26

1.1 GLOBAL SCENARIO OF HERBAL DRUGS

The relation between the man and the nature dates back to the age

old existence of man himself. Since the dawn of civilization, nature has

continued to awe man with its abundant surprise. From the varied

plants and their enumerable uses, every substance in nature has

aroused man’s curiosity to many folds. In spite of nature providing us

with everything it has in store, we are lagging behind in exploiting its

bounty to the hilt and as a consequence are persistently overcome by

obstacles that are not faced by modern medicines.

However, in the last few decades there has been a tremendous growth

in the field of natural medicine113. It is gaining popularity in many

countries owing to its natural origin and lesser side effect. In olden times,

vaidyas/Hakims prepared drugs according to the patient need and

treated patients on individual basis. Today however; herbal medicines

are manufactured on the large scale, where manufacturers come across

many problems such as the availability of raw material, its

authentication, proper standardization methodology and quality control

parameters.

The side effects accompanying allopathic medicines, have led to a

sudden increase in the use of herbal medicines and consequently a rise

in the number of herbal drug manufactures. Plants have been used in

medicine for millennia and modern drug research benefits immensely

from a knowledge of the uses of plants available in several parts of the

27

world. This practice continues today because of its biomedical benefits as

well as different cultural beliefs and has made a great contribution

towards maintaining human health49.

Nature has always stood as a golden mark to exemplify the

outstanding phenomena of symbiosis. Western countries are becoming

aware of the harmfulness and side effects of synthetic drugs, leading to

an increasing interest in the natural product remedies. Natural products

from plants, animals and minerals have been the basis of the treatment

of human disease for centuries. Despite convincing progress in Synthetic

Chemistry and Biotechnology, natural products are the most important

source for preventive and curative medical preparations. WHO has

estimated that at least 80% of all the global inhabitants rely on

traditional medicines for their primary health care; which are derived

largely from plants and animals , thereby elevating alternative medicines

to a ‘need of the day’ status. WHO recommends the use of traditional

herbs/remedies because huge amounts of raw material are easily

available. Also, they are comparatively safer because of their low

toxicities. Even today most of the rural populace relies heavily on herbal

remedies as these have a psychological effect on their impressionable

min deluding them into believing that the ailment will be cured by

nature’s magical hand. However, plants are extremely complex in

composition and their therapeutic activity depends on their chemical

constituents, which in turn depends on their age, geographical location

28

and harvesting processes. Also, improper authentication of herbs,

adulterations by microorganisms, pesticide residue, has made

standardization of herbal drugs an elementary necessity.

Presently official standards are not available for herbal preparations.

Manufactures testing their formulations, have fixed their own parameters

which are of a preliminary importance. It is also very troublesome to

confirm the presence of all the ingredients claimed in a formulation.

Hence the primary need is to develop a parameter based on which the

presence of a range of ingredients can be identified. Various

spectrophotometric and chromatographic methods and evaluation of

physicochemical properties can be performed to develop a pattern for

identifying the presence of different ingredient. Wherever possible, these

methods can be applied for quantitative estimation of bioactive group of

compounds like glycosides, alkaloids, flavonoids, polyphenolic

components or for estimation of a particular compound.

In polyherbal Ayurvedic preparations it is very difficult to estimate

each ingredient, but if major constituents responsible for

pharmacological activity are indicated on the label, these constituents

can be estimated quantitatively along with the other parameters through

which presence of all ingredients can be confirmed. Combined and well

coordinated efforts from the pharmacognosy, botany, ayurveda

department are required for the same.

29

Advantages of natural medicine

1. Natural medicine have long history of use and better patient

tolerance as well as acceptance.

2. Medicinal plants are a renewable resource, which is currently the

only hope for a sustainable supply of cheaper medicines to the

growing population.

3. Medicinal plants are easily available especially in developing

countries like India having rich plant biodiversity.

4. The cultivation and processing of medicinal plants and herbal

products is eco friendly.

5. Prolonged and daily use of herbal medicines may offer proof of

their safety and efficacy.

6. Herbal medicine has provided many potent medicines to the

modern medical science, both in crude form and as a pure

chemical upon which modern medicines are structured e.g.:

quinine, strychnine etc.

1.2: Limitations of Herbal Medicines

The prominent limitations of herbal medicines can be summarized as

follow:

1. Ineffective in acute medical care

Herbal medicines are not effective in treating any acute illness. Most

of the modern medicines are designed to work at molecular level of

physiology; the drug takes its time to exhibit effects. On the other hand,

30

modern system of medicine offers adequate measures to check and

manage acute conditions.

2. Inadequate standardization and lack of quality specifications

Herbal medicines are always condemned on the standardization front.

Each herbal preparation is a source of polypharmacy within itself as

each ingredient contains thousands of chemical constituents with

complex molecular formulae. Hence standardization of herbal

preparation or its ingredients is a highly complex issue.

3. Lack of scientific data

There is a lack of scientific data. Literature on herbal medicines in

support of its medicinal activity and their safety and efficacy cannot be

assured on a hypothetical basis. Hence there is a need to provide the

scientific justification to the claimed uses of the traditional medicines

and herbal formulations. WHO guidelines clearly direct that it is not

necessary to carry out detailed toxicological evaluation of herbs and

herbal preparation originating from traditional system of medicine. One

of the common impediments in the acceptance of the Ayurvedic

formulation is the lack of standard quality control profiles.

The task of laying down standards for quality control of herbal crude

drugs and their formulation involves biological evaluation for a particular

disease, chemical profiling of the material and laying down specifications

for the finished product. Therefore, in case of herbal drugs and product,

31

the word “Standardization” should encompass the entire field of study

from cultivation of medicinal plant to its clinical application.

1.3 AYURVEDA: TRADITIONAL SYSTEM OF MEDICINE

Ayurveda the system of medicine indigenous to India has thousands

of years of history. With all its pride and glory , on a global level even

today it is considered as the alternative system of medicine.

The term Ayurveda comprises of two words Ayuh and Veda. Ayuh

means science or knowledge of. The term life includes life-process and

living states. According the Sushruta the term Ayurveda is interpreted as

the science in which the knowledge of life exists or that which helps man

enjoy a longer duration of life. The term Ayuh or life has been described

as the totality of the events representing the correlation of and

interaction between the body, senses, mind and atma (Spirit). Charaka

defines the ‘Ayuh’ as the union of body, senses, mind and atma (Spirit).

Sushruta states that the main objective of Ayurveda is to cure the

diseased person and preserve/maintain health. According to Charaka,

the utility of the science of Ayurveda consists of the maintenance of

health in the healthy and relief of abnormal states of health in the ailing.

Metal-based formulations have been in use since time immemorial.

Rig-Veda mentions the use of gold, silver, copper and bronze in the

treatment of disease. Similarly, Charaka and Sushruta, two of the

founding fathers of Ayurveda, describe the tonic value of a number of

minerals. Nagarjuna, considered to be the father of Rasa Shastra,

32

endeavored to free the entire world from disease by using processed

mercury. According to the Rasa Shastra, the metals, referred to as Dhatu

and Updhatu, supplement several essential, disease-preventing elements

in the tissues of human body. The metal-based formulations are

particularly effective in curing diseases related to organs where such

metals are naturally present (Rasatarangini and Rsaratnasamuchaya) 74.

1.3.1 Mashi 67,112

It is a well known fact that burning any herbal or animal product

leads to, carbon formation. Modern chemistry proposes that all sendriya

dravyas (i.e. dravyas obtained from living things) are carbon compounds.

So, when any dravya is heated it decomposes, the non-metallic part is

sublimated and what remains behind is only the black carbon. Since

carbon itself is also combustible, it forms smoke which is evaporated, if it

is heated in presence of oxygen or air, leaving behind only nirindriya,

which is a white fluffy material, commonly known as white ash.

Mashi means the black ash obtained from herbal or animal source.

The formulations containing Mashi of crude drugs recommended for

internal use or external application are known as Mashikalpa.

Whenever any herbal or animal product is heated slowly, it undergoes

combustion, upon attainment of a specific temperature. The smoke

appears at the beginning of the process and the material starts

blackening. Then the typical odor of combustion is identified. Ultimately,

when the whole material turns black and the smoke is completely

33

removed, the process of formation of Mashi is assumed to be complete.

This material is ground to a fine powder, which should be perfectly black

like charcoal powder. If this Mashi is heated further, it burns and forms

white ash. As Mashi retains its sendriyatva, it is more palatable by the

body in comparison to the white ash.

Mashi is a dosage form in which bulk of raw material is reduced to a

greater extent by application of a certain quantum of energy. Due to this

treatment, hidden chemical constituent become prominent and/or a new

chemical moiety is formed which is therapeutically active. Also due to the

thermal degradation or decomposition thermo labile constituents are

lost. Thus, without application of any costly method for extraction using

organic solvent, we can get a therapeutically active organic and inorganic

chemical constituent in the form of a black mass known as Mashi.

According to Ayurvedic literature, Mashi can be prepared by two

methods viz. Bahirdhum Padhati (BPM) and Anterdhum Padhati (APM). In

Bahirdhum Padhati method (Fig. 1.1), heating is carried out slowly at

about 145-1500 C, with continuous stirring. In Anterdhum Padhati

method (Fig. 1.2), the material of which Mashi is to be prepared, is

packed in between two Sharav Samput, which are then sealed by Multani

Matti. It is then subjected to Gajaputa in Gajaputa Kund, which is filled

with cow dung cakes. It is then set on fire. When Gajaputa becomes

Swangsheet, Sharav is taken out of Kund and Mashi is collected.

34

Though the ancient vaidyas were unaware of this chemical

phenomena, it was known that such carbon black obtained from herbal

or animal source could be employed for therapy of various diseases or

disorders. Those vaidyas have reported various examples of crude drugs,

which were used in the form of Mashi. Some of the examples are as

follows.

(Meaning: Mayurpicha (peacock feather) mashi is to be taken internally

with honey. This helps for the relief of hiccups, asthma and vomiting)

(Meaning: Hastidanta mashi and rasanjana are triturated together in

water. It promotes hair growth, if applied externally on the non hairy part

of the body even on the palms.)

(Meaning: If the triphala mashi is applied externally with honey, the

syphilis sores rapidly heal.)

35

According to Ayurveda, the Panchamahabhutas are present in every

Dravya. When the balance of these Panchamahabhutas in the body is

altered, a person becomes ill. Therefore the aim of Ayurvedic treatment is

to restore the balance of these Panchamahabhautik dravyas.

Due to conversion of dravya to its Mashikalpa, the Parthiv and Aapya

part in that dravya is lost and only Taijas and Vayaviya part remains.

Therefore these dravyas are used in the treatment of various diseases of

Vatavimargagaman (i.e. disorder in which percentage and /or position of

gas in the body is altered). The gas formed in the digestive system is

absorbed in Mashi. If the black ash is further converted to white ash then

only Taijas part will remain and Vayaviya part will be burnt off.

Therefore the white ash cannot be used in various Vata diseases.

Fig 1.1 Preparation of Bahirdhum Padhati Mashi

36

Fig 1.2 Preparation of Anterdhum Padhati Mashi

37

Table: 1.1-List of crude drugs prescribed in the form of Mashi

Method of

Preparation

References Type of Mashi Mode of Application uses

Anterdhum

padhati

Sushruta Samhita

chikitsa sthana

kusththa chikitsa

1. Krushna sarpa Mashi

(Black snake)

2. Vyaghra or Gaja Charma

Mashi (Tiger or elephant

skin)

Local application with

bibhitik taila

Local application with

vashanika taila

Vitiligo

Ashtanga Sangraha

(Vagbhat)

Kurmakapal Mashi

(Tortoise shell)

Local application Baldness

Chakradanta

(Chakrapani)

Bhul prakran

Mrugshrunga Mashi

(Deer horn)

Internally along with cow

ghee

Cardiac diseases

38

Yogaratnakar

kshudrarog chikitsa

White Horse’s Hoof’s Mashi Local application with

butter

Baldness

Bharat bhaishajya

ratnakar

Triphala mashi Use along with sesame

oil

Ulceration or burn

wounds

Bahirdhum

padhati

Sharangdhar Samhita –

Utter khand

Triphala Mashi Local application with

honey

Gonorrhoea, syphilis

Vrudhavaidyadhar Coconut epicarp Mashi Internally Antiemetic

Sushruta Samhita

chikitsa sthana

Hastidanta Mashi (Ivory) Local application with

rasanjana and goat milk

Baldness

Vrudhavaidyadhar Mayurpicha Mashi

(Peacock feather)

Internally with honey Antiemetic

Vrudhavaidyadhar Corn silk Mashi Internally with honey Diuretic

39

1.3.2 Bhasma

The meaning of term bhasma can be understood by splitting this

word into two words viz. ‘Bhas’ and ‘Sma’. The word ‘Bhas’ means shine,

glitter or luster and the suffix ‘Sma’ indicates a past tense. Thus bhasma

means shining in the past. This indicates that the material used in the

preparation of bhasma loses its luster after undergoing a specific process

called marana.

Bhasma is a metal base formulation. Metal-based formulations have

been in use since time immemorial. Rig-Veda has mentioned the use of

gold, silver, copper and bronze in the treatment of disease. Similarly,

Charaka and Sushruta, has described the usefulness of number of

minerals. Nagarjuna, considered to be the father of Rasa Shastra,

endeavored to free the entire world from disease by using processed

mercury. In metal-based preparations, the metal is not used in original

form, but it undergoes series of processing along with the herbs and

results in the formation of a fine powder called bhasma.

Bhasma is a calcined preparation which involves the conversion of

metal or other minerals. During these transformations, the zero valent

state gets converted into a form with higher state. The most important

aspect of this synthesis (known traditionally as ‘bhasmikarana’) is that

the toxic nature (i.e. systemic toxicity causing nausea, vomiting, stomach

pain, etc.) of the resulting compound is completely destroyed while

inducing the medicinal properties into it.

40

Bhasmikaran is a process by which a substance which is

bioincompatible is made biocompatible by certain samskaras or

processes. The objectives of samskara are: 1) elimination of harmful

matter from the drug 2) modification of undesirable physical properties of

the drug 3) conversion of some of the characteristics of the drug 4)

enhancement of the therapeutic action. Various steps involved in the

preparation of bhasma are:

1) Shodhana -Purification, 2) Marana - Powdering, 3) Chalana- Stirring,

4) Dhavana - Washing, 5) Galana- Filtering, 6) Putan- Heating, 7)

Bhavana- Coating with herbal extract. Selection of these steps depends

on the specific metal.

1.3.2.1 Steps of bhasmikaran 82, 83

1. Shodhana: In Ayurveda, Shodhana is different from chemical

purification which pertains to elimination of foreign material. In

Shodhana of Ayurvedic drugs the objective is 1) elimination of harmful

matter from the drug, 2) Modification of some undesirable properties, 3)

Conversion of some of the properties (gunas) of the drugs and 4) The

enhancement of therapeutic action thereby potentiating the drugs.

Every substance in the natural form is not suitable to be consumed

e.g., we remove seeds from the fruits, we wash vegetables before cooking,

the same is true with the medicinal substances also.

41

The process of shodhana includes many unit operations as per the

requirement like cleaning, sifting, distillation, sorting, dehydration,

straining, filtration, dehusking, peeling, washing, polishing etc. Different

ways to purify the medicinal substances are as follows.

• Prakshalana (washing): This is used to remove the physical

impurities originating from soil, sand and such other physical

substances.

• Chalana (sifting): This is used to remove the impurities like sand,

clay, stones and plant pieces.

• Jalavilayana (water extraction): this method is applicable to purify

the drugs that are water soluble. Here drug is dissolved in water

and water soluble impurities like sand are removed by filtration.

• Twaknishkaasana: This is the process of removing the outer skin

of the material when it is fresh.

• Nimajjana: In this method, the material to be purified (shodya) is

immersed in the shodhana dravya in a vessel. This is covered

properly and kept for the specific time. The shodhana dravya is

removed and the material is spread on the cloth and dried.

• Nirvaapana: This is applicable to the metals like gold, silver and

copper. These are heated on flame till they become red hot and are

immediately immersed into the shodhana dravya.

42

• Oordhwa- patan (Sublimation): For this Damaru-Yantra is used. In

this the material is kept at the bottom and the lower vessel is

heated. The upper vessel is kept cool by pouring water or by

covering it with a wet cloth. The material after sublimation adheres

to the interior surface of the upper vessel in purified form.

• Adha-patan: For this the same assembly (Damaru-Yantra) is used

but it is buried in the earth. The lower vessel is filled with water.

Over this vessel, another vessel which is smeared internally with

medicinal substance is kept upon it in inverted position. Heat is

then applied to the upper surface of the inverted vessel. Thus the

material gradually falls in the lower vessel.

• Svedana: This is the process of boiling the material in shodhana

dravya.

Ayurveda classifies shodhana into a) Samanya (General) process and

b) Vishesha (Specific) process.

General process for shodhana: The mineral substances of same class

posses some toxic substances/doshas in common. In such cases, these

can be treated by samanya shodhana. For this purpose the substance is

treated with different dravyas one after the other as taila, takra, gomutra,

kanjika, kulith etc.

43

Specific process for shodhana: for some metals a specific process is

described for shodhana e.g. for purification of Jasad, the molten mass is

poured in cow’s milk 21 times.

After shodhana, drug is subjected to the Marana process by which it

is reduced to such a state in which it can be absorbed by the body.

2. Marana: Marana literally means killing. As the name suggests in

marana process, a change is brought about in the chemical form or state

of the metal. This causes it to lose its metallic characteristics and

physical nature. After marana, metal is reduced to a state in which it can

be absorbed by the body. To convert various metals into a form

appropriate for human consumption, several techniques have been

employed which ultimately gave birth to the concept: “Bhasma prepared

by using Rasa i.e. mercury is the best, whereas the one prepared using

herbs are of better quality and those prepared using Gandhak (sulfur)

are of inferior quality”.

After marana many different changes occur in different substances,

heavy material getting converted into lighter one (Suvarna), flowing

substance converted to non flowing (Paarad), conversion into non toxic

form (Tamra)

In marana the purified drug is kept into Khalva (stone mortar and

pestle) and ground with juice of the specified plant. It is ground for the

44

specified period of time, then dried l in sunlight and placed in a single

layer in shallow earthen pot (Sharav). It is then closed with another

earthen pot and the edge is sealed with clay smeared cloth and dried.

A pit of specified size is dug. Half the pit is filled with cow dung cakes.

The sealed container is placed in it and the remaining space is filled with

more cow dung cakes. Thereafter it is set on fire. When the burning is

over, it is allowed to cool completely. The earthen pot is removed and seal

is opened and the contents are taken out. The content is ground in

khalva. This process of triturating with the juice (Bhavana) and giving

putas are repeated as many times as prescribed in the texts or till the

proper fineness and quality are obtained 7.

Puttan24, 96: Puttan means ignition. The general term used for heating

in the process of Bhasmikaran is Puta. A special earthen pot, Sharav is

generally used for the process. The putas are described under different

names like Mahaputa, Gajaputa, Varah Puta etc. indicating the size of

the pit and the number of cow’s dung cakes to be used. Puta’s are

repeated as many times as prescribed in the classical texts for each

preparation viz. dasa puta (10 cycles), shatha puta (100 cycles), sahastra

puta (1000 cycles) etc.

3. Bhavana37: In shodhana process the material gets purified and is

made suitable for marana process, where it gets converted into fine

powder. In order to potentiate the drug or to add certain other properties

45

to it, a special treatment referred to as Bhavana is given. Thus bhavana

is the process of combining the drug powder with some principles in the

liquid form. The liquid used for this purpose is called as bhavana

dravyas. E.g. egg shell-bhavana of Aloe vera.

To ensure that the Bhasma is properly prepared, a set of tests are

also specified 74

1. Nisvadu :should not have any taste

2. Avami : should not cause emesis

3. Varitara :should float on water

4. Nirdhoma : When placed on fire should not give out smoke

5. Rekhapurna: When pressed in between fingers should fill the lines

of the phalanges.

6. Laghu: Light

7. Sukshma: Very fine powder

8. Shlakshna :smooth

9. Nishchandra :Should not have any shiny particles

10. Apunarbhava: should have permanent transformation which

cannot be reconverted to its original form.

1.4 BASIC ELEMENTS FOR HUMAN LIFE

Most of the recent investigations have been confined to organic drugs.

Focusing on organic compounds like alkaloids, tannins, glycosides,

46

steroids etc. It is obvious that many therapeutic drugs are organic

compounds with a complex structure. E.g. cardiovascular drugs like

digoxin, ouabain, gitoxin, digitoxin, propranolol, verapamil etc. Having

knowledge of the vital role of minerals in human physiology and

pathology plays a pivotal significance.

Major elements: Calcium, sodium, potassium, magnesium, iron and

phosphorous.

Minor elements: Iodine, fluorine and zinc

Calcium: It constitutes 1.5-2 % of body weight. It gives rigidity and

strength to bones, essential for blood clotting, controls rhythmic activity

of heart. It is also important for the development of muscles and nervous

system. Its deficiency causes rickets in children and osteomalacia in

adults. Depression and anxieties can also be attributed to lower levels of

calcium in the body.

Sodium: It occurs in all tissues and body fluids. It maintains pH, helps

in muscle contraction and transmission of nerve impulses in nerve

fibers. Its deficiency causes cramps, marked general weakness, mouth

dryness and mental lassitude.

Potassium: It also occurs in all tissues and body fluids. Within the cells,

it plays an important role in the maintenance of acid base balance,

47

osmotic pressure and water retention. Its deficiency causes cramps,

marked general weakness, mouth dryness and mental lassitude.

Magnesium: It is a catalyst for many intracellular enzymatic reactions

that helps in carbohydrate metabolism. Low magnesium concentrations

causes increased irritability of nervous system, peripheral vaso-dilatation

and cardiac arrhythmias.

Iron: It is absolutely essential for oxygen transport to tissues and for

operation of oxidative systems within tissue cells, without which life

would cease to exist within a few seconds.

Phosphorous: Phosphate is the major anion of intracellular fluid. It has

the ability to combine reversibly with many co-enzyme systems and also

with many other compounds, thereby part taking in the operation of

metabolic processes.

Iodine: It is essential for formation of thyroxin and tri-iodo thyronine

which maintains normal metabolic rates in all cells. Its deficiency causes

goiter.

Zinc: It forms an integral part of many enzymes like carbonic anhydrase

that helps in carbonic acid formation in RBC of peripheral capillary blood

from water and carbon dioxide and for rapid release of carbon dioxide

from pulmonary capillary blood into alveoli. It is essential for reactions

related to carbohydrate metabolism. It is present in lactic dehydrogenase

48

that helps in inter conversion between pyruvic acid and lactic acid. It is a

component of peptidase that digests protein in GIT.

Fluorine: It is not a necessary element for metabolism but the presence

of small amounts in the body during infancy when childs teeth are

developing, may subsequently give rise to carie formation.

Ayurveda has mentioned the significance of inorganic elements in

drugs. Treatment for diseases with mineral drugs was very common in

Ayurveda. Drugs of mineral origin with rich inorganic elements were

used in ancient Chinese Materia Medica. Sushruta has mentioned the

use of few natural salts such as sodium chloride, impure carbonates of

sodium and potassium, brass and some salts of copper, iron, silver, tin,

lead as well as some precious stones. According to the hypothesis of

Charaka, a better cure of disease results if the living body is treated with

living substances. Based on this principle , the non living materials like

metals, animals bones, horns, sea-shells etc are converted into living

form by combining them with living material (organic, sendriya) like

plants; so that they are easily accepted by body and are more effective.

Many organic compounds in vegetable and herbal drugs exist as salts

with potassium, sodium, magnesium, hydrochlorides, sulphates etc. In

literature, drugs from plants, minerals and animals were seen in which

inorganic element formed a part of their therapeutic basis. E.g. Arjuna

bark does not contain alkaloids or glycosides, but it is a cardio-tonic

49

drug. This is due to the presence of excess calcium, aluminium and

magnesium salts. Raisins contain calcium, potassium, magnesium,

phosphorous and iron in assimilable form that forms general and cardio-

tonic properties. The root of the Boerhaavia diffusa (Punarnava) is used

as a diuretic. Koman (1999) discovered its fairly good diuretic activity in

combination with iron.

Just like plants, food also has immense medicinal value. It’s

containing many inorganic elements that foster and promote good health

and well being largely. Despite the rapid advancements that we are

making in the field of organic compounds, we can not afford to neglect

the hidden potentials of inorganic compounds. The more we understand

and explore their uses, the more they will contribute in benefiting us.

Table 1.2: List of botanical, animal and mineral active constituents

with inorganic part

Botanical source

Drug Constituents Uses

Allium cepa Allyl propyl disulfide Cardiac stimulant,

Hypoglycemic etc.

Abroma angusta Mg salts of hydroxy acids styptic

Acacia arabica Arabin- Ca, K & Mg slats

of arabic acid

For skin disease

and poisoning

50

Adhatodha vasica Vasicine hydrochloride Diuretic,

Antispasmodic

Alstonia scholaris Astonine sulphate Astringent,

carminative

Boerhaavia diffusa Alkaloid sulphate Diuretic

Brassica nigra Sinigrin-Potassium

myronate

Counter irritant,

General stimulant

Glycyrrhiza glabra Glycyrrhizin- Ca &K salt

of glycyrrhizic acid

Anti-rheumatic,

antiulcer etc.

Papaver somniferum Morphine as sulphuric

acid salt

Analgesic

Terminalia arjuna Ca, Al & Mg salts Cardio-tonic

Vitis vinifera (Raisins) Ca, K, Mg, P & Fe General tonic

Mineral source

Drug Constituents Uses

Tara bhasma Silver Aphrodisiac, Heart burns

Lauha bhasma Iron Haematinic, General tonic

51

Swarna bhasma Gold Cardio-tonic, Anti-rheumatic

Kapardika bhasma

Shukti bhasma

Shanka bhasma

Shambuka bhasma

Calcium

(Lime)

Cardio-tonic, antacid and

dyspepsia.

Nag bhasma Lead Cardio-tonic

Animal source

Drug Constituents Uses

Mrugshrunga (Hart’s horn) -

Cervus dama

Calcium phosphate For all types of cardiac

disorders

Stag’s horn- Cervus elephus Calcium phosphate For all types of cardiac

disorders

Cuttle fish bone- Os sepiae Calcium phosphate Antacid, Local sedative

Oyster- Ostrea edulis Calcium phosphate Cardio-tonic,

demulcent

Shells-Cypraea moneta Calcium phosphate Cardio-tonic,

jaundice and dyspepsia

52

Coral- Corallium rubrum Carbonates of lime,

Magnesium carbonate

and iron oxide

Antacid, astringent

and diuretic

White shark oil- Carcharodon

carcharias

Iodine, phosphorus,

vitamins A & D

For vitamin A and D

deficiency

Spongilla-The sponge Gel, albumin & Iodine Astringent

1.5 URINARY DISORDERS-CAUSES AND TREATMENT 108,122

1.5.1 Urinary system:

A human waste material has traditionally been defined as any

substance that has no function in body. This includes excess carbon

dioxide from cellular respiration, toxic nitrogen containing molecules

from the catabolism of proteins such as ammonia and urea; bilirubin

from the breakdown of the haemoglobin and uric acid from the

catabolism of nucleic acids. Also, essential ions such as sodium,

chloride, sulphate, phosphate and hydrogen build up excessively and

hence categorized as wastes. Toxic materials and excess essential

materials must be excreted (eliminated) from the body. Several tissues,

organs and processes contribute to the temporary confinement of waste

materials for disposal, recycling of materials and excretion of toxic

substances from the body. This includes body buffers, blood, liver, lungs,

sweat glands, gastrointestinal tract and kidneys

53

The major function of the urinary system is to help to maintain

homeostasis by controlling the composition, volume and pressure of the

blood. Two kidneys, two ureters, one urinary bladder and urethra make

up the urinary system. The kidneys filter the blood and solute into the

blood stream. The remaining water and solute constitute the urine. Urine

is excreted from each kidney through its ureter and is stored in urinary

bladder, until it is expelled from the body through urethra. Although the

kidneys play a key role in waste management, their other functions are

equally important. These include:

1. Regulation of blood volume and composition.

2. Regulation of blood pH by excreting variable amount of H+ ions.

3. Regulation of blood pressure by secreting the enzyme renin, which

activates renin-angiotensin pathway.

4. Contribution to the metabolism by synthesizing the hormone

calcitriol, the active form of vitamin D, secretion of erythropoietin,

the hormone that stimulates production of RBCs.

1.5.2 Physiology of urine formation

The major work of urinary system is done by the nephrons. The other

parts of the system are primarily passage ways and storage areas. Urine

formation involves three principal processes.

1. Glomerular filtration

2. Tubular reabsorption and

3. Tubular secretion

54

Glomerular filtration: It is the first step in urine formation. It occurs

in the Bowman’s capsule of the kidneys across the endothelial-capsular

membranes. Blood pressure forces water and dissolved blood

components through the endothelial pores of the capillaries, basement

membranes and into the filtration slits of adjoining visceral wall of the

glomerular capsule.

Tubular reabsorption: As the glomerular filtrate passes through the

renal tubules, about 99 % of it is reabsorbed (returned to the blood).

Thus, only 1% of filtrate leaves the body as urine (about 1.5 liters a day).

The movement of water and solutes back into the blood of a peritubular

capillary or vas recta is called tubular reabsorption. The epithelial cells

all along the renal tubule carry out tubular reabsorption. Solutes that

are reabsorbed by both active and passive processes include glucose,

amino acids, urea and ions such as Na+, K+, Ca2+, Cl-, HCO3- and HPO4

2-

Tubular secretion: The third process involved in urine formation is

tubular secretion. Tubular reabsorption returns substances from the

filtrate into blood & tubular secretion removes material from blood and

adds them to the filtrate. These secreted substances include potassium

ions, hydrogen ions, ammonium ions, creatinine and the drugs like

penicillin and para-amino hippuric acid. Tubular secretion has two

principal effects. It rids the body of certain materials and it helps to

controlling blood pH.

55

1.5.3 Disorders- causes and treatment 27

1.5.3.1Urolithiasis (Renal calculi, renal stones)

Stones may form at any level in the urinary tract, but most arise in

kidney. There are four main types of calculi.

1. Most stones (about 75%) are calcium containing composed

largely of calcium oxalate or calcium oxalate mixed with

calcium phosphate.

2. Triple stones or struvite stones (about 15 %) are composed of

magnesium ammonium phosphate. These stones are formed

largely after infections by urea splitting bacteria (e.g. Proteus

and some staphylococci), that converts urea to ammonia. The

resultant alkaline urine causes the precipitation of magnesium

ammonium phosphate salts.

3. Uric acid stones (about 6%) are common in patients with

hyperuricemia such as gout and leukemia

4. cystine stones are caused by the genetic defects in the renal

reabsorption of amino acids including cystine leading to

cystinuria

Condition leading to stone formation includes the ingestion of the

excessive calcium, a decrease in the amount of the water intake,

abnormally acidic or alkaline urine and over activity of parathyroid

glands. The stones can be removed either surgically or by use of

56

diuretics. Surgical removal includes pyelolithotomy, nephrotomy and

partial nephrotomy.

Diuretics increase the flow of urine and so, it continuously increases

the dissolution of the stone and helps to remove the stone. Sometimes a

shock wave lithotripsy technique is used which delivers brief, high

intensity shock waves through water filled cushion.

In calcium oxalate nephrolithiasis, potassium citrate is used. The

citrate complexes with calcium and prevents its combination with oxalic

acid and because of citrate inhibits urate induced crystallization of

calcium oxalate.

In uric acid nephrolithiasis potassium citrate is used to maintain

urinary pH 5-8.5 and increases the solubility of stone. Potassium and

other salts (lactate, acetate) are metabolized and the cations are excreted

with bicarbonate to give alkaline urine. Alkalization is important in

preventing or decreasing the formation of uric acid and cystine stones.

1.5.3.2 Urinary Tract Infection

The term urinary tract infection (UTI) is used to describe either an

infection of a part of the urinary system or the presence of large numbers

of microbes in urine. Included in this are , significant bacteria (the

presence of bacteria in urine in sufficient numbers to indicate active

infection), symptomatic bacteria (the multiplication of large numbers of

bacteria in urine without producing symptoms), urethritis (inflammation

57

of urethra), cystitis (inflammation of urinary bladder) and pyelonephritis

(inflammation of kidneys).

Mainly antibiotics and sulphonamides are useful for the treatment of

UTI.

1.5.3.3 Chronic renal failure (CRF)

It refers to a progressive & usually irreversible decline in glomerular

filtration rate. CRF may result from chronic glomerulonephritis,

pyelonephritis, polycystic disease or traumatic loss of kidney tissue.

Among the effects of renal failure are edemas from salt and water

retention, acidosis due to inability of kidneys to excrete acidic

substances, increased blood urea nitrogen and elevated potassium levels

that can lead to cardiac arrest.

Both herbal (calcurry, cystone) and synthetic (Furosemide,

Spironolactone etc.) diuretics are useful for the treatment of CRF.

1.5.3.4 Urinary Incontinence

A lack of voluntary control over urination is referred to as

incontinence. In infants less than two years old, incontinence is normal

because neurons to external urethral sphincter muscle are not

completely developed. Involuntary micturition in adults may occur as a

route of unconsciousness, injury to spinal nerves controlling to urinary

bladder, irritation due to abnormal constituents in urine, disease of

urinary bladder etc.

58

1.5.4 Concentration of electrolytes in the body:

Electrolytes are the most important substances, which influence the

distribution and retention of body water. The principal electrolytes in the

body are sodium, potassium and chloride. They constitute about 60-80%

of all inorganic material in the body.

Sodium: This element is major component of the cations of the extra

cellular fluids. It is largely associated with chloride and bicarbonate in

regulation of acid-base balance.

Potassium: It is the principal cation of intracellular fluid. Within the

cells it plays an important role in maintenance of acid-base balance,

osmotic pressure and water retention. Intracellular potassium is

essential for several important metabolic reactions catalyzed by enzymes.

It also influences muscle activity of the heart.

Chloride: As a component of sodium chloride, the element chloride is

essential in water balance, osmotic pressure regulation and in acid-base

balance. Gastric juice chloride also plays an important role in production

of hydrochloric acid. The average excretion of sodium in 24 hours is

about 40 mEq /liter. The excretion ratio of K to Na is generally about 3:5

in normal individuals. The absolute quantity of these elements excreted

depends mainly upon the diet. The output of potassium in relation to

sodium may be increased during fever and the condition associated with

acidosis.

59

The average excretion of chloride ranges from 120-250 mEq/L. The

conditions, which favor excessive perspiration, cause a diminution in

urinary output of chlorides. Muscular cramps may result when there is

an excessive loss of sodium, chloride from the body.

1.5.5 Diuretics

A diuretic is a substance that increases the rate of urine volume

output. It also increases urinary excretion of solutes, especially sodium

and chloride. Many diuretics that are used clinically act by decreasing

the rate of sodium reabsorption from the tubules which in turn causes

natriuresis (increased sodium output). i.e. increased water output in

many cases, occurs secondary to inhibition of tubular sodium

reabsorption because sodium remaining in the tubules acts osmotically

to decrease water reabsorption.

Common clinical use of diuretics is to reduce extracellular fluid

volume, especially in disease associated with edema and hypertension.

Loss of sodium from the body mainly decreases extra cellular fluid

volume; therefore diuretics are most often administered in clinical

conditions in which extra cellular fluid volume is expanded. They are

often prescribed to treat congestive heart failure, high blood pressure,

edema and kidney stone.

60

1.5.5.1 Major classes of diuretics:

1. Carbonic anhydrase inhibitors: e.g. Acetazolamide. It slows Na+

reabsorption by inhibiting the enzyme carbonic anhydrase in the

brush border of proximal convoluted tubule.

2. Loop diuretics: e.g. Furosemide. These are the most potent

diuretics. They selectively inhibit the Na+-K+-2Cl- symporters in the

thick ascending loop of henle.

3. Thiazide diuretics: e.g. Chlorothiazide. They are supposed to

inhibit the Na+-Cl- symporters in the distal convoluted tubule.

4. Osmotic diuretics: e.g. Urea, mannitol. They mobilise fluid by

increasing the osmotic pressure of extracellular or tubular fluid.

Hence, if soluble inorganic salts or low molecular organic

compounds enter in glomerular filtrate in concentrations

sufficiently high to exceed tubular reabsorption, then an osmotic

equivalent of water is also excreted.

Due to various side effects of synthetic diuretics such as

hypokalemia, dilutional hyponatremia, hearing loss, allergic

manifestation, hyperuricemia, etc, herbal diuretics should be promoted.

Table 1.3: List of herbal drugs claimed as diuretics 23

Sr.No Botanical name Common name Parts used

1. Boerhaavia diffusa

(Nyctaginaceae)

Punarnava Roots

61

2. Cocos nucifera

(Palmae)

Coconut Water of unripe fruit

3. Crataeva nurvala

(Capparidaceae)

Varuna Bark

4. Cucurbita maxima

(Cucurbitaceae)

Pumpkin Seeds

5. Cucumis sativus

(Cucurbitaceae)

Cucumber seeds Seeds

6. Dolichos biflorus

(Leguminosae)

Kuthi Seeds

7. Mimosa pudica

(Leguminosae)

Lajwanti Root

8. Mallotus philippensis

(Euphorbiaceae)

Kamala Fruit

9. Smilax Spp.

(Liliaceae)

Sarsaparilla Root

10. Tribulus terrestris

(Zygophyllaceae)

Gokharu Fruit

62

11. Tinospora cordifolia

(Menispermaceae)

Guduchi Stem

12. Urginea indica

(Liliaceae)

Indian squill Bulbs

13. Urtica dioica

(Urticaceae)

Buchu Leaf

14. Zingiber officinalis

(Zingiberaceae)

Ginger Rhizome

1.5.6 Potassium as diuretics

Potassium is a major intracellular cation present in a concentration

approximately 23 times higher than its concentrations in extracellular

compartments. Potassium in the diet is rapidly absorbed. Excess

potassium is rapidly excreted by the kidneys. Potassium salts have been

used for their diuretic action because of their efficient excretion by

kidneys, since a certain volume of fluid (urine) will be excreted in order to

keep potassium salts in solution12.

Low potassium intake may play an important role in the genesis of

high blood pressure. Increased potassium intake should be considered

as recommendation for prevention and treatment of hypertension

especially in those who are unable to reduce their intake of sodium.

63

Potassium is an osmotic diuretic 36. The capacity of the renal tubule

to reabsorb various electrolytes and non-electrolytes is limited and varies

for each ionic species. If large amount of these substances are

administered to an individual, their concentration in the body fluids and

subsequently in the glomerular filtrate exceeds the reabsorption capacity

of the tubules, and excess appear in the urine accompanied by increased

volume of water. Substances which increase urine formation in this

manner are called as osmotic diuretics.

Osmotic electrolytes such as potassium and sodium salts, osmotic

non electrolytes such as urea, glycerin, mannitol and acid forming salts

like ammonium chloride are examples of osmotic diuretics.

Many plants are diuretic in nature. The activity may be due to some

active constituents or some of the inorganic radicals such as potassium

salts. E.g. Smilax perfolia has been reported as a diuretic. The root

contains a heteroside parillin, a complex phenolic acid and much

potassium nitrate. The diuretic action of the plant is said to be due to

potassium nitrate.

The diuretic activity of the Tribulus terrestris (chota gokharu) is due

to the presence of large amount of potassium nitrates as well as the

essential oil, which occurs in the seed 59. The root of the Boerhaavia

diffusa (Punarnava) is used as diuretic. The plant contains alkaloid

punarnavine and potassium nitrate 22. Both are responsible for diuretic

activity. The leaves of Hygrophila salicifoia contain 18% ash, rich in

64

potassium and are strongly diuretic 87, 59. The diuretic activity is believed

to be due to a combination of both the inorganic and organic content of

the plants. Potassium-magnesium citrate effectively prevents recurrent

calcium oxalate stones and this treatment given up to three years

reduces risk of recurrences by 85%.

1.6 EMESIS-CAUSES AND TREATMENT 38

Emesis is a general disorder of the gastrointestinal tract (GIT). GIT is

a continuous tube running through the ventral body cavity and

extending from mouth to the anus. The organs comprising the GIT

include the mouth, pharynx, esophagus, stomach, small intestine and

large intestine.

1.6.1 Emesis

Emesis is the means by which the upper gastrointestinal tract rids

itself of toxic waste matter. To its content when almost any part of the

upper tract becomes excessively irritated (copper sulphate, ipecacuanha

causes irritation), over distended or even over excitable. Excessive

distension or irritation of the duodenum provides a strong stimulus for

vomiting. Impulses are transmitted by both vagal and sympathetic

afferent to the bilateral vomiting center of the medulla, which lies near

the tractus solitarius at the level of the dorsal motor nucleus of the

vagus. Appropriate automatic motor reactions are then instituted to

cause the vomiting act. The motor impulses that cause the actual

vomiting are transmitted from the vomiting center, through the 5th, 7th,

65

9th, 10th and 12th cranial nerves to the upper gastrointestinal tract and

through the spinal nerves, to the diaphragm and abdominal muscles.

1.6.2 Antiperistalsis, the prelude to vomiting

In the early stages of excessive gastrointestinal irritation or over

distention, antiperistalsis begins to occur, often many minutes before

vomiting appears. The antiperistalsis may begins as far down in the

intestinal tract as the ileum and the antiperistalsis wave travels

backward up the intestinal at the rate of 2 to 3 cm/sec. This process can

actually push a large share of the intestinal contents all the way back to

the duodenum and stomach within 3-5 minutes. Then, as these upper

portions of the gastrointestinal tract, especially the duodenum become

overly distended, this distention becomes the exciting factor that initiates

the actual vomiting act.

1.6.3 The vomiting act

Once the vomiting center has been sufficiently stimulated, the

vomiting act instituted, the effects are:

1. A deep breath.

2. Raising of the hyoid bone and the larynx to pull the upper esophageal

sphincter open,

3. Closing of the glottis,

4. Elevation of the soft palate to close the posterior nares.

Next comes a strong downward contraction of the diaphragm along

with the simultaneous contraction of all the abdominal wall muscles,

66

building the intra gastric pressure to high level. Finally the lower

esophageal sphincter relaxes completely, allowing expulsion of gastric

contents through esophagus.

1.6.4 Chemoreceptor trigger zone of the medulla for initiation of

vomiting by drugs or by motion sickness.

Aside from the vomiting initiated by irritative stimuli in GIT itself,

vomiting can be caused by vomiting center which is particularly true of a

small area located bilaterally on the floor of the 4th ventricle, near the

area of the postrema and called the chemoreceptor trigger zone (CTZ).

Electric stimulation of this area also initiates vomiting; administration of

certain drugs like apomorphine, morphine and some digitalis derivatives

can directly stimulates the CTZ.

Change in motion of the body also causes certain people to vomit. The

motion stimulates the receptor of the labyrinth and impulses are

transmitted mainly by the way of the vestibular nuclei into cerebellum,

then to CTZ and finally the vomiting center to cause vomiting.

1.6.5 Cerebral excitation of vomiting

Various psychic stimuli, including disquieting scenes, noisome odour

and similar psychological factors can cause vomiting. The precise

neuronal connections for these effects are not known, the impulses pass

directly to the vomiting center and do not involve the CTZ.

67

1.6.6 Antiemetic 86,109

These drugs are used to reduce or to prevent vomiting. Most of the

antiemetic drugs possess at least some degree of central depressant

action.

• Anticholinergics: It acts probably by blocking conduction of nerve

impulses (across a cholinergic link) in the vestibular apparatus or

in the pathway leading from it to vomiting center. E.g.: hyoscine,

dicyclomine.

• H1-antihistaminics: Their antiemetic action is probably based on

anticholinergic and sedative properties. E.g.: promethazine,

diphenhydramine, cyclizine, meclizine.

• Neuroleptics: These are potent anti emetic; acts by blocking D2

receptors in CTZ, antagonize apomorphine induced vomiting. E.g.

chlorpromazine, prochlorperazine, haloperidol.

• Prokinetic drugs: These are drugs which promote gastrointestinal

transit and speed gastric emptying by enhancing coordinated

propulsive motility. E.g.: metoclopramide, domperidone, cisapride.

• Miscellaneous: their mechanism of action is not known. E.g.:

pyridoxine, nabilone, amphetamine.

68

Table 1.4 List of some herbal drugs claimed as antiemetic

Sr. No Botanical name Common name Part used

1. Emblica officinalis

(Euphorbiaceae)

Amla Fruit

2. Piper longum

(Piperaceae)

Pippali Fruit

3. Piper nigrum

(Piperaceae)

Black pepper Fruit

4. Zingiber officinalis

(Zingiberaceae)

Ginger Rhizome

5. Ocimum sanctum

(Labiatae)

Tulsi Leaves

1.7 HELMINTHIASIS: CAUSES AND TREATMENT

Worm infestation is one of the major global health problems especially

in tropical countries. The World Health Organization estimates that a

staggering 2 billion people harbor parasitic worm infections globally 50.

Helminthiasis is common globally, but is more common in developing

countries with poorer personal and environmental hygiene. Multiple

infestations in the same individual are not infrequent. In human body

69

GIT is the abode of many helminthes, but some also live in tissues or

their larvae migrate into tissues. They harm the host by depriving him of

food, causing blood loss injuries to organs, intestinal or lymphatic

obstruction and by secreting toxins109. Although the majority of

infections due to worms are generally limited to tropical countries, they

can occur to travelers who have visited those areas and some of them

can be developed in temperate climates 18. Helminthiasis is rarely fatal,

but is a major cause of ill health.

The helminthes which infect the intestine are cestodes e.g.:

Tapeworms (Taenia solium) nematodes e.g. hookworms (Ancylostoma

duodenale), roundworm (Ascaris lumbricoids) and trematodes or flukes

(Schistosoma mansoni and Schistosoma hematobolium). The disease

originated from the parasitic infections causing severe morbidity

including lymphatic filariasis, onchocerciasis and schistosomiasis. These

infections can affect most populations in prevalent area with major

economic and social consequences.

1.7.1 Drugs for worm infestations 1. Piperazine: It was first used in the 1950s as an anthelmintic. It

acts as a weak GABA-mimetic and causes a flaccid, reversible paralysis

of body wall muscle. Single channel recordings provide evidence that it is

a low efficacy, partial agonist at GABA-gated chloride channels 70

2. Benzimidazoles: Thiabendazole, the first drug of this class was

discovered in 1961 and subsequently a number of further benzimidazoles

70

were introduced as broad spectrum anthelmintic. Their anthelmintic

efficacy is due to their ability to compromise the cytoskeleton through a

selective interaction with β-tubulin 14, 60

3. Levamisole, pyrantel and morantel: These are nicotinic receptor

agonists and elicit spastic muscle paralysis due to prolonged activation of

the excitatory nicotinic acetylcholine (nACh) receptors on body wall

muscle 1, 11.

4. Paraherquamide: Paraherquamide A and marcfortine A are both

members of the oxindole alkaloid family, originally isolated from

Penicillium paraherquei and Penicillium roqueforti, respectively. They

induce flaccid paralysis in parasitic nematodes128

5. Ivermectin (macrocylic lactones and milbemycins): Ivermectin was

introduced in the 1980s by Merck as an anthelmintic. It is a semi-

synthetic derivative of avermectin which is a large macrocyclic lactone

fermentation product of the micro-organism Streptomyces avermitilis. It

has high affinity for nematode glutamate-gated chloride channels and so

acts as potent anthelmintic agent 40.

6. Nitazoxanide: Nitazoxanide, a pyruvate ferredoxin oxidoreductase

inhibitor, acts against a broad spectrum of protozoa and helminths that

occur in the intestinal tract.

Ideal anthelmintic agent should possess a broad spectrum of action,

high percentage of cure with single therapeutic dose, should be free from

71

toxicity to host and should be cost effective. Almost all the synthetic

drugs available do not meet this requirement. Even most common drug

like piperazine salts have side effects like nausea, intestinal disturbances

and giddiness65 Resistance of the parasites to the existing drugs 118 and

high cost warrants the search for the newer anthelmintic drug

People consume several plants, herbal preparation or traditional

remedies to cure helminthic infections93. Generally, tannin containing

plants shows a good anthelmintic activity127.

Table 1.5 List of some herbal drugs claimed as anthelmintic23.

Sr.No Botanical name Common name Part used

1. Areca catechu (Palmae) Supari Nuts

2. Butea frondosa (Leguminosae) Phalsa Seeds

3. Cucurbita maxima

(Cucurbitaceae)

Meetha kaddu Seeds

4. Centratherum anthelminticum

(Asteraceae)

kalijiri Seeds

5. Allium sativum (Liliaceae) Garlic Bulbs

6. Dryopteris filix-mas

(Polypodiaceae)

Male fern Rhizome

72

7. Embelica ribes (Myrtaceae) Vidang Fruit

8. Carica papaya (Caricaceae) Papaya Fruit

9. Semecarpus anacardium

(Anacardiaceae)

Bhilawa Seeds

10. Piper longum (Piperaceae) Pippali Fruit

1.8 ARTHRITIS: CAUSES AND TREATMENT85

Arthritis (from Greek arthro- joint, itis-inflammation) is the condition

involving damage to the body joints.

The different forms of arthritis are as follows

1 Acute Mono Arthritis: Hot painful, tender and swollen joints

(affecting singularly on any of the joint) due to bacterial infection or

crystal arthritis or reactive arthritis or trauma.

2 Polyarthralgia: is a joint pain without clinical evidence of arthritis.

Poly arthritis affects four or more joints.

3 Osteoarthritis (degenerative arthritis or degenerative joint

disease): is a group of mechanical abnormalities involving

degradation of articular cartilage, subchondral bone and

simultaneous proliferation of new bone cartilage and connective

tissue.

4 Inflammatory joint diseases

73

• Rheumatoid arthritis: Autoimmune disease that is usually

displayed in structure of joints.

• Psoriatic arthritis: Sero negative inflammatory arthritis found in

patient with psoriasis.

• Juvenile Idiopathic arthritis: It is inflammatory arthritis in

children and is defined as diagnosis of exclusion.

• Infective arthritis: arthritis arising from direct infection of joints

by microorganisms or as reaction of preceding infection.

Irrespective of the type of arthritis, the common symptoms for all

arthritis disorders include pain, swelling and joint stiffness. Arthritis

is rightfully called as “The king of Human miseries” and the great

crippler as arthritis can almost cripple a man. Description of these

disorders has been found even in Vedas. Arthritis exists throughout

the world and affects about three in every hundred people in Britain.

There are about 800000 new cases per year in North America and

Europe. It is three time more likely to occur with woman at the age 45

and is rare after the age 75, whereas in man it is rare before 45 but

continues to get more common thereafter. It occurs worldwide in all

races, with variation in the age onset and sex differences.

1.8.1 Etiology of the disease9

Rheumatoid arthritis is an autoimmune disease that is usually

displayed in the structure of joints. It is the most common chronic

74

inflammatory disease of the joints. Most arthritic diseases are

characterized by inflammation and tissue damage at joints. In

rheumatoid arthritis also, the immune system attacks the joints. This

auto immune reaction progress through five distinct stages.

Stage I: Generally, it has no symptoms, but deep in certain joints, the

cell forming the synovial membrane begin to attract T cells and the

synovial lining cells stick to each other when proteins on surfaces fit

together like interlocking puzzle piece. Once attached to joint lining

cells, the T cells turn on B cells . Inflammation is detectable by

laboratory results showing elevated number of WBC in the synovial

joint.

Stage II: In this stage, cytokines attract more WBC to the joints and

cause fatigue, mild joint stiffness and swelling that are the earliest

sign of the disease. At this stage more than billion WBC, a day collect

in the knee joints.

Stage III: In response to the activity of stage I and stage II the cells

forming the synovial membrane begin to proliferate and symptoms

intensify.

Stage IV: The disease extends to cartilage, tendons and finally to

bone. Joint swelling is more pronounced. As a result of the increased

75

cell numbers in the connective tissue, the synovial membrane can

weigh hundred times to its normal weight.

Stage V: By this stage overgrowth of cartilage and destruction of bone

are so great that the ligaments surrounding the joints are thrown out

of the position. The destruction that results is irreversible.

In the above mentioned five stages the earlier lesion is vasculitis,

inflammation of small blood vessels, caused by unknown primary

stimulus. The inflammation causes the synovium and infiltration with

polymorphs, lymphocytes and plasma cells. There is the intense local

production of Ig G by the plasma cells. All patients with rheumatoid

arthritis have demonstrable antibodies to immunoglobulin G, the so

called RA factor. Sensitization to self Ig-G is therefore believed to be

an almost universal feature of this disease. The Ig G antiglobulin

complexes formed can cause cartilage breakdown in several ways.

1. In the joint space, they react with polymorphs to release lysosomal

enzymes including proteinase and collagenase, which can destroy

cartilage.

2. They stimulate macrophage like cells of the synovial lining which

grow over the cartilage and destroy it by liberating enzymes.

3. Sensitization to the partially degraded collagen may occur leading

to the formation of anti collagen antibodies and

76

4. Prostaglandins E2, another product of activated macrophages can

cause bone resorption.

Once joints have been damaged by inflammation, they are not very

good at healing. Modern treatment tries to suppress the inflammation

as much as possible. So patients are treated with drugs to relieve the

symptoms of the disease and that is called first line therapy. It

includes conventional analgesic and non steroidal anti inflammatory

drugs. But the major problem with these agents is the gastric

ulceration through prolonged therapy. Eventually the majority of

patients receive second line treatment by anti-rheumatic agents called

Disease Modifying Agents e.g.: penicillamine, sulphasalazine and

methotrexate. Tumor necrosis factor inhibitors have also been shown

to reduce inflammation, pain, morning stiffness and swelling of joints

e.g.: etanercept, infliximab and adalimumab45.

Table 1.6 List of some herbal drugs claimed as anti arthritic and

anti inflammatory23

Sr. No Botanical name Common name Part used

1. Acorus calamus (Araceae) Bach Rhizome

2. Alpinia officinarum (Zingiberaceae) Rasna Rhizome

3. Apium graveolens (Umbelliferae) Ajmod Seed

77

4. Azadirachta indica (Meliaceae) Neem Seed

5. Boswellia serrata (Burseraceae) Salai guggul Gum

6. Commiphora mukul (Burseraceae) Guggul Gum resin

7. Dalbergia sissoo (Leguminosae) Shingshupa Root

8. Nyctanthes arbortristis (Oleaceae) Parijat Leaves

9. Semicarpus anacardium

(Anacardiaceae)

Bhilawa Nuts

10. Vitex negundo (Verbenaceae) Nirgundi Leaves

1.9 ROLE OF ANTIOXIDANTS

Antioxidant is a molecule capable of preventing the oxidation of other

molecules. Oxidation is a chemical reaction which transfers electrons

from substance to an oxidizing agent. Oxidation reactions can generate

free radicals, which start chain reactions that damage cells. Antioxidants

terminate these chain reactions by removing free radical intermediates,

and inhibit other oxidation reactions by being oxidized themselves.

Antioxidants are often reducing agents such as polyphenols99. They are

nutrients (vitamins, minerals) as well as enzymes (body proteins which

assist in chemical reactions). They are believed to prevent the

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development of chronic diseases like stroke, heart disease, cancer

Alzheimer’s disease.

Oxidative stress occurs when the production of free radicals is beyond

the protective capability of the antioxidant defenses. Free radicals are

chemically active atoms or molecular fragments which have a charge due

to an excess or deficient number of electrons. Superoxide anion, hydroxyl

radical, transition metals such as iron and copper, nitric acid, and ozone

are the example of free radicals. In biological systems oxygen gives rise to

a large number of free radicals and other reactive species collectively

known as ‘reactive oxygen species’ (ROS). ROS include the superoxide

and hydroxyl radical, hydrogen peroxide, singlet oxygen, and

hypochlorous acid48.

The generally accepted hypothesis is that in any biological system an

important balance must be maintained between the formation of reactive

oxygen (ROS) and nitrogen species (RNS) and their removal. ROS and

RNS are formed regularly as a result of normal organ functions, or as a

result of excess oxidative stress. The reactive species hydroxyl radical

(HO•), hydrogen peroxide (H2O2), superoxide (O2-), nitrogen oxide (NO•),

peroxynitrite (ONOO-) and hypochlorous acid (HOCl) are all products of

normal metabolic pathways of the human organs, when in excess they

can exert a harmful compounds. Superoxide is produced in mitochondria

during electron chain transfer and it regularly leaks outside of the

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mitochondria. To maintain an oxido/redox balance, organs protect

themselves from the toxicity of excess ROS/RNS in different ways,

including the use of exogenous and endogenous antioxidants47.

Oxidative stress Defense system

Endogenous source

of ROS/RNS

Exogenous source

of ROS/RNS

Enzymatic Non

enzymatic

Mitochondria Radiation Superoxide dismutase Vitamin E

Peroxisomes Ozone Catalase Vitamin C

Inflammatory cells Xenobiotics Glutathione peroxidase Glutathione

Paraoxonase Flavonoids

1.9.1 Classification

There are two main types of antioxidant 1) exogenous antioxidants

and 2) endogenous antioxidants.

Exogenous antioxidants: These antioxidants are present in our diet and

in our supplements e.g. Vitamin A, C and E. They are less potent than

endogenous antioxidants.

Endogenous antioxidants: they are produced inside the body. They are

more potent than exogenous antioxidants.

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Endogenous antioxidants repair all free radical damage from inside

whereas exogenous antioxidants only repair some of the free radical

damage from outside by stimulating cell regeneration.

1.9.3 Benefits of antioxidants46

• Protect the cell integrity as well as the supportive collagen tissue.

• Useful in boosting the immune system.

• Consumption of alcohol causes a host of toxins in the body and

antioxidants are useful in the detoxification process.

• By helping to protect blood vessels from fatty deposits they may

help the veins maintain their elasticity.

• Helps to relieve localized oxidative stress and also promote healthy

joint cells.

• Antioxidants help to reduce the build-up of peroxide from the body

and thus increase the stamina.

Table 1.7 List of some herbal drugs claimed as antioxidant.

Sr. No Botanical name Common name Part used

1. Areca catechu (Palmae) Supari Nuts

2. Curcuma longa (Zingiberaceae) Haldi Roots

3. Zingiber officinalis Adrak Rhizome

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(Zingiberaceae)

4. Emblica officinalis

(Euphorbiaceae)

Amla Fruit

5. Glycyrrhiza glabra

(Leguminosae)

Yashtimadhu Root

6. Picrorrhiza kurroa

(Scrophulariaceae)

Kutki Fruit

7. Piper betle (Piperaceae) Paan Leaf

8. Rubia cordifolia (Rubiaceae) Manjistha Root

9. Terminalia arjuna

(Combretaceae)

Arjuna Bark

10. Trigonella foenum-graecum

(Leguminosae)

Methidana seed