Credibility of Folklore Claims on the Treatment of Malaria in North-East India with Special Reference to Corroboration of their Biological Activities

Ipomoea reniformis Chaos is claimed in Indian traditional medical practice to be useful in the treatment of epilepsy and neurological disorders. In the present study, pretreatment effect of methanolic extract of Ipomoea reniformis on epilepsy and psychosis was evaluated in rodents using standard procedures. Bes des evaluating epileptic and behavior l parameters, neurotransmitters such as Gamma-Amino Butyric Acid (GABA) in epilepsy and in psychosis dopamine, noradrenaline and serotonin contents in the rodent brain were estimated. The extract pretreatment reduced maximal electro shock; Isoniazid (INH) and Pentylenetetrazole (PTZ) induced seizures and also significantly inhibited the attenuation of brain GABA levels by INH and PTZ in mice. These results suggested that the observed beneficial effect in epilepsy may be by enhancing the GABAergic system. The test drug also inhibited the apomorphine induced climbing and stereotyped behavior and showed significantly reduced levels of brain dopamine, noradrenaline and serotonin which may be due to blocking of central dopaminergic, noradrenergic and serotonergic pathways or by enhancing the GABAergic system. The results obtained in present study suggest that the title plant possesses antiepileptic and antipsychotic activities in rodents.


Introduction
Ipomoea reniformis (IR) also called as merremia emarginata (Burm. f.) is a procumbent herb belonging to the family convolvulaceae. In India, it is commonly known as Undirkana and Mushakparni. The plant is widely distributed in India, Sri Lanka, Philippines, Malaysia, Tropical Africa and mainly grows in rainy and winter season. In India, it is found in Southern part mainly counting Chennai, and some places of Andhra Pradesh [1]. Traditionally, IR has been used to treat diverse clinical conditions ranging from pain; fever to neurological disorders [2]. IR has been claimed to be useful for inflammation, headache, fever, cough, neuralgia, rheumatism and also in liver and kidney diseases [3]. The powder of leaves is used as a snuff during epileptic seizures. Juice acts as purgative and the root is having diuretic, laxative actions and applied in the disease of the eyes and gums [4].
The plant contains various neuroprotective chemical constituents such as caffeic, p-coumaric, ferulic and sinapic acid esters. Petroleum ether extract contains fats and fixed oil while aqueous extract contains amino acids, tannins (condensed and pseudo tannins) and starch [5]. IR has been reported to possess various pharmacological actions, mainly antidiabetic [6], antiinflammatory [7], nephroprotective [8], antibacterial [9], antioxidant and antimicrobial activity [10]. Further, the principle constituents of IR such as sinapic and ferulic acids have exhibited behavioural and pharmacological

Introduction
Malaria, caused by Plasmodium species is one of the most severe diseases in the world that kills over 1 million people every year with some 3.2 billion people living in 107 countries or territories currently at risk 1 . The main reasons that explain this worsening situation approach combining botanical, ethnobotanical, phytochemical and biological techniques. Plants continue to provide us new chemical entitities (lead molecules) for the development of drugs against various pharmacological targets, including malaria 7 . Since the discovery of quinine, a number of anti-malarial agents both of plant origin and synthetic have been developed. However, appearance of Plasmodium strains, resistance to these drugs one after another, has made the problem most critical one and triggered intensive efforts on the part of researcher world over to search for alternative agents of batter quality on one hand, and to develop potentiating combinations of the currently used drugs, to prevent the situation from further deterioration, on the other [8][9][10] . At the same time the ethnopharmacology approach used in search for new anti-malarial compounds appears to be predictive 11 .
The North-East region of India situated between 21 0 34 'N to 29 0 50 'N latitude and 87 0 32 'E to 97 0 52 'E longitudes and covers an area of about 262060 sq km. 12 . The area known for its rich flora 13 comprising the states of Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Tripura and Sikkim which includes hills and plains and extends from sea level to snow line, holds approximately 50 percent of the total flora of India with the number of species ranging from 6000-7000 14 . This area of India is also homeland of people belonging to more than 150 ethnic groups (tribal or tribal in origin), including 22 percent aboriginal people 15 . About 90 percent of the total population of the region has a rural background and most of them still live in remote, isolated areas, maintaining individual identities and a primitive economic life 16 . Traditional agriculture is the primary live hood of these people and these people depend mostly upon surrounding plant resources for day to day needs including medicaments.
Over the last few decades, a large number of ethnomedico-botanical explorations has been conducted in the region and information has been collected on the local use of a large number of plants for the treatments of a large number of diseases including malaria 10,[17][18][19][20][21] . Unfortunately the information has been scattered in a wide range of professional journals and periodicals, making the data mostly not easily accessible to researchers. The present communication is a review based on the plant species from Northeastern India used for the treatment of malaria and related diseases reported from the region.

Materials and Methods
Ethno-medico-botanical case studies reported from North-East India up to the year 2008 were reviewed and the reports on prescriptions using plant species for the treatment of malaria were collected. These references are critically examined for the prescriptions referred for the treatment of malaria and not to include general antipyretic plants. A review of literatures pertaining to biological activities of these the plant species was also conducted to verify the validity of the folklore claims and to find out direct or indirect corroboration with the biological activities; so that pharmacological evaluation of those plant species against Plasmodium strains may be prioritized, for which no direct corroboration was found and for which reports are scarcely available.

Results
The plant species with their ethnic uses are arranged prescription wise. For each plant species described, the botanical name followed by family, vernacular name and the name of ethnic community who uses the plant species are provided. Parts of the plant used, method of preparation or formulation and mode of administration along with dosage of folk medicines are listed in Table 1 with their respective references. In Table 2, corroborative biological activities i.e., anti-malarial activity of the cited medicinal plant species available are also given. The table includes only those species whose anti-malarial activity was reported.

Discussion and Conclusion
The present study has brought into light 64 prescriptions of plant folk medicines represented by 74 plant species under 67 genera and 42 families, which have been in use among the ethnic communities in North-East India, for the treatment of malaria and related diseases. Most of the drugs (87.5%) are prepared using single plant species; however, plant species used in combinations are also accounted for 12.5% of the formulations. Most of the preparations are orally administered either as extract, juice and decoction or infusion. The harder In Azadirachta indica leaves have antimalarial properties, but folk claim is obtained for fruits also along with leaves. Likewise in Clerodendrum infortunatum tender shoots are used by the folk healers, but only leaf extract is reported to possess antimalarial activity. Alstonia scholaris Stem bark Echitamine chloride isolated from bark exhibits antimalarial activity in a rodent system infected with Plasmodium berghei. Methanolic extracts of the plant parts also shows pronounced antiplasmodial activity 54,55 Andrographis paniculata

Leaves
Ethanolic and Choloform extracts of show antimalarial activity 56,57 Azadirachta indica Leaves and fruits Leaf extract found to have antimalarial activity. Oral administrations of 0.1 and 0.2 gm/kg of the water extracts of leaves in albino mice are also reportedly found active against acute Plasmodium yoelli nigeriensis infection 58,59 Caesalpinia bonduc Tender twigs and seeds Beta-caesalpin isolated from the plant parts and the seed extracts exhibit antimalarial activity in a rodent test system with Plasmodium berghei 54 Cassia occidentalis Roots Mixture of five plants of a traditional antimalarial formulation including roots of Cassia occidentalis exhibits antimalarial activity.
The ethanolic extracts of leaves of C. occidentalis also exhibit antimalarial activity 60,61

Clerodendrum infortunatum
Tender shoots Leaf extracts possess antimalarial activity. The most potent dose has been reported to be 150mg/kg bw 62 Coptis teeta Rhizomes Rhizome extract shows antimalarial activity. Berbarine isolated from the rhizome also possess antimalarial activity 13,63 Cyperus rotundus Tuber Tubers possess antimalarial activity 64 Tinospora cordifolia Stem juice Both stem and roots possess antimalarial activity. Berberine isolated from aerial parts of the plants also exhibits antiprotozoal activity 65,66 Dichroa febrifuga Roots The alkaloid, febrifugin isolated from the root and leaves shows 100 times as active as compared to quinine, against Plasmodium lophurae 8

Eucalyptus globulus
Leaves and stem bark Essential oil possesses in vitro antimalarial activity on two strains of Plasmodium falciperum 67 Lantana camara Bark or whole plant Extract exhibits antimalarial activity 64

Ocimum tenuiflorum Leaves
Aqueous extracts of the leaves tested in vivo against Plasmodium berghei show antimalarial activity. Inhalation therapy to cure Plasmodium vivax and Plasmodium falciperum infections has also been suggested 68,69,70 Nyctanthes arbor-tristis Leaves Ethanolic extracts of aerial parts shows antimalarial activity 71 Terminalia bellerica Fruits A bioactivity -guided fractionation of an extract of fruit rind led to the isolation of two new lignans named termilignan and thannilignan, together with 7-hydroxy-3' ,4'-(methylenedioxy) flavan and anolignan B. These compounds possess antimalarial activity in vitro 72