Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp

Planta Medica ◽  
2021 ◽  
Author(s):  
Islam Husain ◽  
Olivia R. Dale ◽  
Vamshi Manda ◽  
Zulfiqar Ali ◽  
Bill J. Gurley ◽  
...  
Keyword(s):  
Methanolic Extract ◽  
Water Extract ◽  
Inhibitory Effect ◽  
Global Market ◽  
Dependent Manner ◽  
Aryl Hydrocarbon ◽  
Methanolic Extracts ◽  
Safety Studies ◽  
Pure Compounds

Abstract Bulbine natalensis, an emerging medicinal herb on the global market with androgenic properties, is often formulated in dietary supplements that promote perceived sexual enhancement. However, to date, comprehensive safety studies of B. natalensis are lacking, particularly those related to its herb-drug interaction potential. The purpose of this study was to assess the inductive and inhibitory effects of extracts and pure compounds of B. natalensis on human cytochrome P-450 isozymes in vitro. Our findings demonstrated that both water and methanolic extracts of B. natalensis as well as knipholone, bulbine-knipholone, and 6′-O-methylknipholone dose-dependently increased mRNA expression encoded by CYP2B6, CYP1A2, and ABCB1 genes. Functional analyses showed that water (60 to 2.20 µg/mL) and methanolic (30 to 3.75 µg/mL) extracts and knipholones (10 to 0.33 µM) increased CYP2B6 and CYP1A2 activity in a dose-dependent manner. Additionally, water extract (60 µg/mL), methanolic extract (30 µg/mL), and knipholone (10 µM) caused activation of the aryl hydrocarbon receptor up to 11.1 ± 0.7, 8.9 ± 0.6, and 7.1 ± 2.0-fold, respectively. Furthermore, inhibition studies revealed that methanolic extract attenuated the activity of metabolically active CYP1A2 (IC50, 22.6 ± 0.4 µg/mL) and CYP2B6 (IC50, 34.2 ± 6.6 µg/mL) proteins, whereas water extracts had no inhibitory effect on either isoform. These findings suggest that chronic consumption of B. natalensis may affect normal homeostasis of select CYPs with subsequent risks for HDIs when concomitantly ingested with conventional medications that are substrates of CYP2B6 and CYP1A2. However, more in-depth translational studies are required to validate our current findings and their clinical relevance.

scholarly journals In vitro Activity of Ozoroa pulcherrima Schweinf. Extracts and Fractions on Schistosoma mansoni Cercariae and Adult Worms

2020 ◽  
pp. 17-30
Author(s):  
Nestor Gipwe Feussom ◽  
Hermine Boukeng Jatsa ◽  
Mérimé Christian Kenfack ◽  
Emilienne Tienga Nkondo ◽  
Ulrich Membe Femoe ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Methanolic Extract ◽  
Lower Abdominal Pain ◽  
In Vitro Assays ◽  
Dependent Manner ◽  
In Vitro Activity ◽  
Concentration Dependent Manner ◽  
Methanolic Extracts ◽  
Effective Drugs

Aims: Continuous attempts are being made to develop new and more effective drugs for the treatment of schistosomiasis. Ozoroa pulcherrima Schweinf. is a medicinal plant used in Africa for the treatment of dysmenorrhea, lower abdominal pain, dystocia and intestinal helminthiasis. This study provides findings on the cercaricidal and schistosomicidal activity of extracts and fractions of Ozoroa pulcherrima in in vitro assays. Methodology: The aqueous and methanolic extracts from Ozoroa pulcherrima root parts (62.5 – 2000 µg/mL), as well as the methanol derived fractions (n-hexane and ethyl acetate: 31.25 – 1000 µg/mL) were tested on cercariae and adult worms of Schistosoma mansoni. Niclosamide-olamine 5% (1 µg/mL) and praziquantel (10 µg/mL) were respectively used as reference drugs. During the assays, the mortality of cercariae after 2 hours, and adult worms’ mobility and mortality after 48 hours of incubation were evaluated. Results: Ozoroa pulcherrima extracts and fractions significantly increased cercariae and worm mortality in a concentration-dependent manner. The methanolic extract was the most active on cercariae with a LC50of 20.65 µg/mL after 30 minutes, while the n-hexane fraction was the most active on worm with a LC50 of 79.54 μg/mL (65.58 – 96.47 μg/mL) after 48 hours. Significant reduction of motor activity (18.47 to 100%) was recorded for surviving worms incubated in different concentrations of the extracts and fractions. Conclusion: This study proves that Ozoroa pulcherrima extracts and fractions have cercaricidal and schistosomicidal activities. Ozoroa pulcherrima may have great potential as an anti-schistosomal agent for further research.

scholarly journals In vitro Antibacterial Activity of Zingiber officinale and Orthosiphon stamineus on Enterococcus faecalis

2017 ◽  
Vol 9 (13) ◽  
pp. 112 ◽  
Author(s):  
Zamirah Zainal-Abidin ◽  
Nor Akmal Abdul-Wahab ◽  
Muhamad Kamil Ghazi-Ahmad ◽  
Shahida Mohd-Said
Keyword(s):  
Antibacterial Activity ◽  
Enterococcus Faecalis ◽  
Water Extract ◽  
Zingiber Officinale ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Orthosiphon Stamineus ◽  
Biofilm Disruption

This study evaluates the antibacterial effects of Zingiber officinale essential oil and Orthosiphon stamineus water extract against Enterococcus faecalis. The herbs were prepared in various concentrations to determine their minimum inhibitory concentrations (MIC) and growth inhibitory effect. Anti-adhesion activities of the herbs were determined by co-incubation with E. faecalis cultures for 6 and 24 h. Biofilm disruption activities were determined by adding the studied herbs into preformed E. faecalis biofilm. The effects on the morphology of E. faecalis grown as biofilm were studied using scanning electron microscopy (SEM). The MICs of ginger oil and O. stamineus extract were 0.31 and 25 mg/mL, respectively. Between the tested herbs, ginger exhibited greater inhibitory effects on the growth of E. faecalis grown in suspension mode. Both herbs generally showed anti-adhesion activities in inverse concentration-dependent manner. No significant biofilm disruption activities by both herbs were observed. SEM analyses showed E. faecalis cell surface changes in the treated biofilm. The studied herbs may have compromised the integrity of the bacterial cell membrane. These findings suggest that the studied herbs may have better antibacterial activities against E. faecalis in suspension mode compared to biofilm mode, with ginger oil showed greater antibacterial activity compared to O. stamineus extract.

scholarly journals Uterotonic Effects of Aqueous and Methanolic Extracts of Lannea Acida in Wistar Rats: An in Vitro Study.

2020 ◽  
Author(s):  
esther simo ngadjui ◽  
Jibril Yves Kouam ◽  
Georges Romeo Fozin Bonsou ◽  
Aimé Césaire Tetsatsi Momo ◽  
Patrick Brice Defo Deeh ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Methanolic Extract ◽  
Female Rats ◽  
Organ Bath ◽  
Dependent Manner ◽  
Free Medium ◽  
Concentration Dependent Manner ◽  
Methanolic Extracts ◽  
Oxytocin Receptors

Abstract Background: Lannea acida (Anacardiaceae), commonly called Kikié in the Noun division (West-Cameroon), is a tree whose bark is used locally to solve difficult childbirth. This study aimed to evaluate the in vitro uterotonic effects of aqueous and methanolic extracts of L. acida in female Wistar rats. Uterine strips isolated from female rats pretreated (48h) with oestradiol (5μg) were mounted in a single-organ bath containing a well aerated and thermostated De Jalon solution (37°C). The effects of L. acida extracts were recorded in a non-cumulative manner after application. The effect of the methanolic extract (the most active extract) was monitored in the presence of atosiban (a competitive antagonist of oxytocin receptors), atropine (a specific type 3 muscarinic receptor antagonist), nifedipine (an L-type calcium channel antagonist) and 2-Aminoethoxydiphenyl borate (2-ADB, a specific antagonist of inositol 1,4,5-triphosphate receptors type 1), and in calcium-free medium containing EGTA. Results: L. acidainduced uterine contraction in a concentration-dependent manner with the methanolic extract (1.506 ± 0.032 gf) being the most effective. Administration of atosiban (2 μmol/l), atropine (1 μmol/l), nifedipine (5 μmol), 2-APB (100 μmol), and calcium free medium containing EGTA (2 mmol) reduced the contractile effect of L. acida. Complete inhibition was observed with nifedipine, 2-APB, and calcium free medium containing EGTA.Conclusions: These results suggest that L. acida possesses an uterotonic effect mediated through oxytocin receptors with mobilization of extracellular calcium.

scholarly journals The Effect ofHydrocotyle sibthorpioidesLam. Extracts onIn VitroDengue Replication

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Fitrien Husin ◽  
Yean Yean Chan ◽  
Siew Hua Gan ◽  
Siti Amrah Sulaiman ◽  
Rafidah Hanim Shueb
Keyword(s):  
Viral Replication ◽  
Methanolic Extract ◽  
Morphological Changes ◽  
Plaque Assay ◽  
Water Extract ◽  
Vero Cells ◽  
Inhibitory Effect ◽  
Potential Effect ◽  
Cell Viability Assay

Objective. To investigate the potential effect ofHydrocotyle sibthorpioidesLam. (H. sibthorpioides) extracts againstin vitrodengue viral replication.Methods. The cytotoxicity ofH. sibthorpioideswas evaluated using a cell viability assay. Cells were pre- and posttreated with water and methanol extracts ofH. sibthorpioides, and the viral inhibitory effect was investigated by observing the morphological changes, which were further confirmed by plaque assay.Results. The methanolic extract cytotoxicity was higher in Vero and C6/36 cells than the cytotoxicity of the water extract. Preincubation of the cells withH. sibthorpioidesextract showed nonexistent to mild prophylactic effects. The posttreatment of Vero cells withH. sibthorpioidesmethanolic extract presented higher antidengue activities when compared with the water extract. Surprisingly, posttreatment of C6/36 cells resulted in an enhancement of viral replication.Conclusion.H. sibthorpioideshad variable effects on dengue viral replication, depending on the treatment, cell lines, and solvent types. This study provides important novel insights on the phytomedicinal properties ofH. sibthorpioidesextracts on dengue virus.

scholarly journals Inhibitory Effect of Propolis on Platelet Aggregation In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yun-Xiang Zhang ◽  
Ting-Ting Yang ◽  
Liu Xia ◽  
Wei-Fen Zhang ◽  
Jia-Fu Wang ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Water Extract ◽  
Adenosine Diphosphate ◽  
Caffeic Acid Phenethyl Ester ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Receptor Activator ◽  
Dose Dependent

Platelet hyperactivity plays an important role in arterial thrombosis and atherosclerosis. The present study was aimed to investigate the effects of different extracts of propolis and components of flavonoids on platelet aggregation. Platelet-rich plasma was prepared and incubated in vitro with different concentrations of the tested extracts and components of flavonoids. Platelets aggregation was induced by different agonists including adenosine diphosphate (ADP, 10 μM), thrombin receptor activator peptide (TRAP, 50 μM), and collagen (5 μg/mL). At 25 mg/L to 300 mg/mL, the water extract propolis (WEP) inhibited three agonists-induced platelet aggregations in a dose-dependent manner. The flavonoids isolated from the propolis also showed markedly inhibited platelet aggregation induced by collagen, ADP, and TRAP, respectively. The components including caffeic acid phenethyl ester (CAPE), galangin, apigenin, quercetin, kaempferol, ferulic acid, rutin, chrysin, pinostrobin, and pinocembrin and their abilities of inhibiting platelet aggregation were studied. It was concluded that propolis had an antiplatelet action in which flavonoids were mainly implicated.

Phenolic constituents and inhibitory effects of the leaf of Rauvolfia vomitoria Afzel on free radicals, cholinergic and monoaminergic enzymes in rat’s brain in vitro

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Olubukola H. Oyeniran ◽  
Adedayo O. Ademiluyi ◽  
Ganiyu Oboh
Keyword(s):  
Lipid Peroxidation ◽  
Free Radicals ◽  
Methanolic Extract ◽  
Array Detector ◽  
Oh Radicals ◽  
Inhibitory Effects ◽  
Methanolic Extracts ◽  
Phenolic Constituents ◽  
Rauvolfia Vomitoria

AbstractObjectivesRauvolfia vomitoria is a medicinal plant used traditionally in Africa in the management of several human diseases including psychosis. However, there is inadequate scientific information on the potency of the phenolic constituents of R. vomitoria leaf in the management of neurodegeneration. Therefore, this study characterized the phenolic constituents and investigated the effects of aqueous and methanolic extracts of R. vomitoria leaf on free radicals, Fe2+-induced lipid peroxidation, and critical enzymes linked to neurodegeneration in rat’s brain in vitro.MethodsThe polyphenols were evaluated by characterizing phenolic constituents using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). The antioxidant properties were assessed through the extracts ability to reduce Fe3+ to Fe2+; inhibit ABTS, DPPH, and OH radicals and Fe2+-induced lipid peroxidation. The effects of the extracts on AChE and MAO were also evaluated.ResultsThe phenolic characterization of R. vomitoria leaf revealed that there were more flavonoids present. Both aqueous and methanolic extracts of R. vomitoria leaf had inhibitory effects with the methanolic extract having higher significant (p≤0.05) free radicals scavenging ability coupled with inhibition of monoamine oxidases. However, there was no significant (p≤0.05) difference obtained in the inhibition of lipid peroxidation and cholinesterases.ConclusionThis study suggests that the rich phenolic constituents of R. vomitoria leaf might contribute to the observed antioxidative and neuroprotective effects. The methanolic extract was more potent than the aqueous extract; therefore, extraction of R. vomitoria leaf with methanol could offer better health-promoting effects in neurodegenerative condition.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

scholarly journals SAT0363 DELPHINIDIN DOSE-DEPENDENTLY DIMINISHES PERIPHERAL IL-17 AND IFN-Γ PRODUCING LYMPHOCYTES IN PSORIATIC ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1128.1-1129
Author(s):  
A. Mavropoulos ◽  
S. Tsiogkas ◽  
D. Skyvalidas ◽  
C. Liaskos ◽  
A. Roussaki-Schulze ◽  
...  
Keyword(s):  
Psoriatic Arthritis ◽  
Cell Viability ◽  
Annexin V ◽  
Nkt Cells ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Research Support ◽  
Research Activities ◽  
Ifn Γ

Background:Delphinidin, a dietary anthocyanidin and powerful anti-oxidant from pigmented fruits and vegetables, has broad anti-inflammatory properties. In a human skin model of psoriasis, delphinidin reduced expression of proliferative and inflammatory markers (1).Objectives:The rationale of our study was to assess whether delphinidin can in vitro suppress IL-17 and IFN-γ production in peripheral blood mononuclear cell (PBMC) subsets from patients with psoriatic arthritis (PsA).Methods:PBMCs were obtained from 24 patients with PsA attending the outpatient clinic of the Department of Rheumatology/clinical Immunology at the University General Hospital of Larissa, Greece. 16 age- and sex-matched healthy volunteers were also included in the study. Delphinidin was supplemented at a concentration ranging from 1 to 50μg/ml, one hour prior to cell stimulation. Cell viability (Annexin V staining) and innate/adaptive lymphocyte subpopulations were assessed by flow cytometry with a panel of fluorochrome-conjugated antibodies against CD56, CD3, CD4 and CD8. Intracellular expression of IL-17 and IFN-γ was measured following PMA/ionomycin stimulation for 5 hours using standard cell permeabilization protocols and monoclonal antibodies against IL-17 and IFN-γResults:Delphinidin at concentration ≥10 μg/ml sharply diminished IL-17-production by CD4(+) T cells (Th17) and CD56(+)CD3(+) (NKT) cells from patients with psoriatic arthritis and normal controls (p≤0.05). IFN-γ producing T (CD4 and CD8) cells, as well as NK and NKT cells were also dose-dependently suppressed following delphinidin pre-incubation in both patients and healthy controls. Inhibition of IFN-γ(+) cells ranged from 27 to 69% and peaked at delphinidin concentration 20-50μg/ml. The inhibitory effect of delphinidin on IL-17 and IFN-γ producing lymphocytes was not due to compromised cell viability, as assessed by annexin V binding.Conclusion:Delphinidin exerts, in a dose-dependent manner, a profound in vitro inhibitory effect on T cell and NKT cell IL-17 and IFN-γ production in PsA, and therefore, it may be used as a dietary immunosuppressant, complementary to standard treatment.References:[1]Chamcheu JC Skin Pharmacol Physiol. 2015;28(4):177-88. doi: 10.1159/000368445Disclosure of Interests:ATHANASIOS MAVROPOULOS: None declared, Sotirios Tsiogkas: None declared, Dimitrios Skyvalidas: None declared, Christos Liaskos: None declared, Aggeliki Roussaki-Schulze Grant/research support from: Received a grant to support the educational and research activities of the department from Genesis Pharma (2018), Speakers bureau: Received honoraria from Genesis Pharma and Janssen(2017) and from Roche and Pharmaserve Lilly(2018), Efterpi Zafiriou Speakers bureau: Received honoraria from Genesis Pharma, Abbvie, Novartis, Roche, Jansses(2017) and Novartis, Abbvie(2018), Dimitrios Bogdanos: None declared, Lazaros Sakkas Grant/research support from: Received a grant to support the educational and research activities of the department from Bristol-Meyers Squib, Speakers bureau: Received honoraria from Actellion(2018), Janssen(2017), Novartis(2017), Sanofi-Aventis(2018), Abbvie(2017) and Roche(2017)

Cerebrovascular characterization of clazosentan, the first nonpeptide endothelin receptor antagonist clinically effective for the treatment of cerebral vasospasm. Part I: Inhibitory effect on endothelinA receptor—mediated contraction

2005 ◽  
Vol 102 (6) ◽  
pp. 1101-1107 ◽  
Author(s):  
Hartmut Vatter ◽  
Michael Zimmermann ◽  
Veronika Tesanovic ◽  
Andreas Raabe ◽  
Lothar Schilling ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cerebral Vasospasm ◽  
Isometric Force ◽  
Inhibitory Effect ◽  
Affinity Constant ◽  
Dependent Manner ◽  
Content Type ◽  
The Right ◽  
Fine Print

Object. The central role of endothelin (ET)—1 in the development of cerebral vasospasm after subarachnoid hemorrhage is indicated by the successful treatment of this vasospasm in several animal models by using selective ETA receptor antagonists. Clazosentan is a selective ETA receptor antagonist that provides for the first time clinical proof that ET-1 is involved in the pathogenesis of cerebral vasospasm. The aim of the present investigation was, therefore, to define the pharmacological properties of clazosentan that affect ETA receptor—mediated contraction in the cerebrovasculature. Methods. Isometric force measurements were performed in rat basilar artery (BA) ring segments with (E+) and without (E−) endothelial function. Concentration effect curves (CECs) were constructed by cumulative application of ET-1 or big ET-1 in the absence or presence of clazosentan (10−9, 10−8, and 10−7 M). The inhibitory potency of clazosentan was determined by the value of the affinity constant (pA2). The CECs for contraction induced by ET-1 and big ET-1 were shifted to the right in the presence of clazosentan in a parallel dose-dependent manner, which indicates competitive antagonism. The pA2 values for ET-1 were 7.8 (E+) and 8.6 (E−) and the corresponding values for big ET-1 were 8.6 (E+) and 8.3 (E−). Conclusions. The present data characterize clazosentan as a potent competitive antagonist of ETA receptor—mediated constriction of the cerebrovasculature by ET-1 and its precursor big ET-1. These functional data may also be used to define an in vitro profile of an ET receptor antagonist with a high probability of clinical efficacy.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

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