Antimalarial activity of extracts and alkaloids isolated from six plants used in traditional medicine in Mali and Sao Tome

Methanol and chloroform extracts were prepared from various parts of four plants collected in Mali: Guiera senegalensis (Gmel.) Combretaceae, Feretia apodanthera (Del.) Rubiaceae, Combretum micranthum (Don.) Combretaceae, Securidaca longepedunculata (Fres.) Polygalaceae and two plants -collected in Sao Tome: Pycnanthus angolensis (Welw.) Myristicaceae and Morinda citrifolia (Benth.) Rubiaceae were assessed for their in vitro antimalarial activity and their cytotoxic effects on human monocytes (THP1 cells) by flow cytometry. The methanol extract of leaves of Feretia apodanthera and the chloroform extract of roots of Guiera senegalensis exhibited a pronounced antimalarial activity. Two alkaloids isolated from the active extract of Guiera senegalensis, harman and tetrahydroharman, showed antimalarial activity (IC(50) lower than 4 microg/mL) and displayed low toxicity against THP1. Moreover, the decrease of THP1 cells in S phase of the cell cycle, after treatment with harman and tetrahydroharman, was probably due to an inhibition of total protein synthesis.     

Antimalarial activity screening of some alkaloids and the plant extracts from Amaryllidaceae

Four groups of Amaryllidaceae alkaloids, namely lycorine-, crinine-, tazettine-, and galanthamine-type, as well as plant extracts of the Amaryllidaceae plants (Pancratium maritimum, Leucojum aestivum, and Narcissus tazetta ssp. tazetta) growing in Turkey were evaluated in vitro for their ability to inhibit Plasmodium falciparum growth by a high-throughput screening method with a 96-well microtiter plate. All four groups of alkaloids exhibited antimalarial activity at different potencies. 6-Hydroxyhaemanthamine, haemanthamine and lycorine were found to be the most potent alkaloids against P. falciparum (T9.96) and galanthamine and tazettine had the least potent activity against P. falciparum (K1).     

Antimalarial activity of natural product extracts from Papua New Guinean and Australian plants against Plasmodium falciparum

In the search for new antimalarial compounds, a subset of a natural product extract library prepared from plant samples collected from Papua New Guinea and Australia was screened for in vitro activity against the chloroquine-sensitive 3D7 and chloroquine-resistant Dd2 strains of Plasmodium falciparum. Using the incorporation of ((3)H)-hypoxanthine into parasite nucleic acid as a marker of growth, 93 of the 794 extracts screened displayed >40% inhibition against 3D7 infected erythrocytes at 312 microge/mL. Antimalarial activity was confirmed in 48 of these extracts against both 3D7 and Dd2 infected erythrocytes at concentrations between 78 and 390 microge/mL, 14 of which caused >90% growth inhibition of 3D7 at the lowest concentration screened. Extracts were also tested for mammalian cell cytotoxicity to evaluate selectivity of action.     

Antimalarial alkaloids from a Bhutanese traditional medicinal plant Corydalis dubia

Ethnopharmacological relevance

Corydalis dubia is used in Bhutanese traditional medicine as a febrifuge and for treating infections in the blood, liver and bile which correlate to the signs and symptoms of malarial and microbial infections.

Aim of the study

To validate the ethnopharmacological uses of the plant and to discover potential new therapeutic drug leads.

Materials and methods

C. dubia was collected from Bhutan and the alkaloids were obtained using acid–base fractionation and separation by repeated column and preparative plate chromatography. The alkaloids were identified from analysis of their physiochemical and spectroscopic data and were tested for antiplasmodial, antimicrobial and cytotoxicity activities.

Results

A systematic extraction and isolation protocol yielded one new natural product, dubiamine, and seven known isoquinoline alkaloids, scoulerine, cheilanthifoline, protopine, capnoidine, bicuculline, corydecumbine and hydrastine. Among the four alkaloids tested, scoulerine showed the best antiplasmodial activity with IC₅₀ values of 5.4 μM and 3.1 μM against the antifolate sensitive and the multidrug resistant P. falciparum strains: TM4/8.2 and K1CB1, respectively. None of the alkaloids tested showed significant antimicrobial or cytotoxicity activities.

Conclusions

The antiplasmodial test results, of the isolated alkaloid components, are commensurated with the ethnopharmacological uses of this plant.     

Antimalarial activity of Tiliacora triandra diels against Plasmodium falciparum in vitro

Preparations from the roots of the Thai medicinal plant, Tiliacora triandra Diels, were found to have antimalarial activity against Plasmodium fakiparum in vitro. Methanol extraction yielded two alkaloidal components (water-soluble and water-insoluble). Only the water-insoluble alkaloidal component showed an increase in antimalarial activity. From this component, five different alkaloids of the bisbenzyl-isoquinoline group were isolated and identified as tiliacorine, tiliacorinine, nor-tiliacorinine A, and two uncharacterized alkaloids G and H. Alkaloid G was found to be the most active in vitro schizontocide (ID₅₀, 344 ng/mL) followed by nor-tiliacorinine A and tiliacorine (ID₅₀, 558 and 675 ng/mL, respectively).     

Antimalarial activity of crude extracts from nine African medicinal plants

An ethnobotanical study was conducted in Comores (Ngazidja) about plant species used traditionally for the treatment of various diseases, including malaria. Antimalarial activity of 76 vegetal extracts obtained from 17 species traditionally used to treat malaria symptoms, was evaluated in vitro using Plasmodium falciparum chloroquine-resistant strain (W2). Antiproliferative activity was evaluated on human monocytic THP1 cells and the selectivity index of the plant extracts was calculated. The results showed that 10 plant extracts had a moderate activity (5相似文献   

Tanzanian medicinal plants used traditionally for the treatment of malaria: In vivo antimalarial and in vitro cytotoxic activities

Seventeen fractions of extracts obtained from 11 Tanzanian medicinal plants, which had previously been shown to possess a high antimalarial activity in vitro were submitted to the 4-day suppressive test in Plasmodium berghei-infected mice, and were investigated for cytotoxic activity in human carcinoma cell lines in vitro. Several fractions administered orally to the mice (500 mg/kg body weight/day) produced a significant reduction of parasitaemia. The most effective plant fractions investigated were those of the root and stem bark of Maytenus senegalensis (90% and 63% suppression of parasitaemia, respectively) and of the roots of Cissampelos mucronata (59% suppression). Highest cytotoxic activities were found with all fractions of Maytenus senegalensis (IC₅₀ 1 μg/mL) and with the PE fraction of the roots of Salacia madagascariensis (median IC₅₀=1.2 μg/mL for HT 29 and 2.3 μg/mL for KB).     

Antimalarial activity of extracts of Malaysian medicinal plants.

In vitro and in vivo studies revealed that Malaysian medicinal plants, Piper sarmentosum, Andrographis paniculata and Tinospora crispa produced considerable antimalarial effects. Chloroform extract in vitro did show better effect than the methanol extract. The chloroform extract showed complete parasite growth inhibition as low as 0.05 mg/ml drug dose within 24 h incubation period (Andrographis paniculata) as compared to methanol extract of drug dose of 2.5 mg/ml but under incubation time of 48 h of the same plant spesies. In vivo activity of Andrographis paniculata also demonstrated higher antimalarial effect than other two plant species.     

抗骨质疏松症的单味中药及药用植物研究进展

综述了近年来用于治疗骨质疏松症的常用单味中药及药用植物的研究进展以及机制,希望能为新药开发及中药走向世界提供帮助。     

Anti-plasmodial activity of some Kenyan medicinal plant extracts singly and in combination with chloroquine

Sixty organic and aqueous extracts of eleven plants used for the control of malaria by local communities in Kisii District, Kenya were screened for in vitro anti-plasmodial activity. The plants selection was based on existing ethnobotanical information and interviews with local communities. The extracts were tested against chloroquine sensitive and resistant laboratory adapted strains of Plasmodium falciparum. The study revealed that 63.6% of the plants were active (IC50 < or = 100 microg/mL). Extracts of four plants, Ekebergia capensis, Stephania abyssinica, Ajuga remota and Clerodendrum myricoides gave IC50 values below 30 microg/mL against both chloroquine sensitive and resistant P. falciparum strains. Combination of extracts of E. capensis and C. myricoides with chloroquine against the multi-drug resistant P. falciparum isolate (V1/S) revealed synergistic effect. The plants which showed activity may be useful as sources for novel anti-plasmodial compounds.     

The Traditional Medicine Spilanthes acmella,and the Alkylamides Spilanthol and Undeca‐2E‐ene‐8,10‐diynoic Acid Isobutylamide,Demonstrate In Vitro and In Vivo Antimalarial Activity

Spilanthes spp. are used as traditional herbal medicines in Africa and India to treat malaria. Yet, to date, there are no data on the active constituents or the most effective extraction methods for this indication. The isolated alkylamides, spilanthol and undeca‐2E‐ene‐8,10‐diynoic acid isobutylamide, found in S. acmella Murr., were shown to have IC₅₀s of 16.5 μg/mL and 41.4 μg/mL on Plasmodium falciparum strain PFB and IC₅₀s of 5.8 μg/mL and 16.3 μg/mL for the chloroquine resistant P. falciparum K1 strain, respectively. Further investigations revealed that at relatively low concentrations, spilanthol and the water extract of S. acmella reduced the parasitemia 59% and 53% in mice infected with P. yoelii yoelii 17XNL at 5 mg/kg and 50 mg/kg, respectively. Unexpectedly, the 95% ethanol extract of S. acmella was less effective (36% reduction in parasitemia) at 50 mg/kg. These results provide the first evidence supporting S. acmella against malaria and demonstrating active constituents in S. acmella against P. falciparum. Copyright © 2011 John Wiley & Sons, Ltd.     

In Vivo antimalarial activity of aqueous extracts from Kenyan medicinal plants and their chloroquine (CQ) potentiation effects against a blood-induced CQ-resistant rodent parasite in mice

Hot water extracts from eight medicinal plants representing five families, used for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ) resistant Plasmodium berghei NK65, either alone or in combination with CQ. Extracts of three plants, Toddalia asiatica (root bark), Rhamnus prinoides (leaves and root bark) and Vernonia lasiopus (root bark) showed high chemosuppression in the range 51%-75%. Maytenus acuminata, M. heterophylla, M. senegalensis and Rhamnus staddo had moderate activities of 33%-49% parasitaemia suppression in the root bark and/or leaf extracts, while Withania somnifera (root bark) had a non-significant suppression (21%). In combination with CQ, extracts of V. lasiopus (all parts), leaf extracts of M. senegalensis, R. prinoides and T. asiatica as well as root barks of M. heterophylla, R. staddo and T. asiatica had improved parasitaemia suppression in the range 38%-66%, indicating synergistic interactions. Remarkable parasitaemia suppression by the extracts, either alone or in combination with CQ resulted into longer survival of mice relative to the controls, in some cases by more than 2 weeks. Plants, which showed significant antimalarial activity including V. lasiopus, T. asiatica and R. prinoides, should further be evaluated in the search for novel agents against drug-resistant malaria.     

Proliferative effects of five traditional Nigerian medicinal plant extracts on human breast and bone cancer cell lines

Ethnopharmacological relevance

The medicinal plants Hunteria umbellata (HUL), Cola lepidota (CCL), Persea americana leaf (PAL), Root bark of Persea americana (RPA) and Plukenetia conophora (PCL) are used in Nigerian traditional medicine for the treatment of cancer and cancer related diseases.

Aim of the study

To scientifically evaluate the cell proliferative and apoptotic effects of the plants extracts using breast and osteocarcinoma cell lines, and also to identify the possible components via LC-MS to have a kind of chemical fingerprint.

Materials and methods

The antiproliferative and apoptotic effects of methanolic extracts (10 μg/ml) of the five medicinal plants were subjected to in vitro evaluation using four cancer cell lines (breast-MCF-7 and BT-20; Osteocarcinoma-MG-63 and Saos-2) measured by flow cytometry. Non-tumorigenic controls MCF-12A and primary isolated osteoblasts (POB) were chosen to eliminate negative influence on healthy tissue.

Results

Of the five extracts RPA demonstrated a significant (P < 0.05) anti-proliferative activity against estrogen receptor positive breast cancer cell lines (MCF-7). The proliferative phase was decreased by 18%, whereas, a significant increase in cell proliferation (about 27%) was observed for RPA at a concentration of 10 μg/ml. PCL, CCL, HUL and PAL did not show marked inhibition of the proliferation of cell line MCF-7.

Conclusion

These results give suggestive evidence that the plant extracts exhibit some correlation between the claimed ethnomedicinal uses and the cell proliferative activity. RPA extract includes chemical compounds with estrogen-like activity and validates its potential use as anticancer agent, particularly against breast carcinoma; provided important information potentially helpful in drug designing and discovery. Further studies will involve the isolation of anti tumour compounds in RPA by LC-MS and detailed mechanism of anticancer activities.     

Evaluation of some medicinal plant extracts for antidiarrhoeal activity

The antidiarrhoeal effect of seven plant extracts namely: the aerial parts of Euphorbia paralias L. (EP), Bidens bipinnata L. (BB), Cynachum acutum L. (CyAc), Diplotaxis acris (Forssk.) Boiss (DA), Convolvulus fatmensis (CF) and Schouwia thebaica Webb (ST) and the leaves of Plantago major L. (PM), was evaluated on castor oil-induced diarrhoea, gastrointestinal movement in rats (charcoal meal) and on the motility of duodenum isolated from freshly slaughtered rabbits. A significant antidiarrhoeal effect of the tested plant extracts against castor oil-induced diarrhoea in rats was achieved by 200 and 400 mg/kg. The tested plant extracts decreased the gastrointestinal movement as indicated by the significantly (p<0.05 to 0.001) decreased distance travelled by the charcoal meal. The large dose of the tested plant extracts was slightly more effective than the small one. The antidiarrhoeal effect was confirmed by the reported dose dependent inhibition of the motility of duodenum isolated from freshly slaughtered rabbits. The EP and PM methanol extract produced a transient stimulation followed by inhibition in doses of less than 0.05 and 1.6 mg/kg, respectively. Higher concentrations caused rapid muscle relaxation. Tannins, flavonoids, unsaturated sterols/triterpenes, carbohydrates, lactones and proteins/amino acids were reported as major active constituents of the tested plants.     

53味治疗白癜风中药水提物对蘑菇酪氨酸酶活性的影响

目的:研究治疗白癜风的53味中药对蘑菇酪氨酸酶活性的影响。方法:采用蘑菇酪氨酸酶多巴速率氧化法测定酪氨酸酶活性,反应物2mL,37℃孵育10min后,加0.15%DL-多巴1mL,再孵育2min,用分光光度计于475nm处测定吸光度A值(A475)。共分为4组,每种药物实验均重复3次。结果:生地黄、沙苑子、苍耳子等47味中药有上调蘑菇酪氨酸酶活性的作用。结论:上调酪氨酸酶活性的中药对临床治疗白癜风具有重要参考价值。     

中药新药研发中药材研究需关注的问题

中药新药研发中药材研究是新药研发的前提和基础,它贯穿于整个新药研究全过程。药材研究是中药新药药学研究的主要内容之一,也是新药药学评价的重点内容。该文通过分析目前中药新药研发中药材研究资料中存在的问题,分别从药材研究理念、药材质量稳定、药材质量标准等方面进行了阐述,其中药材研究理念方面应关注重视药材研究重要作用和从新药研究的目的进行顶层设计的问题;药材质量稳定方面应关注基原、药用部位、产地、采收加工、贮藏、种植（养殖）等方面问题;药材质量标准方面应关注建立符合中药新药特点的质量标准问题,为指导中药新药研发和审评的科学性,以及为药材标准的制定提供依据。     

Lysosomal membrane stabilization and anti-inflammatory activity of Clerodendrum phlomidis L.f., a traditional medicinal plant

Ethnopharmacological relevance Clerodendrum phlomidis L.f., is used to treat several inflammatory diseases and arthritis in Indian traditional system and folk medicine.Aim of the study The aim of the present study was to evaluate the scientific basis of antiinflammatory activity of different organic solvent extracts of Clerodendrum phlomidis and to evaluate the active crude extract for its antiarthritic activity in FCA induced animal model.Materials and methods The antiinflammatory activity of Clerodendrum phlomidis was studied using the carrageenan and cotton pellet induced inflammatory models. The crude ethanol extract was standardized with the known standard using HPLC. The antiarthritic activity was studied using Freund's complete adjuvant induced rat model. For antiarthritic activity, the active crude extract was administered at the concentrations of 100, 200 and 400 mg/kg body weight. The effect of the ethanol extract on serum SGOT, SGPT, ALP, levels of pro-inflammatory cytokines, plasma lysosomal enzymes and protein bound carbohydrates of FCA arthritic animals were studied.Results The ethanol extract at 100, 200, and 400 mg/kg, showed maximum inhibition of inflammation induced by carrageenan (100 mg/kg - 47.73%; 200 mg/kg - 54.00% and 400 mg/kg - 65.15%). In cotton pellet induced granuloma, the ethanol extract at different concentrations showed significant reduction in granuloma weight. In FCA induced arthritis, the ethanol extract showed a significant reduction in paw thickness (100 mg/kg - 51.71%; 200 mg/kg - 57.58% and 400 mg/kg - 62.48%). The levels of lysosomal enzymes and protein bound carbohydrates were significantly decreased in the ethanol extract treated groups compared with the arthritic control. The pro-inflammatory cytokine levels were significantly decreased in a dose dependent manner in all the Clerodendrum phlomidis treated groups.Conclusion Clerodendrum phlomidis displays considerable potency in antiinflammatory action and has prominent antiarthritic effect on adjuvant induced arthritis. Future studies will provide new insights into the antiinflammatory activity of Clerodendrum phlomidis and isolation of compound from it may eventually lead to development of a new class of antiinflammatory agent.     

Antimalarial activity of methanolic extracts from plants used in Kenyan ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant rodent parasite, in mice

Methanolic extracts from 15 medicinal plants representing 11 families, used traditionally for malaria treatment in Kenya were screened for their in vivo antimalarial activity in mice against a chloroquine (CQ)-tolerant Plasmodium berghei NK65, either alone or in combination with CQ. The plant parts used ranged from leaves (L), stem bark (SB), root bark (RB), seeds (S) and whole plant (W). When used alone, extracts from seven plants, Clerodendrum myricoides (RB), Ficus sur (L/SB/RB), Maytenus acuminata (L/RB), Rhamnus prinoides (L/RB), Rhamnus staddo (RB), Toddalia asiatica (RB) and Vernonia lasiopus (RB) had statistically significant parasitaemia suppressions of 31.7-59.3%. In combination with CQ, methanolic extracts of Albizia gummifera (SB), Ficus sur (RB), Rhamnus prinoides and Rhamnus staddo (L/RB), Caesalpinia volkensii (L), Maytenus senegalensis (L/RB), Withania somnifera (RB), Ekebergia capensis (L/SB), Toddalia asiatica (L/RB) and Vernonia lasiopus (L/SB/RB) gave statistically significant and improved suppressions which ranged from 45.5 to 85.1%. The fact that these activities were up to five-fold higher than that of extract alone may suggest synergistic interactions. Remarkable parasitaemia suppression by the extracts, either alone or in combination with CQ mostly resulted into longer mouse survival relative to the controls, in some cases by a further 2 weeks. Plants, which showed significant antimalarial activity including Vernonia lasiopus, Toddalia asiatica, Ficus sur, Rhamnus prinoides and Rhamnus staddo warrant further evaluation in the search for novel antimalarial agents against drug-resistant malaria.     

中药提取物及其制剂注册管理研究

该文研究了中药提取物及其制剂注册管理的现状及存在的问题,探讨了影响其质量的因素,从明确概念与外延、监管法律依据,完善和提高质量标准,建立备案管理制度等方面提出了加强其注册管理的对策与建议.     

Antimicrobial activity of Ulopterol isolated from Toddalia asiatica (L.) Lam.: a traditional medicinal plant

Ethnopharmacological relevance

The leaves of Toddalia asiatica (L.) Lam. (Rutaceae) are widely used in folk medicine in India to treat various ailments like cough, malaria, indigestion, influenza lung diseases and rheumatism, fever, stomach ailments, cholera and diarrhea. In our earlier communication we have reported the antimicrobial study on the various extracts of the leaves and the isolation and identification of Flindersine, a quinolone alkaloid as the major active principle. In the present study, we report the antibacterial and antifungal activities of Ulopterol, a coumarin isolated as another major active antimicrobial principle.

Materials and methods

The leaves were successively extracted with hexane, chloroform, ethyl acetate, methanol and water. The extracts were studied for their antimicrobial activity against selected bacteria and fungi by using disc-diffusion method. The ethyl acetate extract which was found to possess highest antimicrobial activity was subjected to activity guided fractionation by column chromatography over silica gel. This resulted in the isolation of the coumarin, Ulopetrol, an active principle besides Flindersine which was reported by us earlier. The structure of the compound was elucidated using physical and spectroscopic data. Flindersine and Ulopterol were quantified by HPLC.

Results

Ulopterol showed activity against the bacteria viz. Staphylococcus epidermidis, Enterobacter aerogenes, Shigella flexneri, Klebsiella pneumoniae (ESBL-3967), Escherichia coli (ESBL-3984) and fungi viz. Aspergillus flavus, Candida krusei and Botrytis cinerea. Quantification by HPLC showed the content of Flindersine and Ulopterol to be 0.361% and 0.266% respectively on dry weight basis of the leaves.

Conclusions

Ethyl acetate extract (successive extraction) contained Ulopterol, a coumarin, besides Flindersine, a quinolone alkaloid, as a major active principle in the antimicrobial studies. This is the first report of the antimicrobial activity of Ulopterol and also its first report from the plant.