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ORIGINAL ARTICLE
Year : 2016  |  Volume : 37  |  Issue : 3  |  Page : 198-205  

Evaluation of Gandhakadi Yoga as an adjuvant therapy in the management of Beejadushtijanya Pandu (thalassemia major)


Department of Kaumarbhritya, IPGT & RA, Gujarat Ayurved University, Jamnagar, Gujarat, India

Date of Web Publication30-Jan-2018

Correspondence Address:
Dr. Anjana Goswami
1073, Kailash Nagar, Near S.T Workshop, Bhuj-Kutch - 370 001, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ayu.AYU_72_15

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   Abstract 


Introduction: Thalassemia major is a malignant type of genetic disorder and iron overload is the main complication of the disease which results due to frequent blood transfusions. Gandhakadi Yoga has been proved effective against iron overload in experimental studies and pilot voluntary study, hence, taken for clinical evaluation in the present study. Aim: The aim of this study is to evaluate the efficacy of Gandhakadi Yoga as an adjuvant therapy in the management of thalassemia major. Materials and Methods: A total of 46 patients of age group 2–12 years were registered and randomly divided into two groups. Group A (trial group-Gandhakadi Yoga with blood transfision (BT)) and Group B (control Group-with BT and iron chelation therapy). The assessment was done based on the subjective and objective parameters after12 weeks of treatment, with a follow-up of 12 weeks. The data obtained in clinical study was analyzed using Student's “t” test. Results: Trial drug provided highly significant result (P < 0.001) in most of the subjective parameters and BT interval was prolonged. In Group A, the maximum improvement was found in three patients (13.04%); moderate improvement in 15 patients (65.22%) and mild improvement in five patients (21.74%). No adverse drug reaction was reported during the clinical study. Conclusion: Gandhakadi Yoga provided better results than control in subjective and objective parameters, BT interval and general health status, hence, has an effective role as an adjuvant in the management of thalassemia major.

Keywords: Beejadushtijanya Pandu, Gandhakadi Yoga, thalassemia major


How to cite this article:
Goswami A, Rajagopala S, Patel KS, Kori VK, Prajapati P. Evaluation of Gandhakadi Yoga as an adjuvant therapy in the management of Beejadushtijanya Pandu (thalassemia major). AYU 2016;37:198-205

How to cite this URL:
Goswami A, Rajagopala S, Patel KS, Kori VK, Prajapati P. Evaluation of Gandhakadi Yoga as an adjuvant therapy in the management of Beejadushtijanya Pandu (thalassemia major). AYU [serial online] 2016 [cited 2020 Feb 17];37:198-205. Available from: http://www.ayujournal.org/text.asp?2016/37/3/198/224182


   Introduction Top


Thalassemia is one of the most challenging hematological disorders which do not have a definite cure in the contemporary medical science. The scientific community is looking at traditional holistic system of medicines for a satisfactory approach. Till date, totally five research works have been carried out on thalassemia major. In these previous studies, a trial was made to develop a systematic approach for the proper understanding of the pathology from the Ayurvedic point of view and to find out better regimen for the disease. The present study is one more approach in this direction.

A disease having signs and symptoms similar to Thalassemia is not described as such in Ayurveda. Following the methodology described by Acharya Charaka in Vimanasthana, thalassemia may be correlated to Tridoshajanya Panduroga.[1]

The pre-clinical studies of Gandhakadi Yoga have already been carried out and also this formulation has been evaluated for iron sorbitol induced iron overload in albino rats with promising results [2] and hence, it has been taken for clinical trial on patients of thalassemia major in the present study.

The aim and objective of the study is to evaluate the efficacy of Gandhakadi Yoga as an adjuvant therapy in the management of thalassemia major.


   Materials and Methods Top


Selection of the patients

Pre-diagnosed patients of thalassemia major attending the outpatient department of Kaumarbhritya and patients registered in the Thalassemia ward, fulfilling the criteria of selection, were registered in the study irrespective of sex, caste etc.

Ethical clearance

The present study has been started after getting clearance from the Institutional Ethics Committee (IEC No. PGT/7-A/Ethics/2013-14/1767, dated 10/09/2013) and was also registered in Clinical Trial Registry of India (CTRI/2014/02/004383, dated 06/02/2014). Written informed consent of the parents of each patient was taken before starting the treatment. Basic information of the disease and treatment was provided to the patients before the trial.

Criteria for selection of patients

  1. Diagnosed cases of thalassemia major
  2. Age group: 2-12 years of either sex.


Criteria for exclusion of patients

  1. Children below 2 years and above 12 years of age
  2. Cases having HIV, Hepatitis B infection, hepatic failure, diabetes mellitus, tuberculosis etc.
  3. Patients having blood transfusion interval for ≤12 days
  4. Patients undergone for splenectomy.


Grouping and posology

The selected patients were randomly divided into two groups using coin toss method, namely treated and control group and examined clinically along with laboratory investigations.

  1. Trial group (Group A): In this group, along with blood transfusion (BT), Gandhakadi Yoga tablets were orally administered with lukewarm water as Anupana for 12 weeks. Adult dose of Gandhakadi Yoga was taken 1 g/day and child dose was calculated according to young's formula [3] for different age group [Table 1]
  2. Control group (Group B): In control group, regular BT along with contemporary iron chelators were continued as per standard protocol.
Table 1: Doses of Gandhakadi Yoga tablets according to different age group

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Duration of treatment in both the groups was 12 weeks with a follow-up period of 12 weeks.

Preparation of Gandhakadi Yoga tablets

Gandhakadi Yoga is a combination of Shudha Gandhaka (Purified Sulfur), Vidanga (Embelia robusta Burm. f.), and Agastya (Sesbenia grandiflora Linn.). Originally Agastyapatra Swarasa Bhavita Vidanga Churna is suggested in the text Ayurveda Prakasha [4] for Apakva Loha Sevanajanya Vikara Prashamana (symptoms produced after intake of improperly prepared Loha Bhasma as well as improper digestion of Loha Bhasma or Iron overload). However, in the present study, Shudha Gandhaka was incorporated in the original formulation.

All the drugs were authenticated for quality and purity by Pharmacognosy laboratory, IPGT and RA, GAU, Jamnagar by employing Ayurvedic Pharmacopoeia of India standards.[5],[6]

First of all known quantity (1.5 kg) of raw Gandhaka was melted by adding a specified quantity of Goghrita (cow-ghee-1/4th of Gandhaka). After complete melting, liquefied Gandhaka in Goghrita was poured in to Bhringaraja (Eclipta alba (L.) Hassk) Swarasa through a clean cotton cloth.

Gandhaka settled at the bottom of the vessel was collected and the process was repeated for six times as per the textual reference.[7]Gandhaka obtained at the base of the vessel after 7th repetition was collected, washed with hot water and dried properly.

Then, the powder of Shudha Gandhaka and Vidanga were taken in equal quantity and triturated with juice of Agastya leaves. Bhavana (trituration) process was repeated for two times. Granules were prepared by sieve (No. 20) and then, tablets were prepared by following standard operating procedure and physico-chemical analysis of the finished product was carried out in the pharmaceutical laboratory [Table 2].
Table 2: The physico chemical analysis of Gandhakadi Yoga tablets

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Assessment criteria

A special proforma was prepared to study the etiopathogenesis and to assess the response of given treatment and any complications. The effect of therapy was assessed by adopting standard scoring pattern for subjective parameters.[8]

Subjective parameters

The subjective parameters include Panduta (pallor), Hriddravatva (palpitation), Daurbalya (weakness), Balakshaya (loss of strength), Akshikutashotha (puffiness around the orbit), Jwara (fever), Aruchi (anorexia), Udarashula (abdominal pain), Pleehavridhi (splenomegaly), Yakritvridhi (hepatomegaly), Atisara (loose motion), Pindikodweshtana (leg cramps) Sandhishula (arthralgia) and Vivarnata (discoloration of skin).

Objective parameters

Following investigations were performed before and after the treatment.

  1. Routine hematological investigations
  2. Biochemical investigations which includes.


Liver function test (LFT): to assess the hepatic toxicity of the drug, renal function test (RFT): to assess the renal toxicity of the drug, serum iron, serum total iron binding capacity and serum ferritin: to assess iron overload in the body.

Dietary advice

Patients were advised to take low iron diet and to avoid the possible aggravating factors of thalassemia.

Assessment of total effect of therapy

The assessment was done after completion of course of treatment, i.e. after 12 weeks. An assessment scale was made to assess the rate of improvement in clinical signs and symptoms. At the end of treatment, the result in view of the percentage of relief in clinical signs and symptoms was classified [Table 3].
Table 3: Overall assessment criteria

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Statistical analysis

Paired't' test was used for the assessment of results in individual groups and unpaired 't' test was used for comparative effect of therapy of both groups were applied.

Observations

In the present study, total 46 patients were registered, 25 in Group A, and 21 in Group B. Out of these, 44 completed the course of treatment (23 in Group A and 21 in Group B). Two patients discontinued the course of treatment in Group A due to irregularity in the subsequent visits as having difficulty to reach the hospital. Maximum, 45 (45.65%) patients were from the age group of 5-10 years, 24 (52.17%) were males and 22 (47.83%) were from the lower socioeconomic background. Majority of the patients, i.e. 31 (67.39%) were diagnosed of thalassemia before the age of 1 year. Most of the patients, i.e. 21 (45.65%) had received BT up to 50 times. Thirty-four (73.91%) had febrile reactions to BT. Among the 46 patients, 21 (45.65%) were taking iron chelator, i.e. deferasirox. History of consanguineous marriage was found in 12 (26.09%) patients. The parents of all the patients (100%) had done naked eye single tube red cell osmotic fragility test and among them, (86.96%) of the patients had identified father and mother carriers of thalassemia. Vishamashana was found in 36 (78.26%) patients, and Amla Rasa predominant diet was observed in 31 (67.39%) patients, while Ruksha Guna in 35 (76.09%) patients. Anger was found in 26 (56.52%) patients. Vata Pitta Prakriti was found in 27 (58.70%) patients, Avara Abhyavaharana Shakti was observed in 25 (54.35%) patients, Vata Pitta Dosha predominance was observed in 27 (58.70%) patients. Majority of the patients, 29 (63.04%) had Mandaagni. Rasavaha and Raktavaha Srotodushti was found in all the (100%) patients while Medavaha and Asthivaha Srotodushti was observed in 24 (52.17%) and 9 (19.57%) patients, respectively.

Panduta, Yakritvriddhi and Vivarnata was found in all the 46 (100%) patients. Pleehavriddhi was found in 45 (97.83%) patients, Daurbalya in 44 (95.65%) patients, Hriddravatva in 41 (89.13%) patients, Aruchi in 39 (84.78%) patients, Pindikodweshtana in 31 (67.39%) patients, Sandhishoola in 21 (45.65%) patients, Balakshaya in 29 (63.04%) patients, Akshikootashotha in 19 (41.30%) patients, Udarashoola in 13 (28.26%) patients, Atisara in 13 (28.26%) patients) and Jwara in 11 (23.91%) patients.


   Results Top


Effect of therapy on subjective parameters

Trial drug provided relief in all the subjective parameters while in control group Udarashula, Atisara, Jwara and Aruchi was found to be relieved and rest of the parameters were aggravated [Table 4], [Table 5], [Table 6].
Table 4: Effect of therapy on subjective parameters in Group A

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Table 5: Effect of therapy on subjective parameters in Group B

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Table 6: Comparative efficacy on subjective parameters of Group A with Group B

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Effect of therapy on body mass index

Body mass index was highly significantly (P < 0.001) increased in trial group while decreased (P > 0.05) in control group [Table 7].
Table 7: Effect of therapy on other parameters in Group A and Group B

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Effect of therapy on objective parameters

  1. Hematological parameters: Hb., total red blood cell (TRBC) and packed cell volume (PCV) were increased significantly (P < 0.05) while ereythrocyte sedimentation rate (ESR) was decreased in trial group. Control drug provided an insignificant increase (P > 0.05) in Hb, TRBC, PCV, platelet count, and ESR
  2. Biochemical parameters: In trial group, serum bilirubin, SGOT and serum albumin were decreased while SGPT, serum alkaline phosphatase, serum total proteins, and serum globulin were increased. However the result was insignificant (P > 0.05). In control group, SGPT, serum alkaline phosphatase and serum globulin were decreased while serum bilirubin, serum total proteins, and serum albumin were increased. Moreovere, the result was also insignificant (P > 0.05). SGOT was decreased significantly (P < 0.05). Insignificant decrease (P > 0.05) found in serum creatinine and blood urea in trial group,


while insignificant increase in control group. In trial group, serum iron was decreased while serum Total iron binding capaicty (TIBC) and serum ferritin were increased, but the result is insignificant (P > 0.05) in all of three parameters. In control group, highly significant increase (P < 0.001) was found in serum TIBC, significant decrease (P < 0.05) in serum iron and insignificant increase (P > 0.05) was found in serum Ferritin. Both groups provided decrease in serum Iron and increase in serum TIBC, but better improvment was found in control group. Serum ferritin was increased in both groups, but the rate of elevation was less in trial group compared to control group. Although, the difference is statistically insignificant in all of three parameters [Table 8], [Table 9], [Table 10].
Table 8: Effect of therapy on objective parameters in Group A

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Table 9: Effect of therapy on objective parameters in Group B

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Table 10: Comparative efficacy on objective parameters of Group A with Group B

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Effect of therapy on blood transfusion interval

BT Interval was increased by a mean of 5.65 days in trial group which is statistically highly significant (P < 0.001) while it was significantly decreased (P < 0.01) by a mean of 3.33 days in control group [Table 7].

Follow-up details

Follow-up was done after 12 weeks after active treatment. No further increase in the severity of signs and symptoms was observed in the trial group. No adverse effects were reported by any of the patients in trial group.

Overall effect of therapy

In trial group, 3 (13.04%) patients had maximum improvement, 15 (65.22%) patients showed moderate improvement, 5 (21.74%) patients had mild improvement and no patient remained unchanged while in control group. Changes were found in subjective and objective parameters as described previously but when considering overall effect of therapy, no improvement was found in any of the patient. Thus, all the 21 (100%) patients remained unchanged [Table 11].
Table 11: The overall effect of therapy in 44 patients

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   Discussion Top


Hemoglobinopathies constitute to be a major public health problem internationally and particularly in the developing world. Thalassemia is such a disease andif corrective steps are not taken, it will burden the world's blood bank supplies and the health system in general. As iron overload is the main complication of thalassemia major, excess iron should be removed from the body. Agasyapatra Swarasa Bhaavita Vidanga Churna has been mentioned in Ayurveda Prakasha in the context of Apakva Loha Sevanajanya Vikara Prashamana.[4] These particular drugs may have chelating effect on Iron overload; thereby their consumption might help to regulate the metabolism of iron and avoid its excess accumulation, thus reducing the chances of possible adverse drug reactions if any. Gandhakadi Yoga has been evaluated for iron overload in experimental study with promising results.[2] Thus, it helps to decrease serum Iron, serum ferritin level and increases serum TIBC. Gandhaka has been used as Lohamarana dravya and is included in Lohamaranagana.[9]Marana is a process by which Dhatus are transformed into absorbable, adaptable and assimilable form.[10] Thus, Gandhaka interacts with metals at considerable temperature and brings about biotransformation of metals. Similarly, in human body, it may combine with free metals and convert them into soluble complexes, which may be easily excreted through urine or other modes of excretion. Bhringaraja swarasa was used for Gandhaka Shodhana before its inclusion in to Gandhakadi Yoga. Bhringaraja have hepatoprotective [11] and anti-inflammatory [12] activities and also it stabilizes human red blood cells (RBC) membrane.[13] Thus, it may help in reducing the hepatic damage encountered in thalassemic patients with tremendous iron overload. Fragile RBC's can also be taken care of to a certain extent by the virtue of its property of stabilizing human RBC membrane. Moreover, Bhringaraja has Rasayana property.[14] Recent concept of Rasayana equates it with immunomodulation and free radical scavenging activities. In thalassemic patients, excess free iron is unbound to ferritin, a specific protein enzyme and thus acts as free radical. This ionized iron causes tissue damage. Thus, Rasayana property of Bhringaraja can sustain the free radical damage to a certain extent. Vidanga contains embelin which is found to form complexes with nearly all metals under suitable pH giving rise to chelate structures. Embelin also showed iron chelating activity in some of the Loha preparations such as Vidangadi Loha, Saptamrita Loha.[15] Protective effect of Agastya against erythromycin estolate-induced hepatotoxicity has been reported.[16] Anxiolytic and anticonvulsive activity of Agastya leaves in experimental animals has also been proved.[17] Evaluation of Agastya for antiurolithiatic and antioxidant properties showed enthusiastic results.[18]Agastya leaf is reported to contain Ca (517 mg Ca in 100 g leaf protein concentrate-LPC).[19] Calcium antagonizes iron and is proven for its chelation.

In short, Amapachana, Deepana, Pandughna, Jwaraghna, Vishagna, and Rasayana properties relieve the signs and symptoms of thalassemia major. Iron chelation was done through Lohamarana and Lohasevanajanya Vikara Prashamana properties of the drug. Raktashodhana, Krimighna and Raktaprasaadana properties decrease the rapid destruction of RBCs and thus prolonging the life span of RBCs which increases the BT interval.

Although control drug found better in decreasing serum iron and increasing serum TIBC, the rate of elevation in serum ferritin is less in trial group as compared to control group. On the other hand, trial drug was found to be better in increasing BT interval and the improvement shown in the subjective parameters could be taken as signs of improvement in the quality of life of the patients.


   Conclusion Top


Gandhakadi Yoga helps to decrease iron overload from the body, normalize iron metabolism, prolong RBCs lifespan, relieve signs and symptoms of the disease, increase BT interval. Hence, it is effective as an adjuvant therapy in the management of thalassemia major.

Financial support and sponsorship

This study was financially supported by IPGTRA, Gujarat Ayurved University, Jamnagar, Gujarat, India.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Acharya YT, editor. Charaka Samhita of Agnivesha, Varanasi, Vimana Sthana. Reprint Edition. Ver. 6. Ch. 4. Varanasi: Chaukhambha Sanskrita Samnsthana; 2004. p. 248.  Back to cited text no. 1
    
2.
Pramod Y, Ashok BK, Modha J, Galib, Prajapati PK, Ravishankar B. Efficacy of Gandhakadi Yoga against Iron sorbitol induced Iron overload in albino Rats. Invent J 2011;2:129-35.  Back to cited text no. 2
    
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Mishra D. Kaumarabhritya, Reprint Edition. Ver. 2013. Ch. 2. New Delhi: Chaukhamba Sanskrit Pratishthan; 2006. p. 30.  Back to cited text no. 3
    
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Madhav A, editor. Ayurveda Prakasha. Reprint Edition. Ver. 3. Ch. 3. Varanasi: Chaukhamba Bharti Academy; 2007. p. 230-3.  Back to cited text no. 4
    
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Yadav P, Harisha CR, Prajapati PK. Pharmacognostical and physicochemical evaluation of Agasti leaf. Int J Ayurveda Res 2010;1:231-6.  Back to cited text no. 5
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Goswami A, Rajagopala S, Patel KS, Harisha CR, Prajapati PK. Quality control parameters of Gandhakadi Yoga tablets w.s.r. To its Microscopic evaluation. Indian J Pharm Biol Res 2014;2:120-5.  Back to cited text no. 6
    
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Madhav A, editor. Ayurveda Prakasha. Reprint Edition. Ver. 3. Ch. 2. Varanasi: Chaukhamba Bharti Academy; 2007. p. 30.  Back to cited text no. 7
    
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Baghel MS, Rajagopala S. Guidelines for Clinical Research Methodology in Ayurveda: A Report Submitted to WHO. Jamnagar: IPGT and RA, Gujarat Ayurved University; 2011.  Back to cited text no. 8
    
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Sarkar P, Prajapati PK, Choudhary AK, Ravishankar B, Subrata D. Conceptual study. Ayurvedic Research Database. IPGT and RA, Gujarat Ayurved University, Jamnagar, Gujarat, India. Dr. Girish KJ; 2005. p. 20.  Back to cited text no. 9
    
10.
Sadanand S, Kashinath SP, editors. Rasatarangini, Saptama Taranga. 11th ed. Delhi: Motilal Banarasidas; 2004. p. 500.  Back to cited text no. 10
    
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Tabassum N, Shyam S Agrawal. Hepatoprotective activity of Eclipta alba hassk. against paracetamol induced hepatocellular damage in mice was reported. JK Practioner 2004; 11/4, October – December; 278-80.  Back to cited text no. 11
    
12.
Murthy VN, Reddy BP, Venkateshwarlu V, Kokate CK. Antihepatotoxic activity of Eclipta alba, Tephrosia purpurea and Boerhaavia diffusa. Anc Sci Life 1992;11:182-6.  Back to cited text no. 12
    
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Singh A, Malhotra S, Subban R. Anti inflammatory and analgesic agents from Indian medicinal plants. Int J Integr Biol 2008;3:72.  Back to cited text no. 13
    
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Chunekar KC. editor. Bhavaprakash Nighantu of Bhavamishra, Guduchyaadi Varga. Ver. 241. 5th ed., Ch. 3. Varanasi: Chaukhambha Bharati Academy; 2010. p. 414.  Back to cited text no. 14
    
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Sandhya P, Grampurohit ND. Interaction of embelin and Iron in ayurvedic formulations. Indian J Pharm Sci 2004;66:739.  Back to cited text no. 15
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Pari L, Uma A. Protective effect of Sesbania grandiflora against erythromycin estolate-induced hepatotoxicity. Therapie 2003;58:439-43.  Back to cited text no. 16
    
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Kasture VS, Deshmukh VK, Chopde CT. Anxiolytic and anticonvulsive activity of Sesbania grandiflora leaves in experimental animals. Phytother Res 2002;16:455-60.  Back to cited text no. 17
    
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Doddola S, Pasupulati H, Koganti B, Prasad KV. Evaluation of Sesbania grandiflora for antiurolithiatic and antioxidant properties. J Nat Med 2008;62:300-7.  Back to cited text no. 18
    
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Kumar A, Revathi K, Mohanalakshmi S. A review on edible herbs as haematinics. Int J Pharm 2012;2:47.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10], [Table 11]



 

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