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Centella asiatica (L.) Urban plants have been used since ancient times for their medicinal properties, and their extracts have proven antioxidant, wound healing, sedative, and neuroprotective activities, among others. The natural compounds responsible for C. asiatica bioactivity are triterpene saponins formed from the dammarene branch of the triterpene biosynthetic pathway, collectively known as centellosides, with madecassoside and asiaticoside and their aglycones, madecassic acid and asiatic acid being the most important. Several biotechnological approaches have been developed for the bioproduction of centellosides, based on cell, hairy root, and in vitro plant cultures. This review summarizes the main therapeutic properties of these compounds, as well as their biosynthetic pathways, referring to genetic studies that have identified genes involved in their formation. The biotechnological production of centellosides from a small scale to bioreactor level is also covered. Finally, we summarize the most effective strategies for increasing centelloside yield, including recent transcriptomic, proteomic, and metabolomic studies that have gained new insights into the centelloside biosynthetic pathway and its control.

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The increasing rate of cancer incidence has encouraged the search for novel natural sources of anticancer compounds. The presence of small quantities of taxol and taxanes in Corylus avellana L. has impelled new potential applications for this plant in the field of biomedicine. In the present work, the cell viability-reducing activity of stems and leaves from three different hazel trees was studiedagainst three human-derived cancer cell lines (HeLa, HepG2 and MCF-7). Both leaf and stem extracts significantly reduced viability of the three cell lines either after maceration with methanol or using taxane extraction methods. Since maceration reduced cell viability to a greater extent than taxane extraction methods, we scaled up the maceration extraction process using a method for solid/liquid extraction (Zippertex technology). Methanol leaf extracts promoted a higher reduction in viability of all cell lines assayed than stem extracts. Fractionation of methanol leaf extracts using silica gel chormatography led to the purification and identification of two compounds by HPLC-MS and NMR: (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl) heptane 3-O-β-d-glucopyranoside and quercetin-3-O-rhamnoside. The isolated compounds decreased viability of HeLa and HepG2 cells to a greater extent than MCF-7 cells. Our results suggest a potential use of C. avellana extracts in the pharmacotherapy of cervical cancer and hepatocarcinoma and, to a lesser extent, breast cancer.

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Since the recent discovery of taxol and other taxanes in Corylus avellana, this plant species has attracted interest as a potential new source of these compounds. However, its low taxane content in comparison with Taxus spp. has restricted research to analytical identification or global quantitation. A feasible and sensitive method based on liquid chromatography-tandem mass spectrometry using a triple quadrupole analyzer was developed for the analysis of taxol and four other taxanes in a Corylus avellana cell suspension medium. Taxanes were extracted from the cell culture medium with dichloromethane and analyzed using electrospray ionization and quantified by multiple-reaction monitoring mode. Methanol and matrix-matching calibration curves using docetaxel as the internal standard were analyzed. Linearity was confirmed over the whole calibration range (0.3-2.1 mg mL À1). The inter-and intra-day precision of taxanes ranged from 80% to 120% and the recovery rates were higher than 80%. Limits of detection were between 0.24-38 ng mL À1 and the limits of quantification were between 0.8-125 ng mL À1. The low detection and quantitation values obtained allowed us to detect small quantities of the released taxanes (120 ng mL À1 of B, 151 ng mL À1 of CF and 105 ng mL À1 of T), which correspond to about 0.5 ng mL À1 of each taxane, in the 20 mL Corylus avellana cell suspension culture medium extracted, even at the beginning of the culture. These results were confirmed by high resolution mass spectrometry.