Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most chronic diseases and for the associated inflammation. The transcription factor, Nuclear Factor-kappaB (NF-kappaB) that controls over 500 different gene products, has emerged as major mediator of inflammation. Thus agents that can inhibit NF-kappaB and diminish chronic inflammation have potential to prevent or delay the onset of the chronic diseases and further even treat them. In an attempt to identify novel anti-inflammatory agents which are safe and effective, in contrast to high throughput screen, we have turned to "reverse pharmacology" or "bed to benchside" approach. We found that Ayurveda, a science of long life, almost 6,000 years old, can serve as a "goldmine" for novel anti-inflammatory agents used for centuries to treat chronic diseases. The current review is an attempt to provide description of various Ayurvedic plants currently used for treatment, their active chemical components, and the inflammatory pathways that they inhibit.

Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: “Reverse Pharmacology” and “Bedside to Bench” Approach

Gallic acid: Molecular rival of cancer

Cancer is a worldwide scourge; it's the leading cause of death in developed countries and is increasing in developing countries Mankind has been trying with effort to find better and cheaper treatments with fewer side effects, to reduce the incidence of the disease and its consequent mortality For many years, phenolic compounds have been intensely studied for their antitumor, proapoptotic and antiangiogenic effects In recent years, the usage of these compounds has increased considerably This manuscript intends to structurally characterize the different phenolic compounds (flavonoids, hydroxycinnamates, hydroxybenzoates, coumarins, xanthones, chalcones, stilbenes, lignins and lignans) and their metabolic pathways as well as review the most important results regarding these compounds and their derivatives in cancer treatment and prevention both in tumor cell lines in vitro, in murine models in vivo and finally some results regarding human trials

/pdf/the-role-of-phenolic-compounds-in-the-fight-against-cancer-a-2twc3vlx3y.pdf

The role of phenolic compounds in the fight against cancer--a review.

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization. Terminalia chebula Retz. (Fam. Combretaceae), is called the ‘King of Medicine’ in Tibet and is always listed at the top of the list of ‘Ayurvedic Materia Medica’ because of its extraordinary power of healing. The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings. Some of the folklore people used this plant in the treatment of asthma, sore throat, vomiting, hiccough, diarrhea, dysentery, bleeding piles, ulcers, gout, heart and bladder diseases. The plant has been demonstrated to possess multiple pharmacological and medicinal activities, such as antioxidant, antimicrobial, antidiabetic, hepatoprotective, anti-inflammatory, antimutagenic, antiproliferative, radioprotective, cardioprotective, antiarthritic, anticaries, gastrointestinal motility and wound healing activity. But no systematic updated information on the therapeutic effectiveness of Terminalia chebula, a popular herbal remedy in India and South-East Asia has so far been reported. This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz. and some of its isolated compounds, along with their safety evaluation. This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.

The development of Terminalia chebula Retz. (Combretaceae) in clinical research

Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages

Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line.

Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation.

High-throughput screening (HTS) involves testing of compound libraries against validated drug targets using quantitative bioassays to identify 'hit' molecules that modulate the activity of target, which forms the starting point of a drug discovery effort. Eicosanoids formed via cyclooxygenase (COX) and lipoxygenase (LOX) pathways are major players in various inflammatory disorders. As the conventional non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit both the constitutive (COX-1) and the inducible (COX-2) isoforms have gastric and renal side effects and the recently developed COX-2 selective anti-inflammatory drugs (COXIBs) have cardiac side effects, efforts are being made to develop more potent and safer antiinflammatory drugs. Current assay methods for these enzymes, such as oxygraphic, radioisotopic, spectrophotometric etc. are not compatible for screening of large number of compounds as in drug discovery programs. In the present study, HTS-compatible assays for COX-1, COX-2 and 5-LOX were developed for screening of compound libraries with the view to identify potential anti-inflammatory drug candidates. A spectrophotometric assay involving co-oxidation of tetramethyl-p-phenylene diamine (TMPD) during the reduction of prostaglandin G2 (PGG2) to PGH2 was adopted and standardized for screening of compounds against COX-1 and COX-2. Similarly, the HTS-compatible FOX (ferrous oxidation-xylenol orange) based spectrophotometric assay involving the formation of Fe3+/xylenol orange complex showing absorption in the visible range was developed for screening of compounds against 5-LOX.

High-throughput screening assays for cyclooxygenase-2 and 5-lipoxygenase, the targets for inflammatory disorders.

Arachidonic acid (AA) metabolism in the non-pregnant sheep uterus was studied in vitro using conventional chromatographic and HPLC techniques. High expression of both lipoxygenase (LOX) as well as cyclooxygenase (COX) enzymes and their activities was found in the uterine tissues. On incubation of uterine enymes with AA, the LOX products formed were identified as 5-hydroperoxyeicosatetraenoic acid (5-HPETE), 12- and 15-hydroxyeicosatetraenoic acids (12- and 15-HETEs), based on their separation on TLC and HPLC. By employing differential salt precipitation techniques, the LOXs generating products 5-HPETE (5-LOX), 12-HETE and 15-HETE (12- and 15-dual LOX) were isolated. Based on their analysis on TLC, the COX products formed were identified as prostaglandins - PGF2alpha and prostacyclin derivative 6-keto PGF1alpha. The study forms the first report on the comprehensive analysis on the metabolism of AA in sheep uterus in vitro via the LOX and COX pathways.

http://nopr.niscair.res.in/bitstream/123456789/118/1/IJBB%2044%284%29%20%282007%29%20216-222.pdf

D. Bharat Reddy

Papers

Chebulagic acid (CA) attenuates LPS-induced inflammation by suppressing NF-κB and MAPK activation in RAW 264.7 macrophages

Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line.

Anti-leukemic effects of gallic acid on human leukemia K562 cells: downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation.

High-throughput screening assays for cyclooxygenase-2 and 5-lipoxygenase, the targets for inflammatory disorders.

Metabolism of arachidonic acid in sheep uterus: in vitro studies.