Biochemistry Research International最新文献

Proteins have shown varying degrees of antioxidant activity. This study examined the potential mechanisms of interactions between proteins and radicals using chemical kinetics and computational methods. The study quantified the antioxidant activity of lactate dehydrogenase (LDH) and bovine serum albumin (BSA) through Trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) assays. BSA was about seven times and LDH 12 times more potent as antioxidants for 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS^•-) than they were for peroxyl radicals. According to the evaluation of Trolox equivalents (TE) of 20 proteinogenic amino acids, tryptophan (with a TE value of 101 μmol TE/μmol) exhibited the highest antioxidant activity for ABTS^•-, followed by tyrosine (38.7 μmol TE/μmol) and cysteine (30.5 μmol TE/μmol), lysine (0.193 μmol TE/μmol), arginine (0.0325 μmol TE/μmol), valine (0.0280 μmol TE/μmol), histidine (0.00689 μmol TE/μmol), and leucine (0.00560 μmol TE/μmol). The EC50 showed a similar order with a swap between valine and histidine. The antioxidant activity of the amino acids and proteins was temperature dependent. The rate laws, activation energy, and pre-exponential factor A of these reactions provided information on the reaction mechanisms, i.e., a biomolecular elementary step for the reaction of ABTS^•- with amino acids tryptophan, tyrosine, cysteine, or protein LDH, and a more complicated mechanism for BSA. The presence of -NH- or hydroxyl groups on aromatic rings enhanced the antioxidant ability of tryptophan and tyrosine. LDH's antioxidant activity did not affect its enzymatic activity, indicating that the radical reaction likely happened on the protein's surface without significantly altering its conformation. The molecular modeling and visualization showed potential reaction sites on the proteins' accessible tryptophan and tyrosine residues. However, the mere surface exposure of tryptophan and tyrosine does not guarantee their antioxidant activities.

Recently, it has been shown that protein phosphatase 2A (PP2A) dysfunction was common in many cancer types and was mediated by various inactivation mechanisms. Although many research studies observed antitumor effect of propolis extracts in various types of cancer, the mechanism of effect are still obscure. In this study, we investigated the effect of propolis on PPP2R1A expression and its relationship with apoptosis in the SW-620 (colorectal cancer), DU-145 and PC-3 (prostate cancer), and MCF-7 (breast cancer) cell lines, with WI-38 (healthy fibroblast) cells serving as the control. Moreover, we aimed to investigate the impact of propolis on apoptosis by analyzing apoptosis markers such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), APAF-1, and caspases-3, -8, and -9. Propolis samples were extracted, and their phenolic compounds were quantified using LC-MS/MS. The RealTime Cell Analysis System-xCELLigence (RTCA-SP) device and software were employed to assess cell viability and cytotoxicity of the propolis samples. The IC₅₀ values for propolis were determined (298 μg/mL for SW-620, 185.6 μg/mL for DU-145, 250.7 μg/mL for PC - 3, 292.9 μg/mL for MCF-7, and 311.2 μg/mL for WI-38). Subsequently, the effects of propolis on PPP2R1A expression and apoptosis markers (TRAIL, Apaf-1, and caspases-3, -8, and -9) were analyzed. When we compared the healthy cell lines to cancer cell lines, a statistically significant increase in caspase-3 (3.62-fold) and in TRAIL (4.38-fold) was observed in the SW-620 cell line after the application of propolis. In addition, in the PC-3 cell line, a 1.4-fold increase in caspase-8 was observed compared with the healthy cell line, which is also statistically significant. Our findings indicated that propolis increased the PPP2R1A levels and apoptosis markers in cancer cell lines. It has been suggested that high PPP2R1A levels induced by propolis treatment might activate the apoptosis pathway. In this study, the inducible effect of propolis on PPP2R1A levels, identified as a new target for cancer treatment, was demonstrated for the first time. The findings suggest that propolis holds promise as a potential cancer therapy by increasing PPP2R1A levels, a key molecule in cancer treatment.

Members of the Costus genus are the conventional medicinal plants used in the therapeutic management of numerous ailments, especially for their antioxidant and pharmacological activities. The crude extract of Costus spicatus was profiled using high-resolution GC-MS and LC-MS/MS techniques to determine possible bioactive compounds that are vital to the antioxidant activity. A total of 52 and 63 bioactive compounds have been detected in GC-MS chromatograms using different solvents (methanol and ethanol) in C. spicatus leaf extracts, representing the presence of certain bioactive compounds. The identified bioactive compounds in both extracts which exhibit neuroprotective effects have been confirmed through various literature studies. They are cholestan-3-amine, loliolide, stigmasterol and methylprednisolone acetate, succinimide, fumaric acid, beta-tocopherol and gamma-tocopherol. The aqueous extract possessed the highest antioxidant activity for DPPH scavenging activity and lipid peroxidation inhibition assays, whereas the alcoholic aqueous extract showed superior efficacy for hydroxyl radical scavenging activity. In this study, we performed molecular docking and found that four compounds exhibited promising binding affinities with predicted binding sites on alpha-synuclein. Notably, Androsta [17-16-b] furan-5'-imine, 4'-methylene-3-methoxy-N-cyclohexyl- showed the highest docking interaction score of -7.4, indicating a strong binding affinity. These findings, combined with the presence of bioactive components in the crude extract of C. spicatus, suggest that this plant may possess neuroprotective properties, warranting further investigation for potential industrial applications in the development of neuroprotective agents.

Age-related macular degeneration (AMD) is a severe eye disease in people aged 60 years and older. Although anti-VEGF therapies are effective in treating neovascular AMD (NvAMD) in the clinic, up to 60% of patients do not completely respond to the therapies. Recent studies have shown that blood-derived macrophages and their associated proinflammatory cytokines may play important roles in the development of persistent disease and resistance to anti-VEGF therapy. To address this issue, we constructed an antibody-based bispecific fusion protein that can simultaneously inhibit IL-17-induced inflammation and VEGF-mediated neovascularization. As a result, the bispecific fusion protein 17V05 effectively inhibited multiple proinflammatory cytokines and chemokines, as well as laser-induced choroidal neovascularization (CNV). More importantly, 17V05 also exhibited stronger and longer inhibitory effects than conbercept in vivo. Thus, we provide a novel and promising strategy for treating AMD patients who are not sensitive to anti-VEGF therapies.

Alzheimer's disease (AD), a neurological disorder, is one of the major reasons for memory loss in the world. AD is characterized by a sequela of cognitive and functional decline caused by brain cell degeneration. Paeoniflorin is a monoterpenoid glycoside found in plants of the Paeoniaceae family, which are known for their medicinal properties including dementia. In this project, we report actions of paeoniflorin on the two related cholinesterases (ChE): acetylChE (AChE) and butyrylChE (BuChE). Paeoniflorin, in a dose-dependent (maximum inhibition at 1 mg/mL) manner, inhibited both AChE (0.06-1 mg/mL) and BuChE (0.007-1 mg/mL) enzymes with maximum inhibition of AChE enzyme at 90.3 ± 1.4%, while 99.4 ± 0.3% for BuChE enzyme. The EC₅₀ value for the inhibitory effect of the compound against AChE was 0.52 mg/mL (0.18-1.52), while against BuChE was 0.13 mg/mL (0.08-0.21). The observed ani-ChE action was like an effect also mediated by the known ChE blocker physostigmine. Molecular interactions between paeoniflorin and both ChE enzymes were additionally sought via molecular docking and molecular dynamics simulations for 100 ns, that showed paeoniflorin interacted with the active-site gorge of AChE and BuChE via hydrogen bonds and water bridging with the many amino acids of the AChE and BuChE enzymes. This study presents the ChE inhibitory potential of paeoniflorin against both AChE and BuChE enzymes. With this kind of inhibitory activity, the chemical can potentially increase ACh levels and may have use in the treatment of dementia of AD.

Blighia sapida oil, a substance with a rich history of use for its nutritional, therapeutic, traditional, and cosmetic benefits, was the focus of our study. We investigated the impact of consuming edible oil from B. sapida arils on Wistar rats. The crude oil from unripe arils was extracted using cold pressing and then administered to the rats. The toxicity was evaluated according to the OECD method. Notably, there were no signs of food poisoning or adverse effects on the weight and behavior of the rats treated with B. sapida oils. The LD50 of the oil was more significant than 5000 mg/kg of body weight, and hematological and biochemical parameters did not differ significantly from the control group. Rats fed with an oil-supplemented diet showed an increase in weight compared to the negative control group. No fatty deposits were found in vital organs, and consuming the oil did not affect the immune system or biochemical biomarkers. However, excessive intake of fat may have harmful effects on tissues. Our findings strongly suggest that B. sapida oil is safe for consumption within reasonable limits. The data we present here reveal that the oil derived from B. sapida is suitable for moderate consumption and may offer various health advantages, a potential that warrants further exploration.

Lignocellulosic biomass (LCB) comprising of wheat bran, coconut husk, rice husk, cereals straw, and other hardwood and softwoods is a good source for the production of xylooligosaccharides (XOS) (prebiotic). XOS produced are nondigestible carbohydrates being stable under stomach pH and digestive enzymes so they can be easily delivered to the intestine in native form, thus stimulating the growth of probiotics. Here we review about the raw material, production, purification, and application of XOS with health benefits. Importance of XOS being valuable food ingredient is increasing as they perform a variety of functions, including reduction in cholesterol levels, gastrointestinal health maintenance, anticancer and antioxidant properties, and modulation of immune system. We also discuss the different characterization methods which are necessary to determine the degree of polymerization (DP) of XOS. Low DP (xylobiose and xylotriose) is usually preferred for the application of XOS in various sectors. This review emphasizes the growing significance of XOS as a prebiotic, serving as nourishment for probiotics.

Background: Moringa oleifera leaf is used for diabetes due to its pharmacologic effects. Patients with hyperglycemia experience beta cell destruction. However, no research on risk awareness has been done to ascertain its safety. The present study describes the antidiabetic effect of Moringa oleifera leaf, such as the protection of pancreatic beta cells and the induction of glycogen synthesis, before addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Methods: Forty-five Wistar rats weighed 160 ± 10 g were divided into nine groups. All animal operations complied with the National Institute of Health (NIH) guidelines for the care and use of laboratory animals as approved by the Animal Ethical Committee, University of Jos. Group I was normal control and Group II was diabetic animals induced with alloxan. Insulin and extract doses of 200, 400, and 800 mg/kg were given to diabetic Groups III-VI. Normal animals in Groups VII-IX were given extract at doses of 200, 400, and 800 mg/kg for 28 days. Tissues were retrieved for biochemical and histological investigations using standard techniques. Results: There was decrease relative body weight of diabetic animals (95.50 ± 5.50) when compared to normal control (142.75 ± 20.08) with increased levels of urea (control 6.13 ± 0.523 and diabetes 29.23 ± 1.267) and creatinine (control 0.70 ± 0.057 and diabetes 2.13 ± 0.185). Histology of the liver and pancreas also points to organ damage due to hyperglycemia. However, oral administration of extract showed antidiabetic effect with protection of pancreatic beta cells and the induction of glycogen synthesis, no glycogen was deposited in the liver, addressing the secondary effects of diabetes, such as hepatic and renal toxicity. Further discovery revealed that extract elevated antioxidant enzyme expression. Conclusion: Leaf extract from Moringa oleifera reduces blood sugar and lessens the damage caused by hyperglycemia in the pancreas and liver.

Background: The study investigates the antioxidant properties of Catharanthus roseus, focusing on identifying its antioxidant compounds and chemical constituents. We compare antioxidant activities across its root, stem, flower, and leaf and examine the inhibition of reactive oxygen species (ROS)-generating enzymes by the plant's phytocompounds. Methods: We conducted a comprehensive analysis that included proximate analysis, mineral content assessment, and in vitro antioxidant characterization of various plant parts-root, stem, flower, and leaf. The levels of bioactive phytochemicals in both ethanol and mixed-solvent extracts of Catharanthus roseus were quantified using high-performance liquid chromatography with a diode array detector (HPLC-DAD). Additionally, we performed molecular docking studies to explore the interactions of quantified phytocompounds. Results: HPLC-DAD analysis quantified catechin hydrate, catechol, (-) epicatechin, rutin hydrate, trans-cinnamic acid, quercetin, vanillic acid, kaempferol, and trans-ferulic acid in Catharanthus roseus. Despite the ethanol extract having higher total antioxidant properties and flavonoid content, the mixed-solvent extract exhibited higher EC₅₀ for reducing power and lower IC₅₀ for ABTS, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and metal chelating activities. Molecular docking studies indicated that compounds such as catechin, rutin, epicatechin, quercetin, and kaempferol significantly inhibit the ROS-generating enzyme microsomal prostaglandin E synthase 1 (mPGES-1). Conclusions: The mixed-solvent extract had higher levels of catechin hydrate, rutin hydrate, trans-ferulic acid, and vanillic acid, whereas the ethanol extract contained more (-) epicatechin, catechol, kaempferol, quercetin, and trans-cinnamic acid. While the extracts displayed antioxidant activity, the phytoconstituents also inhibited ROS-generating mPGES-1. These results identify key compounds with potential for developing new chemotherapeutic agents against ROS.