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Chapter 1
Introduction
1.0 INTRODUCTION
Millions of people in the third world rely on the herbal medicines because they
believe in them and regard them as their medicine in contrast to the “allopathic”
(conventional modern) system of medicine brought in from “outside”. These
medicinal herbs are available locally and are prescribed by the practitioners of
traditional medicine. Even in Western countries, there is now an increased use of
herbal preparation, because of belief that powerful synthetic agents used in western
medicine can exert more unwanted side effects and are too often used
indiscriminately and irrationally. Many people carry impression that medicines
derived from natural plants are harmless. Although natural medicines induce fewer
side effects than conventional drugs, there are plants that cause severe side effects.
Research on medicinal plants should be carried out to determine whether western
therapeutics could add to its armamentarium a few new drugs obtained from
medicinal plants used in the traditional systems. One such area could be hepatitis,
since the traditional system of medicine has plants for centuries for protecting the
liver and for treatment of liver dysfunction. Picrrorhiza kurroa, Phyllanthus amorous
and Andrographis paniculata are some of the widely used hepatoprotective herbs. In
view of their mention in ancient literature laboratory experiment need be carried out
with the plants so that they could be used widely in chemical practice. Similarly,
plants should be investigated in the field of bronchial asthma. The plants Curcuma
longa and Azardichata indica could certainly be tried in cases of arthritis, since the
nonsteroidal anti-inflammatory drugs, although powerful are potentially hazardous
medicines. In the past, pharmacologists have identified important medicines from
plants. Morphine, Quinine, Emetine, Reserpine, Digitalis glycoside, Ergot alkaloids
and Vincristine etc. are the examples of drugs in wide use today that originally were
obtained from plants. It is difficult to accept that there are no more drugs waiting to
be discovered from plants, in spite of unrewarding experiences in this field during the
last 30 years. There may still some such discoveries ahead of us (Chaudhari, 1995).
There are two distinct phases in research on medicinal plants. In the first phase, the
selection of plant is mainly based on their actual use and reputation in Indian
traditional system of medicine, where as in second phase, more broad base, in which
screening of large number of natural products for biological activity is undertaken,
irrespective of the fact whether these plant are being used by the traditional system of
medicine or not. (Rastogi etal 1982).
Rigveda is the earliest celebrated treatise mentioning the use of some medicinal
plants. The work of Agnivesha resulted in the compilation of Charaka-Samhita by
Charaka Sushruta, a brilliant discipline of Dhanvantri, was known for his knowledge
of surgery and medicine. Some Portuguese and Dutch scientist in sixteenth century
came to India for the study of medicinal plants. Van Rheed’s Horetus Malabericus is
the monumental work in 12 volumes on the study of Indian plants published between
1678 and 1703. William Roxburgh, the father on Indian Botany, worked a lot on
Indian plants and his work was published by Carey in 1820 to 1824. Heber Drury
published his monumental work ‘Useful plants of India, Dymock’s Vegetable
Material Medica of India appeared in 1883 and his comprehensive work
Pharmacographic Indices (1890-1893) was prepared in collaboration with Warden
and Hooper, Sir George Watt produced a voluminous dictionary of economic plants
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of India in six volumes (1889-1893). These are outstanding work wealth of
information on economic plants (Kaul, 1997).
1.1 Cordia macleodii
Cordia macleodii belongs to the family Boraginaceae. It includes a variety of shrubs,
trees, and herbs, totaling about 2,000 species in 100 genera found worldwide. A
number of familiar plants belong to this family. The Boraginaceae belong, according
to the Angiosperm Phylogeny Group II (APG II), among the euasterid I group
including the orders Gentianales, Lamiales, and Solanales, but whether they should be
assigned to one of these orders or to their own (Boraginales) is still uncertain. Under
the older Cronquist system they were included in the Lamiales, but it is now clear that
they are no more similar to the other families in this order than they are to families in
several other asterid orders. The Boraginaceae are paraphyletic with respect to
Hydrophyllaceae and the later is included in the former in APG II system. In some
recent classifications the Boraginaceae are broken up into several families:
Boraginaceae s.s., Cordiaceae, Ehretiaceae, Heliotropiaceae, Hydrophyllaceae, and
Lennoaceae.
Most though not all members of this family have hairy leaves. The coarse character of
the hairs is due to Silicon dioxide and Calcium carbonate. In some species,
Anthocyanins cause the flowers to change their color from red to blue when aging.
This is likely used as a signal to pollinators that these old flowers are depleted of
pollen and nectar (Hess etal, 2005).
Cordia is a genus of shrubs and trees in the borage family, Boraginaceae. About 300
species have been identified worldwide, mostly in warmer regions. Many of the
species are commonly called manjack. Many Cordias have fragrant showy flowers
and are popular in gardens, although they are not especially hardy. Like most other
Boraginaceae, most have hairy leaves.
Cordia species are used as food plants by the larvae of some Lepidoptera species
including Endoclita malabaricus and two bucculatricid leaf-miners recorded solely
from Cordia: Bucculatrix caribbea and Bucculatrix cordiaella. A number of the
tropical species have edible fruits, known by a wide variety of names including
clammy cherries, glue berries, sebesten, or snotty gobbles. In India, the fruits of local
species are used as a vegetable, raw, cooked, or pickled, and are known by many
names, including lasora in Hindi. One such species is Cordia dichotoma (fragrant
manjack), which is called gunda in Hindi and lasura in Nepali. The fruit of the
fragrant manjack is called phoà-pò·-chí.
Some of the Cordia species having medicinal use include; Cordia myxa, Cordia
multispicata, Cordia verbanaceae, Cordia fragrantissima, Cordia latifolia, Cordia
spinescens, Cordia linnaei, Cordia piauhiensis, Cordia salicifolia, Cordia francisci,
Cordia alliodora, Cordia trichotoma, Cordia globosa, Cordia gilletii, Cordia
wallichii, Cordia sapinensis, Cordia superba, Cordia rufescens, Cordia
leucomalloides and Cordia curassavica etc. (Germplasm Resources Information
http://www.ars-grin.gov/cgi-bin/npgs/html/genus.pl?2921)
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Taxonomy of C. macleodii:
Domain: Eukaryota
Kingdom: Plantae
Subkingdom: Viridaeplantae
Phylum: Tracheophyta
Subphylum: Euphyllophytina
Infraphylum: Radiatopses
Class: Magnoliopsida
Subclass: Lamiidae
Superorder: Solananae
Order: Boraginales
Family: Boraginaceae
Subfamily: Cordioideae
Genus: Cordia
Specific epithet: macleodii - Hook.f. & Thomson
Botanical name: - Cordia macleodii Hook.f. & Thomson
Cordia macleodii (Griff) Hook. F. & Thomas, is commonly known as Dahiphalas or
Dahivan in Hindi and Bhoti in Marathi (Prajapati etal., 2003). It is an 8-10 m high tree
with a corky grey bark. The leaves are broad ovate, 5 – 10 cm as long as broad,
scabrous, base cordate and crenate-serrate margins. They are arranged alternate to
subopposite. The flowers are white in colour and polygamous, in short terminal
axillary corymbs. The calyx is densely tomentose the corolla lobes are oblong in
shape and 0.6 to 0.8cm long. The drupes are 1.2 to 1.9 cm long, ovoid, acuminate at
apex, seated at persistent calyx. The flowers and fruits appear in February – August
((Patil, 2003)).
Synonyms:
Language
Hindi
Marathi
Oriya
Tamil
Telugu
Kannada
Vernacular Name
Dhengan, Dahipalas, Gonni, Kuhman
Daiwas, Dhalm, Bhoti, Dhaim, Dhaiwan, Dhaman
Borolo
Palandekku
Peddabatuva, Pedda Batava, Iriki, Pedda Botuku, Botuku,
Peddabattava, Peddabotuku
Bili challe, Gaavudi, Haadaga, Moddasi, Billikalle, Kalle,
Bilicalle, Bilicellu, Calle, Cellu, Doddacalle, Doddasale,
Gavudi, Hiricalle, Hiricellu, Hirisele, Moddhasi, Challu,
Dodda Challe, Gowdi, Hadang, Hirichalle, Modhasi
Distribution:
Cordia macleodii is frequently distributed in the deciduous forests of Akola, Dhule,
Nandurbar, Amravati, Kolhapur, Nagpur, Nasik, Pune, Raigarh, Satara Thane and
Yavatmal Districts of Maharashtra. Traditionally the bark of C. macleodii has been
used in the treatment of jaundice (Ambasta, 1994).
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1.2 Leucas ciliata:
Leucas ciliata belongs to the family Lamiaceae. Lamiaceae (Labiatae) also known as
the mint family, is a family of flowering plants. It has been considered closely related
to Verbenaceae but several recent phylogenetic studies have shown that numererous
genera classified in Verbenaceae belong instead in Lamiaceae, whereas the core
genera of Verbenaceae are not closely related to Lamiaceae and are more closely
related to other members of the Lamiales. The enlarged Lamiaceae family contains
233 to 263 genera and 6900 to 7200 species (Cantino etal 1992, Heywood etal 2007).
The plants are frequently aromatic in all parts and include many widely used culinary
herbs, such as basil, mint, rosemary, sage, savory, marjoram, oregano, thyme,
lavender, and perilla. Some are shrubs or trees, rarely vines. Many members of the
family are widely cultivated, owing not only to their aromatic qualities but also their
ease of cultivation: these plants are among the easiest plants to propagate by stem
cuttings. Besides those grown for their edible leaves, some are grown for decorative
foliage, such as coleus. Others are grown for food purposes, but seeds are utilized
instead
of
leaves,
such
as
with
chia
(Angiosperm
Phylogeny,
http://www.mobot.org/mobot/research/APweb/orders/lamialesweb.htm#Lamiales).
The original family name is Labiatae, so given because the flowers typically have
petals fused into an upper lip and a lower lip. Although this is still considered an
acceptable alternate name, most botanists now use the name "Lamiaceae" in referring
to this family.
The leaves emerge oppositely, each pair at right angles to the previous one (called
decussate) or whorled. The stems are frequently square in cross section, but this is not
found in all members of the family, and is sometimes found in other plant families.
The flowers are bilaterally symmetrical with 5 united petals, 5 united sepals. They are
usually bisexual and verticillastrate (a flower cluster that looks like a whorl of flowers
but actually consists of two crowded clusters).
Some of the Leucas species having medicinal use include; Leucas aspera, Leucas
mollissima, Leucas milanjiana, Leucas inflata, Leucas neufliseana, Leucas
cephalotes, Leucas nutans, Leucas lavandulaefolia, Leucas Mollissima, Leucas hirta,
Leucas neufliseana, and Leucas nutans etc.
Taxonomy of L. ciliata:
Domain: Eukaryota
Kingdom: Plantae
Subkingdom: Viridaeplantae
Phylum: Tracheophyta
Subphylum: Euphyllophytina
Infraphylum: Radiatopses
Class: Magnoliopsida
Subclass: Lamiidae
Superorder: Lamianae
Order: Lamiales
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Family: Lamiaceae
Genus: Leucas
Specific epithet: ciliata
Botanical name: - Leucas ciliata
Leucas ciliata (Benth) belongs to the family Lamiaceae (Labiatae). It is commonly
known as Burumbi. It occurs as herbs or under shrubs 30-100 cm high with stems and
branches obtusely four angled and has brownish hairs. The leaves are ovate or
lanceolate in shape, about 3 – 9cm long and 2.5 - 4 cm wide. The lamina is
membranous, sparsely hairy on both sides with an acute apex, a cuneate base and
serrate margin. The flowers are white in colour and have dense globose whorls. They
have slender spinulose bracts equaling calyx. The calyx is tubular, hairy outside, with
a ring of hairs at mouth and measures 1.2 – 1.8 cm in length. The corolla is long tube
annulate inside and measures about 1.8-2.0 cm in length. The nutlets are smooth
oblong-obvoid in shape and brown in colour. The flowers and fruits appear in May –
August (Patil, 2003).
Synonyms:
Language
English
Marathi, Hindi
Tamil
Vernacular Name
Tufted leucas
Burumbi
Muvilai-p-punnai
Distribution:
L. ciliata is frequently distributed along the ghats and in planes along forest edges in
Ahmednagar, Dhule, Nandurbar, Amravati, Kolhapur, Mumbai, Satara, Sindhudurg
and Thane regions of Maharashtra.
1.3 Antioxidant activity:
Reactive Oxygen Species including free radicals such as superoxide anion radicals
(O2 ), hydroxyl radicals (OH) Non free radicals such as H2O2, Singlet Oxygen (1O2)
along with various form of active oxygen are involved oxidative stress on metabolism
(Finkel 2000). Oxidative stress resulting from the toxic effects of free radicals on the
tissue plays an important role in the pathogenesis of various diseases such as
ischemia, anaemia, asthma, arthritis, inflammation, neuro-degenertion, Parkinson's
diseases, mongolism, ageing process and perhaps dementias (Mahakunakorn etal.
2004, Polterait 1997, Droge 2002). Free radical mechanism is one of the most
important mechanisms of liver damage. Free radical induced lipid peroxidation is
believed to be one of the major causes of cell membrane damage leading to a number
of pathological situations (Haliwell 1993, Oberley 1988, Slater 1984).
Antioxidants are radical scavengers, which protect the human body against free
radicals. They may offer resistance against oxidative stress by scavenging free
radicals, inhibiting lipid peroxidation and by other mechanisms and thus prevent
disease (Miller etal. 1997). They are used to counteract deleterious effects of free
radicals in oxidative stress. Antioxidants also have hepatoprotective activity (Orhan
etal, 2003). A large number of plants and plant products are used for their antioxidant
activity (Aqil F, 2006, Devasagayam, 2004, Khalaf, 2008). Many phyto-constituents
like phenolics, polyphenolics, flavonoids etc. have been reported to have antioxidant
activity (Kähkönen 1999, Lu 2001, Zhonghong 1999).
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1.4 Antimicrobial activity:
Infections diseases are the second leading cause of death world wide. (WHO, 2002).
In industrialized nations, despite the progress made in the understanding of
microbiology and their control, incidents of epidemics due to drug resistant
microorganisms and the emergence of hitherto unknown disease-causing microbes,
pose enormous public health concerns (Iwu etal., 1999). The emergence of multidrugresistant bacteria has created a situation in which there are few or no treatment options
for infections with certain microorganisms (Wenzel etal., 2000)
Fungal infections remain a significant cause of morbidity and mortality despite
advances in medicine and the emergence of new antifungal agents (McNeil etal.,
2001). Many plants have been reported to have antifungal activity (Parekh, 2008,
Ertürk 2006).
Although the need for new antimicrobials is increasing, development of such agents
faces significant obstacles (Gilbert etal., 2002). A number of factors make
antimicrobial agents less economically attractive targets for development than other
drug classes. (Spellberg etal., 2004) Pharmaceutical research and development costs,
which are estimated to be $400–$800 million per approved agent (DiMasi etal.,
2003), pose a considerable barrier to new drug development in general.
Historically, plants have provided a good source of anti-infective agents; emetine,
quinine, and berberine remain highly effective instruments in the fight against
microbial infections. Phytomedicines derived from plants have shown great promise
in the treatment of intractable infectious diseases including opportunistic AIDS
infections. Plants containing protoberberines and related alkaloids, picralima-type
indole alkaloids and garcinia biflavonones used in traditional African system of
medicine, have been found to be active against a wide variety of micro-organisms.
(Iwu etal., 1994)
1.5 Hepatoprotective activity:
Liver is an important organ and is actively involved in many metabolic functions is
the frequent target of a number of toxicants. Though it has innate mechanisms like
tissue glutathione to scavenge the toxicants, they are at times overrun and lead to
hepatic damage. (Qureshi etal, 2007) Many drugs and chemicals such as barbiturates,
chlorpromazine, ethionine, erythromycin, paracetamol, tetracyclines, thioacetamide,
alcohol, carbon disulfide, carbon tetrachloride etc. have been reported to cause liver
disorder. (Meyer etal., 2001)
A number of recent reports clearly demonstrated that in addition to hepatic problems,
CCl4 also causes disorders in kidney, lungs, testis and brain as well as in blood
generating free radicals (Chaurbonneua etal., 1986, Ahmad etal.., 1987, Ohata etal,
1997, Ozturk etal, 2003). Lipid peroxides produced from unsaturated fatty acids via
radicals, cause histotoxicity and promote the formation of additional free radicals in a
chain reaction type. It is thought that, if the in vivo activity of enzymes or scavengers
is not high enough to inhibit the radicals, various diseases such as liver disease,
diabetes and accelerated aging may result (Niki, 1995). In the modern medicine,
plants occupy significant berth as raw materials for some important drug preparations
(de Mejia etal., 2002, Iwu etal., 1994, Chopra etal., 1986). The traditional Indian
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medicinal plants act as antiradicals and DNA cleavage protectors (Russo etal.,
2001).Moringa oleifera (Pari etal., 2002), Eclipt alba (Singh etal., 2001), Phyllanthus
niruri (Syamasundar etal., 1985, Venkateswaran etal., 1987, Unander etal., 1995),
Picrorhiza kurroa (Chauhan etal., 1992) possess hepatoprotective property against
toxins and drugs induced hepatotoxicity.
1.6 Anti-inflammatory activity:
Inflammation, though a defense mechanism, owing to its tendency to induce, maintain
and even aggravates several diseases, has always been a matter of concern for the
physicians. It is a complex pathophysiological response of tissue to injury leading to
local accumulation of plasmic fluid and blood cells (Sosa etal, 2002). Although scores
of anti-inflammatory agents are available, the search for better anti-inflammatory
agents continues to avert the side effects of the available agents (Rainsford etal,
1980). Many traditionally used plants have been claimed to have anti-inflammatory
potential (Chaterjee etal, 1984). Flavonoids which are ubiquitously present in plants,
are reported to have anti-inflammatory activity (Ferrandiz etal, 1991). Several plants
containing flavonoids have been studied for anti-inflammatory effect.
1.7 Analgesic activity:
Pain is an unpleasant sensory or emotional experience associated with actual or
potential tissue damage, or described in terms of such damage as defined by the
International Association for the Study of Pain.
Acute pain is a physiological response that warns us of danger. The process of
nociception describes the normal processing of pain and the responses to noxious
stimuli that are damaging or potentially damaging to normal tissue. (Pasero etal.,
1999). This noxious stimulation causes a release of chemical mediators from the
damaged cells including:






Prostaglandin;
Bradykinin;
Serotonin;
Substance p;
Potassium;
Histamine.
Chronic pain can be a major problem for some people and affect their quality of life.
It can be caused by alterations in nociception, injury or disease and may result from
current or past damage to the peripheral nervous system (PNS), CNS, or may have no
organic cause (Calvino etal., 2006).
The exact mechanisms involved in the pathophysiology of chronic pain are complex
and remain unclear. It is believed that following injury, rapid and long-term changes
occur in parts of the CNS that are involved in the transmission and modulation of pain
(nociceptive information) (Ko etal., 2004).
Analgesics are the substances, which decrease pain perception by increasing threshold
to painful stimuli. Severe pain due to cancer metastases needs the use of strong
analgesics like opioids. The addiction liability of opioid analgesics led to intensive
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research for the compounds without this side effect. Pain is a common phenomenon in
all animals, at least in vertebrate animals, similar to that felt by man. Analgesic effects
in animals are comparable with the therapeutic effects in man. Painful stimuli can
consist of direct stimulation of the efferent sensory nerves or stimulation of pain
receptors by various means such as heat or pressure (Vogel etal., 1997). Many plants
have been reported to have good analgesic activity (Sutar etal., 2008, Pooja etal.,
2007).
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