Traditional chemotherapy is being considered due to hindrances caused by systemic toxicity. Currently, the administration of multiple chemotherapeutic drugs with different biochemical/molecular ...targets, known as combination chemotherapy, has attained numerous benefits like efficacy enhancement and amelioration of adverse effects that has been broadly applied to various cancer types. Additionally, seeking natural‐based alternatives with less toxicity has become more important. Experimental evidence suggests that herbal extracts such as Solanum nigrum and Claviceps purpurea and isolated herbal compounds (e.g., curcumin, resveratrol, and matairesinol) combined with antitumoral drugs have the potential to attenuate resistance against cancer therapy and to exert chemoprotective actions. Plant products are not free of risks: Herb adverse effects, including herb–drug interactions, should be carefully considered.
Linked Articles
This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
This study was designed to investigate the antimicrobial activity of two synthetic antimicrobial peptides from an aquatic organism, tilapia piscidin 3 (TP3) and tilapia piscidin 4 (TP4), in vitro and ...in a murine sepsis model, as compared with ampicillin, tigecycline, and imipenem. Mice were infected with (NDM-1)-producing K. pneumonia and multi-drug resistant Acinetobacter baumannii, and subsequently treated with TP3, TP4, or antibiotics for different periods of time (up to 168 h). Mouse survival and bacterial colony forming units (CFU) in various organs were measured after each treatment. Toxicity was determined based on observation of behavior and measurement of biochemical parameters. TP3 and TP4 exhibited strong activity against K. pneumonia and A. baumannii in vitro. Administration of TP3 (150 μg/mouse) or TP4 (50 μg/mouse) 30 min after infection with K. pneumonia or A. baumannii significantly increased survival in mice. TP4 was more effective than tigecycline at reducing CFU counts in several organs. TP3 and TP4 were shown to be non-toxic, and did not affect mouse behavior. TP3 and TP4 are able at potentiate anti-Acinetobacter baumannii or anti-Klebsiella pneumonia drug activity, reduce bacterial load, and prevent drug resistance, indicating their potential for use in combating multidrug-resistant bacteria.
Dipeptidyl peptidase IV (DPP-4), an incretin glucagon-like peptide-1 (GLP-1) degrading enzyme, contains two forms and it can exert various physiological functions particular in controlling blood ...glucose through the action of GLP-1. In diabetic use, the DPP-4 inhibitor can block the DDP-4 to attenuate GLP-1 degradation and prolong GLP-1 its action and sensitize insulin activity for the purpose of lowering blood glucose. Nonetheless the adverse effects of DPP-4 inhibitors severely hinder their clinical applications, and notably there is a clinical demand for novel DPP-4 inhibitors from various sources including chemical synthesis, herbs, and plants with fewer side effects. In this review, we highlight various strategies, namely computational biology (in silico), in vitro enzymatic and cell assays, and in vivo animal tests, for seeking natural DPP-4 inhibitors from botanic sources including herbs and plants. The pros and cons of all approaches for new inhibitor candidates or hits will be under discussion.
Antimicrobial peptides (AMPs) are garnering attention as possible alternatives to antibiotics. Here, we describe the antimicrobial properties of epinecidin-1 against a multidrug-resistant clinical ...isolate of P. aeruginosa (P. aeruginosa R) and a P. aeruginosa strain from ATCC (P. aeruginosa ATCC 19660) in vivo. The MICs of epinecidin-1 against P. aeruginosa R and P. aeruginosa ATCC 19660 were determined and compared with those of imipenem. Epinecidin-1 was found to be highly effective at combating peritonitis infection caused by P. aeruginosa R or P. aeruginosa ATCC 19660 in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that epinecidin-1 enhances the rate of survival of mice infected with the bacterial pathogen P. aeruginosa through both antimicrobial and immunomodulatory effects.
Objectives
The aim of this research is to investigate whether the oxygen atom O(6) in the sydnone ring of 3‐arylsydnone‐4‐carbaldehyde N(4)‐phenylthiosemicarbazones (HArSYTSCs, 3a–d) is a good ...electron donor atom upon metal complexation. Furthermore, ligands 3a–d and the corresponding palladium complexes (Pd(ArSYTSC)Cl, 4a–d) would be expected to find their potent biological activities.
Methods
The desired palladium complexes 4a–d were first synthesized from thiosemicarbazones 3a–d. Then, the antiproliferative activity of ligands 3a–d and complexes 4a‐d were tested against human hepatocellular carcinoma and human cervical epithelioid carcinoma (HeLa) cells by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl trazolium bromide (MTT) assay.
Key findings
According to X‐ray analyses, ligands 3a–d are bonded to the Pd (II) center in an O, N, S‐tridentate coordination mode through sydnone carbonyl oxygen O(6), azomethine nitrogen and the thiolate sulfur atom. The carbonyl oxygen of the sydnone ring is found to be a good electron donor site upon metal complexation. Moreover, MTT assay results reveal that the palladium complexes 4a–d have greater antiproliferative activity than 5‐fluorouracil. In particular, the complexes exhibit obvious better activity than the corresponding ligands 3a–d against HeLa cell.
Conclusions
The results indicate that the synthesized novel palladium complexes have greater antiproliferative activity than both 5‐fluorouracil and the corresponding ligands against HeLa cell. Accordingly, the study of sydnonyl complexes bearing anticancer activities may support the development of coordination chemistry.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
•ACME could restore fatty acid storage in non-induced HSCs.•ACME inhibited several biomarker of the activated HSC.•Antrodia cinnamomea could use as an functional food for the prevention of liver ...fibrosis.
The direct modulation of Antrodia cinnamomea (AC) on the prominent role of liver fibrosis-hepatic stellate cells (HSCs) in situ remains unclear. Firstly, the administration of A. cinnamomea mycelial extract (ACME) could improve liver morphology and histological changes including collagen formation and GPT activity in the liver of thioacetamide (TAA)-injured rats. The morphology and fatty acid restore of TAA-induced HSCs (THSCs) returned to the non-chemical induced HSCs (NHSCs) type as measured by immunofluorescence and Oil Red O staining. PPARγ was upregulated associated with the lowering of α-SMA protein in NHSC-ACME. ACME inhibited the MMP-2 activity in NHSCs by gelatin Zymography. After LC–MS/MS, the cytoskeleton (tubulin, lamin A) and heat shock protein 8 in NHSC-ACME, and guanylate kinase, brain-specific kinase, SG-II and p55 proteins were downregulated in THSC-ACME. Whereas MHC class II, SMC6 protein, and phospholipase D were upregulated in NHSC-ACME. Furthermore, PKG-1 was downregulated in NHSC-ACME and upregulated in THSC-ACME. SG-II and p55 proteins were downregulated in NHSC-ACME and THSC-ACME by Western blotting. Taken together, the beneficial effect of A. cinnamomea on the induction of HSC cellular proteins is potentially applied as an alternative and complementary medicine for the prevention and amelioration of a liver injury.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The antitumor activity of the shrimp anti-lipopolysaccharide factor (SALF), an antimicrobial peptide, was not previously examined. In this study, a synthetic SALF was tested for antitumor activity ...using HeLa cells as the study model. We show that the SALF inhibited the proliferation of HeLa cells and reduced colony formation in a soft agar assay. An enhanced effect was observed when the SALF and cisplatin were used in combination, which caused significant inhibition of HeLa cells. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that the SALF altered the membrane structure similar to what a lytic peptide does. A flow cytometric analysis, qRT-PCR, and Western blotting showed that the SALF induced apoptosis, activated caspases-6, -7, and -9, and downregulated Bcl-2 and nuclear factor (NF)-κB suggesting that the SALF induces apoptosis through the death receptor/NF-κB signaling pathway. An in vivo analysis revealed that the SALF displayed significant tumor suppressive activity in mice with tumor xenografts. Overall, these results indicated that the SALF possesses the potential to be a novel therapeutic agent for treating cervical cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The biological functions of insulin-like growth factor (IGF) I and II are modulated by a family of IGF-binding proteins (IGFBPs) in complex IGF-dependent and IGF-independent pathways. For further ...understanding of the actions of IGFs, some of these binding proteins have been cloned and characterized. We report the molecular cloning of IGFBP-3 cDNA for zebrafish. The tissue-specific and developmental stage-specific expression of IGFBP-3 and the hormonal regulation of its expression have also been determined by comparative reverse transcription polymerase chain reaction. Zebrafish IGFBP-3 cDNA contains an open reading frame of 879 bp, encoding a polypeptide of 293 amino acid residues. Results of this analysis revealed high levels of IGFBP-3 messenger RNA in ovary and fin tissue. Expression of IGFBP-3 mRNA was throughout the entire embryonic development, with the highest level of expression observed at 36 hours after the onset of development. Elevated levels of expression of IGFBP-3 were observed 24 hours after injection with IGF-I and 48 hours with IGF-II or insulin. These results suggest that the expression of IGFBP3 gene might be modulated by IGF-I, IGF-II, and insulin.
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CEKLJ, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Antimicrobial peptides (AMPs) are effective against a wide range of microbes, but still no research results have reported their use in duck disease therapy.
Riemerella anatipestifer (RA) is a ...Gram-negative bacterium which infects ducks and causes very significant economic losses. The minimum inhibitory concentrations (MICs) of epinecidin-1 for the tested RA strains ranged 6.25–50
μg/ml, those of the SALF55–76 cyclic peptide ranged 12.5–25
μg/ml, those of the SALF55–76 linear peptide ranged 6.25–25
μg/ml, those of hepcidin TH1–5 ranged 25–400
μg/ml, and those of hepcidin TH2–3 ranged 100–400
μg/ml. The antimicrobial activities of these peptides were confirmed by transmission electron microscopy which showed that RA disruption of the outer membrane brought about cell death. In addition, pretreatment, co-treatment, and post-treatment with peptides were all effective in promoting a significant decrease in duck mortality and decreasing the number of infectious bacteria. A quantitative RT-PCR was performed to survey levels of gene expressions of Mn superoxide dismutase in the brain, lipoprotein lipase in the liver, and H5 histone in the spleen induced in response to bacterial infection and an injection of the AMPs in experiments with the duck,
Cairina moschata. Our results indicated that the rescue of ducks by the peptides and the behavior of the peptides, which was like an enhancer in immunology, may involve regulation of the expressions of these genes. Collectively, these peptides reduced the mortality in ducks during bacterial challenge, suggesting that AMPs have the potential to serve as therapeutic drugs for use against bacterial infectious diseases in ducks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
It was previously reported that the oral administration of lactoferrin (LF) provides antimicrobial activity in animals against bacterial and viral infections and is involved in immunomodulatory ...properties. In this report, a hybrid strain of
Oreochromis nilotica
(male) ×
O. mossambicus
(female) was fed homemade diets with or without supplementation with 10, 50, 100, and 150 mg bovine LF g
−1
feed for 60 days. After dietary treatment, the experimental fish were infected with
Streptococcus agalactiae
. LF supplementation resulted in a significantly higher survival rate and suppression of bacterial growth at 24–96 h in the liver, spleen, kidneys, eyes, and gills. A reduction in peroxidase activity was followed by a similar reduction in the peroxidase content of leukocytes at 24 h as analyzed by spectrophotometry. Respiratory burst (RB) activity was detected regardless of the time at which LF was administered to fish in relation to the bacterial infection. A beneficial effect of LF on RBs was also detected before bacterial challenge (with 100 mg LF/g) and 24 h after bacterial challenge with 150 mg/g. The results obtained validate LF’s beneficial effects on RBs by phagocytes in tilapia, which was only shown at 48 h after supplementation with 100 mg bovine LF g
−1
feed after the bacterial infection. Moreover, after oral administration of LF, it was detected in the mucosa of the small intestines of tilapia. In conclusion, we demonstrate a reduction in fish mortality after the oral administration of LF, and we examined its immunomodulatory properties in tilapia.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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