p-Coumaric acid protects against D-galactose induced neurotoxicity by attenuating neuroinflammation and apoptosis in mice brain.

D-galactose (D-gal) induced senescence in rodents is a widely used model for assessment of molecules affecting brain ageing. Chronic administration of D-gal causes neuroinflammation leading to cognitive deficit and memory impairment which represent Alzheimer's dementia. In present study, we investigated the neuroprotective effects of the natural phenol, p-Coumaric acid (PCA) and its underlying mechanism in the chronic D-gal treated mice. Subcutaneous administration of D-gal (150 mg/kg) to Swiss albino mice for 42 consecutive days resulted in cognitive impairment as observed in Morris water maize (MWM) and Y maze test, which was ameliorated by concurrent treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.). Importantly, PCA treatment attenuated the D-gal induced oxidative stress and significantly inhibited acetylcholinesterase (AChE) activity in mice brain. Furthermore, PCA treatment significantly lowered levels of inflammatory marker nuclear factor kappa B (NFκB) and reduced levels of proapoptotic enzyme caspase3. We also observed that PCA treatment exhibited ß-secretase enzyme (BACE1) inhibitory effect. However, our results revealed that PCA treatment failed to decrease the level of advanced glycation end products both in vitro and in vivo. Taken together, current study demonstrated the significant neuroprotective effect of PCA against D-gal induced oxidative stress, neuroinflammation, cognitive impairment and apoptosis.

p-Coumaric acid mitigates lipopolysaccharide induced brain damage via alleviating oxidative stress, inflammation and apoptosis.

OBJECTIVES: Systemic administration of lipopolysaccharide induces neuroinflammation leading to cognitive deficit and memory impairment. Herein, we investigated the effects of p-Coumaric acid (PCA) in LPS induced neuroinflammation in mice. PCA is reported to possess free radicle scavenging and neuroprotective action. METHODS: Mice received treatment with PCA (80 mg/kg, and 100 mg/kg, p.o.) for 28 days. LPS (0.25 mg/kg) was administered intraperitoneally from Day 15 to 21, to all groups. Memory impairment and cognitive deficit were assessed by MWM and Y maze test, followed by estimation of ROS, TNF-α, IL-6, caspase-3 and c-Jun in the brain homogenate by ELISA. Histopathological changes were investigated using Nissl and H&E staining. KEY FINDINGS: PCA attenuated increased oxidative stress, significantly increasing SOD, GSH levels and decreasing MDA level and AChE activity in mice brain, lowered the levels of TNF-α and IL-6 indicating protection against neuroinflammatory reaction. PCA also suppressed neuronal apoptosis, as indicated by decreased levels of caspase-3 and c-Jun. Further, histopathological findings revealed that PCA attenuated neuronal loss and pathological abnormalities in the hippocampus. CONCLUSIONS: Our findings give compulsive evidence suggesting a protective effect of PCA in neuroinflammation, cognitive impairment and neuronal apoptosis induced by LPS, through its antioxidant, AChE inhibitory, anti-inflammatory and antiapoptotic activity determined by behavioural, biochemical and histopathological measures.

Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punica granatum Linn. leaves extract.

With an objective to develop Complementary and Alternative Medicine for the treatment of diabetic nephropathy, the present study investigated the protective effects of methanolic extract of Punica granatum leaves (MPGL) in streptozotocin-induced diabetic nephropathy. Diabetic nephropathy has become a leading cause of end stage renal failure worldwide. P. granatum, due to its anti-diabetic, anti-inflammatory and antioxidant activities may retard the progression of diabetic nephropathy. In this study, diabetes was induced by a single injection of streptozotocin (STZ, 45 mg/kg, i.p.) in rats. STZ-diabetic rats were treated with oral doses of MPGL (100, 200 and 400 mg/kg) for 8 weeks. At the end of the experimental period, body and kidney weight and blood glucose levels were determined. Serum and urine parameters were investigated. Antioxidant enzymes and lipid peroxide levels were determined in the kidney along with histopathological examination of the same. MPGL significantly increased body weight, lowered blood glucose levels and ameliorated kidney hypertrophy index in the STZ-diabetic rats. The extract also decreased the levels of creatinine, blood urea nitrogen, total cholesterol, triglycerides, advanced glycation end products and albumin in serum and urine, respectively. MPGL significantly increased the antioxidant parameters in the kidney. Histological evaluation revealed that MPGL treated STZ-diabetic rats demonstrated reduced vacuolar degeneration of tubules; periodic acid Schiff base (PAS) positivity staining intensity in glomeruli and basement membrane thickening. Present findings provide experimental evidence that MPGL has potential antioxidant, antihyperglycemic and anti-glycation activities which might be helpful in slowing the progression of diabetic nephropathy.

Kinetics of Inhibition of Monoamine Oxidase Using Curcumin and Ellagic Acid.

BACKGROUND: Curcumin and ellagic are the natural polyphenols having a wide range of pharmacological actions. They have been reported to have their use in various neurological disorders. OBJECTIVE: This study was aimed to evaluate the effect of curcumin and ellagic acid on the activity of monoamine oxidase (MAO), the enzyme responsible for metabolism of monoamine neurotransmitters which are pivotal for neuronal development and function. MATERIALS AND METHODS: The in vitro effects of these selected polyphenols on MAO activities in mitochondria isolated from rat brains were examined. Brain mitochondria were assayed for MAO type-B (MAO-B) using benzylamine as substrates. Rat brain mitochondrial MAO preparation was used to study the kinetics of enzyme inhibition using double reciprocal Lineweaver-Burk plot. RESULTS: MAO activity was inhibited by curcumin and ellagic acid; however, higher half maximal inhibitory concentrations of curcumin (500.46 nM) and ellagic acid (412.24 nM) were required compared to the known MAO-B inhibitor selegiline. It is observed that the curcumin and ellagic acid inhibit the MAO activity with both the competitive and noncompetitive type of inhibitions. CONCLUSIONS: Curcumin and ellagic acid can be considered a possible source of MAO inhibitor used in the treatment of Parkinson's and other neurological disorders. SUMMARY: Monoamine oxidase (MAO) is involved in a variety of neurological disorders including Parkinson's disease (PD)Curcumin and ellagic acid inhibit the monoamine oxidase activityEllagic acid revealed more potent MAO type-B (MAO-B) inhibitory activity than curcuminKinetic studies of MAO inhibition using different concentrations of curcumin and ellagic acid were plotted as double reciprocal Lineweaver-Burk plotThe mode of inhibition of both compounds toward MAO-B is mixed (competitive and uncompetitive) type of inhibition with both the competitive and noncompetitive type of inhibitions. Abbreviations used: MAO: Monoamine oxidase, IC50: Higher half maximal inhibitory concentrations, PD: Parkinson's disease, LB: Lewy bodies, SNpc: Substantia nigra pars compacta, ROS: Reactive oxygen species, SG: Selegiline, DMC: demethoxycurcumin, BDMC: Bisdemethoxycurcumin.