Ziyuglycoside II, a triterpene glycoside compound in Sanguisorbae officinalis l. extract, suppresses metastasis in osteosarcoma via CBX4-mediated Wnt/ß-catenin signal pathway.

BACKGROUND: Osteosarcoma (OS), the most prevalent primary bone malignancy, exhibits rapid growth and a high tendency for lung metastasis, posing significant treatment challenges. Ziyuglycoside II (ZGS II), a main active compound derived from Sanguisorba officinalis l., has shown potential in cancer treatment. However, the effects of ZGS II and its potential mechanism in OS remain elusive. PURPOSE: This study aims to explore the anti-metastatic potential of ZGS II in OS, offering a novel therapeutic strategy for improved patient outcomes. METHODS: Cell viability and proliferation was detected by cell counting kit-8 (CCK-8) and clone formation assay, respectively. Transwell and wound-healing assay were applied to evaluate the potential metastatic abilities of OS cells in vitro. More critically, the chromobox protein homolog 4 (CBX4) and Wnt/ß-catenin signaling pathway was investigated utilizing Western blotting, immunohistochemistry, shRNA knockdown and immunofluorescence. An orthotopic metastasis mouse model was utilized to evaluate the efficacy of ZGS II in suppressing OS metastasis in vivo, with molecular docking studies conducted to elucidate the interaction between ZGS II and the CBX4 protein. RESULTS: Our study demonstrated the potent inhibitory effects of ZGS II on OS cell proliferation and induced apoptosis in vitro, as evidenced by decreased cell viability, enhanced caspase-3 activation, and mitochondrial dysfunction. Furthermore, using an orthotopic metastasis mouse model, we illustrated that ZGS II effectively suppressed tumor growth and lung metastasis in vivo. Notably, our investigation revealed that the antitumor action of ZGS II is dependent on the reduction of CBX4 levels, leading to the attenuation of the Wnt/ß-catenin signaling pathway activation. Molecular docking analyses supported this pathway's suppression, showing that ZGS II has the capability to directly bind and disrupt CBX4 function. To further confirm this mechanism, we utilized shRNA to silence CBX4 in OS cells, which significantly enhanced the inhibitory impact of ZGS II on cell migration. CONCLUSION: Our study findings reveal that ZGS II efficiently suppresses both metastasis and tumor growth in OS by a novel mechanism that entails the inhibition of the CBX4-regulated Wnt/ß-catenin pathway. These outcomes highlight the promising potential of ZGS II as a therapeutic agent for managing metastatic OS, thus justifying the need for additional clinical investigations.

[Charcoal-frying process and quality markers of Sanguisorbae Radix based on hemostatic effect].

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Ziyuglycoside II-induced apoptosis in human gastric carcinoma BGC-823 cells by regulating Bax/Bcl-2 expression and activating caspase-3 pathway

Ziyuglycoside II is an active compound of Sanguisorba officinalis L. that has anti-inflammation, antioxidation, antibiosis, and homeostasis properties. We report here on the anticancer effect of ziyuglycoside II on human gastric carcinoma BGC-823 cells. We investigated the effects of ziyuglycoside II on cell growth, cell cycle, and cell apoptosis of this cell line. Our results revealed that ziyuglycoside II could inhibit the proliferation of BGC-823 cells by inducing apoptosis but not cell cycle arrest, which was associated with regulation of Bax/Bcl-2 expression, and activation of the caspase-3 pathway. Our study is the first to report the antitumor potential of ziyuglycoside II in BGC-823 gastric cancer cells. Ziyuglycoside II may become a potential therapeutic agent against gastric cancer in the future.