scholarly journals Synergistic Anti-Borreliae Efficacy of a Composition of Naturally-occurring Compounds: an In vitro Study

2019 ◽  
pp. 350-363
Author(s):  
Anna Goc ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath
Keyword(s):  
Synergistic Effect ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Synergistic Action ◽  
Decenoic Acid ◽  
Pathogenic Agent ◽  
Naturally Occurring ◽  
Causative Agents

Background: Borrelia sp, which is a pathogenic agent of Lyme diseases in mammals, has become an increasing problem worldwide due to the emergence of persistence. In this study we investigated whether a defined composition of naturally occurring substances could display a broad and synergistic action in vitro against both active and persistent forms of Borrelia spp.Methods: A formulation of six plant-derived compounds combined at their 1/32-1/2 MIC values was tested in vitro against two species of Borrelia recognized as causative agents of Lyme disease in North America and Europe.Results: The results showed that a composition of baicalein, luteolin, rosmarinic acid, monolaurin, cis-2 decenoic acid, and iodine at their 1/8 MIC values has significant synergistic effect against the active and persisting latent forms. This composition revealed anti-oxidative properties affecting Borrelia’s membrane but not DNA. Finally, we observed its inhibitory effect on the release of IL-1α, IL-1β, and IL-6 by human CD14+ monocytes stimulated with live Borrelia sp.Conclusion: These results suggest that such a formulation of compounds might be considered and further explored for its significant pleotropic anti-Borreliae efficacy. Additional in vivo and human studies are warranted to validate this possibility.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

Modulation by Dipyridamole of the Arachidonic Acid Metabolic Pathway in Platelets an in vivo and in vitro Study

1979 ◽  
Author(s):  
Neri G.G. Serneri ◽  
G. F. Gensini ◽  
R. Abbate ◽  
S. Favilla ◽  
R. Laureano
Keyword(s):  
Arachidonic Acid ◽  
Antiplatelet Agent ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Oral Route ◽  
Radiometric Assay ◽  
Venous Infusion ◽  
Clinical Conditions

Dipyridamole is a useful antiplatelet agent in specific clinical conditions, but its effects on TxEL production by platelets are now being debated, Resting platelets from patients with 1.5-2 fig/ml serum dipyridamole (spectrofluorimetric assay). administered by venous infusion or by oral route, showed an increased concentration (m.v. +60% P<0.001) of cAMP (radiometric assay). After stimulation with thrombin (5U/ml) platelets produced a significantly decreased amount of TxB(m.v. -60%, F< 0.001) (radioimmunoassay with antibody kindly supplied by Doctor J.B. Smith, Philadelphia). However also after stimulation with arachidonic acid (A.A.) 1 mM TxB production was decreased(m.v. -50%, P<0.001). The incubation of control platelets with different concentrations of dipyridamole (0.5, 1 and 2 μg/ml) for 20 min at 37°C resulted in an increase of cAMP and in a decrease of TxB, production after stimulation with thrombin and with A.A.. These results indicate that dipyridamole is endowed with direct antiaggrega= ting activity caused by a decreased production of TxB2. This in tum seems due to an inhibitory modulating effect of cAMP on arachidonic acid cyclo-oxygenation. However our findings do not rule out an inhibitory effect also on phospholipase A2.

scholarly journals Inhibition of isoleucyl-transfer ribonucleic acid synthetase in Echerichia coli by pseudomonic acid

1978 ◽  
Vol 176 (1) ◽  
pp. 305-318 ◽  
Author(s):  
Julia Hughes ◽  
Graham Mellows
Keyword(s):  
Rna Synthesis ◽  
Inhibitory Effect ◽  
Trna Synthetase ◽  
Threonine Deaminase ◽  
Trna Synthetases ◽  
E Coli ◽  
Naturally Occurring ◽  
Pseudomonic Acid

The mode of action of the antibiotic pseudomonic acid has been studied in Escherichia coli. Pseudomonic acid strongly inhibits protein and RNA synthesis in vivo. The antibiotic had no effect on highly purified DNA-dependent RNA polymerase and showed only a weak inhibitory effect on a poly(U)-directed polyphenylalanine-forming ribosomal preparation. Chloramphenicol reversed inhibition of RNA synthesis in vivo. Pseudomonic acid had little effect on RNA synthesis in a regulatory mutant, E. coli B AS19 RCrel, whereas protein synthesis was strongly inhibited. In pseudomonic acid-treated cells, increased concentrations of ppGpp, pppGpp and ATP were observed, but the GTP pool size decreased, suggesting that inhibition of RNA synthesis is a consequence of the stringent control mechanism imposed by pseudomonic acid-induced deprivation of an amino acid. Of the 20 common amino acids, only isoleucine reversed the inhibitory effect in vivo. The antibiotic was found to be a powerful inhibitor of isoleucyl-tRNA synthetase both in vivo and in vitro. Of seven other tRNA synthetases assayed, only a weak inhibitory effect on phenylalanyl-tRNA synthetase was observed; this presumably accounted for the weak effect on polyphenylalanine formation in a ribosomal preparation. Pseudomonic acid also significantly de-repressed threonine deaminase and transaminase B activity, but not dihydroxyacid dehydratase (isoleucine-biosynthetic enzymes) by decreasing the supply of aminoacylated tRNAIle. Pseudomonic acid is the second naturally occurring inhibitor of bacterial isoleucyl-tRNA synthetase to be discovered, furanomycin being the first.

PTH- PTHR1 Axis Control on Anti-Myeloma Effect of Proteasome Inhibitors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5017-5017
Author(s):  
Maurizio Zangari ◽  
Fang Xiao ◽  
Ye Yang ◽  
Hongwei Xu ◽  
Guido J. Tricot ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Proteasome Inhibitors ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Tumor Burden ◽  
Control Group

Abstract Abstract 5017 Multiple myeloma (MM) is a plasma cell malignancy with high osteolytic capacity and impaired bone formation. Our recent studies have demonstrated that PTH serum increases are associated with Bortezomib responses in multiple myeloma patients, indicating a possible role of PTH in anti myeloma effect of Bortezomib. We first tested the 5TGM1 cell line for sensitivity to bortezomib, PTH, and [TYR34]bPTH-(7-34) bovine (a specific PTHR1 inhibitor) in various combinations. In an in vitro study, 5TGM1 cells were sensitive to cytotoxicity of bortezomib and PTH in a dose dependent fashion. TYR compound was found to have no effect as single agent on 5TGM1 cell survival, but was able to partially block the inhibitory effect of bortezomib on cell growth (Figure 1). In an in vivo study using the 5TGM1 C 57BL/KaLwRijmice, we tested PTH-PTHR1 axis on bortezomib anti-myeloma activity. As shown in Figure 1, mice survival was positively affected by bortezomib administration (P = 0.04), and the combination of PTH + bortezomib showed a trend to further improve survival (P = 0.09). Interestingly, the concomitant use of [TYR] compound with bortezomib completely abrogated the efficacy of the proteasome inhibitor on survival. Tumor burden assessed by M-protein levels decreased consistently in mice treated with bortezomib alone, PTH alone, or a combination of PTH + bortezomib compared with the control group treated with PBS (P = 0.003, P = 0.05, P = 0.01 respectively). Importantly the tumor burden in the mice treated with bortezomib was significantly lower than in mice treated with bortezomib plus the PTH inhibitor (TYR), again indicating that the PTHR inhibitor abrogates the effect of Bortezomib on tumor growth. Similar results were obtained using the same systems for other commercially available proteasome inhibitors. Thus, we conclude that the PTH- PTHR1 pathway appears essential for proteasome inhibition activity in myeloma. Our observations may lead to novel treatment approaches in myeloma. Disclosures: No relevant conflicts of interest to declare.

Interaction of Salvianolic Acids and Notoginsengnosides in Inhibition of ADP-Induced Platelet Aggregation

2008 ◽  
Vol 36 (02) ◽  
pp. 313-328 ◽  
Author(s):  
Yan Yao ◽  
Wan-Ying Wu ◽  
Ai-Hua Liu ◽  
Shao-Sheng Deng ◽  
Kai-Shun Bi ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Synergistic Effect ◽  
High Performance ◽  
Platelet Rich Plasma ◽  
Salvia Miltiorrhiza ◽  
In Vitro Study ◽  
Distribution Profile ◽  
Salvianolic Acids

Salvia miltiorrhiza and Panax notoginseng were both considered to be beneficial to cardiovascular diseases in traditional Chinese medicine and often used in combination. To examine the possible interaction between them, the effects of the active fractions of these two herbs, salvianolic acids (SA) and notoginsengnosides (NG), on platelet aggregation were checked respectively or in combination in vitro and in vivo. Both the platelet aggregation of platelet rich plasma (PRP) and washed platelet after ADP induction were checked. In vitro study showed that both SA and NG had an inhibitory effect on platelet aggregation. However, there is no synergistic effect of the combination of SA and NG in vitro. In vivo study showed that i.g. 550 mg/kg/day SA or NG for 5 days could significantly inhibit ADP-induced platelet aggregation of PRP. Moreover, combination of SA and NG at a ratio of 5:1 had a synergistic effect on platelet aggregation of PRP. The mechanism for the synergism of SA and NG in vivo was not clear. High performance liquid chromatography analysis of the plasma of rats received SA, NG or combination of SA and NG showed that co-administration of NG caused change in the plasma distribution profile of SA. The influence of combination on the absorption and/or metabolism of SA may be one of the reasons for the synergism of SA and NG in vivo.

scholarly journals Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3060 ◽  
Author(s):  
Gan Qiao ◽  
Huanli Xu ◽  
Cong Li ◽  
Xiao Li ◽  
Ammad Farooqi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Activity ◽  
Synergistic Effect ◽  
Inhibitory Effect ◽  
Inhibitory Rate ◽  
Chemotherapy Drugs ◽  
Combined Use ◽  
Hcc Cells

Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin.

scholarly journals UTILIZATION OF SAMBUNG NYAWA LEAF EXTRACTS Gynura procumbens (Lour) Merr. FOR TREATMENT OF Vibrio alginolyticus IN TIGER GROUPER (Epinephelus fuscoguttatus Forsskal, 1775)

2019 ◽  
Vol 47 (2) ◽  
pp. 134
Author(s):  
Novi Santika ◽  
Wardiyanto Wardiyanto ◽  
Esti Harpeni
Keyword(s):  
Leaf Extract ◽  
Sea Water ◽  
Economic Value ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Vibrio Alginolyticus ◽  
Leaf Extracts ◽  
Tiger Grouper

Tiger Grouper is one of the sea water fish commodities that is quite popular with the community and has a high economic value. The problem faced by farmers is the attack of Vibriosis, one of which is caused by the Vibrio alginolyticus bacteria. The use of synthetic antibiotics has been widely used but has many adverse effects, so it needs new alternatives for the treatment of Vibriosis disease. One of them is by using the extract of lifelong leaf extract. Life-sustaining plants (Gynura procumbens) contain secondary metabolites such as flavonoids, tannins, and antibacterial saponins. This study aims to determine the best dosage of lifelong leaf extract for the treatment of Vibriosis disease in tiger grouper. The study was conducted in two stages, namely in vitro and in vivo. Before the fish were treated with feed that had been given a sambung deca leaf extract, the fish were challenged using Vibrio alginolyticus with a density of 108 CFU / mL as much as 0.1 mL / head and then fed with treatment and maintained for 21 days. The results of the in vitro study showed that the life of sambung leaf extract at a dose of 700 ppm had a broad inhibitory effect on V. alginolyticus, which amounted to 10.47 mm compared to other treatments. Whereas when continued for in vivo testing, a dose of 350 ppm in general has been applied for the treatment of attacks of Vibrio alginolyticus in tiger grouper.

Melatonin Differentially Modulates NF-кB Expression in Breast and Liver Cancer Cells

2019 ◽  
Vol 18 (12) ◽  
pp. 1688-1694 ◽  
Author(s):  
Jucimara Colombo ◽  
Bruna V. Jardim-Perassi ◽  
João P.S. Ferreira ◽  
Cristine Z. Braga ◽  
Nathália M. Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Transcription Factor ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Hepg2 Cells ◽  
In Vitro Study ◽  
Inhibitory Effect

Background: NF-kB (nuclear factor kappa B) is a transcription factor composed of two subunits, p50 and p65, which plays a key role in the inflammatory process. Melatonin has oncostatic, antiangiogenic and antimetastatic properties, and some recent studies have indicated an inhibitory effect of melatonin on NF-kB in some types of cancer. This work aims to investigate the effects of melatonin treatment on the expression of NFkB in breast and liver cancer models. Method: The breast cancer xenographic model was performed using female Balb/c nude athymic mice injected with MDA-MB-231 cells. The animals were treated with 40 mg/Kg of melatonin for 21 days. Volume of the tumors was measured with a digital caliper. Hepatocarcinoma model was developed by using the HepG2 cells in vitro, treated with 1 mM melatonin for 24 h. The expression of NF-kB protein was verified by immunohistochemistry and immunocytochemistry and quantified by optical densitometry, in vivo study and in vitro study, respectively. NF-kB gene expression was performed by quantitative RT-PCR. Results: The breast cancer xenografts nude mice treated with melatonin showed reduced tumor size (P=0.0022). There was a decrease in NF-kB protein staining (P=0.0027) and gene expression (P=0.0185) in mice treated with melatonin. The opposite results were observed for the hepatocarcinoma model. HepG2 cells treated with melatonin showed an increase in the NF-kB immunostaining when compared to control cells (P=0.0042). Conclusion: Our results indicated that the treatment with melatonin was able to decrease both gene and protein expressions of NF-kB in breast cancer cells and, conversely, increase the transcription factor protein expression in hepatocarcinoma cells. These data highlighted a double role in the expression of NF-kB, depending on the cell type. Further studies are needed to better elucidate the action of melatonin in NF-kB, since this transcription factor acts on different signaling pathways that are fundamental for carcinogenesis.

scholarly journals The Inhibitory Effect of PDIA6 Downregulation on Bladder Cancer Cell Proliferation and Invasion

2017 ◽  
Vol 25 (4) ◽  
pp. 587-593 ◽  
Author(s):  
He-Peng Cheng ◽  
Qian Liu ◽  
Yang Li ◽  
Xiao-Dong Li ◽  
Chao-Yang Zhu
Keyword(s):  
Bladder Cancer ◽  
Close Association ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Volume Weight ◽  
Disulfide Isomerases ◽  
Protein Disulfide ◽  
Proliferation And Invasion

Protein disulfide isomerases A6 (PDIA6) belongs to the PDI family. Recently, PDIA6 was found to have a close association with various cancers. However, there has been little investigation into the biological functions of PDIA6 in bladder cancer (BC). In this study, we explored the expression pattern and functional significance of PDIA6 in BC. We found that PDIA6 was overexpressed in BC tissues and cell lines. The in vitro study showed that PDIA6 downregulation significantly inhibited BC proliferation and invasion. In addition, the in vivo experiment demonstrated that PDIA6 downregulation decreased the volume, weight, and metastasis of tumors. Furthermore, PDIA6 downregulation reduced the protein expression of β-catenin, cyclin D1, and c-Myc and thus suppressed the Wnt/β-catenin signaling pathway. In conclusion, we suggest that PDIA6 could be targeted for the treatment of BC.

scholarly journals Pharmacological features of osthole

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Agata Jarząb ◽  
Aneta Grabarska ◽  
Krystyna Skalicka-Woźniak ◽  
Andrzej Stepulak
Keyword(s):  
Tumor Cells ◽  
Therapeutic Option ◽  
Inhibitory Effect ◽  
Experimental Models ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Anti Inflammatory ◽  
The Impact

Coumarins are a group of naturally occurring compounds common in the plant world. These substances and their derivatives exhibit a broad range of biological activities.One of the naturally occurring coumarins is osthole, which can most frequently be found in plants of the Apiaceae family. Cnidium monnieri (L.) Cusson ex Juss. Angelica pubescens Maxim. and Peucedanum ostruthium (L.). It has anti-proliferative, anti-inflammatory, anti-convulsant, and antiallergic properties; apart from that, inhibition of platelet aggregation has also been proved. The impact of osthole on bone metabolism has been demonstrated; also its hepatoprotective and neuroprotective properties have been confirmed. The inhibitory effect of this metokcompound on the development of neurodegenerative diseases has been proved in experimental models. Anticancer features of osthole have been also demonstrated both in vitro on different cell lines, and in vivo using animals xenografts. Osthole inhibited proliferation, motility and invasiveness of tumor cells, which may be associated with the induction of apoptosis and cell cycle slowdown. The exact molecular mechanism of osthole anti-cancer mode of action has not been fully elucidated. A synergistic effect of osthole with other anti-tumor substances has been also reported. Modification of its chemical structure led to the synthesis of many derivatives with significant anticancer effects.To sum up, osthole is an interesting therapeutic option, due to both its direct effect on tumor cells, as well as its neuroprotective or anti-inflammatory properties. Thus, there is a chance to use osthole or its synthetic derivatives in the treatment of cancer.

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