Polysaccharides derived from Balanophora polyandra significantly suppressed the proliferation of ovarian cancer cells through P53-mediated pathway.

Ovarian cancer (OC) is ranked the first among the cancers threatening women's health. It attracts tremendous attention of cancer researchers because of its extremely high mortality rate. Recent studies have indicated that traditional herbal medicines (THMs) can play a pivotal role in cancer prevention and treatment. THMs are gaining popularity as a source of anti-cancer agents. The plant of Balanophora polyandra, which has been used as a traditional herbal medicine, has been known for exhibiting potential haemostatic, analgesic, anti-inflammatory and anti-cancer properties. However, few studies on inhibitory effect of B. polyandra on OC have been performed. In the present study, we found that B. polyandra polysaccharides (BPP) induced cell cycle arrest at S phase, triggered apoptosis and inhibited migration and invasion of OC cells. Furthermore, we also found that there was a potential and close relationship between BPP and P53-mediated pathway. Overall, these findings suggest that BPP can be a potential therapeutic agent for the treatment of OC.

Uncovering Active Ingredients and Mechanisms of Spica Prunellae in the Treatment of Colon Adenocarcinoma: A Study Based on Network Pharmacology and Bioinformatics.

BACKGROUND: As a well-known herb used in the treatment of colon adenocarcinoma (COAD), Spica Prunellae (SP) shows favorable clinical effect and safety in China for many years, but its active ingredients and therapeutic mechanisms against COAD remain poorly understood. Therefore, this study aims to uncover active ingredients and mechanisms of SP in the treatment of COAD using a combined approach of network pharmacology and bioinformatics. METHODS: A comprehensive approach mainly comprised of target prediction, network construction, pathway and functional enrichment analysis, and hub genes verification was adopted in the current study. RESULTS: We collected 102 compounds-related genes and 3549 differently expressed genes (DEGs) following treatment with SP, and 64 disease-drug target genes between them were recognized. In addition, a total of 25 active ingredients in SP were identified. Pathway and functional enrichment analyses suggested that the mechanisms of SP against COAD might be to induce apoptosis of colon cancer cells by regulating PI3K-Akt and TNF signaling pathways. Recognition of hub genes and core functional modules was performed by constructing protein-protein interaction (PPI) network, from which TP53, MYC, MAPK8 and CASP3 were found as the hub target genes that might play an important part in therapy for COAD. Subsequently we further compared the differential expression level and assessed the prognostic value of these four hub genes. These result of verification suggested that SP exerted therapeutic effects against COAD via a PPI network involving TP53, MYC, MAPK8 and CASP3. CONCLUSION: In this study, active ingredients and mechanisms of SP in the treatment of COAD were systematically discussed, which provided the foundation for further experimental studies and might act to promote its appropriate clinical application.

Saponins from Panax japonicus ameliorate age-related renal fibrosis by inhibition of inflammation mediated by NF-κB and TGF-ß1/Smad signaling and suppression of oxidative stress via activation of Nrf2-ARE signaling.

BACKGROUND: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. METHODS: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), ß2-microglobulin (ß2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. RESULTS: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and ß2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and ß2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-ß1 (TGF-ß1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. CONCLUSION: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-ß1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

Long Non-coding RNAs in Metabolic and Inflammatory Pathways in Obesity.

BACKGROUND: In recent decades, the incidence of obesity has been rising globally. Obesity can often cause various inflammatory reactions, resulting in several diseases that threaten public health. The purpose of this review is to explore the role of long non-coding RNAs in metabolic obesity and find new targets for the prevention and treatment of metabolic diseases. METHODS: We described the relationship between obesity and inflammation, reviewed several signaling pathways in metabolic inflammation, and summarized some of the long non-coding RNAs and their targets associated with metabolic inflammation. The related studies were retrieved through a systematic search of the PubMed database. RESULT: Metabolic stress during obesity can cause inflammation through several metabolic pathways. Many long non-coding RNAs can affect the progression of metabolic inflammation by affecting different pathways. CONCLUSION: Downregulation or antagonization of long non-coding RNAs in metabolic pathways may provide new ideas and therapeutic targets for the prevention and treatment of metabolic inflammation.

Pathophysiological Functions of the lncRNA TUG1.

BACKGROUND: Long non-coding RNAs (lncRNAs) with little or no coding capacity are associated with a plethora of cellular functions, participating in various biological processes. Cumulative study of lncRNA provides explanations to the physiological and pathological processes and new perspectives to the diagnosis, prevention, and treatment of some clinical diseases. Long non-coding RNA taurine-upregulated gene 1(TUG1) is one of the first identified lncRNAs associated with human disease, which actively involved in various physiological processes, including regulating genes at epigenetics, transcription, post-transcription, translation, and posttranslation. The aim of this review was to explore the molecular mechanism of TUG1 in various types of human diseases. METHODS: In this review, we summarized and analyzed the latest findings related to the physiologic and pathophysiological processes of TUG1 in human diseases. The related studies were retrieved and selected the last six years of research articles in PubMed with lncRNA and TUG1 as keywords. RESULTS: TUG1 is a valuable lncRNA that its dysregulated expression and regulating the biological processes were found in a variety of human diseases. TUG1 is found to exhibit aberrant expression in a variety of malignancies. Dysregulation of TUG1 has been shown to contribute to proliferation, migration, cell cycle changes, inhibited apoptosis, and drug resistance of cancer cells, which revealed an oncogenic role for this lncRNA, but some reports have shown downregulation of TUG1 in lung cancer samples compared with noncancerous samples. In addition, the molecular and biological functions of TUG1 in physiology and disease (relevant to endocrinology, metabolism, immunology, neurobiology) have also been highlighted. Finally, we discuss the limitations and tremendous diagnostic/therapeutic potential of TUG1 in cancer and other diseases. CONCLUSION: Long non-coding RNA-TUG1 likely served as useful disease biomarkers or therapy targets and effectively applied in different kinds of diseases, such as human cancer and cardiovascular diseases.

Balanophora polyandra Griff. prevents dextran sulfate sodium-induced murine experimental colitis via the regulation of NF-κB and NLRP3 inflammasome.

Balanophora polyandra Griff. (B. polyandra) is a folk medicine used as an antipyretic, antidote, haemostatic, dressing and haematic tonic, for the treatment of gonorrhea, syphilis, wounds, and the bleeding of the alimentary tract by the local people in China. This study was designed to investigate the effects of B. polyandra on dextran sulfate sodium (DSS)-treated colitis mice in vivo and lipopolysaccharide (LPS)-induced RAW 264.7 macrophages in vitro. Mice were induced with B. polyandra total extract (BPE, 250 and 1000 mg kg-1) and B. polyandra polysaccharides (BPP, 100 and 400 mg kg-1) for 22 days and treated with 3.5% DSS in their drinking water for the last 7 days and the LPS-induced RAW264.7 macrophages were treated with BPE (100 µg ml-1) and BPP (100 µg ml-1). Mice treated with DSS developed severe mucosal colitis, with a marked distortion and crypt loss of colonic surface epithelium and a colonic shortening. B. polyandra significantly inhibited colonic shortening and reduced the severity of colitis in the colon and lowered the colonic inflammation score (p < 0.05) and decreased the expression of interleukin (IL)-1ß, tumor necrosis factor (TNF-α), inducible nitric oxide synthase (iNOS), and anti-serum amyloid A3 (SAA3) as well as the pro-inflammatory chemokine C-X-C motif chemokine 10 (CXCL10). B. polyandra also significantly suppressed the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome and the nuclear factor kB (NF-κB). These results suggest that dietary intake of B. polyandra ameliorates colitis. Such activities of B. polyandra in humans remain to be investigated.