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How To Treat Psoriasis

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TREATMENT OF PSORIASIS

Treatment is given only to manage the symptoms. Ayurvedic medicines are the traditional system of medicines to treat several diseases. It has fewer side effects which can be managed by alternative medicines. Treatment is given to managing the associated co-morbidities. The foremost goal of treatment is to reduce the itching and burning sensation on scales, to provide a soothing and moisturizing effect on the scaly skin. There are other treatments besides ayurvedic medicines. Topical creams, gels containing steroids and vitamin-D analogues are applied directly on the affected skin. Scales present on the scalp is treated by the application of shampoos containing salicylic acids. It acts as keratolytic agents. The drug such as cyclosporine, methotrexate is prescribed to reduce the psoriatic effect on the skin. Phototherapy is given by exposing the affected skin under UV light for shorter durations. UV light acts by reducing the cell growth. The other treatment option includes coal tar therapy, calcineurin inhibitors, calcipotriene, anesthetics and antidepressants. The treatment progress depends on the reduction of scales, plaques, redness, and inflammation.

PLANTS USED IN PSORIASIS:

Complementary and alternative medicines (CAM) assist in the selection of plants as a treatment option to treat several diseases. The plant-based products have less side effects. The plants are selected based on the presence of an active phytoconstituents. The plants such as Nigella sativa, Psoralia corylifolia, Momordica charantia, Aloe vera, Woodfordia fruticosa, Indigo naturalis, Azadirachta indica, Acalypha indica, Allium sativum, Hypericun perforatum, Glycyrrhiza glabra, Cyperus rotundus, and Citrus peel extract possess anti-psoriatic activity. The anti-psoriatic plants selected based on CAM are helpful in reducing the symptoms associated with psoriasis. Allium sativum possess antioxidant and anti-inflammatory property to treat psoriasis. Aloe vera consists of kaempferol, cholesterol, aloe-emodin, aloin, barbaloin, cinnamic acid, salicylic acid and, campesterol. Aloe vera is given prime importance in the study. It is found to inhibit STAT3 activity in psoriasis. Glycyrrhiza glabra consists of Glycitein, genistin, quercitin, aurone, glucose, maltol, sucrose, malic acid, asparagine and, stigmasterol. Glycyrrhiza glabra is found to be active in inhibiting the IL-12 activity in psoriasis.

PHYTOCHEMICALS IN PSORIASIS:

The anti-psoriatic plants are selected by reviewing the various literature related to psoriasis study. The selected plants are identified to be active in the inhibition of targets such as STAT3, TNF-alpha, IL-12, and IL-23 associated with psoriasis. The phytochemicals listed from various plants are run on the software MOE to find the best binding interactions and binding scores. The phytochemicals with best binding interactions and binding scores found are Kaempherol, Glycitein, Corylin, and Cinnamic acid.

RATIONAL SELECTION OF PHYTOCHEMICALS

The rational selection of plants is based on selecting the plants possessing anti-psoriatic activity. The plants are selected based on their activity against STAT3, IL-12, IL-23 and, TNF-alpha inhibitors. The number of anti-psoriatic plants selected is 87 by reviewing the literature. Out of 87 plants, 30 plants are found to possess an inhibiting activity against STAT3, IL-12, IL-23 and, TNF-alpha inhibitors. The phytochemicals from the selected plants are listed. The structures of phytochemicals are drawn on the chem draw software. The chemical structures are docked with the help of MOE software to find the best interaction and binding score with the inhibiting targets. More than 250 phytochemicals are docked by MOE software to find the best interactions and binding scores against the inhibiting targets. The phytochemicals which possess good interactions and binding score against the STAT3, IL-12, IL-23 and, TNF-alpha inhibitors are selected. The top four scoring phytochemicals are selected based on the molecular docking and are included in the study. The phytochemicals selected are Kaempherol from Naringenin possessing STAT3 inhibiting activity, Glycitein from Glycyrrhiza glabra possessing IL-12 inhibiting activity, Corylin from Psoralia corylifolia possessing IL-23 inhibiting activity and Cinnamic acid from Aloe vera possessing TNF-alpha inhibiting activity.

RATIONAL DRUG DESIGN

It is the most suitable method for the identification of the suitable drug candidate and target. It is completely based on the trial and error method. It is useful in the identification of a potential drug candidate with an appropriate molecular target for the disease with the specific predicted binding to the active site of the molecular targets. The rational drug designing is performed by identifying a plant source and involving it in the study of new drug candidate. It is the most reliable method to target a specific disease through molecular docking quantitative structural activity relationship, quantitative structural pharmacokinetic relationship, quantitative structural toxicological relationship, COMFA, COMSIA, and PASS. The current approach of rational drug designing includes identification of the plants source and selecting the phytochemicals. The selected phytochemicals are docked through molecular docking and their interactions with the active amino acids known to bind with the existing drug in the clinical practice are recorded as binding score. The phytochemicals with good binding scores are selected and included in the newly prepared psoriatic formulation.

TOXICITY STUDIES

Toxicity studies are performed to decide the safety of a drug. It gives information about the drug dose which can prove to be lethal or which can produce toxic effects in the body. It is totally based on lethal dose 50 (LD5O). A decrease in LD50 determines the more safety and effectiveness of the drug. The plants are selected based on the literature review but it is not necessary that all the plants selected for the studies should be safe for animal and human use. The toxicity of the phytoconstituents is predicted by software called PROTOX. It predicts the toxicity of phytoconstituents as the toxicity score and toxicity class. More than 250 phytoconstituents are run on the software. Out of which four phytoconstituents are selected with toxicity class-5, class-6 and, less toxicity score. The phytoconstituents selected are Kaempherol, Glycitein, Corylin and Cinnamic acid based on their inhibiting activities against the targets such as STAT3, IL-12, IL-23 and, TNF –alpha involved in the psoriatic pathway.

ANIMAL TOXICITY STUDIES

Animal toxicity studies are performed in laboratory governed by CPSCEA guidelines. Healthy animals are selected for the study. The animals are acclimatized to laboratory conditions prior to the initiation of the study. The proper ventilation is provided. The lighting conditions are provided artificially. Animals should have proper access to food. The continuous supply of water should be provided. Animals should be deprived of food 24 hours prior to the initiation of the study. The animals are checked for the signs of edema and eczema after the application of the formulation.

ACUTE SKIN IRRITATION TEST

Healthy rabbits ranging from the weight 1.5-2.5kgs are taken for the study. The animals are provided with standard laboratory conditions. The animals are acclimatized to laboratory conditions before the initiation of the study. The continuous supply of food and water is provided. Dorsal hairs of the rabbit are removed one day prior to the commencement of the study. Three squares are made of the area 1sqcm. One square is used as a test; a second square is used as a standard and a third square is used as a control. The formulation is applied to one square. The square is covered with a bandage. Animals are checked for edema and erythematic signs. Results are recorded every 24 hours for three consecutive days. Results are recorded in the form of PASI score ranging from 1-5. The edema and erythematic scores recorded are 0.33 for the successive 3 days of the study

REVIEW OF LITERATURE

Sam Shuster et al states the psoriasis patients have fewer chances of occurrence of skin cancer. The regular usage of carcinogens in psoriasis impairs the metabolism of precarcinogens due to the lack of activation of aryl hydrocarbon hydroxylase. The study is based on a speculative hypothesis. If the hypothesis is correct, it provides a basis for the study. Several tissues involved in psoriasis shares the impaired activity of aryl hydrocarbon hydroxylase. Therefore, the incidences of other cancers caused by the environment can be decreased in psoriatic patients. Psoriasis and cancer are more commonly caused due to genetic traits. So, both the diseases are co-related to each other.

B. V. Vakil et al states that anti-psoriatic agents can be better designed by using analytical techniques, QSAR, and VLIFEMDS-QSARPro software. He states the software may be beneficial in stating the potency, biological activity of the newly designed anti-psoriatic drug. The study concluded a newly designed anti-psoriatic drug which consists of Kaempherol and quercitin. Kaempherol and quercitin activity upon subjecting to QSAR models, the best model was found K2 for Kaempherol and Q4 was the best QSAR model for quercitin. The study concludes the safe use of Kaempherol and its analogues in inhibiting psoriasis and increasing the activity of the newly designed drugs. Parakh Sharma et al studied the compounds Kaempherol and quercitin to determine its activity in managing the skin disorder. Psoriasis is caused due to the offensive functioning of the immune system and T cells. He studied the flavanols by performing the docking against calcineurin and calmodulin. The objective of the study was to determine the potential of Kaempherol and quercitin. Insilicoanalysis is performed in the study. The software PyRx performed the docking. The best binding scores were recorded. The study concludes the successful docking and assures the safety of quercitin and Kaempherol in treating psoriasis.

Sandeep R Varma et al states curcumin is proved to be beneficial in managing psoriasis. The actual reasons for psoriasis are not clear. It may cause due to the dysfunction of an immune system. In the previous studies, difficulties arose to determine the activity of new anti-psoriatic drug candidates due to ethical issues on an animal-like model. The recent study is conducted to determine the action of new anti-psoriatic drugs using imiquimod (IMQ) induced differentiated HaCaT cells on in-vitro models. Curcumin is investigated against psoriatic inflammation which is generated by the treatment of differentiated HaCaT cells with IMQ (100 μM). The increased amount of dead cells, apoptosis mechanism, and inhibition of psoriatic cells proliferation is caused due to the active involvement of curcumin against psoriatic inflammations. In the study, curcumin is successful in inhibiting the psoriatic proliferations at a concentration of 25 and 50 μM.

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