The synthesis of collagen and its turnover remained as critical determinants for the progression of atherosclerosis. During this condition, proteases secreted by SMCs and foam cells in the necrotic core degrade collagen. Growing evidences demonstrated that consumption of antioxidant rich diet is highly associated with a reduced risk of atherosclerosis. Oligomeric proanthocyanidins (OPC) have been proved to possess promising antioxidant, anti-inflammatory and cardioprotective activity, based on our previous studies. The present study aims to investigate the efficacy of OPC isolated from Crataegus oxyacantha berries as a natural collagen crosslinker and anti-atherogenic agent. Spectral studies like FTIR, ultraviolet and circular dichroism analysis confirmed the in vitro crosslinking ability of OPC with rat tail collagen when compared to the standard epigallocatechin gallate. The administration of cholesterol:cholic acid (CC) diet induces proteases-mediated collagen degradation that could result in plaque instability. Further, the CC diet fed rats showed significantly increased levels of total cholesterol and triacylglycerols which, in turn, increases the activities of collagen degrading proteases-MMPs (MMP 1, 2 and 9) and Cathepsin S and D. Upon OPC treatment, marked reduction in the lipid content, activation of proteases with concomitant increase in the mRNA levels of collagen Type I and Type III as similar to atorvastatin treatment were observed .Thus, OPC supplementation may contribute to the prevention of atherosclerotic plaque instability by acting as a natural crosslinker of collagen.

The study aimed to carry out the in vitro antioxidant and antimicrobial activities of the methanolic extract of aerial parts of Alternanthera bettzickiana (ABME). ABME showed its ability to scavenge the free radicals in a concentration-dependent manner. The plant extract (100 mg) yielded 92.6±0.13mg/ml gallic acid-equivalent phenolic content and 280.5±0.12 mg/ml quercetin-equivalent flavonoid content. ABME showed total antioxidant activity with a Trolox equivalent antioxidant concentration (TEAC) value of 0.77±0.03. The IC50 values for scavenging of free radicals were 292.578μg/ml, 212.582 μg/ml, 146.1 μg/ml and 434.9μg/ml for DPPH, hydroxyl, superoxide and nitric oxide respectively. The antimicrobial activity was tested against strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Candida albicans and Aspergillus niger. ABME was found to be effective against these tested organisms. The present study provides evidence that aerial parts of Alternanthera bettzickiana are a potential source of natural antioxidants with antimicrobial properties.

Breast cancer treatment strategy depends mainly on the receptor status. Our aim was to identify a herbal preparation, effective against breast cancer, irrespective of hormone sensitivity, and to understand its molecular mechanism. The rich antioxidant composition of hawthorn (Crataegus oxyacantha) makes it a promising anti-cancer drug candidate. Polyphenol-rich methanolic extract of C. oxyacantha berry (M.Co) was found to be cytotoxic on hormone receptor positive (MCF-7) and triple negative (MDA-MB-231) breast cancer cell lines, at a dose (75 μg/ml) safe on normal cells. It could effectively inhibit tumor cell proliferation and arrest cell cycle at G1/S transition in both cell lines. Molecular targets were selected from different levels of canonical Wnt signaling pathway (such as autocrine and antagonistic ligands, receptor, effector, cytoplasmic components, downstream targets, and pathway antagonist), since they are frequently found dysregulated in all breast cancers and their aberrant activation is associated with cancer stem cell expansion. M.Co could significantly downregulate the expression of Wnt pathway agonists and upregulate that of Wnt antagonists at transcriptional and translational levels, in both cell lines. To conclude, C. oxyacantha berry extract is effective against breast cancer irrespective of its hormone dependency, and cancer growth inhibition at stem cell level can be expected.

C-reactive protein (CRP) is a well-established biochemical marker for atherosclerosis. Modification of LDL inside the artery wall favors the elevation of this acute phase protein. Hence, this mechanism is considered an important factor to trigger the monocyte to macrophages differentiation which results in the formation of foam cells. Therefore, this key event should be targeted and focused on how this complex (OxLDL + CRP) proceeds to endothelial dysfunction. Oligomeric proanthocyanidins (OPC) is a well-known cardioprotective flavon-3-ols. The present study is challenged between the cardioprotective roles of OPC against the deleterious effect of OxLDL + CRP complex upon endothelial cells. Protein–protein docking was carried out between CRP and LOX-1. This docked protein complex was again docked with OPC to show the inhibitory mechanism of CRP binding with LOX-1. OPC showed a promising inhibitory mechanism against OxLDL + CRP complex. Docking studies showed that in the absence of ligands (OPC), binding of CRP and LOX-1 was greater and vice versa in the presence of ligands. Based on these molecular docking results, in vitro studies have been carried out. The monolayer of endothelial cells was incubated with THP-1 monocytes for 48 h, induced with OxLDL (10 μg/ml) + CRP (15 μg/ml) and cotreated with OPC (100 μg/ml). Morphological changes, cell migration assay, and capillary tube forming assay were carried out. Myeloperoxidase levels were estimated to determine the adhesion of monocytes onto EC monolayer. RT-PCR analysis of L-Selectin was also done. The quantification of NO levels and analysis of mRNA expressions of eNOS was to determine the nitric oxide demand caused due to OxLDL + CRP complex. LOX-1, scavenger receptor levels were analyzed by mRNA expression. Proinflammatory markers such as IL-6, MCP-1, and IL-1β were studied. Accumulation of ROS levels was measured fluorimetrically using DCF-DA staining. Mitochondrial membrane potential was determined by JC-1 dye and cell cycle analysis was done by FACS analysis. To emphasis the results, the OPC-treated group showed decreased levels of proinflammatory markers, LOX-1 and L-selectin levels. Endothelial nitric oxide levels were increased upon OPC treatment and reduction in the ROS levels was also observed. Endothelial cells apoptosis was prevented by OPC. To conclude, OxLDL + CRP complex inhibitory effects of OPC could maintain the normal homeostasis.

Lung cancer is the leading cause of cancer deaths globally. The objective of this study was to investigate the effect of 1,2-diazole (pyrazole) as an anti-cancer drug on human non-small cell lung carcinoma A549 cells. We attempt to examine the expression level of pro-inflammatory proteins such as TNF-α, NF-κB-p65, MMP-2 and E-Cadherin which are commonly associated with an inflammatory response in epithelial cells and apoptosis in A549 cells. The LPS-induced cytokines and inflammatory mediators include TNF-α, IL-6, iNOS and COX-2 levels in A549 cells and the effect of pyrazole was studied. The present study reveals that, pyrazole inhibits A549 cells by suppressing TNF-α induced MMP-2 expression, thereby inhibiting the nuclear translocation of NF-κB-p65. Pyrazole significantly up-regulate the E-cadherin level and down-regulated MMP-2 expression that could probably preventing A549 cancer cells to invade. The study further substantiated the anti-cancer property of pyrazole by regulating the above mentioned level of LPS-induced cytokines and inflammatory mediators. The observations of the present study open a possibility for the development of an effective therapeutic agent that targets inflammatory and signaling pathway mediators to challenge human non-small cell lung carcinoma.

Antibiotics are essential in many life-threatening diseases. On the other hand, improper use of antibiotics can be disastrous. Cell morphological changes were observed in the ciprofloxacin-treated cells starting at 48 hours. Changes in cell morphology were continuously observed up to 14 days, which showed gradual morphological changes from monocyte to plaque-like cells at day 12, and foam cell, which is an intermediate stage in atherosclerosis was observed at day 8, which was confirmed with Oil Red O staining. Flow cytometry data revealed that oxidized LDL (oxyLDL)-induced cells showed 60.16% of CD64 (proinflammatory macrophage markers) and no expression of CD23 (anti-inflammatory macrophage markers), whereas ciprofloxacin-treated cells expressed 67.97% of CD64 and 13.78% of CD23. Chemokine antibody array analysis revealed that ciprofloxacin exposed cells showed a proinflammatory role (ENA78, Eotaxin1, Eotaxin2, IP-10, MIG, MIP-3 beta, SDF-1 beta, TECK, CXCL16, and Fractalkine). Liquid chromatography with tandem mass spectrometry (LC-MS/MS) revealed that myristic acid was incorporated into a protein with 68 kDa molecular mass in exposing oxyLDL-induced monocytes with ciprofloxacin, which could be a reason for the observed foam cells and in vitro plaque formation. As myristic acid primes atherosclerosis, it is better to limit the intake of antibiotics like ciprofloxacin for common illness, specifically the high-risk patients, which may contribute to atherosclerosis.

M1 macrophages serve one edge as proinflammatory and M2 macrophages serve the other edge as an anti-inflammatory macrophage. It appears that a related "switch" in macrophage morphology may also happen in the course of atherosclerosis, which has not yet been elucidated. An atherogenic diet (AD) was given to rats, and induction of macrophage differentiation and the nuclear localization of nuclear factor-kappa B (NFκB) were investigated by Western blot and immunofluorescence. Chemokines were analyzed using an antibody array with 32 target proteins. M2 macrophage transformation was confirmed in diosgenin-treated aorta by immunofluorescence and was validated in vitro using THP-1 cells. MAC387 (macrophage marker) and NFκBp65 (inflammatory hub) were upregulated in oxidatively-modified low-density lipoprotein (OxyLDL) and AD-induced condition. Macrophage differentiation, which induced the formation of inflammatory mediators, was not significantly suppressed by the inhibition of NFκB using dexamethasone. M1 macrophage polarization was identified in OxyLDL-induced monocytes, which are proinflammatory in nature, whereas M2 macrophage polarization was noticed in diosgenin-treated monocytes, which exhibit anti-inflammatory properties. M1-and M2-specific chemokines were analyzed using chemokine antibody array. Furthermore, the expression of proinflammatory macrophage (M1) was noticed in AD-induced aorta and anti-inflammatory macrophage (M2) was observed in diosgenin-treated aorta. This is the first report where, unifying the mechanism of diosgenin as aan nti-atherosclerotic and the expression of M1 and M2 specific chemokines is shown by downregulating NFκB and not by preventing the differentiation of monocyte into a macrophage, but by allowing macrophage to differentiate into M2, which aids in preventing the atherosclerotic progression.

In aquaculture practices, prawn cultivation holds the major share and Penaeus monodon is the main species cultured. The decline in production of P. monodon is mainly due to the limited availability of domesticated broodstock, which is attributed to its reproductive cycle, controlled by complex coordinated signaling mechanisms. Unilateral eyestalk ablation of domesticated females held in captivity is done to induce ovary development, which has certain disadvantages, including a high rate of mortality. Thus, developing alternative techniques for eyestalk ablation in captive broodstock is necessary to induce maturation of ovary. This study exemplifies the role of 5HT along with a cocktail of inhibitors (U0126, Rp-cAMP, and LY294002) in inducing ovarian maturation. In this study, inhibition of pERK by U0126 inhibited vitellogenesis-inhibiting hormone (VIH), which in turn led to the overexpression of vitellogenin. 5HT induces steroidogenesis (estradiol-17β) through induction of the gonadotropin-releasing hormone by activating calcium-calmodulin signaling. Steroidogenesis is also aided by synthesis of StAR protein. Estradiol-17β stimulates the formation of the maturation-promoting factor (MPF) complex by cdc25 activation and Myt1 inactivation. LY294002 aids in keeping cdc25 activated by inhibiting calcium-calmodulin induced phosphorylation of Akt which is a negative regulator of mitogen-activated protein kinases. VIH induced activation of Myt1, through protein kinase A (PKA), was inhibited by Rp-cAMP which inhibits adenylate cyclase, thus stabilizing the activated MPF complex. To conclude, the coordinated effect of inhibitors and 5HT accelerates the development of ovary from previtellogenic to matured oocytes, yielding high quality and quantity larvae compared with eyestalk-ablated P. monodon.

Foam cells are specialized types of cells which predominate the necrotic core of atherosclerotic plaque. Recently, autophagy-mediated cholesterol efflux from foam cells has been proposed as a beneficial therapy for atherosclerosis. The purpose of this study was to delineate the underlying molecular mechanism of oligomeric proanthocyanidins (OPC) and epigallocatechin gallate (EGCG) induced autophagy of foam cells and associated cholesterol efflux. The oxidized low-density lipoprotein induced foam cells demonstrated impaired autophagy flux through the downregulated expressions of LC3BII/LC3BI, autophagy related gene-5, Class III phosphoinositide 3 kinase (Class III PI3K), Beclin1, ABCA1, and ABCG1 with concomitant increase in the expressions of protein 62, Class I phosphoinositide 3 kinase, Akt, and mammalian target of rapamycin. However, these effects were significantly abolished by treatment with OPC and EGCG through activation of autophagy flux via Class III PI3K/Beclin1 and with upregulated expression of transporter proteins ABCA1 and ABCG1. Furthermore, the cholesterol efflux process in the foam cells was activated by lysosomal acid lipase and cathepsin D facilitated lipolysis of lipid droplets. Taken together, our data demonstrate that OPC and EGCG treatment stimulated the coordinated activation of autophagy and cholesterol efflux through Class III PI3K/Beclin1 pathway in foam cells, suggesting a promising therapeutic strategy against atherosclerosis.

Background: Oral squamous cell carcinoma (OSCC) is a predominant type of cancer in India. It has been observed that OSSC is preceded by premalignant lesions or otherwise reported as potentially malignant disorders (PMD) by WHO during the year 2005. PMD include various oral mucosal diseases such as leukoplakia, erythroplakia, oral submucous fibrosis (OSMF), oral lichen planus, discoid lupus erythematosus and actinic keratosis etc. Literature surveys have highlighted that areca nut–associated oral squamous cell carcinoma is the third most common malignancy in the developing world and OSMF has been reported as the PMD of the oral cavity that has high prevalence rate in India. Since the exact mechanism behind this fibrosis condition is yet to be identified, we propose that, components in areca nut could interfere with certain signaling pathways in the human system that could lead to this precancerous stage. Aim: 1. To investigate the molecular mechanism involved in EMT by cross-talk between TGF-β and Wnt/β-catenin pathways in OSMF patients. 2. To explore the role of HSP90 inhibition in this cross-talk under hypoxic condition. Methods: OSMF tissue samples were obtained via punch biopsy, from patients with areca nut chewing habit and control tissues were collected from healthy individuals. OSMF patients who underwent any local treatment of oral mucosa or those who have any systemic disorder were excluded from the study. Initially, the expression pattern of various TGF-β and Wnt signaling pathway molecules were studied immunohistochemically to confirm the role of these pathways in OSMF. The gene expression of Wnt5a, Wnt3a, GSK-3β, β-catenin, cMyc, TGFβ1, smad3, E-cadherin, snail, α-SMA and Twist were studied by quantitative real time PCR (qRT-PCR). The results of qRT- PCR were further confirmed by Western blot analysis. Human gingival derived fibroblast cells were cultured and the cells were grouped into 2. Group I- normoxia, group II- hypoxia, group III- hypoxia + 17-AAG (an inhibitor of HSP90). mRNA and protein expression patterns were revealed by qRT-PCR and Western blot analysis for HSP90, HIF-1α, Wnt5a, β-catenin, cMyc, TGF-β1, Smad3, p-Smad3, E-cadherin, N-cadherin, Snail and α-SMA. Immunofluorescence analysis of expression of HSP90, HIF-1α, vimentin, snail, TGF-β1, Smad3 were also carried out. Results: The results obtained revealed that, TGF-β and Wnt/β-Catenin signaling molecules are involved in OSMF leading to EMT. The same pattern was observed when the cells were maintained under hypoxic conditions. Conclusion: Overall, this study describes the cross-talk of TGF-β and Wnt/β-Catenin pathways in EMT in tissues collected from OSMF patients and also when the cells were maintained under normoxic and hypoxic conditions. Inhibition of this signaling cross-talk might help to identify a new strategy for therapeutic intervention.

Lung cancer is the leading cause of cancer deaths worldwide and non-small cell lung carcinoma (NSCLC), a heterogeneous class of tumors, represents approximately 85% of all new lung cancer diagnosis. Conventional treatment options have limited efficacy because most cases are in the advanced stage at the time of diagnosis. The present study evaluates the anti-cancer activity of 1,2-diazole (pyrazole), a natural compound from mangrove plant Rhizophora apiculata (R.apiculata) on A549 lung carcinoma cells. In the present study the anti-cancer mechanism of pyrazole, was examined by the expression level of proteins Epidermal growth factor receptor (EGFR), Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) and Cyclin-dependent kinase-2 (CDK-2) which are commonly associated with the cell signaling pathways that control cell survival and apoptosis, that could facilitate to develop a novel target and effective treatment approach for patients with NSCLC. Pyrazole significantly induced cell cycle arrest and initiated apoptosis through inhibition of downstream components of EGFR tyrosine kinase pathway. Pyrazole disrupts the mitochondrial membrane potential and modulated the protein levels of Bax and Bcl-2 which could probably lead to caspase-3 activation. Furthermore, Pyrazole suppresses the expression of CDK-2 resulting in cell cycle arrest at G1 phase and in the G1-S phase transition. Taken together, the current study provides new insight in to the precise molecular mechanisms responsible for the anti-cancer activity of pyrazole in NSCLC, A549 cells. The study opens an avenue for development of a natural compound as a potential therapeutic agent which could target cell signaling pathways to combat human NSCLC.

Due to the idiopathic inflammation of the gastrointestinal tract and ulcerative colitis, there is an increased risk of colorectal cancer in inflammatory bowel disease (IBD) patients. Chemoprevention remains vital and much interest has been focused on targetable inflammatory proteins associated with IBD. Dextran sodium sulfate (DSS) induced colitis mimics human IBD in mouse, which is used as a model to determine the action of Lupeol (a triterpene), found in certain fruits and Indian herbs, in the healing of colitis. DSS causes chronic inflammation of the colonic epithelium by altering mucosal immune system i.e. mucins and inflammatory proteins namely TNF-α, IL 1 and 2 and NF-κB. Lupeol supplement to colitis mice, showed colonic regeneration by altering the MUC 1 & 2 gene expression. Lupeol also modulates TWIST gene expression, NF-κB, mediated inflammation and assists down regulation of TNF-α and IL genes. Thus Lupeol has potent colonic healing activity and also acts as an anti-inflammatory agent in controlling colitis.

Dysregulated synthesis of hepatic cholesterol is a critical determinant of atherosclerosis. The combination of cholesterol and cholic acid (CC) diet supplementation to animal models is associated with hepatic dysfunction-mediated atherosclerosis. The current study was designed to investigate the hepatic cholesterol-lowering effects of oligomeric proanthocyanidins (OPC) in CC diet fed rats. CC diet-induced group exhibited significant increase in the hepatic lipid profile, activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR), PON-1, LCAT, LPL, and LPO levels, and messenger RNA expression of HMGR, low-density lipoprotein receptor (LDLr), and HNF-4 alpha. Administration of OPC (100 mg/kg/bwt) resulted in the significant reduction of lipid profile and HMGR levels, with concomitant increase in the levels of cholesterol-regulating enzymes and upregulated expression of LDLr and HNF-4 alpha, which was similar to atorvastatin. Molecular docking studies also revealed that proanthocyanidins had a strong binding affinity to HMGR, similar to atorvastatin. Our findings suggest that OPC regulate the impaired cholesterol metabolism-associated atherosclerosis through hepatic cholesterol-lowering effect.

The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3. Moreover, post treatment with Vitexin inhibits the ISO induced translocation of CHOP to nucleus during MI. Further results have demonstrated that, activation of Mst1 through ER stress was diminished upon treatment with Vitexin. In addition to this, Vitexin treatment significantly downregulated the expression of p-Yap and p-Mst1 which were enhanced during post myocardial injury. Taken together, our data indicate that co-ordinated activation of ER stress and hipposignaling by ISO was ameliorated by the potent cardioprotective effects of Vitexin.

The activation of two transcription factors, NF kappa B and NICD (notch intracellular domain), plays a crucial role in different stages of atherosclerotic disease progression, from early endothelial activation by modified lipids like oxidized low-density lipoprotein (oxyLDL) to the imminent rupture of the atherosclerotic plaque. Inflammatory mediators and the notch pathway proteins were upregulated in atherogenic diet-induced rats and the same was confirmed by the differentiation of monocyte to macrophage on exposure to oxyLDL. The inflammatory transcription factor NF kappa B and the notch signaling transcription factor NICD were analysed for their molecular interaction in monocyte to macrophage differentiation. Inhibition of NF kappa B by dexamethasone in monocyte to macrophage differentiation resulted in a concomitant downregulation of NICD, whereas inhibition of NICD by N-(N-[3, 5-difluorophenacetyl])-l-alanyl)-S-phenylglycine t-butyl ester (DAPT), a gamma-secretase inhibitor, did not significantly influence the expression of NF kappa B, but downregulated macrophage differentiation. These findings revealed that NF kappa B inhibition using dexamethasone regulated NICD, which turned down macrophage differentiation. Thus, inhibition of both NF kappa B-NICD is a potential target for intervention in atherosclerosis.

OBJECTIVES: Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silico approaches. METHODS: To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds. RESULTS: OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity. CONCLUSION: Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.

Among various oral cavity carcinomas, oral squamous cell carcinoma (OSCC) is considered as the most common oral and maxillofacial malignancy. The morbidity and mortality rate of the disease are still high in most of the countries with a survival rate of 50-63%. Oral submucous fibrosis (OSMF) has been reported as the potentially malignant disorder (PMD) of the oral cavity that has high prevalence rate in India. Chennai is one of the metro cities located in the southern part of India. This study was carried out to evaluate the serum levels of various trace elements such as iron (Fe), zinc (Zn), selenium (Se), and copper (Cu) and serum lipid profile in OSMF patients who live in Chennai and belong to Hindu religion. The alterations in the levels were compared to age, gendermatched normal healthy individuals in order to identify a new non-invasive method for the prevention of its transformation to OSCC. Serum levels of trace elements were analyzed using inductively coupled plasma optical emission spectrophotometer (ICP-OES) and lipid profile was done using autoanalyzer. The results obtained in the present study revealed a significantly low level of iron, zinc and selenium and very high level of copper in the serum of patients with advanced stage of OSMF when compared to healthy individuals. Serum lipid profile of OSMF group also showed a decreasing tendency compared to healthy individuals. Thus, alterations in the levels of serum trace elements and lipid profile could be utilized as an important biomarker for the identification of oral mucosal pathologies. Key-words: Oral submucous fibrosis, Trace elements, Lipid profile, Biomarker -------------------------------------------------------------------------------------------------------------------------------------Date of Submission: 08-05-2018 Date of acceptance: 25-05-2018 --------------------------------------------------------------------------------------------------------------------------------------

The purpose of this study was to investigate the possible prophylactic effects of Alpinia officinarum hance on experimentally induced acute and chronic colitis models, in-vivo and in-vitro. Acute and chronic colitis were induced in Male Wistar rats by administration of Dextran Sulfate Sodium (DSS) in drinking water. DSS induction exhibited colon shrinkage, increased the Disease Activity Index (DAI) score, increased the levels of inflammatory markers and caused severe anemia. DSS induced animals, co-treated with the hexane extract of Alpinia officinarum (HEAO) (200 mg/kg body wt), effectively suppressed colonic injury that was evidenced by the reduced DAI score, colon weight/length ratio, histological damage, proinflammatory markers and MPO activity. Further, it restored the colonic antioxidants near to normal levels by regulating the oxidative stress via attenuation of lipid peroxidation. Our results revealed that the degree of colitis caused by the administration of DSS was significantly attenuated by HEAO. In addition, the in-vitro study showed that HEAO treatment inhibited the proliferation of HT-29 cells and down regulated the mRNA expression of NF-κB and COX-2. Taken together, these results suggest that HEAO is a promising anti-oxidant and anti-inflammatory agent that support its possible therapeutic role in the treatment of colitis.

Atherogenic Diet (AD) was given to rats to understand the key role of inflammatory mediators in atherosclerotic lesion formation, as a serendipitous study, the diet induced inflammatory mediators in liver and brain, whereas pancreas, kidney and spleen were not affected. The efficacy of diosgenin in ameliorating atherosclerotic progression in heart and suppression of inflammatory mediators in liver and brain of Wistar rat fed on AD diet was investigated. Atherogenic diet triggered inflammatory mediators in heart, liver and brain by upregulating TNF-α, COX-2 and NFkBp65 which are the inflammatory hub, played a key role in pathophysiologic conditions. Endothelial dysfunction, liver tissue with prominent steatosis and the stress evoked in the brain by the atherogenic diet triggered these inflammatory mediators. TNF-α and COX-2 expression was upregulated and its elevation was associated with NFkBp65 activation in heart, liver and brain of atherogenic diet induced rat. Diosgenin downregulated these inflammatory mediators, thereby prevented the atherosclerotic disease progression and concomitant suppression of inflammatory mediators in liver and brain.