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1.
Article in English | WPRIM | ID: wpr-929235

ABSTRACT

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.


Subject(s)
Computational Biology , Drugs, Chinese Herbal , Humans , Network Pharmacology , Phosphatidylinositol 3-Kinases , Urinary Bladder Neoplasms/genetics
2.
Article in Chinese | WPRIM | ID: wpr-909572

ABSTRACT

OBJECTIVE Compound Kushen injection (CKI) is a bis-herbal formulation extracted from Kushen (Radix Sophorae Flavescentis) and Baituling (Rhizoma Heterosmilacis Japonicae). Clinically, it is used as the adjuvant treat?ment of cancer. However, with the increased application, the cases of immediate hypersensitivity reactions (IHRs) also gradually rise. In this study, we investigated the underlying mechanism(s) and active constituent(s) for CKI-induced IHRs in experimental models. METHODS T helper 2 (Th2) immunity-amplified mice were prepared by aluminum adjuvant. Anaphylactic shock was detected by measuring rectal thermometry in propranolol pretreated mice. For evaluating micro?vascular permeability, Evans blue extravasation assay was used. Platelet-activating factor (PAF), serum total IgE (tIgE) and mouse mast cell protease 1 (MMCP1) were measured by ELISA. RESULTS The obtained results showed that CKI did not elevate serum tIgE and MMCP1 after consecutive immunization for five weeks, but could induce Evans blue extravasation (local) and cause obvious hypothermia (systemic) after a single injection. Further study showed that alka?loids in Kushen, especially matrine, were responsible for CKI-induced IHRs. Mechanism study showed that various PAF receptor antagonists could significantly counter CKI-induced IHRs locally or systemically. In cell system, CKI was able to promote PAF production in a non-cell-selective manner. In cell lysate, the effect of CKI on PAF production became stron?ger and could be abolished by blocking de novo pathway. CONCLUSION In conclusion, our study identifies, for the first time, that CKI is a PAF inducer. It causes non-immunologic IHRs, rather than IgE-dependent IHRs, by promoting PAF production through de novo pathway. Alkaloids in Kushen, especially matrine, are the prime culprits for IHRs. Our find?ings may provide a potential approach for preventing and treating CKI-induced IHRs.

3.
Chinese Pharmaceutical Journal ; (24): 1363-1366, 2020.
Article in Chinese | WPRIM | ID: wpr-857612

ABSTRACT

OBJECTIVE: To establish a high-performance liquid gel chromatography (HPLC-ELSD) method for the detection of macromolecular substances in Compound Kushen injection. METHODS: TSKgel G2000SWXL (7.8 mm×300 mm, 5 μm) chromatographic column was used. A 20 mmol•L-1 ammonium acetate aqueous solution was used as the mobile phase. The column temperature was maintained at 25℃, the flow rate was 0.8 mL•min-1, and the parameters of the evaporative light detector (drift tube temperature 55℃, atomization temperature 55℃, nitrogen flow rate, 1.8 L•min-1), a method for detecting macromolecular substances was established, and eleven batches of Compound Kushen injection were tested for macromolecular substances. RESULTS: No macromolecular substances was detected in the eleven batches of Compound Kushen injection, indicating that after the step-by-step removal of impurities, macromolecular substances have been removed from the finished Compound Kushen injection products. CONCLUSION: This method is simple and fast, which can be used for the detection of macromolecular substances in Compound Kushen injection, it provides a basis for improving the quality standards of Compound Kushen injection.

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