Telocinobufagin, a PLK1 suppressor that inhibits tumor growth and metastasis by modulating CDC25c and CTCF in HNSCC cells.

BACKGROUND: The high metastasis and mortality rates of head and neck squamous cell carcinoma (HNSCC) urgently require new treatment targets and drugs. A steroidal component of ChanSu, telocinobufagin (TBG), was verified to have anti-cancer effects in various tumors, but its activity and mechanism in anti-HNSCC were still unknown. PURPOSE: This study tried to demonstrate the anti-tumor effect of TBG on HNSCC and verify its potential mechanism. METHODS: The effect of TBG on cell proliferation and metastasis were performed and the TBG changed genes were detected by RNA-seq analysis in HNSCC cells. The GSEA and PPI analysis were used to identify the pathways targeted for TBG-regulated genes. Meanwhile, the mechanism of TBG on anti-proliferative and anti-metastasis were investigated in vitro and in vivo. RESULTS: The in vitro and in vivo experiments confirmed that TBG has favorable anti-tumor effects by induced G2/M phase arrest and suppressed metastasis in HNSCC cells. Further RNA-seq analysis demonstrated the genes regulated by TBG were enriched at the G2/M checkpoint and PLK1 signaling pathway. Then, the bioinformatic analysis of clinical data found that high expressed PLK1 were closely associated with poor overall survival in HNSCC patients. Furthermore, PLK1 directly and indirectly modulated G2/M phase and metastasis (by regulated CTCF) in HNSCC cells, simultaneously. TBG significantly inhibited the protein levels of PLK1 in both phosphorylated and non-phosphorylated forms and then, in one way, inactivated PLK1 failed to activate G2/M phase-related proteins (including CDK1, CDC25c, and cyclin B1). In another way, be inhibited PLK1 unable promote the nuclear translocation of CTCF and thus suppressed HNSC cell metastasis. In contrast, the anti-proliferative and anti-metastasis effects of TBG on HNSCC cell were vanished when cells high-expressed PLK1. CONCLUSION: The present study verified that PLK1 mediated TBG induced anti-tumor effect by modulated G2/M phase and metastasis in HNSCC cells.

Loureirin A Promotes Cell Differentiation and Suppresses Migration and Invasion of Melanoma Cells via WNT and AKT/mTOR Signaling Pathways.

Resina Draconis is a traditional Chinese medicine, with the in-depth research, its medicinal value in anti-tumor has been revealed. Loureirin A is extracted from Resina Draconis, however, research on the anti-tumor efficacy of Loureirin A is rare. Herein, we investigated the function of Loureirin A in melanoma. Our research demonstrated that Loureirin A inhibited the proliferation of and caused G0/G1 cell cycle arrest in melanoma cells in a concentration-dependent manner. Further study showed that the melanin content and tyrosinase activity was enhanced after Loureirin A treatment, demonstrated that Loureirin A promoted melanoma cell differentiation, which was accompanied with the reduce of WNT signaling pathway. Meanwhile, we found that Loureirin A suppressed the migration and invasion of melanoma cells through the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. Taken together, this study demonstrated for the first time the anti-tumor effects of Loureirin A in melanoma cells, which provided a novel therapeutic strategy against melanoma.

Shen-Qi-Jiang-Tang granule ameliorates diabetic nephropathy via modulating tumor necrosis factor signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-Qi-Jiang-Tang granule (SQJTG), a classic traditional Chinese medicine (TCM) prescription, has been widely used in clinical for diabetes, especially type Ⅱ diabetes. Previous anti-diabetic studies stumbled across that SQJTG has a potential kidney protective effect on diabetic nephropathy (DN). However, the protective mechanism of SQJTG on DN still needs to be explored. AIM OF THE STUDY: The purpose of the present study was to explore the therapeutic effect of SQJTG on DN through both bioinformatics analysis and in vivo experiments. METHODS AND MATERIALS: The TCMIP database was used for screening potential compounds and targets of SQJTG, and the GeneCards, OMIM, DrugBank, and TTD databases were used for collecting DN-related genes. Then protein-protein interaction analysis for the common targets of SQJTG and DN was performed by the STRING database. Meanwhile, KEGG and GO were carried out using the Metascape and DAVID databases. In vivo experiments, to testify the potential kidney protective effects of SQJTG, STZ-induced DN mice with different dosages of SQJTG treatment were collected and the renal tissues were detected by H&E, PAS, Masson and TUNEL staining. Immunohistochemistry and immunoblotting were used to assess the proteins' expressions. Flow cytometry and ELISA assay were used to detect the levels of pro-inflammatory cytokines. RESULTS: Among the 338 compounds ascertained by SQJTG, there were 789 related targets as well. Moreover, 1,221 DN-related targets were predicted and 20 core targets were screened by the PPI analyses. According to GO and KEGG pathway analysis, SQJTG may affect DN via the TNF pathway. For the in vivo experiments, renal histomorphological examinations demonstrated that SQJTG treatment significantly ameliorated STZ-induced kidney damage and had a dosage dependence. Meanwhile, mice with DN were found to have dramatic increases in IL-1, TNF-α, IL-6, and IL-12, but markedly decreased after administration of SQJTG. In addition, the protein levels of TNF signaling molecules, like p-P65, p-JNK, and p-p38, showed significantly elevated in kidney tissues of DN mice and attenuated after SQJTG treatment. CONCLUSIONS: SQJTG exerts a kidney protective effect in DN mice via modulating TNF signaling pathways, and it has promising applications for the treatment of DN.

Active components of Solanum nigrum and their antitumor effects: a literature review.

Cancer poses a serious threat to human health and overall well-being. Conventional cancer treatments predominantly encompass surgical procedures and radiotherapy. Nevertheless, the substantial side effects and the emergence of drug resistance in patients significantly diminish their quality of life and overall prognosis. There is an acute need for innovative, efficient therapeutic agents to address these challenges. Plant-based herbal medicines and their derived compounds offer promising potential for cancer research and treatment due to their numerous advantages. Solanum nigrum (S. nigrum), a traditional Chinese medicine, finds extensive use in clinical settings. The steroidal compounds within S. nigrum, particularly steroidal alkaloids, exhibit robust antitumor properties either independently or when combined with other drugs. Many researchers have delved into unraveling the antitumor mechanisms of the active components present in S. nigrum, yielding notable progress. This literature review provides a comprehensive analysis of the research advancements concerning the active constituents of S. nigrum. Furthermore, it outlines the action mechanisms of select monomeric anticancer ingredients. Overall, the insights derived from this review offer a new perspective on the development of clinical anticancer drugs.

Sanggenon C Suppresses Tumorigenesis of Gastric Cancer by Blocking ERK-Drp1-Mediated Mitochondrial Fission.

Sanggenon C is a flavonoid extracted from the root bark of white mulberry, which is a traditional Chinese medicine with anti-inflammatory, antioxidative, and antitumor pharmacological effects. In this study, sanggenon C was found to inhibit human gastric cancer (GC) cell proliferation and colony formation, induce GC cell cycle arrest in the G0-G1 phase, and promote GC cell apoptosis. Moreover, sanggenon C was found to decrease the level of mitochondrial membrane potential in GC cells and inhibit mitochondrial fission. Mechanistically, RNA sequencing, bioinformatics analysis, and a series of functional analyses confirmed that sanggenon C inhibited mitochondrial fission to induce apoptosis by blocking the extracellular regulated protein kinases (ERK) signaling pathway, and constitutive activation of ERK significantly abrogated these effects. Finally, sanggenon C was found to suppress the growth of tumor xenografts in nude mice without obvious side effects to the vital organs of animals. This study reveals that sanggenon C could be a novel therapeutic strategy for GC treatment.

[Protective effect of safflower yellow injection against rat MIRI by TLR-NF-κB inflammatory pathway].

This study was to investigate the mechanism of safflower yellow injection for regulating inflammatory response against myocardial ischemia-reperfusion injury( MIRI) in rats. Male Wistar rats were randomly divided into sham operation group,model group,Hebeishuang group,safflower yellow injection high,medium and low dose groups. MIRI model was established by ligating left anterior descending coronary artery. Myocardial histopathological changes were observed by HE staining; myocardial infarct size was detected by TTC staining; content and changes of tumor necrosis factor-α( TNF-α) and interleukin-6( IL-6),serum creatine kinase( CK),aspartate aminotransferase( AST),and lactate dehydrogenase( LDH) were detected by biochemical method or enzyme-linked immunosorbent assay( ELISA). Western blot assay was used to detect the protein expression of Toll-like receptor 4( TLR4) and nuclear factor-κB( NF-κB p65) in myocardial tissues. The results showed that as compared with the sham operation group,the myocardial arrangement of the model group was disordered,with severe edemain the interstitial,significantly increased area of myocardial infarction,increased activities of AST,CK and LDH in serum,and significantly increased contents of TNF-α and IL-6; the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were also increased. As compared with the model group,the myocardial tissues were arranged neatlyin the Hebeishuang group and safflower yellow injection high,medium and low dose groups; the edema was significantly reduced; the myocardial infarct size was significantly reduced; the serum AST,CK,LDH activity and TNF-α,IL-6 levels were significantly decreased,and the expression levels of TLR4 and NF-κB( p65) protein in myocardial tissues were decreased. As compared with the Hebeishuang group,the myocardial infarct size was larger in the safflower yellow injection high,medium and low dose groups; the activities of AST,CK and LDH in serum and the contents of TNF-α and IL-6 in serum were higher,but there was no statistically significant difference in the expression levels of TLR4 and NF-κB( p65) protein in tissues. It is suggested that safflower yellow injection has a significant anti-MIRI effect,and its mechanism may be related to the regulation of TLR-NF-κB pathway to inhibit inflammatory response.

[Research on whole blending end-point evaluation method of Angong Niuhuang Wan based on QbD concept].

The blending end-point determination of Angong Niuhuang Wan (AGNH) is a key technology problem. The control strategy based on quality by design (QbD) concept proposes a whole blending end-point determination method, and provides a methodology for blending the Chinese materia medica containing mineral substances. Based on QbD concept, the laser induced breakdown spectroscopy (LIBS) was used to assess the cinnabar, realgar and pearl powder blending of AGNH in a pilot-scale experiment, especially the whole blending end-point in this study. The blending variability of three mineral medicines including cinnabar, realgar and pearl powder, was measured by moving window relative standard deviation (MWRSD) based on LIBS. The time profiles of realgar and pearl powder did not produce consistent results completely, but all of them reached even blending at the last blending stage, so that the whole proposal blending end point was determined. LIBS is a promising Process Analytical Technology (PAT) for process control. Unlike other elemental determination technologies such ICP-OES, LIBS does not need an elaborate digestion procedure, which is a promising and rapid technique to understand the blending process of Chinese materia medica (CMM) containing cinnabar, realgar and other mineral traditional Chinese medicine. This study proposed a novel method for the research of large varieties of traditional Chinese medicines..

[Advance in studies on pharmacological effects of licochalcone A].

Licochalcone A (LCA), as a major flavonoid in Glycyrrhiza inflate, has attracted wide attention in recent years. Studies showed that LCA has multiple pharmacological effects such as anti-tumour, anti-inflammation, anti-bacteria and anti-parasite. We made a summary for domestic and foreign study literatures for various pharmacological effects of LCA.

Echinacoside prevents the striatal extracellular levels of monoamine neurotransmitters from diminution in 6-hydroxydopamine lesion rats.

We investigated the effects of echinacoside, a phenylethanoid glycoside isolated and purified from the stems of Cistanche salsa, a Chinese herbal medicine, on the striatal extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in 6-hydroxydopamine (6-OHDA) lesion rats. Seven days after 6-OHDA was injected into the right striatum of rats, the striatal extracellular levels of DA, DOPAC and HVA fell significantly (P<0.01 vs. vehicle), as demonstrated by the method of cerebral microdialysis and high performance liquid chromatography with electrochemical detection. However, simultaneous treatment with echinacoside (7.0, 3.5mg/kg) attenuated the diminution of them (P<0.01 vs. model). The results implied that echinacoside could protect the striatal dopaminergic neurons from injury induced by 6-OHDA and may be useful in the prevention and treatment of Parkinson's disease (PD).

Mechanisms of apigenin-7-glucoside as a hepatoprotective agent.

OBJECTIVE: Ixeris chinesis (Thunb.) Ankai has been used as a Chinese folk medicine, but only scanty information is available on the physiological and biochemical functions of the compounds extracted from I. chinesis. In the present study the effects of apigenin-7-glucoside (APIG) isolated from I. chinesis against liver injury caused by carbon tetrachloride (CCl4) were investigated. METHODS: The contents of malondialdehyde (MDA), glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), and reduced glutathione (GSH) were evaluated by spectrophotography. The content of 8-Hydroxydeoxyguanosine (8-OHdG) was measured with high-performance liquid chromatography (HPLC) equipped with electrochemical and UV detection methods. The antioxidant activity of APIG was evaluated using chemiluminescence single photon counting technology. RESULTS: CCl4 significantly increased the enzyme activities of GPT and GOT in blood serum, as well as the level of MDA and 8-OHdG in liver tissue, and decreased the levels of GSH. Pretreatment with APIG was able not only to suppress the elevation of GPT, GOT, MDA and 8-OHdG, and inhibit the reduction of GSH in a dose-dependent manner in vivo, but also to reduce the damage of hepatocytes in vitro. On the other hand, we also found that APIG had strong antioxidant activity against reactive oxygen species (ROS) in vitro in a concentration-dependent manner. CONCLUSION: The hepatoprotective activity of APIG is possibly due to its antioxidant properties, acting as scavengers of ROS. These results obtained in vivo and in vitro suggest that APIG has protective effects against hepatic oxidative injury induced by chemicals. Further studies on the pharmaceutical functions and immunological responses of APIG may help its clinical application.