Petroleum ether extract of Njavara rice (Oryza sativa) bran upregulates the JAK2-STAT3-mediated anti-inflammatory profile in macrophages and aortic endothelial cells promoting regression of atherosclerosis.

"Njavara" (Oryza sativa L.) is a unique rice variety grown in Kerala that is reported to have significantly higher antioxidant, anti-inflammatory, chemical indices, and bioactive components compared with staple rice varieties. However, the role of NBE in reversing the atherosclerosis development remains unclear. The present study aimed to elucidate the role of NBE in promoting atherosclerotic regression. Male New Zealand white breed rabbits were divided into three groups. Group I was the control, group II was the regression control, and group III was NBE treated (100 mg/kg body mass). Serum and tissue lipids, CRP, antioxidant enzyme activities, mRNA, and protein expression of genes of RTC and mRNA expression of cytokines were studied. The current study showed that hypercholesterolemic rabbits treated with NBE decreased the serum and tissue lipids concentrations, ApoB expression, and CRP levels and enhanced the activities of antioxidant enzymes and PON1expression, JAK2, STAT3, ABCA1, and ApoA. Our results indicate that NBE attenuates proinflammatory cytokine production (IL-1ß), enhanced expression and interactions of ABCA1/ApoA1 leading to JAK2/STAT3 activation in macrophages switching to an anti-inflammatory milieu in the system, and enhanced expression of IL-10 and decreased expression of ApoB, indicating that treatment with NBE facilitates plaque regression.

Dietary Njavara rice bran oil reduces experimentally induced hypercholesterolaemia by regulating genes involved in lipid metabolism.

The present study was carried out to evaluate the anti-atherogenic effect of Njavara rice bran oil (NjRBO) on atherosclerosis by modulating enzymes and genes involved in lipid metabolism in rats fed a high-cholesterol diet (HCD). Adult male rats (Sprague-Dawley strain, weighing 100-120 g) were divided into three groups of nine animals each. Group I served as the control, group II were fed a HCD and group III were fed a HCD and NjRBO (100 mg/kg body weight). The study duration was 60 d. Serum and tissue lipid profile, atherogenic index, enzymes of lipid metabolism, plasma C-reactive protein levels, serum paraoxonase and arylesterase activities, thiobarbituric acid-reactive substances, gene and protein expression of paraoxonase 1 (PON1), PPARα, ATP-binding cassette transporter A1 (ABCA1), apoB and apoA1 in the liver were quantified. Total cholesterol, TAG, phospholipid, NEFA, LDL-cholesterol concentrations in the serum and liver, lipogenic enzyme activities, hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity and atherogenic index were significantly increased in HCD-fed rats, but they decreased after treatment with NjRBO. HDL-cholesterol level and lecithin cholesterol acyl transferase activity were increased in the NjRBO-treated group, but decreased in the HCD-fed group. The expression levels of ABCA1, apoA1, PON1 and PPARα were found to be significantly increased in NjRBO-treated group compared with the HCD-fed group; however, the expression level of apoB was found to be higher in HCD-fed group and lower in the NjRBO-treated group. These data suggest that NjRBO possesses an anti-atherogenic property by modulating lipid metabolism and up-regulating genes involved in reverse cholesterol transport and antioxidative defence mechanism through the induction of the gene expression PON1.

Tricin 4'-O-(erythro-ß-guaiacylglyceryl) ether and tricin 4'-O-(threo-ß-guaiacylglyceryl) ether isolated from Njavara (Oryza sativa L. var. Njavara), induce apoptosis in multiple tumor cells by mitochondrial pathway.

Njavara is an important medicinal rice variety of Kerala, India widely used in Ayurveda for the treatment of rheumatoid arthritis, paralysis, neurodegenerative diseases and in rejuvenation therapy. The study evaluated, for the first time, antitumor effects of the two rare flavonolignans, tricin 4'-O-(erythro-ß-guaiacylglyceryl) ether (compound 1) and tricin 4'-O-(threo-ß-guaiacylglyceryl) ether (compound 2), isolated from 'Njavara' black. Both the compounds induced apoptosis in three cancer cell lines colon adenocarcinoma cell line HCT 116, ovarian cancer cell line SKOV3 and breast cancer cell line MCF-7. Chromatin condensation in the three cancer cell lines by Hoechst staining showed >50 % of apoptosis by compounds 1 and 2 at concentration 40 and 30 µg/ml, respectively after 48 h. Further studies substantiated that both the compounds targeted cancer cells through mitochondrial membrane potential loss and subsequent chromatin condensation. Both compounds significantly increased the Annexin V binding thus confirming compounds 1 and 2 to be potential apoptotic agents.

Molecular mechanisms of anti-inflammatory action of the flavonoid, tricin from Njavara rice (Oryza sativa L.) in human peripheral blood mononuclear cells: possible role in the inflammatory signaling.

Flavonoids are a group of natural substances that are located in sources of vegetal origin and are able to regulate acute and chronic inflammatory responses. The anti-oxidant and anti-inflammatory effects corroborate with the preferential use of Njavara, a rice variety in indigenous medicine and the phytochemical investigations revealed the occurrence of a flavonoid, tricin at significantly higher levels compared to staple varieties. This study describes the new aspects of inflammatory suppression by the Njavara rice by evaluating the role of active constituent, tricin in the regulation of production of various pro-inflammatory markers by human peripheral blood mononuclear cells stimulated with lipopolysaccharide. Treatment with tricin resulted in significant down-regulation of LPS-elicited production of TNF-α, IL-6, PGE(2) and NO. Tricin was found to be a potential blocker of the expression of isoforms of nitric oxide synthase, cyclooxygenase and matrix metalloproteinases. Modulation of the cascade of molecular events in lipopolysaccharide signaling also includes inhibition of transcription factor NF-κB evidenced by the detection of enhanced p65 subunit in the nuclear extracts on tricin supplementation. The present study summarizes the role of the flavonoid, tricin in the modulation of the expression of different inflammatory mediators and revealed that the inhibitory effects on cell signaling pathways are responsible for its anti-inflammatory activity.

Isolation, characterization and quantification of tricin and flavonolignans in the medicinal rice Njavara (Oryza sativa L.), as compared to staple varieties.

Njavara is an important medicinal rice variety of Kerala, India, widely used in Ayurveda as a 'health food' and in the treatment of rheumatoid arthritis, paralysis, neurodegenerative diseases and in rejuvenation therapy. Phytochemical investigations and spectroscopic studies of the diethyl ether fraction of methanolic extract of Njavara Black (NB) rice bran gave three important compounds namely, tricin and two rare flavonolignans- tricin 4'-O-(erythro-ß-guaiacylglyceryl) ether and tricin 4'-O-(threo-ß-guaiacylglyceryl) ether. The EC(50) values of these compounds in DPPH system were 90.39, 352.04 and 208.1 µg/ml, respectively. Quantification of the compounds by HPLC in NB and staple, non-medicinal rice varieties Sujatha (SJ) and Palakkadan Matta (PM) showed that tricin is present 39.64 and 16.12 fold higher in NB, compared to SJ and PM, respectively. This is the first report on the occurrence of tricin at significantly higher levels in Njavara and occurrence of the two flavonolignans in Oryza sativa species. Of the three compounds, tricin and the threo- form of flavonolignan showed anti-inflammatory effect of >65% after 5 h, at 2 mg/kg, in carrageenan-induced, paw edema experiments in rats. The results of the study corroborate with the preferential use of Njavara in indigenous medicine, over staple varieties.