Free radicals and antioxidans

Free radicals, antioxidants, and human disease: curiosity, cause, or consequence?

Disturbed glucose metabolism in diabetes mellitus (DM) patients affects bone metabolism and its microenvironment, which significantly impaired bone regeneration, making bone defect repair in DM patients a big challenge. Although autologous and allogeneic bone grafts are common therapeutic approaches, they do not achieve the desired therapeutic outcome, especially when targeting the complex pathologic microenvironment at the lesion site in DM patients. Therefore, various biomaterials have been developed to facilitate DM bone repair. With advances in bone tissue engineering, the focus of the study has transitioned from biologically inert to bioactive biomaterials. However, due to the lack of a comprehensive understanding of the pathologic microenvironment of diabetic bone defects, many biomaterials have not achieved satisfactory therapeutic results. Here, the mechanisms by which the pathological microenvironment affects bone regeneration are dissected. Then, recent advances in biomaterial therapeutic strategies based on these pathological microenvironments are comprehensively reviewed from seven aspects. Finally, current limitations that still need to be addressed are discussed, and feasible strategies for improvement and perspectives are presented. This review will certainly spark new ideas to develop more high-performance versatile biomaterials to improve the repair of bone defects under pathological conditions.

This study aimed to evaluate the potential benefits of chitosan oligosaccharide (COS) on red claw crayfish (Cherax quadricarinatus) and explore its underlying mechanisms. The crayfish were randomly divided into six groups, and the diets were supplemented with COS at levels of 0 (C0), 0.2 (C1), 0.4 (C2), 0.6 (C3), 0.8 (C4), and 1 (C5) g kg⁻¹. Treatment with COS significantly improved the growth performance of the crayfish with a higher weight gain rate (WGR) and specific growth rate (SGR) in the C2 group compared to the C0 group. Additionally, the content of crude protein in the crayfish muscles in the C1 group was significantly higher than that of the C0 group. Regarding non-specific immunity, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and alkaline phosphatase (AKP), and the levels of expression of the genes related to immunity (SOD; anti-lipopolysaccharide factor [ALF]; thioredoxin1 [Trx1]; C-type lysozyme, [C-LZM]; and GSH-Px) in the hepatopancreas and hemolymph increased significantly (P < 0.05) after supplementation with 0.4 g kg⁻¹ of COS, while the content of malondialdehyde (MDA) decreased (P < 0.05). The survival rate of C. quadricarinatus increased (P < 0.05) in the C2, C3, C4, and C5 groups after the challenge with Aeromonas hydrophila. This study found that COS has the potential to modulate the composition of the intestinal microbiota and significantly reduce the abundance of species of the phylum Proteobacteria and the genera Aeromonas and Vibrio in the gut of C. quadricarinatus, while the abundance of bacteria in the phylum Firmicutes and the genus Candidatus_Hepatoplasma improved significantly. This study suggests that the inclusion of COS in the diet of C. quadricarinatus can enhance growth, boost immunity, and increase resistance to infection with A. hydrophila, especially when supplemented at 0.4–0.8 g kg⁻¹.

The hydrolyzate of wheat germ albumin (WGA) has high biological activity. Under the action of proteases, WGA can release bioactive peptides such as antioxidant, antihypertensive, anti fatigue, antibacterial, etc. Ultrafiltration was used to separate different molecular weight peptides from WGA. The effects of proteases on hydrolysis of WGA and biological activities of different molecular weight peptides were comparatively studied and identified target bioactive peptides. When WGA was hydrolyzed by the enzymatic hydrolysis with papain, alcalase, acid protease, and neutral protease, the results showed that papain had the highest DPPH• scavenging rate. The scavenging rate of O²⁻ radical for peptides with MW (<3 KDa) was higher than that of the other two components (WGA and >3 KDa), with an IC₅₀ of 4.59 mg/mL, and its reducing power was significantly higher than that of WGA and MW (>3 KDa). The speculated identification results showed the screened amino acid (AA) sequences (<3 KDa), which mainly consisted of four types: NIYLNFDALHGDKEHGGVR, TGGDGGPGKPTT, DVFWIPRFFVQ, and EEEDKNDKWHRVE. The molecular weight of the dominant AA sequence was concentrated between 1000 and 2200 Da, and almost all functional peptides had high biological activity AA, such as His, Leu, Cys, Lys, and Tyr.

The current study aims to quantify HPLC-DAD polyphenolics in the crude extracts of Desmodium elegans, evaluating its cholinesterase inhibitory, antioxidant, molecular docking and protective effects against scopolamine-induced amnesia in mice. A total of 16 compounds were identified which include gallic acid (239 mg g^-1), p-hydroxybenzoic acid (11.2 mg g^-1), coumaric acid (10.0 mg g^-1), chlorogenic acid (10.88 mg g^-1), caffeic acid (13.9 mg g^-1), p-coumaroylhexose (41.2 mg g^-1), 3-O-caffeoylquinic acid (22.4 mg g^-1), 4-O-caffeoylquinic acid (6.16 mg g^-1), (+)-catechin (71.34 mg g^-1), (-)-catechin (211.79 mg g^-1), quercetin-3-O-glucuronide (17.9 mg g^-1), kaempferol-7-O-glucuronide (13.2 mg g^-1), kaempferol-7-O-rutinoside (53.67 mg g^-1), quercetin-3-rutinoside (12.4 mg g^-1), isorhamnetin-7-O-glucuronide (17.6 mg g^-1) and isorhamnetin-3-O-rutinoside (15.0 mg g^-1). In a DPPH free radical scavenging assay, the chloroform fraction showed the highest antioxidant activity, with an IC₅₀ value of 31.43 µg mL^-1. In an AChE inhibitory assay, the methanolic and chloroform fractions showed high inhibitory activities causing 89% and 86.5% inhibitions with IC₅₀ values of 62.34 and 47.32 µg mL^-1 respectively. In a BChE inhibition assay, the chloroform fraction exhibited 84.36% inhibition with IC₅₀ values of 45.98 µg mL^-1. Furthermore, molecular docking studies revealed that quercetin-3-rutinoside and quercetin-3-O-glucuronide fit perfectly in the active sites of AChE and BChE respectively. Overall, the polyphenols identified exhibited good efficacy, which is likely as a result of the compounds' electron-donating hydroxyl groups (-OH) and electron cloud density. The administration of methanolic extract improved cognitive performance and demonstrated anxiolytic behavior among tested animals.

Ketorolac tromethamine (KT), is a widely used non-steroidal anti-inflammatory drug (NSAID) for treating moderate to severe pain. However, the use of KT has been restricted due to its highly toxic attributes that lead to severe gastric ulceration and bleeding. The protective effects of exogenous melatonin (MT) has been reported in conditions associated with gastro-intestinal disorders. This study aims at exploring the role of gastric endogenous MT level and it's metabolizing enzyme AANAT, at the onset of ketorolac mediated toxicities in the gastric mucosa. Gastric mucosal damage was induced in experimental rats by oral administration of graded doses of KT, where 50 mg/kg b.w. of KT was observed to incur maximum gastric lesions. However, gastric damages were found to be protected in rats, pre-treated with 60 mg/kg b.w. of MT. Post-sacrifice, mean ulcer index, oxidative status, total melatonin levels and enzyme activities associated with MT biosynthesis and catabolism were estimated. The results reveal that KT decreases AANAT activity with a concomitant decline in endogenous MT level which cumulatively aggravates gastric toxicity. Moreover, exogenous MT administration has been found to be protective in ameliorating this ulcerogenic process in rats, challenged with KT. Biochemical and histo-pathological observations revealed the reduction in oxidative stress level and replenishment of depleted gastric MT levels in MT pre-treated animals, which might be the causative factors in conferring protection to the gastric tissues and residing mitochondria. The results revealed a correlation between depleted gastric MT level and ulcer formation, which unveiled a novel ulcerogenic mechanism. This may bring forth future therapeutic relevance for treating patients suffering from KT mediated acute gastric toxicities.