The need for an alternative drug for malaria initiated intensive efforts for developing new antimalarials from indigenous plants. The information from different tribal communities of northeast India along with research papers, including books, journals and documents of different universities and institutes of northeast India was collected for information on botanical therapies and plant species used for malaria. Sixty-eight plant species belonging to 33 families are used by the people of northeast India for the treatment of malaria. Six plant species, namely, Alstonia scholaris, Coptis teeta, Crotolaria occulta, Ocimum sanctum, Polygala persicariaefolia, Vitex peduncularis, have been reported by more than one worker from different parts of northeast India. The species reported to be used for the treatment of malaria were either found around the vicinity of their habitation or in the forest area of northeast India. The most frequently used plant parts were leaves (33%), roots (31%), and bark and whole plant (12%). The present study has compiled and enlisted the antimalarial plants of northeast India, which would help future workers to find out the suitable antimalarial plants by thorough study.
Alkaloids; malaria; medicinal plants; mosquito repellents; northeast India; traditional knowledge of medicine
The Pahans and the Telis are two of the smallest indigenous communities in Bangladesh. The Pahans, numbering about 14,000 people are widely scattered in several northern districts of the country, while the Telis are such a small community that nothing has been reported on their numbers and lifestyle. Both tribes are on the verge of disappearance. One each of the Pahan and the Teli community was located after much search in two adjoining villages of Natore district, Bangladesh. Since the tribes were found to still depend on their traditional medicinal practitioners for treatment of ailments, it was the objective of the present study to document their traditional usage of medicinal plants and to evaluate such plants against modern research-based pharmacological activity studies on these plants. Interviews were conducted of the practitioners of the Pahan and Teli community of Natore district with the help of a semi-structured questionnaire and using the guided field-walk method. Plant specimens as pointed out by the practitioners were collected and pressed on the field and identification completed at the Bangladesh National Herbarium. The Pahan tribal practitioners used 13 plants distributed into 9 families for treatment of 14 different ailments. The Teli tribal practitioner used 15 plants divided into 14 families for treatment of 17 different ailments. Eight out of the thirteen plants used by the Pahan tribal practitioner (61.5%) had reported relevant pharmacological activities in the scientific literature, while six out of the fifteen plants used by the Teli tribal practitioners (40%) had such relevant pharmacological activities in accordance with their usage. The medicinal plants used by the Pahans and Telis warrant further scientific studies toward discovery of lead compounds and efficacious drugs and the documentation and protection of the traditional medical knowledge held by these tribes.
Asian medicine; CAM; ethnomedicine; alternative therapy
Malaria remains one of the leading public health problems in Cameroon as in other parts of Sub-Saharan Africa. In the past decades, this situation has been aggravated by the increasing spread of drug-resistant Plasmodium falciparum strains. New antimalarial drug leads are therefore urgently needed. Traditional healers have long used plants to prevent or cure infections. This article reviews the current status of botanical screening efforts in Cameroon as well as experimental studies done on antimalarial plants. Data collected from 54 references from various research groups in the literature up to June 2007 shows that 217 different species have been cited for their use as antimalarials in folk medicine in Cameroon. About a hundred phytochemicals have been isolated from 26 species some among which are potential leads for development of new antiamalarials. Crude extracts and or essential oils prepared from 54 other species showed a wide range of activity on Plasmodium spp. Moreover, some 137 plants from 48 families that are employed by traditional healers remain uninvestigated for their presumed antimalarial properties. The present study shows that Cameroonian flora represents a high potential for new antimalarial compounds. Further ethnobotanical surveys and laboratory investigations are needed to fully exploit the potential of the identified species in the control of malaria.
Diabetes mellitus is an endocrinological disorder arising from insulin deficiency or due to ineffectiveness of the insulin produced by the body. This results in high blood glucose and with time, to neurological, cardiovascular, retinal and renal complications. It is a debilitating disease and affects the population of every country of the world. Around 200 million people of the world suffer from this disease and this figure is projected to rise to 300 million in the coming years. The disease cannot be cured with allopathic medicine as the drugs used do not restore normal glucose homeostasis and moreover have side-effects. On the other hand, traditional medicinal practitioners of various countries claim to cure diabetes or at least alleviate the major symptoms and progression of this disease through administration of medicinal plants. The Garos are an indigenous community of Bangladesh, who still follow their traditional medicinal practices. Their traditional medicinal formulations contain a number of plants, which they claim to be active antidiabetic agents. Since observation of indigenous practices have led to discovery of many modern drugs, it was the objective of the present study to conduct a survey among the Marakh sect of the Garos residing in Mymensingh district of Bangladesh to find out the medicinal plants that they use for treatment of diabetes. It was found that the tribal practitioners of the Marakh sect of the Garos use twelve medicinal plants for treatment of diabetes. These plants were Lannea coromandelica, Alstonia scholaris, Catharanthus roseus, Enhydra fluctuans, Terminalia chebula, Coccinia grandis, Momordica charantia, Cuscuta reflexa, Phyllanthus emblica, Syzygium aqueum, Drynaria quercifolia, and Clerodendrum viscosum. A review of the scientific literature demonstrated that almost all the plants used by the Garo tribal practitioners have reported antidiabetic and/or antioxidant properties and have enormous potential for possible development of new and efficacious antidiabetic drugs.
Diabetes; CAM; ethnomedicine; Garo
Malaria is the third leading cause of death due to infectious diseases affecting around 243 million people, causing 863,000 deaths each year, and is a major public health problem. Most of the malarial deaths occur in children below 5 years and is a major contributor of under-five mortality. As a result of environmental and climatic changes, there is a change in vector population and distribution, leading to resurgence of malaria at numerous foci. Resistance to antimalarials is a major challenge to malaria control and there are new drug developments, new approaches to treatment strategies, combination therapy to overcome resistance and progress in vaccine development. Now, artemisinin-based combination therapy is the first-line therapy as the malarial parasite has developed resistance to other antimalarials. Reports of artemisinin resistance are appearing and identification of new drug targets gains utmost importance. As there is a shift from malaria control to malaria eradication, more research is focused on malaria vaccine development. A malaria vaccine, RTS,S, is in phase III of development and may become the first successful one. Due to resistance to insecticides and lack of environmental sanitation, the conventional methods of vector control are turning out to be futile. To overcome this, novel strategies like sterile insect technique and transgenic mosquitoes are pursued for effective vector control. As a result of the global organizations stepping up their efforts with continued research, eradication of malaria can turn out to be a reality.
Malaria vaccine; malaria; newer antimalarials; sterile insect technique; transgenic mosquitoes
The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long. As a result of their strenuous lifestyle, they suffer from various types of pain, and have developed an assortment of formulations for treatment of pain in different parts of the body. Pain is the most common reason for physician consultation in all parts of the world including Bangladesh. Although a number of drugs are available to treat pain, including non-steroidal, steroidal, and narcotic drugs, such drugs usually have side-effects like causing bleeding in the stomach over prolonged use (as in the case of rheumatic pain), or can be addictive. Moreover, pain arising from causes like rheumatism has no proper treatment in allopathic medicine. It was the objective of the present study to document the formulations used by the Bede traditional practitioners for pain treatment, for they claim to have used these formulations over centuries with success. Surveys were conducted among a large Bede community, who reside in boats on the Bangshi River by Porabari village of Savar area in Dhaka district of Bangladesh. Interviews of 30 traditional practitioners were conducted with the help of a semi-structured questionnaire and the guided field-walk method. It was observed that the Bede practitioners used 53 formulations for treatment of various types of pain, the main ingredient of all formulations being medicinal plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain, either exclusively, or along with other types of body pain. A total of 65 plants belonging to 39 families were used in the formulations. The Fabaceae family provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the 53 formulations were used topically, 5 formulations were orally administered, and 1 formulation had both topical and oral uses. 8 formulations for treatment of rheumatic pain contained Calotropis gigantea, suggesting that the plant has strong potential for further scientific studies leading to discovery of novel efficacious compounds for rheumatic pain treatment.
The study of ethnobotany relating to any tribe is in itself a very intricate or convoluted process. This paper documents the traditional knowledge of medicinal plants that are in use by the indigenous Jaintia tribes residing in few isolated pockets of northeast India. The present study was done through structured questionnaires in consultations with the tribal practitioners and has resulted in the documentation of 39 medicinal plant species belonging to 27 families and 35 genera. For curing diverse form of ailments, the use of aboveground plant parts was higher (76.59%) than the underground plant parts (23.41%). Of the aboveground plant parts, leaf was used in the majority of cases (23 species), followed by fruit (4). Different underground plant forms such as root, tuber, rhizome, bulb and pseudo-bulb were also found to be in use by the Jaintia tribe as a medicine. Altogether, 30 types of ailments have been reported to be cured by using these 39 medicinal plant species. The study thus underlines the potentials of the ethnobotanical research and the need for the documentation of traditional ecological knowledge pertaining to the medicinal plant utilization for the greater benefit of mankind.
Despite great international efforts, malaria still inflicts an enormous toll on human lives, especially in Africa. Throughout history, antimalarial medicines have been one of the most powerful tools in malaria control. However, the acquisition and spread of parasite strains that are resistant to multiple antimalarial drugs have become one of the greatest challenges to malaria treatment, and are associated with the increase in morbidity and mortality in many malaria-endemic countries. To deal with this grave situation, artemisinin-based combinatory therapies (ACTs) have been introduced and widely deployed in malarious regions. Artemisinin is a new class of antimalarial compounds discovered by Chinese scientists from the sweet wormwood Artemisia annua. The potential development of resistance to artemisinins by Plasmodium falciparum threatens the usable lifespan of ACTs, and therefore is a subject of close surveillance and extensive research. Studies at the Thai–Cambodian border, a historical epicenter of multidrug resistance, have detected reduced susceptibility to artemisinins as manifested by prolonged parasite-clearance times, raising considerable concerns on resistance development. Despite this significance, there is still controversy on the mode of action of artemisinins. Although a number of potential cellular targets of artemisinins have been proposed, they remain to be verified experimentally. Here, we review the history of artemisinin discovery, discuss the mode of action and potential drug targets, and present strategies to elucidate resistance mechanisms.
antimalarial drugs; artemisinin-based combinatory therapy; drug-resistant malaria; Plasmodium
Artemether and Lumefantrine capsules are indicated for the treatment of P. falciparum malaria cases resistant to both chloroquine and sulphadoxine, pyrimethamine combination. Both artemether and lumefantrine act as blood schizontocides. Artemether is a sesquiterpene lactone derived from artemisinin. Artemisinin is a compound derived from the sweet wormwood plant and has been used for centuries in traditional Chinese medicine to treat fever. Lumefantrine is a synthetic aryl-amino alcohol antimalarial (quinine, mefloquine and halofantrine are members of the same group). Artemether is absorbed fairly rapidly with peak plasma concentrations reached about 2 hours after dosing. Absorption of lumefantrine, a highly lipophilic compound, starts after a lag period of up to 2 hours, with peak plasma concentration about 6-8 hours after dosing. In order to overcome this problem, we have observed that when the drug is given in the soft gelatin dosage form, the bioavailability of the drug is increased. Thus, increasing the absorption of the drug and peak plasma concentration is reached earlier then the conventional dosage form.
Plasmodium falciparum, the deadliest malarial parasite species, has developed resistance against nearly all man-made antimalarial drugs within the past century. However, quinine (QN), the first antimalarial drug, remains efficacious worldwide. Some chloroquine resistant (CQR) P. falciparum strains or isolates show mild cross resistance to QN, but many do not. Further optimization of QN may provide well-tolerated therapy with improved activity vs. CQR malaria. Thus, using the Heck reaction, we have pursued a structure-activity relationship study, including vinyl group modifications of QN. Certain derivatives show good antiplasmodial activity in QN-resistant and QN-sensitive strains, with lower IC50 values relative to QN.
There is increasing resistance of malaria parasites to chloroquine, the cheapest and commonly used drug for malaria in Nigeria. Artemisin, a product from medicinal plant indigenous to China, based on active principle of Artemisia annua, has been introduced into the Nigerian market. However not much has been done to project antimalaria properties of indigenous medicinal plants. This study thus, has the main objective of presenting medicinal plants used for malaria therapy in Okeigbo, Ondo State, South west Nigeria. Focus group discussions and interview were held about plants often found useful for malaria therapy in the community. Fifty species (local names) including for example: Morinda lucida (Oruwo), Enantia chlorantha (Awopa), Alstonia boonei (Ahun), Azadirachta indica (Dongoyaro) and Khaya grandifoliola (Oganwo) plants were found to be in use for malaria therapy at Okeigbo, Southwest, Nigeria . The parts of plants used could either be the barks, roots, leaves or whole plants. The recipes also, could be a combination of various species of plants or plant parts. This study highlights potential sources for the development of new antimalarial drugs from indigenous medicinal plants found in Okeigbo, Nigeria.
Malaria; Medicinal plants; antimalarial drugs; Okeigbo; Southwest Nigeria
Malaria continues to be a devastating parasitic disease that causes the death of 2 million individuals annually. The increase in multi-drug resistance together with the absence of an efficient vaccine hastens the need for speedy and comprehensive antimalarial drug discovery and development. Throughout history, traditional herbal remedies or natural products have been a reliable source of antimalarial agents, e.g. quinine and artemisinin. Today, one emerging source of small molecule drug leads is the world's oceans. Included among the source of marine natural products are marine microorganisms such as the recently described actinomycete. Members of the genus Salinispora have yielded a wealth of new secondary metabolites including salinosporamide A, a molecule currently advancing through clinical trials as an anticancer agent. Because of the biological activity of metabolites being isolated from marine microorganisms, our group became interested in exploring the potential efficacy of these compounds against the malaria parasite.
We screened 80 bacterial crude extracts for their activity against malaria growth. We established that the pure compound, salinosporamide A, produced by the marine actinomycete, Salinispora tropica, shows strong inhibitory activity against the erythrocytic stages of the parasite cycle. Biochemical experiments support the likely inhibition of the parasite 20S proteasome. Crystal structure modeling of salinosporamide A and the parasite catalytic 20S subunit further confirm this hypothesis. Ultimately we showed that salinosporamide A protected mice against deadly malaria infection when administered at an extremely low dosage.
These findings underline the potential of secondary metabolites, derived from marine microorganisms, to inhibit Plasmodium growth. More specifically, we highlight the effect of proteasome inhibitors such as salinosporamide A on in vitro and in vivo parasite development. Salinosporamide A (NPI-0052) now being advanced to phase I trials for the treatment of refractory multiple myeloma will need to be further explored to evaluate the safety profile for its use against malaria.
The Mandais are a little known tribe of Bangladesh inhabiting the north central regions, particularly Tangail district of Bangladesh. Their population has been estimated to be less than 10,000 people. Although the tribe has for the most part assimilated with the mainstream Bengali-speaking population, they to some extent still retain their original tribal customs, including their traditional medicinal practices. Since this practice is also on the verge of disappearance, the objective of the present study was to conduct an ethnomedicinal survey among Mandai tribal practitioners to document their use of medicinal plants for treatment of various ailments. Four traditional practitioners were found in the exclusive Mandai-inhabited village of Chokchokia in Tangail district. Information was collected from the practitioners with the help of a semi-structured questionnaire and guided field-walk method. It was observed that the four traditional practitioners used a total of 31 plants distributed into 23 families for treatment. The various ailments treated included diabetes, low semen density, jaundice, gastrointestinal tract disorders (stomach ache, indigestion, dysentery, and diarrhea), leucorrhea, pain (rheumatic pain, joint pain), skin disorders, respiratory tract disorders (coughs, mucus, and allergy), debility, fever, and helminthiasis. From the number of plants used (seven), it appeared that gastrointestinal tract disorders formed the most common ailment among the Mandai community, possibly brought about by the low income status of the people coupled with unhygienic conditions of living.
Medicinal plants; CAM; ethnomedicine; Mandai
Recent reports indicate that first cases of genuine artemisinin resistance have already emerged along the Thai-Cambodian border. The main objective of this trial was to track the potential emergence of artemisinin resistance in Bangladesh, which in terms of drug resistance forms a gateway to the Indian subcontinent.
We conducted an open-label, randomized, controlled 42-day clinical trial in Southeastern Bangladesh to investigate the potential spread of clinical artemisinin resistance from Southeast Asia. A total of 126 uncomplicated falciparum malaria patients were randomized to one of 3 treatment arms (artesunate monotherapy with 2 or 4 mg/kg/day once daily or quinine plus doxycycline TID for 7 days). Only cases fulfilling a stringent set of criteria were considered as being artemisinin-resistant.
The 28-day and 42-day cure rates in the artesunate monotherapy (2 and 4 mg/kg) and quinine/doxycyline arms were 97.8% (95% confidence interval, CI: 87.8–99.8%), 100% (95% CI: 91.1–100%), and 100% (95% CI: 83.4–100%), respectively. One case of re-infection was seen in the artesunate high dose arm, and a single case of recrudescence was observed in the low dose group on day 26. No differences in median parasite and fever clearance times were found between the 2 artesunate arms (29.8 h and 17.9 h vs. 29.5 h and 19.1 h). Not a single case fulfilled our criteria of artemisinin resistance. Parasite clearance times were considerably shorter and ex vivo results indicate significantly higher susceptibility (50% inhibitory concentration for dihydroartemisinin was 1.10 nM; 95% CI: 0.95–1.28 nM) to artemisinins as compared to SE-Asia.
There is currently no indication that artemisinin resistance has reached Bangladesh. However, the fact that resistance has recently been reported from nearby Myanmar indicates an urgent need for close monitoring of artemisinin resistance in the region.
Assam and Arunachal Pradesh have very rich tradition of herbal medicines used in the treatment of various ailments. Tribal communities practice different types of traditional healing practices. Enough documentation is available on the healing practices in other tribal communities except Mishing community of Assam and foot hill of East Siang district of Arunachal Pradesh hence the attempt was made for the same. A survey on folk medicinal plants and folk healers of Mishing tribe was conducted in few places of Lakhimpur and Dhemaji district of Assam and East Siang district of Arunachal Pradesh, where this ethnic group is living since time immemorial. All information was collected based on interview and field studies with local healers within the community. The identification of medicinal plants collected with help of indigenous healers was done. Such medicines have been shown to have significant healing power, either in their natural state or as the source of new products processed by them. This study is mainly concentrated with plants used to cure diseases and to enquire about different healing systems. Detail note on the method of preparation of precise dose, the part/parts of plants used and method of application is given.
Ethno-medicines; ethnic groups; herbal practitioners
Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS) to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes.
After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells.
This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.
Most investigations into the antimalarial activity of African plants are centered on finding an indigenous equivalent to artemisinin, the compound from which current frontline antimalarial drugs are synthesized. As a consequence, the standard practice in ethnopharmacological research is to use in vitro assays to identify compounds that inhibit parasites at nanomolar concentrations. This approach fails to take into consideration the high probability of acquisition of resistance to parasiticidal compounds since parasite populations are placed under direct selection for genetic that confers a survival advantage. Bearing in mind Africa's long exposure to malaria and extensive ethnobotanical experimentation with both therapies and diet, it is more likely that compounds not readily overcome by Plasmodium parasites would have been retained in the pharmacopeia and cuisine. Such compounds are characterized by acting primarily on the host rather than directly targeting the parasite and thus cannot be adequately explored in vitro. If Africa's long history with malaria has in fact produced effective plant therapies, their scientific elucidation will require a major emphasis on in vivo investigation.
New antimalarial drugs are required, partly because of the emergence of drug resistant strains of malaria parasites and partly because better compounds are needed to cure relapsing tertian malaria. In reviewing the diverse modes of action of currently used anti-malarials, against a background of the pathogenesis of malaria, attention is drawn to deficiencies in our knowledge. Even less do we understand how the malaria parasite becomes resistant to certain drugs, in particular chloroquine. New approaches to the problem include the application of combinations of existing antimalarials, and the search for new drugs on an unprecedentedly vast scale. Out of over a quarter million compounds that have recently been screened, a handful are now in clinical trial and are showing great promise for the treatment of multiple resistant falciparum malaria. The paper concludes by summarizing current recommendations for the prophylaxis and therapy of malaria due to drug resistant parasites.
The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i) re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii) repurposing drugs that are currently used to treat other infections or diseases; (iii) chemically modifying existing antimalarial compounds; (iv) exploring natural sources; (v) large-scale screening of diverse chemical libraries; and (vi) through parasite genome-based (“targeted”) discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum), and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs), and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now) and “long term” (5. Next generation of antimalarial treatment—Approaches and candidates). However, these two categories are interrelated, and the approaches in both should be implemented in parallel with focus on developing a successful, long-lasting antimalarial chemotherapy.
malaria; falciparum; artemisinin resistance; natural products; drug discovery; kinases; HDAC; DHODH
Malaria remains a major cause of morbidity and mortality among children under five years of age in Nigeria. Most of the early treatments for fever and malaria occur through self-medication with anti-malarials bought over-the-counter (OTC) from untrained drug vendors. Self-medication through drug vendors can be ineffective, with increased risks of drug toxicity and development of drug resistance. Global malaria control initiatives highlights the potential role of drug vendors to improve access to early effective malaria treatment, which underscores the need for interventions to improve treatment obtained from these outlets. This study aimed to determine the feasibility and impact of training rural drug vendors on community-based malaria treatment and advice with referral of severe cases to a health facility.
A drug vendor-training programme was carried out between 2003 and 2005 in Ugwuogo-Nike, a rural community in south-east Nigeria. A total of 16 drug vendors were trained and monitored for eight months. The programme was evaluated to measure changes in drug vendor practice and knowledge using exit interviews. In addition, home visits were conducted to measure compliance with referral.
The intervention achieved major improvements in drug selling and referral practices and knowledge. Exit interviews confirmed significant increases in appropriate anti-malarial drug dispensing, correct history questions asked and advice given. Improvements in malaria knowledge was established and 80% compliance with referred cases was observed during the study period,
The remarkable change in knowledge and practices observed indicates that training of drug vendors, as a means of communication in the community, is feasible and strongly supports their inclusion in control strategies aimed at improving prompt effective treatment of malaria with referral of severe cases.
Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68–100% at doses of 62.5–250mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.
Malaria is a major healthcare problem worldwide resulting in an estimated 0.65 million deaths every year. It is caused by the members of the parasite genus Plasmodium. The current therapeutic options for malaria are limited to a few classes of molecules, and are fast shrinking due to the emergence of widespread resistance to drugs in the pathogen. The recent availability of high-throughput phenotypic screen datasets for antimalarial activity offers a possibility to create computational models for bioactivity based on chemical descriptors of molecules with potential to accelerate drug discovery for malaria.
In the present study, we have used high-throughput screen datasets for the discovery of apicoplast inhibitors of the malarial pathogen as assayed from the delayed death response. We employed machine learning approach and developed computational predictive models to predict the biological activity of new antimalarial compounds. The molecules were further evaluated for common substructures using a Maximum Common Substructure (MCS) based approach.
We created computational models using state-of-the-art machine learning algorithms. The models were evaluated based on multiple statistical criteria. We found Random Forest based approach provides for better accuracy as assessed from ROC curve analysis. We further evaluated the active molecules using a substructure based approach to identify common substructures enriched in the active set. We argue that the computational models generated could be effectively used to screen large molecular datasets to prioritize them for phenotypic screens, drastically reducing cost while improving the hit rate.
Tribal peoples are endowed with enriched traditional wisdom to use available nature resources around them. They are well versed
in the usage of plant for treating various diseases. They have used powder or extract or paste form of the plant parts such as root,
shoot, whole plant, fruits and leaves etc. The recipe known by the tribal people was passed on only to their family members and
community through mouth to mouth practice. Hence, the knowledge is confined to particular people alone. It is always expedient
to store information in the database, so that it will be accessible by everyone from everywhere. To achieve this, MEDDB has been
developed, which stores the details of 110 plant species that are commonly used by tribes for fever, asthma, cold, cough, diabetes,
diarrhea, dysentery, eye infections, stomach ache, wounds and snake bite. The details of each plant were collected from the
literature and through web search to give comprehensive and exhaustive information. Each plant entry is compiled under the subheadings
viz., common name, classification, physical characteristics, medicinal uses, active constituents, and references.
Traditional medicine; Active constituents; Ethnomedicine; HTML; database; JPEG
Diarrhoea is a major cause of morbidity and mortality in rural communities in Africa, particularly in children under the age of five. This calls for the development of cost effective alternative strategies such as the use of herbal drugs in the treatment of diarrhoea in these communities. Expenses associated with the use of orthodox medicines have generated renewed interest and reliance on indigenous medicinal plants in the treatment and management of diarrhoeal infections in rural communities. The properties of many phenolic constituents of medicinal plants such as their ability to inhibit enteropooling and delay gastrointestinal transit are very useful in the control of diarrhoea, but problems such as scarcity of valuable medicinal plants, lack of standardization of methods of preparation, poor storage conditions and incertitude in some traditional health practitioners are issues that affect the efficacy and the practice of traditional medicine in rural African communities. This review appraises the current strategies used in the treatment of diarrhoea according to the Western orthodox and indigenous African health-care systems and points out major areas that could be targeted by health-promotion efforts as a means to improve management and alleviate suffering associated with diarrhoea in rural areas of the developing world. Community education and research with indigenous knowledge holders on ways to maximise the medicinal potentials in indigenous plants could improve diarrhoea management in African rural communities.
diarrhea; gastrointestinal transit; indigenous medicinal plants; health-promotion efforts; rural Africa
With the current increase of international travel and increasing drug resistance, United Kingdom residents stand a high risk of contracting malaria when they visit endemic countries. The development of anti-malarial agents from old traditional plant remedies to modern synthetic drugs is briefly reviewed. Resistance to the latter has spread rapidly since the 1950s, culminating in the widespread distribution of multiple drug-resistant strains of Plasmodium falciparum in most endemic areas. There is a danger that such parasites may rapidly develop resistance even to new compounds such as mefloquine, halofantrine or artemisinin unless the use of such compounds is carefully controlled. The few developments, including new drugs and ways of reversing existing resistance, are also briefly reviewed in this paper. Emphasis is laid on the need to revert to classical methods of protection against malaria vectors since it is unlikely that a protective vaccine will become available in the near future.