Ethnopharmacology, phytochemistry, and bioactivities of Hieracium L. and Pilosella Hill (Cichorieae, Asteraceae) species.

ETHNOPHARMACOLOGICAL RELEVANCE: Species of the genera Hieracium and Pilosella have been used in folk medicine for centuries in many parts of the world. The most wiedly used species is P. officinarum Vaill., included in the British and French Pharmacopoeias and sold as part of different commercial products. AIM OF THE STUDY: This review critically appraises the state-of-art of ethnopharmacology, specialised metabolites, bioactivities, and toxicity of members of Hieracium and Pilosella. Thus, gaps in scientific knowledge can be identified, also focusing on the development of products with pharmacological applications. MATERIALS AND METHODS: Literature data of Hieracium and Pilosella species were mainly retrieved using different electronic databases such as Web of Science, Google Scholar, SciFinder, and PubMed. Other electronic resources included worldwide databases on ethnobotany, ethnopharmacology, and phytochemistry as well as government reports. Additionally, ancient texts and local information such as PhD and MSc theses, and books were consulted. RESULTS: A comprehensive analysis of the above mentioned sources revealed that only 34 out of the about 850 described species within the genera Hieracium and Pilosella have been reported in the context of traditional medicinal and ethnobotanical knowledge. The most often mentioned species is P. officinarum which has been widely used due to its diuretic effects. Other popular uses of Hieracium and Pilosella species include the treatment of skin, gastric, and intestinal diseases as well as respiratory and vascular ailments. Moreover, taxa of the two genera have been used as antiobiotics, antiseptics, antidiabetics, tonics, antiepileptics, antiphlogistics, emetics, wound healing drugs, astringents, haemostatics, and detoxificants. Finally, uses as a wild vegetable, fodder, plant for hunting and for charming rituals have also been mentioned. Phytochemical research revealed a richness in phenolic compounds and flavonoids. Moreover, coumarins, sesquiterpene lactones, terpenoids, and phytosterols were found in Hieracium and Pilosella. Experimental research conducted to support traditional uses mainly include in vitro tests, while assays based on in vivo models (including humans) are rather limited. Also, the vast majority of the studies did not identify the compounds responsible for the detected bioactivities. These established bioactivities include antidiabetic, anti-inflammatory, antibacterial, antimycotic, antiviral, cytotoxic and antiproliferative, diuretic, gastroprotective, antiepileptic, hypotensive, anti-obesity, arthropodicidal, and skin rejuvenating activities. Finally, limited toxicity studies have been conducted on members of Hieracium and Pilosella. CONCLUSION: Taxa belonging to Hieracium and Pilosella have been confirmed to exert diuretic, anti-inflammatory, and antimicrobial effects, which is in line with their long traditional use. Moreover, the above mentioned fields of application hint to the most promising routes for the development of new marketable products. Nonetheless, additional data from an in-depth research on bio-active specialised metabolites such as sesquiterpenoids, sesquiterpene lactones, and coumarines, their bioactivities and toxicity, and their biosynthesis are still warranted.

Cytotoxic constituents and a new hydroxycinnamic acid derivative from Leontodon saxatilis (Asteraceae, Cichorieae).

In our ongoing research for the discovery of new constituents with antimyeloma activity, we investigated 15 compounds present in the aerial parts of Leontodon saxatilis for their cytotoxic potential against NCI-H929, U266, and OPM2 cell lines. One of the isolated compounds displayed a new natural product and was identified as 5-feruloyl-2α-hydroxyquinic acid after LC-MS and NMR experiments. Of the remaining compounds, cichoric acid and three flavone glycosides, apigenin 4'-O-ß-d-glucoside, luteolin 7-O-ß-d-glucoside and luteolin 4'-O-ß-d-glucoside, showed moderate cytotoxic activity, whereas the effects of two aglyones apigenin and luteolin were more pronounced. Though the cytotoxic potential of the two aglycones (against other cell lines) was reported in various studies, our work moreover showed that cooccurrence of these two compounds with similar components of lower activity led to comparable results and at the same time minimized the damage of healthy fibroblast cells. Thus, our work could be a starting point for additional studies on the synergistic effect of similar components against myeloma cell lines.

Cytotoxic Properties of Damiana (Turnera diffusa) Extracts and Constituents and A Validated Quantitative UHPLC-DAD Assay.

In our continuing search for new cytotoxic agents, we assayed extracts, fractions, and pure compounds from damiana (Turnera diffusa) against multiple myeloma (NCI-H929, U266, and MM1S) cell lines. After a first liquid-liquid solvent extraction, the ethyl acetate layer of an acetone (70%) crude extract was identified as the most active fraction. Further separation of the active fraction led to the isolation of naringenin (1), three apigenin coumaroyl glucosides 2⁻4, and five flavone aglycones 5⁻9. Naringenin (1) and apigenin 7-O-(4″-O-p-E-coumaroyl)-glucoside (4) showed significant cytotoxic effects against the tested myeloma cell lines. Additionally, we established a validated ultra-high performance liquid chromatography diode array detector (UHPLC-DAD) method for the quantification of the isolated components in the herb and in traditional preparations of T. diffusa.