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Yangzheng Mixture is a traditional Chinese medicine used in clinical practice as an adjuvant therapy for tumors. However, little is known about its active components in tumor treatment. The purpose of this study was to explore the potential anti-tumor components of Yangzheng Mixture to better promote its clinical application. Using LC-MS/MS, 43 components were detected in concentrated Yangzheng Mixture. Six components, comprising astragaloside, calycosin, formononetin, isoquercitrin, ononin, and calycosin-7-O-ß-D-glucoside, were identified in rat plasma. The cancer cell absorption assay showed that the intracellular concentration of four components, calycosin, calycosin-7-O-ß-D-glucoside, formononetin, and ononin, increased with extended incubation time and demonstrated potential anti-tumor effects. The MTT assay results confirmed that Yangzheng Mixture inhibited different tumor cells proliferation. Additionally, the colony formation assay, flow cytometry analysis and wound healing displayed that Yangzheng Mixture and a combination of four components could inhibit colony formation, arrest the cell cycle and impair cell migration of tumor cells, including HCT-116, MHCC-97L, MCF-7 and NCI-H1299. In summary, our study highlighted the plausible application of Yangzheng Mixture as a potential adjuvant treatment for tumors. Furthermore, it identified effective anti-tumor components and provided evidences for the further clinical application of Yangzheng Mixture.
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BACKGROUND: Hepatocellular carcinoma (HCC) is a major subtype of liver cancer, with a high mortality rate, and close relation to chronic hepatitis. The components of the NLRP3 inflammasome are poorly expressed or even lost in HCC. Downregulation of the NLRP3 inflammasome expression significantly affects the clinical stages and pathological grade of HCC. According to previous research, Shuanghua decoction (SHD), a traditional folk prescription, has an inhibitory effect on nasopharyngeal cancer. PURPOSE: This study aimed to reveal the therapeutic potential of the traditional folk recipe, SHD and its demolition recipe for HCC, and to explore the underlying mechanism. METHODS: The effect of SHD and its demolition recipe on HCC cell biological behaviors was assessed using the MTT assay, colony formation, LDH release assay, KFluor-Edu staining, annexin V-FITC/PI staining assay, Hoechst staining, wound-healing assay, transwell assay, reactive oxygen species (ROS) release assay, HPLC, nude mice model, HE staining, IHC, western blot, and immunofluorescence staining in vitro and in vivo. RESULTS: SHD was found to inhibit HCC, and Oldenlandia and OP (Oldenlandia: Prunella spike = 2.5:1) were identified as the main ingredients that inhibited the proliferation and migration of HCC cells via the activation of the ROS-mediated NLRP3 inflammasome and inhibition of the NF-κB signaling pathway in vitro and in vivo. CONCLUSION: Overall, Chinese medicine theory and pharmacology research revealed that SHD, Oldenlandia and OP may be promising traditional Chinese medicine for the treatment of HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Nasofaríngeas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Medicamentos de Ervas Chinesas , Inflamassomos , Neoplasias Hepáticas/tratamento farmacológico , Camundongos , Camundongos Nus , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de SinaisRESUMO
BACKGROUND: Quercetin (Q), tea polyphenols (TP), and rutin (R) are widely used plant-derived active ingredients. They possess antioxidant, anti-inflammatory, and anti-tumor properties, and can reduce the muscle damage caused by mycotoxins. However, few studies have examined the protective mechanisms of quercetin, tea polyphenols, and rutin on muscle quality. To elucidate their protective mechanisms, shrimp were exposed to both T-2 toxin and these three antioxidants for 20 days in a dose-escalating trial. The changes in the protein composition of shrimp muscle were measured. The target proteins associated with T-2 and antioxidants were screened and identified by non-labeled quantitative proteomics. RESULTS: The T-2 toxin induced abnormal expression of 21 target proteins, leading to the deterioration of muscle proteins in shrimp. The three antioxidants ameliorated the T-2 toxin-induced damage to muscle proteins by increasing the sarcoplasmic and myofibrillar protein content and decreasing the alkali-soluble protein content. Quercetin had the strongest protective effect. The protective processes of these antioxidants involved the upregulation of target proteins involved in carbohydrate metabolism (enolase, malate dehydrogenase), protein translation (elongation factor 1-alpha and eukaryotic translation initiation factor 2 subunit alpha), and cytoskeleton component (actin 2, fast-type skeletal muscle actin 1). Quercetin regulated the largest number of target proteins, making it the best protective agent against T-2 toxin. CONCLUSION: The T-2 toxin (4.80-24.30 mg/kg feed) induced changes in target proteins and muscle composition of shrimp, leading to a deterioration in muscle proteins. Quercetin (2.00-32.00 g/kg feed) had significant protective effects against this deterioration in muscle protein in shrimp. © 2022 Society of Chemical Industry.