Algal-Derived Halogenated Sesquiterpenes from Laurencia dendroidea as Lead Compounds in Schistosomiasis Environmental Control.

Schistosomiasis has been controlled for more than 40 years with a single drug, praziquantel, and only one molluscicide, niclosamide, raising concern of the possibility of the emergence of resistant strains. However, the molecular targets for both agents are thus far unknown. Consequently, the search for lead compounds from natural sources has been encouraged due to their diverse structure and function. Our search for natural compounds with potential use in schistosomiasis control led to the identification of an algal species, Laurencia dendroidea, whose extracts demonstrated significant activity toward both Schistosoma mansoni parasites and their intermediate host snails Biomphalaria glabrata. In the present study, three seaweed-derived halogenated sesquiterpenes, (-)-elatol, rogiolol, and obtusol are proposed as potential lead compounds for the development of anthelminthic drugs for the treatment of and pesticides for the environmental control of schistosomiasis. The three compounds were screened for their antischistosomal and molluscicidal activities. The screening revealed that rogiolol exhibits significant activity toward the survival of adult worms, and that all three compounds showed activity against S. mansoni cercariae and B. glabrata embryos. Biomonitored fractioning of L. dendroidea extracts indicated elatol as the most active compound toward cercariae larvae and snail embryos.

The Prospective Use of Brazilian Marine Macroalgae in Schistosomiasis Control.

Schistosomiasis is a parasitic disease that affects more than 250 million people. The treatment is limited to praziquantel and the control of the intermediate host with the highly toxic molluscicidal niclosamide. Marine algae are a poorly explored and promising alternative that can provide lead compounds, and the use of multivariate analysis could contribute to quicker discovery. As part of our search for new natural compounds with which to control schistosomiasis, we screened 45 crude extracts obtained from 37 Brazilian seaweed species for their molluscicidal activity against Biomphalaria glabrata embryos and schistosomicidal activities against Schistosoma mansoni. Two sets of extracts were taxonomically grouped for metabolomic analysis. The extracts were analyzed by GC-MS, and the data were subjected to Pattern Hunter and Pearson correlation tests. Overall, 22 species (60%) showed activity in at least one of the two models. Multivariate analysis pointed towards 3 hits against B. glabrata veliger embryos in the Laurencia/Laurenciella set, 5 hits against B. glabrata blastula embryos, and 31 against S. mansoni in the Ochrophyta set. Preliminary annotations suggested some compounds such as triquinane alcohols, prenylated guaianes, dichotomanes, and xenianes. Despite the putative identification, this work presents potential candidates and can guide future isolation and identification.

Lantana camara Essential Oils from Vietnam: Chemical Composition, Molluscicidal, and Mosquito Larvicidal Activity.

Lantana camara is a troublesome invasive plant introduced to many tropical regions, including Southeast Asia. However, the plant does hold promise as a source of essential oils that may be explored for potential use. Fresh water snails such as Pomacea canaliculata, Gyraulus convexiusculus, and Tarebia granifera can be problematic agricultural pests as well as hosts for parasitic worms. Aedes and Culex mosquitoes are notorious vectors of numerous viral pathogens. Control of these vectors is of utmost importance. In this work, the essential oil compositions, molluscicidal, and mosquito larvicidal activities of four collections of L. camara from north-central Vietnam have been investigated. The sesquiterpene-rich L. camara essential oils showed wide variation in their compositions, not only compared to essential oils from other geographical locations (at least six possible chemotypes), but also between the four samples from Vietnam. L. camara essential oils showed molluscicidal activities comparable to the positive control, tea saponin, as well as other botanical agents. The median lethal concentrations (LC50 ) against the snails were 23.6-40.2 µg/mL (P. canaliculata), 7.9-29.6 µg/mL (G. convexiusculus), and 15.0-29.6 µg/mL (T. granifera). The essential oils showed good mosquito larvicidal activities with 24-h LC50 values of 15.1-29.0 µg/mL, 26.4-53.8 µg/mL, and 20.8-59.3 µg/mL against Ae. aegypti, Ae. albopictus, and Cx. quinquefasciatus, respectively. The essential oils were more toxic to snails and mosquito larvae than they were to the non-target water bug, Diplonychus rusticus (24-h LC50 =103.7-162.5 µg/mL). Sesquiterpene components of the essential oils may be acting as acetylcholinesterase (AChE) inhibitors. These results suggest that the invasive plant, L. camara, may be a renewable botanical pesticidal agent.

Development of a natural molluscicide prototype kit (MoluSchall) for the control of schistosomiasis mansoni transmission.

INTRODUCTION: In Brazil, Biomphalaria glabrata, B. tenagophila, and B. straminea are intermediate hosts of Schistosoma mansoni, the etiological agent of schistosomiasis mansoni. Molluscicide use is recommended by the WHO for controlling the transmission of this parasite. Euphorbia milii latex has shown promising results as an alternative molluscicide. Thus, a natural molluscicide prototype kit based on freeze-dried E. milii latex was developed and evaluated against Biomphalaria spp. METHODS: E. milii latex was collected, processed, and lyophilized. Two diluents were defined for freeze-dried latex rehydration, and a prototype kit, called MoluSchall, was produced. A stability test was conducted using prototype kits stored at different temperatures, and a toxicity assay was performed using Danio rerio. Additionally, MoluSchall was tested against B. glabrata under semi-natural conditions according to defined conditions in the laboratory. RESULTS: MoluSchall was lethal to three Brazilian snail species while exhibiting low toxicity to D. rerio. Regardless of storage temperature, MoluSchall was stable for 24 months and was effective against B. glabrata under semi-natural conditions, with the same LD100 as observed under laboratory conditions. CONCLUSIONS: MoluSchall is a natural, effective, and inexpensive molluscicide with lower environmental toxicity than existing molluscicides. Its production offers a possible alternative strategy for controlling S. mansoni transmission.

Development of a natural molluscicide prototype kit (MoluSchall) for the control of schistosomiasis mansoni transmission

Abstract INTRODUCTION In Brazil, Biomphalaria glabrata, B. tenagophila, and B. straminea are intermediate hosts of Schistosoma mansoni, the etiological agent of schistosomiasis mansoni. Molluscicide use is recommended by the WHO for controlling the transmission of this parasite. Euphorbia milii latex has shown promising results as an alternative molluscicide. Thus, a natural molluscicide prototype kit based on freeze-dried E. milii latex was developed and evaluated against Biomphalaria spp. METHODS E. milii latex was collected, processed, and lyophilized. Two diluents were defined for freeze-dried latex rehydration, and a prototype kit, called MoluSchall, was produced. A stability test was conducted using prototype kits stored at different temperatures, and a toxicity assay was performed using Danio rerio. Additionally, MoluSchall was tested against B. glabrata under semi-natural conditions according to defined conditions in the laboratory. RESULTS MoluSchall was lethal to three Brazilian snail species while exhibiting low toxicity to D. rerio. Regardless of storage temperature, MoluSchall was stable for 24 months and was effective against B. glabrata under semi-natural conditions, with the same LD100 as observed under laboratory conditions. CONCLUSIONS MoluSchall is a natural, effective, and inexpensive molluscicide with lower environmental toxicity than existing molluscicides. Its production offers a possible alternative strategy for controlling S. mansoni transmission.

Evaluation of molluscicidal activity of three mangrove species (Avicennia schaueriana, Laguncularia racemosa and Rhizophora mangle) and their effects on the bioactivity of Biomphalaria glabrata Say, 1818.

Schistosomiasis is a disease of global extent reaching populations in social vulnerability. One of the control measures of this parasitosis is the use of molluscicidal substances that can fight snails of the genus Biomphalaria, intermediate hosts of Schistosoma mansoni. The aim of this work was to study the toxic activity of three mangrove species (Avicennia schaueriana Stapf. & Leech, ex Moldenke, 1939, Laguncularia racemosa (L.) CF Gaertn, 1807 and Rhizophora mangle L. 1753) on the biological activities of snails Biomphalaria glabrata. Hydroalcoholic extracts were prepared from the stem and leaves of each of the three plant species to which mollusks were exposed. The phytochemical analysis of plants showed the presence of important metabolites in the leaves and stems of L. racemosa and R. mangle, such as tannins and saponins, but the absence of these metabolites in A. schaueriana. Leaf and stem extracts of the three plant species showed low molluscicidal activity, not reaching the standards determined by the World Health Organization (WHO, 1983). L. racemosa and R. mangle has interfered with motility, feeding and oviposition of snails, unlike the extracts of A. schaueriana, which had no effect on these activities.

Impact of Moringa oleifera seed aqueous extract on some biological, biochemical, and histological aspects of Biomphalaria alexandrina snails.

Schistosomiasis is one of the neglected tropical diseases. It is a snail-borne trematode infection, and Biomphalaria alexandrina snails are the intermediate host of Schistosoma mansoni in Egypt. The objective of this study is to evaluate the molluscicidal activity of the aqueous seed extract of Moringa oleifera against B. alexandrina snails. The results showed that this aqueous extract was lethal for B. alexandrina snails (LC50 0.27 g/l; LC90 0.41 g/l). Exposure of snails to the sublethal concentrations of this aqueous extract caused a considerable reduction in survival rates and hatchability rates of eggs of these snails. Moreover, it negatively affected some biochemical aspects, where it increased the levels of transaminases (ALT and AST), while it decreased the concentrations of total protein, albumin, and globulin concentration. Histological examinations of the digestive gland of snails exposed to the sublethal concentrations of aqueous seed extract of M. oleifera revealed severe damage in the digestive cells, where they lost their tips and some were degenerated, while the secretory cells increased in number. Regarding the hermaphrodite gland, there were losses of connective tissues and irregular sperms, and the eggs were degenerated. These findings prove the potent activity of aqueous seed extract of M. oleifera against the intermediate hosts of Schistosoma mansoni and provide a considerable scope in exploiting local indigenous resources for snails' molluscicidal agents.

Molluscicidal activity of Solanum elaeagnifolium seeds against Galba truncatula intermediate host of Fasciola hepatica: Identification of ß-solamarine.

CONTEXT: The persistence of fascioliasis in many developing countries urges the search for simple, cheap, and effective substances. In this view, plants provide interesting molluscicidal activities thanks to the secondary metabolites they produce. The genus Solanum is known for its potent effect on vector snails. OBJECTIVE: The molluscicidal activity of Solanum elaeagnifolium Cav. (Solanaceae) seeds against Galba truncatula Müll. (Lymnaeidae), intermediate host of Fasciola hepatica L. (Fasciolidae), was evaluated. MATERIALS AND METHODS: Solanum elaeagnifolium seeds were powdered and successively extracted using n-hexane, methylene chloride, acetone, and methanol, for 20 h each. After filtration, solvents were evaporated. An acid-base treatment was conducted on seed methanolic extract to isolate total alkaloids and ß-solamarine. Total saponins fraction was obtained after successive macerations and evaporations. The molluscicidal activity was evaluated by subjecting snails, in groups of 10, for 48 h to 500 mL of extracts, fractions, and pure product aqueous solutions, each containing amounts, ranging from 1 to 50 mg of plant material in 5 mg increments. RESULTS: The methanolic extract of seeds, ß-solamarine isolated for the first time from this plant and total saponins fraction showed very potent activities on snails, giving respective median lethal concentrations (LC50) of 1.18, 0.49, and 0.94 mg/L. Total alkaloids fraction obtained from the methanolic extract was less active giving an LC50 value of 14.67 mg/L. DISCUSSION AND CONCLUSION: This study emphasizes that glycoalkaloids and saponins of Solanum elaeagnifolium are potent molluscicidal agents. Seed methanolic extract, ß-solamarine, and total saponins fraction may be used as molluscicides.

Anti-infective Natural Products from Cyanobacteria.

Cyanobacteria are a promising yet underexplored source for novel natural products with potent biological activities. While predominantly cytotoxic compounds have been isolated from cyanobacteria in the past, there are also a significant number of compounds known that possess anti-infective activities. As the need for novel anti-infective lead compounds is high, this manuscript aims at giving a concise overview on the current knowledge about anti-infective secondary metabolites isolated from cyanobacteria. Antibacterial, antifungal, antiviral, antiprotozoal, and molluscicidal activities are discussed. Covering up to February 2015.

Chemical compounds toxic to invertebrates isolated from marine cyanobacteria of potential relevance to the agricultural industry.

In spite of advances in invertebrate pest management, the agricultural industry is suffering from impeded pest control exacerbated by global climate changes that have altered rain patterns to favour opportunistic breeding. Thus, novel naturally derived chemical compounds toxic to both terrestrial and aquatic invertebrates are of interest, as potential pesticides. In this regard, marine cyanobacterium-derived metabolites that are toxic to both terrestrial and aquatic invertebrates continue to be a promising, but neglected, source of potential pesticides. A PubMed query combined with hand-curation of the information from retrieved articles allowed for the identification of 36 cyanobacteria-derived chemical compounds experimentally confirmed as being toxic to invertebrates. These compounds are discussed in this review.

Acacetin-7-rutinoside from Buddleja lindleyana, a new molluscicidal agent against Oncomelania hupensis.

Buddleja lindleyana is a medicinally important member of the family Loganiaceae distributed in Eastern China. The plant has been used in different traditional medications for the treatment of various diseases. Acacetin-7-rutinoside was isolated from the n-butanol fraction of fresh B. lindleyana leaves and found to be a new molluscicidal agent against the snail Oncomelania hupensis. The structure of acacetin-7-rutinoside was elucidated based on spectral data, including 1H NMR and 13C NMR.

A penta-substituted pyridine alkaloid from the rhizome of Jatropha elliptica (Pohl) Muell. Arg. is active against Schistosoma mansoni and Biomphalaria glabrata.

Jatropha elliptica is a shrub distributed throughout the north and west of Brazil and reputedly possesses a wide range of therapeutical properties. The roots of this plant possess molluscicidal activity and contain terpenoids, coumarin, lignoid, steroids and alkaloid. In the present study, we assessed the schistosomicidal, miracicidal and cercaricidal activities (against Schistosoma mansoni) and molluscicidal activities (against adults and egg masses of Biomphalaria glabrata) of the alkaloid diethyl 4-phenyl-2,6-dimethyl-3,5-pyridinedicarboxylate, isolated from the ethanol extract of the rhizome of J. elliptica, have been determined. The alkaloid was 100% lethal to adult schistosomes within 4 days at a concentration of 50 µg/mL. Alterations were observed in the schistosome tegument occasioned by treatment with the alkaloid, such as formation of vesicles and vacuolisation. The extent of tegumental damage of the worm was proportional to the time of incubation and to the concentration of compound. The alkaloid also exhibited a potent cercaricidal activity (LC100 = 2 µg/mL); it was totally ineffective against miracicidal forms of the parasite. Moreover, the alkaloid presented strong activity against adult snails (LC90 = 36.43 µg/mL) but was inactive against their egg masses. It is observed then the potential of this compound for the development of new therapies for the treatment of schistosomiasis.

OVICIDAL EFFECT OF PIPERACEAE SPECIES ON Biomphalaria glabrata, Schistosoma mansoni HOST / Efeito ovicida de espécies de Piperaceae em Biomphalaria glabrata, hospedeiro do Schistosoma mansoni

SUMMARY Schistosomiasis is a neglected disease with public health importance in tropical and subtropical regions. An alternative to the disease control is the use of molluscicides to eliminate or reduce the intermediate host snail population causing a reduction of transmission in endemic regions. In this study nine extracts from eight Piperaceae species were evaluated against Biomphalaria glabrata embryos at blastula stage. The extracts were evaluated in concentrations ranging from 100 to 10 mg/L. Piper crassinervium and Piper tuberculatum extracts were the most active (100% of mortality at 20 mg/L and 30 mg/L respectively). .

RESUMO A esquistossomose é uma doença negligenciada de importância para a saúde pública em regiões tropicais e subtropicais. Uma alternativa para o controle da doença é o uso de moluscicidas para eliminar ou reduzir a população de caramujo hospedeiro, acarretando uma redução da transmissão da doença nas regiões endemicas. Neste estudo, nove extratos vegetais provenientes de oito espécies de Piperaceae foram expostos a embriões de Biomphalaria glabrata no estágio de blástula. Os extratos foram avaliados em concentrações que variaram entre 100 e 10 mg/L, sendo Piper crassinervium e Piper tuberculatum os extratos mais ativos (100% de mortalidade a 20 mg/L e 30 mg/L respectivamente). .

Ovicidal effect of Piperaceae species on Biomphalaria glabrata, Schistosoma mansoni host.

Schistosomiasis is a neglected disease with public health importance in tropical and subtropical regions. An alternative to the disease control is the use of molluscicides to eliminate or reduce the intermediate host snail population causing a reduction of transmission in endemic regions. In this study nine extracts from eight Piperaceae species were evaluated against Biomphalaria glabrata embryos at blastula stage. The extracts were evaluated in concentrations ranging from 100 to 10 mg/L. Piper crassinervium and Piper tuberculatum extracts were the most active (100% of mortality at 20 mg/L and 30 mg/L respectively).

[Mollusicidal effects of some species of plants in hilly and mountainous areas].

OBJECTIVE: To valuate the mollusicidal effects of some plants cultivated in the hilly and mountainous areas on Oncomelania hupensis and screen the plants against O. hupensis snails. METHODS: The mollusicidal effects of water extracts of plant materials were tested in laboratory. RESULT: The LC50 of all the species in 24 h, 48 h, and 120 h reached the middle noxious level against O. hupensis snails. According to the taxis of LC50(s) in 120 h, Eucalyptus camaldulensis was best with a LC50 of 0.013%, and Ailanthus altissima, Zanthoxylum bungeanum, Juglans regia, Melia azedarach, Nerium indicum, Pterocarva stenobtera, Cinnamomum camphora, Vetiveria zizanioides, and Citrus reticulata were the second with LC50 (s) between 0.020% and 0.370%, and Zingiber officinale had a lower effect on snail control with a LC50 of above 0.500%. There was a correlation between the death rate of snails and soak time. CONCLUSION: The resources of snail-restrained plants are very abundant, and four plants, such as Eucalyptus camaldulensis, Ailanthus altissima, Cinnamomum camphora, and Vetiveria zizanioides have some mollusicidal effect.

Molluscicidal and larvicidal activities and essential oil composition of Cymbopogon winterianus.

UNLABELLED: CONTEXT. Cymbopogon winterianus Jowitt ex Bor (Poaceae), known as citronella grass, is an aromatic herbaceous plant and the essential oil extracted from this grass is used in cosmetics, perfumes, hygiene and cleanliness products worldwide. OBJECTIVE: This study investigated the composition and molluscicidal and larvicidal activities of the essential oil of C. winterianus cultivated in North Brazil. MATERIALS AND METHODS: The oil was obtained by hydrodistillation, analyzed by gas chromatography (GC) and GC-mass spectrometry and then its molluscicidal and larvicidal activities against snails (Biomphalaria glabrata) and hatched larvae of Artemia salina, respectively, were evaluated at concentrations from 10 to 1000 mg/L. RESULTS: The main constituents of oil were citronellal (26.5%), geraniol (16.2%), elemol (14.5%) and citronellol (7.3%). The molluscicidal test revealed significant lethal concentration (LC) values (LC90=97.0 mg/L, LC50=54.0 mg/L and LC20=22.0 mg/L), indicating the presence of molluscicidal compounds in the oil. In addition, the oil showed moderate larvicidal activity (LC50=181.0 mg/L) against the larvae of A. salina, which could justify its use in the aquatic environment without affecting other living organisms. DISCUSSION AND CONCLUSION: The results suggest that the oil of C. winterianus could be an effective alternative to control schistosomiasis, with an average margin of safety to other living organisms that coexist with snails.

Molluscicidal and leishmanicidal activity of the leaf essential oil of Syzygium cumini (L.) SKEELS from Brazil.

The chemical composition and biological potential of the essential oil extracted from Syzygium cumini leaves collected in Brazil were examined. GC/MS Analyses revealed a high abundance of monoterpenes (87.12%) in the oil. Eleven compounds were identified, with the major components being α-pinene (31.85%), (Z)-ß-ocimene (28.98%), and (E)-ß-ocimene (11.71%). To evaluate the molluscicidal effect of the oil, it was tested against Biomphalaria glabrata and the LC50 obtained was 90 mg/l. The essential oil also showed significant activity against Leishmania amazonensis, with an IC50 value equal to 60 mg/l. In addition, to evaluate its toxicity towards a non-target organism, the essential oil was tested against Artemia salina and showed a LC50 of 175 mg/l. Thus, the essential oil of S. cumini showed promising activity as a molluscicidal and leishmanicidal agent and might be valuable in combating neglected tropical diseases such as schistosomiasis and leishmaniasis. Further research is being conducted with regard to the purification and isolation of the most active essential-oil compounds.

Molluscicidal activity of Balanites aegyptiaca against Monacha cartusiana.

CONTEXT: Balanites aegyptiaca (L.) Delile (Zygophyllaceae) is a tropical tree that has many folk uses in various countries. The bark extract is used for the control of the fresh water snails that act as intermediary host of Schistosoma. OBJECTIVE: Study the molluscicidal activity and chemical constituents of seed oil and seed glycosides of B. aegyptiaca against Monacha cartusiana and determine the structure-activity relationship. MATERIALS AND METHODS: Two bioassay methods (residual film application and the leaf dipping technique) were used to evaluate the toxicity effect of the seed oil and glycosides, in concentrations of 1.000, 0.500, 0.250 and 0.125%. The seed oil was analysed by GC/MS. Acid hydrolysis and chromatographic separation were used to study the seed saponins. RESULTS: The bioassay of B. aegyptiaca against the land snail, M. cartusiana, indicated the activity of the seed oil and the high activity of the seed saponins. The seed glycosides gave 30.0, 53.3, 73.0 and 73.3% mortality for concentrations of 0.125, 0.250, 0.500 and 1.00%, respectively. The LC(50) values were 0.335 and 0.256%, respectively. The seed oil was analysed by GC/MS. Acid hydrolysis of the seed saponins gave a mixture of diosgenin, yamogenin and 3,5-spirostadiene. DISCUSSION AND CONCLUSION: To study the structure-activity relationship, a triterpenoidal saponin and a triterpenoidal saponins rich extract (of Zygophyllum coccenum) were proven to be inactive. Thus, the activity is associated with the steroidal, not triterpenoidal saponins. Moreover, a spirostane aglycone without sugar moiety, was found to be inactive and attained the activity by glycosidation.

Molluscicidal activity of Aglaia duperreana and the constituents of its twigs and leaves.

The methanol (MeOH) extract of the twigs and leaves of Aglaia duperreana was investigated for its molluscicidal activity against Pomacea canaliculata. The extract was found to exhibit significant molluscicidal activity. The ethyl acetate soluble fraction of the extract showed the most potent molluscicidal activity among different solvent fractions. The bioactivity-guided chemical investigation of the ethyl acetate soluble fraction led to a new triterpenoid along with 15 known compounds. Their structures were elucidated by spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance techniques as well as mass spectroscopic analysis. The molluscicidal activities of compounds 2-16 against P. canaliculata were also investigated. Naringenin trimethyl ether showed significant molluscicidal activity with a median lethal concentration (LC(50)) of 3.9 µg/mL, which was indicated higher potency than the positive control, tea saponin (LC(50)=4.5 µg/mL).

Molluscicidal activity of methomyl and cardenolide extracts from Calotropis procera and Adenium arabicum against the land snail Monacha cantiana.

In this work, we have evaluated the molluscicidal activity of two cardenolide extracts from Adenium arabicum Balf f. [the benzene (B) and methanol (M) extracts], one cardenolide extract from Calotropis procera (Aiton) W.T. Aiton (extract C), and methomyl against the harmful land snail Monacha cantiana (Montagu). The contact LD50 values for the above mentioned plant extracts were 12.62, 34.63, and 34.35 mg·kg⁻¹ of body weight, respectively, while the LD50 for methomyl was 116.62 mg·kg⁻¹, that is, the plant extracts were 9.24, 3.37, and 3.4 times more toxic than methomyl. In addition, a simple colorimetric method, based on Kedde reagent, was modified to determine cardenolide concentrations in plant extracts. Thin layer chromatography analysis (TLC) showed several cardiac glycosidal compounds in each plant extract. The results proved that cardiac glycosides are promising candidate compounds that could be used to control land snails, or exploited to develop new, effective, and environmentally friendly molluscicides.