The Role of Daruharidra as Pramehaghna Karma with Special Reference to Madhumeha

There are many drugs described in Ayurveda which can be used in the treatment of ,Madhumeha. Sometime different species of that particular drug is sold in market having no therapeutic use or having no record of therapeutic potential under same vernacular name. In this study the drug Daruharidra has been selected. The exact botanical source of Daruharidra is root of Berberis aristata D.C, but more than 13 species of berberis are available throughout Himalayan region ranging from 3,000-13,000ft height. One of it is Berberis asiatica , which is considered as a substitute of B.aristata but no such scientific work has been done to prove


INTRODUCTION
As we move further into the new era, there is a growing fascination with the traditional wisdom of ancient India, perhaps this is because it is based on law of nature that are timeless. Hence it is as relevant to our well-being today as it was thousands of years ago. This is especially true for Ayurveda, the ancient and holistic healing system and the practice of it in India is for over 5000 years.
One of major stumbling block in the wider acceptance of medicinal plant drug is the lack of or inadequacy of standardization of raw drug and contracting forest area has led to the adulteration, substitute and spurious drugs to such extent that many times the correct identity of the original drug mentioned in the Ayurvedic literature has been found to be forgotten totally.
Sometime different species of that particular drug is sold in market having no therapeutic use or having no record of therapeutic potential under same vernacular name for e.g. Rauwolfia serpentiana replaced by R.canescens,Cassia angustifolia by C.auriculata,S.Chirata by S.angustifolia.
Keeping above view in mind, in this study the drugDaruharidra has been selected. The exact botanical source of Daruharidra 1 by various Ayurvedic scholar is root of Berberis aristata D.C, but more than 13 species of berberis are available throughout Himalayan region ranging from 3,000-13,000ft height. One of it is Berberis asiatica, which is considered as a substitute of B.aristata but no such scientific work has been done to prove it. Secondly now days due to ban in uprooting of Daruharidra, physician has started using stem. So, in this work both species stem is assessed for its efficacy in Prameha. Daruharidra has been mentioned or prescribed in Pramehasince Charka 2 period to Raj Nighantu 3 andit is one of the most important ingredients of ant-diabetic formulation, so it's time to search whether the so-called recommended substitute has same efficacy as genuine drug, moreover to assess role of Daruharidrastem in diabetes mellitus, which will help in formatting new formulation for Diabetes. The aim of this study is to compare the efficacy of both species of Berberis (Daruharidra) in the management of Diabetes mellitus. And to evaluate the role of Daruharidra in Pramehaghna formulations.

MATERIALS AND METHOD Criteria for Selection of Patients
The patients suffering from salient features of Prameha and Diabetes mellitus either attending the O.P.D. or admitted in the I.P.D. of Deptt of Dravya Guna and Kayachikitsa, Major S.D. Singh P.G. Ayurvedic Medical College and Hospital, Farrukhabad, U.P. were selected randomly for this present study irrespective of age, sex, caste, occupation, religion etc.

Diagnostic Criteria
Increase in Blood Sugar level either fasting or postprandial or both were the essential criteria for the selection. The known patients of Diabetes mellitus or the patients preliminary diagnosed on the basis of signs and symptoms of the diseases were confirmed by further investigation. Exclusion Criteria 1) Patients of Sahaja Madhumeha (IDDM) 2) Patients complicated with any cardiac problems 3) Patients suffering from anorectal diseases During this period the strict restriction was kept on regularizing the dietary habits of the patients.

CRITERIA FOR ASSESSMENT
After the completion of the treatment, the results were assessed by adopting the following criteria: • Improvement in signs and symptoms of disease on the basis of the symptoms score.
• F.B.S. and P.P.B.S. levels • Serum Cholesterol • Urine sugar The indoor patients were examined daily and the outdoor patients weekly and the changes observed in the signs and symptoms were assessed by adopting suitable scoring method and the objective signs by using appropriate clinical tools. The detail assessment of clinical signs and symptoms are discussed below: 4,5 1) PrabhutaMutrata (Polyuria) Frequency of urine ▪ 3 -6 times per day, rarely at night 0 ▪ 6 -9 times per day, 0 -2 times per night 1 ▪ 9 -12 times per day, 2 -4 times per night 2 ▪ More than 12 times per day, more than 4 times per night 3

4) Abhyavaharana Shakti (Hunger)
▪ Person taking food in excessive quantity twice in a day 0 ▪ Person taking food in normal quantity twice in a day 1 ▪ Person taking food in moderate quantity twice in a day 2 ▪ Person taking food in less quantity twice in a day 3 ▪ Person taking food in less quantity once in a day 4 ▪ Person not at all taking food 5

Assessment of Overall Effect of The Therapy
1) Control of the disease: The patient whose Fasting and Postprandial blood sugar level came down to normal limits and complete relief in all the signs and symptoms. 2) Markedly improved: Blood sugar relief percent above 50% and above 75% relief in signs and symptoms. 3) Improved: Blood sugar relief percent less than 50% and more than 25% relief in signs and symptoms. 4) Unchanged: No reduction in blood sugar level and less than 25% relief in signs and symptoms.

RESULT A) ANALYTICAL STUDY
Both the tablet under taken for the present study were analyzed by employing various parameters as mentioned in materials and methods B.aristata and B.asiatica stem, the raw material were also estimated for berberine content and water soluble extract. Data evolved has been presented here. The analytical data of physio-chemical analysis of the ghana tablet samples has been presented in table 1. Av.-490.00 mg Max.504.00mg Min-470.00mg As could be seen from the Table-1, the loss on drying of the sample was between 9-10%.This relates to the moisture content in the sample and the value is in higher side. The ash value of B.aristata was more (19.11%) as compared to that of B.asiatica indicating presence of more inorganic content in it. Both water and methanol soluble extractive of both the sample are quite high as expected since the tablet were prepared by using ghana i.e. water soluble extract, The methanol soluble extractive was about 50% higher in B.asiatica (47.55%) than B.aristata (33.41%).this can useful for differentiating between B.aristata and B.asiatica used as raw material. The physico-chemical parameters mentioned in the Ayurvedic pharmacopoeia of India is for root and stem of Daruharidra (Berberis aristata D.C) in different monographs, foreign matters, total ash, acid insoluble ash, extractive values etc. Hence, the above-mentioned parameters were selected for the analysis of the Ghana tablet. The evolved data will be useful as reference for the analysis of Daruharidra tablet and can be used for its quality control. Berberine content, %w/w 0.40 0.67 The data presented indicate that both water soluble extractive and berberine content was much higher in Berberis asiatica 10.70% and 0.67% respectively, as compare to 5.95% and 0.40% in B.aristata respectively. Whereas According to Ayurvedic pharmacopeia of India (Vol-I Pg-33, First edition) the water soluble extractive value of B.aristata should not be less than 6%.

B) PHARMACOGNOSTICALSTUDY
Berberis aristata D.C and Berberis asiaticaRoxb.ex.D.C belong to the Berberdiaceae family, they grow in Himalayan region. Berberis aristata is available at higher altitude whereas B.asiatica is available at lower altitude. Now days stem is used in medicine so it is necessary to study the stem of genuine drug and its substitute pharmacognostically. As plants morphology is concern, even though both belong to same family they can be differentiated by following their peculiar features (

Alasya :
Before treatment mean score of Alasya was 1.25 which came down to 0.25 at the end of therapy with 80% relief which was statistically significant (P<0.05) . Mutramadhurya: Initial mean score of Mutramadhuryawas 1.12 which increased up to 2.25 after treatment with 100.89% increased (P>0.01). Pindiko-udvestan: Complete Relief was Observed in 3 patients. Sthaulya: Mean score of Sthaulya was 1.70 before treatment which reduced to 1.10 after treatment. The relief provided was 35.29% which was statistically significant (P<0.05). Ati-nidra: Initial mean score of Ati-nidra was 1.00 which reduced to 0.60 after treatment with 40.00% relief which was statistically insignificant. Libido: No change was seen. Berberis aristata provided statistically insignificant reduction in Fasting blood sugar (0.40%) and Significant reduction in postprandial Blood sugar with 11.87% relief(P<0.05). It provided statistically insignificant reduction in the S. Cholesterol level with percentage reduction of 4.42%.    Alasya : Before treatment mean score of Alasya was 2.28 which came down to 1.00 at the end of therapy with 56.14% relief which is statistically significant. Pindiko-udvestan : Before treatment mean score of Pindiko-udveshtan was 1.85 which came down to 0.71 at the end of therapy with 61.620% relief which is statistically highly significant (P<0.001). Weight loss: Mean score of weight was 61.67 before treatment which reduced to 60.58 after treatment. The relief provided was 1.76% which is statistically significant (P<0.05). Jiwhatalu kantha sosha: Before treatment means score was 1.75 which reduced to 1.00 after treatment. The relief provided was 42.85% which is statistically significant. Stastistically insignificant change was seen in Sthaulyawhereas mutrmadhurya was increased significantly after treatment.  4.92% relief however in postprandial Blood sugar level the reduction was statistically significant(P<0.05) with 16.39% relief, The reduction in S. Cholesterol level is statistically insignificant(P>0.05)with percentage reduction of 6.73%. The Berberis asiatica group therapy provided statistically insignificant increase in Hb %(7.09%), Insignificant decrease was seen in T.L.C. (6.29%) and statistically significant(P<0.05) decrease was seen in E.S.R.(24.80%).

Effect on Signs & Symptoms:
Berberis aristata Ghana tablet group provided statistically highly significant (P<0.001) relief in PrabhutaMutrata(83.47%), Kar-pad-tal-dah(86.4%) and Daurbalyata(62.5%), whereas significant relief was obtained in Kshudhadhikya and Trishnadhikya. B.asiatica tablet group provided statistically highly significant (P<0.001) relief in PrabhutaMutrata by 59.02% relief and in Kar-pad-tal-dah(62.71%).Statistically significant relief was seen in Trishnadhikya(56.14%).Statistically insignificant relief was observed in Kshudhadhikya(50%) and Daurbalyta (42.85%). In chief complaints both group showing same results, Prabhutamutrata is greately reduced due to the UshnaVeerya, Tikta and Katu rasa, because Tikta rasa help in the depletion of Kleda,Meda, Vasa, Majja, Lasika, Puya, Sweda, Mutra and Pitta, UshnaVeerya and Laghu, Rukshaguna of the drug help in absorption of excessive fluid from the body moreover they stimulate Agni. Kar-pad tal dah may be pacified by the Sheeta property of Tikta rasa. Dourbalyata might be reduced by proper formation of all Dhatu by the stimulation of Agni by UshnaVeerya, Tikata and Katu rasa. Tikta rasa also promote firmness of the skin(Twak) and muscles(mansa).

Effect on Hematological Values
The Berberis aristata Ghana tablet therapy provided increase in T.L.C by 1.03%, whereas Hb% was increased by 1.64% and E.S.R. was decreased by 2.60%, all are statistically insignificant. It indicates that, this group has no effect on hematological values. Berberis asiatica group therapy provided statistically insignificant increase in Hb%(7.09%), Insignificant decrease was seen in T.L.C.(6.29%) and statistically significant (P<0.05) decrease seen in E.S.R. (24.80%).
The decrease in E.S.R in asiatica group might be due to the inhibitory action of berberine against various bacteria.

Effect on Blood Sugar
Berberis aristata provided statistically insignificant reduction in Fasting blood sugar (0.40%) and Significant reduction in postprandial Blood sugar with 11.87% relief (P<0.05). It provided statistically insignificant reduction in the S. Cholesterol level with percentage reduction of 4.42%. Berberis asiatica provided statistically insignificant reduction (P>0.05) in Fasting blood sugar by 4.92% relief and in postprandial Blood sugar level the reduction is significantly decreased (P<0.05) with 16.39% relief, The reduction in S. Cholesterol level is statistically insignificant(P>0.05)with percentage reduction of 6.73%. In both the groups the significant reduction is seen in post-prandial blood sugar, it coincides with the result in pharmacology where the both drugs were showing anti-hyperglycaemic action. This may be due to the presence of berberine alkaloid which helps in utilization of glucose and hampers absorption of glucose from gut.

PROBABLE MODE OF ACTION
The basic principles of Ayurvedic Pharmacology are capable to explain the mode of action in scientific way. Pharmacology of Ayurveda is based on the theory of Rasa, Guna, Veerya, Vipaka and Prabhava which were the simplest parameters in those days to ascertain the action of drug.
Acharya Charaka states that किकिद्रसे नि ु रुते िर्म वीर्ये णचापरर्् ||७१|| द्रव्यं गु णे नपाि े नप्रभावे णचकििन| (Cha. Su. 26/71) Certain drugs act through Rasa; some through Veerya, Some through their Gunas, Some through their Vipaka and some through their Prabhav. 6 Here also the Daruharidra is acting by its Raspanchaka, The Katu-Tikta rasa pacify or balances the bahudravakapha and pitta moreover by its Shoshan properties it reduces excessive meda, Kleda and Lasika etc; Laghu, Rukshaguna helps to normalize bahudravkapha and indirectly stimulate Jatharagni and Dhatwagni; The UshanaVeerya further help to bring vitiated Kapha and Vata Doshas to normal condition and stimulate Jatharagni as well as Dhatwagni.So, in this way the Ras panchak of the Daruharidra normalizes the vitiated Kapha-Pitta -vata, Dushya and Destructs the Samprapti.

Modern View
Berberine present in the Daruharidra was found to effectively inhibit the activity of Diasacchaidases in Caco-2.It also decreased sucrase activity after preincubation with Caco-2 cells for 72 hours. However, Gluconeogenesis and glucose consumption of Caco-2 were not influenced. 2-Deoxyglucosetransporting through Caco-2 cell monolayers was decreased by berberine but the effect was not statistically significant. These results suggest that the anti-hyperglycemic activity of berberine is at least partly due to its ability to inhibit alpha-glucosidase and decrease glucose transport through the intestinal epithelium. 7

CONCLUSION
The word Daruharidrais not found in Vedic periods but since Samhita Period it has been used in medicine. Ayurvedic Classics have described wide range of therapeutic properties of the plant and have indicated in Vrana, Phiranga, Upadansha, Gandmala, Visarpa, Pravahika,Kamala, Aruchi, Bastishotha, Twakdosha, Atisaar, Prameha, Raktapitta, and especially in Eye, Ear, Nose, Throat diseases. (Urdhajatru-gata-roga). From Charka period to Nighantu period it has been mentioned in context of Prameha treatment. Daruharidra has Katu, Tikta rasa; Katuvipaka; Laghu, ruksha Guna; and UshnaVeerya. Its property is similar to the Haridra, which is also considered as a substitute of Daruharidra. Botanical source of Daruharidra is Roots of Berberis aristata D.C. but now days its stem is being used. Other species of Berberis are used in it place but Berberis asiaticaRoxb.ex.D.C. is commonly used. The root and stem of Berberis species are yellow due to presence of Berberine, which is therapeutically important alkaloid. Berberine possesses growth inhibitory activity against Giardiasis, Entamobea histolytic, Chlamydia trachomatis, and has shown good results in Cholera and Liver cirrhosis. Pharmacognosy:Macroscopically both species can be differentiated on the bases of leaves and inflorescence. B.aristata leaves spines are not distinct, are glossy green, venation not prominent and corymbose raceme, whereas B.asiatica leaves spines are distinct, venation prominent and umbellate raceme. Stem is very difficult to differentiate but the yellow intensity of wood is less and bark is more blackish in B.aristata as compare to B.asiatica. In microscopic study B.asiatica can be differentiated by the presence of rhytidoma, starch grains and large vessels which are not present in B.aristata however in case of B.aristata the prismatic crystal of calcium oxalate are more as compare to former and the medullary rays is wider. Analytical Study: No significant difference was observed in most of the physio-chemical parameter between two drugs Ghana tablets, but the methanol extractive value was about 50% higher in B.asiatica as compare to B.aristata. The water-soluble extractive of stem powder of Berberis asiatica (10.70%) was higher as compare to Berberis aristata (5.95%). The berberine quantity by Gravimetric method was also higher in case of Berberis asiatica stem (0.67%) as compare to Berberis aristata stem (0.40%). In TLC also similar spots were seen in both the drug's ghana but the intensity was more in B.aristata. Ayurvedic Pharmacopoeia of India has not mentioned Berberis asiatica stem the Data evolved in the present study will be very useful and serve as reference for its routine analysis. Clinical study: Age of onset of disease was maximum in age group of 41-50yrs, 52.77% patients have positive family history of diabetes mellitus. Most of the patients have Prabhutamutrata, Daurbalyata and Kar-pad-tal dah as chief complaints. In Berberis aristata D.C group 14 patients completed the drug regime, highly significant (P<0.001 relief was seen in Prabhutamutratrata(83.47%), Kar-pad-tal dah(86.40%) and Daurbalyata(62.50%) and postprandial blood sugar was significantly reduced (P<0.05). In this group 14.28% patient markedly improved, 57.14% patients improved and 28.57% patients were in unchanged category. In B.asiatica group 14 patients completed the drug schedule, highly significant(P<0.001) relief was observed in prabhutamutrata (59.02%) and Kar-pad-tal dah(62.71%) and post-prandial blood sugar level was significantly reduced (P<0.05).As overalleffect of drug is concern 07.14% patients controled,14.28% patients markedly improved,57.14% improved, and 21.42% in unchanged category. No difference was observed in the therapeutical potential of Berberis aristata D.C. and Berberis asiaticaRoxb.ex.D.C clinically.