Larvicidal efficacy of plant extracts and isolated compounds from Annonaceae and Piperaceae against Aedes aegypti and Aedes albopictus

The Aedes (Ae.) aegypti and Ae. albopictus mosquitoes are vectors of epidemiologically relevant arboviruses in the public health context, such as the dengue, Zika and chikungunya viruses. Among the alternatives to synthetic insecticides for the control of these vectors, the use of natural plant products deserves attention. This review summarizes findings on the larvicidal potential of plant extracts on Ae. aegypti and Ae. albopictus, as well as the potential of isolated compounds from plants of the Annonaceae and Piperaceae families against these vectors. Descriptors related to larvicidal activity of plant extracts and isolated compounds in Aedes spp. in the Web of Science database were used, for plant extracts considering publications between 2000 and 2019. A total of 859 articles were analyzed for plant extracts and estimates of lethal concentration values (LC50 and LC90). In the end, 95 articles that presented the larvicidal potential of 150 plant species from 52 families were analyzed. The two families most studied for this activity were Fabaceae and Asterace Aedes. The plant families with the best LC50 values against mosquitoes were Piperaceae and Annonaceae. Larvicidal activity of 50 acetogenins has already been identified on Ae. aegypti, and 29 of them presented LC50 below 10 ug/mL, as well as the larvicidal activity of 8 compounds isolated from Piperaceae. Therefore, plants of these two families are promising for the development of commercial botanical larvicides in the form of extracts and isolated substances, as well as the production via organic synthesis of the most active compounds.

Larvicidal efficacy of plant extracts and isolated compounds from Annonaceae and Piperaceae against Aedes aegypti and Aedes albopictus

The Aedes (Ae.) aegypti and Ae. albopictus mosquitoes are vectors of epidemiologically relevant arboviruses in the public health context, such as the dengue, Zika and chikungunya viruses. Among the alternatives to synthetic insecticides for the control of these vectors, the use of natural plant products deserves attention. This review summarizes findings on the larvicidal potential of plant extracts on Ae. aegypti and Ae. albopictus, as well as the potential of isolated compounds from plants of the Annonaceae and Piperaceae families against these vectors. Descriptors related to larvicidal activity of plant extracts and isolated compounds in Aedes spp. in the Web of Science database were used, for plant extracts considering publications between 2000 and 2019. A total of 859 articles were analyzed for plant extracts and estimates of lethal concentration values (LC50 and LC90). In the end, 95 articles that presented the larvicidal potential of 150 plant species from 52 families were analyzed. The two families most studied for this activity were Fabaceae and Asterace Aedes. The plant families with the best LC50 values against mosquitoes were Piperaceae and Annonaceae. Larvicidal activity of 50 acetogenins has already been identified on Ae. aegypti, and 29 of them presented LC50 below 10 ug/mL, as well as the larvicidal activity of 8 compounds isolated from Piperaceae. Therefore, plants of these two families are promising for the development of commercial botanical larvicides in the form of extracts and isolated substances, as well as the production via organic synthesis of the most active compounds.

Eight new cytotoxic annonaceous acetogenins from the seeds of Annona squamosa / 中国天然药物

Eight new annonaceous acetogenins, squamotin A-D (1-4), annosquatin IV-V (5 and 6), muricin O (7) and squamosten B (8), together with four known ones (9-12) were isolated from the seeds of Annona squamosa. Their structures were elucidated by chemical methods and spectral data. The inhibitory activities of compound 1-9 against three multidrug resistance cell lines were evaluated. All tested compounds showed strong cytotoxicity.

Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats

To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine (DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were determined. Results: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity [IC50=(53.7±4.3) μg/mL]. The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.

Annona muricata fruit extract protects against diethylnitrosamine-induced hepatocellular cancer in rats

To evaluate the anticancer potentials of Annona muricata fruit by in vitro and in vivo methods. Methods: The ethanolic extract of Annona muricata fruit was prepared by Soxhlet extraction method and further fractionated with petroleum ether, ethyl acetate and chloroform. The fractions were tested for cytotoxicity, apoptosis, scratch wound assay, and cell cycle analysis. IC50, apoptotic index and percentage cell migration were determined using HepG2 cells. For the in vivo studies, hepatocellular carcinoma was induced by administering 0.01% diethylnitrosamine (DEN) in drinking water in Wistar rats. In pre-treatment, rats were co-administered 200 mg/kg of fruit extract with DEN for 14 weeks. In post-treatment, the extract was co-administered after 8-weeks of DEN-induction for 14 weeks. Liver function test, haematological test, oxidative stress markers, relative liver weight, number of cancer nodules and histopathological parameters were determined. Results: Annona muricata fruit extract =significantly lowered cell proliferation counts. The chloroform-fraction possessed higher activity [IC50=(53.7±4.3) μg/mL]. The chloroform fraction inhibited cell migration, which was significant compared to curcumin. Further investigations regarding the mode of anticancer activity revealed that the chloroform fraction induced apoptosis. The cell cycle analysis indicated that cells were being arrested at G0/G1. In the in vivo studies, the DEN-control group showed a significant decrease in body weights with increased mortality rate, hepatic nodules, and impairment of liver function compared to normal rats. The rats pre-treated and post-treated with the extract showed positive results with significant improvement in the parameters that were adversely affected by DEN. In addition, other adverse effects of DEN, such as blood dyscrasias and hepatic endogenous antioxidant, were significantly attenuated by Annona muricata fruit extract. Conclusions: The Annona muricata fruit extract has anticancer activity when tested by in vitro and in vivo hepatocellular cancer models.

Acetogeninas, alternativa en el tratamiento de cáncer en caninos / Acetogenins, alternative cancer treatment in dogs / Acetogeninas, alternativa no tratamento de câncer em caninos

Resumen El cáncer es una enfermedad que implica la alteración de procesos celulares, como metabolismo celular, activación o silenciamiento de genes y crecimiento descontrolado. Es una las principales causas de muerte en humanos, así como en animales de compañía, por lo cual cada vez es más importante la búsqueda y desarrollo de medicamentos. Algunos de los medicamentos que se producen para tratar el cáncer, provienen de plantas, como el taxol y la vincristina. La necesidad de ampliar el uso de productos naturales para tratar esta enfermedad, no solo en humanos sino en animales de compañía como caninos, abre las puertas a la búsqueda de actividad biológica de plantas que son usadas popularmente por presentar algún efecto con la enfermedad. Este es el caso de la guanábana (Annona muricata), de la cual se han extraído metabolitos secundarios (acetogeninas) que presentan in vitro mayor toxicidad en líneas celulares cancerígenas comparadas con líneas celulares normales. El fin de esta revisión fue realizar una aproximación de los usos de estos metabolitos en cáncer, para ello fue hecha una búsqueda en PubMed con diferentes palabras claves y se concluyó, que las acetogeninas comprenden una fuente potencial para el desarrollo de medicamentos contra el cáncer.

Abstract Cancer is a disease that alter cellular processes, like cell metabolism, activation and deactivation of genes and uncontrolled growth. It is one of the main causes of death in humans, as well as in companion animals, which is why it is increasingly important to seek and develop medicines for the treatment. Some of the drugs that are produced to treat cancer come from plants, such as taxol and vincristine. The necessity to expand the use of natural products to treat this disease, not only in humans but also in companion animals such as dogs, opens the doors to seek biological activity of plants that are commonly used because they present some effect over the disease. This is the case of soursop (Annona muricata), from which secondary metabolites (acetogenins) have been extracted and have presented in vitro greater toxicity in cancer cell lines compared to normal cell lines. Therefore, this review was carried out in order to make an approximation of the uses of these metabolites in cancer, for which a search was carried out in PubMed with different key words and it was concluded that acetogenins comprise a potential source for the development of medicines against cancer.

Resumo O câncer é uma doença que envolve a alteração de processos celulares, como o metabolismo celular, ativação ou silenciamento de genes e o crescimento descontrolado. É uma das principais causas de morte em humanos, assim como em animais de companhia, para os quais a busca e o desenvolvimento de medicamentos são cada vez mais importantes. Algumas das drogas que são produzidas para tratar o câncer são derivadas de plantas, como o taxol e a vincristina. A necessidade de ampliar o uso de produtos naturais para tratar esta doença, não somente em humanos, mas em animais de companhia, como cães, abre as portas para a busca da atividade biológica de plantas que são popularmente usadas para causar algum efeito na doença. Este é o caso da graviola (Annona muricata), da qual se extraíram os metabólitos secundários (acetogeninas), que apresentam maior toxicidade in vitro nas linhagens de células cancerígenas do que nas linhagens normais. O objetivo desta revisão foi fazer uma aproximação dos usos desses metabólitos no câncer, para os quais foi feita uma pesquisa em PubMed com palavras-chave diferentes e concluiu-se que as acetogeninas constituem uma fonte potencial para o desenvolvimento de drogas anti-câncer.

Rollinia mucosa (Jacq) Baillon (Annonaceae) active metabolites as alternative biocontrol agents against the lace bug Corythucha gossypii (Fabricius): an insect pest / Metabolitos activos de la semilla de Rollinia mucosa (Jacq) Baillon (Annonaceae) como agentes alternativos de biocontrol sobre el insecto fitopatógeno Corythucha gossypii (Fabricius) / Metabólitos ativos de Rollinia mucosa (Jacq) Baillon (Annonaceae) como agentes de biocontrole alternativos contra Corythucha gossypii (Fabricius): um inseto-praga

Abstract The lace bug, Corythucha gossypii (Fabricius) is a serious pest affecting over 24 wild and commercially important plant species of the families Annonaceae, Passiflorcae, Caricaceae, Euphorbiaceae, and Solanaceae. Thus far, commercial insecticides, such as 0.1% Dimethoate and 0.1% Imidacloprid have shown effectiveness against this insect, but no botanical pesticides are available to control this bug. In the present study, a Rollinia mucosa (Jacq.) Baillon ethanol extract was evaluated as a biological control agent against the lace bug. Through a toxicity assay involving Artemia salina, the median lethal concentration (LC50) of a raw ethanol extract of R. mucosa seeds was determined, as well as that of its Acetogenin (F1) and Alkaloid (F2) fractions; these LC50 were 0.184, 0.082, and 0.0493 μg/mL, respectively. In addition, with an insecticide assay on lace bug nymphs, a mortality percentage of 86.67% at 5 μg/mL after 72h was observed. These data demonstrate that the R. mucosa seed extract is highly active. Further chemical characterization studies revealed that the main active metabolites contributing to extract activity were acetogenins and alkaloids.

Resumen El hemíptero, Corythucha gossypii (Fabricius) es un insecto que causa daño sustancial en cultivos de más de 24 especies de plantas de las familias Annonaceae, Passifloraceae, Caricaceae, Euphorbiaceae y Solanaceae. En su mayoría estas plantas son de interés económico. Aunque insecticidas comerciales como el Dimetoato (0.1%) y el Imidacloprid (0.1%) permiten un manejo eficiente de este insecto-plaga, no se han reportado alternativas botánicas para estos insecticidas sintéticos. En el presente estudio se evaluó el extracto etanólico de la semilla de Rollinia mucosa (Jacq.) Baillon, como un biocontrolador de C. gossypii. A través de un test de toxicidad con Artemia salina se determinó que la concentración del extracto etanólico letal para el 50% de la población bajo estudio (LC50) fue de 0.184 μg/mL. De igual modo se identificó que las fracciones de acetogeninas (F1) y de alcaloides (F2) de este extracto tienen un LC50 de 0.082 y 0.0493 μg/mL, respectivamente. En el ensayo insecticida con ninfas de C. gossypii se observó una mortalidad del 86.67% después de 72 horas de exposición al extracto etanólico a una concentración de 5 μg/mL. Lo anterior demuestra que el extracto es altamente activo. La caracterización química del extracto evidenció que los principales metabolitos activos que contribuyen a su actividad insecticida son las acetogeninas y los alcaloides.

Resumo Corythucha gossypii (Fabricius) é uma praga séria que afeta mais de 24 plantas silvestre e de interesse comercial, pertencentes as famílias Annonaceae, Passifloraceae, Caricaceae, Euphorbiaceae e Solanaceae. Até o momento, inseticidas comerciais como Dimetoato (0.1%) e Imidacloprid (0.1%) apresentam um controle eficiente sobre este inseto, entretanto não há reportes de pesticidas de origem vegetal para o seu controle. No presente estudo, o extrato etanólico de Rollinia mucosa (Jacq.) Baillon foi avaliado como um controle biológico contra Corythucha gossypii. Por meio do ensaio de toxicidade com Artemia salina a concentração letal média (LC50) para o extrato etanólico das sementes, suas frações de acetogeninas (F1) e fração de alcaloides (F2) foi de 0.184, 0.082 y 0.0493 μg/mL, respetivamente. Adicionalmente, na avaliação do ensaio inseticida, se obteve uma porcentagem de mortalidade de 86.67% à concentração de 5 μg/mL após de 72 horas de exposição, demonstrando uma alta atividade do extrato de sementes de R. mucosa. Os estudos em relação à caracterização química evidenciaram que os principais metabólitos que aportam à atividade do extrato foram as acetogeninas e alcaloides.

Preparation of annonaceous acetogenins nanosuspensions using poloxamer 188 as a stabilizer and their in vitro and in vivo investigation / 药学学报

Annonaceous acetogenins (ACGs) are effective part extracted and separated from Annona squamosa seeds, they have good antitumor activity against a variety of tumor cells. However, the solubility of ACGs is poor with serious toxic and side effects, which greatly limits their application in clinical practice. In this study poloxamer 188 (P188) was selected as a drug carrier or a stabilizer to prepare ACGs nanosuspensions (ACGs-NSps) using anti-solvent precipitation. The nanosuspensions were examined via dynamic light scattering (DLS) method to examine size of the nanosuspensions. Transmission electron microscopy was used to observe their morphology. HPLC assay was used to measure their drug loading content and the in vitro drug release. The stability of ACGs-NSps at room temperature, in various physiological media and plasma, and the hemolytic test and lyophilization were all investigated. MTT assay was performed to study the cytotoxocity of ACGs-NSps against four tumor cell lines. 4T1 bearing tumor model was used to assess their in vivo antitumor therapeutic efficacy. The obtained ACGs-NSps were spherical, the average particle size was 169.4±1.25 nm, the polydispersity index (PDI) value was 0.130±0.020, the zeta potential was -19.8 mV and the drug loading content was 48.18%. ACGs-NSps were stable at room temperature for at least 15 days. They could be lyophilized in the presence of 0.5% glucose and 2.0% P188. ACGs-NSps showed sustained in vitro drug release, and the cumulative drug release reached 80.82% within 144 hours. ACGs-NSps maintained their particle size in various physiological media, and plasma with no hemolysis and then met demands of both oral and intravenous administration. In contrast to free ACGs, ACGs-NSps displayed significantly higher cytotoxicity against 4T1 (IC50, 0.892±0.124 μg·mL-1 vs 2.495±0.108 μg·mL-1, P 50, 0.747±0.051 μg·mL-1 vs 2.204±0.064 μg·mL-1, P 50, 2.265±0.081 μg·mL-1 vs 4.159±0.071 μg·mL-1, P 50, 0.473±0.024 μg·mL-1 vs 1.196±0.022 μg·mL-1, P in vivo study demonstrated that the daily oral administration of ACGs-NSps (3 mg·kg-1) resulted in higher tumor inhibition rate compared to ACGs/oil solution (67.23% vs 53.11%), comparable to the intravenous injection of 0.5 mg·kg-1 ACGs-NSps every other day (70.34%). Nanosuspensions effectively solved the problem of ACGs insolubility and difficulty in drug delivery. Using P188, a pharmaceutic adjuvant approved by FDA for iv injection, the resultant ACGs-NSps appear promising as an anti-tumor drug that can be used in clinic.

Annona muricata: Is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects

Annona muricata (A. muricata) is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses. This review focuses on the research history of its traditional uses, phytochemicals, pharmacological activities, toxicological aspects of the extracts and isolated compounds, as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment. A. muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer. More than 200 chemical compounds have been identified and isolated from this plant, the most important being alkaloids, phenols and acetogenins. Using in vitro studies, its extracts and phytochemicals have been characterized as antioxidant, anti-microbial, anti-inflammatory, insecticidal, larvicidal, and cytotoxic to cancer cells. In vivo studies have revealed anxiolytic, anti-stress, anti-inflammatory, immunomodulatory, antimalarial, antidepressant, gastro protective, wound healing, hepato-protective, hypoglycemic, anticancer and anti-tumoral activities. In silico studies have also been reported. In addition, clinical studies support the hypoglycemic as well as some anticancer activities. Mechanisms of action of some pharmacological activities have been elucidated. However, some phytochemical compounds isolated from A. muricata have shown a neurotoxic effect in vitro and in vivo, and therefore, these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects, optimal dosage, and mechanisms of action, long-term safety, and potential side effects. Additionally, more clinical studies are necessary to support the therapeutic potential of this plant. Some studies were also found to have successfully regenerated the plant in vitro, but with limited success. The reported toxicity notwithstanding, A. muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.

Inhibition of annonaceous acetogenins on cell activities of human gastric cancer cells in vitro / 中草药

Objective To study the effect of annonaceous acetogenins (ACGs) on human gastric cancer cells in vitro. Methods After ACGs were administered to gastric cancer cells in vitro, the cell viability, cell adhesion ability and cell migration ability were assessed by MTT assay, adhesion assay and wound-healing assay, respectively. Results ACGs inhibited the cell viability, adhesion ability and migration ability in a dose-dependent manner in gastric cancer cells. Conclusion ACGs could inhibit cell activities of human gastric cancer cells in viro, and will be developed as a promising anticancer candidate and used in gastric cancer.

Annona muricata: Is the natural therapy to most disease conditions including cancer growing in our backyard? A systematic review of its research history and future prospects

Annona muricata (A. muricata) is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses. This review focuses on the research history of its traditional uses, phytochemicals, pharmacological activities, toxicological aspects of the extracts and isolated compounds, as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment. A. muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer. More than 200 chemical compounds have been identified and isolated from this plant, the most important being alkaloids, phenols and acetogenins. Using in vitro studies, its extracts and phytochemicals have been characterized as antioxidant, anti-microbial, anti-inflammatory, insecticidal, larvicidal, and cytotoxic to cancer cells. In vivo studies have revealed anxiolytic, anti-stress, anti-inflammatory, immunomodulatory, antimalarial, antidepressant, gastro protective, wound healing, hepato-protective, hypoglycemic, anticancer and anti-tumoral activities. In silico studies have also been reported. In addition, clinical studies support the hypoglycemic as well as some anticancer activities. Mechanisms of action of some pharmacological activities have been elucidated. However, some phytochemical compounds isolated from A. muricata have shown a neurotoxic effect in vitro and in vivo, and therefore, these crude extracts and isolated compounds need to be further investigated to define the magnitude of the effects, optimal dosage, and mechanisms of action, long-term safety, and potential side effects. Additionally, more clinical studies are necessary to support the therapeutic potential of this plant. Some studies were also found to have successfully regenerated the plant in vitro, but with limited success. The reported toxicity notwithstanding, A. muricata extracts seem to be some of the safest and promising therapeutic agents of the 21st century and beyond that need to be studied further for better medicinal formulations and diseases management.

Structure-activity relationship of annonaceous acetogenins against multidrug resistant human hepatic carcinoma cell line SMMC-7721/ADR / 中国中药杂志

The present research was launched to investigate the effects of 12 annonaceous acetogenins (ACGs) on human hepatic carcinoma cell line SMMC-7721/ADR, and to find out their structure-activity relationship. SMMC-7721/ADR cells were treated with 12 ACGs including annosquamin A(1)，annosquamin B(2)，annotemoyin-1(3)，uvariamicin Ⅱ(4)，annosquacin D(5)，annosquacin B(6)，isodesacetyluvaricin(7)，uvarigrandin A(8)，squamostatin D(9)，squamostatin E(10)，squamostatin A(11)，and 12,15-cis-squamostatin A(12) for 24 h, and the different expression of the target gene NDUFV2 were detected by quantitative real-time PCR. All the tested compounds made the expression of the target gene NDUFV2 decreased on human hepatic carcinoma cell line SMMC-7721/ADR, of which the bistetrahydrofuran ACGs showed the best activity,which the non-adjacent bistetrahydrofuran ACGs displayed the worst activity.The ACGs with the reducing number of carbons between γ-unsaturated lactone and the close tetrahydrofuran (THF) ring are more potent. For bistetrahydrofuran ACGs with the same nucleus skeleton,they would be more active as more hydroxyls on aliphatic chain, which for the non-adjacent bistetrahydrofuran ACGs with less hydroxyls on aliphatic chain that would be more active. ACGs with 3 hydroxyls on aliphatic chain would be more active. ACGs with threo configuration are more active than erythro configurotion, and the compounds with cis THF ring seem to be superior to those of trans THF ring. Furthermore, the ACGs with the reducing number of carbons between terminal methyl and the close tetrahydrofuran (THF) ring are more potent.

Antibacterial and Antioxidant Activities of Acetogenins from Streptomyces sp. VE2; An Endophyte in Vernonia cinerea (L.) Less.

Strain VE2 was isolated from the stem tissue of Vernonia cinerea (L.) Less. and identified as Streptomyces sp. on the basis of morphology, chemotaxonomy and 16SrDNA sequencing. The fractionation of the crude ethyl acetate (CEA) extract from VE2 cultures led to the isolation of two acetogenins; squamocin and rollidecin B; these compounds and CEA extract had potential in antibacterial and antioxidant activities. The crude extract showed the highest activity against Salmonella typhi ATCC19430 and Bacillus cereus ATCC7064, with MIC values of 32 µg/ml. Squamocin also showed the lowest MIC (32 µg/ml) and Minimum Bactericidal Concentration (MBC) (128 µg/ml) against S. Typhi and B. cereus with corresponding large diameter of the zone of inhibitions (27.5 and 28.2 mm, respectively). Rollidecin B showed the highest DPPH antioxidant activity with SC50 value of 58.92 µg/ml.

Structure activity relationship of annonaceous acetogenins against multidrug resistant human lung cancer cell line A549/Taxol in vitro / 中国中药杂志

10 kinds of annonaceous acetogenins were selected for antitumor activity testing against human lung cancer cell line A549/Taxol and the structure activity relationship was analyzed.MTT assay was used to detect the inhibitory activities of 10 kinds of annonaceous acetogenins and positive drugs against A549/Taxol cells, respectively uvariamicin-Ⅲ(1), uvariamicin-Ⅱ(2), annosquacin D(3), desacetyluvaricin(4), annosquatin A(5), squamostatin D(6), bullatacin(7), squamocin(8), motrilin(9), annosquatin B(10), verapamil and cisplatin. Annonaceous acetogenins showed significant inhibitory activities against A549/Taxol cells, and were more potent than the positive drug verapamil and cisplatin.The more carbon atoms between the tetrahydrofuran ring and the lactone ring of annonaceous acetogenins exhibited more potency.Besides,ACGs with two substituted hydroxyl showed more potency than the compounds with three substituted hydroxyl in the bis-adjacent-THF ACGs. Furthermore, ACGs with three substituted hydroxyl showed more potency than the compounds with four substituted hydroxyl among the no bis-adjacent-THF ACGs.

C15 acetogenins from the Laurencia complex: 50 years of research – an overview

Abstract Acetogenins are secondary metabolites derived from the polyketide pathway and their potential role as chemotaxonomical markers for red algae belonging to the Laurencia complex has been long pointed out. C15 acetogenins from algae are quite different from plant acetogenins: they are usually halogenated, and have an enyne or a bromoallene terminal group. Since they were first reported, laurencin and other algal acetogenins have inspired great curiosity among natural product chemists and also those working with synthesis. This paper reviews the literature about C15 acetogenins, focusing on their distribution, chemical and biological aspects, including their reported biological activities.

Anticancer effect of total annonaceous acetogenins on hepatocarcinoma / 中国结合医学杂志

<p><b>OBJECTIVE</b>To confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma.</p><p><b>METHODS</b>The inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis.</p><p><b>RESULTS</b>The inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs.</p><p><b>CONCLUSION</b>TAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.</p>

Effects of Bullatacin on Proliferation and Apoptosis of A549 Cell Line of Pulmonary Adenocarcinoma / 中国中医药信息杂志

Objective To investigate the apoptosis induction of Bullatacin on A549 cell line of pulmonary adenocarcinoma. Methods The MTT assay was used to detect the growth inhibition rates of A549 cells cultured with Bullatacin in different concentrations (6.25, 12.5, 25, 50, 100μg/mL). 25μg/mL Bullatacin was used to culture A549 cells for 0, 12, 24, 48 h. The cell cycle distribution and apoptosis were measured by flow cytemetry. The protein expressions of ERK, JNK, and p38 were studied by Western blot. Results Dosage dependence was obviously showed after the different concentrations of Bullatacin were used to A549, and 25 μg/mL;Bullatacin blocked A549 cell in G0/G1 periods and induced its apoptosis. Compared with the blank group, protein expressions of P-ERK, P-JNK, and P-p38 were all increased by different degrees. Conclusion Bullatacin significantly inhibits the proliferation and induces the apoptosis of A549 cell. Its mechanism is related to activity of MAPK pathway thought the phosphorylation of the three protein kinases by Bullatacin.

Effects of annonaceous acetogenins against multidrug resistant human breast cancer cell line MCF-7/ADR in vitro / 中草药

Objective: To investigate the effects of 15 annonaceous acetogenins (ACGs) on human breast cancer cell line MCF-7/ADR, and to find out their structure-activity relationship. Methods: MCF-7/ADR cells were treated with 15 ACGs such as annotemoyin-1 (1), annosquamin B (2), annosquamin A (3), annosquamin C (4), annosquacin C (5), urarigrandin A (6), isodesacetyluvaricin (7), annosquacin D (8), annosquacin B (9), 12, 15-cis-squamostatin-A (10), squamostatin-A (11), squamostanin-B (12), squamostanin-A (13), squamostatin-D (14), and squamostatin-E (15) for 48 h, and the inhibition on MCF-7/ADR cells was detected using MTT assay. Results: All the tested compounds showed significant inhibitory activities against MCF-7/ADR cells, and were more potent than the standard control verapamil. The activity of compound 1 was 190 times higher than that of verapamil. Conclusion: The ACGs with more carbons between tetrahydrofuran (THF) ring and γ-unsaturated lactone are more potent. If all other structural features are identical, the ACGs with more hydroxyls on aliphatic chain would be more active, and four hydroxyls might be optimal among bis-nonadjacent-THF ACGs. Moreover, ACGs with stereochemical arrangement of erythro are more active than those of threo, and the compounds with THF ring configuration of cis seem to be superior to those of trans. Furthermore, bis-adjacent-THF ACGs with molecular weight of 622 and with three hydroxyl groups and stereochemical arrangement of erythro partly produce notable cytotoxicity.

Effect of monotetrahydrofuran annonaceous acetogenins on mitochondrial complex I of rats / 中草药

Objective: To investigate the activity of mono-tetrahydrofuran (THF) annonaceous acetogenins (ACGs) against mitochondrial complex I of rats. Methods: The inhibitory activity of mono-THF ACGs with six different chemical structures against mitochondrial complex I of rats was investigated to clarify the carbon number and substituted hydroxyl number between THF ring and lactone ring as well as the effect of the core configuration in THF ring on mitochondrial complex I of rats. Results: The results show that mono-THF ACGs can inhibit the mitochondrial complex I of rats. With analysis of the results from the structure-activity relationship between antitumoral activity and their chemical structure of mono-THF ACGs, the less the carbon number between the two rings is, the better their inhibitory activities are; The number of substituted hydroxyl groups is not the decisive factor for influencing its activity in mono-THF ACGs. Conclusion: The inhibitory activity of compound's configurations with th/t/er is better than that of the compound's configurations with th/t/th in mono-THF ACGs.

The combined action of phytolarvicides for the control of dengue fever vector, Aedes aegypti

Amongst other botanical sources, Annona muricata L., Annonaceae, seeds and Piper nigrum L., Piperaceae, fruits are particularly enriched with acetogenins and piperine-related amides, respectively. These crude ethanolic extracts are potent Aedes aegypti bioactives that can kill Aedes aegypti larvae (dengue fever mosquito). A. muricata displayed a 93.48 µg/mL LC50 and P. nigrum an 1.84 µg/mL LC50. An uncommon pharmacognostical/toxicological approach was used, namely different combinations of both extracts to achieve an improved lethal effect on the larvae. The independence test (χ²) was utilized to evaluate the combination of the two crude extracts. All of the tested combinations behaved synergistically and these novel results were attributed to the completely different biochemical mechanisms of the differentiated chemical substances that were present in the two botanical sources. Besides the two above selected plants, Melia azedarach L., Meliaceae, Origanum vulgare L., Lamiaceae, and Ilex paraguariensis A. St.-Hil., Aquifoliaceae, in order of decreasing toxicity, may also be sought as potential extracts for the sake of synergic combinations.