Pediatric Liver Diseases and its Management by Herbals : A Traditional Siddha Medicine Treatise

Siddha medicine is one of the oldest (5000 years old, pre vedic period) well-documented Indian traditional medicines, compared to Ayurveda, Unani, and traditional Chinese medicine, by way of keen observation and experimentation. It mentions 108 diseases that occur in childhood, which are further classified and described into various subtypes based on the clinical features and different stages of a particular disease. The objective of this review was to collect literature details on pediatric liver diseases and its management as per Siddha medicine. We have referred all the published Siddha books related to the pediatric practice. There were 37 Siddha literature deals pediatric diseases and they use the term kaamaalai or chenkamaari to describe the liver diseases. Most of the literature classifies liver disease into 3 types, but few texts describe 5-6 subtypes. Thus, a total of 9 subtypes of liver diseases in pediatric age group have been described in Siddha literature with a list of herbals to be used for each type. Mostly, the drug therapy is polyhedral formulations of internal and/or external application. A total of 113 herbals, 6 animal products (including black chicken liver, dairy products, donkey’s dung, honey) and 7 mineral based products (including iron, rock salt) were listed as potential agents to treat liver diseases. The safety and efficacy of all the above mentioned herbal/mineral products have not been fully explored in children, but may be a great potential for clinical development.


INTRODUCTION
'Children are not small adult'-this concept is very important in pharmacology research field.Mostly, the drug used in adult are intended to be tested in children or used in children at lesser doses.While considering the children's physiology, in which the body organs are not same as adult, the pharmacodynamics and pharmakinetic parameters for each drug will vary when compared to adult.Thus, special attention should be paid while developing drugs for children.
The drug discovery from natural products for children is delayed as there is lot of research involved in finding safe herbals for children.

Complementary and alternative medicine (CAM) is defined by the National Center for Complementary and Alternative
Medicine (NCCAM, part of the US Departmentof Health and Human Services) as "a group of diverse medical health care systems, practices, and products that are not presently considered to be a part of conventional medicine." [1]The use of CAM among children has increased dramatically in the western population, [2] in which phytotherapy was preferred to homeopathy, and parents with higher education used more CAM for their children. [3]To facilitate communication on specialized information regarding CAM in Canada, the pediatric CAM Research and EducationNetwork (http:// www.pedcam.ca/) was created in 2004. [4]Liver disease in pediatric age group is one of the most dangerous health issues in developing countries.
The systematic Siddha literature review on liver disease and its herbal therapy in pediatric age group is lacking.Thus, the aim of the current review was to collect and summarize the liver diseases and its herbal therapies mentioned in Traditional Siddha literature.

Traditional Siddha medicine
Siddha medicine is one of the oldest and most well documented of Indian traditional medicines, which had its origin in India and Sri Lanka.The period of Siddha tradition was pre-vedic and it is unique for its own specialization such as treatments for fetus, children, women, pregnancy care, post natal care, cancer, skin, varmam, alchemy etc. [5] In 1997, the United Nations Educational Scientific and Cultural Organization(UNESCO) recognized such Tamil medical palm manuscript collections as part of the UNESCO Registry. [6]Siddha literature describes a total of 4448 disease which can occur for man and animals.

Pediatrics in Siddha medicine
Among 4448, 108 diseases occur in childhood age period.Siddhar Agastyar, the father of Siddha medicine further classified the pediatric disease into many subtypes based on the clinical symptoms/signs. [7]Siddha literatures describe a group of herbals suitable for pediatric population based on the pediatric organ developments, keeping pharmacokinetic and pharmacodynamics in mind, which indicates the in depth knowledge of Siddha medicinal system in pediatric diseases management.
In Tamil Nadu and Sri Lanka, even today, we can see the pediatric Traditional Siddha practitioners, who are successful in diagnosing and treating children based on Siddha principles.Vaidyar.Param Jothi Naadar (Kannaiyya Vaidyar) belongs to Murasancode, Kanyakumari, India, was a popular pediatric Siddha vaidyar, who was also the great grandfather of the author Dr. Arul Amuthan.Solomon Vaidayr family is another pediatric Siddha tradition at Kanchiracode, Kanyakumari, India, and still practicing pediatric Siddha medicine.The literature review on pediatric liver disease management through Siddha Medicine is lacking.This work contributes on pediatric liver disease management especially focused on Traditional Siddha medicine.

METHODOLOGY
All the published Siddha literatures related to pediatric diseases were referred for the study.The terms 'Kaamaalai' and 'chenkamaari are the Siddha terms described in literature to describe the liver diseases.Since these original literatures were written in Tamil language using ancient medical terminology, the authors carefully read thoroughly to understand the clinical symptoms related to liver diseases.The herbals mentioned under each liver disease were documented and summarized in a table with their botanical names.

Siddha literatures dealing pediatric diseases
There were 37 Siddha literature deals with pediatric disease.Of which, 23 (no.1-23 in Table 2) are available as printed book and remaining 13 (no.24-36 in Table 1) are preserved in libraries as palm manuscript/paper written documentation.These palm manuscripts were originally documented few centuries ago in palmyra leaves.Many such leaves are preserved in libraries of India/Sri Lanka, thus we were not able to access it.In addition, many other pediatric Siddha literatures such as kumara thanthiram (by Ravanan, Sri Lanka) and Chega Raaja Sekaram (by King Chega Rajan, Sri Lanka) were destroyed due to natural calamities and war, thus not available today.One interesting thing observed was most of the pediatric literatures were written by Agastyar (the father of Siddha Medicine).Star Agastya (Canopus) was named after sage Agastyar (5000 BC), who also authored 25 hymns (nos.166 to 190) of the first 'mandala' of the Rigveda. [8]This gives an idea that possibly Agastyar could be the best pediatrician during prevedic period.

Different stages of pediatric age groups
Siddha system classifies the pediatric age group into three phases based on feeding habits as follows; feeding milk (paalunnum paruvam-1 to 3 years age), feeding milk and solid diet like rice (paalum chorum unnum paruvam-3-7years age) and solid diet phase (choruunnum paruvam>7years).
Based on the physical growth and activities, the phase 1 is further subdivided into 10 stages as given in the Table 2.

Baala vaagadam 200 -
Hand written document on paper by a vaidyar, which is preserved in Government Oriental Library, Chennai, India.

Baala vaidya pothini -
Hand written document on paper by a vaidyar, which is preserved in Government Oriental Library, Chennai, India.For a female child, 1-7 stages remain same.The 8, 9 and 10 stages are named as ammaanai paruvam, kazhangu paruvam and Oosal paruvam respectively. [9]diatric liver diseases in Siddha Medicine: 'Kaamaalai' and 'chenkamaari are the two Siddha terms describe the liver diseases.Most of the Siddha literatures obtained from Sri Lanka [10] and India classified pediatric liver disease into 3 subtypes based on clinical features.They are manjal, varal and oothu (neer) kaamaalai.Whereas, few Siddha literatures (written by Sage Agastyar) obtained from India, have additional two, thus five subtypes. [11]hey are manjal, varal,neer (oothu), maantha, and paandu kaamaalai.These five liver diseases have been described between 757-776 stanzas of Kumba muni baalavaagadam.Kamaalai nithanam, another Siddha literature published from Kanyakumari district of India written by a disciple (name is not mentioned) of Sage Agstyar mentions 6 subtypes such as manjal, varal, vaatha, pitha, silerpana (kaba) and thontha kaamaalai. [12]In all the above three types (3,5,6 subtypes) of classifications, manjal and viral kaamaalai are common.A total of 9 subtypes have been documented in different literatures with different clinical features.

Varal kaamaalai
The cardinal clinical features include greenish discoloration of eye, diminished vision, excess thirst, loss of appetite, dark urine, white colored stool and body muscle wasting.
'Kaamaalai nithanam' [17] mentions additional features such as fatigue, insomnia, less food intake, irritability, lower abdominal pain, burning micturition and yellowish discoloration of skin.If these severe symptoms appears, it leads to death.If the child with these symptoms survive (avadhi in Siddha) up to 36 days, then the child will not die.If untreated, child may develop hematemesis even after 7 -10 months.However, it is better to start treatment before 48 days of onset to cure this condition.These might be the later observation of the disciple of Sage Agastyar, who documented the literature.

Maantha kaamaalai
The cardinal clinical features include ascites, edema, fever, excess thirst, headache, body pain, fatigue, fissures in lips and diarrhea.The polyherbal formulations described for the

Paandu kaamaalai
The cardinal clinical features include fatigue, excess thirst, body pain, fever with rigor followed by sweating, palness of body due to anemia, numbness, ascites, fluid collection in lower abdomen, regurgitation, shrunken eyes and reduction in size of all four limbs.The polyherbal formulations described for the treatment of paandu kaamaalai include thazhuthaazhai vaer Kashayam.

Vaathak kaamaalai
The cardinal clinical features include emaciation of body, nausea, paleness of eye, loss of appetite, excess fatigue, constipation and insomnia.The polyherbal formulations described for the treatment of vaatha kaamaalai include vaatha kaamaalai kudineer, garlic, aya chendooram, gaantha chenooram and kittam chendooram.

Pitha kaamaalai
The cardinal clinical features include numbness of limbs, yellowish discoloration of conjunctiva, indigestion, vomiting, emaciation of body, fatigue and anemic paleness.
The polyherbal formulations described for the treatment of pitha kaamaalai include thumbai karkam and kuppaimeni kashayam. [18]lerpana (kaba) The cardinal clinical features include yellowish discoloration (of tongue, conjunctiva and urine), excess sweating ( in scalp, face, nose), swelling in small joints, insomnia, dyspnea on exertion, shrunken eyes due to muscle wasting, hiccough and cough.The polyherbal formulations described for the treatment of Silerpana kaamaalai include karungozhi eeral (black chicken liver) chooranam and silerpana kaamaalai nei.

Thontha kaamaalai
The cardinal clinical features include yellowish urine, paleness of conjunctiva, severe body pain (similar to inflammatory pain), excess thirst, dryness of mouth, dizziness, mental tiredness and flatulence.The polyherbal formulations described for the treatment of thontha kaamaalai include Sangupushpam root karkam, chitthamuttivaer kashayam and Seeraga karkam.

Polyherbal formulations for all types of kaamaalai
Chitthamutti vaer kashayam, mandoorathi kashayam, Mandoora adai kudineer, kuppaimeni kashayam and arithagi chooranam are the different polyherbal formulations administered orally for the treatment of pediatric liver diseases.Aavuriilai thailam, Bharmmi nei and kaiyaan thailam are administered orally as well as to be applied on scalp.Such topical oil preparations are believed to be absorbed systemically.These topical oils are comparable with current transdermal drug delivery system.

Herbals used for liver diseases
A total of 113 herbals have been listed to be useful in pediatric liver disease management (Table 3).Most of the herbals have been proven for their hepatoportective activity, liver cell regeneration property and diuretic activity.
Ealier studies have proven the hepatoportectiveacticity of many plants which have been listed in Siddha litearure, which include Phyllanthus niruri, Aloe vera, Curcuma longa, Eclipta prostrate, Solanum nigrum, Asparagus racemosus, Azima tetracantha, Indigofera tinctoria, Cuminum cyminum, Withania somnifera, Nigella sativa, Ricinus communis, Moringa oleifera, Hemidesmus indicus, Tinospora cordifolia, etc. [19] Amaranthus spinosus and Hygrophila auriculata have been proven as the best diuretic plants. [20]Many plants listed here have antioxidant activities and nutritional value as well.Thus, the polyherbal formulation described for each types of liver disease could have multiple targets in the management of liver diseases.

Animal and mineral based drugs used for liver diseases
The six animal derived products include black chicken liver powder, dairy products of domestic animals, honey and donkey's dung (Table 4).Purified liver extract has antianemia factor, which is helpful in treating anemia in liver cirrhosis.Liver extract is believed to improve liver function, prevent liver damage and treat liver diseases, but currently not preferred.Donkey's dung (Anbarnesa) has an important role as a drug in Iranian Traditional Medicine. [21]ron supplements when appropriate can prevent chronic liver diseases. [22]Siddha medicine also favors using iron in chendooram (sulfide form preferably in nanozie).
Dietary advices for pediatric liver diseases [23] The porridge prepared using Kovai ilai (Cephalandra indica) leaf juice, paruthi ilai (Gossypium indicum) juice, cow milk, pacharisi (raw rice), paasi payaru (Phaseolus mungo) and sugar cane sugar is to be consumed as a diet.Sweetening agents to be added in the drugs to improve palatability include honey, sugar cane sugar and Glycrrhiza glabra.Salt, sour, tobacco and alcohol should be avoided by the children during the therapy.If the patient is the feeding infant, then the feeding mother should follow these diet restrictions to prevent the pharmacokinetic/dynamic interactions with the herbal therapy given to the baby.

DISCUSSION
The original elegant prose in Tamil could not be retained in English and here the clinical description and treatment were directly translated.Liver disease is a common disease among Indian pediatric population.The detailed classification and description based on symptomatology along the herbal drug therapy is simply amazing.Though, many subtypes are not directly comparable with the liver diseases mentioned in modern medicine text books, it is remarkable that the documentation was based on ancient yogis clinical expertise.
The etiology of infantile liver diseases include physiological, hereditary, genetic abnormality, infections, autoimmune related and protein deficiency in diet.Anemia and anorexia are associated with hemolytic jaundice, whereas greenish (deep yellow) discoloration seen in obstructive jaundice.Deposition of indirect bilirubin in brain leads to neurological symptoms such as irritability, twitching and mental retardation.Further, the pediatric liver diseases are classified into three stages based on clinical phases; early (pre-ascitic stage), intermediate (ascitic or cirrhotic stage) and terminal stage.In early stage, there is a low grade fever, diarrhea, irritability and palpable liver.In pre-cirrhotic stage, there is a severe emaciation, jaundice, yellowish urine, odema, enlarged liver, liver tendernes and ascites.In terminal stage, jaundice becomes deep with hepatomegaly and bleeding episodes. [24] contemporary pediatric liver practice,the severe forms would not usually be encountered, due to the preventive care, early diagnosis and advanced medical therapies.In modern medicine, there is no curative drug known till now for the liver diseases.Exposure to sunlight is the best therapy for physiological jaundice.Blood transfusion and maintaining fluidity are other options for severe hemolytic jaundice.Liver extract, iron supplements, vitamin supplements and steroids are used as drug therapy to manage liver diseases based on the severity.Diuretics with potassium supplements are advised to reduce edema and ascites. [25]It is noteworthy that even Siddha literature describes chicken liver, iron based formulations, diuretic herbals, hepatoprotective herbals and natural salts containing potassium.Most of the herbals listed in Table 3 have been proven for their hepatoprotetive and hepatic regeneration property.
For the non-Tamil-speaking medical community, it is hoped that there will be more translations of pediatric and adult Siddha medicine.To date, there have been no notable reports of significant side effects or, for that matter, comparative studies for efficacy.The same herbal remedies could be tried for liver diseases with similar clinical features.A glimpse into the world of the ancient Indian medical literature may provide some knowledge that many new diseases have been acknowledged as common pediatric conditions for centuries.And also some relief or cure may be possible through herbal medicine, though further exploration into the utility and safety of these agents in small children would be particularly advisable before widespread usage in infants.Careful testing and purification to remove heavy metals is needed to demonstrate safety in infants.For the researcher or herbal manufacturer, this can give a hope for drug discovery.

Table 2 : The sub classification (10 stages) of paalunnum paruvam based on the physical activity
G Senthilvel et al: Pediatric Liver Diseases in Siddha Medicine