Extract from Dioscorea bulbifera L. rhizomes aggravate pirarubicin-induced cardiotoxicity by inhibiting the expression of P-glycoprotein and multidrug resistance-associated protein 2 in the mouse liver.

Chinese herbal medicine is widely used because it has a good safety profile and few side effects. However, the risk of adverse drug reactions caused by herb-drug interactions (HDIs) is often overlooked. Therefore, the task of identifying possible HDIs and elucidating their mechanisms is of great significance for the prevention and treatment of HDI-related adverse reactions. Since extract from Dioscorea bulbifera L. rhizomes (DB) can cause various degrees of liver damage, it is speculated that HDIs may occur between DB extract and chemicals metabolized or excreted by the liver. Our study revealed that the cardiotoxicity of pirarubicin (THP) was increased by co-administration of DB, and the expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (Mrp2) in the liver was inhibited by DB extract, which led to the accumulation of THP in heart tissue. In conclusion, there are risks of the co-administration of DB extract and THP. The mechanism of HDIs can be better revealed by targeting the efflux transporters.

SPOCK1 Involvement in Epithelial-to-Mesenchymal Transition: A New Target in Cancer Therapy?

BACKGROUND: Cancer metastasis is the main obstacle to increasing the lifespan of cancer patients. Epithelial-to-mesenchymal transition (EMT) plays a significant role in oncogenic processes, including tumor invasion, intravasation, and micrometastasis formation, and is especially critical for cancer invasion and metastasis. The extracellular matrix (ECM) plays a crucial role in the occurrence of EMT corresponding to the change in adhesion between cells and matrices. CONCLUSION: SPOCK1 is a critical regulator of the ECM and mediates EMT in cancer cells. This suggests an important role for SPOCK1 in tumorigenesis, migration and invasion. SPOCK1 is a critical regulator of some processes involved in cancer progression, including cancer cell proliferation, apoptosis and migration. Herein, the functions of SPOCK1 in cancer progression are expounded, revealing the association between SPOCK1 and EMT in cancer metastasis. SPOCK1 is a positive downstream regulator of transforming growth factor-ß, and SPOCK1-mediated EMT regulates invasion and metastasis through the Wnt/ß-catenin pathway and PI3K/Akt signaling pathway. It is of significance that SPOCK1 may be an attractive prognostic biomarker and therapeutic target in cancer treatment.

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer.

Natural compounds are highly effective anticancer chemotherapeutic agents, and the targets of plant-derived anticancer agents have been widely reported. In this review, we focus on the main signaling pathways of apoptosis, proliferation, invasion, and metastasis that are regulated by polyphenols, alkaloids, saponins, and polysaccharides. Alkaloids primarily affect apoptosis-related pathways, while polysaccharides primarily target pathways related to proliferation, invasion, and metastasis. Other compounds, such as flavonoids and saponins, affect all of these aspects. The association between compound structures and signaling pathways may play a critical role in drug discovery.

Preparative Separation and Purification of the Total Flavonoids in Scorzonera austriaca with Macroporous Resins.

The use of macroporous resins for the separation and purification of total flavonoids to obtain high-purity total flavonoids from Scorzonera austriaca was studied. The optimal conditions for separation and purification of total flavonoids in S. austriaca with macroporous resins were as follows: D4020 resin columns were loaded with crude flavonoid extract solution, and after reaching adsorptive saturation, the columns were eluted successively with 5 bed volumes (BV) of water, 5 BV of 5% (v/v) aqueous ethanol and 5 BV of 30% (v/v) aqueous ethanol at an elute flow rate of 2 BV·h(-1). Total flavonoids were obtained from the 30% aqueous ethanol eluate by vacuum distillation recovery. The content of flavonoid compounds in the total flavonoids was 93.5%, which represents an improvement by about 150%. In addition, five flavonoid compounds in the product were identified as 2″-O-ß-d-xylopyranosyl isoorientin, 6-C-α-l-arabipyranosyl orientin, orientin, isoorientin and vitexin by LC-ESI-MS analysis and internal standard methods. The results in this study could represent a method for the large-scale production of total flavonoids from S. austriaca.

Flavonoid Glycosides and Their Derivatives from the Herbs of Scorzonera austriaca Wild.

Five flavonoid glycosides and two derivatives were isolated from the herbs of Scorzonera austriaca Wild by silica gel column chromatography and preparative HPLC. Their structures were identified, using chemical and spectroscopic methods, as 5,7,4'-trihydroxyflavone 6-C-(2''-O-ß-d-glucopyranosyl ß-d-glucopyranoside) (1), 5,7,3',4'-tetrahydroxyflavone 6-C-(2''-O-ß-d-glucopyranosyl ß-d-glucopyranoside) (2), quercetin 3-O-rutinoside (3), 5,7,4'-trihydroxyflavone 6-C-ß-d-glucopyranoside (4), 3'-methoxy-5,7,4'-trihydroxyflavone 6-C-ß-d-glucopyranoside (5), 5,7,4'-trihydroxyflavone 8-C-(6''-O-trans-caffeoyl ß-d-glucopyranoside) (6), and 5,7,3',4'-tetrahydroxyflavone 8-C-(6''-O-trans-caffeoyl ß-d-glucopyranoside) (7). Compounds 6 and 7 are new flavonoid glycoside derivatives, and compounds 1-5 were isolated from the herbs of Scorzonera austriaca for the first time. Compounds 6 and 7 were also assayed for their hepatoprotective activities with rat hepatocytes in vitro.