse reactions and side effects can't be avoided yet.Improving the clinical efficacy of radiotherapy and reducing its adverse reactions are the currently facing subjects.A large number of clinical studies showed that using traditional Chinese medicines(TCM)in tumor radiotherapy had significant effects of improving and controlling the clinical symptoms, improving the life quality of cancer patients, improving the sensitization of radiotherapy, preventing the tumor metastasis and recurrence, as well as improving immune function and long-term survival, etc.Meanwhile, TCM also had significant roles in reducing the damage of radioactive inflammation, decreasing the bone marrow suppression to improve peripheral blood, and reducing the toxicity of digestive system, etc.The combination of radiotherapy and TCM provides a broader space for the comprehensive treatment of tumors.
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AIM To study the effects of degreasing-frosting on reducing toxicity and enhancing efficacy of Periplaneta americana L..METHODS The 95％ ethanol extracts from P.americana raw powder and processed products were extracted by petroleum ether,ethyl acetate,n-butanol and water.TLC was applied to comparing the component changes in various fractions.GC-MS was used for analyzing the kinds and contents of liposoluble constituents before and after processing.Shaking flask method combined with UV spectrophotometry method was adopted in the determination of Papp values in octanol-water and different pH values (2.23,3.28,4.22,5.23,6.12,7.24,8.23,9.10,10.15 and pure water) of buffer solutions.RESULTS After the petroleum ether fraction was processed,the colors of TLC spots became much shallower,which changed more significantly with the prolonging of processing time and increase of pressure.The TLC spots in the n-butanol and water fractions were clear without obvious changes.And no TLC spots were found in the ethyl acetate fraction.The kinds of liposoluble constituents were the same before and after processing,whose absolute contents were decreased after processing.Compared with raw powder,the Papp values of minor polypeptides in various processed products at different pH values exhibited significant differences (P ＜0.05,P ＜0.01),which also showed certain differences at the same pH values.CONCLUSION Degreasing-frosting can affect the contents of liposoluble constituents in P.americana and Papp values of minor polypeptides,which may be the mechanism of reducing toxicity and enhancing efficacy.
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This article was aimed to study enhancing efficacy and reducing toxicity on anti-tumor from total flavonoids and total polysaccharides in Taxus mairei compatibility with taxol. MTT assay was performed to analyze the cell proliferation and apoptosis of 4T1, A549, MCF-7 tumor cells after treatment of total flavonoids and total polysaccharides in T. mairei combined with taxol at different concentrations. Isobolograms was used to investigate the behavior of combination therapy. Therapy experiments were conducted on ICR mice bearing S180 sarcoma. The tumor weight was measured to calculate inhibition rate according to uniform design. Blood cells indicators were detected by blood cell analyzer. The results showed that total polysaccharides and total flavonoids can enhance the inhibition effect on 4T1, A549 cells by taxol. Total polysaccharides can enhance the inhibition effect of taxol to MCF-7 in vitro, and S180 sarcoma-bearing mice in vivo. It reduced the toxic effects of anti-tumor effect of taxol in vivo. It was concluded that taxol can achieve the effect of enhancing efficacy and reducing toxicity through combining with total flavonoids and total polysaccharides in T. mairei.
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As the fundamental rule to construct multi-herb prescriptions of Chinese materia medica (CMM), formula compatibility is the key to study the principles of CMM prescriptions. Modern scientific connotation on the formula compatibility could be investigated on the aspects of chemistry, pharmacokinetics, and pharmacodynamics, according to the interactions between CMM prescriptions and the organism. The chemistry of CMM prescriptions is a prerequisite to investigate formula compatibility, and chemical alterations, including quantitative and qualitative changes,induced by formula compatibility are especially emphasized. Formula compatibility can modify the pharmacokinetic behavior of drugs by regulating key steps of pharmacokinetic process to influence the effect and toxicity of CMM prescriptions. Ingredients of a formula affect its therapeutic actions;to elucidate the therapeutic mechanisms of formula compatibility, a new method named "combination of drug targets guided by the pathophysiology of diseases" is proposed to investigate the phenomenon that multi-components of a formula act on multi-target in the organism. It sheds light on understanding the mechanisms of improving effect/reducing toxicity of formula compatibility and provides the reference to enhance the modern scientific research of CMM prescriptions.
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OBJECTIVE: To observe the antitumor effect of FZQL combined with CTX on S180 tumor and the effect of FZQL on reducing CTX s toxieity .METHODS: The models of S180 tumor bering mice were established .The animals were divided into CTX therapy group, CTX and FZQL combined therapy group, FZQL therapy group and control group.The results were compared among these groups.RESULTS: The weight of tumor in FZQL therapy group was less than that in control group.All of the experimental markers in combined iherapy group were better than those in CTX therapy group.CONCLUSION: FZQL has a marked inhibiting effect on tumor(S180), and it can increase the CTX's inhibiting effect on tumor and reduce the side effect of CTX and increasing the body immunity.