thromboxane-a2 and Psoriasis

Topics: Animals; Dermatitis; Disease Models, Animal; Humans; Imiquimod; Interleukin-17; Mice; Mice, Inbred C57BL; Mice, Knockout; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Receptors, G-Protein-Coupled; Receptors, Thromboxane A2, Prostaglandin H2; T-Lymphocytes; Thromboxane A2; Thromboxane-A Synthase

Psoriasis is a chronic relapsing immune mediated disorder of the skin. The disease presents itself with well featured clinical and histological characteristics however the aetiology of the disease still remains obscure. The current systemic therapies aim to eliminate the symptoms of disease rather than offering a complete cure. Parangichakkai chooranam (PC), a Siddha oral herbal formulation has been widely prescribed for the treatment of psoriasis. Though the medication is highly prescribed by the Siddha healers the mechanism of PC for the treatment of psoriasis remains to be elucidated. The current study utilizes an integrated systems pharmacology approach to decipher the mechanism of action of PC. The comprehensive network pharmacological approach resulted in the construction of a Compound-Target network which encloses 155 compounds and 583 protein targets. A Disease-Target network was constructed by assembling disease proteins and their partners. When the compound targets were mapped to the network their involvement as controllers of the disease and triggers of disease associated comorbidities were identified. A Target-Pathway network raised from the pathway enrichment analysis not only identified disease specific pathways but also the pathways mediating secondary complications such as skin hemostasis, wound healing, desquamation and itch. The present work sheds light on the mechanism of action of PC in treating psoriasis. This work not only highlights the pharmacological action of the formulation but also emphasis on safe herbal remedies offered by the Siddha medicinal system.

Topics: Biological Availability; Humans; Inflammation; Medicine, Ayurvedic; Pharmacology; Phytochemicals; Phytotherapy; Plant Extracts; Psoriasis; Signal Transduction; Systems Biology; Thromboxane A2

The aim of the present study was to ascertain the relationship between in vitro hyper-aggregability and alterations in arachidonic acid metabolism in platelets from psoriatic patients. We have studied the response to several concentrations of ADP, collagen, and arachidonic acid of intact platelets from psoriatic patients and normal subjects, with and without irreversible inhibition of platelet cyclooxygenase by aspirin. Apparent kinetic constants (apparent Michaelis constant [Km] and apparent maximum velocity [Vmax]) of cyclooxygenase in platelets from both controls and psoriatic patients were also studied. The maximum percentage and slope of aggregation induced by collagen or sodium arachidonate were significantly greater (p less than 0.05) in platelets from psoriasis patients, whereas lag time was significantly shorter in the psoriasis group in response to arachidonic acid only when compared to controls. Cyclooxygenase pathway blockade inhibited the response to aggregation inducers in the following order: sodium arachidonate greater than collagen greater than ADP. When platelets were pre-treated with aspirin no significant differences were observed between controls and psoriasis patients. We also found a significant increase of the apparent Vmax value (p less than 0.05) for cyclooxygenase activity in platelets from psoriatic patients in comparison with controls. Our results indicate that platelet hyperaggregation in psoriatic patients is related to enhanced cyclooxygenase activity in their platelets.

Topics: Adult; Arachidonic Acid; Aspirin; Blood Platelets; Carbon Radioisotopes; Collagen; Humans; Kinetics; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Psoriasis; Thromboxane A2

A failure of thromboxane (TX) A2 synthesis may be a factor in cancer. Such a loss could explain the susceptibility to mutation, the excess prostaglandin production, the glycolytic mode of metabolism and the deranged calcium pumping characteristic of cancers. Ionising radiation and phorbols both have actions similar to inhibitors of TXA2 synthesis whereas colchicine and oxygen have actions consistent with stimulation of TXA2 synthesis. The concept accounts logically for hitherto unexplained features of cancer and suggests new strategies for the prevention and treatment of cancer.

Topics: Animals; DNA; Humans; Mutation; Neoplasms; Prostaglandins; Psoriasis; Radiation Injuries; Thromboxane A2; Thromboxanes; Ultraviolet Rays; Xeroderma Pigmentosum