Enzyme Therapy: Current Perspectives.

Enzymes control all metabolic processes in human system from simple digestion of food to highly complex immune response. Physiological reactions occuring in healthy individuals are disturbed when enzymes are deficient or absent. Enzymes are administered for normalizing biological function in certain pathologies. Initially, crude proteolytic enzymes were used for the treatment of gastrointestinal disorders. Recent advances have enabled enzyme therapy as a promising tool in the treatment of cardiovascular, oncological and hereditary diseases. Now, a spectrum of other diseases are also covered under enzyme therapy. But, the available information on the use of enzymes as therapeutic agents for different diseases is scanty. This review details the enzymes which have been used to treat various diseases/disorders.

Enzymes in clinical medicine: An overview.

Enzymes are biocatalysts and because of their remarkable properties, they are extensively used in medical diagnosis. Researches in the last two decades have concentrated more on enzymes such as creatine kinase–MB, alanine transaminase, aspartate transaminase, acid phosphatase, alkaline phosphatase etc. for clinical applications. Enzymes are the preferred markers in various disease states such as myocardial infarction, jaundice, pancreatitis, cancer, neurodegenerative disorders, etc. They provide insight into the disease process by diagnosis, prognosis and assessment of response therapy. Even though the literature on the use of enzymes in various disease conditions has accumulated, a comprehensive analysis is lacking and hence this review.

Therapeutic effects of proanthocyanidins on the pathogenesis of periodontitis— An overview.

Periodontitis is a bacterially induced chronic inflammatory disease that destroys the connective tissue and bone that support teeth. Bacteria initiates periodontitis and destruction of the alveolar bone and periodontal connective tissue is clearly observed. But, the events occuring between these two points of time remain obscure and this study focusses on these aspects. The proanthocyanidins (PC) have variable pharmacological and nutraceutical benefits including improvement of ischemic cardiovascular disease, prevention of atherosclerosis and antiarthritic, anticancer and antimicrobial activities. The benefits associated with the antioxidant activity of PC have been evaluated both in vivo and in vitro. But, reports on the ameliorative effects of PC on oral diseases and specifically on periodontitis are very few. Hence, a novel attempt is made to review the possible protective effects of PC and its mechanism of action in periodontitis and also to show whether PC could be developed as a therapeutic agent for periodontitis.

In vitro studies on inhibitory effect of proanthocyanidins in modulation of neutrophils and macrophages.

The role of proanthocyanidins (PC), a novel flavonoid extracted from grape seeds was studied in vitro in the modulation of neutrophil and macrophage function. We attempted to assess the levels of non-enzymatic and enzymatic mediators in the presence or absence of PC in 4-phorbol-12--myristate-13-acetate (PMA)-stimulated neutrophils isolated from humans and rats, E. coli endotoxin-stimulated macrophages and macrophages isolated from E. coli endotoxin-induced experimental periodontitis in rats. Addition of PC at a concentration of 50 µg/ml effectively blocked the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and exhibited a marked inhibition of myeloperoxidase (MPO) and lysosomal enzymes (p<0.001), as compared to PMA-stimulated neutrophils (human and rats) and neutrophils isolated from experimental periodontitis in rats. The levels of ROS, RNS and lysosomal enzymes were found to be elevated (p<0.001) and addition of PC significantly (p<0.001) reduced these levels as compared to those from E. coli endotoxin-stimulatedmacrophages from rats and macrophages isolated from experimental periodontitis in rats (p<0.001). Thus, the study demonstrated that PC decreased the levels of ROS and RNS and also inhibited the MPO and lysosomal enzymes activities in experimental periodontitis in rats. In addition, this study clearly indicated that PC could be developed as an effective antiinflammatory agent.

Arjunolic acid: A novel phytomedicine with multifunctional therapeutic applications.

Herbal plants with antioxidant activities are widely used in Ayurvedic medicine for cardiac and other problems. Arjunolic acid is one such novel phytomedicine with multifunctional therapeutic applications. It is a triterpenoid saponin, isolated earlier from Terminalia arjuna and later from Combretum nelsonii, Leandra chaeton etc. Arjunolic acid is a potent antioxidant and free radical scavenger. The scientific basis for the use of arjunolic acid as cardiotonic in Ayurvedic medicine is proven by its vibrant functions such as prevention of myocardial necrosis, platelet aggregation and coagulation and lowering of blood pressure, heart rate and cholesterol levels. Its antioxidant property combined with metal chelating property protects organs from metal and drug induced toxicity. It also plays an effective role in exerting protection against both type I and type II diabetes and also ameliorates diabetic renal dysfunctions. Its therapeutic multifunctionality is shown by its wound healing, antimutagenic and antimicrobial activity. The mechanism of cytoprotection conferred by arjunolic acid can be explained by its property to reduce the oxidative stress by enhancing the antioxidant levels. Apart from its pathophysiological functions, it possesses dynamic insecticidal property and it is used as a structural molecular framework in supramolecular chemistry and nanoscience. Esters of arjunolic acid function as gelators of a wide variety of organic liquids. Experimental studies demonstrate the versatile effects of arjunolic acid, but still, further investigations are necessary to identify the functional groups responsible for its multivarious effects and to study the molecular mechanisms as well as the probable side effects/toxicity owing to its long-term use. Though the beneficial role of this triterpenoid has been assessed from various angles, a comprehensive review of its effects on biochemistry and organ pathophysiology is lacking and this forms the rationale of this review.

Protective effect of proanthocyanidins on endotoxin induced experimental periodontitis in rats.

The pathogenesis of periodontitis involves anaerobic oral bacteria as well as the host response to infection and several drugs have been developed which can curtail these deleterious effects. Proanthocyanidin, a novel flavanoid extracted from grape seeds, has been shown to provide a significant therapeutic effect on endotoxin (Escherichia coli) induced experimental periodontitis in rats. In this study, protective action of different doses of proanthocyanidins was investigated in blood by assaying the reactive oxygen species such as hydrogen peroxide, superoxide anion, myeloperoxidase and lipid peroxides, lysosomal enzyme activities such as cathepsin B, cathepsin D, β-glucuronidase and acid phosphatase, nonenzymatic antioxidants such as ascorbic acid, -tocopherol, ceruloplasmin, reduced glutathione and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and glutathione-s-transferase. Experimental periodontitis rats showed a reduction in body weight and body weight gain could be noticed when they were administered proanthocyanidins. The levels of reactive oxygen species and lysosomal enzymes were found to increase whereas antioxidant levels were decreased significantly in experimental periodontitis. Proanthocyanidins at an effective dose of 30mg / kg body weight, sc, for 30 days effected a decrease in serum reactive oxygen species, lipid peroxides, lysosomal enzymes, acute phase proteins and an increase in antioxidant levels. Histopathological evidence of experimental periodontitis showed cellular infiltration of inflammatory cells while proanthocyanidin treated groups demonstrated only scattered inflammatory cells and blood vessels. Thus, the results showed that dietary supplementation of proanthocyanidin enhanced the host resistance as well as the inhibition of the biological and mechanical irritants involved in the onset of gingivitis and the progression of periodontal disease.