Modulation of mitochondrial permeability transition pore opening by Myricetin and prediction of its-drug-like potential using in silico approach.

Myricetin has been demonstrated to have multiple biological functions with promising research and development prospects. This study investigated the effect of myricetin on liver mitochondrial membrane permeability transition pores and its inhibitory potential on proteins that are important in the apoptotic process in silico. Mitochondrial swelling was assessed as changes in absorbance under succinate-energized conditions. Cytochrome c release, mitochondrial-lipid peroxidation, caspase 3 and 9 expressions, as well as calcium ATPase, were assessed. Pharmacokinetic properties of myricetin were predicted through the SwissADME server while the binding affinity of myricetin toward the proteins was computed using the AutodockVina Screening tool. The conformational stability of protein-ligand interactions was evaluated using molecular dynamics simulations analysis through the iMODS server. Myricetin inhibited the opening of the mitochondrial permeability transition pore and also reversed the increase in mitochondrial lipid peroxidation caused by calcium and other toxicants. Myricetin also caused a reduction in the expression of caspase 3 and 9 as well as calcium ATPase activity. The molecular docking results revealed that myricetin had a considerable binding affinity to the pocket site of caspase 3 and 9 as well as calcium ATPase. Myricetin showed a good drug-likeness based on the predicted pharmacokinetic properties as revealed by low CYP 450 inhibitory promiscuity and relatively low toxicity. It could therefore be suggested that myricetin could be useful in the management of diseases where too many apoptosis occur characterized by excessive tissue wastage such as neurodegenerative conditions and could as well play a role in protecting the physicochemical properties of membrane bilayers from free radical-induced severe cellular damage.

Combined effect of metformin and gallic acid on inflammation, antioxidant status, endoplasmic reticulum (ER) stress and glucose metabolism in fructose-fed streptozotocin-induced diabetic rats.

Over time, diabetes patients usually need combination therapy involving two or more agents, including phytonutrients to attain therapeutic targets. The purpose of this research is to elucidate the combined effect of metformin and gallic acid (GA) on glucose metabolism, inflammation as well as oxidative and endoplasmic reticulum (ER) stresses in fructose-fed diabetic rats. Thirty-five rats of Wistar strain were arbitrarily distributed into five groups, each containing seven animals as follows: normal control, diabetic control, groups administered 100 mg/kg bw metformin only, 50 mg/kg bw gallic acid only and a combination of both. Experimental animals were made diabetic by single injection of 40 mg/kg streptozotocin (intraperitoneally) subsequent to 14 days administration of 10 % fructose prior. Treatment of rats continued for 21 days following diabetes confirmation. Glucose and insulin levels as well as lipid profile were evaluated in the serum, while activities of catalase and superoxide dismutase were estimated in both liver and pancreas. In addition, levels of malondialdehyde, interleukin-6 and tumor necrosis factor-alpha, as well as expression of activating transcription factor-4 were evaluated in liver and pancreas of diabetic rats. Activities of glucose-6-phosphatase and glucokinase were also determined in liver of diabetic animals. Metformin only, GA only and combination of metformin and GA significantly improved antioxidant status and glucose homeostasis while inflammation and endoplasmic reticulum stress were significantly ameliorated in diabetic rats. Metformin/GA combination appeared to improve glucose metabolism by increasing insulin level and ameliorating the dysregulated activities of glucose metabolizing enzymes and ER stress better than either metformin only or GA only. It could be concluded that coadministration of metformin/GA produced a combined effect in ameliorating diabetes in Wistar rats and could be considered in treatment of diabetes.

Combination of donepezil and gallic acid improves antioxidant status and cholinesterases activity in aluminum chloride-induced neurotoxicity in Wistar rats.

The present study compared the effect of donepezil only and combination of donepezil and gallic acid on oxidative status and cholinesterase activity in the brain of Wistar rats administered AlCl3 for 60 days. Twenty-eight rats (180 - 200 g) were arbitrarily distributed into four groups of seven animals apiece. Group 1 served as normal control and received distilled water throughout the study. Group 2 animals received only AlCl3 throughout the study while animals in groups 3 and 4 were administered donepezil only (10 mg/kg) and combination of donepezil (10 mg/kg) and gallic acid (50 mg/kg), respectively, in addition to AlCl3. Treatments were administered orally by gavage. At the end of the study, animals were sacrificed and activities of acetylcholinesterase, butyrylcholinesterase, superoxide dismutase (SOD) and catalase as well as levels of malondialdehyde (MDA), total thiol and nitric oxide (NO) were evaluated in the brain. Histopathological study was conducted on the hippocampus of experimental animals. Results showed that AlCl3 significantly (p < 0.05) increased brain activities of cholinesterases and levels of MDA and NO with a concomitant decrease in total thiol level as well as activities of SOD and catalase. Donepezil only and combination of donepezil and gallic acid reversed these alterations. Also, combination of donepezil and gallic acid significantly (p < 0.05) improved antioxidant status better than donepezil only. It could be concluded that a synergy might exist between gallic acid and donepezil especially in ameliorating oxidative stress associated with AlCl3-induced neurotoxicity.

Investigation of bioactive compounds in Crassocephalum rubens leaf and in vitro anticancer activity of its biosynthesized gold nanoparticles.

The development of cancer therapies has become difficult due to high metastasis, and lack of tissue selectivity, which in most cases affects normal cells. Demand for anticancer therapy is therefore increasing on daily basis. Gold nanoparticles (AuNPs) have many applications in biomedical field. Biological synthesis of AuNPs using aqueous extract of Crassocephalum rubens (AECR) was designed to investigate the in vitro anticancer potential. The synthesized AuNPs were characterized by UV-vis spectroscopy, high-resolution transmission electron microscopy, and Fourier transform infrared spectroscopy. The characterization results showed the formation of green AuNPs of wavelength 538 nm, and mostly spherical AuNPs with 20 ±â€¯5 nm size. Significant anticancer activity of the AECR-AuNPs on MCF-7 and Caco-2 cells was noted at higher concentrations (125 and 250 µg/mL) during 24 and at all concentrations tested during 48 h. It can therefore be concluded that AECR leaves can mediate stable AuNPs with anticancer properties.

Biological synthesis of gold and silver nanoparticles using leaf extracts of Crassocephalum rubens and their comparative in vitro antioxidant activities.

The use of plant and plant products in the synthesis of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) is made possible because of the natural inherent phytochemicals responsible for the reduction of respective metallic salts to nanoparticle forms, and ensuring therapeutic applicability. In this study, synthesis of AgNPs and AuNPs was performed using two different aqueous extraction methods for Crassocephalum rubens: maceration using laboratory method of extraction (cold aqueous extract of Crassocephalum rubens (AECR)), and decoction using traditional healer's method of extraction (hot aqueous crude extract of Crassocephalum rubens (CECR)). The synthesized nanoparticles were characterized using various methods, and in vitro antioxidant potential were thereafter investigated. The characterization results indicated the formation of mostly spherical-shaped AgNPs and AuNPs with surface plasmon resonance (SPR) band of 470 nm and 540 nm, respectively. The nanoparticles possess high antioxidant potentials but AECR synthesized AuNPs exhibited the least phytochemical contents and antioxidant potential when compared to other nanoparticles. It can therefore be concluded that extraction method and nanoparticle type are important factors that could influence the antioxidant properties of the nanoparticles. Further studies using these nanoparticles as anticancer or anti-inflammatory agent in both in vitro and in vivo are underway.