Ameliorative effect of methanol extract of Rubia cordifolia in N-nitrosodiethylamine-induced hepatocellular carcinoma.

CONTEXT: Rubia cordifolia Linn. (Rubiaceae) is a medicinal plant used in the ayurvedic system of medicine. It is also known as Indian Madder or Manjistha and is traditionally used as an antiinflammatory, antiseptic, and galactopurifier, but its anticancer propertis are yet not known. OBJECTIVE: The ameliorative effect of the Rubia cordifolia methanol extract on N-nitrosodiethylamine-induced experimental hepatocellular carcinogenesis in rats. MATERIALS AND METHODS: Changes in liver weight, serum markers of liver damage, hydroxyl radicals, lipid peroxidation, levels of enzymic and nonenzymic antioxidants; mitochondrial and respiratory chain enzymes were also investigated using various biochemical parameters and histopathological studies. Male albino rats of Wistar strain were divided into four groups for a study period of 3 months. Animals of group I and group IV served as control and drug control, respectively. Hepatocellular carcinoma was induced in animals of groups II and III with 0.02% N-nitrosodiethylamine. RESULTS: Upon Rubia cordifolia methanol extract co-treatment (250, 500, and 750 mg/kg bodyweight) in group III alone levels of serum marker enzymes and antioxidants increased significantly in a dose-dependent manner. The levels of hydroxyl radicals and lipid peroxidation decreased. Mitochondrial enzymes and respiratory chain enzymes, which were decreased in N-nitrosodiethylamine-induced rats, increased significantly in RC treated rats. Further histological analysis of liver confirmed the prevention of pathological changes caused by N-nitrosodiethylamine on Rubia cordifolia supplementation. DISCUSSION AND CONCLUSION: These findings demonstrate that Rubia cordifolia can be a source of potent antioxidants for treatment of diseases such as cancer.

Imperatorin a furocoumarin inhibits periplasmic Cu-Zn SOD of Shigella dysenteriae their by modulates its resistance towards phagocytosis during host pathogen interaction.

Shigella dysenteriae continues to be a major health problem, which leads to death, due to diarrhoea and dysentery, predominantly in children below the age of 5. Bacterial invasion of the colonic epithelium leads to severe inflammation together with bacterial dissemination generates abscesses and ulcerations. Periplasmic copper, zinc super oxide dismutase of Shigella protects it from exogenous superoxide produced by host, during its invasion. Hence, in present study an attempt was made to study the effect of aqueous extract of Aegle marmelos on host and pathogen defence. Histology analysis of rat ileal loop showed the loss of virulence in aqueous extract of A. marmelos pre-treated Shigella and their intracellular survival was also decreased, where active component present in aqueous extract of A. marmelos was identified as imperatorin confirmed by UV absorption spectrum and HPLC. Increase in peripheral blood mononuclear cell viability and decreased in intracellular bacterial count along with transmission electron microscope analysis of imperatorin treated S. dysenteriae succumb to host oxidative stress. Loss of virulence is associated with attenuation of copper, zinc super oxide dismutase activity in Shigella, which was confirmed by using activity staining of bacterial cell lysate. Further, by performing docking analysis it has been proved that imperatorin present in aqueous extract of A. marmelos inhibited copper, zinc super oxide dismutase. From the above study, we concluded that Shigella succumb to oxidative stress (host defence) due to inhibition of copper, zinc super oxide dismutase (pathogen's defence) by imperatorin, an active compound aqueous extract of A. marmelos.

Differential expression of ompC and ompF in multidrug-resistant Shigella dysenteriae and Shigella flexneri by aqueous extract of Aegle marmelos, altering its susceptibility toward beta-lactam antibiotics.

Steadily increasing resistance among Shigella to beta-lactams, aminoglycosides, and tetracycline has compromised the utility of these commonly used antimicrobial agents. Also, undesirable side effects of certain antibiotics have triggered immense interest in search of alternative therapies using medicinal plants. One such medicinal plant used since ancient times to cure diarrhea is Aegle marmelos. The present study exemplifies the susceptibility of beta-lactam-resistant Shigella dysenteriae and Shigella flexneri toward beta-lactam antibiotics, when grown in the presence of aqueous extract of A. marmelos (AEAM), by altering porin channels. This was demonstrated by antibiotic sensitivity test using disc diffusion method and MIC test. Susceptibility toward beta-lactam antibiotic is associated with changes in outer membrane porins OmpC (approximately 42 kDa) and OmpF (approximately 38 kDa) and cytosolic proteins of approximately 26 kDa, OmpR, a transcriptional regulator. Expression of ompF is increased in S. dysenteriae and S. flexneri grown in the presence of AEAM due to down-regulation of ompR, which is conformed by reverse transcriptase polymerase chain reaction. In conclusion, AEAM influences susceptibility of beta-lactam-resistant Shigella toward beta-lactam antibiotics by altering porin channels. Hence, AEAM along with beta-lactam can be used for treatment of multidrug-resistant Shigella.