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Todays complementary medicine is northing but the way of healing of illnesses which is generally originating during ancient societies. A lot of of the traditional medicinal systems are based on centuries of practices by healers involving sound fundamental principles. A holistic approach to the welfare of human's body, mind and the spirit is a common factor which noted in a number of traditional systems1.
1.1 Natural products
Natural products have provided the inspiration for most active ingredients in medicine. Natural products served as an important source of drugs since ancient times and about 67% of today's useful drugs are derived from natural sources2. Plant-based drugs have been used worldwide in traditional medicines for the treatment of various diseases. Recently the information derived from folk medicinal uses of the various plants has become of improved interest in search for new curative agent. Approximately 10,000 of world plants have documented medicinal use3. In Indian history, the uses of plants (about 2000 species) for therapeutic purposes have been mentioned in several books of Ayurveda. The other systems of medicines such as Homeopathy, Siddha, Unani, and Aromatherapy also use plants for therapeutic purposes4.
Still plant species are serves as a rich resource of many new bioactive molecules, but, very few plant species have been scrupulously investigated for their therapeutic properties5. World Health Organization WHO has considered 252 drugs as basic and vital, out of 11% are entirely from plant origin and a considerable numbers of synthetic drugs are obtained from natural precursors6 and were originally synthesized to mimic the action of molecules found in nature7. Natural compounds are highly diverse and often provide highly specific biological activities. This follows from the proposition that essentially all natural products have some receptor binding capacity8. Thus, there is renewing interest in phytomedicines during last decade and now days several medicinal plant species are being evaluated for possible pharmacological activities.
Medicinal plants are having diverse type of curative properties due to the occurrence of a variety of composite chemical substances of diverse chemical compositions which are found as secondary plant metabolites in one or more plant parts 9. Such plant metabolites according to their composition are grouped in various classes such as alkaloids, glycosides, tannins, terpenoids, flavonoids, proteins, carbohydrates etc. The modern techniques for isolation, separation, structural explanation, screening and combinatorial production have led to renaissance of various plant products as source of new drugs.
With recognized potential in drug discovery and development and molecular diversity are an example of biologically active compounds obtained from natural resources. 10. The natural products might be a foremost source of new drug leads is obvious, since, in between 1983-1994 the 520 new drugs has been approved and among them nearly 39% were natural products and their derivatives. A study accounted in 1997 stated that 85% of the healing regimes of 80% of the World's population are basically of natural origin. Moreover, approximately 20 top selling drugs in 1999 were developed from or derived on the basis of leads available from information of properties of natural plant products may from traditional use or modern studies.
Currently, in the process of drug discovery and development of computational methods are having progressively larger and key role and are supposed to offer means of better effectiveness for the industry. The total Expenditure of computer modeling and simulations for Pharmaceutical R & D was 10 % and further they might be rise to 20 % by 2016. They are projected to limit and focus on chemical synthesis as well as biological testing and thus greatly decline traditional resource requirements11.
1.2 Current status of herbal compounds
Plants have been one of the important sources of medicines even since the dawn of human civilization. In spite of tremendous development in the field of medicine during the 20th century, plants still remain to be one of the major sources of drugs in the modern as well as traditional systems throughout the world. Over 60% of all pharmaceuticals are plant-based.12 Natural products are the rich source of biologically active compounds and an example of molecular diversity, with recognized potential in drug discovery and development. Its chemistry should complement on a synergistic perspective, since nature continues to be the most diverse and active compound library known.10 An upturn of attention in medicinal plants has takes place during the last 2 decades. Botany and ethnopharmacology aim at preserving knowledge of plants traditionally used in therapy. These plants continue to represent a better source for pharmacological screening, chemical analysis, and also clinical trial.13
Herbal extracts and isolated phytoconstituents have significantly contributed to the discovery of new drugs and have served as drugs themselves. Natural products constitute a major fraction of drugs in the market and even synthetic drugs owe their origin to the natural resources.
Ephedrine was the first compound from chinese herbs to enter the western market, an amphetamine like stimulant from ma huang (Ephedra sinica). The next was artimisinin, a potent antimalarial from qinghao (Artemisia annua).14, 15
An IND application of Lupin Ltd. is in process and a US patent has been granted for development of herbal-derived antipsoriatic compound which containing Argemone mexicana. Standardized fraction of gugulipid developed by CDRI from Commiphora wightii has been marketed (Guglip, Cipla Ltd) for treating hyperlipidemia and atheriosclerosis .
Regional research laboratory (RRL), Jammu has commercialized gum resin as NSAID (Non-Steroidal Anti-Inflammatory Drug) (Sallaki-Gufic) from Boswellia serrata.
There are some approved drugs from plant origin viz. Apomorphine hydrochloride which is a dopamine receptor agonist isolated from Papaver somniferum, Tiotropium bromide isolated from Atropa belladonna (Solanaceae) & used for the treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD).
Nitisinone from Callistemon citrinus has been used successfully as a treatment of hereditary tyrosinaemia type 1 (HT-1), Galantamine hydrobromide from Galanthus nivalis used for neurological conditions and arteether is antimalarial agent isolated from Artemisia annua (Asteraceae).
Plant-derived compounds currently in clinical trials are combretastatin A4, Ingenol 3- O - angelate, Phenoxodiol, Protopanaxadiol, Triptolide, genistein, various forms of retinoic acid (over 100 clinical trials in progress), tea/epigallocatechin gallate, resveratrol etc.14,16 Several known compounds have already been shown to act on newly validated moleclular targets which were isolated from traditionally used medicinal plants, as exemplified by indirubin, which selectively inhibits cyclin dependent kinases and kamebakaurin, which has been shown to inhibit NFÎºB and betulinic acid, with selective melanoma cytotoxicity through the activation of p38.16
This trend is observed equally in the case of anti-inflammatory drugs. There are numerous compounds in the indigenous herbs, which remain to be systematically evaluated for their biological potentials. Major clues regarding the drug ability of the phytoconstituents lay in the folk remedial use of such plants and extracts.
Thespesia populnea is a plant that has attracted attention of phytochemists and pharmacologists due to its interesting and very potent biological activities.
1.3 Hyperlipidemic disorders: an introduction
Hyperlipidemia is characterized by raised serum triglyceride, total cholesterol, very low density and low-density lipoprotein cholesterol and decreased high-density lipoprotein levels. Hyperlipidemia is associated with lipid disorders which are considered to cause atherosclerotic cardiovascular disease17. Atherosclerosis is a disease that involves the interplay of several factors. There are three main issues to be addressed in atherosclerosis, viz., hyperlipidemia, clotting factors and oxidation of lipoproteins. These factors collectively contribute to the development and rupture of atherosclerotic plaque18. To reduce the increasing risk of ischemic heart disease or the incidence of further cardiovascular disease is the main aim in the treatment of hyperlipidemia19. Currently marketed drugs fail to give 100 % protection against these CVS complications but possess various serious side-effects. Additionally, Gastric irritation, hyperuricemia, diarrhoea, myositis, nausea, abnormal liver function, flushing and dry skin are observed due to the consumption of synthetic drugs20. The traditional systems have immune potential against a variety of diseases. Various pharmacological properties of more than thirteen thousand plants have been studied. The relatively cheap and locally available herbal treatments for hypercholesterolemia have no major side effects and are very much effective in reducing the lipid levels in body 21.
Inflammation is a pathological response by living tissues to injuries that will leads to the accumulation of extracellular fluid and different blood cells. However, it is protective mechanism of body; the many complex events and several mediators concerned in inflammatory reactions can induce, maintain or aggravates many diseases22. In analysis, the research during the last few decades, have estimated that the analgesics are one of the highest therapeutic categories on which research efforts are concentrated23. Still available analgesic compounds in the market have presented a broad range of undesired effects24 hence, leaving an unlocked door for new as well as better natural compounds. With potential curative properties natural products are thought to be an essential source of new chemical substances 25.
Thus the demand for the plant derived drugs is enhanced. It is true that, for acute ailments there is no crude drug. However with no harmful side effects plant preparations are often considered to be useful for the treatment of less serious disease, for the supportive treatment of chronic diseases, for the treatment over long periods of time and possibly for prophylytic medication. Thus, medicinal plants continue to receive attention of scientists for their chemical and pharmacological investigation in India and abroad. Besides these, the studies on folk medicines through ethno botanical surveys are gaining importance in present day as these reveal new biodynamic compounds of therapeutic value.
1.4 Introduction to plant
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Fig 1.1: Thespesia populnea flowers
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Fig 1.2: Thespesia populnea root
1.4.1 Botanical information:26
Kingdom: Plantae (Planta, plants, Vegetal)
Subkingdom: Tracheobionta (Vascular plants)
Division: Magnoliophyta (Angiosperms, flowering plants)
Class: Magnoliopsida (Dicots, dicotyledons)
Family: Malvaceae (mallows, mauves)
Genus: Thespesia Soland. ex Correa
Species: Thespesia populnea (L.) Soland. ex Correa.
1.4.2 Vernacular names:
English: Portia Tree, Tulip tree, Umbrella tree. Sanskrit: Gardha-bhanda. Hindi: Parsipu, porush, paras-pipal, gajadanda. Bengali: Dumbla, parespipal, palaopipal, gojashuni. Marathi: Parsacha-jhada, bhendi-ke-jhar. Gujarat: Paarsapeepala. Telugu: Gangaraavi, munigangaraavi, gangareenu. Tamil: Poovarasam kallal, cheelanthi. Kannada: Hoovarase, kandarola, adavi-bendi, jogiyarale. Malayalam: Poovarasu
1.4.3 Morphological characterisitics:27
Leaves: 7.5-15 cm. Long, broadly ovate, cordate, acuminate, entire, smooth, finely reticulately veined, with 5-7 prominent nerves and often a glandular pore in one or more of the intercostal spaces beneath, sometimes with a few minute peltate scales on one or both surfaces; petioles 5-10 cm.
Flower: Solitary, yellow with purplish centre; Calyx truncate, entire. Petals are five, convulate. Staminal tube toothed at the top, clothed except at the swollen base with the free ends of the filaments. Ovary are five celled; ovules two-three in each cells, styles club-shaped; stigma clavate.
Fruit: Capsules globose, 2.5 cm. diam., covered with minute peltate scales, surrounded at the base by the persistent calyx. Seeds 1 cm. long, ovoid, channeled along the back, pubescent.
Bark: grey to brown, fissured often knobby, fibrous, c. 4.0mm.
1.4.4 Habitat and local use:
Widely distributed throughout the Coast forest of India and Burma, largely grown as a roadside tree in tropical regions. The tree is largely cultivated for ornament and shade, and its blooms throughout the year in the tropics. It can grow everywhere including saline soils, except in hilly areas, but prefers light and porous soils. It thrives in moist and warm situations, but can withstand temperatures as low as -40C. It can easily be raised from the seed or cuttings, the former being preferable. The seed retains its viability even after a prolonged exposure to salt-water. The seed-raised trees are better and more erect than those from the cuttings; the timber from the seed-raised trees being knot-free, straight and even-grained and tough.
The growth is rapid. This tree is much valued on account of the toughness of its timber, which is used for carriage building. Coast forests of India and Burma, largely grown as a roadside tree in tropical regions. Also in China, the Malay Archipelago, the Society Islands, Mauritius, Mozambique, Upper Guinea and Philippines Islands. In hills of satpuda from Nandurbar & Nashik district tribal peoples are using this plant as folk treatment for healing of wounds. 26, 27
1.4.6 Different Species of Thespesia:
Thespesia garckeana (syn. Azanza garckeana) it an African tree whose fruits is used as food by native populations but is also used for its timber.28
Thespesia grandiflora (formerly known as Montezuma speciosissima or Maga grandiflora), common name 'Maga', is an endemic species of Puerto Rico.29
Thespesia populneoides Along with T. populnea, commonly known as 'Pacific Rosewood' and this species are listed on an Australian site about the plants which are used for timber. It is generally confused with T. populnea, from which it differs, among other characteristics, such as it having dehiscent fruits (the pods open when mature to release the seeds). T. populneoides is described as an attractive tree to 15 m (49 feet) with light-green and having heart-shaped leaves. It has hibiscus-like yellow flowers which are, fading to pink and small fruit.30
Thespesia thespesioides plant having a high concentration of gossypol. It is one of the species associated with mangroves in Australia. Aborigines are also used this plant for its medicinal properties and for tools.31
Fig 1.3: Difference between shape of leaves of T. populnea & T. populneoides
Considering folk claim of T. populnea we decided to investigate the flower and root of the plant for their anti-inflammatory, antinociceptive, anti-arthritic, hypolipidemic and antihyperlipidemic and anti-oxidant activities. The present investigation was undertaken to demonstrate the pharmacological potential of T. populnea by using various in-vivo and in-vitro models.
According to the regulations by various governing authorities, regarding the experimentation involves the animal study; the sample size (number of animal) was kept permissible. In certain situations the study was performed with restrictive study groups to avoid the redundant results as well as use of animals. All the necessary procedure was followed during the handling, housing and feeding animals. Furthermore, the successful attempt was made to rehabilitation (might be use for another activity) of the animals instead of scarification.