Pomegranate peel, chokeberry leaves and Ironwort extract as novel natural inhibitors of amylin aggregation and cellular toxicity in pancreatic ß cells.

Impeding or reducing human amylin aggregation and/or its toxicity can be key to preventing pancreatic islet amyloidosis and ß-cell loss in patients with Type 2 Diabetes Mellitus (T2DM). Here, Punica granatum (pomegranate) peel, Sideritis raeseri (ironwort) and Aronia melanocarpa (chokeberry) leaf extracts, were tested for their novel anti-aggregative and antitoxic properties in human amylin (hIAPP) treated rat pancreatic insulinoma (INS) cells. The protein aggregation (Th-T) assay revealed an inhibitory trend of all three plant extracts against amylin aggregates. In agreement with this finding, pomegranate peel and ironwort extracts effectively prevented the transition of hIAPP from disordered, random coil structures into aggregation prone ß-sheet enriched molecular assemblies, revealed by CD spectroscopy. Consistent with their anti-aggregative action, all three extracts prevented, to various degrees, reactive oxygen species (ROS) accumulation, mitochondrial stress, and, ultimately, apoptosis of INS cells. Collectively, the results from this study demonstrate effectiveness of natural products to halt hIAPP aggregation, redox stress, and toxicity, which could be exploited as novel therapeutics against amylin-derived islet amyloidosis and ß-cell stress in T2DM.

Polar constituents, biological effects and nutritional value of Sideritis sipylea Boiss.

The present study focuses on the polar constituents and biological effects of the methanol extract and the infusion of wild Sideritis sipylea Boiss. from Samos island (Greece), as well as on the nutritional and mineral contents of this plant. The total phenolic content and antioxidant activity were examined. In addition, the anti-acetylcholinesterase property was evaluated, revealing strictly lower results than the control, galanthamine. Furthermore, the nutritional value of the plant is reported herein for the first time, revealing a promising source of protein. To the best of our knowledge, this study is the first work on the infusion of this species and the nutritional value of the plant.

Structural study of a pectic polysaccharide fraction isolated from "mountain tea" (Sideritis scardica Griseb.).

The present study was conducted to investigate the structural characteristics of an acid-extracted polysaccharide fraction from mountain tea. The monosaccharide composition revealed that uronic acids (72.4 mol%) considerably predominated in the fraction, followed by smaller amounts of galactose (14.5 mol%) and glucose (6.2 mol%). The fraction contained mostly a highly methyl-esterified homogalacturonan (HG) - 71 mol%. The pectin had a high molecular weight population (∼60-100 kDa). Enzymatic fingerprinting was employed with a combination of HG degrading enzymes and LC-HILIC-MS, HPAEC, HPSEC to examine the structure in greater detail. Unsaturated oligomers released indicated the presence of large blocks of highly methyl-esterified GalA residues. Furthermore, the presence of blocks of non-esterified GalA residues and partly methyl-esterified and acetylated GalA residues in HG domain was demonstrated. The research findings provide a basis for further investigations regarding biological activity and commercial exploitation of mountain tea.

Secondary metabolites from the aerial parts of Sideritis germanicopolitana and their in vitro enzyme inhibitory activities.

Three iridoid glycosides, 5-allosyloxy-aucubine (1), melittoside (2), ajugol (3), five phenylethanoid glycosides, verbascoside (4), martynoside (5), leucoseptoside A (6), lamalboside (7), decaffeoylverbascoside (8), four flavonoids, xanthomicrol (9), isoscutellarein 7-O-[6'''-O-acetyl-ß-allopyranosyl-(1→2)]-ß-glucopyranoside (10), 4'-O-methylisoscutellarein 7-O-[6'''-O-acetyl-ß-allopyranosyl-(1→2)]-ß-glucopyranoside (11), 3'-hydroxy-4'-O-methylisoscutellarein 7-O-[6'''-O-acetyl-ß-allopyranosyl-(1→2)]-ß-glucopyranoside (12), and two lignan glycosides dehydrodiconiferylalcohol 4-O-ß-D-glucopyranose (13) and pinoresinol 4'-O-ß-glucopyranoside (14) were isolated from the aerial parts of Sideritis germanicopolitana. Their structures were determined on the basis of detailed NMR and HRESIMS analyses. To our knowledge, all compounds are being reported for the first time from S. germanicopolitana, while the isolated lignans (13 and 14) are new for the genus Sideritis. In vitro evaluation of AChE, BChE and LOX inhibitory effects of all the tested compounds (1-14) resulted in low to moderate activities.

Secondary Metabolites, Glandular Trichomes and Biological Activity of Sideritis montana L. subsp. montana from Central Italy.

Sideritis montana subsp. montana is a small annual herb occurring in countries bordering the Mediterranean and Balkan regions. The secondary metabolism of this plant has not been fully explored so far. The aim of the present study was to understand the complex mixture of secondary metabolites and the type of secretory structures. The polar constituents were isolated by column chromatography from the ethanolic extract, and their structure was elucidated by NMR and MS. The essential oil was isolated by hydrodistillation and analysed by GC/MS. The plant indumentum was studied by light and scanning electron microscopy. To complete the work, the essential oil antioxidant activity and cytotoxicity on tumor cells were evaluated by DPPH, ABTS, FRAP, and MTT methods. Four different classes of secondary metabolites were isolated, namely flavonoids, caffeoylquinic derivatives, glycosidic hydroquinones and iridoids. The essential oil was mainly characterized by sesquiterpenene hydrocarbons. Peltate and long-capitate hairs were the main sites where terpenes and polar constituents are produced. The secondary metabolites found in S. montana subsp. montana are of chemotaxonomic interest, some of them being typical of the genus Sideritis. The trichomes types observed partially differ from those described in other members of the genus Sideritis. The essential oil showed noteworthy inhibition on tumor cells.

Flavonoids from Sideritis Species: Human Monoamine Oxidase (hMAO) Inhibitory Activities, Molecular Docking Studies and Crystal Structure of Xanthomicrol.

The inhibitory effects of flavonoids on monoamine oxidases (MAOs) have attracted great interest since alterations in monoaminergic transmission are reported to be related to neurodegenerative diseases such as Parkinson's and Alzheimer's diseases and psychiatric disorders such as depression and anxiety, thus MAOs may be considered as targets for the treatment of these multi-factorial diseases. In the present study, four Sideritis flavonoids, xanthomicrol (1), isoscutellarein 7-O-[6'''-O-acetyl-ß-D-allopyranosyl-(1→2)]-ß-D-glucopyranoside (2), isoscutellarein 7-O-[6'''-O-acetyl-ß-D-allopyranosyl-(1→2)]-6''-O-acetyl-ß-D-glucopyranoside (3) and salvigenin (4) were docked computationally into the active site of the human monoamine oxidase isoforms (hMAO-A and hMAO-B) and were also investigated for their hMAO inhibitory potencies using recombinant hMAO isoenzymes. The flavonoids inhibited hMAO-A selectively and reversibly in a competitive mode. Salvigenin (4) was found to be the most potent hMAO-A inhibitor, while xanthomicrol (1) appeared as the most selective hMAO-A inhibitor. The computationally obtained results were in good agreement with the corresponding experimental values. In addition, the x-ray structure of xanthomicrol (1) has been shown. The current work warrants further preclinical studies to assess the potential of xanthomicrol (1) and salvigenin (4) as new selective and reversible hMAO-A inhibitors for the treatment of depression and anxiety.

Assay of urinary excretion of polyphenols after ingestion of a cup of mountain tea (Sideritis scardica) measured by HPLC-DAD-ESI-MS/MS.

Flavonoids and phenolic acid metabolites excreted in human urine after ingestion of Sideritis scardica decoction with characterized polyphenolic composition were studied. A feeding study was carried out with 10 human volunteers, and urine samples were collected for 24 h after ingestion of the Sidertis decoction. Polyphenol metabolites were identified and quantified in urine samples by HPLC with tandem mass spectrometric detection. Thirty-one different metabolites of hypolaetin, methylhypolaetin, isoscutellarein, methylisoscutellarein, and apigenin and 32 phenolic acid metabolites were detected and quantified using a method validated for this purpose. The urinary excretion of polyphenol metabolites corresponded to 5% (n/n) of the intake of polyphenols from the Sideritis decoction. Flavonoid metabolites were dominant in urine samples with 87-94% of total polyphenolic metabolites content. The most abundant metabolites were methylhypolaetin and methylisoscutellarein glucuronides. Urinary excretion of isoscutellarein (35.61%) was 10 times higher than that of hypolaetin (3.67%). Apigenin also showed high urinary excretion (32.46%).

Iron(III) reducing and antiradical activities of three Sideritis from Turkey.

CONTEXT: Sideritis species (Lamiaceae) are widely used as herbal tea and have been used in folk medicine for their anti-inflammatory, anti-rheumatic, digestive, and antimicrobial activities in Turkey. Sideritis dichotoma Huter., Sideritis erythrantha Boiss. var. cedrotorum, and Sideritis vuralii H. Duman et Baser are available as commercial products in Turkey. OBJECTIVE: The antiradical activities of the various solvent extracts of Sideritis species are investigated here for the first time. MATERIALS AND METHODS: Plant samples were sequentially extracted with n-hexane, dichloromethane, methanol, and aqueous methanol (50%, v/v) in Soxhlet apparatus. The extracts of Camellia sinensis (L.) Kuntze (Theaceae) were also prepared for use as a positive control. Total phenolics, iron(III) reductive effects, and 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging activities of the all extracts were measured colorimetrically. RESULTS: The aqueous MeOH and MeOH extracts contained the highest amount of total phenols, whereas the n-hexane extract contained the lowest amounts. The polar extracts of C. sinensis showed higher antiradical activity and also iron(III) reductive effects than the Sideritis species; however, the non-polar extracts of Sideritis species were found to be more active than those from C. sinensis in the iron(III) reductive assay and in the DPPH(•) assay as well. But none of the extracts was found to be as active as with positive controls, viz., ascorbic acid, butylated hydroxyanisole (BHA), and Trolox. DISCUSSION AND CONCLUSION: These results can be shown to have antioxidant activities of these Sideritis species and support the ethnopharmacological use of these Sideritis plants.