Biofilm-Associated Agr and Sar Quorum Sensing Systems of Staphylococcus aureus Are Inhibited by 3-Hydroxybenzoic Acid Derived from Illicium verum.

Biofilm-producing Staphylococcus aureus (S. aureus) is less sensitive to conventional antibiotics than free-living planktonic cells. Here, we evaluated the antibiofilm activity of Illicium verum (I. verum) and one of its constituent compounds 3-hydroxybenzoic acid (3-HBA) against multi-drug-resistant S. aureus. We performed gas chromatography-mass spectroscopy (GC-MS) to identify the major constituents in the methanolic extract of I. verum. Ligand-receptor interactions were studied by molecular docking, and in vitro investigations were performed using crystal violet assay, spreading assay, hemolysis, proteolytic activity, and growth curve analysis. The methanolic extract of I. verum inhibited S. aureus at 4.8 mg/mL, and GC-MS analysis revealed anethole, m-methoxybenzaldehyde, and 3-HBA as the major constituents. Molecular docking attributed the antibiofilm activity to an active ligand present in 3-HBA, which strongly interacted with the active site residues of AgrA and SarA of S. aureus. At a subinhibitory concentration of 2.4 mg/mL, the extract showed biofilm inhibition. Similarly, 3-HBA inhibited biofilm activity at 25 µg/mL (90.34%), 12.5 µg/mL (77.21%), and 6.25 µg/mL (62.69%) concentrations. Marked attrition in bacterial spreading was observed at 2.4 mg/mL (crude extract) and 25 µg/mL (3-HBA) concentrations. The methanol extract of I. verum and 3-HBA markedly inhibited ß-hemolytic and proteolytic activities of S. aureus. At the lowest concentration, the I. verum extract (2.4 mg/mL) and 3-HBA (25 µg/mL) did not inhibit bacterial growth. Optical microscopy and SEM analysis confirmed that I. verum and 3-HBA significantly reduced biofilm dispersion without disturbing bacterial growth. Together, we found that the antibiofilm activity of I. verum and 3-HBA strongly targeted the Agr and Sar systems of S. aureus.

The biochemical alterations following administration of Kalpaamruthaa and Semecarpus anacardium in mammary carcinoma.

BACKGROUND: Breast cancer is one of the most common cancers in women of developed and developing countries. Lipids, lipoproteins and lipid-metabolizing enzymes have been associated with the risk of breast cancer. Kalpaamruthaa (KA) is a modified Siddha preparation, which contains Semecarpus anacardium Linn. (SA), Emblica officinalis (EO) and honey. OBJECTIVE: The present study was embarked to study the variations in lipids, lipid-metabolizing enzymes and lipoproteins in cancerous animals and the effect of KA on the lipid metabolism. MATERIALS AND METHODS: Breast cancer was induced in rats by administrating 7,12-dimethylbenz(a)anthracene orally (25 mg/kg body weight). After 90 days of induction, KA (300 mg/kg body weight) and SA (200 mg/kg body weight) were administered for 14 days, by gastric intubations. The levels of lipids and lipid-metabolizing enzymes were analysed in control and experimental animals. RESULTS AND CONCLUSION: The increased levels of total cholesterol, free cholesterol, phospholipids, triglycerides and free fatty acids and decreased levels of ester cholesterol in plasma, liver and kidney found in cancer suffering animals were reverted back to near normal levels on treatment with KA and SA. In mammary carcinoma bearing animals, the activities of total lipase, cholesterol ester synthase, and cholesterol ester hydrolase were significantly (p < 0.05) increased whereas lipoprotein lipase and lecithin cholesterol-acyl transferase were decreased. The levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) were increased and the level of high-density lipoprotein (HDL) was decreased. These alterations were recouped back upon treatment with KA as well as SA when compared to cancer animals. The effects of KA were found to be more effective than SA. No significant alterations were observed in herbal preparation control animals when compared to control animals.

Anticancer effect of Kalpaamruthaa on mammary carcinoma in rats with reference to glycoprotein components, lysosomal and marker enzymes.

A promising approach to reduce the occurrence of cancer is its treatment, specifically by chemical intervention through minor dietary constituents. Epidemiological studies suggest that specific pharmacologically active agents present in the diet might reduce cancer. A remarkable surge of interest in chemoprevention research has, thus, lead to the identification of many phytochemicals of dietary origin as effective potential chemotherapeutic agents. In the present investigation, attempt has been made to study the potency of Kalpaamruthaa (KA), a herbal preparation, against cancer. The changes in level of glycoprotein components, marker enzymes and lysosomal enzymes were carried out in 7,12-dimethylbenz(a)anthracene (DMBA) induced Sprague-Dawley rats. The changes in the body weights and volume were also determined. KA was administered at the dosage level of 100, 200, 300, 400 and 500 mg/kg body weight (BW) in olive oil orally for 14 d, after the induction period is completed (90 d). On administration of KA, the levels of the above enzymes and the changes in the body weights and volume were significantly normalized in a dose dependent manner. The present study shows that KA is effective at the dosage level of 300 mg/kg body weight in mammary carcinoma bearing rats.