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1.
Acta Pharmaceutica Sinica ; (12): 3252-3260, 2021.
Article in Chinese | WPRIM | ID: wpr-906843

ABSTRACT

Drug combination can effectively enhance the anti-tumor effect, reduce the drug dose, and improve medication safety. The use of nano-carrier for drug co-delivery can effectively avoid the differences in drug delivery behavior in vivo. Triptolide and celastrol are the main anti-tumor active components of Tripterygium wilfordii Hook f. Modern studies have shown that the combination of triptolide and celastrol can significantly enhance the antitumor effect, but they are limited by poor water solubility and low tumor tissue delivery rate. In this study, a biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol was prepared to characterize the morphology, particle size, potential, drug release, serum stability, and other properties. The immunogenicity, uptake behavior, and anti-cell proliferation ability of the biomimetic liposome was compared. All the animal experiments were carried out in accordance with protocol evaluated and approved by the Ethics Committee of Chengdu University of Traditional Chinese Medicine (Chengdu, China). The results showed that the biomimetic erythrocyte membrane liposome co-loaded with triptolide and celastrol (C+T/RBCm@Lip) in this study had an average particle size of 119.12 ± 2.78 nm and a spherical "core-shell" structure. The zeta potential value was -16.9 ± 1.2 mV, and the drug release behavior in vitro was slow. In addition, the process of coating the cell membrane maintained the characteristics of erythrocyte membrane protein, had good stability in serum, and could effectively avoid the recognition and clearance of macrophages, without causing immunogenicity in vivo. The uptake effect of co-loaded biomimetic liposomes on HepG2 hepatocellular carcinoma cells was enhanced compared with that of uncoated cell membrane liposomes, and the inhibitory effect on proliferation of HepG2 cells was enhanced. In conclusion, the biomimetic liposomes coated with erythrocyte membrane prepared in this study is beneficial to the anti-tumor delivery of triptolide and celastrol, and could enhance the inhibitory effect on the growth of HepG2 liver cancer cells, providing a new idea for the anti-tumor application of Tripterygium wilfordii Hook f.

2.
Article in Chinese | WPRIM | ID: wpr-906138

ABSTRACT

Objective:Considering the efficacy of Gegen Qinliantang (GQT) in releasing exterior and clearing interior to alleviate dampness-heat dysentery, we analyzed the mechanism of the chloroform extract of GQT in alleviating enterotoxicity caused by irinotecan to provide an experimental basis for the development of GQT. Method:Kunming mice (<italic>n</italic>=60) were randomly divided into a blank group, a model group, a loperamide group (positive drug of loperamide hydrochloride capsule, 0.4 mg·kg<sup>-1</sup>), and high- (2.3 g·kg<sup>-1</sup>) and low-dose (1.16 g·kg<sup>-1</sup>) GQT chloroform extract groups. The mouse model of delayed diarrhea was established by intraperitoneal injection of irinotecan hydrochloride (CPT-11, 55 mg·kg<sup>-1</sup>) for four consecutive days, meanwhile, the mice in the blank group only received the same volume of normal saline. Corresponding drugs were administered by gavage on the fifth day, respectively, while the ones in the blank group and model group were given distilled water for five consecutive days. The general condition of mice in each group was observed, and diarrhea indexes of mice were recorded. Pathological changes in colon tissues of mice were observed by hematoxylin-eosin (HE) staining. The tumor necrosis factor (TNF)-<italic>α</italic>, interleukin (IL)-1<italic>β</italic>, cyclooxygenase (COX)-2, intercellular adhesion molecule (ICAM)-1, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) levels in colon tissues were detected with the assay kits. Furthermore, the expression levels of Kelch sample epoxy chloropropane associated protein 1 (Keap1), nuclear factor E<sub>2</sub> related factor 2 (Nrf2), tight junction protein-1 (ZO-1), heme oxygenase-1 (HO-1) and tight junction protein (Occludin) were detected by Western blot. Result:Compared with the blank group, the model group showed declined body weight and reduced contents of GSH-Px and SOD (<italic>P</italic><0.01), whereas increased diarrhea indexes and TNF-<italic>α</italic>, IL-1<italic>β</italic>, COX-2, ICAM-1, MDA and NO levels (<italic>P</italic><0.01). Abundant inflammatory cells and colonic mucosa with defects, swelling, bleeding, and inflammatory exudation were revealed by HE staining in the mice of the model group. The expression levels of Keap1, Nrf2, ZO-1, HO-1 and Occludin in colon tissues significantly declined (<italic>P</italic><0.01). Compared with the model group, the loperamide group and the high- and low-dose GQT chloroform extract groups exhibited improved weight loss, reduced diarrhea indexes, diminished TNF-<italic>α</italic>,<italic> </italic>IL-1<italic>β</italic>, COX-2, ICAM-1, MDA and NO, and elevated GSH-Px and SOD. HE staining indicated that the cells were compactly arranged with clear nuclei in the high- and low-dose GQT chloroform extract groups, and the expression levels of Keap1, Nrf2, HO-1, Occludin, and ZO-1 were up-regulated. Conclusion:GQT chloroform extract may alleviate CPT-11-induced delayed diarrhea by regulating inflammation and oxidative stress for enhancing the intestinal barrier function. These findings are expected to provide a reference for exploring the toxicity-attenuating effect of Chinese medicinals on chemotherapy drugs and for developing famous classical formulas.

3.
Article in Chinese | WPRIM | ID: wpr-887974

ABSTRACT

Overtaking lung cancer,breast cancer is now the most commonly diagnosed cancer seriously threatening people's health and life. As the main effective component of Tripterygium wilfordii,triptolide( TP) has attracted increasing attention due to its multitarget and multi-pathway anti-tumor activity. Recent studies have revealed that breast cancer-sensitive TP enables the inactivation of breast cancer cells by inducing tumor cell apoptosis and autophagy,interfering in tumor cell metastasis,resisting drug resistance,arresting tumor cell cycle,and influencing tumor microenvironment. It has been recognized as a promising clinical antitumor agent by virtue of its widely accepted therapeutic efficacy. This paper reviewed the anti-breast cancer action and its molecular mechanisms of TP on the basis of the relevant literature in the past ten years,and proposed application strategies in view of the inadequacy of TP to provide a reference for further research on the application of TP in the treatment of breast cancer.


Subject(s)
Breast Neoplasms/genetics , Diterpenes/pharmacology , Epoxy Compounds , Female , Humans , Phenanthrenes , Tumor Microenvironment
4.
Article in Chinese | WPRIM | ID: wpr-873079

ABSTRACT

Objective::To develop high performance liquid chromatography-diode array detector (HPLC-DAD) wavelength switching for simultaneously determining the contents of inosine, loganic acid, chlorogenic acid, amygdalin, hydroxysafflor yellow A, gentiopicroside, ferulic acid and liquiritin in 15 batches of material benchmarks of Shentong Zhuyutang. Method::The quantitative analysis was carried out on a Thermo Hypersil GOLD C18 column (4.6 mm×250 mm, 5 μm) with mobile phase of acetonitrile-0.1%phosphoric acid aqueous solution for gradient elution, the flow rate was 1.0 mL·min-1, the detection wavelengths were set as 248 nm (0-11 min, inosine), 235 nm (11-14 min, loganic acid), 324 nm (14-16 min, chlorogenic acid), 220 nm (16-19 min, amygdalin and hydroxysafflor yellow A), 274 nm (19-26 min, gentiopicroside), 247 nm (26-54 min, ferulic acid and liquiritin), the column temperature was maintained at 25 ℃. According to the contents of eight active components in 15 batches of material benchmarks, orthogonal partial least squares discriminant analysis (OPLS-DA) in SIMCA 14.1 was used to evaluate the quality difference of each batch of samples. Result::Each component had good separations, the linear ranges of the above 8 components were 2.1-67.2, 1.812 5-58, 1.937 5-62, 5.212 5-166.8, 8.45-270.4, 7.075-226.4, 1.775-56.8, 3.875-124 mg·L-1, respectively (r≥0.999 6). The average recoveries of them were 99.23%, 100.09%, 99.33%, 98.85%, 99.15%, 98.75%, 99.42%, 98.96%, respectively (RSD<2%). The contents of the above eight components in 15 batches of material benchmarks were 0.183 5-0.250 3, 0.173 1-0.265 3, 0.069 5-0.169 8, 0.959 2-1.458 2, 1.905 4-2.553 3, 0.933 3-1.997 5, 0.084 6-0.143 4, 0.212 5-0.704 3 mg·g-1, respectively. Liquiritin, ferulic acid, gentiopicroside and hydroxysafflor yellow A were determined to have significant impact on the quality of different batches of material benchmarks of Shentong Zhuyutang through OPLS-DA. Conclusion::The established method for simultaneous determination of multi-components is reliable, simple and in line with the requirements of methodological verification. It is suitable for the quality control of research and development of compound preparations of Shentong Zhuyutang.

5.
Acta Pharmaceutica Sinica ; (12): 1774-1783, 2020.
Article in Chinese | WPRIM | ID: wpr-825153

ABSTRACT

In recent years, multi-modal combined anti-tumor has become an effective strategy for clinical tumor treatment. Photothermal therapy with its characteristics of minimally invasive, controllable, high efficiency, and strong specificity, can effectively make up for the toxic side effects and tumor resistance caused by traditional drug treatment. The research shows that the combination of photothermal therapy and chemotherapy has better synergistic antitumor effect. However, chemotherapeutic drugs and photothermal agents may have different pharmacokinetic behaviors in vivo, so it is difficult to ensure their effective transmission in tumor site, and the free form is easy to be metabolized and degraded in vivo. How to deliver the two therapeutic modes of drugs / photothermal reagents to tumor tissues in a specific, efficient and synchronous manner to achieve the best combined antitumor effect is an important problem to be solved in the combined antitumor application. The development of nano-drug delivery technology provides a new idea for the application of tumor treatment. In this paper, combined with the latest research progress in this field, the anti-tumor mechanism of photothermal therapy combined with chemotherapy, the advantages of nano drug delivery, the types and characteristics of commonly used nano materials and the principle of drug delivery are reviewed in order to provide a reference for the further development of multi-mode combined treatment of tumor.

6.
Article in Chinese | WPRIM | ID: wpr-802141

ABSTRACT

Objective: To prepare standard decoction of Chuanxiong Rhizoma and conduct its quality analysis.Method: According to the requirements of standard decoction,15 batches of standard decoction of Chuanxiong Rhizoma from three producing areas were prepared,the HPLC fingerprint was established and the quality analysis was carried out by cluster analysis;under common pattern of fingerprint,the simultaneous determination of four index components (ferulic acid,senkyunolide I,senkyunolide A and ligustilide) was established by HPLC.The transfer rates of main components,dry extract yield,pH value of samples were measured.Result: A total of 15 batches of standard decoctions of Chuanxiong Rhizoma were fingerprinted by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (edition of 2012A).Twenty-two common peaks were identified,and their similarities were all greater than 0.92,and peak 11,13,17,18,19 and 20 were identified qualitatively as ferulic acid,senkyunolide I,senkyunolide A,n-butylphthalide,coniferyl ferulate and ligustilide,respectively.The quality overview of standard decoction of Chuanxiong Rhizoma from three producing areas could be distinguished through cluster analysis,which showed that there were differences in quality of Chuanxiong Rhizoma from different producing areas,but the quality was relatively stable in different batches of samples from the same origin.Under common pattern,there were four major components in 15 batches of standard decoction of Chuanxiong Rhizoma,including ferulic acid,senkyunolide I,senkyunolide A and ligustilide.Contents of senkyunolide A (0.176 3-0.249 8 g·L-1) and senkyunolide I (0.065 2-0.103 4 g·L-1) was high in the standard decoction,content of ligustilide (0.040 0-0.089 8 g·L-1) followed,and content of ferulic acid (0.022 0-0.042 3 g·L-1) was the lowest,transfer rates of the above four components were 6.63%-11.82%,33.32%-55.98%,1.26%-3.73% and 16.39%-33.05%,respectively.Dry extract yield of the standard decoction was 12.69% to 19.78%,and the pH was 4.54 to 4.82.Conclusion: This study establishes the fingerprint and multi-component determination methods of standard decoctions of Chuanxiong Rhizoma from various producing areas,which is suitable for quality control of this standard decoction.

7.
Chinese Traditional Patent Medicine ; (12): 1083-1087, 2018.
Article in Chinese | WPRIM | ID: wpr-710273

ABSTRACT

AIM To establish the UPLC fingerprints of Gegen Qinlian Pills (Puerariae lobatae Radix,Scutellariae Radix,Coptidis Rhizoma and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle) and to determine the contents of puerarin,baicalein,palmatine,wogonin,daidzin,daidzein and jateorhizine.METHODS The analysis of 70% methanol extract of this drug was performed on a 30 ℃ thermostatic Waters ACQUITY UPLC(C) BEH C18column,with the mobile phase comprising of methanol-0.1% glacial acetic acid flowing at 0.3 mL/min in a gradient manner,and the detection wavelength was set at 260 nm.RESULTS There were twenty-five common peaks in the fingerprints of ten batches of samples with the similarities of more than 0.98.Seven constituents showed good linear relationships within their own ranges (r > 0.999 0),whose average recoveries were 98.99%-103.6% with the RSDs of 1.13%-2.03%.CONCLUSION This simple,reliable and reproducible method can be used for the quality control of Gegen Qinlian Pills.

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