Curcumin (diferuloylmethane) derived from the rhizome of Curcuma longa L. has been used for thousands of years in traditional Chinese medicine and Ayurvedic medicine in Asian countries to treat liver diseases, rheumatoid diseases, diabetes, atherosclerosis, infectious diseases and cancer. It exhibits a wide range of pharmacological properties, which include antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer activity. Herein the mechanisms of curcumin impact on oxidative stress, angiogenesis and inflammatory processes are described indicating that curcumin use may inhibit those pathological conditions and restore body homeostasis. Its effectiveness was also proved for major eye diseases. In this review, the influence of curcumin on eye diseases, such as glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, corneal neovascularization, corneal wound healing, dry eye disease, conjunctivitis, pterygium, anterior uveitis are reported. The analysis of a number of clinical and preclinical investigations indicates that curcumin may be used as a therapeutic agent in the treatment of various eye disorders.

The adult mouse heart possesses an extensive lymphatic plexus draining predominantly the subepicardium and the outer layer of the myocardial wall. However, the development of this plexus has not been entirely explored, partially because of the lack of suitable methods for its visualization as well as prolonged lymphatic vessel formation that starts prenatally and proceeds during postnatal stages. Also, neither the course nor location of collecting vessels draining lymph from the mouse heart have been precisely characterized. In this article, we report that murine cardiac lymphatic plexus development that is limited prenatally only to the subepicardial area, postnatally proceeds from the subepicardium toward the myocardial wall with the base-to-apex gradient; this plexus eventually reaches the outer half of the myocardium with a predominant location around branches of coronary arteries and veins. Based on multiple marker immunostaining, the molecular marker-phenotype of cardiac lymphatic endothelial cells can be characterized as: Prox-1 1 , Lyve-1 1 , VEGFR3 1 , Podoplanin 1 , VEGFR2 1 , CD144 1 , Tie2 1 , CD31 1 , vWF 2 , CD34 2 , CD133 2 . There are two major collecting vessels: one draining the right and left ventricles along the left conal vein and running upwards to the left side of the pulmonary trunk and further to the nearest lymph nodes (under the aortic arch and near the trachea), and the other one with its major branch running along the left cardiac vein and further on the surface of the coronary sinus and the left atrium to paratracheal lymph nodes. The extracardiac collectors gain the smooth muscle cell layer during late postnatal stages.

The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells.

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Co-operation of the endogenous and exogenous defense system maintains redox homeostasis and is essential for health. The endogenous defense system includes enzymatic (e.g. superoxide dismutase, catalase) and non-enzymatic, low molecular-weight scavengers (e.g. glutathione, ascorbic acid). Pathogenesis of many serious diseases (e.g. cancer, ischemic heart disease) includes oxidative stress which can disturb angiogenesis, the process of formation of new blood vessels sprouting from the existing one. Antioxidants, through reduction of oxidative stress and influence on neovascularization, may modulate progress and results of therapy in those diseases where such processes play an important role. Herein the impact of exogenous antioxidants on angiogenesis and factors modulating this process is presented. Most synthetic antioxidants whose activity has been described (namely N-acetylcysteine, pentoxifylline, synthetic analogue of curcumin, synthetic analogue of epigallocatechin-3 gallate [EGCG], tripertenoids) exert an inhibitory effect on neovascularization. A similar effect was also exhibited by several natural origin antioxidants (e.g. resveratrol, EGCG), which suggests that their application in therapy might normalize excessive angiogenesis. Some natural origin antioxidants e.g. purple coneflower and preparations consisting of natural antioxidants such as Padma 28 and Immunal forte increase a too low baseline level of angiogenesis and decreases a too high level. These preparations exert a regulatory effect on and may normalize neovascularization. They can be used in the case of diseases associated with too low or too high angiogenesis.

Angiogenesis is important for normal functioning of organism and its disturbances are observed in many diseases, called angiogenesis-related states. Reactive oxygen species (ROSs) play an important role in physiology, but high level of cellular ROSs is cytotoxic and mutagenic for the cells, i.e. it can lead to oxidative stress. In this review we discuss close relationship between ROSs and angiogenesis process. Substances counteracting free radicals or their action and oxidative stress are known as antioxidants. We postulate that antioxidants, by affecting angiogenesis, may modulate therapy results in the case of angiogenesis-related disease. Herein, we present some antioxidant preparations of synthetic (N-acetylcysteine, curcumin and its analogs, Probucol, oleane tripertenoid, EGCG synthetic analogs) and nature-identical (vitamin E and C) origin. Then, we analyze their angiogenic properties and their multidirectional molecular effect on angiogenesis. Most preparations reduce neovascularization and diminish the level of proangiogenic molecules, downregulating signaling pathways related to angiogenesis. Moreover, we discuss studies concerning anticancer properties of presented synthetic antioxidants and their application in several angiogenesis-related diseases. We conclude that therapy in angiogenesis-related diseases should be planned with consideration of the angiogenic status of the patient.

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Disturbances of angiogenesis and oxidative stress can lead to many serious diseases such as cancer, diabetes or ischemic heart disease. Substances neutralizing oxidative stress are known as antioxidants. They can affect angiogenesis process also, and thus, they modulate therapy results. Antioxidants become more and more frequently used in order to maintain homeostasis of the organism and diminish the risk of disease. Herein, we introduce some antioxidant preparations of natural plant origin (Rhodiola, Aloe vera, Resveratrol, Echinacea, Plumbagin) and antioxidant supplements (Padma 28, Reumaherb, Resvega). Analyses of their angiogenic properties, their multidirectional molecular effect on angiogenesis as well as medical application are within the scope of this review. Most of presented preparations down regulate neovascularization. They can be safely administered to patients with abnormally high angiogenesis. Rhodiola modulates, and Echinacea, Aloe vera and Plumbagin inhibit tumour-related angiogenesis in vitro and in vivo (animal models). Resveratrol and Resvega reduce neovascularization in the eye and may be applicable in eye disorders. Padma 28 preparation exhibits angioregulatory activity, decreasing high angiogenesis of cancer cells and increasing physiological angiogenesis, therefore can be used in therapy of patients with various disturbances of angiogenesis. Antioxidant application in the case of angiogenesis-related diseases should take into consideration angiogenic status of the patient.