Study on the metabolism of natural sesquiterpene lactones in human liver microsomes using LC-Q-TOF-MS/MS.

Sesquiterpene lactones are naturally occurring, highly active -specialised metabolites, which are biosynthesized by important medicinal plants, fulfilling many functions. The in vitro metabolism of parthenolide (1), grosheimin (2), carbetolide C (3), 8α-O-(3,4-dihydroxy--methylenebutanoyloxy)-dehydromelitensin (4) and arteludovicinolide A (5) was examined using human liver microsomes. Phase I, phase II (glucuronidation), as well as combined phase I + II metabolism were studied. Metabolites were identified via liquid chromatography-high resolution quadrupole time-of-flight mass spectrometry. Monohydroxylated, hydrated, carboxylated, methylated derivatives, together with corresponding monoglucuronides were detected, suggesting that the metabolism of sesquiterpene lactones is changeable due to structural features and scaffold diversity, though the lactone ring is the main site of metabolism.

Phytochemical Characterization of Phitosia crocifolia, a Monotypic Representative of Greek Flora.

Within the large Compositae family, Phitosia is considered a monotypic genus of the Greek flora, with its only species P. crocifolia (Boiss. & Heldr.) Kamari & Greuter growing wild with limited distribution, exclusively on the mountains Taigetos and Parnonas in Peloponnese. P. crocifolia's chemical profile was obtained, herein, for the first time and led to the isolation of 20 compounds, thirteen of which were characterized as sesquiterpene lactones and the rest mainly as phenolic derivatives. The isolates 1: -3, 5:  - 7: and 11:  - 13: represent new chemical structures. Compounds 2: and 3: especially are substituted with a pentose moiety, a rare phenomenon in sesquiterpene lactone backbones. A series of spectrometric and spectroscopic techniques were used to elucidate their structures. The relative configurations of the unreported compounds were established via extensive analysis of NMR spectroscopic and HRESIMS data, assisted by CD spectroscopic measurements. Throughout the entire isolation procedure, selected fractions rich in sesquiterpene lactones were tested against HeLa cancerous cell line for their cytotoxic effects with the lowest IC50 values being 18.84 µg/mL. Accordingly, among the tested isolates, compounds 5: and 9: exerted IC50 values of 13.5 µM and 11.4 µM, respectively.

A Bio-Guided Screening for Antioxidant, Anti-Inflammatory and Hypolipidemic Potential Supported by Non-Targeted Metabolomic Analysis of Crepis spp.

This study was designed to evaluate the chemical fingerprints and the antioxidant, anti-inflammatory and hypolipidemic activity of selected Crepis species collected in Greece, namely, C. commutata, C. dioscoridis, C. foetida, C. heldreichiana, C. incana, C. rubra, and Phitosia crocifolia (formerly known as Crepis crocifolia). For the phytochemical analyses, sample measurements were carried out by using nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled with mass spectrometry (LC-MS). Τhe extracts were evaluated both in vitro (radical scavenging activity: DPPH assay and total phenolic content: Folin-Ciocalteu) and in vivo (paw edema reduction and hypolipidemic activity: experimental mouse protocols). Among the tested extracts, C. incana presented the highest gallic acid equivalents (GAE) (0.0834 mg/mL) and the highest antioxidant activity (IC50 = 0.07 mg/mL) in vitro, as well as the highest anti-inflammatory activity with 32% edema reduction in vivo. Moreover, in the hypolipidemic protocol, the same extract increased plasma total antioxidant capacity (TAC) by 48.7%, and decreased cholesterol (41.3%) as well as triglycerides (37.2%). According to fractionation of the extract and the phytochemical results, this biological effect may be associated with the rich phenolic composition; caffeoyl tartaric acid derivatives (cichoric and caftaric acid) are regarded as the most prominent bioactive specialized metabolites. The present study contributes to the knowledge regarding the phytochemical and pharmacological profile of Crepis spp.

Hypericum Essential Oils-Composition and Bioactivities: An Update (2012-2022).

Hypericum genus, considered to comprise over 500 species that exhibit cosmopolitan distribution, has attracted human interest since ancient times. The present review aims to provide and summarize the recent literature (2012-2022) on the essential oils of the title genus. Research articles were collected from various scientific databases such as PubMed, ScienceDirect, Reaxys, and Google Scholar. Scientific reports related to the chemical composition, as well as the in vitro and in vivo pharmacological activities, are presented, also including a brief outlook of the potential relationship between traditional uses and Hypericum essential oils bioactivity.

In vitro cytotoxic and anti-inflammatory activities of sesquiterpene lactones from Centaurea papposa (Coss.) Greuter.

In the pursuit of highly active specialized metabolites from endemic plants, Centaurea papposa (Coss.) Greuter, an endemic plant in Algeria and Tunisia, was investigated and afforded eleven sesquiterpene lactones (1-11). Cytotoxic evaluation of these compounds using the in vitro MTT assay on three human cancerous cell lines (HeLa, SK-MEL-28 and HepG2), revealed that isolates 4, 8 and 9 (IC50 ≤ 10 µM) could be potential anti-cancer drugs for cervical cancer according to the National Cancer Institute. Further evaluation of the in vitro anti-inflammatory activity showed that compounds 1 and 4 inhibited the TNF-α induced ICAM-1 expression in HMEC-1 endothelial cells at a maximum of 21% and 2% of the control (IC50 values 21.9 and 5.7 µM, respectively). The Michael reactions of the α-methylene-γ-lactone ring seem to be responsible for the strong activity, while no toxicity was observed in the HMEC-1 cells in all the range of tested concentrations (6.25-50.0 µM).

Prenylated Acylphloroglucinols from Hypericum jovis with Anti-inflammatory Potential.

Thirteen prenylated acylphloroglucinols (1: -13: ), including 2 previously undescribed compounds (1: ) and (2: ), were isolated from Hypericum jovis. Their structures were elucidated by high-field NMR spectroscopy. The isolated prenylated acylphloroglucinols were evaluated for their anti-inflammatory effects in vitro through the reduction of the intercellular adhesion molecule 1 expression induced by TNF-α in the human microvascular endothelial cells 1 cell line. Compounds 3, 5, 6, 8,: and 12: significantly reduced intercellular adhesion molecule 1 expression in a concentration-dependent manner with IC50 values of 16.9, 34.4, 4.0, 3.2, and 7.7 µM, respectively. In addition, compound 12: showed notable inhibitory activity on the formation of cyclooxygenase-1- and 12-lipoxygenase-derived inflammatory mediators in an ex vivo cyclooxygenase-lipoxygenase assay. Eleven further constituents were isolated (14: -24: ), including the rare quercetin 3-O-(2-O-acetyl)-arabinofuranoside (18: ).

The genus Genista L.: A rich source of bioactive flavonoids.

The genus Genista L. (family Fabaceae, subfamily Papilionoideae), with its cosmopolitan distribution, has attracted the human interest since ancient times, as it is used in folk medicine and mainly in the Mediterranean area for the treatment of respiratory diseases, rheumatic disorders, diabetes and ulcer, while it is also well known for its yellow pigment. The chemical composition of the Genista species revealed the presence of more than 108 flavonoids. Isoflavones, belonging to the group of phytoestrogens, are important secondary metabolites of the genus. The extracts of the Genista species may act as important source of bioactive phytochemicals for the treatment of many human ailments, mainly inflammation and pain, estrogen related pathology, hyperglycaemia, cancer and microbial infections. Therefore, the present review summarizes and discusses the flavonoid derivatives from the genus Genista, together with their structural features and pharmacological properties, aiming to highlight the recent advances in current knowledge on Genista species as a source of bioactive flavonoids.

Cytotoxicity and Anti-cancer Activity of the Genus Achillea L.

BACKGROUND: The genus Achillea L. is rich in bioactive sesquiterpenes and flavonoids; most of the studied species exhibit several biological activities and are used as emmenagogue, wound healing and analgesic agents. Some species are also used in local folklore medicine. OBJECTIVE: Following a literature survey, we discuss the anti-cancer properties of Achillea species, taking into consideration ethnopharmacological data on their use in traditional medicine for the treatment of cancer. In addition, we screened extracts and isolated secondary metabolites from A. coarctata for cytotoxicity, upon information based on local traditional medicine. The plant was collected in Kozani (Northern Greece), where it is locally used for treating gastrointestinal disorders, including stomach cancer. METHODS: A selection of the relevant data was performed through a search in PubMed, Scopus, Google Scholar and Science Direct databases. In addition, extracts and isolated compounds from A. coarctata were tested for their in vitro activity against the human cancer cell lines MCF-7 and HeLa. CONCLUSION: The genus Achillea L. is a valuable source of bioactive secondary metabolites. The most significant outcome of the investigation of medicinal plants is the documentation and the assessment of the traditional information and its use and perspectives in the light of modern pharmacology.

Antiproliferative Activity of (-)-Rabdosiin Isolated from Ocimum sanctum L.

Background: Ocimum sanctum L. (holy basil; Tulsi in Hindi) is an important medicinal plant, traditionally used in India. Methods: The phytochemical study of the nonpolar (dichloromethane 100%) and polar (methanol:water; 7:3) extracts yielded fourteen compounds. Compounds 6, 7, 9, 11, 12, and 13, along with the methanol:water extract were evaluated for their cytotoxicity against the human cancer cell lines MCF-7, SKBR3, and HCT-116, and normal peripheral blood mononuclear cells (PBMCs). Results: Five terpenoids, namely, ursolic acid (1), oleanolic acid (2), betulinic acid (3), stigmasterol (4), and ß-caryophyllene oxide (5); two lignans, i.e., (-)-rabdosiin (6) and shimobashiric acid C (7); three flavonoids, luteolin (8), its 7-O-ß-D-glucuronide (9), apigenin 7-O-ß-D-glucuronide (10); and four phenolics, (E)-p-coumaroyl 4-O-ß-D-glucoside (11), 3-(3,4-dihydroxyphenyl) lactic acid (12), protocatechuic acid (13), and vanillic acid (14) were isolated. Compound 6 was the most cytotoxic against the human cancer lines assessed and showed very low cytotoxicity against PBMCs. Conclusions: Based on these results, the structure of compound 6 shows some promise as a selective anticancer drug scaffold.

Assessment of Fatty Acid Allocation in Plasma and Tissues in Piglets, Using Feed Supplemented with Byproducts from Processed Olive Mill Wastewater.

BACKGROUND/AIM: A previous study revealed the improvement of redox status in blood and tissues of young piglets (ablactation period), that consumed feed containing polyphenolic additives from byproducts of processed olive mill wastewater (OMWW). The polyphenolic additives strengthened the antioxidant defense of the piglets. Herein we analyzed the fatty acid (FA) composition of these animals in various tissues. MATERIALS AND METHODS: The steps followed during the analysis were: Preparation and isolation of byproducts containing polyphenolic compounds from OMWW processing, silage and piglet feed preparation, blood and tissue collection, fatty acid methyl esters synthesis and GC/MS analysis. RESULTS: The young piglets, that consumed feed containing polyphenolic additives from byproducts of processed OMWW, were found to have a decreased ω6/ω3 ratio, compared to samples of the control group. For example, in the quadriceps tissue the control group has a ω6/ω3 ratio of 10.1, while in the polyphenolic group this ratio was decreased to 2.93. Regarding the ratio of UFA/SFA, no significant differences were observed. Finally, the polyphenolic group exhibited almost in all tissues lower values of the ratio of PUFA/MUFA than the control group.