Antileishmanial Activity of the Essential Oil from Bixa orellana

Leishmaniasis is a neglected tropical disease caused by Leishmania protozoa. There is currently no vaccine against leishmaniasis, and chemotherapy remains the only effective control. However, conventional drugs are toxic, expensive, and require long periods of treatment, and resistance to clinical chemotherapeutic agents is emerging. Recent research on plants has shown a successful approach to obtain new antileishmanial alternatives. Herein, the in vitro and in vivo effects of the essential oil from Bixa orellana seeds against Leishmania amazonensis were evaluated. A total of 73 compounds were detected by gas chromatography–mass spectrometry analysis, of which ishwarane (18.6%) and geranylgeraniol (9.1%) were the major components. The oil showed activity against intracellular amastigote form (IC₅₀ = 8.5 µg/mL), while the cytotoxic concentration was sevenfold higher for the host cells. The ability of Bixa oil to control disease progression of established cutaneous leishmaniasis in BALB/c mice was demonstrated, after a treatment with 30 mg/kg by intraperitoneal administration over 14 days. The present study reports for the first time the antileishmanial potentialities of the essential oil from B. orellana. Copyright © 2013 John Wiley & Sons, Ltd.     

Chemical Characterization,Antileishmanial Activity,and Cytotoxicity Effects of the Essential Oil from Leaves of Pluchea carolinensis (Jacq.) G. Don. (Asteraceae)

Current strategies to control leishmaniasis are mainly based on chemotherapy. However, none of the available drugs can be considered to be ideal to treat this disease. Because of the hydrophobic nature and bioactivities of their components, essential oils (EOs) can be considered as important sources for developing agents against intracellular pathogens, such as Leishmania parasites. In this study, we report the chemical characterization, antileishmanial activities, and cytotoxicity effect of the EO from Pluchea carolinensis (Jacq.) G. Don. (Asteraceae). Chemical analysis revealed that EO from aerial part from P. carolinensis is composed of 44 compounds. The main component was selin‐11‐en‐4α‐ol, which made up 51.0%. In vitro antileishmanial studies showed that P. carolinensis EO inhibited the growth of promastigotes (IC₅₀ = 24.7 ± 7.1 μg/mL) and amastigotes (IC₅₀ = 6.2 ± 0.1 μg/mL) of Leishmania amazonensis, while cytotoxicity evaluation revealed fivefold higher values than those for the parasites. In a model of experimental cutaneous leishmaniasis in BALB/c mice, five doses of EO at 30 mg/kg by intralesional route demonstrated smaller lesion size and parasite burden (p < 0.05) compared with animals treated with Glucantime® and untreated mice. In conclusion, in vitro and in vivo results showed the potentialities of EO from P. carolinensis with the future possibility of a new alternative in the treatment for leishmaniasis. Copyright © 2017 John Wiley & Sons, Ltd.     

Interaction of ascaridole,carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes

The antileishmanial activity of the essential oil (EO) from Chenopodium ambrosioides L. has been demonstrated in vitro and in animal models, attributed to the major components of the EO. This study focused on the effects of the three major EO compounds carvacrol, caryophyllene oxide (Caryo), and the antileishmanial endoperoxide ascaridole (Asc) on mitochondrial functions in Leishmania tarentolae promastigotes (LtP). EO and Caryo were able to partially inhibit the leishmanial electron transport chain, whereas other components failed to demonstrate a direct immediate effect. Caryo demonstrated inhibition of complex III activity in LtP and in isolated complex III from other species. The formation of superoxide radicals was studied in Leishmania by electron spin resonance spectroscopy in the presence of iron chelators wherein selected compounds failed to trigger a significant immediate additional superoxide production in LtP. However, upon prolonged incubation of Leishmania with Asc and especially in the absence of iron chelators (allowing the activation of Asc), an increased superoxide radical production and significant impairment of mitochondrial coupling in Leishmania was observed. Prolonged incubation with all EO components resulted in thiol depletion. Taken together, the major components of EO mediate their leishmanicidal activity via different mitochondrial targets and time profiles. Further studies are required to elucidate possible synergistic effects of carvacrol and Asc and the influence of minor compounds.     

In Vitro and In Vivo leishmanicidal activities of natural and synthetic quinoids

The activities of various compounds isolated from plants traditionally used against leishmaniasis in populations from the tablelands of the Guyanas have been examined. The leishmanicidal activity of plant extracts was evaluated by in vitro testing on promastigote and amastigote stages of Leishmania amazonensis and by in vivo tests on L. amazonensis in mice. The leaves of Jacaranda copaia (Aublet) D. Don yielded two compounds: ursolic acid and jaracanone. Ursolic acid showed an interesting activity in vitro with an ED₅₀ against amastigotes of 0.02 mM and no toxicity to macrophages at twice this dose. Jacaranone displayed a marked activity against promastigotes in vitro with an ED₅₀ of 0.02 mM. Both compounds have weak in vivo antileishmanial activity. Similar synthetic compounds such as quinol and quinone acetates were prepared and showed increased activity in experimental cutaneous leishmaniasis in mice.     

Antiparasitic activity of C-geranyl flavonoids from Mimulus bigelovii

Bioactivity‐directed fractionation of the MeOH fraction of the extract of Mimulus bigelovii by means of an axenic Leishmania amastigote assay and chromatographic techniques resulted in the isolation of four C‐geranyl flavanones, diplacone (1), 3′‐O‐methyldiplacone (2), 4′‐O‐methyldiplacone (3), 3′‐O‐methyldiplacol (4), together with a geranylated flavone, cannflavin A (5). These compounds were separated from M. bigelovii for the first time. All compounds showed moderate antileishmanial activity against axenic Leishmania donovani amastigotes with IC₅₀ values ranging from 4.8 to 14.6 μg/mL. The compounds were also tested against the related kinetoplastid parasite Trypanosoma brucei brucei and they showed activity with IC₅₀ values ranging from 1.4 to 7.2 μg/mL. Copyright © 2011 John Wiley & Sons, Ltd.     

In Vitro Assessment of Plants Growing in Cuba Belonging to Solanaceae Family Against Leishmania amazonensis

In this study, an in vitro antileishmanial assessment of plant extracts from 12 genera and 46 species growing in Cuba belonging to Solanaceae family was performed. A total of 226 extracts were screened against promastigotes of Leishmania amazonensis, and cytotoxicity of active extracts [median inhibitory concentration (IC₅₀) promastigotes <100 µg/mL] was determined on peritoneal macrophage from BALB/c mice. Extracts that showed selective index >5 were then assayed against intracellular amastigote. Metabolomics analysis of promissory extracts was performed using chemical profile obtained by ultra performance liquid chromatography. Only 11 extracts (4.9%) from nine plants were selected as potentially actives: Brunfelsia cestroides A. Rich, Capsicum annuum L., Capsicum chinense Jacq., Cestrum nocturnum L., Nicotiana plumbaginifolia Viv., Solanum havanense Jacq., Solanum myriacanthum Dunal, Solanum nudum Dunal and Solanum seaforthianum And., with IC₅₀ < 50 µg/mL and selectivity index >5. Metabolomics analysis demonstrated significant differences in the chemical profiles with an average of 42.8 (range 31–88) compounds from m/z 104 to 1477, which demonstrated the complex mixture of compounds. In addition, no common markers among active extracts were identified. The results demonstrate the importance of the Solanaceae family to search new antileishmanial agents, particularly in unexplored species of this family. Copyright © 2016 John Wiley & Sons, Ltd.     

天然间苯三酚类成分抗菌活性研究进展

抗菌药物的广泛使用甚至滥用使得细菌的耐药性日趋严重,耐药菌感染已成为威胁全球公共健康的重大问题。间苯三酚类成分广泛分布于陆地植物及海洋生物中,该类成分结构新颖、生物活性多样,其中不乏抗菌活性显著的新颖化合物,具有良好的开发前景。具有抗菌活性的天然间苯三酚类成分主要分布在桃金娘科及藤黄科植物中,该类成分对金黄色葡萄球菌及其耐药菌株、枯草芽孢杆菌、肠球菌等革兰阳性菌具有良好的抗菌效果。对近30年来报道的230个间苯三酚类成分的抗菌活性研究进行综述,以期为该类成分进一步研究和开发提供参考。     

Antipromastigote activity of the malabaricones of Myristica malabarica (rampatri)

A major problem in the management of visceral leishmaniasis, especially in the Indian subcontinent, is the growing unresponsiveness to conventional antimonial therapy, indicating the urgent need to identify new antileishmanial compounds. This study was undertaken to evaluate the antileishmanial activity of the fruit rind of Myristica malabarica that is used as a spice and is also credited with medicinal properties. The antipromastigote activity of different extracts/fractions of M. malabarica and its constituent diarylnonanoids were evaluated in Leishmania donovani promastigotes (MHOM/IN/83/AG83) using the MTS-PMS assay. Preliminary screening of the ether extract (R1) with its crude methanol fraction (R2) and two fractions (R3 and R4) revealed that R2 had potent leishmanicidal activity (IC(50) 31.0 microg/mL), whereas R3 and R4 showed poor activity. Fractionation of R2 yielded four diarylnonanoids (malabaricones A-D, designated as Mal A, Mal B, Mal C and Mal D, respectively). The IC(50) values of Mal A-D were 16, 22, 27 and >50 microg/mL, respectively. Taken together, the data suggest that the methanol extract of M. malabarica, especially its constituent compounds, Mal A and Mal B, have promising antileishmanial activity meriting further investigations regarding the underlying molecular mechanism(s) of action with a view towards future drug development.     

Rosmarinus plants: Key farm concepts towards food applications

Rosmarinus species are aromatic plants that mainly grow in the Mediterranean region. They are widely used in folk medicine, food, and flavor industries and represent a valuable source of biologically active compounds (e.g., terpenoids, flavonoids, and phenolic acids). The extraction of rosemary essential oil is being done using three main methods: carbon dioxide supercritical extraction, steam distillation, and hydrodistillation. Furthermore, interesting antioxidant, antibacterial, antifungal, antileishmanial, anthelmintic, anticancer, anti‐inflammatory, antidepressant, and antiamnesic effects have also been broadly recognized for rosemary plant extracts. Thus the present review summarized data on economically important Rosmarinus officinalis species, including isolation, extraction techniques, chemical composition, pharmaceutical, and food applications.     

In vitro antiprotozoan activity and mechanisms of action of selected Ghanaian medicinal plants against Trypanosoma,Leishmania, and Plasmodium parasites

Trypanosomiasis, leishmaniasis, and malaria are protozoan infections of public health importance with thousands of new cases recorded annually. Control of these infection(s) with existing chemotherapy is limited by drug toxicity, lengthy parenteral treatment, affordability, and/or the emergence of resistant strains. Medicinal plants on the other hand are used in the treatment of various infectious diseases although their chemical properties are not fully evaluated. In this study, we screened 112 crude extracts from 72 selected Ghanaian medicinal plants for anti‐Trypanosoma, anti‐Leishmania, and anti‐Plasmodium activities in vitro and investigated their mechanisms of action. Twenty‐three extracts from 20 plants showed significant antiprotozoan activity against at least 1 of 3 protozoan parasites screened with IC₅₀ values less than 20 μg/ml. Eleven extracts showed high anti‐Trypanosoma activity with Bidens pilosa whole plant and Morinda lucida leaf extracts recording the highest activities. Their IC₅₀ (selectivity index [SI]) values were 5.51 μg/ml (35.00) and 5.96 μg/ml (13.09), respectively. Nine extracts had high anti‐Leishmania activity with Annona senegalensis and Cassia alata leaf extracts as the most active. Their IC₅₀ (SI) values were 10.8 μg/ml (1.50) and 10.1 μg/ml (0.37), respectively. Six extracts had high anti‐Plasmodium activity with the leaf and stem‐bark extracts of Terminalia ivorensis recording the highest activity. Their IC₅₀ (SI) values were 7.26 μg/ml (129.36) and 17.45 μg/ml (17.17), respectively. Only M. lucida at 25 μg/ml induced significant apoptosis‐like cell death in Trypanosoma parasites. Anti‐Leishmania active extracts induced varying morphological changes in Leishmania parasites such as multiple nuclei and/or kinetoplast, incomplete flagella division, or nuclear fragmentation. Active extracts may be potential sources for developing new chemotherapy against these infections.     

Phytochemistry and Antileishmanial Activity of the Leaf Latex of Aloe calidophila Reynolds

Leishmaniasis is a major protozoal disease threatening the lives of 350 million people throughout the world. However, the therapeutic options for the disease are limited. In the present study, the antiprotozoal activity of the latex obtained from the Ethiopian plant Aloe calidophila Reynolds was evaluated by in vitro testing against Leishmania aethiopica and Leishmania major. It was found that the latex possesses moderate activity against both parasites with IC₅₀ values of 64.05 and 82.29 µg/mL, respectively. Phytochemical investigation resulted in the isolation of three anthrones identified as aloinoside, aloin, and microdontin on the basis of IR, MS, ¹H NMR, and ¹³C NMR spectral data. The isolated compounds showed strong antileishmanial activity with IC₅₀ values ranging from 1.76 to 6.32 µg/mL against L. aethiopica and from 2.09 to 8.85 µg/mL against L. major. Although these values were higher than those of amphotericin B (IC₅₀ = 0.109 and 0.067 µg/mL), the selectivity indices (813.35 and 694.90, respectively, against L. aethiopica and L. major) of aloinoside were much better than those of the standard drug (423.49 and 688.96). The results indicate that the isolated compounds have the potential to be used as a scaffold for the development of safe and cost‐effective antileishmanial agents. Copyright © 2014 John Wiley & Sons, Ltd.     

Antiprotozoal activity of quinoline alkaloids isolated from Galipea longiflora,a Bolivian plant used as a treatment for cutaneous leishmaniasis

The stem bark of Galipea longiflora is used by the Chimane Indians in Bolivia for the treatment of cutaneous leishmaniasis produced by Leishmania braziliensis. Petroleum ether and chloroform extracts of stem, root bark and leaves were found active in vitro against Leishmania ssp and Trypanosoma cruzi at 100 μg/mL. The activity guided fractionation of the extracts by chromatography afforded 12 active compounds identified as 2-substituted quinoline alkaloids. BALB/c mice were infected with Leishmania amazonensis (strain PH8 or H-142) and treated 24 h after infection with the major alkaloids from the crude alkaloidal extract; 2-phenylquinoline and 2-n-pentylquinoline. 2-phenylquinoline was as potent as Glucantime (Rhǒne-Poulenc) against the strain H-142, but less active than the reference drug against the virulent strain PH8 of L. amazonensis. 2-n-pentylquinoline did not exhibit any activity. Assays of single local treatments on the rear footpad infection, 2 weeks after the parasitic inoculation, indicated an effect for 2-phenylquinoline by reducing the severity of lesion. However, this activity was found to be slightly lower than that obtained using Glucantime.     

The chemistry and pharmacology of alkaloids and allied nitrogen compounds from Artemisia species: A review

Several reviews have been published on Artemisia's derived natural products, but it is the first attempt to review the chemistry and pharmacology of more than 80 alkaloids and allied nitrogen compounds obtained from various Artemisia species (covering the literature up to June 2018). The pharmacological potential and unique skeleton types of certain Artemisia's alkaloids provoke the importance of analyzing Artemisia species for bioactive alkaloids and allied nitrogen compounds. Among the various types of bioactive Artemisia's alkaloids, the main classes were the derivatives of rupestine (pyridine–sesquiterpene), lycoctonine (diterpene), pyrrolizidine, purines, polyamine, peptides, indole, piperidine, pyrrolidine, alkamides, and flavoalkaloids. The rupestine derivatives are Artemisia's characteristic alkaloids, whereas the rest are common alkaloids found in the family Asteraceae and chemotaxonomically links the genus Artemisia with the tribes Anthemideae. The most important biological activities of Artemisia's alkaloids are including hepatoprotective, local anesthetic, β‐galactosidase, and antiparasitic activities; treatment of angina pectoris, opening blocked arteries, as a sleep‐inducing agents and inhibition of HIV viral protease, CYP450, melanin biosynthesis, human carbonic anhydrase, [3H]‐AEA metabolism, kinases, and DNA polymerase β¹. Some of the important nitrogen metabolites of Artemisia include pellitorine, zeatin, tryptophan, rupestine, and aconitine analogs, which need to be optimized and commercialized further.     

Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata

The present study was carried out to evaluate anti‐Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC₅₀, 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti‐H. pylori agents possessing urease inhibition. Copyright © 2015 John Wiley & Sons, Ltd.     

乌头属藏药化学成分研究进展

我国毛茛科乌头属藏药植物达60种15变种,该属植物中含有多种类型的的化学成分,其中大部分为二萜生物碱,此外还有黄酮、酚酸以及其他类型的化合物等。目前国内外学者已经从乌头属藏药中分离得到了339个化合物。该文将对乌头属藏药的化学成分进行综述,为该属植物的开发利用提供依据。     

穿山龙皂苷的药理作用及机制的研究现状

穿山龙属于薯蓣科植物,广泛分布于我国的华北、东北、青海等地区,其根茎是一种重要的中药材,在我国具有几千年的应用历史。据中医学记载,该药材具有止咳化痰、祛风止痛、舒筋活血等功效。现代研究表明,该药材的主要活性成分为皂苷,具有抗肿瘤、抗炎、降血脂、抑菌和抗病毒等作用。鉴于其诸多的生物学活性及药理作用,针对其开发和应用具有良好的前景。该文对穿山龙皂苷的药理活性、治疗作用及机制的研究现状加以总结,为进一步研发穿山龙皂苷提供理论基础。     

Isolation of antileishmanial sterol from the fruits of Cassia fistula using bioguided fractionation

Natural products represent a rich source of new chemical entities for the development of drugs for neglected diseases. Leishmaniasis still afflicts the poorest populations in the world, with 12 million cases worldwide. This work analysed crude extracts and fractions from the fruits of Cassia fistula against the most dramatic and fatal disease form of leishmaniasis, the visceral form (VL). Hexane extract from the fruits showed significant antileishmanial activity against the promastigote form of Leishmania L. chagasi. The bioguided fractionation resulted in the isolation of a sterol, clerosterol, which was further analysed in different models. Promastigotes presented an inhibitory concentration 50% (IC50) of 10.03 microg/mL and intracellular amastigotes demonstrated high susceptibility, with an IC50 of 18.10 microg/mL. Mammalian cytotoxicity was evaluated and it was demonstrated that clerosterol was 3.6-fold less toxic than the standard drug pentamidine. No antifungal activity of the isolated clerosterol was found. Future studies of the extracted compounds of Cassia fistula could be a useful tool for the development of new therapeutic agents for VL.     

The clinical effectiveness of chokeberry: a systematic review

Products derived from the black chokeberry, Aronia melanocarpa, are claimed to be beneficial in disorders or diseases associated with oxidative stress. The claims are based on evidence from in vitro studies and animal experiments. The active principle – a mixture of procyanidins, anthocyanins and phenolic acids – constitutes one of the most potent natural antioxidants. A systematic review was carried out of the quality of the clinical trials on chokeberry products that had been published up to December 2009, and conventionally established criteria were used to assess the strength of the evidence for their clinical effectiveness. Thirteen studies were identified. The quality of most of the trials and, correspondingly, the evidence of effectiveness for Aronia products is poor. Though laboratory and clinical data indicate that chokeberry products may well be useful as ‘functional food’ for disorders or diseases related to oxidative stress, these promising indications need to be confirmed in more rigorous studies before putative therapeutic uses can be confidently recommended for chokeberry products. Copyright © 2010 John Wiley & Sons, Ltd.     

盐肤木属植物研究进展

盐肤木属植物是一类很重要的资源植物,具有很大的科学研究和资源开发潜力,在许多国家都长久的应用于各种疾病的治疗和预防;具有很高的药用价值;也具有十分广泛的工业应用,和具有很高的经济价值。且盐肤木R. chinensis 的虫瘿俗称"五倍子",是一种化工原料和药用原料。为了对盐肤木属植物的进一步研究开发提供参考,通过检索国内外相关参考文献,从植物种类和分布、化学成分、药理活性、临床应用等方面,归纳了盐肤木属植的国内外研究进展。盐肤木属植物中分离得到的化合物主要包括三萜类、 黄酮类、鞣质与酚酸类等;药理活性方面的报道集中在以抗HIV病毒为主的抗病毒活性为主,同时也有关于抗肿瘤、抗腹泻、抗炎、抗龋齿和保肝等其他活性的研究报道,其活性方面的研究还具有很大的空间。结果对深入开展盐肤木属植物的研究和对药用资源的开发、利用和保护有重要意义。     

Diterpenes as lead molecules against neglected tropical diseases

Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant‐based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.