Efficacy of standardized herbal extracts in type 1 diabetes - an experimental study

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EFFICIACY OF STANDARDISED HERBAL EXTRACTS IN TYPE- 1 DIABETES –AN EXPERIMENTAL STUDY

 

 

 

 

 

 

THESIS

 

SUBMITTED

IN PARTIAL FULFILEMENT OF THE REQUIREMENTS FOR

THE DEGREE OF

 

M.D.

(DRAVYAGUNA)

 

OF THE

GOVERNMENT AYURVEDIC COLLEGE,

POST-GRADUATE TRAINING & RESEARCH CENTRE,

 KADAM KUAN, PATNA

INDIA

AFFILIATED TO BABASAHEB BHIMRAO AMBEDKAR BIHAR UNIVERISTY, MUZAFFARPUR

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

   February 2006                                            Dr. Amritpal Singh

GOVEREMENT AYURVEDIC COLLEGE,

POST-GRADUATE TRAINING & RESEARCH CENTRE,

 KADAM KUAN, PATNA

 

 

CERTIFICATE

 

This is to certify that the work incorporated in this thesis entitled, “EFFICIACY OF STANDARDISED HERBAL EXTARCTS IN TYPE 1 DIABETES– AN EXPERIMENTAL STUDY” for the degree of M.D. (Dravyaguna) has been carried out by DR.AMRITPAL SINGH under our direct supervision and guidance.

 

The work done in connection with this thesis has been carried out by the candidate himself and is genuine.

           GUIDE                                                     GUIDE

DR. SURYA BHOOSHAN                             DR. BHARAT SINGH

M.D. Ayur, Professor                                        M.D. Ayur, Reader

Govt. Ayurvedic College,                               Govt. Ayurvedic College,

Post-graduate                                               Post-graduate

Training & Research                                     Training & Research                

Centre, Kadam Kuan, Patna                          Centre, Kadam Kuan, Patna                                   

       

         GUIDE                                                        GUIDE

DR. DEENA NATH TIWARI                        DR. VACHASPATI MISHRA

M.D. Ayur, Reader                                         M.D. Ayur, Sr. Lecturer

Govt. Ayurvedic College,                             Govt. Ayurvedic College,

Post-graduate                                             Post-graduate

Training & Research                                   Training & Research                

Centre, Kadam Kuan, Patna                        Centre, Kadam Kuan, Patna                                   

 

 

Acknowledgements

 

 

Confronted with the monumental task of writing this thesis, mixed feelings of apprehension and excitement gripped me at first and as the thesis took shape, I was exhilarated but quickly realized that it was only possible; due to the unstinted efforts of my teachers and colleagues.

 

 

It is great pleasure for me to acknowledge the contributions of all who have been instrumental in the successful completion of this work.

 

The critical and demanding role of the guide was most capably executed by Dr. Bharat Singh (M.D. Ayur, Reader), Dr Deena Nath Tiwari (M.D. Ayur), Dr. Vachspati Mishra (M.D. Ayur, Senior Lect) and Dr. Surya Bhooshan Sharma (M.D. Ayur, Prof). It gives me immense pleasure to express my deep sense of gratitude to them for guiding me through all the stages of my thesis. There invaluable experience, guidance, constant motivation and reprimand helped me in reaching the deadlines on time. I am also deeply grateful to my guides for there keen interest, advice and guidance throughout the course of the study.

 

I sincerely thank, Dr.Raghav Dutt Pathak (Principal, Govt. Ayurvedic College, Post-graduate Training & Research Centre, Kadam Kaun, Patna), for his suggestions, cooperation and help whenever needed.

 

Words are not sufficient to express my gratitude towards all my friends and colleagues who were always beside me during the exciting and frustrating moments of this study. I would like to thank the garden supervisor and all other people associated with this study. And to all my well-wishers who wished me the completion of this project.

 

I acknowledge the encouragement and mental support of my family members during the course of this study.

 

 

 

February 2006                                            Dr. Amritpal Singh

 

 

CONTENTS

 

TOPIC                                                                    PAGE NUMBER

 

    INTRODUCTION TO DIABETES SCINERIO                        1-2

 

  FUNDAMENTALS OF ĀYURVEDIC PHARMACOLOGY         3-19

 

   RECENT TRENDS IN ĀYURVEDA/HERBAL SCIENCES        20-26

 

   ĀYURVEDIC PERSPECTIVE OF DIABETES                          27-33

 

   AIMS AND OBJECTIVES                                                      34

 

   MATERIALS AND METHODS                                                35-38

 

   STATISTICAL ANALYSIS                                                       39

 

   RESULTS                                                                              40-43

 

   DISCUSSION                                                                         44-49

 

   BIBLIOGRAPHY                                                                      50-57

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

        

 

 

 

 

 

 

 

 

 

 

 

INTRODUCTION TO DIABETES SCINERIO

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

The prevalence of diabetes in India is estimated to be 1-5% (Rao et al., 1989). Also, the number of diabetics is projected to rise from 15 million in 1995 to 57 million by the year 2025 making it the country with the highest number of diabetics in the world (King et al., 1998).

         Although, insulin and oral hypoglycaemic agents are the mainstay of treatment of diabetes, they have prominent side effects and fail to alter the course of diabetic complications. The high cost of some agents and potential for adverse effects have led several investigators to focus their attention on the traditional medicines.

       The World Health Organization has estimated that a low income Indian family with a diabetic patient devotes 25% of the income to the care of that patient. One third of the diabetic patients take alternative medications; that they consider efficacious (Ryan et al., 2001). Garlic, Echinacea, herbal mixtures and glucosamine are the most commonly used alternative medications.

       According to ethno-botanical information, about 800 plants may possess anti-diabetic potential (Alascon-Agmlara et al., 1998). Several of traditional plants have shown anti-diabetic potential, when assessed in experimental models of diabetes.

      In India, indigenous remedies have been used in the treatment of diabetes mellitus since sixth century BC (Grover and Vats., 2001). There are several medicinal herbs used for the treatment of diabetes in Āyurvedic system of medicine. Withania somnifera Dunal (Solanaceae) is used as rejuvenator in Āyurvedic system of medicine. Modern investigations have demonstrated anti-stress (adaptogen) effect of Withania somnifera. Anti-stress drugs are useful in management of stress related disorders such as arthritis, hypertension, diabetes and general debility. Allium sativum Linn. (Liliaceae) is used as traditional remedy for diabetes. Gymnema sylvestre (Retz.) Schult (Asclepiadaceae) is traditional Ayurvedic remedy for the treatment of diabetes. Suśruta, the great Indian Surgeon described the herb as best medicinal agent for treating diabetes.

Ferula foetida (Bunge.) Reg. (Apiaceae) is used as antispasmodic in Ayurvedic system of medicine. It is part of list of promising medicinal plants targeted for antidiabetic research (Akhtar and Shah., 1993). Murraya koenigii (L.) Spreng. (Rutaceae) is a folk remedy for treating diabetes. Fine powder of fresh leaves is recommended on empty stomach in treating diabetes. Recent investigations have demonstrated hypoglycemic and antihyperglycemic activity of Murraya koenigii leaves in diabetic rats (Yadev et al., 2002).

 

 

 

 

 

 

         

 

 

              

 

 

FUNDAMENTALS OF      ĀYURVEDIC PHARMACOLOGY

 

    Āyurveda is the science which literally means ‘the science of life’. It is also known as Indian system of medicine (Gupta., 1997). Āyurveda is an ancient medical system, which treats what is advantageous and what is harmful for the body and stresses on happy and unhappy states of life (Sharma., 1982). In other words, Āyurvedic system of medicine gives importance to the involvement of the patient’s well being.

    Āyurveda was derived from Artharva Veda and Vedic era is considered to be the time, when Āyurveda flourished as a science (Sharma., 1987). It is estimated that around 1000 B.C., two principle texts of Āyurveda, Charaka Samhita and Suśruta Samhita were written (Kapoor., 1990). Charaka Samhita deals with medicine and Suśruta Samhita deals with surgery (Shastri., 1979). Distinguished scholars were attracted to the science of Āyurveda and visited India for acquiring scientific language (Singh., 2005). Hippocrates, the father of modern science, was an intensive learner of Āyurveda.

    Āyurveda is based on peculiar fundamental principles like Tridośa (three humors vāta, pitta and kapha) theory, and Paňca-mahābhuta (five elements ether, air, fire, water and earth) theory (Sharma., 1987). Imbalance of the three humors is considered to be the root cause of the disease.

  1.  Vāta is a combination of air and ether.
  2.  Pitta is combination of earth and fire.
  3.  Kapha is a combination of ether and water.

 

Further five subtypes of vāta, pitta and kapha have been described in Āyurveda. These are tabulated below:                         

 

 

Types and functions  of Vāta

S.No

Name

Function

1

Prāna

Breathing, blood circulation and swallowing.

2

Udāna

Sound, speech, memory.

3

Vyāna

Perspiration, blinking and other movements.

4

Samāna

Digestion and formation of stools.

5

Apāna

Excretion of the waste products.

 

Table 1: It shows types of vāta (air) humour.

 

 

Types and functions  of Pitta

S.No

Name

 

1.

Raňjaka

Colour of blood, bile and stools.

2.

Sādhaka

Deals with intellect and memory.

3.

Ālocaka

Visual perception.

4.

Bhārajaka

Colour of the skin.

5.

Pācaka

Digestion of food stuffs.

 

Table 2: It shows types of pitta (bile) humour.

 

 

Types and functions  of Kapha

S.No

Name

Function

1.

Tarpaka

Sense and hearing.

2.

Avalambaka

Protects heart and lungs.

3.

Kledaka

Digestion.

4.

Bodhaka

Gustatory perception.

5.

Sleśaka

Lubrication in the joints.

 

Table 3: It shows types of kapha (water) humour.

The aim of the treatment is in correcting the imbalance of the biological humors. The great seers of Āyurveda developed peculiar methods for testing the potency of the drugs. If the literature is consulted, it can be concluded that drugs like Harade, Arjuna, Atibalā and Śilājeet seems to be thoroughly investigated for their medicinal activities (Sharma & Das., 1990).

    Diagnosis of a disease is based on pulse examination (Lochan., 2003). The diagnostic parameters of Āyurveda were established way back and are still valid today. An expert Āyurvedic physician is in a position to tell about the disease process by examining the pulse. Detailed investigation includes (Gupta., 1997).

  1.   Interrogation of the patient in terms of body constitution, exercising and digestive capacity.
  2.   Objective examination to assess the progress of the disease.
  3.   Examination by inference like colour of skin, urine, and state of the pupil.

    Āyurvedic pharmacy is a vast subject. Dravyaguna deals with the study of drugs derived from nature and Rasa-Śastra deals with study of minerals. Drug formulation in Āyurveda is based on following seven parameters:

  • Dravya (Substance).
  • Rasa (Taste).
  • Guna (Property).
  • Vīrya (Potency).
  • Vipāka (Post-digestion effect).
  • Prabhāva (Therapeutics).
  • Karma (Pharmacological activity).

Dravya (Substance)

    According to Caraka Samhita, dravya is an organized moiety. Āyurvedic system uses drug as a whole instead of isolating active bioactive constitutes; again a point based on organized nature of the dravya. When we isolate the active constituent, the dravya no longer remains organized and chances of having side effects are more (Singh., 2005).

    As we have already discussed that study of Dravyaguna involves study of seven parameters (see under introduction). Dravya can be defined as store house of guna and karma parameters. For example atoms combine to form molecules and similarly molecule can be dissociated into basic atoms. The combinations and separations are karma.  All these changes take place at the molecular level within the substance and can not be seen with the naked eye (Singh., 2005).

    According to    Āyurvedic concept guna parameter also resides in the dravya as when two things combine together to form a new thing and only extensive study it can de said that the new thing has extra property (Singh., 2005).

Classification of dravya

(1) According to origin

A. Audbhida: It includes dravya derived from plant origin. Majority of the natural products come from green flora. In fact all the systems of medicine are largely dependent on medicinal herbs for obtaining drugs. Until the discovery of antibiotics and analgesic plant based medicines were the primary healthcare system. Today we see the reemergence of plant based medicine. According to W.H.O., sixty to seventy percent of drug used in synthetic system of medicine are derived from herbal source. With development of disciplines like botany, biochemistry and chemotaxonomy the study of medicinal plants has taken a new path. Keeping in mind, the non-availability of scientific devilments, the scholars of Ayurveda did a tremendous job in classifying the audbhida dravya into four distinct classes.

a. Vanaspati: It includes herbs, under shrub, shrub and trees.

b. Vanspatya: It includes plants in which fruit appears after flowering.

c. Auśadi: The dravyas which gets destroyed after maturation.

d. Virūdha: This group includes climbers and twiners.

B. Jāňgama: This group includes man, animals, birds and insects. Drugs obtained from animal source are included in this group. They are further divided in to four distinct classes:

  1.  Jarāyuga: It includes animals from mammalia.
  2.  Aňdaja: It includes birds and fishes.
  3.  Svedaja: This group includes insects.
  4.  Udbhija: It includes animals from ambhibia.

(2) According to usage

A. Āhara: It includes routine diet consumed by human beings for maintaining optimal health. Rasa factor is predominant in āhara dravya

B. Auśada: It includes drugs taken in various forms for alleviating diseases.

(3) According to specific action

A. Dośa praśamana: In Āyurveda the disturbed biological humours vāta, pitta and kapha are considered to be the root cause of all diseases. Texts have described various drugs or methods to pacify the disturbed humours. Oil application and internal administration is best option for pacifying vāta humour.

B. Dhātū pradūśaka: Some drugs aggravate the biological humours and disturb the function of body tissues. Āyurveda has described various diet incompatibilities and contraindications for drugs. For instance a drug aggravates pitta humour in a person or produces pathology in blood tissue; this is refereed to dhātū pradūśaka.

C. Svasthahita: Some drugs help in maintaining good health of human body and mind.

(4) According to elemental composition

According to Āyurveda, dravya is made of five elements. Depending on the predominance of the elements the dravya can be ākaśiya, vāyavya, āgneya, āpya or pārthiva (Singh., 2005).

(5) According to therapeutics

Drugs are used for pacifying disturbed biological humours (samśamana dravya). Sometimes drugs are used for removing humours from the body (samśodhana dravya). In modern science drugs are classified according to therapeutic use. For example a drug used for lowering blood sugar is known as hypoglycemic agent(Singh., 2005).

(6) According to pharmacological action

Caraka has classified drugs according to pharmacological action. For example a drug which is used in the treatment of jvara (fever) is known as jvaraghana (febrifuge).

Guna (Property)

Guna (property) parameter is a vast topic. Most probably this parameter represents specification of the drug. Āyurveda has described forty-one properties. Guna parameter represents partly physical and chemical properties and partly physiological properties of drugs.

These are further divided into

1. Gurvādi guna (20).

2. Parādi guna (10).

3. Viśisata guna (5).

4. Adyātamika guna (6).

Gurvādi guna have been explained in following table.

 S.No

Synonym.

Composition

Effect on Biological humours

Function

1.

Gurū (Heavy).

Earth and water.

Increases K, decreases V.

Tonic, diaphoretic and diuretic.

2.

Laghu (Light).

Fire and air.

Increases V, decreases K.

Vulnerary, digestive, appetizer,

3.

Śita (Cold).

Air and water.

Increases V&K, Decreases  P.

Cooling and anti-diaphoretic.

4.

Uśana (Hot).

Fire.

Increases P, decreases K& P.

Carminative, appetizer and

diaphoretic.

5.

Snigdha.

Earth and water.

Increases K&P, decreases  P.

Tonic.

6.

Rukśa.

Fire and air.

Increases V, decreases K& P.

 

7.

Mrdu (Soft).

Water and ether.

Increases K, decreases V.

Laxative.

8.

Tikśna (Sharp).

Fire and air.

Increases P, decreases V

 

9.

Sthira (Immobile)

Earth and water.

Increases K.

Causes constipation.

10.

Sara (Mobile).

Water.

Decreases V.

Carminative, mild laxative.

11.

Manda (Dull).

Earth and water.

Increases K.

 

12.

Kathina (Hard).

Earth.

Increases V.

 

13.

Pichila (mucilaginous).

Water.

Increases K.

Promotes union of fracture.

14.

Viśada.

Earth and air.

Increases V, decreases K.

Promotes healing of wounds.

15.

Śalaksana.

Water.

Increases K.

Promotes healing of wounds and union of fracture.

16.

Khara.

Air.

Increases V.

Produced emaciation.

17.

Sthūla (Macroscopic).

Earth.

Increases K.

Nutritive.

18.

Śūksama (Microscopic).

Air.

Increases V.

 

19.

Sāndra (Semi-solid).

Water and air.

Increases K.

Tonic.

20.

Drava (Liquid).

Water.

Increases K.

 

 

Table 4: It shows composition, effect on biological humours and functions of Gunas.

Parādi guna have specific role in medicine. A brief description is given below:

A. Para: In Ayurvedic language para signifies best. What is best for the patient diet or medicine; this is represented by para. Even in today’s clinic practice we can see doctor prescribes complete bed rest in some disease for speedy recovery. Diseases like diabetes and arthritis require rational approach. Mixed blend of medicine, diet and exercise in must for keeping symptoms in control.

B. Apara: It signifies what is harmful for the body. Ayurvedic system of medicine treats diet as medicine and vice versa. Like consumption of proteins in gout and consumption of solanceous vegetables in rheumatoid arthritis can aggravate the problem. Similarly intake of pain killers in patients having history of peptic ulcer is harmful.

C. Yuktī: It can be described as ‘doing something in a schematic manner’. The formulation described in Āyurveda are prepares after keeping in mind the aggravated humour (vāta or pitta or kapha), patients constitution and when to be administered (Singh., 2005).

D. Sāmkhya: It signifies number. For example Āyurveda considers vīrya (potency of drug) of two types; ushan and cold. Two types of jaundice are mentioned in Ayurvedic texts kośtaśrita (confined to abdomen) and śākāśrita (confined to limbs) whereas in modem medicine jaundice is if three types hemolytic, hepatic and obstructive.

E. Samjoga: It can be defined as combination of two or more substances. While preparing Triphalā, we incorporate definite proportions of Hāritaki (Terminalia chebula), Vibhītuka (Terminalia bellerica) and Āmalaki (Phyllanthus emblica).

F. Vibhāga: It can be defined as separation of one substance from another. It can be simply compared with extraction of bioactive constituents from medicinal plants. Drugs like vinblastine and vincrisitne have been isolated and purified from Madagascar periwinkle (Vinca rosea) are potent anticancer drugs. According to Āyurvedic experts, vibhāga also stand for ability of our body to distinguish between two substances (Singh., 2005).

G. Parimāna: It signifies measurement of liquid or solid. Like one teaspoonful (5 ml) tablespoonful (15 ml) for liquids. Similarly Āyurvedic system of medicine has its own concept of measurement like rati, māśa or tolā

H.  Samskāra: Āyurveda has described some medicinal plants as poisonous. They are properly purified before using in preparing in a formulation. All the process adopted to render pant les toxic are referred to as samskāra. While doing phytochemical screening, a plant is selected for tasting. Let us say that an alkaloid or glycoside is active constituent of the plant and we wish to isolate it. A plant contains number of chemical constituents and numbers of procedures are adopted by plant chemists to separate the active constituent.

Rasa (Taste)

Rasa (taste) has got significant place in Āyurvedic medicine. A diagnosis of a disease is based on three biological humours (vāta, pitta and kapha) and treatment is based on six tastes (sweet, sour, salt, pungent, bitter and astringent). Our tongue experiences these tastes when drug is administered orally. The taste parameter actually reveals dynamic of Āyurvedic preparations (Singh., 2005).

Evolution of Tastes

Taste

Evolution

Sweet.

Earth + Water.

Sour

Earth + Fire.

Salt

Fire + Water.

Pungent

Fire + Air.

Bitter

Ether + Air.

Astringent

Earth+ Air.

Table 5: It shows evolution of six tastes

Properties of Tastes

Taste

Properties

Sweet

Moist, cold & heavy.

Sour

Moist, hot & light.

Salt

Moist, hot & light.

Pungent

Dry, hot and light.

Bitter

Dry, cold & light.

Astringent

Dry, cold & light.

Table 6: It shows properties of six tastes

5.3: Composition of tastes

Water is primary constituent in composition of tastes. When water element interacts with other elements, evolution of tastes takes place. The taste of a particular thing depends on the predominance of the elements (Sharma., 1987).

5.4: Taste and humours

Enhancing effect

  1. Vāta is increased by bitter, astringent and pungent.
  2. Pitta is increased by sour, pungent and salt.
  3. Kapha is increased by sweet, salt and sour.

Retarding effect

  1. Vāta is decreased by salt, sour and sweet.
  2. Pitta is decreased by bitter, astringent and sweet.
  3. Kapha is decreased by pungent, bitter and astringent.

5.5: Taste and dhātū(tissues)

  1. Sweet, sour and salt supplement the body tissues.
  2. Pungent, bitter and astringent reduces the body tissues.

5.6: Taste and mala (waste products)

  1. Sweet, sour and salt enhance the removal of waste products.
  2. Pungent, bitter and astringent cause retention of waste products.

5.7: Actions of tastes

  1. Sweet:  Nootropic, demulcent, tonic, expectorant and mild laxative.
  2.  Salt: Laxative, appetizer, digestive, expectorant and emetic (large doses)
  3.  Sour: Carminative and appetizer.
  4.  Pungent:  Stimulant, carminative, diaphoretic, bronchodilator and anthelmintic.
  5.  Bitter: Alterative, anthelmintic, febrifuge, bitter tonic and cholagouge.
  6.  Astringent: Styptic and antidiarrhoeal. 

The evolution, properties and functions of six tastes have been summarized below:

 

S.No

Taste

Evolution

Properties

Functions.

1.

Sweet.

Earth + Water.

Moist, cold & heavy.

Nutritive, thirst depressant, vāta and pitta pacifying.

2

Sour.

Earth + Fire.

Moist, hot & light.

Appetizer, cardiac tonic and nervine tonic.

3

Salt.

Fire + Water.

Moist, hot & light.

Digestive, mild laxative, vāta pacifying and sialagouge.

4

Pungent.

Fire + Air.

Dry, hot and light.

Anti-inflammatory, anti-obesity and anthelmintic.

5

Bitter.

Ether + Air.

Dry, cold & light.

Anthelmintic, anti-pruritic and thirst depressant.

6

Astringent.

Earth+ Air.

Dry, cold & light.

Styptic and antidiarrhoeal.

       

             Table 7: It shows evolution, properties and functions of six tastes.

Further it is not necessary that a drug can have only one taste. As an instance, rasona (Allium sativum) has all the tastes except sour.

Vīrya (potency)

Vīrya is derived from Sanskrit word ‘Vira vikranto’ which signifies energy or potency (Singh., 2005). Caraka has defined vīrya as driving force behind the therapeutic activity of the drug (Sharma & Das., 1990). According to some experts, vīrya is comparable to active constituency of a drug. 

Types:

A. Caraka has accepted two types: Uśna and śita.

B. Suśruta accepts eight guna (snighda, rukśa, ushna, śita, mrdu, tikśana, viśada and pichila) as vīrya.

 

 

Vīrya and dośa (humours)

       Uśna vīrya

       Śita vīrya

Aggravates pitta

Aggravates vāta

Pacifies vāta

Pacifies kapha

Pacifies kapha

Pacifies pitta

                 

                         Table 8: It shows effect of vīrya on three dośa

Actions of vīrya

       Uśna vīrya

       Śita vīrya

Increases hot factor

Increases cold factor

Digestive

Anabolic

Diaphoretic

Spermopiotic

Emaciation

Tonic

 

Table 9: It shows action of vīrya

Vipāka (Post digestion effect)

Vipāka is defined as the final taste of a drug, which is encountered after exposure to digestive enzymes (Sharma & Das., 1990). It is comparable with metabolism and therapeutic activity of the drug (Sharma., 1982). Although number of theories have been put forward, but generalized view is that vipāka is of three types; sweet, sour and pungent (Singh., 2005). The vipāka of various tastes are tabulated below:

Taste

Post digestion effect

Sweet

Sweet

Sour

Sour

Salt

Sweet

Pungent

Pungent

Bitter

Pungent

Astringent

Pungent

                          

                                Table 10: It shows vipāka of six tastes

Sāmānya pratyāyarabdha

The drugs are classified according to potency as hot or cold. Every drug mentioned in Āyurvedic texts irrespective of the fact it is derived from plant or animal or marine source, has specific potency. In Āyurvedic language such drugs are known as sāmānya pratyāyarabdha (Singh., 2005).

Vicītra pratyāyarabdha

Some drugs are exception to the concept of pratyāyarabdha. Depending on metabolic and chemical changes a substance goes in human body, the configuration of a substance changes and taste or potency may change. In Āyurvedic language such drugs are known as vicītra pratyāyarabdha. For instance sunthī (Zingiber officinale) has pungent taste but sweet in vipāka (Singh., 2005)..

Prābhava (Specific action)

 As we have studied that a drug works according to taste, potency and post digestion effect. Every drug has specific configuration. There are some exceptions when a drug having typical taste, potency and post digestion effect produces entirely different action from that of expected action (Upadhya., 1984). According to experts again the role of digestive juices and enzymes is critical. As a result the alignment of the atoms changes and it produces different action. In Āyurveda, this change is referred to as prābhava (Upadhya., 1984). This can be seen in organic synthesis, where new molecules are being created by changing configuration of functional group of the molecule (Singh., 2006). Like vipāka concept, prābhava is also debatable topic and it demands further research.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

RECENT TRENDS IN AYURVEDA/HERBAL SCIENCES

 


    Medicinal plants constitute an effective source of traditional (e.g., Āyurvedic, Chinese, Unani and Homeopathy) and modern medicine. Herbal medicine has been shown to have genuine utility and about 80% of rural populations depend on medicinal herbs as their sole source of primary health care. A study from the U.S. demonstrated that about 34% of the general population used one or the other system at least once a year. In Germany and France, which together represent 39% of the $14 billion global retail market, the use of herbal remedies is well established. In fact, today approximately 70% of “synthetic” medicines are derived from plants.

    A medicinal herb can be viewed as a biosynthetic laboratory as it contains a number of chemical compounds. These compounds, responsible for medicinal activity of the herb, are secondary metabolites. For example, alkaloids are nitrogenous principles of organic compounds and combine with acids to form crystalline salts. Morphine, Atropine, Codeine and Cocaine are familiar examples. Glycosides are crystalline compounds, which are neutral in reaction that when acted upon by acids, split into sugar and non-sugar parts. Salicin and Digioxin are familiar examples of glycosides. In addition, herbs contain saponins, resins, oleoresins, lactones and volatile oils.

    Most of medicinal herbs are not—in their natural state—fit for administration. Preparations suitable for administration are made according to pharmacopoeial directions. Herbal infusions are prepared by treating the herb to be extracted with water or alcohol. An herbal drug reduced to powder form is known as pulverata. Tinctures are solutions of the active principles of a drug in alcohol. A coarsely bruised drug boiled in water for a definite period is known as decoction.

    Herbal extracts are considered to be scientific pharmacopoeial preparations. Liquid extracts, concentrated soft extracts and dry extracts are all used for industrial applications. Herbal extracts are prepared by extracting an herb of a specific particle size with suitable solvent.  Depending on the solvent used, extracts are known as aqueous, alcoholic or etheral extracts. The extracts also contain marker compounds that are important for the quality of the finished product. Markers are chemically defined constituents of an herbal drug, which are of interest for quality control purposes (independent of whether they have any therapeutic activity or not). Extract of Hypericum perforatum L. (St. John’s Wort) is a good example of how extracts are standardized to marker compounds (0. 3% hypericin) and active constituent (2. 8% hyperforin).

    In the case of medicinal herbs, before a consignment is evaluated, a sample is drawn for analysis and considerable care is exercised to ensure that the sample is truly representative. Macroscopic and sensory characters are usually sufficient to enable the drugs to be identified. Thin Layer Chromatography (TLC) is a good tool for determining the botanical identity of the herb. Moisture content, extractive value and ash value are also used as standards for preliminary examination. Swelling index is standard specified, applicable to mucilage-containing drugs. Inadequate quality control of herbal drugs is a significant concern for consumers and manufacturers.

    Once botanical identity is established, the next step is preliminary phytochemical screening. This screening involves extraction, purification and characterization of the active constituents of pharmaceutical importance. The herbal drug or herbal drug preparation in its entirety is regarded as the active substance. These constituents are either of known therapeutic activity or are chemically defined substances or groups of substances generally accepted to contribute substantially to the therapeutic activity of an herbal drug. Qualitative chemical examination is done to detect and isolate the active constituent(s). High performance liquid chromatography (HPLC) is the main analytical technique for quantitative measurements of active compounds. In cases when active ingredients are not known or are too complex, the quality of plant extracts can be assessed by a "fingerprint" chromatogram.

    Standardization means adjusting the herbal drug preparation to a defined content of a constituent or a group of substances with known therapeutic activity by adding excipients or by mixing herbal drugs or herbal drug preparations. Botanical extracts made directly from crude plant material show substantial variation in composition, quality and therapeutic effects. Standardized extracts are high quality extracts containing consistent levels of specified compounds, and they are subjected to rigorous quality controls during all phases of the growing, harvesting and manufacturing processes.

    Medicinal herbs are moving from fringe to mainstream use with greater numbers of people seeking remedies and health approaches free of the side-effects caused by synthesized chemicals. The crude medicinal herbs for this industry have long been grown and traded in many countries around the world. The herbal, raw materials are comprised of dried plant materials in the form of roots, barks, flowers, and fruits.  Besides being important to consumers of herbal remedies, the quality of medicinal herbs is also vital to growers and suppliers of these crude botanicals. It is reasonable to expect that herbs of superior quality will sell for the premium price.

    Alternative systems of medicine have become increasingly popular in recent years. The efficacy of some herbal products is beyond doubt, the most recent examples being Artemisia annua L. (i.e., artemesinin: wormwood derivative used to target cancers), Silybum marianum L.  (i.e., silymarin (seeds of the milk thistle effective in treating diseases of the liver) and Taxus brevifolia Nutt. (i.e., taxols: pacific yew derivative that exhibits antimitotic activity and is used for treating refractory tumors). A number of recent findings have focused on the adverse effects of herbal products. Hepatotoxicity, nephrotoxicity and most critically, drug interactions with synthetic medicines are common in herbal practice. In light of above discussion, consumers and clinicians should be increasingly cautious about following the latest trends in medicinal herbs and be alert to the potential risks herbal medicines pose.

    The Āyurvedic texts describe a term ‘vīrya’ which seems to be the Āyurvedic equivalent of active constituent. Caraka Samhita has mentioned that therapeutic activity of a medicinal plant is due to factor known as vīrya’. The formulations used in ancient texts are based on plant in natural form. They do not believe in extracting the active constituent from the plant. According to experts during extraction some significant virtues of the plant are lost.

    With introduction of scientific procedures, the scenario for Āyurveda, particularly Dravyaguna has changed. The fundamentals of Āyurvedic drug formulations were well established by Caraka, Suśrūta, Ātreya, Vāgabhatta, Kaśyapa, Mādhava, Agniveśa and many more. The advancement these people made is really astonishing keeping in view the lack of scientific procedures. Organoleptic testing of the drug seems to be principal method for testing the potency of the drug. Although these types of methods are difficult to describe in modern language and scientists are trying hard to understand basic of Ayurvedic drug formulations.

    Today the concept of research in plant based medicine has changed. It was Sterner who isolated morphine from Papaver somniferum L. (Ahiphena of Āyurveda) and showed the world that plant based medicines contain chemicals; which are responsible for biological action. Indian scientists have also isolated chemicals from medicinal plants used in Indian System of Medicine. In recent years, numbers of papers and books have been published on plant based medicine.

    Dravyaguna is a vast subject and for its better application in Ayurveda, knowledge of botany, chemistry and pharmacognosy is must. As we have already discussed, scientists are more interested in chemical aspects of plant based medicine. Arjuna (Terminalia arjuna (Roxb.) W. & A.) is reputed Ayurvedic remedy for heart ailments but we do not know exactly which compound is responsible for cardio protective activity of Arjuna (Terminalia arjuna (Roxb.) W. & A.). Recently compounds like arjunetin and fridelin have been studied as possible active constituents of Terminalia arjuna.

    Studying the Āyurvedic drugs at chemical levels may unreveal the mechanism of action which has eluded the scientists for long time. A far as disease segment is concerned, hepatology and rheumatology are two areas where Āyurvedic remedies are even prescribed by Allopathic Physicians. Silybum marianum L.  is well-documented western herbal remedy used for liver diseases.  In India, we have Picrorhiza kurroa Royle. ex Benth. (kutki), which is a priced drug for liver diseases. Picrorhiza kurroa, when compared with Silybum marianum, the hepatoprotective effect of Picrorhiza kurroa was found to be similar, or in many cases, superior to the effect of Silybum marianum. But we can see Silybum marianum more popular than Picrorhiza kurroa.  Silymarin the active constituent of Silybum marianum has been isolated and purified and above all pharmacological and pharmacokinetic data is available for the drug. These types of data are missing for drugs used in Indian System of medicine.

    Āyurvedic remedies have been tried for centuries but not documented. Today we can witness Āyurveda as global phenomenon but still people are reluctant to adopt it as primary healthcare system. Dravyaguna is the subject which should be properly explored. For better understanding of the subject basic botany and chemistry should be studied along with Dravyaguna. If we look at Western Herbal Medicine; chemistry, botany, microbiology and biochemistry are fundamental subjects of academic study and new subjects like Phytopharmacognosy, Phytopharmacotherapy and Medicinal Botany are emerging.


 

 

 

 

 

 

 

 

 

        

 

 

ĀYURVEDIC PERSPECTIVE OF DIABETES MELLITUS

 

 

 

 

 

 

Introduction:

    According to Āyurveda; mūtrakrcca (dysuria), aśmarī (renal calculus or stone) and prameha roga (polyuria) are included under mūtra vikāra (diseases of the renal system). As we are aware that urine is filtered from the blood by the kidneys, collects in the urinary bladder via the ureters and excreted out via the penis. In disease like mūtrakrcca there is scarcity difficulty of urination where as in diseases like prameha, there is increases urination (Pullaiah & Chandrasekhar., 2003). 

    In Āyurveda; meha roga indicates disease of the urinary system. Any thing being excreted out in urine abnormally indicates meha roga Lochan., 2003).  When the function of the kidney is impaired, certain substances are excreted out by the kidneys which are normally required for nutrition of the body. Under these circumstances, urine becomes foul-smelling and there is increased frequency (Singh., 2005).

Etiology

Following factors lead to prameha roga (Gupta., 1997).

  1. Sedentary life style
  2. Hypersomnia
  3. Consumption of curd, flesh of goat and fish, milk, jaggery, fresh rain water and foods aggravating kapha.

Pathogenesis (Gupta., 1997).

  1. Kapha prameha: Kapha present in basti (urinary bladder) pollutes meda, māmsa and jala.
  2. Pitta prameha: Pitta (aggravated by consumption of hot foods) present in basti (urinary bladder) pollutes meda, māmsa and jala.
  3. Vāta prameha: When kapha and pitta are scare, vāta pollutes vasā, majjā, āoja and lasikā and leads to vāta prameha.

    According to Āyurveda, like all diseases, the three biological humors viz; vāta, pitta and kapha are effected in prameha (Gupta.,1997). In addition, there are ten dusya (body tissues) viz; meda (subcutaneous fat), rakat (blood), śukra (seminal fluid), jala-tatva (water), vasā, lasīkā (lymph), majjā (marrow), rasa (plasma), aoja (immunity) and māmsa (flesh).

Prodromal symptoms of prameha (Gupta.,1997).

  1. Coated tongue, palate, throat and teeth
  2. Burning sensation in the extremities
  3. Thirst
  4. Sweet taste in the mouth

Common symptoms of prameha (Lochan., 2003).

  1. Polyuria
  2. Contaminated urine

Types of prameha including signs and symptoms (Gupta., 1997; Lochan., 2003):

Āyurveda considers twenty type of prameha roga. The types are diagnosed on the basis of color, taste, smell and organo-leptic resting of the urine.

 

Kapha prameha

It is of 10 types.

  1. Ŭdakameha: Urine in this type is clear, comparatively increased, white, cool, without any smell, picila and contaminated.
  2. Ikśumeha: Urine is sweet like sugarcane.
  3. Sāndrameha: Urine when kept in a vessel becomes concentrated.
  4. Sūrāmeha: Urine like alcohol is clear at the top and concentrated at the bottom. This can be tested in a test tube.
  5. Piśtameha: Urine is white and concentrated. There is sensation while voiding.
  6. Sūkrameha: Here urine is mixed with seminal fluid.
  7. Siktāmeha: Urine is contaminated with sands particles.
  8. Śītameha: Urine is excessively sweet and cold.
  9. Lālāmeha: Urine is similar to saliva in appearance.
  10. Śarneyameha: Urination is slow.

Pitta prameha is of six types.

  1. Kśāramaeha: Here the colour, smell, taste is similar to lime water.
  2. Nīlameha: The colour of the urine is blue.
  3. Kālameha: The colour of the urine is black or inky.
  4. Hāridrameha: The colour of the urine is smile to turmeric.
  5. Māňjistameha: The colour of the urine is yellow-red. It is smells foul.
  6. Rakatmeha: The urine is red coloured, foul-smelling and salt in taste.

Vāta prameha is of four types.

  1. Vasāmeha: The urine contains fat globules.
  2. Majjāmeha: The urine contains marrow.
  3. Kśaudrameha: Urine is slightly astringent, sweet and ruksa.
  4. Hastimeha: There is involuntary passage of the urine. 

All the types describe above, if not cured properly, leads to madhumeha Gupta., 1997). Description of various types of prameha in different Āyurvedic texts is tabulated below:

Kapha Prameha

Caraka

Śusrūta

Vāgbhata

Mādahva

Ŭdakameha

Ŭdakameha

Ŭdakameha

Ŭdakameha

Ikśumeha

Ikśumeha

Ikśumeha

Ikśumeha

Sāndrameha

Sāndrameha

Sāndrameha

Sāndrameha

Sāndraprasadameha

Sūrāmeha

Sūrāmeha

Sūrāmeha

Śuklameha

Piśtameha

Piśtameha

Piśtameha

Sūkrameha

Sūkrameha

Sūkrameha

Sūkrameha

Śītameha

xxxx

Śītameha

Śītameha

Siktāmeha

Siktāmeha

Siktāmeha

Siktāmeha

Śarneyameha

Śarneyameha

Śarneyameha

Śarneyameha

Lālāmeha

Lalameha

Lalameha

Lalameha

xxxx

Lavanmeha

xxxx

xxxx

xxxx

Phenmeha

xxxx

xxxx

 

                                                  Table 11: It shows types of kapha prameha

Pitta Prameha

Caraka

Śusrūta

Vāgbhata

Mādahva

Kśāramaeha

Kśāramaeha

Kśāramaeha

Kśāramaeha

Kālameha

xxxx

Kālameha

Kālameha

Nīlameha

Nīlameha

Nīlameha

Nīlameha

Lohitmeha

Sonitameha

Rakatmeha

Rakatmeha

Māňjistameha

Māňjistameha

Māňjistameha

Māňjistameha

Hāridrameha

Hāridrameha

Hāridrameha

Hāridrameha

xxxx

Amlameha

xxxx

xxxx

                                                

Table 12: It shows types of pitta prameha

  Vāta prameha

Caraka

Śusrūta

Vāgbhata

Mādahva

Vasāmeha

Vasāmeha

Vasāmeha

Vasāmeha

Majjāmeha

Majjāmeha

Majjāmeha

Majjāmeha

Hastimeha

Hastimeha

Hastimeha

Hastimeha

Madhumeha

Kśaudrameha

Madhumeha

Madhumeha

 

                                                  Table 13: It shows types of vāta prameha

 

Complications (Gupta.,1997)

1. Kapha prameha: Indigestion, anorexia, polsomnia, cough and rhinitis.

2. Pitta prameha: Pain in the bladder and vital parts, fever, burning-sensation, thirst, hyperacidity, apoplexy and diarrhea.

3. Vāta prameha: Flatulence, tremors, stiffness in cardiac region, disturbed taste, pain, insomnia, consumption, cough and asthma.

Prognosis:

1. Kapha prameha:  It is curable.

2. Pitta prameha: It can be cured.

3. Vāta prameha: It is incurable.

Madhumeha

    It was known to the Āyurvedic physician for more than 2500 years ago as can be seen from medical tests such as Caraka and Suśrūta Samhita (400 BC). Caraka and Suśrūta have described madhumeha in which a person passes urine resembling honey (Chopra, Chopra, Handa & Kapur., 1982).

Caraka in Sutra Stahna 24 discuss that madhumeha sometimes is hereditary in nature (Sharma & Das., 1990). Apparently the patient is comfortable and as the time passes, the disease becomes chronic.

Ayurveda describes two types madhumeha:

  1. Caused by aggravated vāta due to malnutrition.
  2. Caused by kapha and pitta in combination with vāta (Sharma & Das., 1990).

According to Āyurveda, second type is difficult to cure.

Treatment:

Before stating the proper anti-diabetic medication, the body is purified by emetic or purgative drugs (Sharma, R.K. & Das, B. 1990; Lochan., 2003).

Some important Āyurvedic formulations used for the treatment of diabetes are discussed below (Krishnamurthy., 1969; Chaturvedi & Shastri., 1980; Sivarajan., 1994; Joshi., 1998; Singh., 2006).

Āmalakī curana: 500 mg twice a day.

Candraprabhā vatī: 1-2 tabs twice a day.

Indra vatī: 1-2 tabs twice a day.

Karela Swa-rasa: 30 ml twice a day.

Nāga Bhasma: 125-250 mg twice a day.

Nygodhorādi quatha: 3-6 teaspoonfuls thrice a day.

Śilajita vatī: 1-2 tabs twice a day.

Trivang bhasma: 125-250 mg twice a day.

Vasantkusumākara rasa: 120 mg twice a day.

 

 

 

 

 

 

 

 

 

 

 

 

         AIMS AND OBJECTIVES

 

 

 

 

 

 

 

 

 

 

 

This study is aimed to prove or disprove the hypoglycemic potential of some of the Indian herbs by using the following:

        1. Alcoholic extract of root of Withania somnifera Dunal.

        2. Alcoholic extract of bulb of Allium sativum Linn.

        3. Alcoholic extract of leaves of Gymnema sylvestre R.Br.

        4. Aqueous extract of oleoresin of Ferula foetida Linn. (Asafoetida)

        5. Hexane extract, chloroform extract, methanol extract and aqueous extract of leaves of Murraya koenigi Spreng.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

MATERIALS

AND

METHODS


Chemicals

    Streptozotocin was obtained from Sigma Chemical Co. (USA). DPEC-GOD/POD kit for quantitative blood glucose determination was purchased from Ranbaxy Co. (INDIA). Insulin was purchased from Knoll Pharmaceuticals, Mumbai.

Plant extracts

Following extracts were used:

        a) Alcoholic extract of root of Withania somnifera Dunal. (Winter Cherry) containing 1.5% withanolides,

        b) Alcoholic extract of bulb of Allium sativum Linn. (Garlic) containing 0.6% allicin = 0.03 of allin.

        c) Alcoholic extract of leaves of Gymnema sylvestre R.Br. (Periploca of Woods) containing 70% of gymnemic acids.

        d) Aqueous extract of oleoresin of Ferula foetida Linn. (Asafoetida) containing 60% ferulic acid including resinous substances.

        e) Extracts of leaves of Murraya koenigi Spreng. (Curry leaves) – hexane extract, chloroform extract, methanol extract and aqueous extract.

            These extracts were tested for their efficacy in type 1 diabetes animal model and also, to compare their efficacy with insulin therapy. All extracts (except Murraya) were procured from Sanat Products, New Delhi. Before evaluation of Murraya koenigii, a sample was drawn for analysis. Considerable care was exercised to ensure that this sample was truly representative. Fresh leaves of Murraya koenigii were collected from vicinity of Chandigarh from a natural population. The leaves of the plant were collected from the botanical garden of The Government Ayurvedic College, Post-graduate Training & Research Centre, Kadam Kuan, Patna. A voucher specimen has been collected for the herbarium of the institute.

            Murraya extract was prepared in the laboratory from M. koenigi leaves by soxhlet extraction procedure using solvents of increasing polarity in succession; hexane, chloroform, methanol. Aqueous extract of Murraya leaves was prepared by maceration. Following active principles were possibly present in the different fractions of Murraya extracts:

            Withania, Garlic, Asafoetida, Gymnema and Murraya aqueous extracts were dissolved in normal saline; hexane, chloroform and methanol fractions of Murraya were dissolved in dimethyl sulfoxide (DMSO).

            Withania (20 mg/kg), Garlic (100 mg/kg), Gymnema (100 mg/kg), Asafoetida (100 or 200 mg/kg) and Murraya (200 mg/kg) extracts were administered to diabetic rats intraperitoneally once daily. Insulin was administered subcutaneously daily in a dose of 5 U/kg.

Animal Experiments

    Sprague Dawley rats of either sex weighing 150-200 g were housed in an air-conditioned room on a 12 - hour light/dark cycle at 21 + 3oC and supplied with standard pellet diet and tap water ad libitum. Procedures involving animals and their care were

Solvent used for extraction

Active principles extracted

Hexane

Triterpenes, fatty acids, steroids, amino acids

Chloroform

Alkaloids, other amine like compounds

Methanol

Carbohydrates, alkaloids and glycosides

Water

Mono-saccharides, saponins.

                                                

Table 14: Table shows solvent used for extraction and active principles studied

         

conducted in conformity with the guidelines of the institute animal ethics committee, which also approved the study.

    The animals were randomly divided into six experimental groups; vehicle-treated diabetic control group, Withania extract treated diabetic rats, garlic extract treated diabetic rats, Gymnema extract treated diabetic rats, Asafoetida extract treated diabetic rats, Murraya fractions (hexane, chloroform, methanol or aqueous fraction) treated diabetic rats, and insulin treated diabetic rats. Each group had six animals.

    All the above treatments were made for three weeks. Blood glucose determinations were performed in overnight fasted rats at first, second and third weeks of the treatments.

Induction of Type 1 Diabetes

    Experimental type 1 diabetes was induced by a single intraperitoneal injection of STZ to animals fasted overnight at a dose of 60 mg/kg body weight (fresh solution in 0.1 N citrate buffer, pH 7.5) (Suresh Babu and Srinivasan., 1998). The rats had free access to 5% of glucose water and basal diet ad libitum during the next 24 hours. Blood samples were obtained from retroorbital plexus in STZ injected animals at 72 h, after an overnight fast. Fasting blood glucose levels were determined by glucose oxidase method (Huggert and Dixon., 1957). Rats with fasting blood glucose levels above 250 mg/dl were used as diabetic animals.

 

 

 

 

 

 

 

 

 

 

   

 

 

 

 

 

STATISTICAL ANALYSIS

 

    Percent decrease in blood glucose level from diabetic values (72 h after STZ- administration) was calculated as:

Diabetic blood glucose-blood glucose after treatment

X 100

Diabetic blood glucose

    Data was presented as mean + SE. Baseline values were compared with treatment values and the inter-group comparisons were also made. Differences between groups were calculated using one-way ANOVA supplemented with Dunnett’s ‘t’ test. A paired student’s `t’ test was applied to the data for evaluation of differences between pre- and post- treatment values. P value <0.05 was considered to be statistically significant.

 

 

 

 

 

 

 

 

 

 

 

 

 

RESULTS


Control group

    The normal (baseline) blood glucose values of the rat were 69.89+ 8.9 mg/dl. Fasting blood glucose levels, 72 h after STZ injection were 290.4 ± 13.2 mg/dl and thereafter, at 1, 2 and 3 weeks of vehicle administration were found to be 300.9 ± 9, 311 + 10.4 and 316.2 + 10.2 mg/dl, respectively. Though the blood glucose was rising every week but the rise was not statistically significant as compared to diabetic glucose values.

Percent increase in blood glucose from baseline at 72 h, 1, 2 and 3 week after STZ treatment were 315.51+6.7, 330.53+4.7, 344.98+5.9 and 352.42+8.6 respectively.

 

Withania group

    With Withania extract treatment, the blood glucose was progressively lowered at 1, 2 and 3 week (226 ± 15.9, 196.3 ± 19.5 and 163.5 ± 25.6 mg/dl) This decrease in blood glucose was statistically significant as compared to control group and insulin treated rats at 2 and 3 week but was not significantly different from insulin treated rats at 1 week (Figure 1).

There was a statistically significant decrease in blood glucose levels (%) from diabetic levels i.e. 21.4 ± 17.1, 31.9 ± 22.2 and 43.3 ± 27.8 at 1, 2 and 3 weeks of Withania treatment.

Garlic group

    Administration of alcoholic extract of A. sativum to diabetic rats with blood glucose 282.1 ± 6.2 mg/dl, attenuated the hyperglycemia induced by STZ significantly. The fasting blood glucose at 1, 2 and 3 week of garlic administration was 226.8 ± 12.8 mg/dl, 178.55 mg/dl and 143.5 ± 15.6 mg/dl respectively (Table 1). The decrease in FBG with garlic was statistically significant at 1, 2 and 3 week as compared to control group, and was also significantly different from insulin group, except at 1 week interval (Figure 2).

A progressive percent decrease in FBG from diabetic blood glucose was observed with garlic treatment, the values being 19.6 ± 10.9, 35.4 ± 11.5 and 48.2 ± 22.4 at 1, 2 and 3 week of treatment, which was significant versus control group and insulin group.

Gymnema group

    STZ induced hyperglycemia (281.1 ± 6.6 mg/dl) was significantly and progressively decreased with extract treatment (233.5±3.3 mg/dl, 192.6 ± 9.9 mg/dl and 150.3 ± 7.6 mg/dl at 1, 2, and 3 week of treatment) (Figure 3).

Percent decrease in blood glucose at various time intervals of treatment from diabetic values with treatment was 16.9 ± 4.9, 31.4 ± 14.8 and 48.2 ± 7.9, which was statistically significantly, but was less than insulin.

Asafoetida group

    Hyperglycaemia induced by STZ was not different in all the groups, it was 290.4 ± 13.2 mg/dl in control group, 293.9 ± 5.3 mg/dl in Asafoetida (100 mg/kg), 293±2.3 mg/dl in Asafoetida (200 mg/kg) and 283.1±16.1 mg/dl in insulin group.

Administration of Asafoetida at two doses 100 mg/kg and 200 mg/kg could not decrease the FBG levels, rather the FBG was significantly increased at 3 weeks from baseline i.e. 340.4 ± 1.2 mg/dl in asafoetida 100 mg/kg and 341 ± 10.5 mg/dl in asafoetida 200mg/kg groups as compared to 316.2 ± 10.2 mg/dl in control group (Figure 4).

    The percent increase in FBG from blood glucose levels 72h after STZ- administration was 10.8 ± 6.2, 15.4 ± 7.1 and 19.5 ± 8.7 in asafoetida.100 group and 10.7 ± 8.9, 14.4 ± 9 and 15.2 ± 10.7 in Ferula foetida 200 group, at the first, second and third week of treatments which is not dissimilar when compared to control group, but were highly significant when compared to insulin treated rats.

Murraya group

    Four fractions of Murraya koenigii extract (hexane, chloroform, methanol and aqueous) were administered to the different groups of rats. None of the four extracts reduced the hyperglycemia induced by STZ. The FBG values at different time intervals of treatment were not statistically different from the control group (Figure 5).

    The percent change in FBG from that obtained 72h after STZ- administration was –6.7 ± 8, -8.1 ± 8.5, -11.3 ± 9 in M. koenigii (hexane) group; - 3.9 ± 5.6, -6.6 ± 6.2 and –12.5 ± 14.9 in M. koenigi (chloroform) group; -5 ± 3.6, -7.4 ± 5.2 and –10.7 ± 6 in M. koenigi (methanol) group and –3.2 ± 2.3, -6.5 ± 5.7 and –8.3 ± 5.2 in M. koenigi (aqueous) group at first, second and third weeks of treatment correspondingly, indicating increase in FBG from baseline but not statistically significant when compared to values 72h after STZ- administration as well as control group at corresponding time intervals.

Insulin group

    The fasting blood glucose after STZ – injection (283.1 ± 16.1mg/dl) was tremendously decreased with insulin treatment to 215.6 mg/dl, 148.9 mg/dl and 100.3 ± 7.8 mg/dl at 1, 2 and 3 weeks of insulin treatment respectively. This decrease was highly significant in comparison to control group (Table 1).

    The percent decrease in blood glucose levels from diabetic values in insulin treated rats was 23.9 ± 6.8, 47.4 ± 8.6 and 63.5 ± 4.9 at 1, 2 and 3 weeks of treatment, respectively.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

DISSCUSION

 

    Plants are a potential source of many drugs used in modern medicine, for example, quinine, opium alkaloids, paclitaxel, atropine, cardiac glycosides (digitalis, ouabain) and many more. Even the discovery of widely used anti-diabetic drug metformin was from the traditional approach of using Galega officinalis L. But still the herbs as medicines have not gained enough momentum in scientific community. One of the factors for this is the lack of specific standards being prescribed for herbal medicines (Gupta., 1994). In the present study, the main emphasis was laid on the use of standardized herbal extracts containing a quantified amount of active principle.

    In the present study, the standardized extract of Withania somnifera has shown prominent hypoglycemic effect in STZ-treated diabetic rats. In a study, Trasina (an Ayurvedic polyherbal formulation containing Withania somnifera, Tinospora cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa and shilajit) induced a dose related decrease in STZ-induced hyperglycemia and attenuation of STZ-induced decrease in islet superoxide dismutase SOD activity (Bhattacharya et al., 1997).    This it can be concluded that standardized extract of Withania somnifera or combination with other herbs has prominent hypoglycemic effect. But at the same time it is warranted that in poly-herbal formulations like Trasina, the hypoglycaemic activity can not be alone attributed to Withania somnifera. Antioxidant property of shilajit, Withania somnifera and Picrorrhiza kurrao may be responsible for hypoglycemic effect.

    In this study, it was not clear which of the specific herb was accountable for the hypoglycaemic effect. Our study indicates that Withania somnifera alone is capable of lowering blood glucose in type 1 diabetes model. It has been observed that pancreatic islet cells possess very low levels of free radicals scavenging enzymes, including superoxide dismutase and are therefore, vulnerable to free radical toxicity (Mason and Chingnell., 1981). STZ-induced cytotoxicity of islets is reduced by SOD, considered to be the first cellular defense against superoxide radical toxicity (Grankvist et al., 1981). STZ-induced hyperglycemia in rats was significantly attenuated by standardized extract of Allium sativum, but the effect seen was less than that of insulin. An earlier study showed that oral administration of ethanol, petroleum ether and ethyl ether extracts of Allium sativum (dose 0.25 g/kg) caused 18.9, 17.9 and 26.2% reduction in blood sugar in alloxan-diabetic rats, respectively (Jain and Vyas., 1975). In another study oral administration of 0.25 g/kg allicin produced hypoglycemia comparable to tolbutamide in mildly diabetic rabbits (glucose levels ranging from 180 to 300 mg %) while it showed no effect in severely diabetic animals (blood sugar > 350 mg %) (Mathew and Augusti., 1973). Similar results were observed in our study, that the efficacy of garlic declined from the second through the third weeks of the study. This may be attributed to the fact that STZ-induced hyperglycemia progressively increased with time.

    Allicin is the chief sulfur containing principle of garlic. It combines readily with compounds containing – SH groups (Skinner., 1955; Stoll and Juckes., 1955), like cysteine, glutathione and serum albumin fractions, which combine with insulin and inactivate it; hence sparing the already available endogenous insulin from degradation. This may be probable mechanism of action of allicin.

    Results of the present study demonstrate that standardized extract of Gymnema sylvestre significantly decreased the blood glucose levels progressively at every week of treatment in type 1 diabetes model. Earlier studies have also demonstrated the hypoglycemic effect of this herb. Dried leaf powder of Gymnema sylvestre, when given to alloxanized rabbits, led to antihyperglycemic effect along with decrease in activity of gluconeogenic enzymes and reversal of pathological changes in liver initiated during the hypoglycemic phase (Shanmugasundaram et al., 1983). Oral administration of aqueous extract of leaves of Gymnema sylvestre for 20-60 days normalized blood sugar levels of STZ-diabetic rats through β-cell regeneration (Shanmugasundaram et al., 1990). Single as well as chronic (32-35 days) oral administration of aqueous extract of G. sylvestre leaves to 18 h fasted non-diabetic and STZ-induced mildly diabetic rats showed significant reduction in blood glucose on OGTT without any significant effect on immuno-reactive insulin levels (Okabayashi et al., 1990). Oral administration of varying doses (50, 100, 200 and 500 mg/kg) of aqueous extract to normal and STZ-diabetic rats showed significant dose-dependent hypoglycemic action of sylvestre leaves extract for seven days on insulin resistance in STZ-diabetic rats (Taminaga et al., 1995).

    The hypoglycemic principles of Gymnema sylvestre isolated from the saponin fraction of the plant are referred as gymnemosides and gymnemic acids (Murakani et al., 1996; Yoshikawa et al., 1997). Triterpene glycosides isolated from the plant inhibited glucose utilization in muscle (Shimizu et al., 1996). Gynmemic acid fraction has been shown to inhibit glucose uptake in intestine (Shimizu et al., 1997). Alcoholic extract of Gymnema sylvestre also stimulates insulin secretion from the rat islet of Langerhans and several pancreatic β-cell lines in absence of other stimuli (Persaud et al., 1999). Among the four gymnemic acids, gymnemic acid I lacked antihyperglycemic effect (Yoshikawa et al., 1997), suggesting that gymnemic acids II, III, IV could have been responsible for the effects seen in our study.

    Gymnemic acids appear to be effective in type 1 diabetes model by virtue of their effect on pancreatic β-cells to stimulate insulin secretion and, on intestine to inhibit glucose uptake.

    An extract comprising of Nigella sativa, Myrrh, Gum olibanum, Gum asafoetida and aloe was administrated to STZ-diabetic rats (Al-Awadi et al., 1991). The plant mixture had a blood glucose lowering effect, which was shown to be partly mediated through decreased hepatic gluconeogenesis. It has been postulated that the extract may prove to be useful in the treatment of type 2 diabetes. Since, it is not clear, how much of this activity can be ascribed to asafoetida, we investigated if  Ferula foetida alone, a common condiment in Indian meals have any such effect. Our results in type 1 diabetes model were negative suggesting no action of asafetida in insulin deficiency.

    In an earlier study, it was observed that oral feeding of Murraya koenigii leaves diet (10% w/v) for 60 days to normal rats resulted in hypoglycaemia associated with increased hepatic glycogen contents due to increased glycogenesis and decreased glycogenolysis and gluconeogenesis (Khan et al., 1995). Dietary supplementation with curry leaves have been shown to increase lecithin cholesterol acyltransferase activity (Khan et al., 1996).

    Earlier studies were conducted using leaf powder, but we used the extracts of Murraya leaves extracted with solvents of different polarity so as to capture all possible active constituents in the extract, which appears to be a better approach. In the present study, none of the Murraya extracts was able to lower the blood glucose raised by STZ-administration.

    Several experimental and clinical studies have earlier shown the efficacy of herbs in diabetes. However, they had serious limitations. Most of the studies have used either a part of plant or its powder for administration. Clinical studies conducted have mostly used small sample size and inappropriate controls. So, the information about the effect of a particular phyto-constituent from the herb in animal model of type 1- diabetes was lacking. Therefore, we have investigated the effect of standardized plant extracts in STZ-induced hyperglycemia, a proven model of type 1 diabetes.

    This study demonstrates the efficacy of standardized extracts of Withania somnifera, Allium sativum and Gymnema sylvestre in type 1 diabetes model, though not at par with insulin that is the standard conventional therapy for type 1 diabetes.

    This study raised several questions pertinent to the clinical use of herbs as antidiabetic agents, for instance, whether these herbs can be used as monotherapy or add-on therapy in diabetes management. Secondly, their indiscriminate use by the patients may lead to possibility of hypoglycemia. Thirdly, both experimental and clinical studies to elucidate the mechanism of action of herbs demonstrated to be efficacious need to be conducted. Also, randomized controlled clinical trials are required to prove the safety and efficacy of these herbs in diabetic patients.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

BIBLIOGRAPHY

 

 

 

 

 

 

 

 

 

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