Evaluation of Phytochemistry and Antidiabetic Potential of an Astragalus Species: Astragalus kurdicus Boiss.

Astragalus kurdicus Boiss. roots are used in folk medicine for antidiabetic purposes. Different metabolites of Astragalus plants have a notable potential in antidiabetic activity via differing mechanisms. Herewith this study designed to assess the antidiabetic activity of Astragalus kurdicus, utilizing a range of diabetes-related in vitro methodologies and to investigate the chemical composition of the plant. According to the results of the activity tests, water extract (AKW) was the most active extract in PTP1B, DPP4, and α-amylase inhibition tests (87.17%, 82.4%, 91.49% respectively at 1 mg/ml). Total extract, AKM (85.63%), showed the highest AGEs inhibition activity. To test possible improvement effects of the extracts on diabetes through gut-microbiota, cell growth rates of three probiotic microorganisms were measured. AKM showed highest potential of prebiotic activity among tested extracts and caused higher biomass increase than standard prebiotics. Furthermore, flavonoid-rich extract was found to be mostly responsible for the high antioxidant activity. The highest saponin and astragalosides content were seen in AKB extract in HPTLC analysis. Among the measured saponins, the abundance of Astragaloside IV (27.41 µg/mg in AKM) was the highest in all fractions. Thus, for the first time, the antidiabetic activity of A. kurdicus was evaluated from various perspectives.

Towards a better understanding of commonly used medicinal plants from Turkiye: Detailed phytochemical screening and biological activity studies of two Teucrium L. species with in vitro and in silico approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Since ancient times, Teucrium L. species have been among the most commonly used traditional medicinal plants mainly in the Mediterranean region. From tackling gastrointestinal problems to maintaining the healthy functioning of endocrine glands, and from treating malaria to severe dermatological disorders, Teucrium species are known to have extensive therapeutic applications. Teucrium polium L. and Teucrium parviflorum Schreb. are the two members of the genus that have been used in Turkish folk medicine for various medicinal purposes. AIM OF THE STUDY: To determine the phytochemical compositions of the essential oils and ethanol extracts of Teucrium polium and Teucrium parviflorum collected from different locations in Turkiye along with the investigation of in vitro antioxidant, anticancer, antimicrobial activities, and both in vitro and in silico enzyme inhibitory activities of the extracts. MATERIALS AND METHODS: Ethanol extracts of Teucrium polium aerial parts and roots, and aerial parts of Teucrium parviflorum were prepared. Volatile profiling of the essential oils by GC-MS, phytochemical profiling of the ethanol extracts by LC-HRMS, antioxidant activity by DPPH radical scavenging, ABTS cation radical scavenging, CUPRAC, and metal chelating activity assays, anticholinesterase, antityrosinase, antiurease, activities by different enzyme inhibitory activity assays, anticancer activity by SRB cell viability assay, and antimicrobial activity against a standard panel of bacteria and fungi by the microbroth dilution technique. Molecular docking studies were performed by Autodock Vina (Ver. 1.1.2). RESULTS: The studied extracts were found to be quite rich in various biologically important volatile and phenolic compounds. (-)-Epigallocatechin gallate, which is a molecule renowned for having great therapeutic potential, was the major compound of all extracts. Teucrium polium aerial parts extract was revealed as a great source for naringenin with 16327 ± 685.23 µg/g extract. All extracts exerted significant antioxidant activity by different methods. All extracts demonstrated antibutrylcholinesterase, antityrosinase, and antiurease activities by in vitro and in silico assays. Teucrium polium roots extract stood out with remarkable tyrosinase and urease inhibitory and cytotoxic activities. CONCLUSION: The obtained results from this multi-disciplinary study proves that the traditional use of these two Teucrium species is justified, and the mechanisms behind are enlightened.

The Therapeutic Potential of Ethnomedicinally Important Anatolian Thyme Species: A Phytochemical and Biological Assessment.

Thyme has been used for various therapeutic purposes in many different cultures, which makes it one of the most riveting medicinal plants throughout history. From its beneficial effects on the respiratory tract or the gastrointestinal system, to its unique skin-related activities, the investigation of the medicinal properties of thyme has always been an alluring topic for researchers aiming to develop conventional medications from this traditional herb. With an incentive to contribute to the extensive thyme research, three Thymus L. species namely Thymus cariensis Hub-Mor. & Jalas (endemic), Thymus praceox subsp. grossheimii (Ronniger) Jalas, and Thymus pubescens Boiss. et Kotschy ex Celak from Turkey were deeply investigated within this study. The analysis of the phytochemical constituents of the extracts was conducted by LC-MS/MS. 12 biologically important secondary metabolites (p-coumaric acid, caffeic acid, salicylic acid, quinic acid, fumaric acid, vanillin, malic acid, rutin, apigenin, naringenin, and nicotiflorin) were detected in all extracts. Their total phenolic and flavonoid contents were calculated (11.15 ± 0.17-61.12 ± 2.59 µg PEs/mg extract, 2.53 ± 0.04-40.28 ± 0.92 µg QEs/mg extract, respectively), and the antioxidant potential of the extracts was evaluated by DPPH and ABTS radical scavenging and CUPRAC activity methods, accordingly, the extracts were shown to possess significant antioxidant activity. Among them, Thymus cariensis Hub-Mor. & Jalas was the most active with IC50 values of 34.97 ± 1.00 µg/ml and 9.98 ± 0.04 µg/ml regarding the DPPH and ABTS radical scavenging assays, respectively, and an A0.5 value of 5.80 ± 0.02 µg/ml according to CUPRAC activity method. Their anticholinesterase, antityrosinase, and antiurease activities were also tested, Thymus cariensis Hub-Mor. & Jalas (35.61 ± 1.20%) and Thymus pubescens Boiss. et Kotschy ex Celak aerial part extract (33.49 ± 1.39%) exhibited moderate antibutyrylcholinesterase activity at 200 µg/ml concentration. The results of the cell viability assay indicated that the extracts demonstrated moderate-to-low cytotoxicity on A498 human renal cell lines. Furthermore, all studied extracts exerted noteworthy antimicrobial activity, especially against Candida tropicalis (MIC values: 19.53-78.12 µg/ml). The presented data substantiates the use of thyme extracts as therapeutic agents in both ethnomedicine and conventional therapies.

Cytotoxic and apoptotic effects of Hypericum androsaemum on prostate adenocarcinoma (PC-3) and hepatocellular carcinoma (Hep G2) cell lines with identification of secondary metabolites by LC-HRMS.

The study aims to determine the secondary metabolites of Hypericum androsaemum L. extracts by liquid chromatography-high resolution mass spectrometry (LC-HRMS), and investigate the antioxidant and cytotoxic activities of the plant. Cytotoxic activity was evaluated by MTT assay, and apoptosis induction abilities on human prostate adenocarcinoma (PC-3), and hepatocellular carcinoma (Hep G2) cell lines. Accordingly, major secondary metabolites were found as hederagenin (762 ± 70.10 µg/g) in the leaves dichloromethane (LD), herniarin (167 ± 1.50 µg/g) in fruit dichloromethane (FD), (-)-epicatechin (6538 ± 235.36 µg/g) in the leaves methanol (LM), (-)-epigallocatechin gallate (758 ± 20.46 µg/g) in the fruit methanol (FM), and caffeic acid (370 ± 8.88 µg/g) in the fruit water (FW), and (3313 ± 79.51 µg/g) in the leaves water (LW) extracts. LM exerted strong antioxidant activity in DPPH free (IC50 10.94 ± 0.08 µg/mL), and ABTS cation radicals scavenging (IC50 9.09 ± 0.05 µg/mL) activities. FM exhibited cytotoxic activity with IC50 values of 73.23 ± 3.06 µg/mL and 31.64 ± 2.75 µg/mL on PC-3 and Hep G2 cell lines, respectively. Being the richest extract in terms of quillaic acid (630 ± 18.9 µg/g), which is a well-known cytotoxic triterpenoid with proven apoptosis induction ability on different cells, FM extract showed apoptosis induction activity with 64.75% on PC-3 cells at 50 µg/mL concentration. The study provides promising results about the potential of Hypericum androsaemum on cancer prevention.

Antiproliferative effects of Turkish pomegranate (Punica granatum L.) extracts on MCF-7 human breast cancer cell lines with focus on antioxidant potential and bioactive compounds analyzed by LC-MS/MS.

In this study, eight different pomegranate (Punica granatum L.) cultivars from Turkey were evaluated for their antioxidant and cytotoxic effects on the MCF-7 breast cancer cell lines and MCF-10A breast fibrocystic epithelial cell lines with a focus on their chemical compositions by LC-MS/MS. Cell lines were treated with pomegranate juice extracts in different doses at selected time intervals (24th, 48th, and 72nd hour). Afterwards, WST-1 cell proliferation assay was performed to investigate the cytotoxicity of the extracts. Accordingly, all extracts decreased the cell viability of MCF-7 breast cancer cell lines and had no cytotoxic effect on the cell viability of MCF-10A cell lines. Among eight extracts, P7 (Izmir 1513), which was rich in anthocyanins such as cyanidin chloride (69.76 ± 8.02 µg/g extract), cyanidin-3-O-glucoside (903.66 ± 101.89 µg/g extract), and punicalagin (992.09 ± 174.53 µg/g extract), was found to demonstrate the strongest cytotoxic activity on MCF-7 breast cancer cell lines by decreasing the cell viability in half at 24th hour with an IC50 value of 49.08 µg/ml. PRACTICAL APPLICATIONS: Eight commercially valuable pomegranate (Punica granatum) cultivars from Turkey were examined. Pelargonidin, cyanidin, cyanidin-3-O-gl, callistephin, and delphinidin-3-O-gl were quantified. Two cultivars (P1 and P3) showed comparatively higher antioxidant effects. A cultivar (P7) showed strongest cytotoxic activity against MCF-7 breast cancer cell line. The cultivars have potential to be used as natural antioxidant and anticancer agents.

Volatile and phenolic profiling of a traditional medicinal plant, Hypericum empetrifolium with in vitro biological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypericum empetrifolium Willd is a member of the Hypericaceae family, mainly known in southern Greece, and western Turkey. Being a centuries-old medicinal plant, the aerial parts of the plant have been used for the treatment of herpes, kidney stones, gastric ulcer, and also for their anti-helminthic, and diuretic purposes traditionally. AIM OF THE STUDY: The current study aimed to investigate the phytochemical profiles of the essential oil, and two ethanol extracts prepared from the aerial parts (H. empetrifolium aerial parts extract - HEA), and roots of the plant (H. empetrifolium roots extract - HER), and to provide data on antioxidant, anticholinesterase, antityrosinase, antiurease, cytotoxic, and antimicrobial activities of the extracts. MATERIALS AND METHODS: In this study, volatile and phenolic compounds of the HEA and HER were analyzed by GC-MS and LC-MS/MS, respectively. Antioxidant potential of the extracts was clarified by using DPPH radical scavenging assay, ABTS cation radical assay, and the CUPRAC assay. Acetylcholinesterase, butyrylcholinesterase, urease, and tyrosinase inhibitory activity assays were used to determine enzyme inhibition capacity of the extracts. Cytotoxic activity of the extracts was established by using XTT assay. The antimicrobial activity of the extracts was determined by the microbroth dilution technique. RESULTS: The major compounds of the essential oil were revealed as alloaromodendrene (24.7%), α-pinene (14.7%), ß-pinene (10.7%), and α-terpineol (7.7%) by the GC-MS analysis. According to the LC-MS/MS analysis results, quinic acid was the most abundant constituent in both extracts with 20612.42 ± 169.02 µg/g extract in HEA extract, and with 2254.34 ± 18.49 µg/g extract in HER extract, respectively. The HEA extract was also found to be rich in terms of chlorogenic acid (5583.14 ± 38.52 µg/g extract), isoquercitrin (3076.77 ± 40.92 µg/g extract), and malic acid (2822.90 ± 31.90 µg/g extract). HEA extract exhibited a significant antioxidant effect with an IC50 value of 11.98 ± 0.22 µg/mL according to the DPPH radical scavenging assay. Similar results were obtained with the ABTS cation radical assay, and the CUPRAC assay. HER extract showed a strong butyrylcholinesterase inhibitory effect with 88.69 ± 0.62% at 200 µg/mL concentration. Both extracts were considered to have moderate anti-tyrosinase activity compared to the standard at 200 µg/mL. The best antimicrobial activity was obtained for HEA against C. parapsilosis with an MIC value of 4.88 µg/mL. HEA also exhibited antifungal activity against C. tropicalis with 19.53 µg/mL. Only HER exhibited low cytotoxicity on A498 renal cell lines with 60.6% cell viability. CONCLUSION: Unquestionably, H. empetrifolium Willd has ethnopharmacological importance according to these results, and further investigations are required to evaluate other therapeutic properties of the plant.

Neopapillarine, an Unusual Coumarino-Alkaloid from the Root Extract of Neocryptodiscus papillaris with Cytotoxic Activity on Renal Cancer Cells.

Several simple and prenylated coumarin derivatives were isolated from the dichloromethane extract of the root of Neocryptodiscus papillaris based on moderate cytotoxic activity of the extract in COLO205, KM12 and MCF7 cancer cells. While the major prenylated furanocoumarin derivatives and osthol isolated from the dichloromethane extract were responsible for the activity in the colon and breast cancer cell lines, the 4'-acylated osthol derivatives including a novel coumarino-alkaloid; neopapillarine) demonstrated selective cytotoxic activity in A498 and UO31 renal cancer cell lines.

Comprehensive analysis of an uninvestigated wild edible medicinal garlic species from Turkey: Allium macrochaetum Boiss. & Hausskn.

The study was aimed to investigate the phenolic compounds of Allium macrochaetum by LC-MS/MS, as well as the antioxidant, antialzheimer, and antimicrobial activities of the extracts, and determination of the essential oil and fatty acid compositions by GC-MS. The results indicate that malic acid and t-caffeic acid are the major compounds in the bulbs. The main components of fatty acids were found to be linolenic (40.72%), oleic (19.79%), and palmitic (18.45%) acids. The allyl disulfide (66.97%) was found as major compound in the essential oil. The ethanol extract of the bulbs exhibited stronger ABTS cation (IC50 : 55.90 ± 1.08 µg/ml) and DPPH free (IC50 : 204.43 ± 2.17 µg/ml) radical scavenging activities than the other extracts. The extract also showed moderate cupric reducing activity with 1.52 absorbance at 100 µg/ml concentration. Only the ethanol extract of the bulbs showed weak inhibition (23.34 ± 0.11%) against butrylcholinesterase enzyme at 200 µg/ml. PRACTICAL APPLICATIONS: Allium macrochaetum is a wild and edible garlic species which grown in Turkey, Iran, Iraqi, and Syria. A. macrochaetum has been used by local people in Turkish folk medicine as an antibiotic, and for the treatment of alopecia. The health benefits and nutritional values of A. macrochaetum were clarified in the first time. Phenolic compounds of A. macrochaetum were detected by LC-MS/MS. The essential oil and fatty acid compositions of A. macrochaetum were identified by GC-MS. Antioxidant, antialzheimer, and antimicrobial activities potential of A. macrochaetum were determined.