- 1. Antidiabetic activity of medium-polar extract from the leaves of Stevia rebaudiana Bert. (Bertoni) on alloxan-induced diabetic rats.
OBJECTIVE:
To investigate the medicative effects of medium-polar (benzene:acetone, 1:1, v/v) extract of leaves from Stevia rebaudiana (family Asteraceae) on alloxan-induced diabetic rats.
MATERIALS AND METHODS:
Diabetes was induced in adult albino Wistar rats by intraperitoneal (i.p.) injection of alloxan (180 mg/kg). Medium-polar extract was administered orally at daily dose of 200 and 400 mg/kg body wt. basis for 10 days. The control group received normal saline (0.9%) for the same duration. Glibenclamide was used as positive control reference drug against Stevia extract.
RESULTS:
Medium-polar leaf extract of S. rebaudiana (200 and 400 mg/kg) produced a delayed but significant (P < 0.01) decrease in the blood glucose level, without producing condition of hypoglycemia after treatment, together with lesser loss in the body weight as compared with standard positive control drug glibenclamide.
CONCLUSIONS:
Treatment of diabetes with sulfonylurea drugs (glibenclamide) causes hypoglycemia followed by greater reduction in body weight, which are the most worrisome effects of these drugs. Stevia extract was found to antagonize the necrotic action of alloxan and thus had a re-vitalizing effect on β-cells of pancreas....(more)
Misra H, et al. J Pharm Bioallied Sci 2011 Apr;3(2):242-8.
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- 2. Stevia rebaudiana Bertoni extract supplementation improves lipid and carnitine profiles in C57BL/6J mice fed a high-fat diet.
BACKGROUND:
Stevia (Stevia rebaudiana Bertoni) is a non-caloric natural-source alternative to artificially produced sugar substitutes. This study investigated the effect of stevia extract on lipid profiles in C57BL/6J mice. Forty mice were divided into four groups: N-C (normal diet and distilled water), H-C (high-fat diet and distilled water), H-SC (high fat diet and sucrose, 1 mL kg(-1) per day), and H-SV (high-fat diet and stevia extract, 1 mL kg(-1) per day).
RESULTS:
Body weight gain was significantly higher in the H-SC group than in the H-SV group. Triglyceride concentrations in serum and liver were lower in the H-SV group than in the H-SC group. Serum total cholesterol concentrations were lower in the H-SV and H-C groups compared to the H-SC group. The concentrations of acid-insoluble acylcarnitine (AIAC) in serum were higher in the H-SV group than in the H-C and H-SC groups and the acyl/free carnitine level in liver was significantly higher in the H-SV group than in the N-C group. These results were supported by mRNA expression of enzymes related to lipid metabolism (ACO, PPARalpha, ACS, CPT-I, ACC) assessed by real-time polymerase chain reaction.
CONCLUSION:
These results suggest that the supplementation of stevia extract might have an anti-obesity effect on high-fat diet induced obese mice....(more)
Park JE, et al. J Sci Food Agric 2010 May;90(7):1099-105.
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- 3. Physical properties and bioactive constituents of powdered mixtures and drinks prepared with cocoa and various sweeteners.
In the present study the physical properties of powdered cocoa drink mixtures prepared from two cocoa powders with various fat contents and different sweeteners, as well as the bioactive content and sensory properties of cocoa drinks prepared from them, were investigated. Particle size and bulk density of the used sugars and sweeteners, as well as the formulated mixtures, were determined and their influence on cohesion index was evaluated. To compare the content of polyphenols in the formulated cocoa drink mixtures, UV-vis spectrophotometric methods were applied. Antioxidant capacity of cocoa drinks was evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and ferric reducing/antioxidant power (FRAP) assays. The analyzed cocoa drinks prepared from cocoa powder and different sugars or sweeteners delivered a substantial content of cocoa antioxidants, whereas the content and the type of sugar or sweetener did not affect the polyphenolic constituents of the prepared cocoa mixtures. Cocoa powder mixtures prepared with the cocoa powder containing higher fat content (16-18%) generally provided lower total polyphenol, total flavonoid, flavan-3-ol, and proanthocyanidin contents, compared to the mixtures prepared with cocoa containing lower fat content (10-12%). Total phenol content of cocoa drinks prepared from experimental mixtures ranged from 320.45 to 480.45 mg of GAE/L, whereas the ranking of the antioxidant capacities varied depending on the used assay, and the fat content of cocoa powder did not affect the antioxidant capacity of cocoa mixtures. As determined, the addition of sugar to cocoa powder increases the solubility and dispersibility of the mixtures; on the basis of their cohesion index all mixtures can be classified as very cohesive or hardened/extremely cohesive. Results of the sensory evaluation, using the 9-point hedonic scale, showed that there was a preference for the cocoa drinks made with sweeteners (aspartame/acesulfame K and stevia extract), and there was a significant difference in the sensory attributes between the experimental mixtures and the control. The displayed results indicate the significant potential of using alternative sweeteners for the preparation of cocoa drink mixtures, which may provide good physical and sensory properties and also enhance the already existing beneficial effects of cocoa....(more)
Belscak-Cvitanovi? A, et al. J Agric Food Chem 2010 Jun 23;58(12):7187-95.
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- 4. Phenolic-linked biochemical rationale for the anti-diabetic properties of Swertia chirayita (Roxb. ex Flem.) Karst.
The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti-diabetic-linked anti-hyperglycemia potential using in vitro biochemical assays. There was moderate-to-high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate-to-high α-glucosidase inhibitory activity. Although the anti-diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti-hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α-glucosidase and 2,2-diphenyl-1-picrylhydrazyl radical inhibitory activity indicating anti-hyperglycemia potential....(more)
Phoboo S, et al. Phytother Res 2013 Feb;27(2):227-35.
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- 5. Anti-diabetic Activity of Swertiamarin is due to an Active Metabolite, Gentianine, that Upregulates PPAR-γ Gene Expression in 3T3-L1 cells.
We have previously shown the anti-diabetic effects of swertiamarin; however, pharmacokinetic analysis showed that swertiamarin had a plasma half-life of 1.3 h. Gentianine is an active metabolite of swertiamarin that possesses a pharmacophoric moiety. The aim of this study was to explore the possibility whether the anti-diabetic effect of swertiamarin is due to gentianine. Swertiamarin treatment had no significant effect on adipogenesis, or the mRNA expression of PPAR-γ and GLUT-4; however, there was a significant increase in the mRNA expression of adiponectin. On the other hand, treatment with gentianine significantly increased adipogenesis, which was associated with a significant increase in the mRNA expression of PPAR-γ, GLUT-4 and adiponectin. These findings suggest, for the first time, that the anti-diabetic effect of swertiamarin is due to gentianine, an active metabolite of swertiamarin. Copyright © 2012 John Wiley & Sons, Ltd....(more)
Vaidya H, et al. Phytother Res 2013 Apr;27(4):624-7.
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- 6. Hepatoprotective effects of Gentiana asclepiadea L. extracts against carbon tetrachloride induced liver injury in rats.
This study is an attempt to evaluate the hepatoprotective activity of Gentiana asclepiadea L. against carbon tetrachloride-induced liver injury in rats. Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at doses of 100, 200, and 400mg/ kg b.w. were orally administered to Wistar rats once daily for 7 days before they were treated with CCl(4). The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. In CCl(4) treated animals, GAA and GAR significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein. Treatment with the extracts resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione, accompanied with a marked reduction in the levels of malondialdehyde, as compared to CCl(4) treated group. The histopathological studies confirmed protective effects of extracts against CCl(4)-induced liver injuries. No genotoxicity was observed in liver cells after GAA treatment, while GAR showed only slight genotoxic effects by comet assay. Phytochemical analysis revealed the presence of sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts. It could be concluded that the use of G. asclepiadea extracts in the treatment of chemical-induced hepatotoxicity....(more)
Mihailovi? V, et al. Food Chem Toxicol 2013 Feb;52:83-90.
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- 7. Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (ΔΨ<sub>m</sub>) by Gentiana kurroo root extract.
The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (Miapaca-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like α-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73±1.02 and 46±2.05mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (Miapaca-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced cell cycle arrest in Miapaca-2 cells at G0/G1 phase of the cell cycle. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100μg/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (ΔΨm) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species. Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4″-O-β-d-glucosyl-6'-O-(4-O-β-d-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo....(more)
Wani BA, et al. Phytomedicine 2013 Feb 28.
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- 8. Spatial variation profiling of four phytochemical constituents in Gentiana straminea (Gentianaceae).
Gentiana straminea is the famous Tibetan folk medicine thought to cure various diseases. Historically, the Qinghai-Tibetan region has been considered as the geo-authentic production area of "Mahua Jiao," where large quantities of the medicine are grown. However, there is still little known about the phytochemical constituent spatial variation of this species. In order to find the differences between the main phytochemical constituents of G. straminea and to provide comprehensive information for quality evaluation, four main bioactive compounds (loganic acid, swertiamarin, gentiopicroside and sweroside) were analysed in 26 populations grown in areas with elevations ranging from 2320 to 4720 m across the Qinghai-Tibetan Plateau. The results showed that the four phytochemical constitutes' concentrations varied greatly in the spatial profiling of the Qinghai-Tibetan region. Throughout the range of distribution of this species, no altitudinal, latitudinal or longitudinal trends have proven to be significant in any of the four constitutes' concentrations or their summation. Furthermore, hierarchical clustering analysis and statistical tests showed that four populations (Liu0609-18, Liu0609-15, Liu2006-13-9 and Liu0609-22) had total constitute contents that were higher than other populations. The spatial profiling of the four phytochemical constituents suggests that the geo-authentic producing area of this species exists at a few regions within the Qinghai province, which could be attributed to specific environmental or genetic factors....(more)
Yang H, et al. J Nat Med 2013 Apr 21.
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- 9. Inhibition of Vascular Smooth Muscle Cell Proliferation by Gentiana lutea Root Extracts.
Gentiana lutea belonging to the Gentianaceae family of flowering plants are routinely used in traditional Serbian medicine for their beneficial gastro-intestinal and anti-inflammatory properties. The aim of the study was to determine whether aqueous root extracts of Gentiana lutea consisting of gentiopicroside, gentisin, bellidifolin-8-O-glucoside, demethylbellidifolin-8-O-glucoside, isovitexin, swertiamarin and amarogentin prevents proliferation of aortic smooth muscle cells in response to PDGF-BB. Cell proliferation and cell cycle analysis were performed based on alamar blue assay and propidium iodide labeling respectively. In primary cultures of rat aortic smooth muscle cells (RASMCs), PDGF-BB (20 ng/ml) induced a two-fold increase in cell proliferation which was significantly blocked by the root extract (1 mg/ml). The root extract also prevented the S-phase entry of synchronized cells in response to PDGF. Furthermore, PDGF-BB induced ERK1/2 activation and consequent increase in cellular nitric oxide (NO) levels were also blocked by the extract. These effects of extract were due to blockade of PDGF-BB induced expression of iNOS, cyclin D1 and proliferating cell nuclear antigen (PCNA). Docking analysis of the extract components on MEK1, the upstream ERK1/2 activating kinase using AutoDock4, indicated a likely binding of isovitexin to the inhibitor binding site of MEK1. Experiments performed with purified isovitexin demonstrated that it successfully blocks PDGF-induced ERK1/2 activation and proliferation of RASMCs in cell culture. Thus, Gentiana lutea can provide novel candidates for prevention and treatment of atherosclerosis....(more)
Kesavan R, et al. PLoS One 2013 Apr 18;8(4):e61393.
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- 10. Inhibitory effects of secoiridoids from the roots of Gentiana straminea on stimulus-induced superoxide generation, phosphorylation and translocation of cytosolic compounds to plasma membrane in human neutrophils.
Gentiana straminea Maxim. has been used widely as a traditional Chinese medicine for the treatment of rheumarthritis, icterepatitis, constipation, pain and hypertension. Five secoiridoids, gentiopicroside (GTP), 6'-O-(2-hydroxy-3-O-β-D-glucopyranosyl-benzoyl)-sweroside (HGBS), 6'-O-β-D-glucosylgentiopicroside (GGTP), sweroside (SW) and swertiamarin (STM) were isolated from the roots of G. straminea. The effect of these secoiridoids on stimulus-induced superoxide generation in human neutrophils was assayed by measuring the reduction of ferricytochrome c. Tyrosyl or serine/threonine phosphorylation of neutrophil proteins, and translocation of the cytosolic compounds to the cell membrane were also investigated using specific monoclonal antibodies. The five secoiridoids used in the present experiment suppressed N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration dependent manner. GTP and HGBS also suppressed phorbol 12-myristate 13-acetate (PMA) and arachidonic acid (AA)-induced superoxide generation. However, the other three secoiridoids showed no effect on PMA- and AA-induced superoxide generation. fMLP-, PMA- and AA-induced tyrosyl or serine/threonine phosphorylation and translocation of the cytosolic proteins to the cell membrane were suppressed in parallel with the suppression of the stimulus-induced superoxide generation....(more)
Wei S, et al. Phytother Res 2012 Feb;26(2):168-73.
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- 11. Introgression of the heterologous nuclear DNAs and efficacious compositions from Swertia tetraptera Maxim. into Bupleurum scorzonerifolium Willd. via somatic hybridization.
Swertia tetraptera Maxim. is an important source of secoiridoid glucosides. To produce these pharmacologically valuable compounds heterologously in somatic hybrid cell lines, S. tetraptera protoplasts were irradiated with various doses of UV light and fused with protoplasts from a long-term cell line of Bupleurum scorzonerifolium Willd. This recipient was chosen as the cell line is cytogenetically stable and fast growing; furthermore, protoplasts isolated from the cell line are readily regenerable. From a set of 86 putative hybrid calli, only two were able to regenerate viable green plants. The hybridity of the 19 of the 86 selections was revealed by a combined isozyme and RAPD analysis, supported by a karyotypic study based on genomic in situ hybridization (GISH). Clone I-3 contained 0.014% swertiamarin while the regenerants had 0.069% swertiamarin and 0.409% gentiopicroside while the III-4 plants contained only 0.015% gentiopicroside....(more)
Jiang L, et al. Protoplasma 2012 Jul;249(3):737-45.
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- 12. Genetic and biochemical characterization of somatic hybrids between Bupleurum scorzonerifolium and Gentianopsis paludosa.
Ultraviolet-irradiated protoplasts of Gentianopsis paludosa were fused with those of Bupleurum scorzonerifolium and 28 independent hybrid calli were identified, five of which later differentiated into plants. A genetic analysis of these calli and regenerated plants based on chromosome number, esterase, random amplified polymorphic DNA, and 5S rDNA spacer profiling showed that the majority of their nuclear genomes were represented by the recipient biparent B. scorzonerifolium. A restriction fragment length polymorphism analysis of the plastidial genomes confirmed that DNA from both biparents was present in some of the hybrids. The secondary metabolite composition of the hybrids was analyzed by a combination of high-performance liquid chromatography and gas chromatography-mass spectrometry analysis. The content of oleanolic acid in two of the hybrid lines was substantially higher than in the donor G. paludosa, while that of swertiamarin was equal to that in G. paludosa in two of the six hybrids analyzed. A number of both G. paludosa and B. scorzonerifolium specific compounds were detected in the three hybrids analyzed by GC-MS as were several not present in either of the biparents....(more)
Yu Y, et al. Protoplasma 2012 Oct;249(4):1029-35.
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- 13. Beneficial effects of swertiamarin on dyslipidaemia in streptozotocin-induced type 2 diabetic rats.
Dyslipidaemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. Lipid changes associated with diabetes mellitus are attributed to increases in free fatty acid flux, secondary to insulin resistance. In the present study, we have investigated the beneficial effects of swertiamarin on dyslipidaemic conditions associated with type 2 diabetes in streptozotocin-induced type 2 diabetic rats. Swertiamarin (50 mg/kg, i.p.) administered once a day for 6 weeks resulted in significant (p < 0.001) reductions in serum triglycerides, cholesterol and low-density lipoprotein levels in diabetic animals as compared with diabetic control animals. Serum fasting glucose was significantly (p < 0.05) decreased, moreover, the insulin sensitivity index was significantly (p < 0.05) increased in swertiamarin treated animals. Overall the data suggest that swertiamarin has beneficial effects on diabetic associated complications such as dyslipidaemia....(more)
Vaidya H, et al. Phytother Res 2012 Aug;26(8):1259-61.
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- 14. Study of the photocatalytic transformation of synephrine: a biogenic amine relevant in anti-doping analysis.
The occurrence of some cases of positive results in anti-doping analysis of octopamine requires clarification as to whether its methylated derivative synephrine could be a metabolic precursor of octopamine itself. Synephrine is a natural phenylethylamine derivative present in some food supplements containing Citrus aurantium, permitted in sport regulations. A simulative laboratory study had been done using a photocatalytic process, to identify all possible main and secondary transformation products, in a clean matrix; these were then sought in biological samples obtained from three human volunteers and four rats treated with synephrine; the parent compound and its new potential metabolic products were investigated in human urine and rat plasma samples. The transformation of synephrine and octopamine and the formation of intermediate products were evaluated, adopting titanium dioxide as photocatalyst. Several products were formed and characterized using the HPLC-HRMS(n) technique. The main intermediates identified in these experimental conditions were compared with the major synephrine metabolites found in in vivo studies on rats and humans. Some more oxidized species, already formed in the photocatalytic process, were also found in urine and plasma samples of treated animals. These new findings could be of interest in further metabolism studies. The main photocatalytic pathway involving synephrine appears to be N-demethylation to give octopamine. On the contrary, we demonstrate the inconsistency of this reaction in both rat and human in vivo determinations, resulting in forensic importance....(more)
Medana C, et al. Anal Bioanal Chem 2013 Jan;405(2-3):1105-13.
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- 15. Phytochemical profile and antioxidant activity of physiological drop of citrus fruits.
The phytochemical content and the antioxidant activity (AA) of physiological drop of the main citrus species grown in China were investigated. Among the flavonoids, hesperidin was found mostly in mandarin and sweet orange, naringin was found mostly in sour orange, pummelo, grapefruit and a hybrid (Gaocheng), narirutin was found in most varieties, neohesperidin was found in Gaocheng and Huyou, and nobiletin and tangeretin were found in most varieties. Hydroxycinnamic acids were the main phenolic acids present, ferulic acid and caffeic acid were the dominant in most cases. There was a greater amount of free (extractable) than bound (insoluble) phenolic acids. Levels of limonoids were higher in Foyou, Eureka lemon, and Gaocheng than those in the other cultivars. The highest level of synephrine was found in Ponkan and Weizhang Satsuma. AA was highest in Ponkan and Weizhang Satsuma and lowest in Huyou, pummel, and lemon. These results suggest that physiological drop of citrus fruits have good potential as sources of different bioactive compounds and antioxidants. PRACTICAL APPLICATION: Physiological drop of citrus fruits may be a good resource of bioactive compounds including flavonoids, phenolic acids, limonoids, synephrine, and a good material of nutraceuticals....(more)
Sun Y, et al. J Food Sci 2013 Jan;78(1):C37-42.
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- 16. Gustatory sensing mechanism coding for multiple oviposition stimulants in the swallowtail butterfly, Papilio xuthus.
The swallowtail butterfly, Papilio xuthus, selectively uses a limited number of plants in the Rutaceae family. The butterfly detects oviposition stimulants in leaves through foreleg chemosensilla and requires a specific combination of multiple oviposition stimulants to lay eggs on the leaf of its host plants. In this study, we sought to elucidate the mechanism underlying the regulation of oviposition behavior by multiple oviposition stimulants. We classified chemosensilla on the tarsomere of the foreleg into three types (L1, L2, and S) according to their size and response to oviposition stimulants and general tastants. The L1 was more abundant in females than in males and responded preferentially to oviposition stimulants. Both L2 and S were common to both sexes and responded to general tastants. We found that five oviposition stimulants (synephrine, stachydrine, 5-hydroxy-Nω-methyltryptamine, narirutin, and chiro-inositol) elicited spikes from three specific gustatory receptor neurons (GRNs) within L1 sensilla. These three GRNs responded to a mixture of the five stimulants at concentrations equivalent to those found in the whole-leaf extract of citrus, and the mixture induced oviposition at levels comparable to whole-leaf extract. We propose that oviposition is triggered by the firing of three specific GRNs in L1 sensilla that encode the chemical signatures of multiple oviposition stimulants....(more)
Ryuda M, et al. J Neurosci 2013 Jan 16;33(3):914-24.
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- 17. A 60day double-blind, placebo-controlled safety study involving Citrus aurantium (bitter orange) extract.
Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p-synephrine are widely consumed in dietary supplements for weight management and sports performance. p-Synephrine is also present in foods derived from a variety of Citrus species. Bitter orange extract is commonly used in combination with multiple herbal ingredients. Most clinical studies conducted on bitter orange extract alone have involved single doses. The purpose of this study was to assess the safety of bitter orange extract (approximately 49mg p-synephrine) alone or in combination with naringin and hesperidin twice daily given to 25 healthy subjects per group for 60days in a double-blinded, placebo-controlled protocol. No significant changes occurred in systolic or diastolic blood pressures, blood chemistries or blood cell counts in control or p-synephrine treated groups. Small, clinically insignificant differences in heart rates were observed between the p-synephrine plus naringin and hesperidin group and the p-synephrine alone as well as the placebo group. No adverse effects were reported in the three groups. Bitter orange extract and p-synephrine appear to be without adverse effects at a dose of up to 98mg daily for 60days based on the parameters measured....(more)
Kaats GR, et al. Food Chem Toxicol 2013 May;55:358-62.
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- 18. Cardiovascular Toxicity of Citrus aurantium in Exercised Rats.
When safety concerns forced the removal of ephedra from the market, other botanicals, including Citrus aurantium or bitter orange (BO) were used as replacements. A major component of the BO extract is synephrine, a chemical that is structurally similar to ephedrine. Because ephedrine has cardiovascular effects that may be exacerbated during physical exercise, the purpose of this study was to determine whether extracts containing synephrine produced adverse effects on the cardiovascular system in exercising rats. Sprague-Dawley rats were dosed daily by gavage for 28 days with 10 or 50 mg of synephrine/kg body weight from one of two different extracts; caffeine was added to some doses. The rats ran on a treadmill for 30 min/day, 3 days/week. Heart rate, blood pressure, body temperature, and QT interval were monitored. Both doses of both extracts significantly increased systolic and diastolic blood pressure for up to 8 h after dosing. Effects on heart rate and body temperature appeared to be due primarily to the effects of caffeine. These data suggest that the combination of synephrine, caffeine, and exercise can have significant effects on blood pressure and do not appear to be effective in decreasing food consumption or body weight....(more)
Hansen DK, et al. Cardiovasc Toxicol 2013 Feb 9.
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- 19. High-performance liquid chromatographic analysis of biogenic amines in pharmaceutical products containing Citrus aurantium.
A reverse-phase (RP)-HPLC method is reported for determining L-tyrosine, p-octopamine, synephrine, tyramine and hordenine as chemical markers of the species Citrus aurantium in raw material, dry extracts and phytotherapeutic herbal formulations. Using RP-HPLC with diode array detection (DAD) and gradient elution, the amines were determined in 12 different products from different Brazilian states labelled as containing C. aurantium. The presence of the amines was confirmed by mass spectrometry using electrospray ionisation (ESI-MS/MS). This RP-HPLC method allowed the separation of the amines from complex mixtures containing caffeine, ephedrine, salicin and other raw materials (e.g. Garcinia camboja, Phaseolus vulgaris, Caralluma fimbriata, Cassia nomane, Ephedra sp. and Cordia ecalyculata). The method proved useful and selective for inspecting herbal medicines containing p-synephrine and structural analogues. The herbal products analysed had a p-synephrine content ranging from 0.005 to 4.0% (w/w)....(more)
Viana C, et al. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2013 Feb 19.
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- 20. Analysis of octopamine in human doping control samples.
The biogenic amine octopamine [4-(2-amino-1-hydroxyethyl)phenol] is prohibited in sports owing to its stimulating and performance-enhancing properties. Adverse analytical findings in athletes' doping control samples commonly result from surreptitious applications; however, the occurrence of octopamine in nutritional supplements and in selected invertebrates as well as the assumption that its N-methylated analog synephrine [4-(1-hydroxyethyl-2-methylamino)phenol, not banned by anti-doping authorities but currently monitored in prevalence studies) might be converted in-vivo into octopamine have necessitated a study to investigate the elimination of synephrine and octopamine present in over-the-counter products. Urine samples collected after administration of nutritional supplements containing octopamine and/or synephrine as well as urine samples collected after therapeutic application of octopamine- or synephrine-containing drugs were analyzed using a validated solid-phase extraction-based procedure employing a weak cation exchange resin and liquid chromatographic/tandem mass spectrometric detection with electrospray ionization and multiple reaction monitoring. In the case of therapeutic octopamine application, the urinary concentration of the target compound increased from baseline levels below the lower limit of detection to 142 µg/mL, while urine samples collected after synephrine as well as dietary supplement administration did not yield any evidence for elevated renal excretion of octopamine....(more)
Thevis M, et al. Biomed Chromatogr 2012 May;26(5):610-5.
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- 21. Molecularly imprinted polymers for selective extraction of synephrine from Aurantii Fructus Immaturus.
In this work, molecularly imprinted solid-phase extraction (MISPE) has been used to selectively enrich, purify, or remove synephrine from Aurantii Fructus Immaturus. To this end, a molecularly imprinted polymer (MIP) was prepared by self-assembly from the template synephrine, the functional monomer methacrylic acid, and the crosslinker ethylene glycol dimethacrylate in 1:4:20 molar ratio. Subsequent molecular interrogation of the MIP binding sites revealed preferential structural selectivity for synephrine relative to other structurally related naturally occurring compounds (i.e. octopamine and tyramine ). This selectivity was subsequently exploited to achieve substantial sample clean-up of extracts of crude Aurantii Fructus Immaturus and Aurantii Fructus Immaturus stir-baked with bran. The purity of synephrine in the extracts after MISPE represented approximately 24.21-fold enrichment of the synephrine in the untreated extracts of Aurantii Fructus Immaturus stir-baked with bran. High recoveries (85-90%) from the samples proved that the method was valid for selective enrichment, purification, or removal of synephrine from Aurantii Fructus Immaturus....(more)
Fan JP, et al. Anal Bioanal Chem 2012 Jan;402(3):1337-46.
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- 22. Detection of hazardous weight-loss substances in adulterated slimming formulations using ultra-high-pressure liquid chromatography with diode-array detection.
The presence on the market of illegal products for slimming purposes or the treatment of overweight is a public health issue. These products may contain illicit chemicals in order to improve their effectiveness. Some of these weight-loss compounds are responsible for adverse events, including fatal outcomes. A general strategy for the analysis of any suspect formulation begins with a large screening for the general search of a wide range of compounds. A methodology for the qualitative and quantitative determination of 34 compounds in slimming preparations (such as dietary supplements or medicinal products) was used for the control of slimming formulations from the market, including over the Internet. The fast liquid chromatography system (ultra-high-pressure liquid chromatography) used a gradient of solvent (phosphate buffer and acetonitrile), a C18 endcapped column and a diode array detector. This system allows dual identification based on retention time and UV spectra. The analytical method is simple, fast and selective since 34 weight-loss compounds can be detected in a 15-min run time. Thus, 32 commercial slimming formulations were analysed using this method, allowing the detection and quantification of hazardous active substances: caffeine, clenbuterol, nicotinamide, phenolphthalein, rimonabant, sibutramine, didesmethylsibutramine, synephrine and yohimbine....(more)
Rebiere H, et al. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2012;29(2):161-71.
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- 23. p-Synephrine stimulates glucose consumption via AMPK in L6 skeletal muscle cells.
Interest in p-synephrine, the primary protoalkaloid in the extract of bitter orange and other citrus species, has increased due to its various pharmacological effects and related adverse effects. The lipolytic activity of p-synephrine has been repeatedly revealed by in vitro and in vivo studies and p-synephrine is currently marketed as a dietary supplement for weight loss. The present study investigated the effect of p-synephrine on glucose consumption and its action mechanism in L6 skeletal muscle cells. Treatment of L6 skeletal muscle cells with p-synephrine (0-100μM) did not affect cell viability and increased basal glucose consumption up to 50% over the control in a dose-dependent manner. The basal- or insulin-stimulated lactic acid production as well as glucose consumption was significantly increased by the addition of p-synephrine. p-Synephrine stimulated the phosphorylation of AMPK but not of Akt. p-Synephrine-induced glucose consumption was sensitive to the inhibition of AMPK but not to the inhibition of PI3 kinase. p-Synephrine also stimulated the translocation of Glut4 from the cytoplasm to the plasma membrane; this stimulation was suppressed by the inhibition of AMPK, but not of PI3 kinase. Taken together, p-synephrine can stimulate glucose consumption (Glut4-dependent glucose uptake) by stimulating AMPK activity, regardless of insulin-stimulated PI3 kinase-Akt activity in L6 skeletal muscle cells....(more)
Hong NY, et al. Biochem Biophys Res Commun 2012 Feb 24;418(4):720-4.
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- 24. Polymethoxyflavonoids tangeretin and nobiletin increase glucose uptake in murine adipocytes.
Tangeretin and nobiletin are polymethoxyflavonoids that are contained in citrus fruits. Polymethoxyflavonoids are reported to have several biological functions including anti-inflammatory, anti-atherogenic, or anti-diabetic effects. However, whether polymethoxyflavonoids directly affect glucose uptake in tissues is not well understood. In the current study, we investigated whether tangeretin and nobiletin affect glucose uptake in insulin target cells such as adipocytes. We observed that treatment with tangeretin or nobiletin significantly increased the uptake of [(3) H]-deoxyglucose in differentiated 3T3-F442A adipocytes in a concentration-dependent manner. Data showed that phosphatidyl inositol 3 kinase, Akt1/2, and the protein kinase A pathways were involved in the increase in glucose uptake induced by polymethoxyflavonoids. These data suggest that the anti-diabetic action of polymethoxyflavonoids is partly exerted via these signaling pathways in insulin target tissues....(more)
Onda K, et al. Phytother Res 2013 Feb;27(2):312-6.
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- 25. Mild Mitochondrial Depolarization is Involved in a Neuroprotective Mechanism of Citrus sunki Peel Extract.
Mitochondrial membrane potential (Ψm ) contributes to determining a driving force for calcium to enter the mitochondria. It has been demonstrated that even a small mitochondrial depolarization is sufficient to prevent mitochondrial calcium overload and the subsequent apoptosis. Therefore, mild mitochondrial depolarization has been recently evaluated as a novel mechanism of neuroprotection via inhibiting neurotoxic mitochondrial calcium overload during neuronal insults. In the present study, using both real-time recording and flow cytometric analyses of Ψm , we demonstrated that ethanolic peel extract of Citrus sunki Hort. ex Tanaka (CPE) and its active compounds are capable of inducing a mild mitochondrial depolarization. Polymethoxylated flavones such as nobiletin and tangeretin were found as the active compounds responsible for CPE effects on Ψm . Neuronal viability was significantly increased in a dose-dependent manner by CPE treatment in H2 O2 -stimulated HT-22 cells as an in vitro neuronal insult model. CPE treatment significantly inhibited H2 O2 -induced apoptotic processes such as chromatin condensation, caspase 3 activation and anti-poly (ADP-ribose) polymerase (PARP) cleavage. CPE treatment significantly blocked mitochondrial calcium overload in H2 O2 -stimulated HT-22 neurons as indicated by rhod-2 acetoxymethyl ester. Taken together, our findings suggest that CPE and its active compounds may be considered as promising neuroprotective agents via inducing a mild mitochondrial depolarization. Copyright © 2012 John Wiley & Sons, Ltd....(more)
Wu JJ, et al. Phytother Res 2013 Apr;27(4):564-71.
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- 26. HPLC-PDA-MS and NMR characterization of a hydroalcoholic extract of Citrus aurantium L. var. amara peel with antiedematogenic activity.
The phytochemical profile of a hydroalcoholic extract of Citrus aurantium var. amara L. peel, used as herbal medicine, was characterized by HPLC-PDA-MS. Two di-C-glycosyl flavones (vincenin II and diosmetin 6,8-di-C-glucoside), a series of flavones (luteolin 7-O-neohesperidoside, rhoifolin, and neodiosmin), and flavanone (neoeriocitrin, naringin, and neohesperidin) 7-O-neohesperidosides and two methoxyflavones (nobiletin and tangeretin), commonly present in Citrus, were identified. Furthermore, brutieridin and melitidin, two 3-hydroxy-3-methylglutaryl flavanone glycosides, were also characterized along with rhoifolin 4'-glucoside and three coumarins (8,3'-β-D-glucopyranosyloxy-2'-hydroxy-3'-methylbutyl-7-methoxycoumarin, merazin hydrate, and isomerazin). A preparative isolation procedure followed by NMR spectroscopy confirmed the proposed structures of the major flavonoids and identified the coumarins. The phenolic content was found to be 14.8 mg mL(-1), and naringin and neohesperidin were the compounds present in the highest concentration (3.6 and 2.6 mg mL(-1)). The extract of C. aurantium peel inhibited significantly (p < 0.05) both histamine- and dextran-induced edema in rats in a concentration-dependent manner (IC(50) = 119.6 and 118.3 mg kg(-1), respectively), providing evidence for the therapeutic use of C. aurantium var. amara peel....(more)
Mencherini T, et al. J Agric Food Chem 2013 Feb 27;61(8):1686-93.
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- 27. Antioxidant activity and effective compounds of immature calamondin peel.
The antioxidant activity and the flavonoids of mature and immature calamondin (Citrus mitis Blanco) peel were investigated. The hot water extract of immature calamondin peel exhibited the highest oxygen radical absorbance capacity (ORAC), reducing power, and superoxide scavenging effect. 3',5'-Di-C-β-glucopyranosylphloretin, naringin, hesperidin, nobiletin, and tangeretin are the five major flavonoids found in hot water extract with the levels of 6888±522, 2333±157, 1350±94, 165±13, and 8±4 mg/100 g dry basis, respectively. The contents of nobiletin and tangeretin increased after ripening. The hot water extract of immature calamondin peel was fractionated using a semi-preparative HPLC. Fraction VI showed the highest ORAC value (28.02±2.73 mmol Trolox equivalents (TE)/g fraction) and two compounds, naringin and hesperidin, were identified as the major active components attributed to the antioxidant activity. Fraction V contained 3',5'-di-C-β-glucopyranosylphloretin, which revealed low ORAC value with 7.43 mmol TE/g fraction. However, it might also contribute to antioxidant activity in immature calamondin peel due to its greatest quantity....(more)
Yu MW, et al. Food Chem 2013 Feb 15;136(3-4):1130-5.
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- 28. Citrus flavonoids and lipid metabolism.
PURPOSE OF REVIEW:
Citrus flavonoids are polyphenolic compounds with powerful biological properties. This review aims to summarize recent advances towards understanding the ability of citrus flavonoids to regulate lipid metabolism and other metabolic parameters relevant to the metabolic syndrome, type 2 diabetes and cardiovascular disease.
RECENT FINDINGS:
Citrus flavonoids, including naringenin, hesperidin, nobiletin and tangeretin, have emerged as promising therapeutic agents for the treatment of metabolic dysregulation. Epidemiological studies report that intake of citrus flavonoid-containing foods attenuates cardiovascular diseases. Experimental and a limited number of clinical studies reveal lipid-lowering, insulin-sensitizing, antihypertensive and anti-inflammatory properties. In animal models, citrus flavonoid supplements prevent hepatic steatosis, dyslipidemia and insulin sensitivity primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose tissue, kidney and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters and also through direct impact on the vessel wall.
SUMMARY:
These recent studies suggest an important role of citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity and atherosclerosis. The favorable outcomes are achieved through multiple mechanisms. Human studies focussed on dose, bioavailability, efficacy and safety are required to propel the use of these promising therapeutic agents into the clinical arena....(more)
Assini JM, et al. Curr Opin Lipidol 2013 Feb;24(1):34-40.
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- 29. Identification of active compounds from Aurantii Immatri Pericarpium attenuating brain injury in a rat model of ischemia-reperfusion.
Ischemic stroke is caused by brain injury due to prolonged ischemia by occlusion of cerebral arteries. In this study, we isolated active compounds from an ethanol extract of Aurantii Immatri Pericarpium (HY5356). We first showed by DNA fragmentation assay that HY5356 improved human hepatocellular carcinoma cells (HepG2) under hypoxic conditions by inhibiting apoptosis. When HY5356 was fractionated with dichloromethane (MC), ethyl acetate (EA) and n-butanol (BU), the MC fraction improved cell viability at the lowest concentration (100 μg/ml). Intraperitoneal injection of HY5356 (200 mg/kg) or the MC fraction (200 mg/kg) to rats prior to occlusion attenuated brain injury significantly in a rat model of ischemia-reperfusion. Adopting cell viability under hypoxic conditions as an activity screening system, we isolated nobiletin and tangeretin as active compounds. The results suggest that intake of Aurantii Immatri Pericarpium containing nobiletin and tangeretin as active compounds might be beneficial for preventing ischemic stroke....(more)
Yang EJ, et al. Food Chem 2013 May 1;138(1):663-70.
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- 30. Phytochemical profile and antioxidant activity of physiological drop of citrus fruits.
The phytochemical content and the antioxidant activity (AA) of physiological drop of the main citrus species grown in China were investigated. Among the flavonoids, hesperidin was found mostly in mandarin and sweet orange, naringin was found mostly in sour orange, pummelo, grapefruit and a hybrid (Gaocheng), narirutin was found in most varieties, neohesperidin was found in Gaocheng and Huyou, and nobiletin and tangeretin were found in most varieties. Hydroxycinnamic acids were the main phenolic acids present, ferulic acid and caffeic acid were the dominant in most cases. There was a greater amount of free (extractable) than bound (insoluble) phenolic acids. Levels of limonoids were higher in Foyou, Eureka lemon, and Gaocheng than those in the other cultivars. The highest level of synephrine was found in Ponkan and Weizhang Satsuma. AA was highest in Ponkan and Weizhang Satsuma and lowest in Huyou, pummel, and lemon. These results suggest that physiological drop of citrus fruits have good potential as sources of different bioactive compounds and antioxidants. PRACTICAL APPLICATION: Physiological drop of citrus fruits may be a good resource of bioactive compounds including flavonoids, phenolic acids, limonoids, synephrine, and a good material of nutraceuticals....(more)
Sun Y, et al. J Food Sci 2013 Jan;78(1):C37-42.
Related Products: Tangeretin
- 31. Naturally occurring flavonoids against human norovirus surrogates.
Naturally occurring plant-derived flavonoids are reported to have antibacterial, antiviral, and pharmacological activities. The objectives of this study were to determine the antiviral effects of four flavonoids (myricetin, L-epicatechin, tangeretin, and naringenin) on the infectivity of food borne norovirus surrogates after 2 h at 37 °C. The lab-culturable surrogates, feline calicivirus (FCV-F9) at titers of ~7 log10 PFU/ml (high titer) or ~5 log10 PFU/ml (low titer) and murine norovirus (MNV-1) at ~5 log10 PFU/ml, were mixed with equal volumes of myricetin, L-epicatechin, tangeretin, or naringenin at concentrations of 0.5 or 1 mM, and incubated for 2 h at 37 °C. Treatments of viruses were neutralized in cell culture medium containing 10 % heat-inactivated fetal bovine serum, serially diluted, and plaque assayed. Each treatment was replicated thrice and assayed in duplicate. FCV-F9 (low titer) was not found to be reduced by tangeretin or naringenin, but was reduced to undetectable levels by myricetin at both concentrations. Low titer FCV-F9 was also decreased by 1.40 log10 PFU/ml with L-epicatechin at 0.5 mM. FCV-F9 at high titers was decreased by 3.17 and 0.72 log10 PFU/ml with myricetin and L-epicatechin at 0.5 mM, and 1.73 log10 PFU/ml with myricetin at 0.25 mM, respectively. However, MNV-1 showed no significant inactivation by the four tested treatments. The antiviral effects of the tested flavonoids are dependent on the virus type, titer, and dose. Further research will focus on understanding the antiviral mechanism of myricetin and L-epicatechin....(more)
Su X, et al. Food Environ Virol 2013 Jun;5(2):97-102.
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- 32. Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells.
Hepatocyte growth factor (HGF), and its receptor, c-Met activation has recently been shown to play important roles in cancer invasion and metastasis in a wide variety of tumor cells. We use HGF as an invasive inducer of human HepG2 cells to investigate the effect of four flavones including apigenin, tricetin, tangeretin, and nobiletin on HGF/c-Met-mediated tumor invasion and metastasis. Among them, nobiletin markedly inhibited HGF-induced the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay and transwell-chamber invasion/migration assay under non-cytotoxic concentrations. Data also showed nobiletin inhibited HGF-induced cell scattering and cytoskeleton changed such as filopodia and lamellipodia. Furthermore, nobiletin could inhibit HGF-induced the membrane localization of phosphorylated c-Met, ERK2, and Akt, but not phosphorylated JNK1/2 and p38. Next, nobiletin significantly decreased the levels of phospho-ERK2 and phospho-Akt in ERK2 or Akt siRNA-transfected cells concomitantly with a marked reduction on cell invasion and migration. In conclusion, nobiletin attenuates HGF-induced HepG2 cells metastasis involving both ERK and PI3K/Akt pathways and are potentially useful as anti-metastatic agents for the treatment of hepatoma....(more)
Shi MD, et al. Phytomedicine 2013 Mar 25.
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- 33. Simultaneous quantification of paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin from Si-Ni-San extract in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.
In this study, a sensitive and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of seven bioactive components including paeoniflorin, nobiletin, tangeretin, liquiritigenin, isoliquiritigenin, liquiritin and formononetin in rat plasma and tissues after oral administration of Si-Ni-San extract using astragaloside IV as internal standard (IS). The plasma and tissue samples were extracted by solid-phase extraction. Chromatographic separation was accomplished on a C18 column with a multiple-step gradient elution. The quantification was obtained by scanning with multiple reaction monitoring via an electrospray ionization source that was operated by switching between the positive and negative modes in two MS/MS scan segments. Full validation of the assay was implemented. In conclusion, this method demonstrated good linearity and specificity. The lower limits of quantification for the analytes were <7.5 ng/mL. Intra- and inter-day precisions (RSD) were <12.5% and accuracy (RE) ranged from -10.2 to 7.3%. The average recoveries of the analytes from rat plasma and tissues were >65.2% and 58.6%, respectively. The validated method was further applied to the determination of actual rat plasma and tissues after oral administration of Si-Ni-San extract. The results provided a meaningful basis for the clinical application of this prescription. Copyright © 2013 John Wiley & Sons, Ltd....(more)
Li T, et al. Biomed Chromatogr 2013 Apr 11.
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- 34. Tanshinone derivatives: a patent review (January 2006 - September 2012).
INTRODUCTION:
Tanshinone IIA (TSIIA), cryptotanshinone and tanshinone I are major bioactive constituents of Danshen, a Chinese herbal medicine. Sodium tanshinone IIA sulfonate (STS) is a water-soluble derivative of TSIIA and it is currently used for treating cardiovascular diseases in China.
AREAS COVERED:
The article presents a review of the anti-atherosclerosis, cardioprotective effects, neuroprotection and anti-tumor activities of TSIIA and a review of patents on tanshinone derivatives from January 2006 to September 2012.
EXPERT OPINION:
Mechanistic studies have discovered that TSIIA modulates ion channels, kinases, hormone receptors, apoptosis proteins, growth factors, cytokines, microRNA, tumor suppressor and many other targets, revealing an intricate biological network modulated by TSIIA. Many patents have attempted to overcome the low water solubility of TSIIA and tanshinone I by attaching a polar substituent or by a prodrug strategy. However, biological activities of these tanshinone derivatives need to be further evaluated. Given the extensive in vitro and in vivo biological activities of TSIIA, this compound is a promising candidate to be further developed as a novel therapeutics for treating atherosclerosis, cardiovascular diseases, neurodegenerative diseases and cancer....(more)
Tian XH, et al. Expert Opin Ther Pat 2013 Jan;23(1):19-29.
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- 35. Enzyme kinetic and molecular docking studies for the inhibitions of miltirone on major human cytochrome P450 isozymes.
Previous studies have shown that major tanshinones isolated from Danshen (Salvia miltiorrhiza) inhibited human and rat CYP450 enzymes-mediated metabolism of model probe substrates, with potential in causing herb-drug interactions. Miltirone, another abietane type-diterpene quinone isolated from Danshen, has been reported for its anti-oxidative, anxiolytic and anti-cancer effects. The aim of this study was to study the effect of miltirone on the metabolism of model probe substrates of CYP1A2, 2C9, 2D6 and 3A4 in pooled human liver microsomes. Miltirone showed moderate inhibition on CYP1A2 (IC(50)=1.73 μM) and CYP2C9 (IC(50)=8.61 μM), and weak inhibition on CYP2D6 (IC(50)=30.20 μM) and CYP3A4 (IC(50)=33.88 μM). Enzyme kinetic studies showed that miltirone competitively inhibited CYP2C9 (K(i)=1.48 μM), and displayed mixed type inhibitions on CYP1A2, CYP2D6 and CYP3A4 with K(i) values of 3.17 μM, 24.25 μM and 35.09 μM, respectively. Molecular docking study further confirmed the ligand-binding conformations of miltirone in the active sites of these human CYP450 isoforms, and provided some information on structure-activity relationships for the CYPs inhibition by tanshinones. Taken together, CYPs inhibitions of miltirone were weaker than dihydrotanshinone, but stronger than cryptotanshinone, tanshinone I and tanshinone IIA....(more)
Zhou X, et al. Phytomedicine 2013 Feb 15;20(3-4):367-74.
Related Products: Tanshinone I