Gongronema latifolium Benth. leaf extract attenuates diabetes-induced neuropathy via inhibition of cognitive, oxidative stress and inflammatory response.

BACKGROUND: Gongronema latifolium (G. latifolium) Benth. leaves are traditionally used to treat diabetes mellitus (DM) and other diseases in Nigeria and West Africa. This study was performed to evaluate the neuroprotective effect of aqueous extract of G. latifolium leaf against DM. Antidiabetic activity of G. latifolium extracts (6.36, 12.72 and 25.44 mg kg-1 , i.p.) was determined in alloxan-induced diabetic rats. Fasting blood glucose level and oxidative stress markers catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA), and nitric oxide (NO) levels were measured. Cognitive biomarkers acetylcholinesterase (AChE), butyrylcholinesterase (BChE), dopamine (DOPA), serotonin, epinephrine and norepinephrine and cyclooxygenase (COX-2) were measured in the brain of controls and of G. latifolium-treated diabetic rats. RESULTS: Administration of G. latifolium leaf extract to diabetic rats significantly restored the alterations in the levels of fasting blood glucose (FBG). The MDA and NO levels were significantly reduced with an improvement in CAT, SOD, and GPx activity in the kidneys and brains of diabetic rats treated with G. latifolium. Gongronema latifolium also significantly decreased the levels of AChE, BChE, DOPA, serotonin, epinephrine, and nor-epinephrine in diabetic rats. G. latifolium effectively ameliorated COX-2 in diabetic rats. CONCLUSION: This study showed that leaf extract of G. latifolium improved antioxidant defense against oxidative stress. It displays a neuroprotective effect resulting in the modulation of brain neurotransmitters, which could be considered as a promising treatment therapy. © 2020 Society of Chemical Industry.

Effect of sub-dermal exposure of silver nanoparticles on hepatic, renal and cardiac functions accompanying oxidative damage in male Wistar rats.

Silver nanoparticles (AgNPs) have been generally used due to their strong antibacterial, antiviral and antifungal and antimicrobial properties. However, their toxicity is a subject of sustained debate, thus requiring further studies. Hence, this study examines the adverse effects of the sub-dermal administered dose of AgNPs (200 nm) on the liver, kidney and heart of male Wistar rats. Thirty male rats were randomly distributed into six groups of five animals per group. Group A and D served as the control and received distilled water for 14 and 28 days respectively. Groups B and C were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 14 days while E and F were sub-dermally exposed to AgNPs at 10 and 50 mg/kg daily for 28 days. The liver, kidney and heart of the animals were collected, processed and used for biochemical and histological analysis. Our results revealed that the subdermal administration of AgNPs induced significant increased (p < 0.05) activities of aspartate aminotransferase (AST), alanine transferase (ALT), alkaline phosphatase (ALP), urea, creatinine, and malondialdehyde (MDA) while decreasing the levels of glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and total thiol groups in the rat tissues. Our findings suggest that the subdermal administration of AgNPs induced oxidative stress and impaired the hepatic, renal and cardiac functions of male Wistar rats.

Therapeutic efficacy of Clompanus pubescens leaves fractions via downregulation of neuronal cholinesterases/Na+-K+ATPase/IL-1 ß, and improving the neurocognitive and antioxidants status of streptozotocin-induced diabetic rats.

The increasing global burden of diabetes mellitus has called for the search for a therapeutic alternative that offers better activities and safety than conventional chemotherapy. Herein, we evaluated the neuroprotective and antioxidant properties of different fractions (ethyl acetate, N-butanol and residual aqueous) of Clompanus pubescens leaves in streptozotocin (STZ)-induced diabetic rats. Our results revealed a significant elevation in the levels of blood glucose, pro-inflammatory cytokines, lipid peroxidation, neuronal activities of acetylcholinesterase, butyrylcholinesterase, nitric oxide, epinephrine, norepinephrine, and Na+/K+-ATPase in diabetic non treated rats. In addition, decreased levels of enzymatic and non-enzymatic antioxidants were observed. Treatment with different fractions of C. pubescens leaves resulted in significant reversal of the biochemical alteration and improved the neurocognitive deficit in STZ induced diabetic rats. However, the ethyl-acetate fraction demonstrated higher activities than the other fractions and was characterized for its phytoconstituents, revealing the presence of Gallic acid (713.00 ppm), catechin (0.91 ppm), ferulic acid (0.98 ppm), rutin (59.82 ppm), quercetin (3.22 ppm) and kaempferol (4.07 ppm). Our molecular docking analysis revealed that these compounds exhibited different binding affinities and potentials for targeting BChE/AChE/ IL-1 ß/Na+ -K+ -ATPase. However, only Kampferol and ferulic exhibited good drug-like, ADMET, and permeability properties suitable for use as a neuronal drug target agent. Hence, the ethyl-acetate fraction of C. pubescens leaves could be considered as a source of promising bioactive metabolite for the treatment and management of cognitive impairments related to type II diabetes mellitus.

Luteolin-Rich Extract of Thespesia garckeana F. Hoffm. (Snot Apple) Contains Potential Drug-Like Candidates and Modulates Glycemic and Oxidoinflammatory Aberrations in Experimental Animals.

The present study evaluated the polyphenolic contents and hypoglycemic, antioxidant, and anti-inflammatory effects of the diethyl ether fraction of Thespesia garckeana using various in vitro and in vivo models. Total phenol and flavonoid contents of the extract were 613.65 ± 2.38 and 152.83 ± 1.56 mg/100 g dry weight, respectively. The extract exhibited in vitro antioxidant activities against DPPH, FRAP, LPO, and ABTS with respective half-maximal inhibitory concentration (IC50) values of 30.91 ± 0.23, 16.81 ± 0.51, 41.29 ± 1.82, and 42.39 ± 2.24 µg/mL. In vitro anti-inflammatory studies using membrane stabilization, protein denaturation, and proteinase activities revealed the effectiveness of the extract with respective IC50 values of 54.45 ± 2.89, 93.62 ± 3.04, and 56.60 ± 2.34 µg/mL, while in vitro hypoglycemic analysis of the extract revealed inhibition of α-amylase (IC5064.59 ± 3.29 µg/mL) and enhancement of glucose uptake by yeast cells. Interestingly, the extract demonstrated in vivo hypoglycemic and anti-inflammatory effects in streptozotocin- (STZ-) induced diabetic and xylene-induced ear swelling models, respectively. In addition, the extract improved insulin secretion, attenuated pancreatic tissue distortion and oxidative stress, and increased the activities of superoxide dismutase (SOD), catalase, and reduced glutathione (GSH), while reducing the concentration of LPO in the diabetic rats. A high-performance liquid chromatography (HPLC) analysis identified the presence of catechin (6.81e - 1 ppm), rutin (8.46 e - 1 ppm), myricetin, apigenin (4.019 e - 1 ppm), and luteolin (15.09 ppm) with respective retention times (RTs) of 13.64, 24.269, 27.781, 29.58, and 32.23 min, and these were subjected to a pharmacoinformatics analysis, which revealed their drug-likeness and good pharmacokinetic properties. A docking analysis hinted at the potential of luteolin, the most abundant compound in the extract, for targeting glucose-metabolizing enzymes. Thus, the present study provides preclinical insights into the bioactive constituents of T. garckeana, its antioxidant and anti-inflammatory effects, and its potential for the treatment of diabetes.

Sterculia tragacantha Lindl Leaf Extract Ameliorates STZ-Induced Diabetes, Oxidative Stress, Inflammation and Neuronal Impairment.

BACKGROUND: Sterculia tragacantha is a medicinal plant commonly used in the western part of Nigeria, for managing diabetes mellitus. However, there is a dearth of scientific information on the antidiabetic and neuroprotective properties of the plant. METHODS: The in silico, in vitro and in vivo models were used to evaluate the antioxidants, antidiabetic, anti-inflammatory and neuroprotective potential of aqueous extract of Sterculia tragacantha leaf (AESTL) in streptozotocin (STZ)-induced diabetic rats. Thirty (30) male albino rats (155.34±6.33 g) were intraperitoneal injected with 40 mg/kg of freshly prepared streptozotocin and were divided into 5 groups (A-E) of 6 animals each. Groups A-D were treated with 0, 150 and 300 mg/kg of AESTL, and 200 mg/kg body weight of metformin respectively, while group E serve as the normal control. RESULTS: The results of in vitro analysis revealed dose-dependent antioxidant activities; ABTS (IC50 = 63.03±2.57 µg/mL), DPPH (117.49±2.35 µg/mL), FRAP (15.19±0.98 mmol/100g), TAC (43.38±0.96 mg/100g), hypoglycaemic effect; α-amylase (IC50 = 77.21±4.35 µg/mL) and α-glucosidase (IC50 = 443.25±12.35), and anti-cholinesterase; AChE (IC50 = 113.07±3.42 µg/mL) and BChE (IC50 = 87.50±4.32 µg/mL) activities of AESTL. In vivo study revealed dose-dependent hypoglycemic effect and body weight improvement in rats treated with the AESTL. In addition, AESTL improved the antioxidant status and attenuated STZ-induced dysregulations of Na+-K+-ATPase, cholinesterases and neurotransmitters in the brain tissue of experimental rats. The results also demonstrated that AESTL could regulate anti-inflammatory response via inhibition of COX-2/NO signaling axis in the brain of diabetic rats. Molecular docking analysis revealed that epicatechin and procyanidin B2, the bioactive compounds from AESTL, docked well to the binding cavities of acetylcholinesterase, butyrylcholinesterase, α-amylase and α-glucosidase with binding affinities ranges between -8.0 and -11.4 kcal/mol, suggesting that these compounds are the bioactive component that could be responsible for the antidiabetic and neuroprotective activities of AESTL. CONCLUSION: The results of the present study strongly suggested that the AESTL extract could be very useful for halting diabetes progression and its associated neuroinflammation complications.