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1.
Cell Biol Toxicol ; 37(4): 611-631, 2021 08.
Article in English | MEDLINE | ID: mdl-33219891

ABSTRACT

Identifying drug candidates to target cellular events/signaling that evades von Hippel-Lindau tumor suppressor (VHL) gene interaction is critical for the cure of renal cell carcinoma (RCC). Recently, we characterized a triterpene-squalene derived from marine brown alga. Herein, we investigated the potential of squalene in targeting HIF-signaling and other drivers of RCC progression. Squalene inhibited cell proliferation, induced cell dealth and reverted the cells' metastatic state (migration, clonal expansion) independent of their VHL status. Near-identical inhibition of HIF-1α and HIF-2α and the regulation of downstream targets in VHL wild type and mutant cell lines demonstrated squalene efficacy beyond VHL-HIF interaction. In a rat model of chemically induced RCC, squalene displayed chemopreventive capabilities by substantial reversal of lipid peroxidation, mitochondrial redox regulation, maintaining ∆ψm, inflammation [Akt, nuclear factor κB (NF-κB)], angiogenesis (VEGFα), metastasis [matrix metalloproteinase 2 (MMP-2)], and survival (Bax/Bcl2, cytochrome-c, Casp3). Squalene restored glutathione, glutathione reductase, glutathione-s-transferase, catalase, and superoxide dismutase and stabilized alkaline phosphatase, alkaline transaminase, and aspartate transaminase. The correlation of thiobarbituric acid reactive substance with VEGF/NF-κB and negative association of GSH with Casp3 show that squalene employs reduction in ROS regulation. Cytokinesis-block micronuclei (CBMN) assay in VHLwt/mut cells revealed both direct and bystander effects of squalene with increased micronucleus (MN) frequency. Clastogenicity analysis of rat bone marrow cells demonstrated an anti-clastogenic effect of squalene, with increased polychromatic erythrocytes (PCEs), decreased MNPCE,s and MN normochromatic erythrocytes. Squalene could effectively target HIF signaling that orchestrate RCC evolution. The efficacy of squalene is similar in VHLwt and VHLmut RCC cells, and hence, squalene could serve as a promising drug candidate for an RCC cure beyond VHL status and VHL-HIF interaction dependency. Summary: Squalene derived from marine brown algae displays strong anti-cancer (RCC) activity, functionally targeting HIF-signaling pathway, and affects various cellular process. The significance of squalene effect for RCC is highlighted by its efficiency beyond VHL status, designating itself a promising drug candidate. Graphical abstract.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Animals , Basic Helix-Loop-Helix Transcription Factors , Carcinoma, Renal Cell/drug therapy , Disease Progression , Gene Expression Regulation, Neoplastic , Hypoxia-Inducible Factor 1, alpha Subunit , Matrix Metalloproteinase 2 , Rats , Squalene , Von Hippel-Lindau Tumor Suppressor Protein/genetics
2.
Mar Pollut Bull ; 152: 107891, 2020 Mar.
Article in English | MEDLINE | ID: mdl-27423443

ABSTRACT

Nowadays, marine ecosystem monitoring and assessment are increasingly depending on variety of molecular tools. With these background, DNA barcoding play a key role in species identification with increasing speed and accuracy, and although the suitability for developing genetic tools like genomic AMBI (gAMBI). Presently we have submitted 13 benthic polychaete species using mtCOI to GenBank. Of these, nine species were newly submitted, and hence they act as a benchmark and reference organism for identifying respective polychaete species worldwide in the near future. Based on that, our study results tend to be helpful for motivating among the researcher in order to implementing the genomic AMBI (gAMBI).


Subject(s)
DNA Barcoding, Taxonomic , Ecosystem , Environmental Monitoring
3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-500618

ABSTRACT

Objective: To study the production, purification and characterization of bacteriocin fromLactobacillus murinus against fish pathogens.Methods:AU06 isolated from marine sediments and its broad spectrum of inhibition bacteriocin. In addition, purified bacteriocin was tested for its antimicrobial activity against fish pathogens.Results:In the present study, the bacteriocin production was found to be higher at 35 °C, pH The selected strain was used in production, purification and characterized of 6.0 and was purified to 4.74 fold with 55. 38 U/mg of specific activity with the yield of 28.92%. The molecular weight of the purified bacteriocin was estimated as 21 kDa. The purified bacteriocin exhibited complete inactivation of antimicrobial activity when treated with proteinase K, pronase, chymotrypsin, trypsin, pepsin and papain. The purified bacteriocin exhibited broad inhibitory spectrum against both Gram positive and negative bacteria.Conclusions:It is concluded that the ability of bacteriocin in inhibiting a wide-range of pathogenic bacteria is of potential interest for food safety and may have future applications in food preservative.

4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-499626

ABSTRACT

Objective: To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host–pathogen interaction model.Methods:ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug.Results:Thirty species of marine plants were subjected to Soxhlet extraction using water, formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection.Conclusions:Nine plant isolates exhibited significant survivability in host. The drug MP07X thus The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.

5.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-499620

ABSTRACT

Objective: To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host–pathogen interaction model.Methods:Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti–WSSV property in Litopenaeus vannamei. The best anti–WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug.Results: Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection.Conclusions:The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.

6.
Article in English | WPRIM (Western Pacific) | ID: wpr-270602

ABSTRACT

We investigated the anti-nociceptive effect of Excoecaria agallocha (E.agallocha) against chemically and thermally induced nociception, Albino mice received a dose of 10, 15, 20, or 25 mg/kg of alkaline chloroform fraction (Alk-CF) of E.agallocha by oral administration. Compared with controls, Alk-CF decreased the writhing numbers (P<0.01) in a dose dependent manner. Further we determined that, Alk-CF contained, a potent compared to control, also potent anti-nociceptive agent that acted via opioid receptors and using HPLC, identified this compound as Rutin. Docking simulation demonstrated that Rutin interacted strongly with cyclooxygenase, forming a number of specific hydrogen bonds. In conclusion we have identified peripheral and central anti-nociceptive activities of E.agallocha that involve opioid receptor, and in which the active compound is Rutin.


Subject(s)
Animals , Female , Male , Mice , Analgesics , Therapeutic Uses , Drug Evaluation, Preclinical , Euphorbiaceae , Chemistry , Pain , Drug Therapy , Phytotherapy , Plant Extracts , Chemistry , Therapeutic Uses , Rutin , Therapeutic Uses
7.
Article in English | WPRIM (Western Pacific) | ID: wpr-343262

ABSTRACT

<p><b>OBJECTIVE</b>To study the production, purification and characterization of bacteriocin from Lactobacillus murinus AU06 isolated from marine sediments and its broad spectrum of inhibition against fish pathogens.</p><p><b>METHODS</b>The selected strain was used in production, purification and characterized of bacteriocin. In addition, purified bacteriocin was tested for its antimicrobial activity against fish pathogens.</p><p><b>RESULTS</b>In the present study, the bacteriocin production was found to be higher at 35 °C, pH 6.0 and was purified to 4.74 fold with 55. 38 U/mg of specific activity with the yield of 28.92%. The molecular weight of the purified bacteriocin was estimated as 21 kDa. The purified bacteriocin exhibited complete inactivation of antimicrobial activity when treated with proteinase K, pronase, chymotrypsin, trypsin, pepsin and papain. The purified bacteriocin exhibited broad inhibitory spectrum against both Gram positive and negative bacteria.</p><p><b>CONCLUSIONS</b>It is concluded that the ability of bacteriocin in inhibiting a wide-range of pathogenic bacteria is of potential interest for food safety and may have future applications in food preservative.</p>

8.
Article in English | WPRIM (Western Pacific) | ID: wpr-233301

ABSTRACT

<p><b>OBJECTIVE</b>To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various marine floral ecosystems and to evaluate the efficacy of the same in host-pathogen interaction model.</p><p><b>METHODS</b>Thirty species of marine plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. By means of chemical processes, the purified anti-WSSV plant isolate, MP07X was derived. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug.</p><p><b>RESULTS</b>Nine plant isolates exhibited significant survivability in host. The drug MP07X thus formulated showing 85% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of MP07X required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 1 000 mg/kg body weight/day survived at the rate of 85%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection.</p><p><b>CONCLUSIONS</b>The drug MP07X derived from Rhizophora mucronata is a potent anti-WSSV drug.</p>

9.
Article in English | WPRIM (Western Pacific) | ID: wpr-233300

ABSTRACT

<p><b>OBJECTIVE</b>To screen, isolate and optimize anti-white spot syndrome virus (WSSV) drug derived from various terrestrial plants and to evaluate the efficacy of the same in host-pathogen interaction model.</p><p><b>METHODS</b>Thirty plants were subjected to Soxhlet extraction using water, ethanol, methanol and hexane as solvents. The 120 plant isolates thus obtained were screened for their in vivo anti-WSSV property in Litopenaeus vannamei. The best anti-WSSV plant isolate, TP22C was isolated and further analyzed. The drug was optimized at various concentrations. Viral and immune genes were analysed using reverse transcriptase PCR to confirm the potency of the drug.</p><p><b>RESULTS</b>Seven plant isolates exhibited significant survivability in host. The drug TP22C thus formulated showed 86% survivability in host. The surviving shrimps were nested PCR negative at the end of the 15 d experimentation. The lowest concentration of TP22C required intramuscularly for virucidal property was 10 mg/mL. The oral dosage of 750 mg/kg body weight/day survived at the rate of 86%. Neither VP28 nor ie 1 was expressed in the test samples at 42nd hour and 84th hour post viral infection.</p><p><b>CONCLUSIONS</b>The drug TP22C derived from Momordica charantia is a potent anti-white spot syndrome virus drug.</p>

10.
Int J Biol Macromol ; 54: 84-9, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23220595

ABSTRACT

Although hyaluronic acid research pursuits ahead in exploring its biomedical perspective, very limited investigations were carried out in their isolation shape view point, furthermore, most of the investigations were targeted towards the terrestrial source. To swerve from that, the present study was projected through the marine superstore, where in high molecular weight hyaluronic acid of 13, 65,863 Da was isolated from the liver of stingray Aetobatus narinari. The purified HA was confirmed at the preliminary level by their stains all dye binding nature. Their analytical composition including carbon, hydrogen, nitrogen, N-acetyl glucosamine, glucuronic acid contents was analysed. The HA was characterized by agarose-gel electrophoresis, FTIR, HPTLC, and (1)H NMR. The DPPH radical scavenging activity of HA and its reducing power was evident to all the tested concentrations, but lower than that of ascorbic acid. HA showed significant inhibition against the proliferation of cells, substantiating its influence in regulation of cell functions.


Subject(s)
Hyaluronic Acid/isolation & purification , Hyaluronic Acid/pharmacology , Liver/chemistry , Seawater , Skates, Fish/metabolism , Absorption , Animals , Biphenyl Compounds/metabolism , Cell Proliferation/drug effects , Free Radical Scavengers/pharmacology , Free Radicals/metabolism , Humans , Magnetic Resonance Spectroscopy , Picrates/metabolism , Reference Standards , Spectrophotometry, Infrared
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-500646

ABSTRACT

Objective: To evaluate the in vitro antioxidant activity of Sargassum wightii (S. wightii) andUlva lactuca (U. lactuca). Methods: Dried seaweeds of S. wightii and U. lactuca were tested for total phenolic content. In vitro antioxidant activity was determined by DPPH assay and ferric reducing antioxidant power (FRAP) assay. Functional groups of two seaweeds were analysed by fourier transform infrared spectroscopy (FTIR). Results: The highest total phenolic content was observed in S. wightii (0.65±0.02 mg GAE/g) when compared with U. lactuca. In vitro antioxidant activity of S. wightii showed higher activity in all assays than U. lactuca with the higher total antioxidant activity (123.40±4.00 mg ascorbic acid/g), DPPH radical scavenging activity (108.06±1.02)% and ferric reducing antioxidant power (153.40±1.41 mg GAE/g). FITR spectrum of standard gallic acid was compared with seaweeds and same number of peaks lying between 449.32 and 3 495.89 cm-1 and 462.89 and 3 407.05 cm-1 was recorded. Conclusions: These results show that S. wightii has higher antioxidant capacity than U. lactuca. Further study is necessary to exploit the multifunctional properties of seaweeds which will be usefull to treat many diseases.

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