A Comparative Clinical Study of Gokshuradi Guggulu with Anupanabheda in The Management of Vatarakta with special reference to Gout

Gout is condition in which person become immobile and inactive due to joint pains and swelling. Gout occurs, when urate crystal deposition of in the joints . Vatarakta is considered as a vata pradhana vyadhi and rakta dushti. Gokshuradi Guggulu is having vatahara and raktashodhak properties. Guduchi kwatha selected as anupana because of its Rasayana, Vatashamaka, Balya, vedana sthapana and Ama pachana properties will help to disrupt the Samprapti vighatana of vatarakta . The objectives of the study were to evaluate the effect of Gokshuradi Guggulu with Anupanabheda in the management of Vatarakta and to compare the result of both groups. This study was randomized, parallel comparative clinical trial of two groups each of 20 patients. From OPD of DBACH Mandigobindgarh; 40 patients of vatarakta taken which were randomly divided into two groups. Group A, 20 patients for 60 days received Gokshuradi Guggulu 1 gm. BD with lukewarm water and Group B,20 patients received Gokshuradi Guggulu 1gm BD with Guduchi Kwatha for 60 days. In Group A, among 20 patient’s 55% patients showed moderate response and 45% patients showed mild response. In Group B among 20 patients, 95 % patients showed moderate response and 5 % patients showed mild response. Both shows statistically highly significant results in both subjective and objective except erythema & discoloration. Treatment modality in Group B (i.e. Gokshuradi Guggulu with Guduchi Kwatha ) is effective in comparison of treatment modality in Group A (i.e. Gokshuradi Guggulu with lukewarm water).


Introduction
In Ayurvedic texts, illnesses produced by the conjugation of vitiated Vata and Rakta cause several health ailments. Vatarakta is one of them; Vata prakopa, rakta dushti and obstruction in the path of vata is the core pathology in the disease. The pathology of this disease originates in blood, spreads through blood vessels and nerves and then finally get settled in the joints. In Vatarakta, the symptom which disturbs daytoday life of the patients i.e. severe joint pain, which primarily seen in Hasta-Pada-Mulagata sandhi (1) and then migrates to other joints in a way similar to Akhuvisha (2).
Vatarakta as mentioned in Ayurvedic texts have very close resemblance with Gout available in modern texts. Gout is musculoskeletal disorder, having the incidence of 2-26 per 1000 (3). In developing countries rate of gout has increased in recent decades. Gout is rare in children and pre-menopausal females in India. Its effects men in their 40s and 50s and is common in female after menopause (4).
The predisposing factors are protein rich diet, consumption of alcohol and sedentary lifestyle. The disorder has been considered for the study keeping in mind the dire need of the hour to find some safe, sure and permanent cure effective for the disease.
Allopathic treatment has adverse effects like hepatic and renal impairment, which are contraindicated in pregnancy and lactation and harms the individual immune system. if Continuously NSAIDS are taken for long time which lead to gastric irritation, peptic ulcers etc (5).
On the other hand, Ayurveda with safe & effective goodness has been pouring its valuable treasures to mankind since time unknown. In recent days, people are approaching back to nature and prefer to avoid synthetic preparations. Guggulu preparations are supposed to be one among the finest shamana aushadha in the vatavyadhis (6).  a. Guduchi Kwatha -20 gms of guduchi (already cut into pieces) is mixed with 320 ml of water. This mixture is boiled on low heat till 1/8 is left. When palatable (warm) then to be taken with the drug (9).

Selection of patients
Total 40 Patients suffering from vatarakta, fulfilling the criteria of Vatarakta (Gout) from OPD & IPD of Kayachikitsa Dept. of Desh bhagat ayurvedic college and hospital, Mandigobindgarh Punjab; were selected randomly with coin toss method and divided into following 2 groups.
• Group-A: Gokshuradi Guggulu with Lukewarm Water in the dose of 1gm twice a day was given to 20 patients of Vatarakta for 60 days. • Group-B: Gokshuradi Guggulu with Guduchi Kwatha in the dose of 1gm twice a day was given to 20 patients of Vatarakta for 60 days.
Study design: Open Randomized Parallel Group Trial.

Inclusion Criteria
Patients of age group between 16-70 years; having clinical signs and symptoms of Vatarakta and having serum uric acid level >7 mg/dl with associated features like joint pain and inflammation were included in the study.

Exclusion Criteria
• Any other joint inflammatory disorder like RA.
• Uncontrolled Diabetes and Hypertension. Chronic renal disease. • Patients having chronicity more than 10 years. • Disease associated with marked joint destruction.

Assessment criteria
Patients were diagnosed based on performa prepared with signs and symptoms of Vatarakta. The improvement was assessed on the relief found in the cardinal features of the disease. To assess the effect of therapy all the sign and symptoms were assigned score depending upon their severity as elaborated below:  Following objective scale with numerical values was used to assess the severity of abovementioned subjective criteria (table 3 to 10):

Results and discussion
The effect of trial drug in 40 patients for duration of 60 days, various assessment criteria were obtained after statistical analysis of the data and is presented in tabular form as below

Comparison of Overall Effect of Both Groups
It is observed from the comparative study that no patient got complete remission or marked improvement in both the groups whereas number of patients improved moderately was 11 and 19 in group A & B respectively. 09 patient in group A and 01 patients in group B got mild improvement in sign & symptoms. No patient had zero improvement or worsening of disease in any group (Table no.

Probable mode of action
Action of drug is based on 5 mechanism of actions or attributes; namely rasa, guna, virya and vipaka along with certain specific properties called prabhava. The drugs jointly act as an antagonist to the morbid dosha and dushya and cause 'Samprapti Vighatana'.
In the trial drug guggulu is associated with 8 other drugs-Gokshura, Musta, Haritaki, Amalaki, Bibhitaki, Pippali, Marich and Shunthi as the main ingredients. The probable effect of all the constituent drugs of gokshuradi guggulu can be explained as further.

Rasa
Due to predominance of tikta, kashaya rasa, it pacifies pitta dosha. Tikta rasa is said to have deepana karma by which it corrects mandagni and pachana karma which helps in amapachana. Both kashaya as well as tikta rasa also reduces the kled guna of rakta, kapha and ama. It has also lekhana and shoshana guna which clears the srotas and sira marga, avrita with sama rakta.

Guna
Laghu guna of most of the constituent drugs like trikatu has srotoshodhaka, agnideepak properties. Other than this, being ruksha guna pradhan, it helps in absorption of mala and ama.

Virya
As most of the drugs in trial drug have ushna virya, it has vatakaphahara property and said to be deepana and pachana. It also helps in vilayan of doshas which is necessary step in bringing shakhagata dosha towards koshtha.

Vipaka
Madhura vipaka is predominant in the drug which has snigdha and vatapittashamaka properties and helps in easy passage of urine and stool.

On the basis of dosha Karma
In general, the formulation has tridosha shamak as well as raktashodhaka properties. Most of the drugs selected have their rasayana guna. Rasayana is said to be 'vyadhi vidhwansi' (which means effective in curing the disease). It helps in maintaining homeostasis between all doshas and dhatus by its action through rasa, guna, virya and vipaka.

Deepana karma
Most of the drugs i.e. guduchi, amalaki, haritaki, mustak, pippali, marich, and shunthi exhibit deepana guna due to pradhanata of vayu and agni mahabhoota. As agnimandya is one of the factors in causation of disease, it corrects abnormality in jatharagni as well as dhatvagni.

Pachana karma
The formulation contains drugs having pachana guna like guduchi, haritaki, mustak and trikatu. Pachana dravyas are agni and vayu pradhan, enhance jaran shakti and helps in ama pachana. As sama rakta cause sthan sanshraya in asthivaha srotas by obstructing the normal pathway of vata, pachana dravyas help in clearing that obstruction caused by ama.

Vedanasthapana
Guggulu, guduchi, haritaki, vibhitak, gokshur pippali, marich and shunthi, all these drugs are said to have vedanasthapak (analgesic) action. One function of vata is 'Pravartak cheshtanam uchchavachanam'. So, when there is vata prakopa, this perception of senses aggravates and manifests in the form of vedana. Most of these drugs are ushna virya due to which they pacify vata dosha and vedana as well.

Vishyandan and srotoshodhan
Means liquification of deeply embedded dosha for their easy flow.
According to acharya Chakrapani, vishyandan and vilayan both are synonyms. A drug should have ushna, tikshna guna for vilayan karma. Among all 9 drugs present in formulation, 6 drugs are known to be ushna virya and 3 drugs (Guggul, Marich, Shunthi) are tikshna in nature, due to which they help in dissolving doshas as well as ama. Tikshna dravya has also the property of lekhan karma which leads to srotoshodhan at the level of microchannels.

Shothahara and doshapkarshana
The drugs, by above mentioned karma help in moving doshas from shakha to koshtha. These doshas when expelled into koshtha, are excreted out of body by different means of urine, stool etc.
Besides all these, some of these drugs have Shothahara, vatanuloman, rasayana and balya properties which help in relieving the symptoms of vatarakta.

Pharmaco-dynamical aspects of Gokshuradi Guggulu in Modern parlance
The management of hyperuricemia goes through two ways: 1. Management of Symptoms 2. Breaking down the Pathology-this comprises of two set of medications: a. Inhibition of Xanthine Oxidase-Xanthine Oxidase inhibitors decrease the production of Uric Acid by interfering with Xanthine Oxidase enzyme. b. Excretion of Uric acid through Uricosuric-Uricosuric increase the excretion of uric acid by reducing its re-absorption once the kidneys have filtered it out of the blood. An important content of Gokshuradi Guggulu is Guggulu which possesses the properties of antiinflammatory (10,11), antioxidant (12,13), Uricosuric (14), anti-rheumatoidal (15) helps in breaking the pathophysiology of Gout.
Gokshur showed better anti-inflammatory results and analgesic action. According to a clinical study, significant analgesic effect of methanolic extract of gokshur was observed (16).
Triphala works as a Xanthine Oxidase inhibitor (17) like Allopurinol which suppresses the production of Uric Acid. Its content Haritaki has antioxidant (18,19) and adaptogenic (20) properties which help in  (21) function which retards the Urolithiasis and dissolves already formed stones in kidney while Amalaki has antiinflammatory, analgesic, antipyretic (22) and antioxidant (23) properties which help reducing the local and systemic inflammatory effects of Gout. Maricha has Antioxidant (24), immunemodulatory (25) property subsides the hyperactive immune responses precipitated due to Uric Acid. Vasodilatory property (26) increases the blood circulation to the affected joint and enhances the process of phagocytosis of antigen-antibody complexes responsible for hypersensitivity which gave rise to inflammation.
Piperine found in pippali and marich significantly inhibited the production of two important pro inflammatory mediators, IL₆ and PGE₂. The inhibition of PGE₂ production is important due to its central role in triggering pain. It has been seen that P. longum root has weak opioid but potent NSAID type of analgesic activity. As per Ayurveda vedana is chiefly manifestation of vata dosh prakopa. Vata due to its sheeta guna exhibits vedana. Most of the drugs in gokshuradi guggulu are ushna virya which inhibit the sheeta guna of vata thus giving relief of pain.
Shunthi is an inhibitor of both prostaglandin and leukcotrine biosynthesis (27,28) and its beneficial effects could be, to a large extent, due to these inhibitory effects. It is a potent anti-inflammatory agent and the active principles include sesquiterpene lactones (29).
Musta rhizomes are considered as astringent, diaphoretic, diuretic, analgesic, antispasmodic (30), antiarthritis, antiinflammatory, antipyretic, analgesic, a n t i d i a b e t i c , a n t i d i a r r h e a l , c y t o p r o t e c t i v e , antimutagenic, antimicrobial, antioxidant and apoptotic (31).
In this way, Gokshuradi Guggulu has all the aspects of Pharmaco-therapeutic effect required for the management of Hyperuricemia induced Gout like Antiinflammatory, Antioxidant, Immuno-modulator, Xanthine Oxidase Inhibitor, Uricosuric and Diuretic effects.
The effect of Guduchi kwatha is due to antiinflammatory (32,33) activity of Amrita which reduces the inflammation and gives symptomatic relief as well as its uricosuric action which excretes excess amounts of Uric Acid from the body (34).
Thus, Gokshuradi Guggulu with Guduchi kwatha which helped in reducing the symptoms and excreting the surplus amount of Uric Acid from the body. Hence, Gokshuradi Guggulu with guduchi kwatha anupana has shown comparatively better results over Gokshuradi Guggulu with lukewarm water anupana.

Conclusion
Treatment modality Gokshuradi Guggulu with Guduchi Kwatha shows better efficacy in reliving subjective features as well as objective features than Gokshuradi Guggulu with lukewarm water. The trial drug gokshuradi guggulu used for study in both groups is a good combination of vedanasthapan, shothaghna, deepana and amapachak dravyas. guduchi, triphala, guggulu and trikatu with their tridosha shamak mainly vatanashak, rasayana, balya raktprasadaka property helps in maintaining homeostasis in dhatus as well as doshas.