ABSTRACT
Peganum harmala L., a traditional medicinal plant in China, is renowned for its significant alkaloid content in seeds and roots exhibiting a wide range of pharmacological activities, including antidepressant, antiseptic, and antiviral. However, the volatile composition of the herb remained unclear. Apart from that, the extraction of volatile compounds through essential oil presents challenges due to the low yield and the degradation of volatile active compounds at high temperatures. This study used multiple sample preparation methods including headspace (HS), needle trap device (NTD), and liquid-liquid extraction (LLE) coupled with gas chromatography-mass spectrometry (GC-MS) to analyze the volatile compounds from the areal part of P. harmala L.. A total of 93 compounds were identified with NTD facilitating the first detection of harmine among the volatile organic compounds. Through network pharmacology and protein interaction analysis, the compounds' potential therapeutic targets of the compounds were explored, and 23 key targets were obtained (AKT1, ALB, PTGS2, MAOA, etc). KEGG pathway enrichment analysis indicated significant involvement in neuroactive ligand-receptor interactions and serotonergic synapses. The results enhanced the understanding of P. harmala's pharmacological mechanisms and supported its ethnopharmacological use.
Subject(s)
Antidepressive Agents , Gas Chromatography-Mass Spectrometry , Peganum , Volatile Organic Compounds , Gas Chromatography-Mass Spectrometry/methods , Peganum/chemistry , Volatile Organic Compounds/analysis , Volatile Organic Compounds/chemistry , Antidepressive Agents/analysis , Antidepressive Agents/chemistry , Antidepressive Agents/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Oils, Volatile/chemistry , Oils, Volatile/analysis , Liquid-Liquid Extraction/methods , Humans , Protein Interaction MapsABSTRACT
Seventeen phenolic glycosides were isolated from the Nitraria sibirica. Their structures were identified by the spectroscopic data and comparison with literatures as isovanillyl alcohol-7-O-ß-d-glucopyranoside (1), benzyl ß-primeveroside (2), benzyl-O-ß-d-glucopyranoside (3), 1-O-ß-d-glucopyranosyl-4-(8-hydroxyethyl)-2-methoxyphenyl (4), dehydrosyringin (5), trans-ferulic acid-4-O-ß-d-glucoside (6), cis-ferulic acid 4-O-ß-d-glucopyranoside (7), glucosyringic acid (8), 1-O-feruloyl-ß-d-glucoside (9), sachaloside VII (10), (3S, 5R, 6R, 7E, 9S)-megastigmane-7-ene-3-hydroxy-5,6-epoxy-9-O-ß-d-glucopyranoside(11), 3-hydroxy-4,5-dimethoxybenzyl alcohol (12), pinoresinol 4-O-ß-d-glucopyranoside (13), eucommin A (14), isoeucommin A (15), acanthoside (16), liriodendrin (17). All these compounds except compound 13 were isolated from the Nitraria genus for the first time. In bioactivity assays for all compounds, the compounds 8 and 15 were exhibited strong antioxidant activity (IC50 = 18.11 and 16.29 µM respectively), while compounds 3 and 11 were exhibited strong PTP1B enzymatic inhibition (IC50 = 6.97 and 11.76 µM, respectively). Furthermore, the compounds 10 and 17 were presented strong inhibitory capacities against Candida albicans (14.5 and 13.5 mm, respectively).
Subject(s)
Antioxidants/pharmacology , Glycosides/isolation & purification , Glycosides/pharmacology , Magnoliopsida/chemistry , Plant Leaves/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Candida albicans/drug effects , Carbon-13 Magnetic Resonance Spectroscopy , Glycosides/chemistry , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Inhibitory Concentration 50 , Microbial Sensitivity Tests , Proton Magnetic Resonance SpectroscopyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: For more than ten scores years, the leaves and fruits of Nitraria sibirica have been used as a natural remedy for indigestion, irregular manes, and hypertension in the Middle East and Central Asia, especially, are recommended for hypertension treatment in the northwest region, China. AIM OF THE STUDY: we aimed to support the traditional usage of N. sibirica leaves as pharmaceuticals or dietary supplements in treatment of hypertension by investigating their chemical constituents and anti-hypertensive activity. METHODS: We identified the chemical composition of N. sibirica leaves ethanolic purified extract (NSL-EPE) using UHPLC-quadrupole-orbitrap-MS, and quantified the main chemical constituents by an analytical method established and validated. We also evaluated anti-hypertensive activity of NSL-EPE using spontaneously hypertensive rats (SHR): blood pressure was measured weekly by non-invasive blood pressure (NIBP) measurements; hemodynamic parameters, biochemical and clinical chemistry variables in plasma, serum and kidney tissue were measured after 10 weeks of treatment with NSL-EPE as well. RESULTS: UHPLC-quadrupole-orbitrap-MS analysis identified 52 compounds, of which 40 compounds were reported for the first time in N. sibirica. 11 phenolic compounds further quantitatively analyzed, among which the most abundant compound was found to be clovin (8.8%). Systolic blood pressure decreased progressively from the second treatment week compared to that in non-treated SHRs. The plasma endothelin, aldosterone, angiotensin II levels were significantly increased, while the level of NOX was significantly decreased; glutathione to oxidized glutathione ratio, superoxide dismutase and total catalase levels in the kidney tissue were markedly accelerated, while malondialdehyde level was significantly reduced in NSL-EPE treated SHRs. Moreover, the serum cholesterol, triglyceride, blood uria nitrogen and creatinine were attenuated in NSL-EPE treated SHRs (P < 0.05), but in sharp contrast to those values in the water-treated SHRs. CONCLUSION: This study screened out leading compounds from N. sibirica and offered a new understanding of the antihypertensive properties of N. sibirica leaves, by which inhibit oxidative stress-induced endothelial dysfunction and improve lipid profiles.
Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Chromatography, High Pressure Liquid , Hypertension/drug therapy , Magnoliopsida , Phenols/pharmacology , Plant Leaves , Tandem Mass Spectrometry , Animals , Antihypertensive Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/pharmacology , Biomarkers/blood , Disease Models, Animal , Hypertension/blood , Hypertension/physiopathology , Kidney/drug effects , Kidney/metabolism , Lipids/blood , Magnoliopsida/chemistry , Male , Oxidative Stress/drug effects , Phenols/isolation & purification , Plant Leaves/chemistry , Rats, Inbred SHR , Rats, Inbred WKYABSTRACT
OBJECTIVE: To study the chemical constituents of supercritical CO2 extract from Xinjiang Daucus carota seed(called “D. carota seed extract” for short), and to preliminarily evaluate its antimicrobial and antioxident activity, so as to provide reference for the development and quality control of related products of the plant. METHODS: The non-polar volatile part of Xinjiang D. carota seed was extracted by supercritical CO2 extraction method. The chemical constituents of the extract were identified and quantified by GC-MS and standard spectral labrary. The relative percentage content of each component was calculated by peak area normalization method. The antibacterial activity of D. carota seed extract against Staphylococcus aureus,Escherichia coli and Candida albicans were investigated by trace broth dilution method and AGAR medium plate method. Its antioxidant activity was investigated by TLC-bioautography method. RESULTS: Twenty chemical constituents were identified from D. carota seed extract (the total relative percentage content was 98.76%), mainly including β-bisabolene, α-asarone, α-pinene, β-caryophyllene, aspidinol, etc. D. carota seed extract has certain antimicrobial activity on S. aureus, E. coli and C. albicans. The minimum inhibitory concentrations were 0.039, 0.833, 0.625 mg/mL, and minimum bactericidal concentrations were 0.078, 1.667, 1.250 mg/mL, respectively. The extract has a certain scavenging ability to DPPH radical. CONCLUSIONS: D. carota seed extract obtained by supercritical CO2 extraction contains monoterpenes and sesquiterpenes, and possesses certain antibacterial and antioxidant activity.
ABSTRACT
Vernonia anthelmintica Willd. seeds have been used in folk medicine for the treatment of leukoderma in Xinjiang, China, for more than 300 years. The promoting activities of its volatile oil (AVO) in melanogenesis and its chemical composition were investigated in this paper. The bioactivities of AVO were examined by melanin synthesis and tyrosinase activity assay in B16 cells. Using GC-QTOF-MS technology, each compound of AVO contains a single separated peak in GC and the retention indices of every GC peak were calculated by the retention times of C7~C30 n-alkanes that were injected at the same chromatographic conditions. Then each individual peak was identified by comparing its mass spectrum with the MS library (NIST 14). As a result, AVO increased the melanin content and tyrosinase activity in a dose-dependent manner at concentrations of 10-30µg·mL-1. The 64 compounds were identified in AVO which occupied 95.15% of total peak area in GC. They mainly contained caryophyllene (23.73%), sabinene (18.15%), α-thujene (6.57%), thymol (5.29%), 4-epi-α-acoradiene (4.98%), limonene (4.92%), anethole (3.44%), etc. According to the results the AVO can promote melanogenesis and upregulate tyrosinase activity in B16 cells.
ABSTRACT
Nitraria sibirica is a traditional Uighur medicine. This study was undertaken to investigate the bioactivity of N. sibirica fruit extract and to evaluate their chemical compositions. The ethyl acetate extract from N. sibirica fruits exhibited the potential antioxidant activity (SC50 = 30.17 ± 0.06 µg/mL) and protein tyrosine phosphatase 1B inhibitory activity (IC50 = 7.15 ± 0.03 µg/mL) in vitro. In order to investigate the active constituents in this extract, a LC-QTOF-MS/MS method was developed and established. A total of 28 compounds including seven cinnamic acids, nine benzoic acids and 12 flavonoids were identified or partially characterised according to the accurate mass and the characteristic fragment ions at low and high collision energy. Most of them were reported for the first time in this plant. Phytochemical profiles of the active extract will help the development and utilisation of N. sibirica in food and medicine.
Subject(s)
Fruit/chemistry , Magnoliopsida/chemistry , Phytochemicals/analysis , Plant Extracts/chemistry , Acetates , Antioxidants/chemistry , Chromatography, Liquid , Flavonoids/analysis , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Tandem Mass SpectrometryABSTRACT
At present, liquid phase adsorption (LPA) is still being quantitatively characterized in the way of manual sampling and off-line determination because of the complexity of the system comparing to gas adsorption. This paper describes a novel method for in situ, real-time measurement of LPA in general based on fiber-optic sensing (FOS) with the aid of membranes for the first time. A self-made measurement vessel was assembled from an adsorption bag, thermostatic devices with a stirrer, and a fiber-optic dipping probe. Also, macroporous adsorption resins (MARs) and rutin were chosen as model adsorbent and adsorbate to establish the FOS system. Here, in situ light absorption measurement was achieved by eliminating interference of adsorbent particles via encapsulating them with a membrane into the adsorption bag. In situ LPA measurement of rutin solution on MARs was obtained by detecting light absorption at 353 nm using dipping probe, in the broad concentration range from 0.3 to 60 mg/L with excellent linearity (R 2 = 0.9996). In situ measurements of adsorption and desorption kinetics on five kinds of MARs with different polarities were systematically carried out, showing that the adsorption process obeyed the pseudo-second-model. As well as, the system was proved to be highly accurate and reproducible. More importantly, this method enabled to study the initial stage of the adsorption process, starting from the time of the first second, which is the most important part in the adsorption kinetics, and this is impossible for traditional sampling methods. The successful application of FOS to in situ measurement of LPA not only contributes to fast, automatic, and real-time monitoring of LPA process but also enriches the research connotation of adsorption.
ABSTRACT
The total alkaloids from Nitraria sibirica leaves have been confirmed to exhibit significant protective effects against inflammatory renal injury, hypertension and albuminuria in angiotensin II-salt hypertension. In the present study, a separation method of pH-zone-refining counter-current chromatography was established for separation of the alkaloids from N. sibirica. The separation was performed with a solvent system of MtBE-n-BuOH-H2O (2:2:5, v/v) at a flow rate of 2.0mL/min. And 15mM triethylamine (TEA) was added to the upper organic phase, while 10mM hydrochloric acid was added to the lower aqueous phase. As a result, a new alkaloid, schobemine (5.6mg), and a known alkaloid, nitraramine (5.0mg), together with fractions A and B were obtained from the total alkaloids of N. sibirica. The fractions A and B were further purified by means of pH-zone-refining counter-current chromatography with solvent systems of n-hexane-n-BuOH-H2O (1.5:3.5:5, v/v) and (2:3:5, v/v), respectively. TEA (10mM) was added to the upper phase, and 10mM of HCl was added to the lower phase in above two solvent systems, respectively. As a result, a known alkaloid, schoberidine (5.0mg), and a new alkaloid, schoberimine (3.0mg) were obtained from fractions A and B, respectively. The purities of the compounds were measured by HPLC-ELSD, and their structures were identified by ESI-MS, 1D and 2D NMR.
Subject(s)
Alkaloids/isolation & purification , Countercurrent Distribution/methods , Magnoliopsida/chemistry , Plant Leaves/chemistry , Alkaloids/analysis , Chromatography, Thin Layer , Models, MolecularABSTRACT
In traditional Chinese medicine, Nitraria sibirica Pall. (Nitrariaceae) is used to treat hypertension. This study determined the effects of the total alkaloids of the leaves of Nitraria sibirica (NSTA) on blood pressure and albuminuria in mice treated with angiotensin II and a high-salt diet (ANG/HS). Adult mice were divided into three groups: control; infused with angiotensin II and fed a diet containing 4% NaCl (ANG/HS; and ANG/HS plus injection of NSTA (1 mg·kg(-1)·d(-1), i.p.). After treatment of these regimens, daily water and food intake, kidney weight, blood pressure, urinary albumin excretion, renal concentrations of inflammatory markers, including soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1), and the expression of renal fibrosis markers were determined. Compared to the control group, the ANG/HS group had higher blood pressure and urinary albumin excretion. Treatment with NSTA in ANG/HS mice for three weeks significantly reduced blood pressure and urinary albumin excretion. ANG/HS treatment caused elevated levels of sICAM-1 and MCP-1, as well as increased fibrosis markers. Concurrent treatment with ANG/HS and NSTA attenuated the levels and expression of renal inflammatory and fibrosis markers. Treatment with NSTA effectively reduces hypertension-induced albuminuria through the reduction of renal inflammatory and fibrosis markers.
Subject(s)
Albuminuria/drug therapy , Alkaloids/administration & dosage , Angiotensin II/metabolism , Drugs, Chinese Herbal/administration & dosage , Hypertension/drug therapy , Magnoliopsida/chemistry , Albuminuria/metabolism , Albuminuria/physiopathology , Animals , Blood Pressure/drug effects , Chemokine CCL2/metabolism , Humans , Hypertension/metabolism , Hypertension/physiopathology , Male , Mice , Rats, Sprague-Dawley , Sodium Chloride, Dietary/adverse effects , Sodium Chloride, Dietary/metabolismABSTRACT
INTRODUCTION: Rosa rugosa flowers used as herbal medicine possess many activities. A fraction extracted by ethyl acetate exhibited strong inhibitive activity against protein tyrosine phosphatase 1B (PTP1B) in vitro. OBJECTIVE: Establish an efficient method of LC coupled to quadrupole time-of-flight (QTOF) with tandem MS/MS to investigate the compositions in the active fraction. METHODS: Chemical compositions were separated and investigated by LC/QTOF-MS/MS in negative electrospray ionisation (ESI) mode at different collision energy (CE) values. The maximal structural information was obtained for the identification of components. RESULTS: A total of 75 compounds including tannins, their related compounds and flavonoids were identified or partially characterised according to accurate mass and the characteristic fragments at low and high CE. Meanwhile, the fragmentation pathways of gallotannins and ellagitannins (hexahydroxydiphenoyl group and lactonised valoneoyl group) were studied and proposed and were used to trace tannins in crude extracts. CONCLUSION: The results suggest that this fraction is a source of PTP1B inhibitory activity with a potential for treating diabetes.
Subject(s)
Enzyme Inhibitors/isolation & purification , Flavonoids/isolation & purification , Plant Extracts/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Rosa/chemistry , Tannins/isolation & purification , Chromatography, Liquid , Enzyme Inhibitors/metabolism , Flavonoids/metabolism , Flowers/chemistry , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Tandem Mass Spectrometry , Tannins/metabolismABSTRACT
Soluble epoxide hydrolase (sEH) is an enzyme involved in the metabolism of endogenous inflammatory and anti-apoptotic mediators. In the present study, we determined the effects of the inhibition of sEH on glucose homeostasis and islet damage in mice treated with streptozotocin (STZ), a model of chemical-induced diabetes. STZ increased daily water intake and decreased visceral (spleen and pancreas) weight in mice; sEH inhibition in STZ mice decreased water intake, but did not affect visceral weight. Hyperglycemia induced by STZ treatment in mice was attenuated by inhibiting sEH. The beneficial effects of sEH inhibition were accompanied, after 2 and 4 weeks of initial administration, by improving glucose tolerance. In contrast, sEH inhibition did not affect insulin tolerance. Using LC/MS analysis, neither STZ nor STZ plus sEH inhibition affected pancreatic and plasma ratios of epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), an index of EETs levels. Western blot analysis showed that mouse cytochrome P450 (CYP) 2C enzymes are the major epoxygenases in islets. On day 5 after initial STZ treatment, STZ induced islet cell apoptosis, while sEH inhibition in STZ mice significantly reduced islet cell apoptosis. These studies provide pharmacological evidence that inhibiting sEH activity provides significant protection against islet ß-cell damage and improves glucose homeostasis in STZ-induced diabetes.
Subject(s)
Benzoates/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Enzyme Inhibitors/pharmacology , Epoxide Hydrolases/antagonists & inhibitors , Glucose/metabolism , Islets of Langerhans/drug effects , Urea/analogs & derivatives , 8,11,14-Eicosatrienoic Acid/analogs & derivatives , 8,11,14-Eicosatrienoic Acid/metabolism , Animals , Apoptosis/drug effects , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Drinking/drug effects , Epoxide Hydrolases/metabolism , Glucose Tolerance Test , Homeostasis/drug effects , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Male , Mice , Organ Size/drug effects , Oxidative Stress/drug effects , Pancreas/drug effects , Pancreas/metabolism , Pancreas/pathology , Spleen/drug effects , Spleen/metabolism , Spleen/pathology , Streptozocin , Urea/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Fruits of Nitraria sibirica Pall. are traditionally used in Uighur medicine to treat hypertension. This study aimed to support that folk use by defining their vasoactive and hypotensive properties. MATERIALS AND METHODS: The vasorelaxant activity and the underlying mechanisms of a hydroalcoholic extract from the fruits of Nitraria sibirica Pall. (NSHE) were evaluated on thoracic aortic rings isolated from Wistar rats. In addition, the acute hypotensive effect of NSHE was assessed in anesthetized spontaneously hypertensive rats (SHR) and in their normotensive control Wistar Kyoto (WKY) rats. RESULTS: NSHE (0.1-10 g/l) was clearly more effective to induce vasodilation of phenylephrine- (PE, 1 µM) than high KCl- (60mM) pre-contracted aortic rings with respective E(max) values of 82.9±2.2% and 34.8±3.6%. The removal of endothelium almost abolished the relaxant effect of the extract. In addition, pre-treatment with N(w)-nitro-L-arginine-methyl ester (L-NAME, 100 µM), atropine (1 µM) or charybdotoxin (30 nM) plus apamin (30 nM), respective blockers of nitric oxide (NO) synthase, muscarinic receptors and endothelium-derived hyperpolarizing factor (EDHF), significantly reduced the observed effect of NSHE. By contrast, the cyclooxygenase (COX) inhibitor indomethacin (10 µM) or the K(+) channels blockers glibenclamide (10 µM), iberiotoxin (30 nM) and 4-amino-pyridine (4-AP, 1 mM) failed to modify the vasodilation. Finally, the acute intravenous injection of NSHE (1, 5, 10, 20 mg/kg) induced an immediate and transient hypotensive effect in anesthetized SHR and in WKY rats. CONCLUSIONS: This experimental animal study suggests that hydroalcoholic extract from the fruits of Nitraria sibirica Pall. induces vasorelaxation through an endothelium-dependent pathway involving NO synthase (NOS) activation, EDHF production and muscarinic receptor stimulation. Additionally, our results determine that this vasorelaxant effect is translated by a significant hypotensive effect.
Subject(s)
Antihypertensive Agents/pharmacology , Blood Pressure/drug effects , Ethanol/chemistry , Hypertension/drug therapy , Magnoliopsida , Plant Extracts/pharmacology , Solvents/chemistry , Vasodilation/drug effects , Vasodilator Agents/pharmacology , Animals , Antihypertensive Agents/chemistry , Antihypertensive Agents/isolation & purification , Biological Factors/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Enzyme Activation , Fruit , Hypertension/metabolism , Hypertension/physiopathology , Magnoliopsida/chemistry , Male , Nitric Oxide/metabolism , Nitric Oxide Synthase/metabolism , Phenols/isolation & purification , Phenols/pharmacology , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plants, Medicinal , Potassium Channels/drug effects , Potassium Channels/metabolism , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Rats, Wistar , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/metabolism , Vasodilator Agents/chemistry , Vasodilator Agents/isolation & purificationABSTRACT
OBJECTIVE: To establish a HPLC fingerprint of Rosae Rugosae Flos. METHODS: Inertsil ODS-3 (4.6 mm x 250 mm, 5 microm) was used with the mixture of methanol, acetonitrile and 0.06% TFA as mobile phase. The flow rate was 1.0 mL/min, the column temperature was 32degrees C, and the detection wavelength was 254 nm. RESULTS: HPLC fingerprint of 9 main peaks was established preliminarily from 13 samples of Rosae Rugosae Flos which achieved the technical requirements of the fingerprint of traditional Chinese medicine. CONCLUSION: The method is reliable, accurate and can be used for quality comtrol of Rosae Rugosae Flos.