The Genus Adonis as an Important Cardiac Folk Medicine: A Review of the Ethnobotany, Phytochemistry and Pharmacology

The genus Adonis L. (Ranunculaceae), native to Europe and Asia, comprises 32 annual or perennial herbaceous species. Due to their cardiac-enhancing effects, Adonis spp. have long been used in European and Chinese folk medicine. These plants have been widely investigated since the late 19th century, when the cardiovascular activity of Adonis vernalis L. was noted in Europe. The present paper provides a review of the phytochemistry, biological activities and toxicology in order to highlight the future prospects of the genus. More than 120 chemical compounds have been isolated, with the most important components being cardiac glycosides as well as flavones, carotenoids, coumarins and other structural types. Plants of the genus, especially A. vernalis L. and A. amurensis Regel & Radde, their extracts and their active constituents possess broad pharmacological properties, including cardiovascular, antiangiogenic, antibacterial, antioxidant, anti-inflammatory and acaricidal activities, and exhibit both diuretic effects and effects on the central nervous system. However, most plants within the 32 species have not been comprehensively studied, and further clinical evaluation of their cardiovascular activity and toxicity should be conducted after addressing the problem of the rapidly decreasing resources. This review provides new insight into the genus and lays a solid foundation for further development of Adonis

The Anti-diarrheal Activity of the Non-toxic Dihuang Powder in Mice

Dihuang powder (DHP) has been used in the traditional Chinese medicine for the treatment of diarrhea in some regions of China. But up to now, the anti-diarrheal activity of DHP haven’t been performed with modern pharmacological technology. This study aims to investigate the quality control, the potential toxicity and anti-diarrheal activity of Dihuang powder in mice. High performance liquid chromatography (HPLC) and thin layer chromatography (TLC) were used to detect five active compounds in DHP for quality control, and the acute toxicity and sub-acute toxicity for 28-day oral administration of DHP were then evaluated. The anti-diarrheal activity was investigated using mouse model. Results showed that the levels of quercetin and berberine in DHP were 0.054 and 0.632 mg/g, respectively, and atractylodin, matrine, and patehouli aleohal were also detected in DHP. At the given doses, DHP was safe in terms of acute and sub-acute toxicity. Meanwhile, DHP exhibited strong anti-diarrheal effects as well as decreased gastrointestinal motility and the secretions induced by Sennae and castor oil in a dose-dependent manner. It could decrease the content of IL-1β, IL-6, and TNF-α in the small intestine, and improve the histopathological changes of small intestine and large intestine induced by Sennae. The antinociceptive and anti-inflammatory activities in vivo also were presented. Based on all of the results, we thought that DHP has anti-diarrheal activity, and could be used to treat diarrhea as well as alleviate the pain and inflammation induced by diarrhea. This study provides a theoretical basis for the clinical use of DHP and may assist in the development of new drugs for the treatment of diarrhea. The mechanism of the anti-diarrheal activity should be investigated in the future

Coexistence of superconductivity and topological phase in kagome metals ANb3Bi5 (A = K, Rb, Cs)

Abstract The AV3Sb5 prototype kagome materials have been demonstrated as a versatile platform for exploring exotic properties in condensed matter physics, including charge density waves, superconductivity, non-trivial electron topology, as well as topological superconductivity. Here we identify that ANb3Bi5 (A = K, Rb, Cs) exhibit non-trivial coexisting superconductivity and topological properties via first-principles calculations. The negative formation energy and the absence of imaginary phonon dispersion demonstrate both thermodynamics and dynamics stabilities of ANb3Bi5 (A = K, Rb, Cs) under ambient conditions. By analytically solving the Allen-Dynes-modified McMillan formula, the superconducting transition temperatures are predicted to be 2.11, 2.15 and 2.21 K for KNb3Bi5, RbNb3Bi5, and CsNb3Bi5, respectively. More importantly, the kagome materials proposed here can be classified into $${{\mathbb{Z}}}_{2}$$ Z 2 topological metals due to the non-trivial topological index and the obvious surface states around the Fermi level. Such coexistence of superconductivity and non-trivial band characters in ANb3Bi5 (A = K, Rb, Cs) offer us more insights to study the relationship between superconductivity and topological properties, and to design innate topological superconductors

Anti-cancer Effects of Glypican-3 on Huh-7 Hepatocellular Carcinoma Cells

Aim: Previous studies have suggested Glypican-3 (GPC3) could be a valuable diagnostic marker for hepatocellular carcinoma. This study examined the effects of overexpression of GPC3 on Huh-7 hepatoma cells. Methods: We constructed a recombinant plasmid vector pcDNA3.1 (+)-GPC3 for GPC3 overexpression studies in Huh-7 cells. RT-PCR and Western blotting were used to confirm GPC3 gene expression. Cell proliferation was evaluated by 5-ethynyl-2-deoxyuridine (EdU) incorporation assay. Cell cycle progression and apoptosis were determined by flow cytometry using propidium iodide (PI) and Annexin V-FITC/PI staining, respectively. Cell migration and invasion were examined by Boyden Transewll and Matrigel assays. Results: GPC3 overexpression effectively inhibited proliferation, induced cell cycle arrest at S phase and increased apoptosis in Huh-7 cells. Furthermore, GPC3 overexpression significantly inhibited the migration and invasion ability of Huh-7 cells. Conclusion: Our results demonstrate that GPC3 could be a new therapeutic target for hepatocellular carcinoma

AURKB/CDC37 complex promotes clear cell renal cell carcinoma progression via phosphorylating MYC and constituting an AURKB/E2F1-positive feedforward loop

Abstract As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC

Venlafaxine antagonizes the noradrenaline-promoted colon cancer progression by inhibiting the norepinephrine transporter

Abstract Epidemiological studies have demonstrated that the use of antidepressants is associated with a decreased risk of colorectal cancer (CRC); however, the mechanisms behind this association are yet unknown. Adrenergic system contributes to the stress-related tumor progression, with norepinephrine (NE) mainly secreted from adrenergic nerve fibers. Norepinephrine serotonin reuptake inhibitors are successfully used antidepressants. This study demonstrates that a widely used antidepressant venlafaxine (VEN) antagonizes NE-promoted colon cancer in vivo and in vitro. Bioinformatic analysis suggested that NE transporter (NET, SLC6A2), a target of VEN, was closely associated with the prognosis of clinical patients with CRC. In addition, the knockdown of NET antagonized the effect of NE. The NET-protein phosphatase 2 scaffold subunit alpha/phosphorylated Akt/vascular endothelial growth factor pathway partially mediates the antagonizing effect of VEN on NE’s actions in colon cancer cells. These were also confirmed by in vivo experiments. Our findings revealed for the first time that, in addition to its primary function as a transporter, NET also promotes NE-enhanced colon cancer cell proliferation, tumor angiogenesis, and tumor growth. This provides direct experimental and mechanistic evidence for the use of antidepressant VEN in the treatment of CRC and a therapeutic potential for repurposing existing drugs as an anti-cancer approach to improve the prognosis of patients with CRC

Nei Endonuclease VIII-Like1 (NEIL1) Inhibits Apoptosis of Human Colorectal Cancer Cells

The study is aimed at investigating the role of Nei endonuclease VIII-like1 (NEIL1) in the pathogenesis of colorectal cancer (CRC). The human CRC (HCT116 and SW480) cells were subjected to the siRNA silencing and recombinant plasmid overexpression of NEIL1. Transfection of siNEIL1 significantly inhibited the cell growth. It also increased the Bax expression levels, while it decreased the Bcl-2 expression levels in human CRC cells, leading the Bax/Bcl-2 balance toward apoptosis. Moreover, the apoptosis was promoted through the caspase-9 signaling pathway. One the other hand, high expression of NEIL1 promoted the cell viability and reduced the apoptosis, inducing the balance of Bax/Bcl-2 in the human colon cancer cells to be antiapoptotic. In addition, the caspase-9 signaling pathway inhibited apoptosis, contrary to the results obtained by downregulating NEIL1 expression. Furthermore, NEIL1 was negatively regulated by miR-7-5p, indicating that miR-7-5p inhibited the NEIL1 expression after transcription. Overexpression of miR-7-5p reversed the effects of NEIL1 on these CRC cells. In conclusion, NEIL1 promotes the proliferation of CRC cells, which is regulated negatively by miR-7-5p. These findings suggest that NEIL1 is a potential therapeutic target for CRC