Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2014

Open Access 01-12-2014 | Research article

Effects of Eleutheroside B and Eleutheroside E on activity of cytochrome P450 in rat liver microsomes

Authors: Sixun Guo, Yan Liu, Zhiping Lin, Sheng Tai, Shuo Yin, Gaofeng Liu

Published in: BMC Complementary Medicine and Therapies | Issue 1/2014

Login to get access

Abstract

Background

Chemicals of herbal products may cause unexpected toxicity or adverse effect by the potential for alteration of the activity of CYP450 when co-administered with other drugs. Eleutherococcus senticosus (ES), has been widely used as a traditional herbal medicine and popular herbal dietary supplements, and often co-administered with many other drugs. The main bioactive constituents of ES were considered to be eleutherosides including eleutheroside B (EB) and eleutheroside E (EE). This study was to investigate the effects of EB and EE on CYP2C9, CYP2D6, CYP2E1 and CYP3A4 in rat liver microsomes in vitro.

Method

Probe drugs of tolbutamide (TB), dextromethorphan (DM), chlorzoxazone (CLZ) and testosterone (TS) as well as eleutherosides of different concentrations were added to incubation systems of rat liver microsomes in vitro. After incubation, validated HPLC methods were used to quantify relevant metabolites.

Results

The results suggested that EB and EE exhibited weak inhibition against the activity of CYP2C9 and CYP2E1, but no effects on CYP2D6 and CYP3A4 activity. The IC50 values for EB and EE were calculated to be 193.20 μM and 188.36 μM for CYP2E1, 595.66 μM and 261.82 μM for CYP2C9, respectively. Kinetic analysis showed that inhibitions of CYP2E1 by EB and EE were best fit to mixed-type with Ki value of 183.95 μM and 171.63 μM, respectively.

Conclusions

These results indicate that EB and EE may inhibit the metabolism of drugs metabolized via CYP2C9 and CYP2E1, and have the potential to increase the toxicity of the drugs.
Appendix
Available only for authorised users
Literature
1.
Li T: Siberian ginseng. Horsetechnology. 2001, 11: 79-84.
2.
Pharmacopoeia Commission of People's Republic of China: Pharmacopoeia of the People’s Republic of China. 2010, Beijing: China Medical Science Press
3.
Drozd J, Sawicka T, Prosińska J: Estimation of humoral activity of Eleutherococcus senticosus. Acta Pol Pharm. 2002, 59 (5): 395-401.PubMed
4.
Han YM, Shi XQ: The research progress of Eleutherococcus senticosus. J Tradit Chin Med. 2011, 1: 54-55.
5.
Zhu YY, Wei XH: Determination of Eleutheroside B and Eleutheroside E in Acanthopanax senticosus by HPLC-PAD. Chin Pharm J. 2011, 16 (46): 1280-1282.
6.
Li C, Wang XY, Hu XW: Determination of eleutheroside B in antifatigue fraction of Acanthopanax senticosus by HPLC. Zhongguo Zhong Yao Za Zhi. 2008, 23 (33): 2800-2802.
7.
Lee S, Son D, Ryu J: Anti-oxidant activities of Acanthopanax senticosus stems and their lignan components. Arch Pharm Res. 2004, 1 (27): 106-110.CrossRef
8.
Díaz Lanza AM, Abad Martínez MJ, Fernández Matellano L, Recuero Carretero C: Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity. Planta Med. 2001, 3 (67): 219-223.CrossRef
9.
Kapil A, Sharma S: Immunopotentiating compounds from Tinospora cordifolia. J Ethnopharmacol. 1997, 2 (58): 89-95.CrossRef
10.
Cho JY, Nam KH, Kim AR: In-vitro and in-vivo immunomodulatory effects of syringin. J Pharm Pharmacol. 2001, 9 (53): 1287-1294.CrossRef
11.
Niu HS, Liu IM, Cheng JT: Hypoglycemic effect of syringin from Eleutherococcus senticosus in streptozotocin-induced diabetic rats. Planta Med. 2008, 2 (74): 109-113.CrossRef
12.
Niu HS, Hsu FL, Liu IM, Cheng JT: Increase of beta-endorphin secretion by syringin, an active principle of Eleutherococcus senticosus, to produce antihyperglycemic action in type 1-like diabetic rats. Horm Metab Res. 2007, 12 (39): 894-898.CrossRef
13.
Tohda C, Ichimura M, Bai Y: Inhibitory effects of Eleutherococcus senticosus extracts on amyloid beta (25–35)-induced neuritic atrophy and synaptic loss. J Pharmacol Sci. 2008, 3 (107): 329-339.CrossRef
14.
Bai Y, Tohda C, Zhu S: Active components from Siberian ginseng (Eleutherococcus senticosus) for protection of amyloid beta (25–35)-induced neuritic atrophy in cultured rat cortical neurons. J Nat Med. 2011, 3–4 (65): 417-423.CrossRef
15.
Tokiwa T, Yamazaki T, Sakurai S: Anti-inflammatory effect of eleutheroside E from Acanthopanax senticosus. Foods Food Ingred J Jpn. 2006, 7 (211): 576-582.
16.
Huang LZ, Wei L, Zhao HF: The effect of Eleutheroside E on behavioral alterations in murine sleep deprivation stress model. Eur J Pharmacol. 2011, 2–3 (658): 150-155.CrossRef
17.
Huang LZ, Huang BK, Ye Q: Bioactivity-guided fractionation for anti-fatigue property of Acanthopanax senticosus. J Ethnopharmacol. 2011, 1 (133): 213-219.CrossRef
18.
Pelkonen O, Urpeinen MT, Hakkola J: Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol. 2008, 10 (82): 667-715.CrossRef
19.
Gibbson GG, Sheet P: Introduction to Drug Metabolism. 1994, London: Blackie Academic and Professional
20.
Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 1–2 (72): 248-254.CrossRef
21.
Bjornsson TD, Callaghan JT, Einolf HJ: The conduct of in vitro and in vivo drug-drug interaction studies: a Pharmaceutical Research and Manufacturers of America (PhRMA) perspective. Drug Metab Dispos. 2003, 7 (31): 815-832.CrossRef
22.
Xia CH, Sun JG, Wang GJ: Herb-drug interactions: in vivo and in vitro effect of Shenmai injection, a herbal preparation, on the metabolic activities of hepatic cytochrome P450 3A1/2, 2C6, 1A2, and 2E1 in rats. Planta Med. 2009, 3 (76): 245-250.
23.
Babbar S, Chanda S, Bley K: Inhibition and induction of human cytochrome P450 enzymes in vitro by capsaicin. Xenobiotica. 2010, 12 (40): 807-816.CrossRef
24.
Fayer JL, Petullo DM, Ring BJ: A novel testosterone 6 beta-hydroxylase activity assay for the study of CYP3A-mediated metabolism, inhibition, and induction in vitro. J Pharmacol Toxicol Methods. 2002, 2 (46): 117-123.
25.
Khojasteh SC, Prabhu S, Kenny JR: Chemical inhibitors of cytochrome P450 isoforms in human liver microsomes: a re-evaluation of P450 isoform selectivity. Eur J Drug Metab Pharmacokinet. 2011, 1 (36): 11-16.
26.
Donovan JL, DeVane CL, Chavin KD: Siberian ginseng (Eleutheroccus senticosus) effects on CYP2D6 and CYP3A4 activity in normal volunteers. Drug Metab Dispos. 2003, 5 (31): 519-522.CrossRef
27.
Martignoni M, Groothuis GM, de Kanter R: Species differences between mouse, rat, dog, monkey and human CYP-mediated drug metabolism, inhibition and induction. Expert Opin Drug Metab Toxicol. 2006, 2 (6): 875-894. 10.1517/17425255.2.6.875.CrossRefPubMed
28.
Turpeinen M, Ghiciuc C, Opritoui M, Tursas L, Pelkonen O, Pasanen M: Predictive value of animal models for human cytochrome P450 (CYP)-mediated metabolism: a comparative study in vitro. Xenobiotica. 2007, 37 (12): 1367-1377. 10.1080/00498250701658312.CrossRefPubMed
29.
Obach RS: Inhibition of human cytochrome P450 enzymes by constituents of St. John's Wort. an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther. 2000, 1 (294): 88-95.
30.
Winitthana T, Niwattisaiwong N, Patarapanich C: In vitro inhibitory effects of asiaticoside and madecassoside on human cytochrome P450. Toxicol In Vitro. 2011, 4 (25): 890-896.CrossRef
31.
Qiu F, Zhang R, Sun J: Inhibitory effects of seven components of danshen extract on catalytic activity of cytochrome P450 enzyme in human liver microsomes. Drug Metab Dispos. 2008, 7 (36): 1308-1314.CrossRef
32.
Chatterjee P, Franklin MR: Human cytochrome p450 inhibition and metabolic- intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos. 2003, 11 (31): 1391-1397.CrossRef
33.
Pekthong D, Martin H, Abadie C: Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide. Ethnopharmacol. 2008, 3 (115): 432-440.CrossRef
34.
Pandit S, Mukherjee PK, Ponnusankar S: Metabolism mediated interaction of alpha-asarone and Acorus calamus with CYP3A4 and CYP2D6. Fitoterapia. 2011, 3 (82): 369-374.CrossRef
35.
Liu G, Liu Y, Liu R: Effects of Flos carthami on CYP2D6 and on the Pharmacokinetics of Metoprolol in Rats. Evid Based Complement Alternat Med. 2011, 207076-doi:10.1155/2011/207076
36.
Doehmer J, Weiss G, McGregor GP, Appel K: Assessment of a dry extract from milk thistle (Silybum marianum) for interference with human liver cytochrome-P450 activities. Toxicol In Vitro. 2011, 1 (25): 21-27.CrossRef
37.
Cao Y, Yan X: Study on effects of 36 cases of propofol combined with Acanthopanax Injection for the treatment of insomnia patients. Zhongguo Shi Yong Yi Yao. 2011, 14 (6): 135-
38.
Chu X, Liu D: 60 cases of Acanthopanax injection combined with choline injection in the treatment of cervical vertigo. J Tradit Chin Med. 2011, 10 (20): 1699-1700.
39.
Gai Y, Zhang T: Clinical study on the effect of Acanthopanax Injection combined with Liposomal Alprostadil in the treatment of stage-IV diabetic nephropathy. J Tradit Chin Med. 2011, 4 (18): 535-537.
40.
Du Y: Analysis of literature of 228 cases of adverse drug reactions caused by Acanthopanax Senticosus injection. Zhongguo Lin Chuang Xin Yi Xue. 2011, 10 (4): 946-948.
41.
Hu J, Shang H, Li J, Zhang L: 521 cases of adverse drug reactions of Eleutherococcus senticosus Injection based on 944 studies. J Evid Based Med. 2010, 2 (10): 182-188.
Metadata
Title
Effects of Eleutheroside B and Eleutheroside E on activity of cytochrome P450 in rat liver microsomes
Authors
Sixun Guo
Yan Liu
Zhiping Lin
Sheng Tai
Shuo Yin
Gaofeng Liu
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2014
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/1472-6882-14-1

Other articles of this Issue 1/2014

BMC Complementary Medicine and Therapies 1/2014 Go to the issue

Research article

Variations in energy metabolism along the pericardium meridian and its relationship with visceral function adjustments during electroacupuncture

Research article

Differentiation therapy: sesamin as an effective agent in targeting cancer stem-like side population cells of human gallbladder carcinoma

Research article

Anti-cancer activity of Ginger (Zingiber officinale) leaf through the expression of activating transcription factor 3 in human colorectal cancer cells

Research article

Acupuncture and moxibustion for lateral elbow pain: a systematic review of randomized controlled trials

Research article

In vitro biological evaluation of eight different essential oils against Trypanosoma cruzi, with emphasis on Cinnamomum verum essential oil

Research article

Acupuncture on GB34 activates the precentral gyrus and prefrontal cortex in Parkinson’s disease