Dietary docosahexaenoic acid (DHA) downregulates liver DHA synthesis by inhibiting eicosapentaenoic acid elongation.

DHA is abundant in the brain where it regulates cell survival, neurogenesis, and neuroinflammation. DHA can be obtained from the diet or synthesized from alpha-linolenic acid (ALA; 18:3n-3) via a series of desaturation and elongation reactions occurring in the liver. Tracer studies suggest that dietary DHA can downregulate its own synthesis, but the mechanism remains undetermined and is the primary objective of this manuscript. First, we show by tracing 13C content (δ13C) of DHA via compound-specific isotope analysis, that following low dietary DHA, the brain receives DHA synthesized from ALA. We then show that dietary DHA increases mouse liver and serum EPA, which is dependant on ALA. Furthermore, by compound-specific isotope analysis we demonstrate that the source of increased EPA is slowed EPA metabolism, not increased DHA retroconversion as previously assumed. DHA feeding alone or with ALA lowered liver elongation of very long chain (ELOVL2, EPA elongation) enzyme activity despite no change in protein content. To further evaluate the role of ELOVL2, a liver-specific Elovl2 KO was generated showing that DHA feeding in the presence or absence of a functional liver ELOVL2 yields similar results. An enzyme competition assay for EPA elongation suggests both uncompetitive and noncompetitive inhibition by DHA depending on DHA levels. To translate our findings, we show that DHA supplementation in men and women increases EPA levels in a manner dependent on a SNP (rs953413) in the ELOVL2 gene. In conclusion, we identify a novel feedback inhibition pathway where dietary DHA downregulates its liver synthesis by inhibiting EPA elongation.

In vitro Evaluation of Skin Related Enzyme Inhibitory Effect and Emulgel Formulation Development Studies of Onobrychis Argyrea subsp. Argyrea with Phytochemical Analysis.

Species of Onobrychis have been used to treat skin disorders such as wounds and cuts in folk medicine and Onobrychis argyrea subsp. argyrea (OA) commonly known as 'silvery sainfoin', is a member of this genus. In this study, it was aimed to investigate the skin-related biological activities and phytochemical characterization of OA. Moreover, an emulgel formulation was developed from the main methanolic extract of the plant (OAM). Initially, to identifiy of the active fractions, aerial parts of the plant material was extracted with methanol and fractionated by n-hexane, chloroform, ethyl acetate and n-butanol, respectively. Antioxidant activity was determined by CUPRAC, TOAC, FRAP and DPPH assays. Thereafter, the inhibition potential of OAM, novel formulation and all fractions was measured against elastase, collagenase, tyrosinase and hyaluronidase enzymes. OAM was analyzed and characterized by LC/MS-MS. The major bioactive flavonoids which are rutin and isoquercetin were measured and compared as qualitative and quantitative via high performance thin layer chromatography (HPTLC) analysis in OAM and fractions. The results showed that extracts of OA can be a potential cosmeceutical agent for skin related problems.

The pharmacological properties of Gypsophila eriocalyx: The endemic medicinal plant of northern central Turkey.

The aim of this study is to evaluate and compare the biological properties of different extracts (methanol, ethanol, and water) obtained from Gypsophila eriocalyx (G. eriocalyx), a medicinal plant traditionally used in Turkey. The components of different extracts were defined using the GC-MS method. The effects of G. eriocalyx extracts on cell proliferation, apoptosis, and cell cycle arrest in MDA-MB-231 breast cancer as well as in vitro antioxidant, enzyme inhibition, and antimicrobial activities were investigated. In accordance with the results obtained, although ethanol and methanol extracts of G. eriocalyx show higher antioxidant activity than G. eriocalyx water extract, enzyme inhibition activities of the extracts were not found to be significant compared to the reference drug. The methanol and ethanol extract of G. eriocalyx exhibited moderate antimicrobial activity against Staphylococcus aureus and methanol extract showed significant antimicrobial activity against Bacillus cereus. In addition, both extracts significantly inhibited cell viability in a dose-dependent manner in breast cancer cells. The cell growth inhibition by methanol and ethanol extracts induced S phase cell-cycle arrest and apoptosis in MDA-MB-231 cells. Lastly, in order to compare the activities of the chemicals found in Gypsophila eriocalyx plant extract, their activities against various proteins that are breast cancer protein (PDB ID:1A52 and 1JNX), antioxidant protein (PDB ID: 1HD2), AChE enzyme protein (PDB ID: 4M0E), BChE enzyme protein (PDB ID: 5NN0), and Escherichia coli protein (PDB ID: 4PRV)were compared. Then, ADME/T analysis calculations were made to examine the effects of molecules with high activity on human metabolism. Eventually, G. eriocalyx is thought to be a potent therapeutic herb that can be considered as an alternative and functional therapy for the management of diseases of a progressive nature related to oxidative damage such as infection, diabetes, cancer, and Alzheimer's disease.

Exploring the therapeutic mechanism of potential phytocompounds from Kalanchoe pinnata in the treatment of diabetes mellitus by integrating network pharmacology, molecular docking and simulation approach.

Since ancient times, bioactive phytocompounds from different parts of medicinal plants have been used to heal various disease ailments and they are now regarded as a valuable source of disease prevention globally. Kalanchoe pinnata is a member of the Crassulaceae family; it has a long history of usage in traditional ayurvedic treatment. Analysis of bioactive compounds for their potential anti-type-2 diabetes mellitus (T2DM) mechanism along with in-vitro and in-silico approaches was studied in the present research. The alpha-amylase and alpha-glucosidase inhibitory activity of methanolic extract of Kalanchoe pinnata (α-amylase: IC50 29.50 ± 0.04 µg/ml; α-glucosidase IC50 32.04 ± 0.35 µg/ml) exhibit a high degree of similarity to the standard drug acarbose (IC50 35.82 ± 0.14 µg/ml). Different biological databases were used to list phytocompounds from the plant, and ADME analysis using swissADME was carried out to screen compounds that obeyed the Lipinski rule of 5 and were employed further. STRING and KEGG pathway analysis was performed for gene enrichment analysis followed by network pharmacology to identify key target proteins involved in DM. AMY2A, NOX4, RPS6KA3, ADRA2A, CHRM5, and IL2 were identified as core targets for luteolin, kaempferol, alpha amyrin, stigmasterol compounds by modulating neuroactive ligand interaction, P13-AKT, MAPK, and PPAR signaling pathways. Molecular docking was performed to study the binding affinity among bioactive compounds of K. pinnata against aldose reductase, alpha-amylase, alpha-glucosidase, and dipeptidyl peptidase IV. Alpha-amylase-friedelin [FRI] and alpha-amylase-acarbose [STD] complexes were subjected to molecular simulation for a 200 ns duration that depicted the stability of the compounds and proteins. In the current study, employing dual approach in-silico and in-vitro enzyme assays has yielded a comprehensive and strong understanding of its potential therapeutic properties, making a significant step towards the development of novel anti-diabetic treatment.

Optimized Conditions for the Extraction of Phenolic Compounds from Aeginetia indica L. and Its Potential Biological Applications.

Aeginetia indica L., a parasitic root in the Orobanchaceae family, is used as a food colorant in traditional Thai desserts. However, scant information is available on its food applications as well as medicinal properties, while overharvesting by the local people has severely depleted wild plant populations. This research, thus, aimed to extract optimized total phenolic content (TPC) in varying extraction conditions using response surface methodology (RSM) and the Box-Behnken design (BBD). Results indicated that an extraction temperature of 90 °C, 80% (v/v) aqueous ethanol, and 0.5% (w/v) solid-to-liquid ratio yielded the highest TPC at 129.39 mg gallic acid equivalent (GAE)/g dry weight (DW). Liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified the predominant phenolics as apigenin (109.06 mg/100 g extract) and luteolin (35.32 mg/100 g extract) with trace amounts of naringenin and rutin. Under the optimal extraction condition, the plant extract exhibited antioxidant activities of 5620.58 and 641.52 µmol Trolox equivalent (TE)/g DW determined by oxygen radical absorbance capacity (ORAC) and ferric ion reducing antioxidant power (FRAP) assay, while the scavenging capacity of total radicals at 50% (SC50) was determined to be 135.50 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The plant extract also exhibited inhibitory activities against the key enzymes relevant to type II diabetes, obesity, and Alzheimer's disease, suggesting the potential for medicinal applications.

Variation in Phenolic Content, Antioxidant Activity and Alpha-amylase and Acetylcholinesterase Inhibitory Capacities of Different Extracts from Tunisian Satureja barceloi (Willk) L.

The antioxidant activity and the anti-α-amylase and anti-acetylcholinesterase capacities of secondary metabolites from different organs (roots, stems, leaves and flowers) of Tunisian Satureja barceloi were determined. The variation in the distribution of phenolic metabolites among roots, stems, leaves and flowers extracts of S. barceloi with various solvent systems (methanol, ethyl acetate, hexane and distilled water) has not been characterized before. Significant variation of phenolic compounds was observed according to organs rather than to extracting solvents. The analyzed organs show a high level of phenolic compounds although the stems contains the highest total polyphenols (132.53±0.48 mg AGE/g Ex), flavonoids (48.99±0.65 mg RE/g Ex) and flavonols (34.93±0.29 mg QE/g Ex) contents. The phenolic fraction was dominated by sagerinic acid, caffeic acid glucoside and epigallocatechin, detected using HPLC-PDA/ESI-MS. The antioxidant activity of all extracts, evaluated by four in vitro tests, was high and varied significantly according to the type of solvent used and the plant organ. The aqueous extracts of leaves exhibited the greatest inhibitory effect on alpha-amylase while the methanolic extract of leaves and stems revealed the most important acetylcholinesterase inhibitory effect. Hence, S. barceloi extracts could be used as a source of various bioactive molecules in pharmaceutical industry.

Evaluation of Bioactive Effects of Five Plant Extracts with Different Phenolic Compositions against Different Therapeutic Targets.

Plant extracts rich in phenolic compounds have been reported to exert different bioactive properties. Despite the fact that there are plant extracts with completely different phenolic compositions, many of them have been reported to have similar beneficial properties. Thus, the structure-bioactivity relationship mechanisms are not yet known in detail for specific classes of phenolic compounds. In this context, this work aims to demonstrate the relationship of extracts with different phenolic compositions versus different bioactive targets. For this purpose, five plant matrices (Theobroma cacao, Hibiscus sabdariffa, Silybum marianum, Lippia citriodora, and Olea europaea) were selected to cover different phenolic compositions, which were confirmed by the phytochemical characterization analysis performed by HPLC-ESI-qTOF-MS. The bioactive targets evaluated were the antioxidant potential, the free radical scavenging potential, and the inhibitory capacity of different enzymes involved in inflammatory processes, skin aging, and neuroprotection. The results showed that despite the different phenolic compositions of the five matrices, they all showed a bioactive positive effect in most of the evaluated assays. In particular, matrices with very different phenolic contents, such as T. cacao and S. marianum, exerted a similar inhibitory power in enzymes involved in inflammatory processes and skin aging. It should also be noted that H. sabdariffa and T. cacao extracts had a low phenolic content but nevertheless stood out for their bioactive antioxidant and anti-radical capacity. Hence, this research highlights the shared bioactive properties among phenolic compounds found in diverse matrices. The abundance of different phenolic compound families highlights their elevated bioactivity against diverse biological targets.

Unveiling the chemical profiling and remarkable modulation of carbohydrate metabolism by costus root, Dolomiaea costus (Falc.) in streptozotocin (STZ)-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Dolomiaea costus (Falc.), formerly Saussurea costus (Falc.) Lipsch., an ayurvedic medicinal plant, has long been recognized and utilized in diverse indigenous systems of medicine for its multifaceted therapeutic properties, including anti-inflammatory, carminative, expectorant, antiarthritic, antiseptic, aphrodisiac, anodyne, and antidiabetic effects. AIM OF THE STUDY: The potential and underlying mechanisms of D. costus root as an antidiabetic agent were investigated in this study. Additionally, the quantification of phenolic and flavonoid compounds, which dominate the extracts, was of particular interest in order to elucidate their contribution to the observed effects. MATERIALS AND METHODS: High-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was employed to analyze the chemical constituents in D. costus root aqueous extract (DCA) and D. costus root ethanolic extract (DCE). Furthermore, the inhibitory potentials of DCE and its respective fractions as well as DCA against α-amylase, α-glucosidase, and lipase enzymes were assessed. Subsequently, the efficacy of DCA and DCE extracts was evaluated using an established streptozotocin (STZ)-induced diabetic animal model; this involved administering the extracts at doses of 200 and 400 mg/kg bwt. and comparing them with a positive control (glibenclamide (Glib.) at 0.6 mg/kg bwt.). After induction of diabetes (except for negative control), all animals received the treatments orally for 21 days consecutively, followed by the collection of rat serum to assess various parameters including, glycemic and lipid profiles, liver and kidney functions, antioxidant activity, glycolysis, and gluconeogenesis pathways. RESULTS: The results of HPLC-ESI-MS/MS revealed that isochlorogenic acid A (8393.64 µg/g) and chlorogenic acid (6532.65 µg/g) were the predominant compounds in DCE and DCA, respectively. Both extracts exhibited notable antidiabetic properties, as evidenced by their ability to regulate blood glycemic and lipid profiles (glucose, insulin, HBA1C; HDL, TC, TGs), liver enzymes (ALT, ALP, AST), kidney function (urea, creatinine, uric acid), oxidative stress biomarkers (MDA), antioxidant enzymes (CAT, GSH, SOD), as well as glycolysis (glucokinase) and gluconeogenesis (G-6-P, FBP1) pathways. CONCLUSIONS: Furthermore, the administration of D. costus extracts significantly mitigated STZ-induced diabetic hyperglycemia. These results can be attributed, at least partially, to the presence of several polyphenolic compounds with potent antioxidant and anti-inflammatory activities.

Antioxidant and anti-inflammatory potentials of Ammodaucus leucotrichus Coss. & Durieu seeds' extracts: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Ammodaucus leucotrichus Coss. & Durieu (Apiaceae) is traditionally used in southern Algeria as a remedy against a wide range of disease due to its health-promoting properties. AIM OF THE STUDY: To investigate anti-oxidant and anti-inflammatory potentials of plant methanolic extract and its fractions in vitro and in vivo. MATERIALS AND METHODS: Anti-radical activity was assessed in vitro using ABTS•+, superoxide anion (O2•-) and nitric oxide radical (•NO). Lipid peroxidation inhibition was also investigated in the linoleic acid system. Enzyme inhibition assay was performed against α-amylase and α-glucosidase. The anti-inflammatory effect of extracts was screened in vitro through thermal induction of human serum albumin, and in vivo on a skin acute inflammation model induced by λ-carrageenan paw injection, xylene and croton oil topical application. Analgesic effect was evaluated by acetic acid-induced writhing test. RESULTS: The highest contents of polyphenols and flavonoids was recorded by the crude extract (77.14 ± 0.01 µg GAE/mg E and 19.59 ± 0.08 µg QE/mg E, respectively). Among the extracts, ethyl acetate extract showed a promising anti-radical activity of ABTS•+, O2•- and •NO, in addition to a remarkable inhibition activity of the tested enzymes. Meanwhile, all extracts effectively protected linoleic acid against lipid peroxidation and human serum albumin structure in thermal condition even at low concentration (0.31 mg/ml). Oral administration of 200 mg/kg of crude extract successfully inhibited acetic acid induced nociception and reduced edema formation induced by xylene and carrageenan. However, a dose-dependent manner was observed to decrease ear edema by a microscopic examination in croton oil induced acute inflammation. Nitrite and malondialdehyde levels together with catalase activity were modulated in the presence of plant-derived bioactive compounds. CONCLUSIONS: This study showed that Ammodaucus leucotrichus is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds.

Phytochemical analyses by LC-HRMS, FTIR spectral analysis, antioxidant, antidiabetic and antityrosinase activity of Crataegus orientalis Pall. ex M. Bieb fruit extracted with various solvents.

BACKGROUND: Crataegus orientalis Pall. ex M. Bieb fruit (COPMB) is extensively used as a source of various products in the medicinal-aromatic field and holds the potential for erosion control, ornamental purposes, food source, and economic benefits for forest villagers from its fruits. This study aims to determine the chemical components and biological activities of extracts prepared from COPMB using different solvents. RESULTS: The present work was designed to define the antioxidant activity [phosphomolybdenum (total antioxidant capacity), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), cupric ion-reducing antioxidant capacity (CUPRAC) and metal chelating activity (MCA)], phytochemical screening analysis, enzyme inhibitor (α-amylase, α-glucosidase and tyrosinase) potential, and liquid chromatography-high resolution mass spectrometry (LC-HRMS) secondary metabolite profiling in different extracts of COPMB. The results of LC-HRMS revealed that fumaric acid was the main phenolic compound in all extracts. Among the extracts, ethyl acetate extract has the highest phytochemical and antioxidant properties [total phenolic content (TPC): 32.5 mg GAE/g, total flavonoid content (TFC): 12.2 mg QE/g, ABTS: 213.0 mg TE/g; CUPRAC: 126.0 mg TE/g, MCA: 145.0 mg EDTA/g; FRAP: 122.8 mg TE/g; TAC: 2.8 mmol TE/g]. Ethyl acetate and methanol extracts are more effective in α-amylase (0.27 ± 0.01 mg/mL; 0.12 ± 0.00 mg/mL), α-glucosidase (0.63 ± 0.02 mg/mL; 0.77 ± 0.02 mg/mL) and tyrosinase (0.03 ± 0.00 mg/mL; 0.03 ± 0.00 mg/mL) enzyme inhibition potentials compared to standard acarbose (0.75 ± 0.02 mg/mL for α-amylase; 1.11 ± 0.03 mg/mL for α-glucosidase) and kojic acid (0.04 ± 0.00 mg/mL). CONCLUSION: The findings from this study suggest that COPMB could serve as a valuable source of natural agents for the food and pharmaceutical industry. © 2024 Society of Chemical Industry.

Chemical Profiling, in-vitro biological evaluation and molecular docking studies of Ruellia tweediana: An unexplored plant.

Many Ruellia species have been utilized in traditional medicine and despite the prevalent use of Ruellia tweediana in folk medicine, its antioxidant potential and polyphenol content have not been investigated. Therefore, the present study aimed to explore the medicinal value of R. tweediana by evaluating its total phenolic (TPC) and flavonoid contents (TFC), GC-MS analysis, antioxidant, antibacterial, and enzyme inhibition activities. The TPC and TFC of the extract/fractions were assessed using the Folin-Ciocalteu and aluminum trichloride methods, respectively. To determine the antioxidant capacity, five different assays were used: DPPH, ABTS, CUPRAC, FRAP, and metal chelating assays. The inhibition activity against α-glucosidase, α-amylase, cholinesterases, and lipoxygenase enzymes was also analyzed. Furthermore, GC-MS was performed for chemical screening of non-polar fraction. The methanol extract showed the maximum TPC (167.34 ± 2.23 mg GAE/g) and TFC (120.43 ± 1.71 mg RE/g) values among all the tested samples. GC-MS screening of the n-hexane fraction showed the presence of 40 different phytoconstituents. The results demonstrated the highest scavenging potential of the methanol extract against DPPH (167.79 ± 2.75 mg TE/g) and ABTS (255.32 ± 2.91 mg TE/g) radicals, as well as the metal-reducing capacity measured by CUPRAC (321.34 ± 3.09 mg TE/g), FRAP (311.32 ± 2.91 mg TE/g), and metal chelating assay (246.78 ± 10.34 mg EDTAE/g). Notably, the n-hexane fraction revealed the highest α-glucosidase and α-amylase inhibition activity (186.8 ± 2.84 and 179.7 ± 4.32 mg ACAE/g, respectively) while methanol extract showed highest acetylcholinesterase and butyrylcholinesterase inhibition activity (198.6 ± 3.31 and 184.3 ± 2.92 mg GALE/g, respectively). The GC-MS identified Lupeol showed best binding affinity with all docked enzymes as compared to standard compounds. The presence of bioactive phytoconstituents showed by GC-MS underscores the medicinal importance of R. tweediana, making it a promising candidate for natural medicine.

HPLC-MS/MS Profiles, Antioxidant, Neuroprotective, Antidiabetic and Skin Protective Effects of Different Extracts of Vicia peregrina L. Collected from the Eastern Region of Turkey.

Many Vicia species (Fabaceae) were proven to possess bioactive compounds with potential health beneficial properties. The present study was designed to determine the phenolic constituents, antioxidant and enzyme inhibition activities of aerial parts and seed of V. peregrina. Hexane, ethyl acetate and methanol extracts were prepared by maceration and aqueous extract by infusion. The chemical compositions of the extracts were determined using HPLC-MS/MS technology. The antioxidant activities were examined using various assays including free radical scavenging (ABTS and DPPH), reducing ability (CUPRAC and FRAP), metal chelation, and phosphomolybdenum. The enzyme inhibitory effects were investigated against cholinesterase, tyrosinase, amylase and glucosidase. The highest total phenolics and flavonoids contents were recorded in the methanol extracts of the seed (45.42 mg GAE/g) and aerial parts (40.33 mg RE/g) respectively. The aerial parts were characterized by higher accumulation of chlorogenic acid (9893.86 µg g-1 ), isoquercitrin (9400.33 µg g-1 ), delphindin 3,5 diglucoside (9113.28 µg g-1 ), hyperoside (6337.09 µg g-1 ), rutin (3489.83 µg g-1 ) and kaempferol-3-glucoside (2872.84 µg g-1 ). Generally, the methanol and aqueous extracts of the two studied parts exerted the best antioxidant activity with highest anti-DPPH (61.99 mg TE/g), anti-ABTS (101.80 mg TE/g) and Cu++ (16169 mg TE/g) and Fe+++ (172,36 mg TE/g) reducing capacity were recorded from the seed methanol extract. Methanol extract of the seed showed the best anti-tyrosinase activity (75.86 mg KAE/g). These results indicated that V. peregrina is rich with bioactive phenolics suggesting their use in different health promoting applications.

Evaluation of Biological Potency of two Endemic Species Integrated with in vitro and in silico Approches: LC-MS/MS Analysis of the Plants.

In the present study, the main phytochemical components of endemic plant extracts and inhibitory potency were screened related to different biological activities. Seven compounds were quantified, and cyanidin-3-o-glucoside was the dominant secondary metabolite in the extract of plants. The extract from P. asiae-minoris (PAM) exhibited the best enzyme inhibitory activity against BChE (1.73±0.23 µg mL-1 ), tyrosinase (2.47±0.28 µg mL-1 ), α-glucosidase (5.28±0.66 µg mL-1 ), AChE (8.66±0.86 µg mL-1 ), and ACE (19.27±1.02 µg mL-1 ). In vitro antioxidant assay, PAM extract possessed the highest activity in respect of DPPH radical scavenging (24.29±0.23 µg/mL), ABTS⋅+ scavenging (13.50±0.27 µg/mL) and FRAP reducing power (1.56±0.01 µmol TE/g extract). MIC values ranged from 1-8 mg/mL for antibacterial ability, and the PAM extract showed a stronger effect for B. subtilis, E. faecalis, and E. coli at 1 mg/mL. The antiproliferative ability of A. bartinense (AB) extract demonstrated a suppressive effect (IC50 : 70.26 µg/mL) for pancreatic cancer cell lines. According to the affinity scores analysis, the cyanidin-3-o-glucoside demonstrated the lowest docking scores against ACE, AChE, BChE, and collagenase. It was found that the PAM extract exhibited better inhibitory capabilities than A. bartinense. The P. asiae-minoris plant, reported to be in the Critically Endangered (CR) category, should be conserved by culturing, considering its biological abilities.

Biochemical, Toxicological, and in Silico Aspects of Trillium govanianum Wall. ex D.Don (Trilliaceae): A Rich Source of Natural Bioactive Compounds.

Trillium govanianum is a high-value medicinal herb, having multifunctional traditional and culinary uses. The present investigation was carried out to evaluate the phytochemical, biological and toxicological parameters of the T. govanianum Wall. ex D. Don (Family: Trilliaceae) roots collected from Azad Kashmir, Pakistan. Phytochemical profiling was achieved by determining total bioactive contents (total phenolic and flavonoid contents) and UHPLC-MS analysis. For biological evaluation, antioxidant activities (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation assays) and enzyme inhibition activities (against AChE, BChE, glucosidase, amylase, and tyrosinase) were performed. Moreover, cytotoxicity was assessed against three human carcinoma cell lines (MDA-MB-231, CaSki, and DU-145). The tested extract was found to contain higher total phenolics (7.56 mg GAE/g dry extract) as compared to flavonoid contents (0.45 mg RE/g dry extract). Likewise, for the antioxidant activity, higher CUPRAC activity was noted with 39.84 mg TE/g dry extract values. In the case of enzyme assays, higher activity was pointed out against the cholinesterase, glucosidase and tyrosinase enzymes. The plant extract displayed significant cytotoxicity against the cell lines examined. Moreover, the in-silico studies highlighted the interaction between the important phytochemicals and tested enzymes. To conclude, the assessed biological activity and the existence of bioactive phytochemicals in the studied plant extract may pave the way for the development of novel pharmaceuticals.

Uncovering chemical profiles, biological potentials, and protection effect against ECM destruction in H2 O2 -treated HDF cells of the extracts of Stachys tundjeliensis.

The genus Stachys L., one of the largest genera of the Lamiaceae family, is highly represented in Turkey. This study was conducted to determine the bio-pharmaceutical potential and phenolic contents of six different extracts from aerial parts of Stachys tundjeliensis. The obtained results showed that the ethanol extract exhibited the highest antioxidant activity in the antioxidant assays. Meanwhile, the ethanol extract displayed strong inhibitory activity against α-tyrosinase, the dichloromethane extract exhibited potent inhibition against butyrylcholinesterase, and the n-hexane extract against α-amylase. Based on ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry analysis, more than 90 secondary metabolites, including hydroxybenzoic acid, hydroxycinnamic acid, and their glycosides, acylquinic acids, phenylethanoid glycosides, and various flavonoids were identified or tentatively annotated in the studied S. tundjeliensis extracts. It was observed that the application of S. tundjeliensis eliminated H2 O2 -induced oxidative stress. It was determined that protein levels of phospho-nuclear factor kappa B (NF-κB), receptor for advanced glycation endproducts, and activator protein-1, which are activated in the nucleus, decreased, and the synthesis of matrix metalloproteinase (MMP)-2 and MMP-9 also decreased to basal levels. Overall, these findings suggest that S. tundjeliensis contains diverse bioactive compounds for the development of nutraceuticals or functional foods with potent biological properties.

In vitro and in silico cholinesterase inhibitory and antioxidant effects of essential oils and extracts of two new Salvia fruticosa mill. cultivars (Turgut and Uysal) and GC-MS analysis of the essential oils.

The EtOH extracts of the leaves of two new cultivars (Uysal-SFU and Turgut-SFT) of Salvia fruticosa Mill. was tested against acetylcholinesterase (IC50: 30.62 ± 3.27 and 32.97 ± 2.33 µg/mL for SFU and SFT, respectively) and butyrylcholinesterase (IC50: 69.91 ± 1.08 µg/mL and 86.55 ± 1.26 µg/mL), respectively, relevant to Alzheimer's disease. The essential oils showed a stumpy inhibition against AChE and no inhibition against BChE. DPPH radical scavenging activity of the extracts (86.70 ± 0.17% and 86.14 ± 1.13% for SFU and SFT, respectively) was stronger than that of quercetin (85.51 ± 0.17%): Their (1.24 ± 0.05 and 1.04 ± 0.16 for SFU and SFT, respectively) ferric-reducing antioxidant power were close to that of the reference (e.g. quercetin, 1.42 ± 0.14). Molecular docking simulations were performed on their major monoterpenes. Our findings revealed that the leaf EtOH extracts of two cultivars are promising inhibitors of both AChE and BChE.

Exploring Major Flavonoid Phytochemicals from Nelumbo nucifera Gaertn. as Potential Skin Anti-Aging Agents: In Silico and In Vitro Evaluations.

Nelumbo nucifera Gaertn., an aquatic medicinal plant (Nelumbonaceae family), has a history of use in traditional medicine across various regions. Our previous study demonstrated the skin anti-aging potential of its stamen ethanolic extract by effectively inhibiting collagenase and tyrosinase enzymes. While the major constituents of this extract are well documented, there is a lack of research on the individual compounds' abilities to inhibit skin aging enzymes. Therefore, this study aimed to evaluate the anti-aging potential of the primary flavonoids found in N. nucifera using both in silico and in vitro approaches. Our initial step involved molecular docking to identify compounds with the potential to inhibit collagenase, elastase, and tyrosinase. Among the seven flavonoids studied, kaempferol-3-O-robinobioside (Kae-3-Rob) emerged as the most promising candidate, exhibiting the highest docking scores for three skin aging-related enzymes. Subsequent enzyme-based inhibition assays confirmed that Kae-3-Rob displayed robust inhibitory activity against collagenase (58.24 ± 8.27%), elastase (26.29 ± 7.16%), and tyrosinase (69.84 ± 6.07%). Furthermore, we conducted extensive 200-ns molecular dynamics (MD) simulations, revealing the stability of the complexes formed between Kae-3-Rob and each enzyme along the MD simulation time. MM/PBSA-based binding free energy calculations indicated the considerably stronger binding affinity of Kae-3-Rob for collagenase and tyrosinase compared to elastase, which was related to the greater percentage of hydrogen bond occupations. These computational findings were consistent with the relatively high inhibitory activity of Kae-3-Rob against collagenase and tyrosinase observed in our in vitro experiment. In conclusion, the results obtained from this comprehensive study suggest that Kae-3-Rob, a key flavonoid from N. nucifera, holds significant potential as a source of bioactive compounds for anti-aging cosmeceutical and other phytopharmaceutical application.

Phytochemical analysis, antioxidant, antimicrobial, and anti-enzymatic properties of Alpinia coriandriodora (sweet ginger) rhizome.

Alpinia coriandriodora, also known as sweet ginger, is a medicinal and edible plant. A. coriandriodora rhizome is popularly utilized in traditional Chinese medicine and as flavouring spices, but there are few reports on its constituents and bioactivities. This study analyzed the phytochemical components of A. coriandriodora rhizome by GC-MS and UHPLC-Q-Orbitrap-MS and evaluated its antioxidant, antimicrobial, and anti-enzymatic properties. According to the GC-FID/MS data, its rhizome essential oil (EO) consisted mainly of (E)-2-decenal (53.8%), (E)-2-decenyl acetate (24.4%), (Z)-3-dodecenyl acetate (3.5%), and (E)-2-octenal (3.5%). Its water extract (WE) and 70% ethanol extract (EE) showed high total phenolic content (TPC, 52.99-60.49 mg GAEs/g extract) and total flavonoid content (TFC, 260.69-286.42 mg REs/g extract). In addition, the phytochemicals of WE and EE were further characterized using UHPLC-Q-Orbitrap-MS, and a total of sixty-three compounds were identified, including fourteen phenolic components and twenty-three flavonoid compounds. In the antioxidant assay, WE and EE revealed a potent scavenging effect on DPPH (IC50: 6.59 ± 0.88 mg/mL and 17.70 ± 1.15 mg/mL, respectively), surpassing the BHT (IC50: 21.83 ± 0.89 mg/mL). For the antimicrobial activities, EO displayed excellent antibacterial capabilities against Proteus vulgaris, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus with DIZ (12.60-22.17 mm), MIC (0.78-1.56 mg/mL), and MBC (3.13 mg/mL) and significantly inhibited Aspergillus flavus growth (MIC = 0.313 mg/mL, MFC = 0.625 mg/mL, respectively). In addition to weak tyrosinase and cholinesterase inhibition, EE and WE had a prominent inhibitory effect against α-glucosidase (IC50: 0.013 ± 0.001 mg/mL and 0.017 ± 0.002 mg/mL), which was significantly higher than acarbose (IC50: 0.22 ± 0.01 mg/mL). Hence, the rhizome of A. coriandriodora has excellent potential for utilization in the pharmaceutical and food fields as a source of bioactive substances.

Comparison of inhibitory activities of 50 Salvia species against α-Glucosidase.

Objectives: Type 2 diabetes is a common metabolic disease affecting millions of people worldwide. α-Glucosidase inhibitors can be used as one of the therapeutic approaches to decrease the postprandial glucose levels through the inhibition of carbohydrate hydrolysis. Medicinal plants are one of the main sources of α-glucosidase's natural inhibitors. In this study, we report the inhibitory effects of 50 different accessions of 32 Salvia species against α-glucosidase. Methods: To estimate the relative potency of the crude extracts, the inhibitory activities of the 80% methanol of the plants extracts were determined in three different concentrations (1000, 500 and 250 µg/ml) and compared to that of acarbose as the positive control. Results: S. multicaulis, S. santolinifolia, S. dracocephaloides, and S. eremophila were stronger inhibitors than acarbose (p < 0.05) with IC50 values in the range of 26.23- 92.35 µg/mL. According to the LC-PDA-ESIMS and NMR analysis of crude extracts of the studied Salvia species, 8 phytochemicals including luteolin-7-O-glucoside (1) luteolin-7-O-glucuronide (2), apigenin-7-O-glucoside (3), apigenin-7-O-glucuronide (4), Hispidulin-7-O-glucuronide (5), hispidulin-7-O-glucoside (6), rosmarinic acid (7), carnosol (8) and carnosic acid (9) were identified as the most common α-glucosidase inhibitors. The above compounds constituted the major compounds in the active Salvia species in the range of 1.5-95.0%. Among them rosmarinic acid (39-95%) was detected in almost all potent α -glucosidase inhibitor species. Therefore, it can be considered as a biochemical marker in the antidiabetic Salvia species in addition to the other minor compounds. Conclusions: Considering the high α-glucosidase inhibitory potential of the four- out of fifty Salvia species, they are suggested for further in vivo antidiabetic tests as potential medicinal plants.

Antioxidant, LC-MS Analysis, and Cholinesterase Inhibitory Potentials of Phoenix dactylifera Cultivar Khudari: An In Vitro Enzyme Kinetics and In Silico Study.

We evaluated the therapeutic potentials of Khudari fruit pulp, a functional food and cultivar of Phoenix dactylifera, against neurological disorders. Our results demonstrate a good amount of phytochemicals (total phenolic content: 17.77 ± 8.21 µg GA/mg extract) with a high antioxidant potential of aqueous extract (DPPH assay IC50 = 235.84 ± 11.65 µg/mL) and FRAP value: 331.81 ± 4.56 µmol. Furthermore, the aqueous extract showed the marked inhibition of cell-free acetylcholinesterase (electric eel) with an IC50 value of 48.25 ± 2.04 µg/mL, and an enzyme inhibition kinetics study revealed that it exhibits mixed inhibition. Thereafter, we listed the 18 best-matched phytochemical compounds present in aqueous extract through LC/MS analysis. The computational study revealed that five out of eighteen predicted compounds can cross the BBB and exert considerable aqueous solubility. where 2-{5-[(1E)-3-methylbuta-1,3-dien-1-yl]-1H-indol-3-yl}ethanol (MDIE) indicates an acceptable LD50. value. A molecular docking study exhibited that the compounds occupied the key residues of acetylcholinesterase with ΔG range between -6.91 and -9.49 kcal/mol, where MDIE has ∆G: -8.67 kcal/mol, which was better than that of tacrine, ∆G: -8.25 kcal/mol. Molecular dynamics analyses of 100 ns supported the stability of the protein-ligand complexes analyzed through RMSD, RMSF, Rg, and SASA parameters. TRP_84 and GLY_442 are the most critical hydrophobic contacts for the complex, although GLU_199 is important for H-bonds. Prime/MM-GBSA showed that the protein-ligand complex formed a stable confirmation. These findings suggest that the aqueous extract of Khudari fruit pulp has significant antioxidant and acetylcholinesterase inhibition potentials, and its compound, MDIE, forms stably with confirmation with the target protein, though this fruit of Khudari dates can be a better functional food for the treatment of Alzheimer's disease. Further investigations are needed to fully understand the therapeutic role of this plant-based compound via in vivo study.