Effect of Casearia sylvestris on the obliteration of dentinal tubules and the control of dental sensitivity / Efecto de Casearia sylvestris sobre la obliteración de los túbulos dentinarios y el control de la sensibilidad dental

The present study evaluated the efficacy of the mineralizing action of Casearia sylvestris ethanolic extract on bovine dentin blocks in its pure form and in dental paste, through scanning electron microscopy. The dentin blocks were immersed in artificial saliva and incubat ed at 37°C for 7 days. Subsequently, six groups were treated with different test substances and analysed qualitatively and quantitatively at 30 and 60 days. The tests used were Kruskal - Wallis and Dunn's. Shapiro - Wilk and ANOVA. The qualitative analysis at 30 days showed a difference between the groups treated with ethanolic extract and toothpaste. Quantitatively, at 30 days, treatment with ethanolic extract of Casearia showed a greater number of open dentinal tubules. At 60 days, the difference persisted on ly for the blocks treated with toothpaste. The results obtained indicated that there is a positive relationship between the use of Casearia sylvestris and obliteration of dentinal tubules

El presente estudio evaluó la eficacia de la acción mineralizante del extracto etanólico de Casearia sylvestris sobre bloques de dentina bovina en su forma pura y en pasta dental, mediante microscopía electrónica de barrido. Los bloques de dentina se sumergieron en saliva artificial y se incubaron a 37°C durante 7 días. Posteriormente, se trataron seis grupos con diferentes sustancias de ensayo y se analizaron cualitativa y cuantitativamente a los 30 y 60 días. Las p ruebas utilizadas fueron Kruskal - Wallis y Dunn's. Shapiro - Wilk y ANOVA. El análisis cualitativo a los 30 días mostró una diferencia entre los grupos tratados con extracto etanólico y pasta dentífrica. Cuantitativamente, a los 30 días, el tratamiento con ex tracto etanólico de Casearia mostró un mayor número de túbulos dentinarios abiertos. A los 60 días, la diferencia persistió sólo para los bloques tratados con pasta dentífrica. Los resultados obtenidos indicaron que existe una relación positiva entre el us o de Casearia sylvestris y la obliteración de los túbulos dentinarios

Bioactive diterpenoids isolated from the twigs and leaves of Casearia velutina.

Nine previously undescribed clerodane-type diterpenoids (1-9), named caseabalanspenes A-I, along with six know compounds (10-15), were isolated from the twigs and leaves of Casearia velutina. Spectroscopic data (1D and 2D NMR) analysis permitted the definition of their structures and then determination of the molecular formula of the compound by high resolution mass spectrometry (HR-ESI-MS). It is worth noting that compound 7 contains N- heterocycle. Compounds 1-8 were tested the anti-inflammasome activity, and compound 3 exhibited potent activity and decreased LDH level in a dose-dependent manner, with IC50 values of 2.90 µM.

Casearia Essential Oil: An Updated Review on the Chemistry and Pharmacological Activities.

Casearia species are found in the America, Africa, Asia, and Australia and present pharmacological activities, besides their traditional uses. Here, we reviewed the chemical composition, content, pharmacological activities, and toxicity of the essential oils (EOs) from Casearia species. The EO physical parameters and leaf botanical characteristics were also described. The bioactivities of the EOs from the leaves and their components include cytotoxicity, anti-inflammatory, antiulcer, antimicrobial, antidiabetic, antioxidant, antifungal, and antiviral activities. The main components associated with these activities are the α-zingiberene, (E)-caryophyllene, germacrene D, bicyclogermacrene, spathulenol, α-humulene, ß-acoradiene, and δ-cadinene. Data on the toxicity of these EOs are scarce in the literature. Casearia sylvestris Sw. is the most studied species, presenting more significant pharmacological potential. The chemical variability of EOs components was also investigated for this species. Caseria EOs have relevant pharmacological potential and must be further investigated and exploited.

16,17-dinor-abietane diterpenoids from Casearia kurzii.

Eleven undescribed 16,17-dinor-abietane diterpenoids, caseazins A-K (1-11), and ten known diterpenoids (12-21) were isolated from the twigs and leaves of Casearia kurzii (Flacourtiaceae). Caseazins A-K were the first abietane -type dinorditerpenoids to have been isolated from the plant of Casearia kurzii. Their chemical structures were elucidated using a combination of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configurations of 5 and 10 were established by electronic circular dichroism calculations. Moreover, compounds 2, 3, 13, 14, and 18 exhibited anti-inflammatory activity with IC50 values of 0.17, 0.36, 6.55, 1.30, and 4.53 µM, respectively. IL-1ß and caspase-1 analyses suggested that compound 14 inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis.

Caseatardies A-K, eleven undescribed clerodane diterpenoids isolated from Casearia tardieuae and their anti-inflammatory activity.

A phytochemical investigation to obtain bioactive substances as lead compounds or agents for anti-inflammatory led to the obtainment of eleven previously undescribed clerodane diterpenoids, named caseatardies A-K (1-11), and four known clerodane diterpenoids (12-15) from the twigs and leaves of Casearia tardieuae. The structural elucidation of these clerodane diterpenoids was based on 1D and 2D-NMR spectroscopy (COSY, HSQC, HMBC and ROESY) as well as high resolution mass spectrometry (HR-ESI-MS). The relative configurations were defined by ROESY correlations. The anti-inflammatory activity of all the isolated compounds was screened and compound 15 decreased LDH level in a dose-dependent manner, showing IC50 value of 2.89 µM.

In Vitro Schistosomicidal Activities of the Leaf Extracts from Casearia sylvestris Varieties.

Schistosomiasis, a tropical disease caused by flatworms, may affect the liver, spleen, bladder, and intestine. Casearia sylvestris Swartz, a medicinal plant, displays antiprotozoal, antimicrobial, antifungal, and antiulcer activities. We have evaluated the in vitro schistosomicidal activity of two C. sylvestris varieties against Schistosoma mansoni adult worms at concentrations between 12.5 and 200 µg/mL. At 100 and 200 µg/mL, the ethanolic C. sylvestris var. sylvestris leaf extract enriched in casearin-like diterpenes eliminated 100 % of the parasites after incubation for 72 h and 48 h, respectively, whilst the same extract at 200 µg/mL eliminated 96 %, 100 %, and 100 % of the parasites after incubation for 24, 48, and 72 h, respectively. On the other hand, the hydroalcoholic C. sylvestris var. lingua leaf extract at 200 µg/mL eliminated 60.4 and 66.7 % of the parasites after incubation for 48 and 72 h, respectively. The presence of casearin-like diterpenes and glycosylated flavonoids was confirmed based on chromatographic techniques and mass spectrometry data.

Casearia sylvestris Essential Oil Degradation Products Generated by Leaf Processing.

Casearia sylvestris is an endemic tree of the Latin America that the essential oil (EO) has anti-inflammatory and gastroprotective actions. This study evaluates the chemical composition of the EO from the volatile fractions of in natura, fresh, and dried C. sylvestris var. sylvestris and var. lingua leaves. For both varieties, the dried leaves presented higher EO yield as compared to fresh leaves. The major EO chemical components were (E)-caryophyllene, α-humulene, germacrene D, bicyclogermacrene, spathulenol, caryophyllene oxide, and humulene epoxide II. In both varieties, the content of sesquiterpene hydrocarbons decreased and oxygenated sesquiterpenes increased on going from in natura to fresh and dried leaves, which indicated that leaf drying and hydrodistillation modified the volatile composition. The results also suggested that bicyclogermacrene and (E)-caryophyllene were oxidized during processing, to generate spathulenol and caryophyllene oxide, respectively. C. sylvestris varieties and in natura, fresh, and dried leaves differed in terms of the chemical composition of volatiles, which could affect the EO biological activities.

Fragmentation study of clerodane diterpenes from Casearia species by tandem mass spectrometry (quadrupole time-of-flight and ion trap).

RATIONALE: Clerodane-type diterpenes from Casearia species show important pharmacological activites such as antitumor, antimicrobial and anti-inflamatory. There are several mass spectrometry (MS)-based methods for identification of diterpenes; however, there is still a lack of MS procedures capable of providing characteristic fragmentation pathways for a rapid and unambiguous elucidation of casearin-like compounds. METHODS: Casearin-like compounds were investigated by electrospray ionization tandem mass spectrometry (ESI-MS/MS). The fragmentation studies were carried out by tandem mass spectrometry in space (quadrupole time-of-flight (QTOF)) using different collision energies and also by tandem mass spectrometry in time (QIT) by selective isolation of product ions. RESULTS: Casearin-like compounds presented a predominance of sodium- and potassium-cationized precursor ions. Both QIT and QTOF techniques provided sequential neutral losses of esters related to the R1 to R5 substituents linked to the nucleus of the clerodane diterpenes. The fragmentation pathway is initiated with a cleavage of the ester moieties R2 followed by the elimination of the ester groups R3 , both losing neutral carboxylic acids. Using QIT, it was also possible to observe the cleavage of the ester groups R1 or R5 by MS4 experiments. CONCLUSIONS: Through a rational analysis of the fragmentation mechanisms of Casearia diterpenes it was possible to suggest an annotation strategy based on the sequential cleavages of the ester groups related to the R2 , R3 and R5 substituents. These results will assist studies of the dereplication and metabolomics involving casearin-like compounds present in complex extracts of Casearia species.

Casearia decandra leaves present anti-inflammatory efficacy in a skin inflammation model in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia decandra (guaçatonga) is popularly used as an anti-inflammatory. We investigated the antioxidant and anti-inflammatory effect of C.decandra leaves (CdE) ethanolic extract and of the rutin standard (present in the CdE). MATERIALS AND METHODS: Male adult Swiss mice were used (25-30 g; 5-6 animals by a group). CdE phytochemical analysis was performed by HPLC method. The antioxidant potential of CdE and rutin was assessed by different methods. Topical anti-inflammatory effect of CdE (0.001-1mg/ear) and rutin (0.003-0.03mg/ear) was evaluated by ear edema formation and inflammatory cells infiltration (MPO activity and histology) on a skin inflammation model induced by topical application of croton oil (1mg/ear). RESULTS: Rutin (27.81 ± 1.11 mg/g) was identified in CdE by HPLC analysis. The required amounts of CdE, rutin and ascorbic acid to reduce the initial concentration of radical DPPH by 50% (IC50) were 7.77 (6.31-9.57) µg/mL, 3.62 (3.26-4.01) µg/mL and 3.74 (3.37-4.14) µg/mL with a radical DPPH reduction of 91 ± 1.2%, 91 ± 0.5%, and 96 ± 0.44% (at 30 µg/mL), respectively. Moreover, CdE and rutin presented H2O2 scavenging activity with H2O2 levels reduction of 41 ± 7% and 46 ± 6%, respectively and SOD-like activity of 60 ± 4% and 51 ± 14%, respectively. On the other hand, just rutin presented nitric oxide scavenging activity of 54 ± 6%. CdE and rutin topically applied inhibited the ear edema with a maximum inhibition of 70 ± 5% (1 mg/ear) and 78 ± 10% (0.03 mg/ear), respectively. Treatments reduced the MPO activity (42 ± 4% to CdE; 1mg/ear and 30 ± 8% to rutin; 0.03 mg/ear). Histologically, the topical treatments also reduced the dermis thickness and the inflammatory cells infiltration. CONCLUSION: We demonstrated the antioxidant and anti-inflammatory effect of C.decandra leaves and rutin. Its antioxidant potential may contribute to inflammatory process attenuation, supporting the C.decandra leaves used as a promising alternative in the therapy of the inflammatory diseases.

Antimicrobial and antibiofilm activities of Casearia sylvestris extracts from distinct Brazilian biomes against Streptococcus mutans and Candida albicans.

BACKGROUND: Dental caries is a biofilm-diet-dependent worldwide public health problem, and approaches against microorganisms in cariogenic biofilms are necessary. METHODS: The antimicrobial and antibiofilm activities of 12 Casearia sylvestris extracts (0.50 mg/mL) from different Brazilian biomes (Atlantic Forest, Cerrado, Caatinga, Pampa, and Pantanal) and varieties (sylvestris, lingua, and intermediate) were tested against two species found in cariogenic biofilms (Streptococcus mutans and Candida albicans). The extracts effective against S. mutans were used to evaluate the "adhesion strength" of this bacterium to the salivary pellicle and initial glucan matrix and the S. mutans-GtfB activity. Also, the antimicrobial activity against S. mutans of three fractions (methanol, ethyl acetate, and hexane; 0.25 mg/mL) from the extracts was evaluated. RESULTS: Three extracts from the Atlantic Forest variety sylvestris (FLO/SC, GUA/CE, PRE/SP) reduced ≥50% (> 3 logs) S. mutans viable population (p < 0.0001 vs. vehicle), while two extracts from the same biome and variety (PAC/CE, PRE/SP) decreased ≥50% of the viable counts of C. albicans (p < 0.0001 vs. vehicle). For S. mutans biofilms, three extracts (GUA/CE, PAC/CE, PRE/SP) reduced the biomass by ≥91% (p > 0.0001 vs. vehicle) and 100% of the microbial population (p < 0.0001 vs. vehicle). However, for the fungal biofilm, two extracts (PAC/CE, PRE/SP) reduced the viable counts by ≥52% (p < 0.0001 vs. vehicle), but none reduced biomass. The extracts with higher antimicrobial and antibiofilm activities presented higher content of clerodane-type diterpenes and lower content of glycosylated flavonoids than the less active extracts. The extracts had no effect on the removal of cells adhered to the pellicle (p > 0.05 vs. vehicle) while promoted the detachment of a larger number of S. mutans cells from GtfB-glucan matrix (p < 0.0031 vs. vehicle), and FLO/SC, GUA/CE and PRE/SP reduced the quantity of glucans (p < 0.0136 vs. vehicle). Only the ethyl acetate fractions reduced the microbial population of S. mutans (p < 0.0001 vs. vehicle), except for one (PAC/CE). Among the ethyl acetate fractions, three from var. lingua (two from Cerrado, and one from Cerrado/Caatinga) reduced ≥83% of the microbial population. CONCLUSIONS: C. sylvestris extracts from Atlantic Forest var. sylvestris and ethyl acetate fractions from Cerrado and Cerrado/Caatinga var. lingua may be used as a strategy against cariogenic microorganisms.

Clerodane diterpenoids from Casearia kurzii and their cytotoxic activities.

A search for bioactive natural products as anticancer lead compounds resulted in the isolation of one previously undescribed and three known clerodane diterpenoids (1-4) from Casearia kurzii. The structures of these compounds were established by analysis of their NMR, MS, and electronic circular dichroism data. The cytotoxic activities of four compounds against three human cancer cell lines were evaluated. Compound 2 was found to be the most active with an IC50 value of 4.1 µM against HeLa cells, and was selected to investigate the possible cytotoxic mechanism.

Acidic and hepatic derivatives of bioactive clerodane diterpenes casearins J and O.

Clerodane diterpenes from Casearia sylvestris are antiulcerogenic and anti-inflammatory. The finding that they may undergo acid degradation or hepatic metabolization led to an investigation of their degradation products. Purified clerodane diterpenes (casearins J and O) were subjected to in vitro assays to simulate their oral administration. Resulting derivatives were identified using chromatographic and spectrometric techniques. Nitric oxide synthesis by LPS-stimulated macrophages was assayed to verify whether structural modifications alter the anti-inflammatory activity of diterpenes. Nine compounds (1-9) were identified after acid degradation remaining 5.05% of casearin J. Besides the remaining casearin O (13.1%), eight compounds (10-17) were identified. The dialdehydes from each casearin were the major constituents. S9 rat liver treatment of casearins J and O generated two compounds identical to some of those produced by acid degradation, which remained 36.8% and 36.5% intact, respectively. Both casearins and its derivatives were not cytotoxicity at concentrations lower than 0.312 µg/mL (0.555 µM for casearin J and 0.516 µM for casearin O) and did not inhibit the nitric oxide production in this concentration. Thus, the structural modifications conducted did not alter the activity of casearins and the anti-inflammatory pathway of diterpenes probably is not involved on nitric oxide modulation.

Chemical variability between different organs of the medicinal plant Casearia sylvestris

The phytochemical profile of essential oils and extracts from Casearia sylvestris leaves, flowers and fruits have been investigated here. Leaf and flower extracts were prepared by sonication and analyzed by thin-layer chromatography and high-performance liquid chromatography. The phenolic content was determined by ultraviolet spectrophotometry. Leaves, flowers, and fruits essential oils were extracted by hydrodistillation. The highest extracts yields were 20.3 % (leaves) and 23.4 % (flowers) with ethanol 70 %. Essential oil extraction yields were 0.3 % (leaves) and 0.1 % (flowers and fruits). Bicyclogermacrene was the major component in all essential oil. Thin-layer chromatography suggests a chemical profile similar for leaves and flowers. The leaves and flowers phenolic content were similar (14.0 and 15.0 %, respectively). Chromatography analyses indicated the predominance of casearin clerodane diterpenes in leaves (λmax 232-235), whereas in flowers, diterpenes with a different standard diene in side-chain C13(16) and C14 (λmax 223-229). The different phytochemical profile of C. sylvestris flowers as compared to the leaves could be explored by the search for new bioactive components. This is the first report on the fruit and flower C. sylvestris essential oil composition. These data could be used as quality control of herbal medicine derived from C. sylvestris leaves.(AU)

Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw.

Casearia genus (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 160-200 species. It is a medicinal plant used in South America, also known as "guaçatonga", "erva-de-tiú", "cafezinho-do-mato". In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro, including Casearia sylvestris Sw. There are many studies related to the chemical profile and cytotoxic activities of extracts from these plants, although few studies about the antifungal potential of the essential oil have been reported. In this work, we have studied the antifungal properties of the essential oil of C. sylvestris leaves, as well as of their fractions, against four yeasts (Saccharomyces cerevisae, Candida albicans, C. glabrata and C. krusei) for the first time. The chemical analysis of the essential oil revealed a very diversified (n = 21 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). These sesquiterpenes included α-humulene (17.8%) and α-copaene (8.5%) and the oxygenated sesquiterpene spathulenol (11.8%) were also identified. Monoterpenes were not identified. The fractions are mainly composed of oxygenated sesquiterpenes, and the most active fraction is rich in the sesquiterpene 14-hydroxy -9-epi-ß-caryophyllene. This fraction was the most effective in inhibiting the growth of three yeast strains.

Antifungal activities of the essential oil and its fractions rich in sesquiterpenes from leaves of Casearia sylvestris Sw

ABSTRACT Casearia genus (Salicaceae) is found in sub-tropical and tropical regions of the world and comprises about 160-200 species. It is a medicinal plant used in South America, also known as "guaçatonga", "erva-de-tiú", "cafezinho-do-mato". In Brazil, there are about 48 species and 12 are registered in the State of Rio de Janeiro, including Casearia sylvestris Sw. There are many studies related to the chemical profile and cytotoxic activities of extracts from these plants, although few studies about the antifungal potential of the essential oil have been reported. In this work, we have studied the antifungal properties of the essential oil of C. sylvestris leaves, as well as of their fractions, against four yeasts (Saccharomyces cerevisae, Candida albicans, C. glabrata and C. krusei) for the first time. The chemical analysis of the essential oil revealed a very diversified (n = 21 compounds) volatile fraction composed mainly of non-oxygenated sesquiterpenes (72.1%). These sesquiterpenes included α-humulene (17.8%) and α-copaene (8.5%) and the oxygenated sesquiterpene spathulenol (11.8%) were also identified. Monoterpenes were not identified. The fractions are mainly composed of oxygenated sesquiterpenes, and the most active fraction is rich in the sesquiterpene 14-hydroxy -9-epi-β-caryophyllene. This fraction was the most effective in inhibiting the growth of three yeast strains.

Effect of Using Different Vehicles on the Physicochemical, Antimicrobial, and Biological Properties of White Mineral Trioxide Aggregate.

INTRODUCTION: This study evaluated the physicochemical, antimicrobial, and biological properties of white mineral trioxide aggregate (MTA) mixed with aqueous and propylene glycol extracts of Arctium lappa L. and Casearia sylvestris Sw. METHODS: The setting-time test was performed according to American Society for Testing and Materials 266/2008 and flowability by American National Standards Institute/American Dental Association 57/2012 standard specifications. The following parameters were assessed: volumetric change by micro-computed tomography; pH level and calcium ion release measured after 3 hours and 1, 3, 7, and 15 days; antimicrobial effect by the dentin decontamination method with intratubular Enterococcus faecalis viability, verified by using confocal laser scanning microscopy; and biocompatibility by histologic-morphometric analyses of inflammatory infiltrate at subcutaneous implant sites after 15, 30, and 60 days. In addition, rat alveolar tissues with implants were processed to measure tumor necrosis factor-alpha and interleukin-10 cytokines by enzyme-linked immunosorbent assay. RESULTS: The plant extracts associated with MTA significantly increased the final setting time; however, they did not influence volumetric change (P > .05) and maintained medium alkalinity and calcium ion release. Propylene glycol extracts showed higher flowability. Casearia sylvestris increased the cementing effect against E. faecalis after 24-hour and 168-hour periods. Histologic evaluation of inflammatory infiltrate showed no significant differences between plant extracts groups and the distilled water group for all periods. Tumor necrosis factor-alpha and interleukin-10 expression was similar among groups (P > .05). CONCLUSIONS: Casearia sylvestris extracts increased the antimicrobial effect of MTA and did not influence biocompatibility but changed some physicochemical properties.

Antileishmanial Activity and Immunomodulatory Effects of Tricin Isolated from Leaves of Casearia arborea (Salicaceae).

Bioactivity-guided fractionation of antileishmanial active extract from leaves of Casearia arborea led to isolation of three metabolites: tricin (1), 1',6'-di-O-ß-d-vanilloyl glucopyranoside (2) and vanillic acid (3). Compound 1 demonstrated the highest activity against the intracellular amastigotes of Leishmania infantum, with an IC50 value of 56 µm. Tricin (1) demonstrated selectivity in mammalian cells (SI > 7) and elicited immunomodulatory effect on host cells. The present work suggests that tricin modulated the respiratory burst of macrophages to a leishmanicidal state, contributing to the parasite elimination. Therefore, the natural compound tricin could be further explored in drug design studies for leishmaniasis treatment.

Behavioral effects induced by antitumor cleronade diterpenes from Casearia sylvestris and in silico interactions with neuron receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties. AIM OF THE STUDY: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors. MATERIALS AND METHODS: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed. RESULTS: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D1 complex is up to 1000-fold more favourable than the Cas X-GABAA complex. All ∆G° values obtained for Cas X-D1 complexes were more negative than those seen with Cas X-GABAA complexes. CONCLUSIONS: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system.

A New Cytotoxic Clerodane Diterpene from Casearia graveolens Twigs.

The first phytochemical investigation of Casearia graveolens twigs led to the isolation and identification of a new clerodane diterpene, caseariagraveolin (1), together with six known compounds (2-7). Their structures were elucidated by intensive analysis of their spectroscopic data. Compound 1 showed strong cytotoxicity against oral cavity and breast cancer cell lines with IC50 values of 2.48 and 6.63 µM, respectively.

Di- and Triterpenoids from the Leaves of Casearia balansae and Neurite Outgrowth Promoting Effects of PC12 Cells.

A bioassay-guided phytochemical investigation of the leaves of Casearia balansae led to the isolation of six new cucurbitane-type triterpenoid derivatives (balanterpenes A-F, 1-6) and four new clerdoane-type diterpenoids (balanterpenes G-J, 7-10). The structures of 1-10 were established on the basis of extensive analysis of NMR spectroscopic data, X-ray crystallography, and experimental and calculated electronic circular dichroism spectra. Compound 1 features a ring-expanded triterpenoid skeleton with the C-19 methyl involved in the ring formation, compound 6 possesses a rare hexanortriterpenoid scaffold, and compounds 7-10 may be four new diterpenoid artifacts presumably formed during the extraction and purification processes. Compounds 3 and 7-10 showed promoting effects on neurite outgrowth of PC12 cells with EC50 values in the range 2.9-10.0 µM.