Alteration in bioenergetic regulators, SirT1 and Parp1 expression precedes oxidative stress in rats subjected to transient cerebral focal ischemia: molecular and histopathologic evidences.

The present study was undertaken to identify the time-dependent changes in bioenergetic regulators and oxidative stress markers levels and also to ascertain which occurs early in focal cerebral ischemia. The status of bioenergetic regulators (nicotinamide adenine dinucleotide, Silent information regulator Transporter 1 (SirT1) and Poly adenosine diphosphate--ribose polymerase 1 (Parp1)) and oxidative stress markers' (lipid peroxidation and nitric oxide) levels along with excitatory neurochemical glutamate, neuronal nuclei (NeuN), glial fibrillary acidic protein (GFAP), and caspase 3 at various durations of reperfusion viz 0, 1, 6, 24, 72, and 166 hours was investigated in rats subjected to 2 hours of middle cerebral artery occlusion. Six hours after reperfusion, a significant downregulation in SirT1 and upregulation in Parp1 expressions were observed in striatal region of ischemic-reperfused rats compared with ischemic rats. Peak elevation in glutamate content was recorded at 72 hours, and maximum level of lipid peroxidation and nitric oxide contents were observed at 166 hours. A significant decrease in NeuN and increase in GFAP-positive cells were observed at 24 and 72 hours, respectively, in cortical, striatal, and hippocampal regions. These data reveal that change in bioenergetic regulators occurs earlier than excitotoxicity and oxidative stress in cerebral stroke. From the data, it can also be inferred that appropriate therapeutic intervention, that is, bioenergetic modulators at early period and either glutamatergic and/or antioxidant therapy at delayed period may yield a better therapeutic outcome.

Venthamarai chooranam, a polyherbal Siddha medicine, alleviates hypertension via AT1R and eNOS signaling pathway in 2K1C hypertensive rats.

The present study was aimed to scientifically demonstrate the anti-hypertensive action of Venthamarai chooranam (VMC) in renal hypertensive rats. Two Kidney One Clip (2K1C) Goldblatt model was adopted to induce hypertension in rats. Male Sprague Dawley rats (270-320 g) were randomized into sham (n = 6), vehicle-treated 2K1C (n = 9) and VMC-treated 2K1C (400 mg/kg, p.o; n = 8) and monitored for nine weeks. Systolic blood pressure (SBP), plasma nitrate/nitrite, carotid endothelial nitric oxide synthetase (eNOS), renal angiotensin type 1 receptor (AT1R), angiotensin type 2 receptor (AT2R), TNFα, IL-6, thioredoxin 1 (TRX1), and thioredoxin reductase 1 (TRXR1) mRNA expressions were studied. VMC upregulated eNOS expression which in turn improved plasma nitric oxide and decreased SBP in hypertensive rats. It down-regulated AT1R and simultaneously upregulated AT2R expression in comparison to vehicle-treated 2K1C rats. Further, renal TNFα and IL-6 expressions were down-regulated while TRX1 and TRXR1 were upregulated by VMC. VMC potentially interacts with renin-angiotensin components and endothelial functions, and thereby exerts its antihypertensive action. This is the first study to demonstrate the mechanism of anti-hypertensive action of VMC in an animal model of renovascular hypertension.

Cuminum cyminum, a dietary spice, attenuates hypertension via endothelial nitric oxide synthase and NO pathway in renovascular hypertensive rats.

Cuminum cyminum (CC) is a commonly used spice in South Indian foods. It has been traditionally used for the treatment and management of sleep disorders, indigestion, and hypertension. The present study was carried out to scientifically evaluate the anti-hypertensive potential of standardized aqueous extract of CC seeds and its role in arterial endothelial nitric oxide synthase expression, inflammation, and oxidative stress in renal hypertensive rats. Renal hypertension was induced by the two-kidney one-clip (2K/1C) method in rats. Systolic blood pressure (SBP), plasma nitrate/nitrite, carotid-eNOS, renal-TNF-α, IL-6, Bax, Bcl-2, thioredoxin 1 (TRX1), and thioredoxin reductase 1 (TRXR1) mRNA expressions were studied to demonstrate the anti-hypertensive action of CC. Cuminum cyminum was administered orally (200 mg/kg b.wt) for a period of 9 weeks; it improved plasma nitric oxide and decreased the systolic blood pressure in hypertensive rats. It also up-regulated the gene expression of eNOS, Bcl-2, TRX1, and TRXR1; and down-regulated Bax, TNF-α, and IL-6. These data reveal that CC seeds augment endothelial functions and ameliorate inflammatory and oxidative stress in hypertensive rats. The present report is the first of its kind to demonstrate the mechanism of anti-hypertensive action of CC seeds in an animal model of renovascular hypertension.

Polyphenols in madhumega chooranam, a Siddha medicine, ameliorates carbohydrate metabolism and oxidative stress in type II diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Present study was undertaken to demonstrate the mode of anti-diabetic action of a polyherbal Siddha Medicine, Madhumega chooranam (MMC). MATERIALS AND METHODS: MMC was fractionated into phenolic (PMMC) and non-phenolic (NPMMC) portions in order to identify bioactive fraction. Study was performed in type II diabetic rats. Role of PMMC and NPMMC on liver glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucokinase and glycogen content were determined. Their role on superoxide dismutase, reduced glutathione and lipid peroxidation were investigated. In addition, their effects on GLUT4 and PPARγ gene expression were studied. Pancreas and liver histopathology was studied using hematoxylin and eosin stain. RESULTS: PMMC improved carbohydrate metabolism by decreasing glucose-6-phosphatase and fructose-1,6-bisphosphatase and increasing glucokinase and glycogen contents in diabetic rats liver. It alleviated oxidative stress by increasing superoxide dismutase, glutathione and decreasing lipid peroxidation content. PMMC up-regulated liver GLUT4 and PPARγ mRNA expression in comparison to the vehicle or NPMMC rats. CONCLUSION: Madhumega chooranam mediates its anti-diabetic action through the inhibition of gluconeogenesis and activation of glycolytic pathways in type II diabetic rats. Increased GLUT4 and PPARγ expressions provide additional information on its glucose uptake/sensitising and hypolipidemic potential. Phenolic components of MMC were found to be the bioactive principles.