ABSTRACT
Alzheimer's disease (AD) is a chronic neurodegenerative condition characterized by progressive cognitive impairment. While the formation of ß-amyloid plaques and neurofibrillary tangles are the hallmarks features of AD, the downstream consequence of these byproducts is the disruption of the cholinergic and glutamatergic neural systems. Growing evidence for the existence of interplay between AChE and NMDARs has opened up new venues for the discovery of novel ligands endowed with anticholinesterase and NMDAR-blocking activity. Plants belonging to the stachys genus have been extensively explored for having a broad range of therapeutic applications and have been used traditionally for millennia, to treat various CNS-related disorders, which makes them the ideal source of novel therapeutics. The present study was designed to identify natural dual-target inhibitors for AChE and NMDAR deriving from stachys genus for their potential use in AD. Using molecular docking, drug-likeness-profiling, MD simulation and MMGBSA calculations, an in-house database of biomolecules pertaining to the stachys genus was shortlisted based on their binding affinity, overall stability and critical ADMET parameters. Pre- and post-MD analysis revealed that Isoorientin effectively binds to AChE and NMDAR with various vital interactions, exhibits a stable behavior with minor fluctuations relative to two clinical drugs used as positive control, and displays strong and consistent interactions that lasted for the majority of the simulation. Findings from this study have elucidated the rationale behind the traditional use of Stachys plants for the treatment of AD and could provide new impetus for the development of novel dual-target therapeutics for AD treatment.Communicated by Ramaswamy H. Sarma.
Subject(s)
Alzheimer Disease , Stachys , Humans , Acetylcholinesterase/chemistry , Alzheimer Disease/drug therapy , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/chemistry , Computer Simulation , Molecular Docking Simulation , Stachys/chemistry , Receptors, N-Methyl-D-Aspartate/antagonists & inhibitorsABSTRACT
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.
Subject(s)
Stachys , Stachys/chemistry , Plant Extracts/chemistry , Butyrylcholinesterase , Receptor for Advanced Glycation End Products , Structure-Activity Relationship , Antioxidants/pharmacology , Antioxidants/chemistry , Glycosides , EthanolABSTRACT
Two new compounds geobomlin A (1) and geobomlin B (2) were isolated from the roots of Stachys geobombycis C. Y. Wu. Structural determinations were established principally by two-dimensional NMR and MS data analyses. Geobomlin B showed moderate inhibitory activity against α-glucosidase with IC50 = 248.77 µM. We have also determined the mechanism by which geobomlin B elicit its inhibitory effect on α-glucosidase, for which we have established a competitive inhibition mode. Docking studies confirmed our results on geobomlin B α-glucosidase inhibitory properties.
Subject(s)
Glycosides , Stachys , Glycosides/chemistry , Stachys/chemistry , alpha-Glucosidases/metabolism , Magnetic Resonance Spectroscopy , Plant Roots/chemistry , Glycoside Hydrolase Inhibitors/pharmacology , Glycoside Hydrolase Inhibitors/chemistry , Molecular Docking Simulation , Molecular StructureABSTRACT
Stachys brachyclada de Noé ex Coss. (Lamiaceae) is a quite rare medicinal plant endemic to the Mediterranean basin. In this study, seven secondary metabolites from a methanol extract of its leaves have been isolated and identified by a combination of chromatographic and spectroscopic methods (1D and 2D NMR experiments and ESIMS analysis). They include one ethyl 4-hydroxybenzoate (1), three acylated flavone glycosides (2-4), one diapigenin derivative (5) and two flavone aglycones (6-7). Stachysetin (5) was found the major compound of the extract (74.0 mg/g of dry matter). Moreover, the produced extract showed the ability in inhibiting the α-glucosidase enzyme (IC50 = 13.7 µg/mL), in quenching the radical 1,1-diphenyl-2-picrylhydrazyl (EC50 = 74.6 µg/mL), and in reducing the intracellular oxidative stress level in Human Dermal Fibroblast (64% inhibition at 50 µg/mL).
Subject(s)
Flavones , Stachys , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Stachys/chemistry , Hypoglycemic Agents/pharmacology , Methanol , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytochemicals/pharmacology , Phytochemicals/chemistryABSTRACT
Chinese artichoke tuber (Stachys sieboldii Miq.) is used as an herbal medicine as well as edible food. This study examined the effect of the Chinese artichoke extracts on the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway that induces the expression of antioxidant enzymes to explore its novel characteristics. Hot water extracts exhibited relatively high ARE activity. ARE activity was observed in two fractions when the hot water extracts were separated in the presence of trifluoroacetic acid using HPLC. Conversely, the highly active fraction disappeared when the hot water extracts were separated in the absence of trifluoroacetic acid. These results indicate that acidic degradation produces active ingredients. The structural analysis of the two active fractions identified harpagide, which is an iridoid glucoside, and harpagogenin. In vitro experiments revealed that harpagide was converted into harpagogenin under acidic conditions and that harpagogenin, but not harpagide, had potent ARE activity. Therefore, this study identified harpagogenin, which is an acid hydrolysate of harpagide, as an ARE activator and suggests that Nrf2-ARE pathway activation by Chinese artichoke contributes to the antioxidative effect.
Subject(s)
Stachys , Antioxidant Response Elements , Antioxidants/pharmacology , NF-E2-Related Factor 2 , Plant Extracts/pharmacology , Plant Extracts/chemistry , Stachys/chemistry , Trifluoroacetic Acid , WaterABSTRACT
Stachys is a large genus of economically important plants belonging to Lamiaceae family that includes about 300 species as annual or perennial herbs. Several species of this genus are extensively used in various traditional medicines. In the present study the chemical composition of the essential oil from aerial parts of Stachys spreitzenhoferi Heldr., a very rare plant, belonging to Section Candidae, endemic of South Greece and collected in the island of Kythira, was analysed by GC-MS. No one reports have been previously published on this species. The result showed the presence of large quantity of diterpenoids with manoyl oxide (22.1%), as the most abundant component. Other metabolites present in high quantity were trans-nerolidol (18.5%), ß-caryophyllene (11.0%) and germacrene D (8.1%). Chemotaxonomic considerations with respect all the other oils of Stachys taxa, belonging to the same section studied so far, were carried out.
Subject(s)
Lamiaceae , Oils, Volatile , Stachys , Oils, Volatile/chemistry , Lamiaceae/chemistry , Greece , Stachys/chemistry , Plant Components, Aerial/chemistryABSTRACT
The Stachys L. genus has been used in traditional medicine to treat skin inflammations, stomach disorders, and stress. The aim of this study was to investigate the chemical profile and biological activity of the methanolic extract of Stachys spreitzenhoferi Heldr. (Lamiaceae) aerial parts, collected on the island of Kythira, South Greece. The analysis by liquid chromatography coupled with electrospray ionization and high-resolution mass spectrometry [LC-(-)ESI/HRMSn] of the methanol extract revealed the occurrence of thirty-six compounds - flavonoids, phenylethanoid glycosides, iridoids, quinic acid derivatives, aliphatic alcohol glycosides, and oligosaccharides - highlighting the substantial presence, as main peaks, of the iridoid melittoside (2) along with flavonoid compounds such as 4'-O-methylisoscutellarein mono-acetyl-diglycoside/chrysoeriol mono-acetyl-diglycoside (24), trimethoxy- (35) and tetramethoxyflavones (36). This extract was tested for its antimicrobial properties against Gram-positive and negative pathogenic strains. The extract was not active against Gram-negative bacteria tested, but it possessed a good dose-dependent antimicrobial activity towards S. aureus (MIC: 1.0 mg/mL) and L. monocytogenes (MIC: 1.0 mg/mL) Gram-(+) strains. Furthermore, this extract has been tested for its possible antioxidant activity in vitro. In particular, it has been shown that these molecules cause a decrease in DPPH, ABTS, and H2O2 radicals. The extract of S. spreitzenhoferi exhibited anti-DPPH activity (IC50: 0.17 mg/mL), anti-H2O2 activity (IC50: 0.125 mg/mL), and promising antiradical effect with an IC50 value of 0.18 mg/mL for anti-ABTS activity. S. spreitzenhoferi extract caused a decrease in ROS (at the concentration of 200 µg/mL) and an increase in the activity of the antioxidant enzymes SOD, CAT, and GPX in OZ-stimulated PMNs. Furthermore, it exhibited antiproliferative activity against acute myeloid leukemia (U937 cell), causing 50% of cell death at the 0.75 mg/mL.
Subject(s)
Anti-Infective Agents , Lamiaceae , Stachys , Anti-Bacterial Agents , Antioxidants/chemistry , Antioxidants/pharmacology , Flavonoids/chemistry , Flavonoids/pharmacology , Glycosides/chemistry , Glycosides/pharmacology , Greece , Humans , Iridoids , Methanol , Plant Components, Aerial , Plant Extracts/chemistry , Plant Extracts/pharmacology , Quinic Acid , Reactive Oxygen Species , Stachys/chemistry , Staphylococcus aureus , Superoxide Dismutase , U937 CellsABSTRACT
INTRODUCTION: The genus Stachys L., belonging to the family Lamiaceae, is one of the largest genera with remarkable medicinal properties. Plants of this genus produce a broad range of secondary metabolites. OBJECTIVES: Due to the incomplete comprehensive assessment of chemical profiles in Stachys species, we conducted an untargeted metabolomics study and identified potential biomarkers in the six sections of Stachys with chemotaxonomic importance. MATERIAL AND METHODS: Dried leaves of 17 taxa were utilized for analysis of all the constituents using HPLC-MQ-API-MS. The obtained data were processed and analyzed using multivariate statistical methods, including heatmaps, PLS-DA score plots, functional analysis of metabolic pathways, metabolite set enrichment analysis, and biomarker and network analysis. RESULTS: Among the 129 metabolites, 111 flavonoids and 18 non-flavonoids were recognized. The most represented flavonoids, including 41 flavones and 20 flavonols, displayed remarkable abundance. In non-flavonoid compounds, a total of six coumarins and six phenolic acids were present at high levels. In terms of approved markers in six sections, 76 chemical compounds, mainly flavonoids, coumarins, quinic acids, and cinnamic acids, were identified as potential biomarkers or chemotaxonomic indicators. Accordingly, the taxonomic complexities of some Stachys species in sections Fragilicaulis, Aucheriana, and Setifolia were properly resolved. CONCLUSION: An HPLC-MS/MS-based metabolomics approach integrated with multivariate statistical methods was employed to identify (1) valuable markers and analyze metabolic diversity and (2) predict the pharmaceutical properties of Stachys species. The obtained chemical profiles provide a new perspective for investigation of the Stachys genus.
Subject(s)
Lamiaceae , Stachys , Biomarkers , Chromatography, High Pressure Liquid/methods , Coumarins/analysis , Flavonoids/analysis , Metabolomics , Stachys/chemistry , Tandem Mass Spectrometry/methodsABSTRACT
Herbal medicines harbor essential therapeutic agents for the treatment of cholestasis. In this study, we have assessed the anticholestatic potential of Stachys pilifera Benth's (SPB's) hydroalcoholic extract encapsulated into liposomes using bile duct ligation- (BDL-) induced hepatic cholestasis in rats. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total thiol (T-SH) content, protein carbonyl (PCO), total bilirubin (TBIL), albumin (ALB), and nitric oxide (NO) metabolite levels were measured in either liver tissue or plasma to assess liver damage. Moreover, expression of proinflammatory cytokines (IL-1ß and TNF-α) and liver fibrosis markers (TGF-ß and SM-α) which are driving forces of many liver disorders was also determined. The activity of AST, ALT, and ALP was significantly enhanced in the BDL group in comparison to the control group; however, treatment with liposomal (SPB) hydroalcoholic extract significantly reduced AST and ALT's activity. Increases in MDA, TBIL, and NO levels and T-SH content due to BDL were restored to control levels by liposomal (SPB) hydroalcoholic extract treatment. Similarly, hepatic and plasma oxidative marker MDA levels, significantly enhanced by BDL, were significantly decreased by liposomal (SPB) hydroalcoholic extract treatment. Moreover, histopathological findings further demonstrated a significant decrease in hepatic damage in the liposomal (SPB) hydroalcoholic extract-treated BDL group. In addition, liposomal (SPB) hydroalcoholic extract treatment decreased the liver expression of inflammatory cytokines (IL-1ß, TNF-α) and liver fibrosis markers (TGF-ß and SM-α). Since liposomal (SPB) hydroalcoholic extract treatment alleviated the BDL-induced injury of the liver and improved the hepatic structure and function more efficiently in comparison to free SPB hydroalcoholic extract, probable liposomal (SPB) hydroalcoholic extract exhibits required potential therapeutic value in protecting the liver against BDL-caused oxidative injury.
Subject(s)
Antioxidants/pharmacology , Cholestasis, Intrahepatic/drug therapy , Liver/drug effects , Plant Extracts/pharmacology , Stachys , Actins/genetics , Actins/metabolism , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Antifibrotic Agents/isolation & purification , Antifibrotic Agents/pharmacology , Antioxidants/isolation & purification , Cholestasis, Intrahepatic/metabolism , Cholestasis, Intrahepatic/pathology , Common Bile Duct/surgery , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Inflammation Mediators/metabolism , Ligation , Liposomes , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Biliary/drug therapy , Liver Cirrhosis, Biliary/metabolism , Liver Cirrhosis, Biliary/pathology , Male , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , Protein Carbonylation/drug effects , Rats, Wistar , Stachys/chemistry , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolismABSTRACT
Today, bacterial cellulose has received a great deal of attention for its medical applications due to its unique structural properties such as high porosity, good fluid uptake, good strength, and biocompatibility. This study aimed to fabricate and study bacterial cellulose/graphitic carbon nitride/nettles/trachyspermum nanocomposite by immersion and PVA/BC/g-C3 N4 /nettles/trachyspermum nanofiber by electrospinning method as a wound dressing. The g-C3 N4 and g-C3 N4 solution were synthesized and then were characterized using Fourier transform infrared, X-ray diffraction, Zeta Potential, and scanning electronic microscope analyzes. Also, the antibacterial properties of the synthesized materials were proved by gram-positive and gram-negative bacteria using the minimum inhibitory concentration method. Besides, the toxicity, migration, and cell proliferation results of the synthesized materials on NIH 3T3 fibroblasts were evaluated using MTT and scratch assays and showed that the BC/PVA/g-C3 N4 /nettles/trachyspermum composite not only had no toxic effect on cells but also contributed to cell survival, cell migration, and proliferation has done. To evaluate the mechanical properties, a tensile strength test was performed on PVA/BC/g-C3 N4 /nettles/trachyspermum nanofibers, and the results showed good strength of the nanocomposite. In addition, in vivo assay, the produced nanofibers were used to evaluate wound healing, and the results showed that these nanofibers were able to accelerate the wound healing process so that after 14 days, the wound healing percentage showed 95%. Therefore, this study shows that PVA/BC/g-C3 N4 /nettles/trachyspermum nanofibers effectively inhibit bacterial growth and accelerate wound healing.
Subject(s)
Anti-Bacterial Agents , Bandages , Cellulose , Graphite , Nitrogen Compounds , Wound Healing/drug effects , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Apiaceae/chemistry , Bacteria/chemistry , Bacteria/drug effects , Cell Survival/drug effects , Cellulose/chemistry , Cellulose/pharmacology , Graphite/chemistry , Graphite/pharmacology , Mice , Microbial Sensitivity Tests , NIH 3T3 Cells , Nanofibers/chemistry , Nitrogen Compounds/chemistry , Nitrogen Compounds/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Polyvinyl Alcohol/chemistry , Stachys/chemistryABSTRACT
This work analysed the chemical composition, antioxidant, and enzyme inhibitory activities of solvent extract (SJ-ME) and fractions (SJ-HF, SJ-EAF, and SJ-MF) of the Stachys riederi var. japonica (Miq.) (SJ). Furthermore, the effect of SJ-EAF in STZ induced type 2 diabetic mice was examined. Among the samples, SJ-EAF exhibited a lower IC50 concentration of 64.2 ± 0.48 µg/mL for DPPH and 82.6 ± 0.09 µg/mL for ABTS+. The SJ-EAF concentration of 2.89 ± 0.03 µg and 2.27 ± 0.98 µg was equivalent to 1 µg of acarbose mediated enzyme inhibitory effect against α-amylase and α -glucosidase, respectively. The SJ-EAF did not show cytotoxicity (<80%) to NIH3T3 nor HepG2 cells but enhanced the glucose uptake in the IR-HepG2. LC-MS/MS of SJ-EAF showed the presence of a total of 16 compounds. Among the identified compounds, rosmarinic acid, caffeic acid, oleanolic acid, and ursolic acid showed high catalytic activity of α-amylase and α-glucosidase. The treatments of SJ-EAF restored the level of blood glucose, body weight, insulin, HDL and mRNA level of IRS1, GLUT2, GLUT4 and Akt whereas it reduced the excess elevation of total cholesterol, total triglycerides, LDL, AST, ALT, ALP, BUN, and creatinine in STZ induced diabetic mice. Overall, the present study concluded that the SJ-EAF exhibited promising antidiabetic activity.
Subject(s)
Antioxidants/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Plant Extracts/therapeutic use , Stachys/chemistry , Animals , Antioxidants/chemistry , Antioxidants/metabolism , Antioxidants/toxicity , Cell Line, Tumor , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetes Mellitus, Type 2/chemically induced , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Gene Expression/drug effects , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/toxicity , Male , Mice, Inbred ICR , Molecular Docking Simulation , Plant Extracts/chemistry , Plant Extracts/metabolism , Plant Extracts/toxicity , Protein Binding , Streptozocin , alpha-Amylases/metabolism , alpha-Glucosidases/metabolismABSTRACT
Stachys pilifera Benth is an endemic species of Stachys family found in Iran with a wide application as an herbal tea. The objective of this research was to evaluate the antimicrobial, antioxidant and cytotoxic activity of the essential oil from the aerial parts of S. pilifera. Essential oil (EO) composition analysis showed that cis-Chrysanthenyl acetate (24.9%), viridiflorol (18.3%), trans-Caryophyllene (9.8%), caryophyllene oxide (4.6%), α-terpineol (3.3%) and linalool (3.1%) were the most abundant components. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the EO showed a higher antimicrobial activity against Gram-positive bacteria (Bacillus cereus and Staphylococcus aureus) than Gram-negative organisms (Escherichia coli, Shigella sonnei, Pseudomonas aeruginosa and Salmonella enterica subsp. Enterica). The antioxidant activity of EO was studied using DPPH, FRAP and ß-carotene/linoleic acid assays. IC50 for the DPPH, FRAP and ß-carotene/linoleic acid tests were 23.2, 28.7 and 16.1 µg/mL, respectively, that it was higher than the results for BHT (P ≤ 0.05). The cytotoxic activity of the EO was evaluated using HT29 and HUVEC cells and it was observed that by increasing in EO concentration from 0.026 to 19.4 ug/mL, the viability of the cells for HT29 and HUVEC reduced to 6.8 and 7.1%, respectively. The results from this study suggest the possibility to use the essential oils from S. pilifera Benth as a natural preservative in processed or packaged food due to its high antibacterial, antioxidant and cytotoxic activities.
Subject(s)
Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Bacteria/drug effects , Oils, Volatile/analysis , Oils, Volatile/pharmacology , Plant Leaves/chemistry , Stachys/chemistry , Anti-Bacterial Agents/chemistry , Antioxidants/chemistry , Bacteria/classification , Cell Survival/drug effects , Gram-Negative Bacteria/drug effects , Gram-Positive Bacteria/drug effects , HT29 Cells , Humans , Microbial Sensitivity Tests , Teas, HerbalABSTRACT
Stachys sieboldii MiQ (SSM) is an important food and medicinal herb in Korea, used to improve memory of patients with senile dementia and cardiovascular diseases. However, little information on bioactive components from SSM or standardized extraction methods for these components is available. This study isolated and purified major components from SSM for the first time, and assessed their ability to inhibit soluble epoxide hydrolase (sEH). The results showed that acteoside is the most potent inhibitor of sEH, with an IC50 of 33.5 ± 0.5 µM. Additional active components, including harpagide, tryptophan, and 8-acetate-harpagide, along with acteoside, were tentatively identified using high-performance liquid chromatography photodiode array tandem mass spectrometry (HPLC-PDA-MS/MS) and quantified using an ultraviolet detector at 210 nm. Further, an ultrasonic-assisted extraction technique for extraction of four bioactive compounds in SSM was developed and optimized using response surface methodology (RSM). The optimal extraction conditions were: extraction time, 30.46 minutes; extraction temperature, 67.95 °C, and methanol concentration 53.85%. The prediction model of RSM was validated with laboratory experiments. The similarity between predicted and actual values was 97.84%. The extraction method is thus a rapid, environment-friendly, energy-saving method can be applied to extract bioactive components from SSM in large quantities.
Subject(s)
Epoxide Hydrolases/antagonists & inhibitors , Epoxide Hydrolases/chemistry , Liquid-Liquid Extraction/methods , Models, Statistical , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Stachys/chemistry , Chromatography, High Pressure Liquid/methods , Glucosides/isolation & purification , Glucosides/pharmacology , Inhibitory Concentration 50 , Iridoid Glycosides/isolation & purification , Iridoid Glycosides/pharmacology , Methanol/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Pyrans/isolation & purification , Pyrans/pharmacology , Solubility , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Temperature , Tryptophan/isolation & purification , Tryptophan/pharmacology , Ultrasonic WavesABSTRACT
Stachys species are considered as important medicinal plants with numerous health benefit effects. In continuation of our research on the Greek Stachys species, the chemical profile of the aerial parts of cultivated S. iva Griseb. has been explored. The NMR profiles of the plant extract/infusion were used to guide the isolation process, leading to the targeted isolation of seventeen known compounds. The rare acylated flavonoid, stachysetin, was isolated for the third time from plant species in the international literature. Identification of the characteristic signals of stachysetin in the 1D 1H-NMR spectrum of the crude extract was presented. In order to evaluate the potential of the identified chemical space in Stachys to bear possible bioactivity against diabetes, we performed an in silico screening against 17 proteins implicated in diabetes, as also ligand based similarity metrics against established anti-diabetic drugs. The results capitalized the anti-diabetic potency of stachysetin. Its binding profile to the major drug carrier plasma protein serum albumin was also explored along with its photophysical properties suggesting that stachysetin could be recognized and delivered in plasma through serum albumin and also could be tracked through near-infrared imaging. Communicated by Ramaswamy H. Sarma.
Subject(s)
Hypoglycemic Agents/pharmacology , Plant Extracts/pharmacology , Stachys , Flavonoids/pharmacology , Magnetic Resonance Spectroscopy , Molecular Docking Simulation , Stachys/chemistryABSTRACT
AIMS AND OBJECTIVES: The intake of Stachys sieboldii MIQ. has been associated with relieving inflammation and maintaining optimal gut health function. We investigated the diversity and composition of microflora in feces of S. sieboldii MIQ.-fed mice. In addition, we evaluated the production of major cytokines (Interleukin-6 and -10) related to inflammation and fatty acid composition of several tissues. MATERIALS AND METHODS: 16S ribosomal DNA sequencing-based microbiome taxonomic profiling analysis was performed using EzBioCloud data base. The total RNA from the mesenteric lymph node was isolated and then synthesized with prime script 1st strand cDNA synthesis kit. Quantitative real-time PCR was performed on cDNA samples using the SYBR™ Green PCR Master Mix. RESULTS: Mice fed on S. sieboldii MIQ. showed significantly reduced counts of aerobic and coliform in the feces compared with control. 16S rDNA sequencing analysis of fecal samples showed that supplementation with S. sieboldii MIQ. increased beneficial intestinal microflora (Ruminococcaceae and Akkermansia muciniphila) and decreased the community of harmful microflora (Enterobacteriaceae, including Escherichia coli and Bacteroides sp.) in feces compared with that in the control (P<0.05 for all). Mice showed a significantly lower mRNA expression of cytokines IL-6 and IL-10 in mesenteric lymph node compared with that in control (P<0.05). The fecal fatty acid composition in the S. sieboldii MIQ. group showed a higher percentage of 6:0 and 18:2n-6 compared with that in the control group (P<0.05). The percentages of 6:0 and 20:3n-6 fatty acids were also significantly higher in the intestines of S. sieboldii MIQ. group (P<0.05). No differences were revealed between the two groups in terms of the percentages of total saturated, monounsaturated, n-6 and n-3 polyunsaturated fatty acids found in feces and tissues. CONCLUSION: The present results showed that supplementation of mice with S. sieboldii MIQ. increased beneficial gut microflora and decreased harmful microflora. Moreover, lower mRNA expression of pro-inflammatory cytokine IL-6, and anti-inflammatory cytokine IL-10 in the mesenteric lymph node of supplemented mice might be associated with the lower abundances of harmful fecal microflora.
Subject(s)
Cytokines/biosynthesis , Gastrointestinal Microbiome/drug effects , Plant Roots/chemistry , Polysaccharides/pharmacology , Stachys/chemistry , Animals , Body Weight/drug effects , Dietary Supplements , Feces/chemistry , Mice , Polysaccharides/chemistryABSTRACT
This study aimed at investigating the anti-obesity and anti-dyslipidemic effects of Stachys sieboldii Miq. root (SS) powder in rats following a high-fat and high-cholesterol (HFC) diet for 6 weeks. Thirty-two Sprague-Dawley rats were fed one of the following diets: a regular diet (RD), HFC, HFC supplemented with 3% SS (HFC + 3SS) or HFC supplemented with 5% SS (HFC + 5SS). Following an HFC diet increased body weight (BW) gain (p < 0.001) and the food efficiency ratio (FER; p < 0.001); however, SS consumption gradually prevented the HFC-induced BW gain (p < 0.001) and increase in FER (p < 0.01). The HFC diet resulted in increased liver size (p < 0.001) and total adipose tissue weight (p < 0.001), whereas the SS supplementation decreased hepatomegaly (p < 0.05) and body fat mass (p < 0.001). SS consumption prevented the increased activities of serum alanine aminotransferase (ALT; p < 0.001), aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.01 in HFC + 5SS) and lactate dehydrogenase (LDH; p < 0.001 in HFC + 5SS) induced by the HFC diet (p < 0.001). The SS supplementation improved lipid profiles in the circulation by lowering triglyceride (TG; p < 0.01), total cholesterol (TC; p < 0.001) and non-HDL cholesterol (non-HDL-C; p < 0.001) levels, as well as the atherogenic index (p < 0.01) and cardiac risk factor (p < 0.01). The lipid distribution in the liver (p < 0.05) and white adipose tissues (WAT; p < 0.001) of the HFC + SS diet-consuming rats was remarkably lower than that of the HFC diet-consuming rats. The average size of the epididymal adipose tissue (p < 0.001) was significantly lower in the HFC + SS diet-fed rats than in the HFC diet-fed rats. The fecal lipid (>3% SS; p < 0.001) and cholesterol (5% SS; p < 0.001) efflux levels were significantly elevated by the SS supplementation compared to those measured in the RD or HFC diet-fed groups. In addition, the hepatic lipid and cholesterol metabolism-related gene expressions were affected by SS consumption, as the hepatic anabolic gene expression (Acc; p < 0.001, Fas; p < 0.001 and G6pdh; p < 0.01) was significantly attenuated. The HFC + 5SS diet-fed rats exhibited elevated hepatic Cyp7a1 (p < 0.001), Hmgcr (p < 0.001) and Ldlr (p < 0.001) mRNA expression levels compared to the HFC diet-fed rats. These results suggest that SS may possess anti-adipogenic and lipid-lowering effects by enhancing lipid and cholesterol efflux in mammals.
Subject(s)
Adipogenesis/drug effects , Anti-Obesity Agents , Anticholesteremic Agents , Cholesterol, Dietary/adverse effects , Diet, High-Fat/adverse effects , Dietary Supplements , Dyslipidemias/drug therapy , Dyslipidemias/etiology , Phytotherapy , Plant Extracts/administration & dosage , Plant Extracts/pharmacology , Plant Roots/chemistry , Stachys/chemistry , Weight Gain/drug effects , Animals , Dyslipidemias/metabolism , Lipid Metabolism/drug effects , Liver/metabolism , Male , Rats, Sprague-DawleyABSTRACT
Genus Stachys, the largest genera of the family Lamiaceae, and its species are frequently used as herbal teas due to their essential oils. Tubers of some Stachys species are also consumed as important nutrients for humans and animals due to their carbohydrate contents. Three new neo-clerodane diterpene peroxides, named stachaegyptin F-H (1, 2, and 4), together with two known compounds, stachysperoxide (3) and stachaegyptin A (5), were isolated from Stachys aegyptiaca aerial parts. Their structures were determined using a combination of spectroscopic techniques, including HR-FAB-MS and extensive 1D and 2D NMR (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY) analyses. Additionally, a biosynthetic pathway for the isolated compounds (1-5) was discussed. The chemotaxonomic significance of the isolated diterpenoids of S. aegyptiaca in comparison to the previous reported ones from other Stachys species was also studied.
Subject(s)
Diterpenes, Clerodane/analysis , Phytochemicals/analysis , Plant Components, Aerial/chemistry , Plant Extracts/analysis , Stachys/chemistry , Biosynthetic Pathways , Classification , Diterpenes/analysis , Diterpenes/isolation & purification , Diterpenes, Clerodane/chemistry , Diterpenes, Clerodane/isolation & purification , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Structure , Peroxides/analysis , Peroxides/isolation & purification , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Plant Extracts/chemistry , Teas, Herbal/analysisABSTRACT
The present study aimed to identify the chemical constituents and to assess the in-vitro, antimicrobial, anticancer, antioxidant, metabolic enzymes and cyclooxygenase (COX) inhibitory properties of essential oil (EO) of Stachys viticina Boiss. leaves. The S. viticina EO was isolated and identified using microwave-ultrasonic and GC-MS techniques, respectively. Fifty-two compounds were identified, of which endo-borneol was the major component, followed by eucalyptol and epizonarene. The EO was evaluated against a panel of in-vitro bioassays. The EO displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Epidermophyton floccosum, with MIC values of 0.039, 0.078 and 0.78 mg/mL, respectively. The EO exhibited cytotoxicity against HeLa (cervical adenocarcinoma) and Colo-205 (colon) cancer cell lines with percentages of inhibition of 95% and 90%, for EO concentrations of 1.25 and 0.5 mg/mL, respectively. Furthermore, it showed metabolic enzyme (α-amylase, α-glucosidase, and lipase) inhibitory (IC50 = 45.22 ± 1.1, 63.09 ± 0.26, 501.18 ± 0.38 µg/mL, respectively) and antioxidant activity, with an IC50 value of 19.95 ± 2.08 µg/mL. Moreover, the S. viticina EO showed high cyclooxygenase inhibitory activity against COX-1 and COX-2 with IC50 values of 0.25 and 0.5 µg/mL, respectively, similar to those of the positive control (the NSAID etodolac). Outcomes amassed from this investigation illustrate that S. viticina EO represents a rich source of pharmacologically active molecules which can be further validated and explored clinically for its therapeutic potential and for the development and design of new natural therapeutic preparations.
Subject(s)
Cell Proliferation/drug effects , Oils, Volatile/pharmacology , Stachys/chemistry , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Epidermophyton/drug effects , Escherichia coli/drug effects , HeLa Cells , Humans , Methicillin-Resistant Staphylococcus aureus/drug effects , Oils, Volatile/chemistryABSTRACT
Genotoxicity of B. officinalis, G. officinalis, V. luteum and V. hirundinaria extracts, which demonstrated strong antioxidant capacity, was tested using chromosome aberration, sister chromatid exchange (SCE), cytokinesis-block micronucleus and alkaline single-cell gel electrophoresis (comet) assays in human lymphocytes in vitro and Ames Salmonella/microsome test. All tested extracts were not mutagenic in S. typhimurium strains TA98 and TA100 with and without metabolic activation and did not induce chromosome aberrations in human lymphocytes in vitro. Extract from G. officinalis was the only one, which induced significant increase in micronuclei, indicating possible aneugenic effect. All investigated plant extracts induced DNA damage evaluated by the comet assay, while B. officinalis and V. luteum extracts induced slight increase in SCE values. The determined variation in response might be due to the plant extract tested and donor susceptibility.
Subject(s)
Lamiales/chemistry , Mutagens/toxicity , Plant Extracts/toxicity , Stachys/chemistry , Vincetoxicum/chemistry , Comet Assay , Humans , Lymphocytes/drug effects , Micronucleus Tests , Salmonella typhimurium/geneticsABSTRACT
In this paper, the isolation of one new iridoid glucoside, 6ß-acetoxyipolamiide (1: ), and thirteen (2: â-â14: ) known congeners from two Lamiaceae species, Stachys ocymastrum and Premna resinosa, leaf extracts is reported. The structural determination of the isolated compounds was performed by mono- and bidimensional NMR spectroscopic analysis as well as MS experiments. The isolates were assayed for their antiangiogenic activity by two in vivo models, zebrafish embryos and chick chorioallantoic membrane assays. The compounds with a significant antiangiogenic activity in both assays were ß-hydroxyipolamiide (2: ), ipolamiide (3: ), and buddlejoside A5 (8: ). 6-O-α-l-(3â³-O-p-Methoxycinnamoyl-4â³-O-acetyl)rhamnopyranosyl catalpol (13: ) and 6-O-α-l-(2â³-trans-caffeoyl)rhamnopyranosyl catalpol (6: ) showed the best antiangiogenic response on blood vessel growth in zebrafish embryos, whereas saccatoside (10: ) and 6-O-α-l-(2â³-O - : p-methoxycinnamoyl-3â³-O-acetyl)rhamnopyranosyl catalpol (14: ) resulted in a strong reduction of capillary formation in the chorioallantoic membrane assay.