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Periplocae Cortex is a traditional Chinese medicine in China, which is mainly produced in northeast China, north China, northwest China, southwest China. In recent years, the increasing in-depth research resulted in the discovery of anti-tumor and cardiac pharmacological activities of Periplocae Cortex, which has broad application prospects. On the basis of summarizing chemical components and pharmacological effects, combined with the theoretical system of Q-marker, the quality control components of Periplocae Cortex were predicted from the aspects of the correlation between chemical composition and traditional medicinal properties, traditional efficacy, and new clinical use, plasma composition, measurable composition, storage time by analyzing literature. Among the components, periplocoside, periplocin, periplogenin, 4-methoxy salicylaldehyde showed significant activity, which provides a scientific basis for quality evaluation of Periplocae Cortex.
Subject(s)
Biomarkers , China , Drugs, Chinese Herbal , Medicine, Chinese Traditional , Quality ControlABSTRACT
Objective To investigate the biopharmaceutical classification of periplocin, periplocymarin and periplogenin by biopharmaceuticals classification system (BCS). Methods The solubility and permeability of periplocin, periplocymarin and periplogenin were studied by using experimental and computer prediction software Pipeline Pilot 8.5 and ChemDraw. These three substances were sorted based on experimental and predicted values by BCS classification method. Results According to the test results, periplocin, periplocymarin and periplogenin were classified as BCS III, which are different from the classification results predicted by different software. The permeability results based on ClgP was consistent with the experimental results; The solubility based on lgCs and the permeability based on AlgP and lgD were opposite to the experimental results. Conclusion The periplocin, periplocymarin and periplogenin are BCS III drugs, the solubility is decreased in turn, but they are still highly soluble components. The permeability is the key factor affecting its absorption. The predicted value of biopharmaceutical properties of active ingredients of A-type cardiac glycosides based on the chemical structure are significant different with the test results, for the BCS study and the in vitro and in vivo correlation evaluation of oral absorption of traditional Chinese medicine preparations containing such ingredients, it is recommended to use a variety of methods to correct the data and increase the reliability of the results.
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Objective:To study the serum pharmacochemistry of Periploca forrestii rhizomes,and to investigate the pharmacological material basis of extract of P. forrestii rhizomes in rats. Method:Rapid identification of constituents absorbed into blood was carried out by UPLC-Q-TOF-MS,according to retention time,accurate relative molecular mass and standard substance comparison,these constituents were identified and speculated by Data Analysis,Metabolite Detect and other softwares,then preliminary determination of constituents absorbed into blood of rats after oral administration of extract of P. forrestii rhizomes was investigated. Result:Totally 17 constituents absorbed into blood were detected in serum,ten of them were prototype constituents and the other were metabolites.Seven of the prototypes were identified as 5-O-caffeoylquinic acid,4-O-caffeoylquinic acid,3-O-caffeoylquinic acid,3,4-di-O-caffeoylquinic acid,3,5-di-O-caffeoylquinic acid,4,5-di-O-caffeoylquinic acid and periplocin. Conclusion:These constituents absorbed into blood may be substances that act directly in vivo of P. forrestii rhizomes,and it is helpful to clarify pharmacological material basis and mechanism of this herb.
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OBJECTIVE:To establish the method for content determination of chlorogenic acid and periplocin in Miao medicine Periploca forrestii. METHODS:HPLC method was adopted. The determination was performed on Xtimate C18 column with mobile phase consisted of acetonitrile-0.1% phosphoric acid solution(gradient elution)at the flow rate of 1.0 mL/min. The detection wavelength was set at 220 nm,and column temperature was maintained at 25 ℃. The sample size was 10 μL. Cluster analysis was conducted according to the content of chlorogenic acid and periplocin in samples by SPSS 23.0 software. RESULTS:The linear range of chlorogenic acid and periplocin were 0.040 6-1.8 μg(r＝0.999 4)and 0.016 8-2.3 μg(r＝0.999 9),respectively. RSDs of precision,stability and repeatability tests were all lower than 5.0%. The quantitation limits were 0.918 0,0.084 3 μg/mL, and detection limits were 0.102 0,0.025 3 μg/mL, respectively. RSD of durability were lower than 3.0%. The recoveries were 102.66%-104.00%(RSD＝0.53%,n＝6),96.44%-100.79%(RSD＝1.73%,n＝6),respectively. RSD of durability were lower than 3.0%. The result indicated that 18 batches of samples were divided into 3 categories by cluster analysis. S2,S4,S10,S12 and S14-S18 were divided into one category;S1,S3,S5-S7,S9,S11 and S13 were divided into another category;S8 was regarded as one category. CONCLUSIONS:The method can be applied for quality control and evaluation of P. forrestii. The contents of chlorogenic acid and periplocin in P. forrestii from different producing areas are different greatly. There is a certain correlation between the content of each component and the producing area.
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Cortex Periplocae Radicis (CPR) is the dried root barks of Periploca spium Bge. It has been used in China for treating rheumatoid arthritis and strengthening the bone and the musculature for thousands of years. Recently, an increasing number of bioactivities of CPR have been recognized, including tumor suppression and anti-chronic heart failure function. However, long-term use or large doses of CPR may produce adverse reactions, which constrains its applications in clinical therapy. Therefore, it is critical to know the chemical components of CPR in order to understand the toxicity mechanism. Nearly a hundred chemical compositions have been found, however, various classes, obfuscated names of different compounds, and disaccord between chemical structure and name were major obstacles to studying pharmacodynamics and toxicity of CPR. In this paper, 94 chemical components of CPR are classified and reviewed, which is valuable for the comprehensive understanding of its biological functions and safe clinical use.
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Cortex Periplocae Radicis(CPR)is the dried root barks of Periploca spium Bge. It has been used in China for treat?ing rheumatoid arthritis and strengthening the bone and the musculature for thousands of years. Recently,an increasing number of bio?activities of CPR have been recognized,including tumor suppression and anti-chronic heart failure function. However,long-term use or large doses of CPR may produce adverse reactions,which constrains its applications in clinical therapy. Therefore,it is critical to know the chemical components of CPR in order to understand the toxicity mechanism. Nearly a hundred chemical compositions have been found,however,various classes,obfuscated names of different compounds,and disaccord between chemical structure and name were major obstacles to studying pharmacodynamics and toxicity of CPR. In this paper,94 chemical components of CPR are classified and reviewed,which is valuable for the comprehensive understanding of its biological functions and safe clinical use.
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Objective To investigate the effects of periplocin from Cortex Periplocae (CPP) on apoptosis of human lung cancer A549 cells and expression of survivin, and demonstrate its anti-tumor effect and the possible mechanism. Methods Inhibitory effect of CPP at different concentrations (1. 25, 2. 50, 5. 00, 10. 00, 20. 00 ng·mL-1 ) and for different time length (24, 48, 72 h) on A549 cell proliferation was tested by MTT method. Apoptosis rate of A549 cells treated with CPP at different concentrations (2. 50, 5. 00, 10. 00 ng·mL-1 ) were measured using flow cytometry (FCM) for 6, 12, 24, 48, 72 h, respectively. The morphological and ultrastructural changes of the apoptosis cells were observed by acridine orange/ ethidium bromide (AO/ EB) staining and transmission electron microscopy (TEM). The effects of CPP on mRNA and protein expression of apoptosis associated gene survivin were assessed by RT-PCR and Western blotting. Results CPP could significantly inhibit the growth of A549, and the inhibition rate reached (93. 46±2. 35)% . The results of FCM showed that the apoptosis rate of A549 cells treated with CPP was increased significantly as compared to the control group ( P<0. 05). Meanwhile, typical apoptotic peaks were detected. The characteristic morphological changes of apoptosis were observed in A549 exposed to CPP, including cell shrinkage, the nuclei became yellow-red by AO/ EB staining, and typical ultrastructural changes, including nuclear chromatin condensation along the nuclear membrane, vacuolar degeneration of cytoplasm observed by TEM. The result of RT-PCR indicated that survivin mRNA expression decreased obviously in A549 cells exposed to CPP. The protein expression of survivin in A549 cells treated with 10. 0 ng·mL-1 CPP(0. 251±0. 012)was weaker than that in control group(0. 928±0. 016). Conclusion CPP can induce apoptosis in human lung cancer cell lines A549, and the probable mechanism is related to the down-regulation of survivin mRNA and protein.
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Objective: To study the dynamic variation of Mn, Cu, Zn, Fe, K, Ca, and Mg in velamen and stem bark of Periploca sepium and their correlation with the elements such as periplocin and 4-methoxysalicylic aldehyde in different harvesting periods, and to reveal dominant factors on the accumulation of two active components. Methods: The contents of periplocin and 4-methoxysalicylic aldehyde were detected by FAAS and electric heating wet digestion, and the data were analyzed by SPSS 19.0. Results: The seven elements were varied widely in velamen and stem bark. The variation trends of Ca and periplocin, Fe and 4-methoxysalicylic aldehyde in velamen were similar, equally, those of Fe and 4-methoxysalicylic aldehyde, Ca and Mg in stem bark were similar and like double peaks. Periplocin has highly significant positive correlation with Ca in velamen and significant negative correlation with Zn in stem bark. To 4-methoxysalicylic aldehyde, when in velamen, it has highly significant positive correlation with 4-methoxysalicylic aldehyde and Fe in stem bark, significant negative correlation with Mn in stem bark, and significant positive correlation with Fe in velamen; when in stem bark, it has highly significant positive correlation with Fe in both velamen and stem bark. Conclusion: Ca, Zn, Fe, and Mn are dominant elements of accumulation, the key factors for periplocin are Ca in velamen and Zn in stem bark, and Mg in velamen is indierect acting factors; The key factors for 4-methoxysalicylic aldehyde are Mn in stem bark and Fe, Ca and Mg in stem bark are indirect acting factors.
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Objective To investigate the inhibitory effects of periplocin from cortex periplocae (CPP) on human lung cancer cell line QG56 and to discuss its mechanism. Methods QG56 cells were cultured in vitro. The final concentrations of CPP in control group were 1.25, 2.50, 5.00, 10.00 and 20.00μg/L. QG56 cells were treated with ascending concentration of CPP for 24 h, 48 h and 72 h. The cell proliferation was measured using MTT method. The morphological changes of QG56 cells were observed under inverted microscope. Flow cytometry (FCM) was used to detect the effects of CPP on cell cycle and cell apoptosis. The expression of apoptosis associated gene bax mRNA in QG56 cells was detected by RT-PCR. The expres-sion of bax protein before and after treatment of CPP was examined by SP immunocytochemistry. Results The inhibitory ef-fect of CPP on the proliferation of QG56 cells was increased with the increasing concentrations of CPP and the prolonged du-ration of treatment. The morphological changes were displayed in QG56 exposed to CPP. The results of FCM showed that CPP caused cell cycle arrest at G0/G1 phase. The apoptotic rate of QG56 cells was significantly increased after CPP treatment for 48 h (P<0.05). The expression of bax mRNA was increased in QG56 exposed to CPP. The result of immunocytochemis-try indicated that CPP up-regulated the expression of bax protein. Conclusion CPP showed significant inhibitory effect on human lung cancer cell lines QG56 through inducing cell cycle arrest and apoptosis.
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Objective To increase the ultimate yield of periplocin in Periploca sepium adventitious root cultures by a two-stage culture based on nitrogen source.Methods Firstly,the effects of nitrogen source(NH-NO-)at different ratios and different total initial nitrogen amounts on the accumulation of biomass and secondary metabolites in adventitious root cultures of P sepium were investigated,and growth and production media for the two-stage culture based on the above results were established.Results The highest biomass and periplocin content were obtained in the culture medium of 15 mmol/L total nitrogen amount with NH-NO(1:2)and 30 mmol/L total nitrogen amount with nitrate as the sole nitrogen source.By adopting a fed-batch cultivation strategy,the dry weight adventitious root,periplocin content and yield were increased by 136%,108%,and 389%,respectively when compared with those of the control,reaching up to 8.13 g/L,157.15 μg/g,and 1277.63 μg/L,respectively.Furthermore,it was found that in the process of two-stage culture,the adventitious roots grew thicker significantly after they were transferred into production medium directly.Conclusion The ultimate yield of periplocin in P.sepium adventitious root cultures could be significantly increased by a two-stage culture based on nitrogen source.
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AIM: To investigate the immune mechanisms for Periplocin from Cortex Periplocae (CPP) in tumor-bearing mice. METHODS: H_(22) tumor-bearing model BALB/c mice were applied to evaluated in vivo immunoregulatory effect of CPP. The influence of different dose CPP (0.25, 0.50 and 1.00 mg/kg) on immune organs in tumorbearing mice were observed. T cell subsets of mice spleen were detected by flow cytometry. MTT assay was used to determine the influence of CPP on lymphocyte proliferation of mice spleen stimulated by ConA. The levels of TNF-α, IL-2 and IL-12 in serum from mice were detected by means of ELISA. RESULTS: Thymus index and spleen index of H_(22) tumor-bearing model control mice became less than that of normal mice (P < 0.05). Compared to both model and normal control groups, thymus index and spleen index of H_(22) tumor-bearing mice treated with CPP increased obviously (P < 0.05). CPP had no influence on the number of CD8~+ T cells, but up-regulated markedly the number of CD3~+, CD4~+ T cells and the ratio of CD4~+/CD8~+ in tumorbearing mice. In CPP-treated mice, the percentage of CD3~+, CD4~+ T cells were not different from normal mice (P<0.05), the ratio of CD4~+/CD8~+ was higher than that of normal mice (P < 0.05). CPP enhanced obviously lymphocyte proliferation of mice spleen induced by ConA, the SI scores were even higher than that of nornal mice. The levels of TNF-α, IL-2 and IL-12 in serum from CPP-treated mice, increased significantly compared to model control group (P<0.05) in a dose-dependent manner, were similar to or higher than that of normal mice. CONCLUSION: CPP protected immune organs of tumor-bearing mice, increased obviously the percentage of CD4~+ and CD4~+/ CD8~+ among the T cell line, and enhanced lymphocyte proliferation of mice spleen significantly, stimulated the production of TNF-α, IL-2 and IL-12. The results suggested that CPP possessed potent immunoregulatory effect.
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Objective To investigate the effect of periplocin of cortex periplocae (CPP) on Stat3 signaling and its probable molecular mechanism of inducing apoptosis and anti-tumor activity. Methods Cell proliferation was detected by MTT. Cell apoptosis and cell cycle were investigated by flow cytometry. Expression of Stat3 protein in SMMC-7721 cells was analyzed by Western blot. Mcl-1, Survivin and XIAP mRNA expressions were measured by RT-PCR. Results CPP inhibited the proliferation of SMMC-7721 cells significantly, induced their apoptosis and arrested their cell cycle at G2/M phase. Decreased expression of Stat3 protein in the cell nucleus was observed after CPP treatment, but no significant changes were found in cytoplasma. Mcl-1, Survivin and XIAP mRNA expression levels were decreased in a time-dependent manner. Conclusion CPP inhibits cell proliferation and induces apoptosis by inhibiting Stat3 signal transduction in human hepatocellular carcinoma cell line SMMC-7721.