Cyanidin prevents cardiomyocyte apoptosis in mice after myocardial infarction.

Myocardial infarction is a worldwide disease with high morbidity and mortality and a major cause of chronic heart failure, seriously affecting patients' quality of life. Natural medicine has been used to cure or prevent cardiovascular disease for decades. As a natural flavonoid, anthocyanidin has been used to treat many diseases due to its antioxidative, anti-inflammatory, and other properties. A mouse model (C57BL/6) weighing 30-40 g was utilized to induce myocardial infarction by ligating the left anterior descending coronary artery. Cyanidin (30 mg/kg) was administered orally to mice for four weeks. A variety of assessments were used to evaluate cardiac function. The gene expression was measured using RNAseq and Western blot. Histological changes in myocardial tissue were assessed using staining techniques, including Masson, Hematoxylin Eosin (HE), and transmission electron microscopy. Tunnel staining was implemented as a method to detect cellular apoptosis. For the quantification of B-type natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in the serum, an enzyme-linked immunosorbent assay (ELISA) was employed. Furthermore, autodock simulation was executed in order to assess the interaction between cyanidin and a subset of genes. Cyanidin treatment inhibited myocardial cell apoptosis, improved cardiac function, and reduced serum concentrations of BNP and atrial natriuretic peptide ANP, as well as mitigated histological cardiac tissue damage. Cyanidin also inhibited the activity of matrix metalloproteinases (MMP2/9) and Fibronectin 1 (Fn1). Cyanidin improves heart function and reduces myocardial damage in mice after MI. Furthermore, cyanidin can prevent cardiomyocyte apoptosis. These effects are most likely caused by suppression of MMP9/2 and control of the Akt signaling pathway, suggesting an appropriate therapeutic target.

Static Magnetic Fields Regulate T-Type Calcium Ion Channels and Mediate Mesenchymal Stem Cells Proliferation.

The static magnetic fields (SMFs) impact on biological systems, induce a variety of biological responses, and have been applied to the clinical treatment of diseases. However, the underlying mechanisms remain largely unclear. In this report, by using human mesenchymal stem cells (MSCs) as a model, we investigated the biological effect of SMFs at a molecular and cellular level. We showed that SMF exposure promotes MSC proliferation and activates the expression of transcriptional factors such as FOS (Fos Proto-Oncogene, AP-1 Transcription Factor Subunit) and EGR1 (Early Growth Response 1). In addition, the expression of signal-transduction proteins p-ERK1/2 and p-JNK oscillate periodically with SMF exposure time. Furthermore, we found that the inhibition of the T-type calcium ion channels negates the biological effects of SMFs on MSCs. Together, we revealed that the SMFs regulate T-type calcium ion channels and mediate MSC proliferation via the MAPK signaling pathways.

Atractylenolide II induces cell cycle arrest and apoptosis in breast cancer cells through ER pathway.

In this research, atractylenolide II (ATR II) on apoptosis, cell cycle cells via ER pathway in breast cancer (MDA-MB-231 and MCF-7) cells are assessed. The effect of ATR II on cell proliferation was detected by MTT assay. Additional flow cytometry, luciferase, the western blot were performed to detect the signaling pathway cytotoxicity of ATR II. We have also carried out autodock measurements to validate our results. Our findings showed ATR II could inhibit breast cancer cell growth by apoptosis mainly through G2/M-phase cell cycle arrest. Besides, the cytotoxicity of ATTR II on breast cancer was also correlated by the regulation of endrogen receptors and promising an anti-inflammatory activity via inhibiting NF-KB signaling pathways. Taking together, ATR II could be a potential anti-cancer drug for breast cancer.

Mesenchymal stem cell-derived exosome microRNA as therapy for cardiac ischemic injury.

Cardiovascular diseases (CVD) are a significant cause of human health harm. In the past, stem cell therapy was reported to have functional defects, such as immune rejection, tumorigenicity, and infusion toxicity. Exosomes are extracellular vesicles with lipid bilayer membrane structure, containing proteins, lipids, mRNA, miRNA, DNA, and other molecules, which can mediate various biological functions such as immune response, inflammatory response, cell migration, and differentiation intercellular communication. Exosomal miRNAs have outstanding advantages in disease diagnosis and curative effect prediction. Likewise, paracrine factors could also mediate the main therapeutic effect of mesenchymal stem cells. Research has shown that mesenchymal stem cell-derived micro-exosomes, which may come from stem cells, accumulate in the ischemic tissue and regulate cell proliferation, apoptosis, inflammation, and angiogenesis sites of myocardial injury after being transplanted. This review reviewed the molecular mechanisms of exosomes and internal microRNAs derived from mesenchymal stem cells in cardiac ischemic injury repair.

Hispolon: A natural polyphenol and emerging cancer killer by multiple cellular signaling pathways.

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus. The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halting cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researches are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future.

Efficiency of Traditional Chinese medicine targeting the Nrf2/HO-1 signaling pathway.

Cardiovascular disease (CVD) is a significant cause of death worldwide. Because of its major individual differences in genetic background, pathogenesis, and disease progression pattern, the mortality risk rate remains high following conventional Western medicine diagnosis under current guidelines. Traditional Chinese medicine (TCM) has important multi-target, multi-pathway, and multi-layer benefits that can effectively address western medicine deficiencies. It was therefore commonly used in CVD diagnosis. Oxidative stress is also one of the main factors of CVD. Likewise, this main reaction regulator is the nuclear factor erythroid-2-related (Nrf2) factor. When activated, it can be transferred to the nucleus and initiated in the downstream pathway, thus playing an anti-oxidant stress role. As one of the most crucial endogenous protection systems in the body, Nrf2-related / heme oxygenase 1 (Nrf2/HO-1) signaling pathway is Nrf2's most classic approach to playing roles. Recently, various advances have been made to research and explain TCM by manipulating this pathway to treat CVD using modern molecular biology and other approaches. This analysis summarized the relationship between Nrf2/HO-1 signaling route, CVD and TCM. Further, Autodock calculation was also conducted to determine the binding amino acid on this TCM to Nrf2 and HO-1.

Eriocalyxin B induces apoptosis in human triple negative breast cancer cells via inhibiting STAT3 activation and mitochondrial dysfunction.

Eriocalyxin B (EriB), a potent ent-kaurene extracted from Isodon eriocalyx, has turned up as novel anti-cancer agent during recent years against a range of cancer types. TNBC (Triple negative breast cancer) is highly aggressive breast cancer, which is resistant towards current therapeutics due to absence of drug targets. Here, we have probed the molecular mechanism of EriB-induced apoptosis in TNBC (MDA-MB231) cells to check whether its anticancer activity is mediated by modulation of STAT3 and NF-Ï°B. EriB induced apoptosis in MDA-MB231 cells via inhibiting NF-Ï°Bp65, STAT3 phosphorylation, increasing Bax/Bcl-2 ratio, MMP dissipation, and activation of caspase-3. These results provide a rationale for further in vivo investigations on EriB, which might also prove to be a potential drug candidate for developing novel therapeutics against TNBC.

Hispolon induces apoptosis against prostate DU145 cancer cells via modulation of mitochondrial and STAT3 pathways.

Hispolon, a bioactive polyphenolic entity extracted from Phellinus linteus, possesses anticancer, antiinflammatory and anti-oxidant properties. Despite the reported therapeutic effects of this natural chemical entity, inhibitory potential of hispolon towards prostate carcinoma DU145 cells and mechanism of its action are yet to be explicated. Deregulated STAT3 pathway performs multifaceted functions in facilitating the development of cancer. Here, we have investigated the mechanism of hispolon by which it exerts its anticancer effects in DU145 cells and whether its anticancer activity is mediated by modulation of STAT3. Our outcomes show that hispolon significantly halted the multiplication of DU145 cells as well as arrested cell cycle at S phase. S phase arrest induced by hispolon was associated with downregulation of cyclin B1, cyclin D1 and CDK4 while up-regulation of p21. Moreover, hispolon treatment leads towards induction of apoptosis in a dose-dependent mode in DU145 cells. Hispolon induced modulation of Bcl-2 family proteins lead towards loss of MMP allowing the discharge of cytochrome c from mitochondrial porin channels which triggered the cascade of caspases ultimately causing cellular death. We further investigated the role of hispolon in mediating deregulated STAT3 pathways in DU145 cells. Hispolon has potential to downregulate the p-STAT3 expression with no effect on total STAT3. Contemporaneously, these results represent that hispolon's anticancer mechanism of action proceeds via downregulating the phosphorylation of STAT3 and induction of apoptosis via mitochondrial pathway.

CD147-induced cell proliferation is associated with Smad4 signal inhibition.

CD147 is a multifunctional trans-membrane glycoprotein, which is highly expressed in many cancers. However, the mechanism by which CD147 modulates cell proliferation is not fully understood. The aim of this study is to investigate the role of CD147 in cell proliferation associated with the TGF-ß/Smad4 signaling pathway. Here, we used cell viability and clone formation assays in LNCaP prostate cancer cells to demonstrate that CD147 promotes cell proliferation. The luciferase assay and western blotting show that silencing CD147 using shRNA enhances transcription and expression of p21WAF1. Using immunofluorescence and nuclear-cytoplasmic separation, we show that this is primarily attributed to transport of Smad4 from the cytoplasm to nucleus. Other assays (GST pull-down, co-immunoprecipitation and immunofluorescence) demonstrate that Smad4 is a new interaction partner of CD147, with the Smad4 MH2 domain and CD147 intracellular domain (CD147-ICD) being involved in the interaction. Furthermore, we report that a phosphoserine (pSer) in CD147 (pSer252) is responsible for this interaction and inhibition of the Smad4/p21WAF1 signal that promotes cell proliferation. Our results provide a novel molecular mechanism for CD147-induced cell proliferation associated with Smad4 signal inhibition.

Cordycepin induces apoptosis in SGC­7901 cells through mitochondrial extrinsic phosphorylation of PI3K/Akt by generating ROS.

Medicinal plants are affluent sources of several effectual natural drugs. Among them cordycepin which is extracted from Cordyceps militaris is a hopeful chemotherapy agent due to its extensive anti-inflammatory, anti-proliferative, antioxidant, and antitumor characteristics. This study investigated the efficacy of cordycepin in the context of human gastric cancer SGC­7901 and searched for the cell death procedure. Cordycepin incorporates mitochondrial-mediated apoptosis in SGC­7901 cells with the help of regulating mitochondrial extrinsic pathways by inhibition of A3AR and drive activation of DR3, which promote the activation of PI3K/Akt protein expression as well as collapse of mitochondrial membrane potential (MMP). In addition, phosphorylation of PI3K/Akt and DNA damage by cordycepin induced the production of reactive oxygen species (ROS), and mediates SGC­7901 cell cycle cessation at S phase. Collectively, this study suggests that cordycepin might be effective as a modern chemotherapy drug for gastric cancer.

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells.

Altholactone, a natural compound isolated from Goniothalamus spp., has demonstrated anti-inflammatory and anticancer activities, but its molecular mechanisms are still not fully defined. Nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3) play pivotal roles in the cell survival of many human tumors. The objective of this study was to elucidate the mechanism of action of altholactone against prostate cancer DU145 cells and to evaluate whether its effects are mediated by inhibition of NF-κB and STAT3 activity. Altholactone inhibited proliferation of DU145 cells and induced cell cycle arrest in S phase and triggered apoptosis. Reporter assays revealed that altholactone repressed p65- and TNF-α-enhanced NF-κB transcriptional activity and also inhibited both constitutive and IL-6-induced transcriptional activity of STAT3. Consistent with this, altholactone down-regulated phosphorylation of STAT3 and moreover, decreased constitutively active mutant of STAT3 (STAT3C)-induced transcriptional activity. Altholactone treatment also results in down-regulation of STAT3 target genes such as survivin, and Bcl-2 followed by up regulation of pro-apoptotic Bax protein. However, pre-treatment with the antioxidant N-acetylcysteine (NAC) significantly inhibited the activation of Bax and prevented down-regulation of STAT3 target genes. Collectively, our findings suggest that altholactone induces DU145 cells death through inhibition of NF-κB and STAT3 activity.