Artemisinin: From Chinese Herbal Medicine to Modern Chemotherapy

Malaria is a disease that has blighted humankind since early times. The first antimalarial treatment available to Europeans was the dried bark of the cinchona tree from Peru. The main problem in its use was adulteration by other material. The ‘active principle’ was first extracted in 1820 and named quinine. It was found to be a more powerful and reliable drug than cinchona bark. Once its chemical structure had been determined, it was possible to synthesize substances chemically related to quinine that were equally powerful but could be manufactured industrially. Mepacrine (atabrine) was amongst the most successful, but had adverse side effects. To avoid these side effects, further chemical modification gave chloroquine, a highly successful drug. This sequence is a common way of converting an herbal remedy into a modern-style chemical drug. It parallels, to some extent, the process of potentiation common in traditional herbal medicine. By the 1970s, drug resistance had developed with chloroquine. To find and develop a new antimalarial drug that worked on an entirely different pharmacological principle, Chinese scientists turned to their herbal compendia (ben cao) and found that Artemisia annua (qing hao) was frequently mentioned as a treatment for intermittent fever. Whether, in view of the distinctive doctrines of Chinese medicine, it should be possible to extract an active principle as described above is discussed. After a very careful reading of the procedure given for the use of qing hao, an active substance, artemisinin, was extracted. Artemisinin has a truly remarkable chemical structure, and chemical modification produced artesunate, the drug of choice. To prevent the development of resistance, artesunate is used in combination with other antimalarial drugs. Modern pharmacology has largely ignored that other substances in artemisia and the cinchona bark may contribute to their therapeutic effect. This matter is also discussed

Biological Activities of Extracts from Sumac (Rhus spp.): A Review

Sumac is the common name for a genus (Rhus) that contains over 250 individual species of flowering plants in the family Anacardiaceae. These plants are found in temperate and tropical regions worldwide, often grow in areas of marginal agricultural capacity, and have a long history of use by indigenous peoples for medicinal and other uses. The research efforts on sumac extracts to date indicate a promising potential for this plant family to provide renewable bioproducts with the following reported desirable bioactivities: antifibrogenic, antifungal, antiinflammatory, antimalarial, antimicrobial, antimutagenic, antioxidant, antithrombin, antitumorigenic, antiviral, cytotoxic, hypoglycaemic, and leukopenic. As well, the bioactive components can be extracted from the plant material using environmentally benign solvents that allow for both food and industrial end-uses. The favorable worldwide distribution of sumac also suggests that desirable bioproducts may be obtained at source, with minimal transportation requirements from the source through processing to end consumer. However, previous work has focussed on only a few members of this large plant family. In addition, not all of the species studied to date have been fully characterized for potential bioactive components and bioactivities. Thus, there remains a significant research gap spanning the range from lead chemical discovery through process development and optimization in order to better understand the full potential of the Rhus genus as part of global green technology based bioproduct and bioprocess research programs

An overview of anti-diabetic plants used in Gabon: Pharmacology and Toxicology

© 2017 Elsevier B.V. All rights reserved.Ethnopharmacological relevance: The management of diabetes mellitus management in African communities, especially in Gabon, is not well established as more than 60% of population rely on traditional treatments as primary healthcare. The aim of this review was to collect and present the scientific evidence for the use of medicinal plants that are in currect by Gabonese traditional healers to manage diabetes or hyperglycaemia based here on the pharmacological and toxicological profiles of plants with anti-diabetic activity. There are presented in order to promote their therapeutic value, ensure a safer use by population and provide some bases for further study on high potential plants reviewed. Materials and methods: Ethnobotanical studies were sourced using databases such as Online Wiley library, Pubmed, Google Scholar, PROTA, books and unpublished data including Ph.D. and Master thesis, African and Asian journals. Keywords including ‘Diabetes’ ‘Gabon’ ‘Toxicity’ ‘Constituents’ ‘hyperglycaemia’ were used. Results: A total of 69 plants currently used in Gabon with potential anti-diabetic activity have been identified in the literature, all of which have been used in in vivo or in vitro studies. Most of the plants have been studied in human or animal models for their ability to reduce blood glucose, stimulate insulin secretion or inhibit carbohydrates enzymes. Active substances have been identified in 12 out of 69 plants outlined in this review, these include Allium cepa and Tabernanthe iboga. Only eight plants have their active substances tested for anti-diabetic activity and are suitables for further investigation. Toxicological data is scarce and is dose-related to the functional parameters of major organs such as kidney and liver. Conclusion: An in-depth understanding on the pharmacology and toxicology of Gabonese anti-diabetic plants is lacking yet there is a great scope for new treatments. With further research, the use of Gabonese anti-diabetic plants is important to ensure the safety of the diabetic patients in Gabon.Peer reviewedFinal Accepted Versio

Pharmacokinetic Herb-Drug Interactions: Insight into Mechanisms and Consequences

Herbal medicines are currently in high demand, and their popularity is steadily increasing. Because of their perceived effectiveness, fewer side effects and relatively low cost, they are being used for the management of numerous medical conditions. However, they are capable of affecting the pharmacokinetics and pharmacodynamics of coadministered conventional drugs. These interactions are particularly of clinically relevance when metabolizing enzymes and xenobiotic transporters, which are responsible for the fate of many drugs, are induced or inhibited, sometimes resulting in unexpected outcomes. This article discusses the general use of herbal medicines in the management of several ailments, their concurrent use with conventional therapy, mechanisms underlying herb-drug interactions (HDIs) as well as the drawbacks of herbal remedy use. The authors also suggest means of surveillance and safety monitoring of herbal medicines. Contrary to popular belief that "herbal medicines are totally safe," we are of the view that they are capable of causing significant toxic effects and altered pharmaceutical outcomes when coadministered with conventional medicines. Due to the paucity of information as well as sometimes conflicting reports on HDIs, much more research in this field is needed. The authors further suggest the need to standardize and better regulate herbal medicines in order to ensure their safety and efficacy when used alone or in combination with conventional drugs

Ethnomedicine of the Kagera Region, north western Tanzania. Part 3: plants used in traditional medicine in Kikuku village, Muleba District.

BACKGROUND\ud \ud The Kagera region of north western Tanzania has a rich culture of traditional medicine use and practice. Traditional medicines are the mainstay of healthcare in this region and are known to support the management of many illnesses such as malaria, bacterial infections, epilepsy, gynecological problems and others. However, most of the plants being used have either not been documented or evaluated for safety and efficacy or both. This study, the sixth of an ongoing series, reports on the medicinal plants that are used at Kikuku village, Muleba District.\ud \ud METHODOLOGY\ud \ud A semi-structured questionnaire was used to collect information on the common/local names of the plants, parts of the plants used, diseases treated, methods of preparing the herbal remedies, dosage of the remedies administered, frequency and duration of treatment and toxicity of the medicines. A literature review was carried out for information on the ethnomedical uses of the reported plants.\ud \ud RESULTS\ud \ud A total of 49 plant species belonging to 47 genera and 24 plant families were documented. The family Euphorbiaceae and Asteraceae had the highest representation. The plants are used for the treatment of skin conditions (10 plants; 20%), bacterial infections and wounds (14 plants; 28.6%), malaria (14 plants; 28.6%), gastrointestinal disorders (11 plants; 22.4%), gynecological problems including infertility (8 plants; 16.3%), hypertension (5 plants; 10.2%), viral infections (7 plants; 14.3%), chest problems (5 plants; 10.2%), diabetes (3 plants; 6.1%), cancer (2 plants; 4.1%), inflammatory conditions (arthritis, rheumatism), HIV and AIDS, and hernia each treated by 1 plant (3 plants in total; 6.1%). Information obtained from the literature indicate that 25 (51.0%) of the therapeutic claims are supported by laboratory results or have similar claims of ethnomedical use from other countries.\ud \ud CONCLUSION\ud \ud Herbal remedies comprise an important and effective component of the healthcare system in Kikuku village with plants in the families Euphorbiaceae and Asteraceae comprising an important part of plants used in the indigenous healthcare management in the village. Malaria and bacterial infections dominate the list of diseases that are managed using traditional medicines

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

The Trypanosoma cruzi enzyme TcGPXI is a glycosomal peroxidase and can be linked to trypanothione reduction by glutathione or tryparedoxin.

Trypanosoma cruzi glutathione-dependent peroxidase I (TcGPXI) can reduce fatty acid, phospholipid, and short chain organic hydroperoxides utilizing a novel redox cycle in which enzyme activity is linked to the reduction of trypanothione, a parasite-specific thiol, by glutathione. Here we show that TcGPXI activity can also be linked to trypanothione reduction by an alternative pathway involving the thioredoxin-like protein tryparedoxin. The presence of this new pathway was first detected using dialyzed soluble fractions of parasite extract. Tryparedoxin was identified as the intermediate molecule following purification, sequence analysis, antibody studies, and reconstitution of the redox cycle in vitro. The system can be readily saturated by trypanothione, the rate-limiting step being the interaction of trypanothione with the tryparedoxin. Both tryparedoxin and TcGPXI operate by a ping-pong mechanism. Overexpression of TcGPXI in transfected parasites confers increased resistance to exogenous hydroperoxides. TcGPXI contains a carboxyl-terminal tripeptide (ARI) that could act as a targeting signal for the glycosome, a kinetoplastid-specific organelle. Using immunofluorescence, tagged fluorescent proteins, and biochemical fractionation, we have demonstrated that TcGPXI is localized to both the glycosome and the cytosol. The ability of TcGPXI to use alternative electron donors may reflect their availability at the corresponding subcellular sites

Effects of Raw Ethanolic Seed Extract of Tetracarpidium conophorum on Heamatological and Histopathological Parameters in Swiss Albino Mice Infected with Plasmodium berghei

Study was carried out to determine the heamatological and histopathological effects of raw ethanolic seed extract of Tetracarpidium conophorum in swiss albino mice infected with Plasmodium berghei (NK65). Standard methods were employed to determine the heamatological, histopathological indices and biochemical assay. The experimental mice were acclimatized for seven days before the commencement of treatment. Mice were grouped into six groups (A, B, C, D, E and F) of four mice each. The mice in group B were treated with a standard antimalarial drug (chloroquine as positive control) at a dose of 5 mg/kg body weight, while mice in groups D, E and F was administered with increasing dosages (200, 400, 600 mg/kg body weight) of seed extracts for four consecutive days respectively. Group C (Normal control) served as mice that was not infected and treated. Heamatological analysis revealed an increase in Packed Cell Volume, Red Blood Cells, Heamoglobin and Platelet values of all mice in groups D, E and F (mice administered different concentrations of the extract). Mice in group B (chloroquine treated group) have the highest value. Mice in group A (negative control) exhibited lowest values of Heamoglobin, Platelet, Red blood cells, and Packed Cell Volume. There was significant increase in the levels of Alanine Transaminase and Aspartate Transaminase in group A (infected and not treated) compared to mice in groups C, D, and E. Restorative effects of seed extract was observed on the liver and kidney of mice at dose levels (400 and 600 mg/kg) used, but the seed extract at the dose of 600 mg/kg was observed to have adverse effects on the liver of the mice. This study therefore shows that Tetracarpidium conophorum was able to boost the formation of heamatological indices and was not toxic to the organs (liver and kidney) in mice

Diversity of secondary metabolites from Genus Artocarpus (Moraceae)

Abstrak. Hakim A. 2010. Keanekaragaman metabolit sekunder Genus Artocarpus (Moraceae). Nusantara Bioscience 2:146-156. Beberapa spesies dari genus Artocarpus (Moraceae) telah diteliti kandungan bahan alamnya. Metabolit sekunder yang berhasil diisolasi dari genus Artocarpus terdiri dari terpenoid, flavonoid, stilbenoid, arilbenzofuran, neolignan, dan adduct Diels-Alder. Kelompok flavonoid merupakan senyawa yang paling banyak ditemukan dari tumbuhan Artocarpus. Senyawa flavonoid yang telah berhasil diisolasi dari tumbuhan Artocarpus memiliki kerangka yang beragam seperti calkon, flavanon, flavan-3-ol, flavon sederhana, prenilflavon, oksepinoflavon, piranoflavon, dihidrobenzosanton, furanodihidrobenzosanton, piranodihidrobenzosanton, kuinonosanton, siklolopentenosanton, santonolid, dihidrosanton. Kata kunci: Artocarpus, Moraceae, flavonoid, Diels-Alder, metabolit sekunder

Antimalarial, anticancer, antimicrobial activities and chemical constituents of essential oil from the aerial parts of Cyperus kyllingia Endl.

The chemical constituents of the essential oil from Cyperus kyllingia Endl. were analyzed by a GC, GC-MS. Twenty-three compounds were identified, accounting for 93.75% of the total oil that consisted mainly of oxygenated sesquiterpenes (53.52%), particularly sesquiterpene hydrocarbons (38.97%), and carboxylic acid (1.26%). The most representative compounds were α-cadinol (19.32%), caryophyllene oxide (12.17%), α-muurolol (11.58%), α-humulene (9.85%), and α-atlantone (6.07%). The oil showed significant activities against Plasmodium falcipalum (K1, multi drug resistant strain) and NCI-H187 (Small Cell Lung Cancer) with the IC50 values of 7.52 and 7.72 μg/mL, respectively. The oil exhibited highly active against Staphylococcus aureus ATCC25923 and moderately active against Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27553, Aspergillus flavus and Candida albicans