Bioassay-guided fractionation of hexane extracts of Gymnosperma glutinosum (Asteraceae) leaves, collected in North Mexico, afforded the known compounds hentriacontane (1) and (+)-13S,14R,15-trihydroxy-ent-labd-7-ene (2), as well as the new ent-labdane diterpene (−)-13S,14R,15-trihydroxy-7-oxo-ent-labd-8(9)-ene (3). In addition, D-glycero-D-galactoheptitol (4) was isolated from the methanolic extract of this plant. Their structures were established on the basis of high-field 1D- and 2D NMR methods supported by HR-MS data. The cytotoxic activity was determined by using the in vitro L5178Y-R lymphoma murine model. Hentriacontane (1) and the new ent-labdane 3 showed weak cytotoxicity, whereas the ent-labdane 2 showed significant (p < 0.05) and concentration dependent cytotoxicity (up to 78%) against L5178Y-R cells at concentrations ranging from 7.8 to 250 µg/mL.
Pachycereus marginatus (DC.) Britton & Rose and Ibervillea sonorae (S. Watson) Greene have been used in the Mexican traditional medicine for the treatment of various diseases, including cancer. The present study aims to investigate the cytotoxic activity of these plants against a murine lymphoma. Soxhlet extraction of dried and powdered plant material was performed with methanol. Also, a further partitioning of these methanolic extracts with hexane and ethyl acetate was achieved. The in vitro cytotoxic activity against the murine lymphoma L5178Y-R cell line was assessed via the colorimetric MTT assay. The methanol extract from P. marginatus exhibited high cytotoxic activity (up to 94%) at concentrations ranging from 3.9 to 500 µg/mL; however, hexane and ethyl acetate partitions from this methanolic extract showed lower but significant (p < 0.05) concentration-dependent cytotoxicity (hexane partition up to 94% at 500 µg/mL; ethyl acetate partition up to 94% at 65.5 µg/mL). The methanolic extract and partitions derived from I. sonorae also showed significant (p < 0.05) and concentration-dependent cytotoxicity against L5178Y-R cells at concentrations ranging from 7.81 to 500 µg/mL (methanolic extract up to 63% at 500 µg/mL; hexane partition up to 76% at 250 µg/mL; ethyl acetate partition up to 73% at 500 µg/mL). These results demonstrate that the methanol extracts and partitions from P. marginatus and I. sonorae possess significant cytotoxic activity against the murine lymphoma L5178Y-R and validate the ethnobotanical use of these plants for the treatment of diseases consistent with cancer symptomatology. Previous scientific reports describe the isolation of isoquinoline alkaloids of P. margi-* Corresponding author. R. Quintanilla-Licea et al. 1522natus as well as cucurbitacins from I. sonorae, phytochemicals that could be responsible for their observed cytotoxic activity in this research. The direct extraction with methanol of medicinal plants allows extracting of both high and low-polarity compounds, contrary to the simple extraction with water that only allows obtaining compounds of high polarity. The subsequent partition of the methanol extract with a solvent of low polarity (hexane) and another of medium polarity (ethyl acetate) allows making a preliminary fractionation of the bioactive molecules present in the plant that will facilitate the bioguided chromatographic isolation of the pure compounds responsible for the biological activity of the plant.
Pachycereus marginatus (DC.) Britton & Rose is a species belonging to the family Cactaceae. In traditional medicine, it is recommended to treat diabetes and gastrointestinal infections; however, there are no studies related to its use in cancer treatment. The in vitro antitumor effect of P. marginatus hexane, chloroform, methanol, and methanol-aqueous partition stem extracts, against murine lymphoma L5178Y-R and skin melanoma B16F10 cells, was evaluated in liquid medium by the colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The extracts resulted in up to 84, 85, 84, and 82% cytotoxicity (p < 0.05) to L5178Y-R cells, respectively, and up to 39, 51, 48, and 42% cytotoxicity (p < 0.05) to B16F10 cells, respectively. Vehicle controls were not cytotoxic for tumor cells, and along with the extracts they did not affect viability of resident murine thymus and spleen lymphocytes. Taken together, the present results showed that P. marginatus extracts possess antitumor potential against L5178Y-R lymphoma and B16F10 skin melanoma cells.
Cancer is one of the leading causes of death worldwide and commonly becomes resistant to chemotherapy, therefore, it is important to search for and evaluate novel sources of nontoxic antitumor agents. The cactus Pachycereus marginatus is native to Mexico and is traditionally recommended to treat gastrointestinal infections. Tumor-bearing mice survival, liver function, and histopathology by P. marginatus extracts and the in vitro effects of isolated compounds lophenol, β-sitosterol, and palmitic acid were investigated, using the L5178Y-R lymphoma murine model. In vivo oral administration of the aqueous partition at 0.5 mg/kg caused 60% survival at 60 days, without altering liver parenchyma and enzymes, as compared with 40% survival induced by vincristine (0.05 mg/kg), and no survival of tumor-bearing mice without treatment. Furthermore, P. marginatus n-hexane extract, lophenol, β-sitosterol, and palmitic acid compounds caused up to 89%, 73%, and 83% in vitro cytotoxicity to L5178Y-R cells, respectively. These results may support the evaluation of P. marginatus extracts and bioactive compounds in clinical studies.
It is indisputable that every day it is demonstrated that natural products present diverse therapeutic benefits, which has boosted their incorporation within various products for clinical use. However, this must be accompanied by knowledge of their effect on cell lines to ensure their use is safe. The objective of this study was to evaluate the cytotoxic effect of two ethanolic extracts based on Peruvian natural products, on three human cell lines. Cervical cancer cell lines (HeLa), human gingival fibroblasts (HGF-1 - ATCC CRL-2014) (HGF-1) and peripheral blood mononuclear cells (PBMCs) were cultured and subsequently treated with preparations of ethanolic extracts of propolis (EEP) and Psidium guajava (EEG) from a concentration of 50 mg/mL to 0.024 mg/mL, by the 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazole bromide reduction assay. At a concentration of 0.24 mg/mL EEG, viability of 99.7±1.24%, 99.8±2.2% and 99.7±2.7% was observed in HeLa, HGF-1 and PBMCs, respectively; >90% cell viability values were observed with EPP at 0.024 mg/mL, with HGF-1 showing the highest viability (96.9±1.15%). A dose-dependent effect was observed for both extracts with a decrease in cell viability as concentrations increased (up to 50 mg/mL). EEP and EEG extracts at low concentrations do not show cytotoxicity in human cell lines, these findings are an advance in the preclinical evaluation on their safety and open a continuity to further studies for their potential applications in dentistry and medicine.
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