Asian Pacific Journal of Tropical Biomedicine

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Objective: To evaluate the neutralizing effects of flavonoids on snake venom toxicity by stand-alone and combinatorial approaches. Methods: Synthetic flavonoids were assessed, either individually or in combination with antivenom, for their neutralization of phospholipase A₂ (PLA₂), protease, antioxidant (DPPH) assay and hemotoxic activity. Molecular docking studies were performed to understand possible binding of flavonoids with Naja naja venom PLA₂. In vivo studies were carried out to confirm the neutralisation effects using a mouse model. Moreover, inhibition of PLA₂ was monitored using combinatorial approaches. Results: Among the flavonoids used, quercetin and naringenin inhibited PLA₂ (56% and 45%), protease (71% and 64%), DPPH scavenging (69.0% and 77.5%) and hemotoxic (70%) activities. Molecular docking studies indicated that the flavonoids bind to the substrate-binding site of PLA₂ (Cys44 and Tyr63). In vivo studies showed a reduction in the venom toxicity level in the presence of naringenin. Additionally, combinatorial studies using the mixture of flavonoid and anti-venom revealed the possibility of synergistic effect (up to 32% enhancement) in neutralising the venom enzymes. Conclusions: These flavonoids can be used as additives for the treatment of snake bites, which may exert synergistic effects in combination with antivenom and decrease the post-therapeutic effects caused by excessive use of antivenom.

Acute kidney injury, previously known as acute renal failure (AKI), is defined as an abrupt decrease in kidney function that occurs within hours or days. This new nomenclature opens a new door for possibility of treatment of developing renal injury before progression to unresolved renal failure. AKI arises due to diverse etiologic factors that rely mainly on three categories namely, pre-renal, intrinsic renal, and post-renal factors with different clinical pictures, and confers a spectrum of injury ranging from mild to severe and sometimes leads to end-stage renal disease. Complexity of pathogenesis and other factors generate barriers to developing effective treatments despite a large number of experimental and clinical studies. In this review, recent advances in the potential of the currently used drugs for renoprotection, novel pharmacological targets, and prospective therapeutics for AKI are discussed. The information in this review was extracted from electronic resources (PubMed, Google Scholar, Wiley, Science Direct, Springer), and English scientific books by using keywords including kidney, injury, recent therapy, and pharmacological targets. The articles were carefully checked for their relevance to the current manuscript. Recent targets of cellular repair or regenerative processes involved in AKI such as autophagy, ferroptosis inhibition, and p53 antagonism seem to be effective in disease control. This may help researchers and clinicians to understand how to target the interrelated molecular and cellular mechanisms underlying the pathogenesis of AKI.

Objective: To investigate the antioxidant and cytotoxic properties of the most active extracts from Ulva lactuca and Laurencia obtusa against colon and cervical cancer cell lines. Methods: The antioxidant radical scavenging activity of the algal extracts was estimated using the 2,2-diphenyl-1-picrylhydrazyl colorimetric assay. Moreover, the cytotoxic potential of these bioactive extracts was studied against HCT-116 and HeLa cells by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Wound healing analysis was adopted to evaluate the anti-metastatic effects of protein extracts from both algae. Cell cycle analysis was performed by flow cytometry, and apoptotic bodies were detected using 4’,6-diamidino-2-phenylindole fluorescent staining. Amino acids of hydrolyzed protein extract were separated and identified chromatographically by high performance liquid chromatography. Results: The green algae Ulva lactuca had higher lipid content than Laurencia obtusa, whereas the latter had higher protein content with high antioxidant capacity. Protein extracts had significant dose- and time-dependent cytotoxicity and anti-metastatic activity against HCT-116 cells. Protein b extracts of both algae obtained from the chloroform:hexane solvent lipid-free residue caused morphological changes and induced apoptosis of HCT-116 cells. Further analysis revealed that apoptosis induced upon Laurencia obtusa protein b treatment was triggered via the ROS pathway, causing a significant increase in the sub-G₁ population. Glycine and arginine (5.94 and 5.47 μM, respectively) were the most common amino acids in Laurencia obtusa protein b extract. Conclusions: Proteins of Laurencia obtusa and Ulva lactuca could be considered as an adjuvant nutraceutical source of pro-apoptotic and anti-metastatic biomolecules against colon cancer.

Objective: To investigate anti-tumor effect of rice bran hydrolysates (RBH) on proliferation, migration, invasion, and angiogenesis of cholangiocarcinoma (CCA) cells, and elucidate the underlying mechanisms. Methods: RBH was prepared from Tubtim Chumprae rice (Oryza sativa L.) by hydrothermolysis followed by protease digestion. Phenolic content in RBH was analyzed by high-performance liquid chromatography. Human CCA cells, KKU-156, KKU-452, and KKU-100, were used to study the effects of RBH on proliferation, migration, invasion, and adhesion by wound healing, Transwell chamber, and fibronectin cell adhesion assays. Angiogenesis was evaluated using human umbilical vein endothelial cells. Proteins associated with cancer progression were analyzed by immunobloting assays. Results: RBH contained carbohydrates, proteins, lipids, and various phenolic compounds and flavonoids. RBH did not inhibit CCA proliferation, but strongly suppressed migration, invasion, adhesion of CCA cells, and the formation of tube-like capillary structures of human umbilical vein endothelial cells. Moreover, RBH down-regulated phosphorylation of FAK, PI3K, and Akt, suppressed NF-κB nuclear translocation, decreased the expression of ICAM-1, vimentin and vascular endothelium growth factor (VEGF), and increased the expression of E-cadherin. Conclusions: RBH suppresses CCA cell migration and invasion and decreases expression of proteins involved in cancer metastasis. RBH is a potential food supplement for cancer prevention.

Online since 13^th December 2017