EGFR gene regulation in colorectal cancer cells by garlic phytocompounds with special emphasis on S-Allyl-L-Cysteine Sulfoxide.

Colorectal cancer is one among the most common cancers in the world and a major cause of cancer related deaths. Similar to other cancers, colorectal carcinogenesis is often associated with over expression of genes related to cell growth and proliferation, especially Epidermal Growth Factor Receptor (EGFR). There is an increasing attention towards the plant derived compounds in prevention of colorectal carcinogenesis by downregulating EGFR. Among plants, garlic (Allium sativum L.) is emerging with anticancer properties by virtue of its organosulfur compounds. The present study was aimed to analyze the interaction ability of garlic compounds in the active region of EGFR gene by in silico molecular docking studies and in vitro validation. This was conducted using the Discovery studio software version 4.0. Among the tested compounds, s-allyl-l-cysteine-sulfoxide (SACS)/alliin showed higher affinity towards EGFR. Furthermore, wet lab analysis using cell viability test and EGFR expression analysis in colorectal cancer cells confirmed its efficacy as a potent anticancer agent.

Deep fried edible oils disturb hepatic redox equilibrium and heightens lipotoxicity and hepatosteatosis in male Wistar rats.

Hepatosteatosis is a complex disorder, in which insulin resistance and associated dyslipidemic and inflammatory conditions are fundamental. Dietary habit, especially regular consumption of fat and sugar-rich diet, is an important risk factor. Coconut and mustard oils (CO and MO) are medium-chain saturated and monounsaturated fats that are common dietary ingredients among the Indian populations. Present study analyzed the effect of prolonged consumption of the fresh and thermally oxidized forms of these oils on glucose tolerance and hepatosteatosis in male Wistar rats. Thermally oxidized CO (TCO) and MO (TMO) possessed higher amount of lipid peroxidation products and elevated p-anisidine values than their fresh forms. Dietary administration of TCO and TMO along with fructose altered glucose tolerance and increased hyperglycemia in rats. Dyslipidemia was evident by elevated levels of triglycerides and reduced high density lipoprotein cholesterol (HDLc) levels in fructose and edible oil-fed group ( p < 0.05). Additionally, hepatic antioxidant status was diminished and oxidative stress markers were elevated in TCO- and TMO-fed rats. Substantiating these, hike in liver function marker enzyme activities were also observed in these animals. Supporting this, histological analysis revealed higher incidence of microvesicles and hepatocellular ballooning. Results thus suggest that consumption of thermally oxidized fats may cause hepatic damage.

Plant Phenolics Ferulic Acid and P-Coumaric Acid Inhibit Colorectal Cancer Cell Proliferation through EGFR Down-Regulation.

BACKGROUND: Colorectal cancer (CRC) or bowel cancer is one of the most important cancer diseases, needing serious attention. The cell surface receptor gene human epidermal growth factor receptor (EGFR) may have an important role in provoking CRC. In this pharmaceutical era, it is always attempted to identify plant-based drugs for cancer, which will have less side effects for human body, unlike the chemically synthesized marketed drugs having serious side effects. So, in this study the authors tried to assess the activity of two important plant compounds, ferulic acid (FA) and p-coumaric acid (pCA), on CRC. MATERIALS AND METHODS: FA and pCA were tested for their cytotoxic effects on the human CRC cell line HCT 15 and also checked for the level of gene expression of EGFR by real time PCR analysis. Positive results were confirmed by in silico molecular docking studies using Discovery Studio (DS) 4.0. The drug parallel features of the same compounds were also assessed in silico. RESULTS: Cytotoxicity experiments revealed that both the compounds were efficient in killing CRC cells on a controlled concentration basis. In addition, EGFR expression was down-regulated in the presence of the compounds. Docking studies unveiled that both the compounds were able to inhibit EGFR at its active site. Pharmacokinetic analysis of these compounds opened up their drug like behaviour. CONCLUSIONS: The findings of this study emphasize the importance of plant compounds for targeting diseases like CRC.

Cytotoxic and antioxidant properties of selected Scutellaria species from the Western Ghats of Peninsular India.

CONTEXT: Scutellaria (Lamiaceae), commonly known as 'Skullcaps', has been extensively used in Traditional Chinese Medicine (TCM). Recently, much emphasis has been given to this genus due to the rich source of bioflavonoids that contribute to its biological properties. Therefore, different species of Scutellaria are being explored worldwide. OBJECTIVES: Cytotoxic, antioxidant, and phytochemical properties of Scutellaria colebrookiana Benth and S. violacea (Heyne ex Benth) Don collected (October 2009-February 2010) from Western Ghats of India have been analysed. MATERIALS AND METHODS: In vitro cytotoxicity and free radical scavenging effects of root extracts in various solvents were analysed. Spectrophotometric and HPLC methods were performed for phytochemical analysis. RESULTS: Chloroform extract exhibited significant cytotoxicity in Dalton's Lymphoma Ascites (DLA) and Ehrlich Ascites Carcinoma (EAC) cells with IC(50) values 150 and 140 µg/mL for S. colebrookiana and 250 and 280 µg/mL for S. violacea, respectively. Moreover, the extract was effective in scavenging free radicals and inhibiting membrane peroxidation in vitro with IC(50) values 158.3 and 167.5 (superoxide), 17.5 and 28.0 (hydroxyl), 76.25 and 69.75 (DPPH), 24.5 and 28.0 (ABTS), 69.75 and 64.6 (lipid peroxidation), 41 and 31.5 µg/mL (erythrocyte hemolysis), respectively. Antioxidant effect observed with acetone extract was also comparable to that of chloroform extract. Phytochemical screening revealed the presence of baicalein. DISCUSSION AND CONCLUSION: Scutellaria species of Western Ghats showed cytotoxic and antioxidant potential and the presence of baicalein. This suggests that S. colebrookiana and S. violacea could be used as alternative sources for baicalein in view of the reported scarcity of S. baicalensis.

Comparative phytochemical and biological analysis to detect the genuineness of substitutes of the plant Moovila in drug preparations.

Pseudarthria viscida is the preferred source of the raw drug Salaparni in Ayurvedic system of medicine, especially in the preparation of Dasamoolarishtam. Due to its scarcity, other trifoliate leguminous plants, particularly the species of Desmodium and Uraria are used as substitutes. The phytochemical and biological properties of these plants were analyzed to sort out the genuineness of the substitutes. Qualitative as well as quantitative chemical profiles obtained for P. viscida showed similarity to U. rufescens. In vitro antioxidant and in vivo gastroprotective assays carried out to determine the biological properties of the extracts revealed that the acetone extract of P. viscida inhibited the formation of hydroxyl, superoxide, nitric oxide radicals, and lipid peroxidation. The oral administration of P. viscida extract significantly reduced ethanol-induced gastric ulceration in mice. Even though more or less the same chemical profile was obtained for P. viscida and U. rufescens, only P. viscida exhibited significant biological properties.

Loose shell syndrome of farmed Penaeus monodon in India is caused by a filterable agent.

Loose shell syndrome (LSS) of farmed black tiger shrimp Penaeus monodon has been reported from Indian shrimp farms since 1998 and is recognized as a major disease problem causing significant economic loss to the shrimp aquaculture sector. Unlike the rapid mortalities associated with viral pathogens such as white spot syndrome virus and yellow head virus, progression of LSS is gradual, leading to low-level progressive mortalities. The signs of LSS include a flaccid spongy abdomen due to muscular dystrophy, space between the exoskeleton and muscle, and a shrunken hepatopancreas. The feed conversion efficiency is reduced, and shrimp have poor meat quality, caused by impairment of the hepatopancreatic functions such as digestion and absorption as evidenced by the atrophy of the hepatopancreas. Histopathological investigations on LSS-affected shrimp showed shrinkage of extensor and flexor muscles with occasional hemocytic infiltration. The hepatopancreas showed inflammation of hepatopancreatic tubules with enlargement of intertubular spaces, hemocytic infiltration, and low levels of lipid reserves in the R cells. In advanced stages of LSS, many tubules were in highly necrotic condition with a sloughed epithelium, reflecting the dysfunction of the digestive gland. LSS could be induced in healthy tiger shrimp by challenge studies using membrane-filtered LSS-affected shrimp tissues, suggesting involvement of a filterable infectious agent.

Isolation and structural determination of new sphingolipids and pharmacological activity of africanene and other metabolites from Sinularia leptoclados.

Two new sphingolipids, (2S,3S,4R)-1,3,4-trihydroxy-2-[((R)-2'-hydroxytetradecanoyl) amino] tricosane (4) and (2S,3S,4R)-1,3,4-triacetoxy-2-[((R)-2'-acetoxyoctadecanoyl) amino]octadecane (5) along with africanene (1, reasonably good yield), 23-demethylgargosterol (2) and batylalcohol (3) have been isolated from the soft coral Sinularia leptoclados. Preliminary studies for pharmacological activity (blind screening and toxicity studies) of africanene were conducted. Africanene exhibited in vitro and in vivo cytotoxicity, dose dependent hypotensive activity as well as antiinflammatory activity. The pharmacological and toxicity studies on africanene are being reported for the first time and findings strongly encourage further investigation. Compounds 1, 4 and 5 were studied for the antibacterial, antifungal and antiviral activity while compounds 4 and 5 were also studied for the short term in vitro cytotoxic activity.

Biologically active principles isolated from Salacia oblonga wall.

From the petroleum ether extract of the root bark of Salacia Oblonga wall, two biologically active fractions have been isolated by column and thin layer chromatography. The methanol eluted fraction of the extract absorbed on a column of silica gel at a concentration of 50 micrograms/ml showed 100 percent cytotoxicity on Ehrlich ascites tumour cells. The chloroform eluted fraction of the pet. ether extract and a fluorescent compound separated from it by TLC demonstrated about 60% and 76% hypoglycemic potency of an equal dose of tolbutamide (250 mg/kg) in albino rats. The results indicate the therapeutic importance of S. Oblonga wall.

Cytotoxic and anti-tumour properties of certain taxa of Umbelliferae with special reference to Centella asiatica (L.) Urban.

Centella asiatica (L.) Urban (Umbelliferae) is commonly used in the Ayurvedic system of medicine to treat various diseases. The present study examines the anti-tumour effect of the crude extract (CE) of Centella asiatica as well as its partially purified fractions (AF) from chromatographic procedures by both in vitro short and long term chemosensitivity and in vivo tumour model test systems. AF dose dependently inhibited the proliferation of the transformed cell lines significantly more than did the CE and other solvent fractions. Fifty percent effective doses on hour 3 exposure to AF were 17 and 22 micrograms/ml for Ehrlich ascites tumour cells (EAC) and Dalton's lymphoma ascites tumour cells (DLA), respectively. However, practically no toxic effects were detected in normal human lymphocytes. AF also significiantly suppressed the multiplication of mouse lung fibroblast (L-929) cells at a concentration of 8 micrograms/ml in long term culture. Oral administration of the extracts (CE and AF) retarded the development of solid and ascites tumours and increased the life span of these tumour bearing mice. Tritiated thymidine, uridine and leucine incorporation assay suggest that the fraction acts directly on DNA synthesis.