Trypanocidal and cytotoxic activities of essential oils from medicinal plants of Northeast of Brazil

Chagas disease, caused by Trypanosoma cruzi, is an important cause of mortality and morbidity in Latin America. There are no vaccines available, the chemotherapy used to treat this illness has serious side effects and its efficacy on the chronic phase of disease is still a matter of debate. In a search for alternative treatment for Chagas disease, essential oils extracted from traditional medicinal plants Lippia sidoides, Lippia origanoides, Chenopodium ambrosioides, Ocimum gratissimum, Justicia pectorales and Vitex agnus-castus were investigated in vitro for trypanocidal and cytotoxic activities. Essential Oils were extracted by hydrodistillation and submitted to chemical analysis by gas chromatography/mass spectrometry. The concentration of essential oils necessary to inhibit 50% of the epimastigotes or amastigotes growth (IC(50)) and to kill 50% of trypomastigote forms (LC(50)) was estimated. The most prevalent chemical constituents of these essential oils were monoterpenes and sesquiterpenes. All essential oils tested demonstrated an inhibitory effect on the parasite growth and survival. L. sidoides and L. origanoides essential oils were the most effective against trypomastigote and amastigote forms respectively. No significant cytotoxic effects were observed in mouse peritoneal macrophages incubated with essential oils which were more selective against the parasites than mammalian cells. Taken together, our results point towards the use of these essential oils as potential chemotherapeutic agent against T. cruzi.     

Trypanocidal,leishmanicidal and cytotoxic effects of anthecotulide-type linear sesquiterpene lactones from Anthemis auriculata

Trypanosomiasis and leishmaniasis pose major public health threats for many countries, particularly those in sub-Saharan Africa and South America. In the present study, we evaluated the in vitro antiprotozoal activity of three irregular, linear sesquiterpene lactones recently isolated from Greek Anthemis auriculata, namely anthecotulide (1), 4-hydroxyanthecotulide (2) and 4-acetoxyanthecotulide (3). Trypomastigote forms of Trypanosoma brucei rhodesiense and T. cruzi as well as axenic amastigotes of Leishmania donovani were used for testing. The cytotoxic potential of the compounds was also assessed against mammalian (rat) skeletal myoblasts (L6 cells). All compounds showed potent trypanocidal and leishmanicidal activity. 4-Hydroxyanthecotulide (2) appeared to be the most active compound against all parasites, particularly towards T. b. rhodesiense (IC₅₀ 0.56 μg/ml), whereas 4-acetoxyanthecotulide (3) was the least active. All three metabolites possessed toxicity on mammalian cells, which might limit their use as antiprotozoal agents.     

Screening of potential cytotoxic activities of some medicinal plants of Saudi Arabia

Phytochemicals from plant extracts belong to an important source of natural products which have demonstrated excellent cytotoxic activities. However, plants of different origins exhibit diverse chemical composition and bioactivities. Therefore, discovery of plants based new anticancer agents from different parts of the world is always challenging. In this study, methanolic extracts of different parts of 11 plants from Saudi Arabia have been tested in vitro for their anticancer potential on human liver cancer cell line (HepG2). Particularly, for this study, plants from Asteraceae, Resedaceae and Polygonaceae families were chosen on the basis of locally available ethnobotanical data and their medicinal properties. Among 12 tested extract samples, three samples obtained from Artemisia monosperma stem, Ochradenus baccatus aerial parts and Pulicaria glutinosa stem have demonstrated interesting cytotoxic activities with a cell viability of 29.3%, 28.4% and 24.2%, respectively. Whereas, four plant extracts including Calendula arvensis aerial parts, Scorzonera musilii whole plant, A. monosperma leaves show moderate anticancer properties bearing a cell viability ranging from 11.9 to 16.7%. The remaining extracts have shown poor cytotoxic activities. Subsequently, GC-MS analysis of methanolic extracts of four most active plants extracts such as C. comosum, O. baccatus, P. glutinosa and A. monosperma detected the presence of 41 phytomolecules. Among which 3-(4-hydroxyphenyl) propionitrile (1), 8,11-octadecadiynoic acid methyl ester (2), 6,7-dimethoxycoumarin (3) and 1-(2-hydroxyphenyl) ethenone (4) were found to be the lead compounds of C. comosum, O. baccatus P. glutinosa and A. monosperma, respectively.     

Analysis of antibacterial and cytotoxic potential of medicinal plants from Cholistan desert,Pakistan

This study aimed to investigate the antibacterial and cytotoxic activity of 03 medicinal plants, Calligonum polygonides, Farsetia hamiltonii, and Pulcaria crispa, from Cholistan desert, Pakistan. The active constituents of plants species were extracted in 05 different solvents and the extracts were tested against various bacterial strains and brine shrimps. Although all Calligonum polygonides’s extracts except chloroform were active against Staphylococcus aureus the most active was the acetone extract (21 ± 0.00 mm at 200 μg/disc) and activity was better than Caricef (p-value 0.03). While its water extract was more potent (18 ± 1.45 mm at 200 μg/disc) than Augmentin and Caricef (p-value < 0.005). The methanol extract’s activity (15 ± 0.39 mm in 200 μg/disc) was comparable to Fucidin against Proteus vulgaris (p-value > 0.99) and activity of diethyl ether extract against Escherichia coli (10 ± 1.16 mm in 200 μg/disc) was same as of Urixin (p-value 0.91). Farsetia hamiltonii’s acetone extract against Pseudomonas aeruginosa (10 ± 0.15 mm in 1 μg/disc) was more active than Augmentin Caricef and Cefotax (p-value < 0.02) and against Staphylococcus aureus (15 ± 1.15 mm in 200 μg/disc) activity was higher than Caricef (p-value 0.03). All Pulicaria crispa’s extracts except water extract were found active against Staphylococcus aureus. However, the diethyl ether extract was most effective (25 + 0.00 mm at 150 μg /disc) and activity was more than Augmentin, Oxy-tetracycline, Fucidin, Urixin, Ceftriaxone (p-value < 0.05). Although all extracts were exhibited cytotoxic activity, the Calligonum polygonides’s acetone extract (100%), Farsetia hamiltonii’s diethyl ether extract (90%) and Pulicaria crispa’s methanol extract (100%) were most active at 1000 μg/ml concentration. This study validated the medicinal significance of the studied plants and thus opens the way for their therapeutic applications.     

Systematics and health effects of chemically distinct tannins in medicinal plants

The research began with an investigation of tannins from traditional medicinal plants and resulted in isolation and structure determination of hundreds of ellagitannins and dehydroellagitannins, as well as their oligomers and oxidized derivatives with various structures specific to each plant species. These polyphenols have been classified according to the stage of oxidative structural transformation and oligomerization, into types I-IV and I+ to IV+, etc. Parallels were found between their oxidative transformations and plant evolution. They were also classified by the linkage units between the monomers, into DOG, GOD, GOG and DOGOD types (D=Diphenoyl, G=Galloyl, O=Oxygen), etc. Besides their fundamental activities, e.g., reduction and anti-peroxidation properties, remarkable biological and pharmacological activities of various potencies have also been found, including, amongst others, inhibition of lipid-peroxidation, mutagenicity of carcinogens and tumor promotion, host-mediated antitumor effects specific to particular tannin structures, antiviral activity and potentiation of antibacterial activity.     

Antibacterial and anti-inflammatory effects of Jeju medicinal plants against acne-inducing bacteria

Propionibacterium acnes and Staphylococcus epidermidis are pus-forming bacteria that trigger inflammation in acne. The present study was conducted to evaluate the antimicrobial activities of Jeju medicinal plants against these etiologic agents of acne vulgaris. Ethanol extracts of Jeju plants were tested for antimicrobial activities by disc diffusion and broth dilution methods. The results from the disc diffusion assays revealed that four medicinal plants, Mollugo pentaphylla, Angelica anomala, Matteuccia orientalis, and Orixa japonica inhibited the growth of both pathogens. Among these, A. anomala had strong inhibitory effects. Its MIC values were 15.6 microg/ml and 125 microg/ml against P. acnes and S. epidermidis, respectively. The cytotoxic effects of the four extracts were determined by colorimetric MTT assays using two animal cell lines: human dermal fibroblasts and HaCaT cells. Although the M. orientalis root extract had moderate cytotoxicity in HaCaT cells at 200 microg/ml, most extracts exhibited low cytotoxicity at 200 microg/ml in both cell lines. In addition, the extracts reduced the P. acnes-induced secretion of interleukin-8 and tumor necrosis factor-alpha (TNF-alpha) in THP-1 cells, an indication of their anti-inflammatory effects. Based on these results, we suggest that M. pentaphylla, A. anomala, M. orientalis, and O. japonica are attractive acne-mitigating candidates for topical application.     

Trypanocidal constituents in plants: 7. Mammea-type coumarins

Calophyllum brasiliense and Mammea americana (Clusiaceae) are two trees from the tropical rain forests of the American continent. A previous screening showed high trypanocidal activity in the extracts of these species. Several mammea-type coumarins, triterpenoids and biflavonoids were isolated from the leaves of C. brasiliense. Mammea A/AA was obtained from the fruit peels of M. americana. These compounds were tested in vitro against epimastigotes and trypomastigotes of Trypanosoma cruzi, the etiologic agent of Chagas disease. The most potent compounds were mammea A/BA, A/BB, A/AA, A/BD and B/BA, with MC100 values in the range of 15 to 90 g/ml. Coumarins with a cyclized ,-dimethylallyl substituent on C-6, such as mammea B/BA, cyclo F + B/BB cyclo F, and isomammeigin, showed MC100 values > 200 g/ml. Several active coumarins were also tested against normal human lymphocytes in vitro, which showed that mammea A/AA and A/BA were not toxic. Other compounds from C. brasiliense, such as the triterpenoids, friedelin, canophyllol, the biflavonoid amentoflavone, and protocatechuic and shikimic acids, were inactive against the epimastigotes. The isopropylidenedioxy derivative of shikimic acid was inactive, and its structure was confirmed by X-ray diffraction. Our results suggest that mammea-type coumarins could be a valuable source of trypanocidal compounds.     

Screening of Korean medicinal plants for possible osteoclastogenesis effects in vitro

Bone undergoes continuous remodeling through bone formation and resorption, and maintaining the balance for skeletal rigidity. Bone resorption and loss are generally attributed to osteoclasts. Differentiation of osteoclasts is regulated by receptor activator of nuclear factor NF-kB ligand (RANKL), a member of tumor necrosis factor family. When the balance is disturbed, pathological bone abnormality ensues. Through the screening of traditional Korean medicinal plants, the effective molecules for inhibition and stimulation of RANKL-induced osteoclast differentiation in mouse bone marrow macrophages were identified. Among 222 methanol extracts, of medicinal plants, 10 samples exhibited ability to induce osteoclast differentiation. These include Dryobalanops aromatica, Euphoria longana, Lithospermum erythrorhizon, Prunus mume, Prunus nakaii, and Polygonatum odoratum. In contrast, Ailanthus altissima, Curcuma longa, Solanum nigrum, Taraxacum platycarpa, Trichosanthes kirilowii, and Daphne genkwa showed inhibitory effects in RANKL-induced osteoclast differentiation.     

Comparison of the total antioxidant content of 30 widely used medicinal plants of New Mexico

Teas made from medicinal plants are commonly used by a majority of the inhabitants of New Mexico and Mexico to treat various ailments including infections, arthritis, heart disorders, headaches, fever, asthma and menstrual pain. However, little is known about the identity or chemical nature of the bioactive substances and compounds responsible for the therapeutic effects of the teas made from the leaves, seeds, flowers stems, and roots of these medicinal plants. Some of the beneficial effects of these teas may be attributable to antioxidants contained in the medicinal plants from which they are brewed. In the present study we collected 30 medicinal plants that are widely used in the Rio Grande Valley and, using a two-stage Trolox based assay, analyzed the total antioxidant capacity of aqueous extracts prepared from these plants. The antioxidant content of the aqueous extracts was substantial, ranging from 27 to 972 micromol Trolox equivalent per gram dry weight. An extract of the leaves of the plant Ilex paraguensis (Mate leaf) contained the highest amount of antioxidant, followed by the flowers of the Rosa sp. (Rosa de Castillo, 804 micromol/g), the bark of Chinchona sp. (Copalquin, 692 micromol/g), Rumex hymenosepalus stems (Cana Agria, 672 micromol/g) and the leaves of Marrubium vulgare (Mastranzo, 560 micromol/g). The plants that had the lowest antioxidant capacity were the seeds of Linum lewissii (Linasa, 29 micromol/g) and Yucca sp. plant root (Amole, 27 micromol/g). It will be useful to further analyze those plants that contain the most antioxidant activity in order to identify the active principles.     

Trypanocidal and cytotoxic evaluation of synthesized thiosemicarbazones as potential drug leads against sleeping sickness

Thiosemicarbazones have become one of the promising compounds as new clinical candidates due to their wide spectrum of pharmaceutical activities. The wide range of their biological activities depends generally on their related aldehyde or ketone groups. Here, we report the pharmacological activities of some thiosemicarbazones synthesized in this work. Benzophenone and derivatives were used with N(4)-phenyl-3-thiosemicarbazide to synthesize corresponding five thiosemicarbazones (1–5). Their structures were characterized by spectrometrical methods analysis IR, NMR ¹H & ¹³C and MS. The compounds were then screened in vitro for their antiparasitic activity and toxicity on Trypanosoma brucei brucei and Artemia salina Leach respectively. The selectivity index of each compound was also determined. Four thiosemicarbazones such as 4, 2, 3 and 1 reveal interesting trypanocidal activities with their half inhibitory concentration (IC₅₀) equal to 2.76, 2.83, 3.86 and 8.48 μM respectively, while compound 5 (IC₅₀ = 12.16 μM) showed a moderate anti-trypanosomal activity on parasite. In toxicity test, except compound 1, which showed a half lethal concentration LC₅₀ >281 μM, the others exerted toxic effect on larvae with LC₅₀ of 5.56, 13.62, 14.55 and 42.50 μM respectively for thiosemicarbazones 4, 5, 3 and 2. In agreement to their selectivity index, which is greater than 1 (SI >1), these compounds clearly displayed significant selective pharmaceutical activities on the parasite tested. The thiosemicarbazones 2–5 that displayed significant anti-trypanosomal and cytoxicity activities are suggested to have anti-neoplastic and anti-cancer activities.     

Antineoplastic potential of medicinal plants

Cancer is one of the most dreaded diseases worldwide and the incidence is on the rise in both developing and developed countries. It is treated by chemotherapy, radiotherapy and surgery. In spite of advances in treatment strategies, cancer still remains a major cause of death. Research is on for development of better drugs which are more effective and simultaneously cause fewer side effects. Plants have been used for the treatment of various ailments of man and animals since ages. They are being screened extensively to explore the possibility of development of economically viable anticancer drugs. Natural products of plant origin currently constitute a considerable proportion of commercially available antineoplastic drugs. This review gives an insight into commercially available anticancer drugs of plant origin and also patents granted to plant derived components, extracts and polyherbal formulations possessing anticancer activity. The exhaustive work reviewed here on antineoplastic activity of various plants both in vitro and experimental models throughout the world will help design further research in this field.     

Drug discovery from medicinal plants

Current research in drug discovery from medicinal plants involves a multifaceted approach combining botanical, phytochemical, biological, and molecular techniques. Medicinal plant drug discovery continues to provide new and important leads against various pharmacological targets including cancer, HIV/AIDS, Alzheimer's, malaria, and pain. Several natural product drugs of plant origin have either recently been introduced to the United States market, including arteether, galantamine, nitisinone, and tiotropium, or are currently involved in late-phase clinical trials. As part of our National Cooperative Drug Discovery Group (NCDDG) research project, numerous compounds from tropical rainforest plant species with potential anticancer activity have been identified. Our group has also isolated several compounds, mainly from edible plant species or plants used as dietary supplements, that may act as chemopreventive agents. Although drug discovery from medicinal plants continues to provide an important source of new drug leads, numerous challenges are encountered including the procurement of plant materials, the selection and implementation of appropriate high-throughput screening bioassays, and the scale-up of active compounds.