The Cationminus signpi Interaction.

Free radicals are common outcome of normal aerobic cellular metabolism. In-built antioxidant system of body plays its decisive role in prevention of any loss due to free radicals. However, imbalanced defense mechanism of antioxidants, overproduction or incorporation of free radicals from environment to living system leads to serious penalty leading to neuro-degeneration. Neural cells suffer functional or sensory loss in neurodegenerative diseases. Apart from several other environmental or genetic factors, oxidative stress (OS) leading to free radical attack on neural cells contributes calamitous role to neuro-degeneration. Though, oxygen is imperative for life, imbalanced metabolism and excess reactive oxygen species (ROS) generation end into a range of disorders such as Alzheimer's disease, Parkinson's disease, aging and many other neural disorders. Toxicity of free radicals contributes to proteins and DNA injury, inflammation, tissue damage and subsequent cellular apoptosis. Antioxidants are now being looked upon as persuasive therapeutic against solemn neuronal loss, as they have capability to combat by neutralizing free radicals. Diet is major source of antioxidants, as well as medicinal herbs are catching attention to be commercial source of antioxidants at present. Recognition of upstream and downstream antioxidant therapy to oxidative stress has been proved an effective tool in alteration of any neuronal damage as well as free radical scavenging. Antioxidants have a wide scope to sequester metal ions involved in neuronal plaque formation to prevent oxidative stress. In addition, antioxidant therapy is vital in scavenging free radicals and ROS preventing neuronal degeneration in post-oxidative stress scenario.

Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options.

Turmeric, derived from the plant Curcuma longa, is a gold-colored spice commonly used in the Indian subcontinent, not only for health care but also for the preservation of food and as a yellow dye for textiles. Curcumin, which gives the yellow color to turmeric, was first isolated almost two centuries ago, and its structure as diferuloylmethane was determined in 1910. Since the time of Ayurveda (1900 Bc) numerous therapeutic activities have been assigned to turmeric for a wide variety of diseases and conditions, including those of the skin, pulmonary, and gastrointestinal systems, aches, pains, wounds, sprains, and liver disorders. Extensive research within the last half century has proven that most of these activities, once associated with turmeric, are due to curcumin. Curcumin has been shown to exhibit antioxidant, anti-inflammatory, antiviral, antibacterial, antifungal, and anticancer activities and thus has a potential against various malignant diseases, diabetes, allergies, arthritis, Alzheimer's disease, and other chronic illnesses. These effects are mediated through the regulation of various transcription factors, growth factors, inflammatory cytokines, protein kinases, and other enzymes. Curcumin exhibits activities similar to recently discovered tumor necrosis factor blockers (e.g., HUMIRA, REMICADE, and ENBREL), a vascular endothelial cell growth factor blocker (e.g., AVASTIN), human epidermal growth factor receptor blockers (e.g., ERBITUX, ERLOTINIB, and GEFTINIB), and a HER2 blocker (e.g., HERCEPTIN). Considering the recent scientific bandwagon that multitargeted therapy is better than monotargeted therapy for most diseases, curcumin can be considered an ideal "Spice for Life".

Curcumin: The Indian solid gold

Reactive oxygen species (ROS) are generated as by-products of normal cellular metabolic activities. Superoxide dismutase, glutathione peroxidase, and catalase are the enzymes involved in protecting cells from the damaging effects of ROS. ROS are produced in response to ultraviolet radiation, cigarette smoking, alcohol, nonsteroidal anti-inflammatory drugs, ischemia-reperfusion injury, chronic infections, and inflammatory disorders. Disruption of normal cellular homeostasis by redox signaling may result in cardiovascular, neurodegenerative diseases and cancer. ROS are produced within the gastrointestinal (GI) tract, but their roles in pathophysiology and disease pathogenesis have not been well studied. Despite the protective barrier provided by the mucosa, ingested materials and microbial pathogens can induce oxidative injury and GI inflammatory responses involving the epithelium and immune/inflammatory cells. The pathogenesis of various GI diseases including peptic ulcers, gastrointestinal cancers, and inflammatory bowel disease is in part due to oxidative stress. Unraveling the signaling events initiated at the cellular level by oxidative free radicals as well as the physiological responses to such stress is important to better understand disease pathogenesis and to develop new therapies to manage a variety of conditions for which current therapies are not always sufficient.

Oxidative Stress: An Essential Factor in the Pathogenesis of Gastrointestinal Mucosal Diseases

Melatonin was discovered to be a direct free radical scavenger less than 10 years ago. Besides its ability to directly neutralize a number of free radicals and reactive oxygen and nitrogen species, it stimulates several antioxidative enzymes which increase its efficiency as an antioxidant. In terms of direct free radical scavenging, melatonin interacts with the highly toxic hydroxyl radical with a rate constant equivalent to that of other highly efficient hydroxyl radical scavengers. Additionally, melatonin reportedly neutralizes hydrogen peroxide, singlet oxygen, peroxynitrite anion, nitric oxide and hypochlorous acid. The following antioxidative enzymes are also stimulated by melatonin: superoxide dismutase, glutathione peroxidase and glutathione reductase. Melatonin has been widely used as a protective agent against a wide variety of processes and agents that damage tissues via free radical mechanisms.

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Actions of melatonin in the reduction of oxidative stress

Neem (Azadirachta indica A. Juss) is perhaps the most useful traditional medicinal plant in India. Each part of the neem tree has some medicinal property and is thus commercially exploitable. During the last five decades, apart from the chemistry of the neem compounds, considerable progress has been achieved regarding the biological activity and medicinal applications of neem. It is now considered as a valuable source of unique natural products for development of medicines against various diseases and also for the development of industrial products. This review gives a bird’s eye view mainly on the biological activities of some of the neem compounds isolated, pharmacological actions of the neem extracts, clinical studies and plausible medicinal applications of neem along with their safety evaluation. MEDICINAL plants are part and parcel of human society to combat diseases, from the dawn of civilization. Azadirachta indica A. Juss (syn. Melia azadirachta) is well known in India and its neighbouring countries for more than 2000 years as one of the most versatile medicinal plants having a wide spectrum of biological activity. A. indica A. Juss and M. azedarach are two closely related species of Meliaceae. The former is popularly known as Indian neem (margosa tree) or Indian lilac, and the latter as the Persian lilac. Neem is an evergreen tree, cultivated in various parts of the Indian subcontinent. Every part of the tree has been used as traditional medicine for household remedy against various human ailments, from antiquity 1–6 . Neem has been extensively used in ayurveda, unani and homoeopathic medicine and has become a cynosure of modern medicine. The sanskrit name of the neem tree is ‘Arishtha’ meaning ‘reliever of sickness’ and hence is considered as ‘Sarbaroganib arini’. The tree is still regarded as ‘village dispensary’ in India. The importance of the neem tree has been recognized by the US National Academy of Sciences, which published a report in 1992 entitled ‘Neem – a tree for solving global problems’. The advancement of neem research has earlier been documented 7,8

Biological activities and medicinal properties of neem (Azadirachta indica)

Turmeric (Curcuma longa) is extensively used as a spice, food preservative and colouring material in India, China and South East Asia. It has been used in traditional medicine as a household remedy for various diseases, including biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism and sinusitis. For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of turmeric and its extracts. Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has been shown to have a wide spectrum of biological actions. These include its antiinflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. Its anticancer effect is mainly mediated through induction of apoptosis. Its antiinflammatory, anticancer and antioxidant roles may be clinically exploited to control rheumatism, carcinogenesis and oxidative stress-related pathogenesis. Clinically, curcumin has already been used to reduce post-operative inflammation. Safety evaluation studies indicate that both turmeric and curcumin are well tolerated at a very high dose without any toxic effects. Thus, both turmeric and curcumin have the potential for the development of modern medicine for the treatment of various diseases.

Turmeric and curcumin: Biological actions and medicinal applications

Reactive oxygen species (ROS) such as O2–, H2O2 and OH are highly toxic to cells. Cellular antioxidant enzymes, and the free-radical scavengers normally protect a cell from toxic effects of the ROS. However, when generation of the ROS overtakes the antioxidant defense of the cells, oxidative damage of the cellular macromolecules (lipids, proteins, and nucleic acids) occurs, leading finally to various pathological conditions. ROS-mediated lipid peroxidation, oxidation of proteins, and DNA damage are well-known outcomes of oxygen-derived free radicals, leading to cellular pathology and ultimately to cell death. The mechanism of ROS-mediated oxidative damage of lipids, proteins, and DNA has been extensively studied. The site-specific oxidative damage of some of the susceptible amino acids of proteins is now regarded as the major cause of metabolic dysfunction during pathogenesis. ROS have also been implicated in the regulation of at least two well-defined transcription factors which play an important role in the expression of various genes encoding proteins that are responsible for tissue injury. One of the significant benefits of the studies on ROS will perhaps be in designing of a suitable antioxidant therapy to control the ROS-mediated oxidative damage, and the disease processes.

Ranajit K. Banerjee

Papers

Biological activities and medicinal properties of neem (Azadirachta indica)

Turmeric and curcumin: Biological actions and medicinal applications

Reactive oxygen species: oxidative damage and pathogenesis

Hydroxyl radical is the major causative factor in stress-induced gastric ulceration.

A novel antioxidant and antiapoptotic role of omeprazole to block gastric ulcer through scavenging of hydroxyl radical