Cytotoxic triterpenoid saponins from the root of Olax subscorpioidea Oliv. (Olacaceae).

Bioactivity-guided phytochemical fractionation of the methanol extract of Olax subscorpioidea root has led to the isolation of six triterpenes. Three of these compounds are previously undescribed triterpenoid saponins: oleanolic acid 3-O-[α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranosyl-(1 â†’ 2)-6-O-methyl-ß-D-glucuronopyranoside]-28-O-ß-D-glucopyranosyl ester (2), oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucopyranosyl-(1 â†’ 3)-ß-D-glucopyranoside] (3), and oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-6-O-methyl-ß-D-glucuronopyranoside] ester (5). Other reported known compounds include two triterpene glycosides: oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-6-O-methyl-ß-D-glucuronopyranoside]-28-O-ß-D-glucopyranosyl ester (1) and oleanolic acid 3-O-[ß-D-glucopyranosyl-(1 â†’ 4)-ß-D-glucuronopyranoside] (4); and a triterpene acid, oleanolic acid (6). The structures of these compounds were elucidated by spectroscopic means. The isolated compounds were tested against human cervical cancer (HeLa), colorectal cancer (Caco-2) and breast cancer (MCF-7) cell lines using the in vitro 3-[4,5-dimethylthiazole-2-yl] 3,5-diphenyltetrazolium bromide (MTT) assay, with vincristine as positive control. The cytotoxicity assay showed that compounds 3 and 5 exhibited significant inhibitory effects on the HeLa cell line, with IC50 values of 7.42 ± 0.34 µM and 10.27 ± 1.26 µM; and moderate effects on MCF-7 (IC50 values, 36.67 ± 1.23 µM and 43.83 ± 0.65 µM) and Caco-2 (IC50 values, 35.83 ± 0.55 µM and 39.03 ± 4.38 µM, respectively) cell lines. They were also more selectively cytotoxic than vincristine against the cancer cell lines, when compared with cytotoxicity against the normal lung cell line MRC5.

Isolation and structure elucidation of cyclopeptide alkaloids from the leaves of Heisteria parvifolia.

Heisteria parvifolia Sm. is prescribed in traditional medecine against numerous diseases in Côte d'Ivoire. Due to the shortcoming in scientifical knowledge of use of this species, our investigations revealed five undescribed cyclopeptide alkaloids added to one known derivative namely anorldianine. These compounds were elucidated by 1D and 2D-NMR experiments and comparison with literature data, and confirmed by HR-ESI-MS. Cytotoxic activity evaluation of these compounds against the chronic myeloid leukemia (K565) cell line exhibited an antiproliferative activity with cell growth inhibition from 13% to 46%.

Root hemiparasitism in Malania oleifera (Olacaceae), a neglected aspect in research of the highly valued tree species.

Malania oleifera (Olacaceae) is a valued tree species, mostly because its seeds have high precious fatty acid content (particularly nervonic acid). However, seedling mortality rates are often high and regeneration of this tree has been problematic, which greatly hinders its utilization at a large scale. Cultivation difficulties of some tree species in the family Olacaceae have been attributed to their root hemiparasitic habit. Prompted by field observations and the taxonomic proximity of M. oleifera to root hemiparasites in Olacaceae, we hypothesized that tuberous structures observed on the roots of M. oleifera are parasitic organs known as haustoria. To test this hypothesis, we collected root samples from M. oleifera plants of various ages and growth conditions, investigated the morphological and anatomical features of tuberous structures and their connections to neighboring roots. Our analyses confirmed that M. oleifera are root hemiparasites. To the best of our knowledge, this is the first empirical report on root hemiparasitism in M. oleifera. Because life strategies of root hemiparasitic plants differ greatly from autotrophic plants, the root hemiparasitic habit needs to be taken into account for successful seedling regeneration of M. oleifera. This study establishes the foundation for investigations into a long-neglected but essential aspect in research of these highly valued tree species.

Contribution of Secondary Metabolites to the Gastroprotective Effect of Aqueous Extract of Ximenia americana L. (Olacaceae) Stem Bark in Rats.

Ximenia americana L. (Olacaceae) is used in ethnomedicine as cicatrizant and for the treatment of gastric disorders. This study identified the chemical constituents of the aqueous extract of X. americana (XaAE) and evaluated its antiulcerogenic activity. After lyophilization, XaAE was analyzed by liquid chromatography-mass spectrometry (LC-MS) and its antiulcerogenic effect was evaluated in acute gastric lesions induced by ethanol, acidified ethanol, and indomethacin. Antisecretory action, mucus production and the participation of sulfhydryl groups (-SH) and nitric oxide (NO) were also investigated. The chromatographic analysis identified procyanidins B and C and catechin/epicatechin as major compounds. Oral administration of XaAE (100, 200 and 400 mg/kg) inhibited the gastric lesions induced by ethanol (76.1%, 77.5% and 100%, respectively), acidified ethanol (44.9%, 80.6% and 94.9%, respectively) and indomethacin (56.4%, 52.7% and 64.9%, respectively). XaAE reduced gastric contents and acidity (51.4% and 67.7%, respectively) but did not alter the production of gastric mucus. The reduction of the -SH and NO groups promoted by N-ethylmaleimide (NEM) and Nω-nitro-l-arginine-methyl-ester (L-NAME) respectively, reduced the gastroprotective effect of XaAE. In conclusion, XaAE has gastroprotective activity mediated in part by -SH, NO and antisecretory activity. This antiulcer action was initially correlated to its major constituents, procyanidins B and C and catechin/epicatechin.

EFICÁCIA DA FONOFORESE COM XIMENIA AMERICANA L. NA INFLAMAÇÃO DE TENDÃO DE RATOS / PHONOPHORESIS EFFECTIVENESS WITH XIMENIA AMERICANA L. IN RATS TENDON INFLAMMATION / EFICACIA DE LA FONOFORESIS CON XIMENIA AMERICANA L. EN LA INFLAMACIÓN DE TENDÓN DE RATAS

RESUMO Introdução: Diversos recursos terapêuticos, como laser e ultrassom isolado, combinados com fármacos e fonoforese têm sido utilizados em casos de inflamação e reparo de tendão, sendo o ultrassom pulsado bastante eficaz em tendinites crônicas. Objetivo: Analisar a eficácia do uso da fonoforese com o extrato etanólico das cascas do caule da Ximenia americana L. na resolução do processo inflamatório crônico em Rattus norvegicus. Métodos: A amostra consistiu em 120 animais para análise da resposta inflamatória, utilizando-se como variáveis edema, força biomecânica, número de fibroblastos e análise histológica. Resultados: Nos 7° e no 14° dia, verificou-se diferença significativa entre o grupo ultrassom com gel do caule de Ximenia americana L. e o grupo ultrassom com placebo (p < 0,05) quanto à redução de edema, aumento da força máxima de ruptura, redução extremamente significativa da deformação máxima (p < 0,001), além de aumento dos fibroblastos. Na análise histológica, houve melhora do processo inflamatório inicial e aceleração do reparo tendíneo, com redução de células inflamatórias e com deposição de colágeno organizado com matriz extracelular densa. Conclusão: O ultrassom pulsado combinado com o gel do caule de Ximenia americana L. é uma forma terapêutica eficaz para a resolução do processo inflamatório crônico.

ABSTRACT Introduction: Several therapeutic resources such as laser and isolated ultrasound combined with drugs and phonophoresis have been used in cases of inflammation and tendon repair, and the pulsed ultrasound is quite effective in chronic tendinitis. Objective: To analyze the efficacy of phonophoresis with the ethanol extract of the stem bark of Ximenia americana L. to manage the chronic inflammatory process in Rattus norvegicus. Methods: The sample consisted of 120 animals for analysis of the inflammatory response using edema, biomechanical strength, number of fibroblasts and histological analysis as variables. Results: On the 7th and 14th day, there was a significant difference between the group ultrasound with Ximenia americana L. gel and the ultrasound with placebo group (p<0.05) for edema reduction, increased maximum rupture strength, highly significant reduction of the maximum deformation (p<0.001), in addition to an increase in fibroblasts. In the histological analysis, there was improvement in the inflammatory process and acceleration of tendon repair with reduction of inflammatory cells and deposition of organized collagen with dense extracellular matrix. Conclusion: The pulsed ultrasound combined with gel of Ximenia americana L. is an effective therapy to manage the chronic inflammatory process.

RESUMEN Introducción: Varios recursos terapéuticos, tales como láser y ultrasonido aislado, en combinación con fármacos y la fonoforesis se han utilizado en casos de inflamación y reparación del tendón, y el ultrasonido pulsado ha sido muy eficaz en la tendinitis crónica. Objetivo: Analizar la eficacia de la fonoforesis con el extracto de etanol de la corteza del tallo de Ximenia americana L. en la resolución del proceso inflamatorio crónico en Rattus norvegicus. Métodos: La muestra fue de 120 animales para analizar la respuesta inflamatoria, utilizando como variables el edema, la resistencia biomecánica, el número de fibroblastos y el análisis histológico. Resultados: En el 7° y en el 14° día, se observó una diferencia significativa entre el grupo de ultrasonido con gel de Ximenia americana L. y el grupo ultrasonido con placebo (p < 0,05) en la reducción del edema, el aumento de la resistencia máxima a la rotura, la reducción altamente significativa de la deformación máxima (p < 0,001), además del aumento de los fibroblastos. En el análisis histológico hubo una mejoría en el proceso inflamatorio y la aceleración de la reparación del tendón, con reducción de células inflamatorias y deposición de colágeno organizado con matriz extracelular densa. Conclusión: La eficacia del ultrasonido pulsado combinado con gel de Ximenia americana L. es una forma eficaz para la resolución del proceso inflamatorio crónico.

Flavonoid glycosides from Olax mannii: Structure elucidation and effect on the nuclear factor kappa B pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax mannii Oliv. (Olacaceae) is among the many medicinal plants used in Nigeria for the ethnomedicinal management of both cancer and inflammation. Such plants represent potential sources of innovative therapeutic agents for the treatment of cancer and other malignant disorders. While the majority of medicinal plants exert their anticancer effects by direct cytotoxicity on tumor cells, it is important that other mechanisms through which these plants can exhibit anticancer effects are investigated. Preliminary studies indicated that Olax mannii leaves are rich sources of novel flavonoid glycosides. The detailed chemistry as well the mechanisms through which these flavonoid constituents may exert their cancer chemo-preventive and therapeutic effects are, however, not yet investigated. AIM OF THE STUDY: The aim of this study is to carry out a detailed chemical investigation of Olax mannii leaves and the effects of the isolated constituents on the nuclear factor kappa B (NF-κB) pathway. MATERIALS AND METHODS: A methanol leaf extract was subjected to various chromatographic separations to achieve isolation of flavonoid glycosides and the structures of the isolated compounds were elucidated by a combination of 1D and 2D NMR and high resolution mass spectrometry. Biological activities were assessed by measurement of cellular viability and proliferation using quantitative IncuCyte videomicroscopy, trypan blue staining and by quantification of the number of metabolically active K562 cells based on quantitation of ATP. The effect of the compounds on the inhibition of the NF-κB pathway as well as toxicity towards peripheral blood mononuclear cells to evaluate differential toxicity was also assayed. RESULTS: Chemical investigation of the methanol leaf extract of the plant material led to the isolation of three new flavonoid triglycosides, kaempferol 3-O-[α-D-apiofuranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (1), kaempferol 3-O-[ß-D-glucopyranosyl-(1 → 2)-α-L-arabinofuranoside]-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-[ß-D-arabinopyranosyl-(1→4)-α-L-rhamnopyranoside]-7-O-α-L-rhamnopyranoside (3), in addition to fourteen known flavonoid glycosides (4-17). Of all the tested compounds, only compound 9 (kaempferol 3-O-α-L-rhamnopyranoside) exhibited promising and specific antiproliferative activity on human K562 chronic myelogenous leukemia cells and dose-dependently inhibited NF-κB transactivation. CONCLUSION: The presence of this flavonoid glycoside and derivatives may account for the reported efficacy of Olax mannii leaf extract in the ethnomedicinal management of cancer and inflammation.

Triterpenos das folhas de Minquartia guianensis Aubl. (Olacaceae) / Triterpenes from the leaves of Minquartia guianensis Aubl. (Olacaceae)

Este artigo descreve o isolamento dos triterpenos lupeol, taraxerol, lupen-3-ona e esqualeno obtido do extrato diclorometânico das folhas da espécie Minquartia guianensis Aubl., pertencente à família Olacaceae. Estes terpenóides foram isolados através de técnicas cromatográficas e identificados utilizando Ressonância Magnética Nuclear (RMN) de ¹H e de 13C. Na literatura disponível, este é o primeiro relato destes triterpenos em M. guianensis.

This article describes the isolation of the triterpenes lupeol, taraxerol, lupen-3-one and squalene from the dichloromethane extract of the leaves of Minquartia guianensis Aubl. belonging to the Olacaceae family. These terpenoids were isolated through chromatographic techniques and identified using ¹H and 13C Nuclear Magnetic Resonance (NMR). At the best of our knowledge, this is the first report of these triterpenes in M. guianensis.