Subhash C. Mandal

COX-2 as a target for cancer chemotherapy

Cyclooxygenase-1 and -2 (COX-1/2) catalyze the initial step in the formation of prostaglandins. Very recently their role in carcinogenesis has become more evident. They influence apoptosis, angiogenesis, and invasion, and play a key role in the production of carcinogens. Usually, a high level of COX-2 expression is found in cancer cells. Large epidemiological trials studying users and non-users of aspirin have shown that cyclooxygenase inhibitors and non-steroidal anti-inflammatory drugs (NSAIDs) could be of benefit against the development and growth of malignancies. Moreover, clinical trials in patients with familial adenomatosis polyposis syndrome have shown the efficacy of selective COX-2 inhibitors in the reduction of the number and size of colorectal polyps. Several preclinical studies show promising results with combinatorial treatments of either chemotherapy or radiotherapy with COX inhibitors. Preclinical studies with the simultaneous use of inhibitors of the epidermal growth factor receptor and COX-2 inhibitors have shown also promising results. Encouraging results from the first clinical trials combining chemotherapy with COX-2 inhibitors in patients with cancer in the advanced and neoadjuvant setting have recently been reported. Thus, it appears that targeting the COX-2 pathway is a promising strategy in the prevention and treatment of solid tumors.

Antidiabetic potential of Barleria lupulina extract in rats.

The methanol extract of aerial parts of Barleria lupulina orally tested at doses of 100, 200 and 300 mg/kg exerted significant antihyperglycemic effect in streptozotocin-induced hyperglycemia in rats [correction].

Evaluation of hepatoprotective activity of Cassia fistula leaf extract.

Hepatoprotective activity of the n-heptane extract of Cassia fistula leaves was investigated in rats by inducing hepatotoxicity with carbon tetrachloride:liquid paraffin (1:1). The extract has been shown to possess significant protective effect by lowering the serum levels of transminases (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). The extract of C. fistula at a dose of 400 mg/kg showed significant hepatoprotective activity which was comparable to that of a standard hepatoprotective agent.

Studies on antidiarrhoeal activity of Punica granatum seed extract in rats

Methanol extract of Punica granatum seed was evaluated for antidiarrhoeal activity against different experimental models of diarrhoea in rats. P. granatum seed extract treated animals showed significant inhibitory activity against castrol-oil induced diarrhoea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastro-intestinal motility in charcoal meal test in rats. The results obtained established the efficacy of P. granatum seed extract as an antidiarrhoeal agent.

Anti-inflammatory, analgesic and antipyretic properties of Clitoria ternatea root

Clitoria ternatea roots methanol extract when given by oral route to rats was found to inhibit both the rat paw oedema caused by carrageenin and vascular permeability induced by acetic acid in rats. Moreover, the extract exhibited a significant inhibition in yeast-induced pyrexia in rats. In the acetic acid-induced writhing response, the extract markedly reduced the number of writhings at doses of 200 and 400 mg/kg (p.o.) in mice.

Antioxidant protection: A promising therapeutic intervention in neurodegenerative disease

Abstract Oxidative stress has been consistently linked to ageing-related neurodegenerative diseases. Neurodegenerative diseases are characterized by progressive dysfunction and death of neurons. Oxidative stress is associated with dysfunction of the mitochondria and endoplasmic reticulum, inducing apoptosis and protein misfolding in neurons. Decreased activities of antioxidant enzymes like SOD, catalase, glutathione, glutathione peroxidase in neurodegenerative states signifies role of reduced antioxidant potential in neurodegeneration. Among the cellular pathways conferring protection against oxidative stress, a key role is played by vitagenes, which include Hsp70, heme oxygenase-1, thioredoxin and sirtuins. Cellular signalling pathways and molecular mechanisms that mediate hormetic responses typically involve antioxidant enzymes and transcription factors such as Nrf-2 and NFκB. Vitagenes, either individually or by acting in concert, contribute to counteract the ROS mediated damage. In this review the importance of oxidative stress and the potential use of antioxidants in the prevention and treatment of neurodegenerative disorders are discussed.

Hepatoprotective activity of Cassia fistula leaf extract

Hepatoprotective activity of the n-heptane extract of Cassia fistula leaves was investigated by inducing hepatotoxicity with paracetamol in rats. The extract at a dose of 400 mg/kg body wt. exhibited orally, significant protective effect by lowering the serum levels of transaminases (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). The effects produced were comparable to that of a standard hepatoprotective agent.

Anti-inflammatory evaluation of Ficus racemosa Linn. leaf extract.

The anti-inflammatory activity of Ficus racemosa extract was evaluated on carrageenin, serotonin, histamine and dextran-induced rat hind paw oedema models. The extract at doses of 200 and 400 mg/kg has been found to possess significant anti-inflammatory activity on the tested experimental models. The extract (400 mg/kg) exhibited maximum anti-inflammatory effect, that is 30.4, 32.2, 33.9 and 32.0% at the end of 3 h with carrageenin, serotonin, histamine, dextran-induced rat paw oedema, respectively. In a chronic test the extract (400 mg/kg) showed 41.5% reduction in granuloma weight. The effect produced by the extract was comparable to that of phenylbutazone, a prototype of a non-steroidal anti-inflammatory agent.

Studies on analgesic activity of Cleome viscosa in mice

The analgesic activity of methanol extract of Cleome viscosa, given orally at the doses of 100, 200, 400 mg/kg was evaluated for its analgesic activity in mice using the acetic acid-induced writhing and the tail flick, tail clip, tail immersion methods. The extract showed promising activity in all the tests.

Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism

Activation of nuclear factor-kappa B (NF- κ B) as a mechanism of host defense against infection and stress is the central mediator of inflammatory responses. A normal (acute) inflammatory response is activated on urgent basis and is auto-regulated. Chronic inflammation that results due to failure in the regulatory mechanism, however, is largely considered as a critical determinant in the initiation and progression of various forms of cancer. Mechanistically, NF- κ B favors this process by inducing various genes responsible for cell survival, proliferation, migration, invasion while at the same time antagonizing growth regulators including tumor suppressor p53. It has been shown by various independent investigations that a down regulation of NF- κ B activity directly, or indirectly through the activation of the p53 pathway reduces tumor growth substantially. Therefore, there is a huge effort driven by many laboratories to understand the NF- κ B signaling pathways to intervene the function of this crucial player in inflammation and tumorigenesis in order to find an effective inhibitor directly, or through the p53 tumor suppressor. We discuss here on the role of NF- κ B in chronic inflammation and cancer, highlighting mutual antagonism between NF- κ B and p53 pathways in the process. We also discuss prospective pharmacological modulators of these two pathways, including those that were already tested to affect this mutual antagonism.