Insight into antioxidant-like activity and computational exploration of identified bioactive compounds in Talinum triangulare (Jacq.) aqueous extract as potential cholinesterase inhibitors.

BACKGROUND: Recent reports have highlighted the significance of plant bioactive components in drug development targeting neurodegenerative disorders such as Alzheimer's disease (AD). Thus, the current study assessed antioxidant activity and enzyme inhibitory activity of the aqueous extract of Talinum triangulare leave (AETt) as well as molecular docking/simulation of the identified phytonutrients against human cholinesterase activities. METHODS: In vitro assays were carried out to assess the 2,2- azinobis (3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) cation radicals and cholinesterase inhibitory activities of AETt using standard protocols. High performance liquid chromatography coupled with diode-array detection (HPLC-DAD) was employed to identify compounds in AETt. Also, for computational analysis, identified bioactive compounds from AETt were docked using Schrodinger's GLIDE against human cholinesterase obtained from the protein data bank ( https://www.rcsb.org/ ). RESULTS: The results revealed that AETt exhibited a significant concentration-dependent inhibition against ABTS cation radicals (IC50 = 308.26 ± 4.36 µg/ml) with butylated hydroxytoluene (BHT) as the reference. Similarly, AETt demonstrated a significant inhibition against acetylcholinesterase (AChE, IC50 = 326.49 ± 2.01 µg/ml) and butyrylcholinesterase (BChE, IC50 = 219.86 ± 4.13 µg/ml) activities with galanthamine as the control. Molecular docking and simulation analyses revealed rutin and quercetin as potential hits from AETt, having showed strong binding energies for both the AChE and BChE. In addition, these findings were substantiated by analyses, including radius of gyration, root mean square fluctuation, root mean square deviation, as well as mode similarity and principal component analyses. CONCLUSION: Overall, this study offers valuable insights into the interactions and dynamics of protein-ligand complexes, offering a basis for further drug development targeting these proteins in AD.

Nephroprotective Effects of Caffeine, Vanillin, and Their Combination against Experimental AlCl3-Induced Renal Toxicity in Adult Male Wistar Rats.

Aluminum (Al) is known to be a nephrotoxic metal that can cause renal toxicity in both humans and animals. The use of functional foods has been reported to have significance in managing the toxic effects associated with such metals. This study aimed to assess the potential protective effects of caffeine, vanillin, and their combination in mitigating AlCl3-induced renal toxicity in adult male Wistar rats. A total of thirty (30) adult male Wistar rats weighing between 150 and 200 g were randomly divided into five groups, each consisting of six rats (n = 6). Group 1 served as the control, while the remaining treatment groups received a daily oral dose of 100 mg/kg AlCl3 for a duration of 21 days. In addition, groups 3-5 were coadministered 50 mg/kg body weight (bw) of caffeine, vanillin, and a combination (50/50 mg/kg bw) of both substances, respectively. In the results, AlCl3-treated showed a significant (p < 0.05) increase in serum biomarkers such as ALT, ALP, urea, and creatinine, and a significant (p < 0.05) decrease in serum total proteins (TPs). The renal tissue's antioxidant system, including SOD, CAT, GPx, and GSH, exhibited a significant (p < 0.05) reduction, accompanied by an elevated MDA level. However, the administration of caffeine, vanillin, and their combination resulted in a significant (p < 0.05) decrease in serum ALT, ALP, urea, and creatinine, and a significant (p < 0.05) increase in serum TP. Furthermore, following the treatment, there was a significant (p < 0.05) increase in renal SOD, CAT, GPx, and GSH levels, along with a reduction in the MDA level. In addition, the treatment for 21 days caused a significant (p < 0.05) reversal to the altered histomorphological architecture. These findings suggest that caffeine, vanillin, and their combination could potentially be an effective regimen in managing AlCl3-induced renal toxicity.

Antioxidant evaluation and computational prediction of prospective drug-like compounds from polyphenolic-rich extract of Hibiscus cannabinus L. seed as antidiabetic and neuroprotective targets: assessment through in vitro and in silico studies.

BACKGROUND: Reports have implicated diabetes mellitus (DM) and Alzheimer's disease (AD) as some of the global persistent health challenges with no lasting solutions, despite of significant inputs of modern-day pharmaceutical firms. This study therefore, aimed to appraise the in vitro antioxidant potential, enzymes inhibitory activities, and as well carry out in silico study on bioactive compounds from polyphenolic-rich extract of Hibiscus cannabinus seed (PEHc). METHODS: In vitro antioxidant assays were performed on PEHc using standard methods while the identification of phytoconstituents was carried out with high performance liquid chromatography (HPLC). For the in silico molecular docking using Schrodinger's Grid-based ligand docking with energetics software, seven target proteins were retrieved from the database ( https://www.rcsb.org/ ). RESULTS: HPLC technique identified twelve chemical compounds in PEHc, while antioxidant quantification revealed higher total phenolic contents (243.5 ± 0.71 mg GAE/g) than total flavonoid contents (54.06 ± 0.09 mg QE/g) with a significant (p < 0.05) inhibition of ABTS (IC50 = 218.30 ± 0.87 µg/ml) and 1, 1-diphenyl-2-picrylhydrazyl free radicals (IC50 = 227.79 ± 0.74 µg/ml). In a similar manner, the extract demonstrated a significant (p < 0.05) inhibitory activity against α-amylase (IC50 = 256.88 ± 6.15 µg/ml) and α-glucosidase (IC50 = 183.19 ± 0.23 µg/ml) as well as acetylcholinesterase (IC50 = 262.95 ± 1.47 µg/ml) and butyrylcholinesterase (IC50 = 189.97 ± 0.82 µg/ml), respectively. Furthermore, In silico study showed that hibiscetin (a lead) revealed a very strong binding affinity energies for DPP-4, (PDB ID: 1RWQ) and α-amylase (PDB ID: 1SMD), gamma-tocopherol ( for peptide-1 receptor; PDB ID: 3C59, AChE; PDB ID: 4EY7 and BChE; PDB ID: 7B04), cianidanol for α-glucosidase; PDB ID: 7KBJ and kaempferol for Poly [ADP-ribose] polymerase 1 (PARP-1); PDB ID: 6BHV, respectively. More so, ADMET scores revealed drug-like potentials of the lead compounds identified in PEHc. CONCLUSION: As a result, the findings of this study point to potential drug-able compounds in PEHc that could be useful for the management of DM and AD.

Synthesized gold nanoparticles mediated by Crassocephalum rubens extract down-regulate KIM-1/NGAL genes and inhibit oxidative stress in cadmium-induced kidney damage in rats.

Cadmium (Cd) exposure induces kidney damage by mediating oxidative stress and inflammation. In this study, the role of Crassocephalum rubens-gold nanoparticles (C. rubens-AuNPs) in down-regulating kidney injury molecules-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) genes and inhibiting oxidative stress in Cd-induced kidney damage in rats was investigated. Thirty male Wistar rats were distributed randomly into six groups (n = 5). Group I served as control, while groups II, III, IV, and V rats were administered with 20 mg/kg b.w. cadmium chloride (CdCl2) for five consecutive days. Groups III, IV, and V rats were treated, 24 h after the last dose of CdCl2, with silymarin, 5 mg/kg and 10 mg/kg C. rubens-AuNPs, respectively, for 14 days. Group VI rats received 10 mg/kg C. rubens-AuNPs only for 14 days. Animals were sacrificed 24 h after the last dose of the treatment. Biochemical parameters such as kidney function markers, biomarkers of nephrotoxicity, and oxidative stress markers were assayed. Results indicated that 20 mg/kg b.w. CdCl2 caused kidney damage, as evidenced by significant (p < 0.05) increase in the levels of serum urea and creatinine, malondialdehyde, reduced level of superoxide dismutase (SOD), and increased mRNA expression of the kidney injury biomarkers (KIM-1 and NGAL genes), when compared with the control. However, these changes were attenuated by both doses of C. rubens-AuNPs when compared with Cd-induced nephrotoxic rats. It can be suggested that C. rubens-AuNPs have the potential to ameliorate kidney damage induced by Cd via oxidative stress inhibition and down-regulation of KIM-1/NGAL genes.

Polyphenolic-rich extracts of Andrographis paniculata mitigate hyperglycemia via attenuating ß-cell dysfunction, pro-inflammatory cytokines and oxidative stress in alloxan-induced diabetic Wistar albino rat.

BACKGROUND: This study sought to investigate anti-hyperglycemic potentials of free and bound phenolic-rich extracts of Andrographis paniculata (A. paniculata) leaves, commonly called "king of the bitter", a plant locally employed in folkloric alternative medicine. METHOD: In vitro antioxidant potentials such as total phenolic and flavonoid contents were evaluated in addition to phosphomolybdenum reducing total antioxidant activity in bound and free polyphenol-rich extracts of A. paniculata. Also, following induction of diabetes through a single intraperitoneal injection of freshly prepared alloxan monohydrate (150 mg/kg body weight, b.w), diabetic rats were divided into seven (7) treatment groups with six rats each (n = 6) i.e. group 1 (normal control), 2 (diabetic untreated), 3 (5 mg/kg glibenclamide -treated control), while 4-7 were administered 50 and 100 mg/kg b.w of free and bound phenolic extracts of A. paniculata, respectively for twenty-one (21) days. RESULTS: There was a significant (p < 0.05) difference in hematological indices, hepatic biomarkers, total protein, antioxidant enzymes activities, total thiol and fasting blood glucose levels of diabetic groups administered polyphenolic-rich extracts of A. paniculata compared to diabetic untreated control. Similarly, serum insulin levels, hexokinase and glucose-6-phoshatase activities were significantly (p < 0.05) improved in phenolic-rich extracts of A. paniculata-treated diabetic groups compared to diabetic untreated control. A significant (p < 0.05) reduction was as well observed in the levels of inflammatory biomarkers such as interleukin-6 (IL-6) and tumor necrosis factor (TNFα) among extract of A. paniculata administered diabetic groups compared diabetic untreated group. CONCLUSIONS: Anti-hyperglycemic activities demonstrated by polyphenolic-rich extracts of A. paniculata when compared to glibenclamide and normal control, could possibly have been occasioned by ß-cell protection, restoration of glycolytic enzymes as well as mitigation of inflammatory markers via antioxidant defensive/protective properties of the extracts.