Resveratrol (3, 5, 4'-trihydroxystilbene) is a phytoalexin contained in a variety of plants, such as grapes, berries and especially in the dried roots of Polygonum cuspidatum Sieb. et Zucc. It has been shown to exhibit anti-oxidative and anti-inflammation activity, and to reverse the effects of aging. Its ability to suppress cell proliferation, induce apoptosis and suppress the metastasis and invasion in a number of cell lines has prompted a large interest from people for its use as an anti-tumor component. In this review, evidence of resveratrol's anti-tumor effects and molecular mechanisms are recapitulated. First, we present the anti-apoptosis, anti-invasion/metastasis and anti-inflammation effect of resveratrol; second, the main signaling pathways involved in these activities are described and summarized with the studies of different tumors involved. Resveratrol not only induces apoptosis of tumor cells through intrinsic/extrinsic pathways and cell cycle arrest, but also inhibits the invasion and metastasis abilities of tumors via modulating collagen degradation-related molecular targets. Altogether, the present findings suggest the anti-tumor potential of resveratrol against various types of cancers.
Oligonol is a phenolic product derived from lychee fruit extract containing catechin-type monomers and oligomers of proanthocyanidins, produced by a manufacturing process which converts polyphenol polymers into oligomers. These proanthocyanidins have been reported to exhibit beneficial bioactivities in many studies, and so oligonol, a rich source of polyphenol, is expected to show favorable effects on various chronic diseases. This article summarizes recent work whether oligonol has an ameliorative effect on diabetic indices and renal disorders associated with gluco-lipotoxicity-mediated oxidative stress, inflammation, and apoptosis in db/db mice with diabetes. Oligonol was able to improve diabetic indices, prevent the development of diabetic renal disease, and preserve renal cells and the renal morphological structure via the attenuation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-induced oxidative stress, inhibition of advanced glycation endproduct (AGE) generation, and prevention of apoptosis-induced cell death in db/db mice, being independent of changes in the body weight or serum glucose levels. The present study provides important evidence that oligonol exhibits a pleiotropic effect, representing renoprotective effects against the development of diabetic complications in type 2 diabetic db/db mice.
Ginseng, Panax ginseng (C. A. Mey.), is a well-known Chinese traditional medicine in the Far East and has gained popularity in the West during the last decade. There is extensive literature on the chemical constituents and bioactivities of ginseng. In this paper we compiled the chemical constituents isolated and detected from ginseng including polysaccharides, ginsenosides, peptides, polyacetylenic alcohols, fatty acids, etc. Meanwhile we summarized the biological activities of ginseng, which have been reported over the past few decades, including: anti-aging activity, anti-diabetic activity, immunoregulatory activity, anti-cancer activity, neuroregulation activity, wound and ulcer healing activity, etc. Nevertheless, further studies to exploit other kinds of constituents and new biological activities of ginseng are still necessary to facilitate research and development in the future.
The search for new antibiotics or antifungal agents is crucial for the chemotherapies of infectious diseases. The limited resource of soil bacteria makes it difficult to discover such new drug candidate. We, therefore, focused on another bacterial resource than soil bacteria, the microbial flora of insect species. In the present study, we isolated 40 strains of bacteria and fungi from the mycangia of three species of stag beetle, Dorcus hopei binodulosus, Dorcus rectus, and Dorcus titanus pilifer. We identified those species with their ribosomal DNA sequences, and revealed that Klebsiella spp. are the most frequent symbiont in the stag beetle mycangia. We examined whether these microorganisms produce antibiotics against a Gram-negative bacterium, Escherichia coli, a Gram-positive bacterium, Staphylococcus aureus, or a fungus, Cryptococcus neoformans. Culture supernatants from 33, 29, or 18 strains showed antimicrobial activity against E. coli, S. aureus, or C. neoformans, respectively. These findings suggest that bacteria present in the mycangia of stag beetles are useful resources for screening novel antibiotics.
Ectopic ossification occurs in a wide range of common and genetic diseases, but its molecular mechanisms and effective therapeutic targets remain to be clarified. The aim of the study is to investigate whether endoplasmic reticulum (ER) stress is involved in ectopic ossification and ER stress inhibitor tauroursodeoxycholic acid (TUDCA) has potential to treat the pathological conditions. In this study, inorganic phosphate (Pi)-induced NIH3T3 fibroblasts induced osteogenesis and mineralization was used as an in vitro model for ectopic ossification. Various concentrations of TUDCA (0.1, 1, 5, 10 μM) were added during osteogenic induction. Osteoblast differentiation and minerlization were determined by RT-qPCR, alkaline phosphatase (ALP) activity assay, Alizarin Red-S (AR-S) staining, and calcium deposition. ER stress signalling components were detected by Western-blot analysis. We found ER stress was activated by inorganic phosphate in NIH3T3 cells. During osteogenic induction, TUDCA inhibited NIH3T3 cells ALP activity and mineral nodule formation. In addition, TUDCA caused decreased expression of osteoblastic markers Runx2, Col1a1, ALP, OCN. Mechanistically, TUDCA inhibited the ER stress response PERK-eIF2α-ATF4 pathway during osteogenesis. In conclusion, TUDCA could inhibit fibroblasts mineralization via supressing the ER stress response PERK-eIF2α-ATF4 pathway, and has potential pharmacologic and therapeutic applications for treating ectopic ossification associated diseases.
The clinical use of 5-fluorouracil (5-FU) is increasingly limited by low response rates, adverse reactions, and toxicity. A drug combination offers a new strategy for appropriate use of 5-FU. Bestatin, an aminopeptidase N (APN) inhibitor, has been used as an adjuvant chemotherapy drug because of its actions to suppress tumorigenesis and invasion. The current study evaluated the anticancer efficacy of 5-FU plus Bestatin at the cellular and animal level. The combination killed more colonic cancer, hepatic carcinoma, and ovarian cancer cells and fewer nonmalignant human embryonic kidney (HEK293) and Chinese hamster ovary (CHO) cells than 5-FU or Bestatin alone. Moreover, 41.58% of ES-2 and 20.86% of PLC/PRF/5 cell apoptosis was caused by the combination of the two, while 5-FU caused apoptosis of 20.86% of ES-2 cells and 8.85% of PLC/PRF/5 cells. The cell cycle was arrested in the S and G0/G1 phases when a combination of the two was used. In an experiment involving mice bearing tumors, a combination of the two had a rate of tumor inhibition of 61.98%, while 5-FU alone had a rate of tumor inhibition of just 49.17%. In addition, the combination of the two was safer than either drug alone and did not cause weight loss or death. In conclusion, combining 5-FU and Bestatin could enhance the anticancer activity of 5-FU and decrease its cytotoxicity. These results suggest that 5-FU plus Bestatin has greater efficacy as a tumor therapy.
Anacardic acid is a major constituent of nutshell of cashew. In this study, we have isolated it from the leaves of Anacardium Occidentale L. using polarity-based fractionation and confirmed the structure using GC-MS, NMR and FT-IR. The main focus of this study is to harness the molecular mechanism of anti-metastatic action of anacardic acid (A1). We have used MCF-7, a weak metastatic and U-87, a highly metastatic, breast and glioma cell lines respectively, for our study. We have shown that VEGF increases migration and invasion activities of MCF-7 cells, upon overexpression of Twist and Snail genes. It is observed from the current study that exposure of MCF-7 cells to A1 resulted in upregulation of epithelial marker E-cadherin with a concomitant decrease in the expression of mesenchymal markers Twist and Snail gene expression besides exhibiting a strong anti-migratory and anti-invasive activity. In metastatic U-87 glioma cells, treatment with A1 decreased the phosphorylation of MAP kinases, inhibited the translocation of Sp1 and down regulated VEGF and Flt-1 gene expression. Overall, the current findings demonstrate for the first time that anacardic acid functions as a potent EMT inhibitor by targeting VEGF signaling pathway, providing a novel template for drug discovery.
Cell cycle related molecules in mammalian cochleae could provide a new avenue to restore hearing loss caused by a variety of genetic and environmental insults. CyclinA2 is one of the most important regulators of cell cycle, but its role in the mammalian cochlea is still unknown. So, it is necessary to construct an adenovirus vector carrying cyclinA2 gene for clarifying its function in the cochlea. In this study, the cyclinA2 genes were cloned into the shuttle plasmid pDC316-mCMV-EGFP to construct pDC316-CyclinA2-mCMV-EGFP, which was co-transfected with the rescue plasmid pBHGlox∆E1,3Cre into 293 cells to obtain the recombinant adenovirus Ad.CyclinA2-EGFP. Then, the plasmid pDC316-CyclinA2-mCMV-EGFP and recombinant adenovirus Ad.CyclinA2-EGFP were identified by restriction enzymes and reverse transcription-polymerase chain reaction (RT-PCR). The recombinant adenovirus vector was purified by CsCl banding, and was titrated. Finally, the recombinant adenovirus vector carrying cyclinA2 gene was constructed and confirmed by restriction enzyme analysis and RT-PCR. The titer of the recombinant adenovirus vectors reached 2.5 × 10‒11 v.p/mL. Thus, we had successfully established the Ad.CyclinA2-EGFP vector, and it could express efficiently in various cells of cochlea. This study established the foundation for the further research of cyclinA2 gene's function in the cochlea.
The circadian time structure of serum 25 (OH) vitamin D (25-OHD), calcium (Ca) and phosphorus (P) may prove to be helpful in prevention, efficacy and management of diabetes mellitus. Ten newly diagnosed patients with type-2 diabetes mellitus (6 men and 4 women), 30-65 years of age, and 10 age-matched clinically healthy volunteers (7 men and 3 women) were synchronized for one week with diurnal activity from about 06:00 to about 22:00 and nocturnal rest. Breakfast was served around 08:00, lunch around 13:30 and dinner around 20:00. Drugs/nutraceuticals known to affect the vitamin D-calcium metabolism and status were not taken. Blood samples were collected at 6-h intervals for 24 h under standardized, 24-h synchronized conditions. Serum 25-OHD, Ca, P, Ca-P product and Ca-P ratio were determined. A marked circadian variation was demonstrated for 25-OHD in healthy volunteers (p = 0.030) and of borderline statistical significance in the diabetic patients (p = 0.083) by population-mean cosinor analysis. Similarly, healthy volunteers showed borderline significance for serum Ca, P and Ca-P ratio. The circadian acrophase of Ca occurred later in the patients as compared to healthy controls. Mapping the circadian rhythm (an important component of the broader time structure or chronome, which includes a.o., trends with age and extra-circadian components) of vitamin D and calcium is needed for exploring their role as markers in the treatment and management of diabetic patients.
The prognosis of cutaneous angiosarcoma is very poor compared with that of other skin malignancies. The main reason for this is the limited regimens of chemotherapy available for angiosarcoma, because it is resistant to most common chemotherapeutic agents. Therefore, there is an urgent need to identify new treatment options. Recently, S-1 and docetaxel therapy was reported to be effective for advanced gastric cancer and metastatic extramammary Paget's disease. Therefore, we treated paclitaxel-resistant angiosarcoma patient with S-1/docetaxel chemotherapy. The progression-free survival was 5.0 months although grade 3 adverse events such as diarrhea and neutropenia developed. Our data need to be confirmed in a large number of patients, but S-1/docetaxel chemotherapy as an additional regimen seems to be an effective treatment option for paclitaxel-resistant angiosarcoma.