Title:Evaluation of Herb-Drug Interaction of Synacinn™ and Individual Biomarker through Cytochrome 450 Inhibition Assay
VOLUME: 12 ISSUE: 1
Author(s):Nur Syukriah Ab Rahman, Fadzilah Adibah Abd Majid*, Mohd Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, Nirbhay Kumar Tiwari, Sanjeev Giri and Vijaya Bhargava
Affiliation:Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030, Kuala Nerus, Terengganu, Proliv Life Sciences Sdn Bhd, D-1-16, Residensi Bistaria, Jalan Ulu Kelang, Taman Ukay Bistari, 68000, Ampang, Selangor, Proliv Life Sciences Sdn Bhd, D-1-16, Residensi Bistaria, Jalan Ulu Kelang, Taman Ukay Bistari, 68000, Ampang, Selangor, Department of Bioprocess Engineering, Faculty of Chemical & Energy Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Drug Metabolism and Pharmacokinetics, Aurigene Discovery Technologies, Ltd. Bollaram Road, Miyapur Hyderabad 500 049, Telangana, Drug Metabolism and Pharmacokinetics, Aurigene Discovery Technologies, Ltd. Bollaram Road, Miyapur Hyderabad 500 049, Telangana, Drug Metabolism and Pharmacokinetics, Aurigene Discovery Technologies, Ltd. Bollaram Road, Miyapur Hyderabad 500 049, Telangana
Keywords:Polyherbal, biomarkers, herb-drug interaction, LC-MS/MS, cytochrome P450, SynacinnTM.
Abstract:Background: SynacinnTM contains five standardized herbal extracts of Orthosiphon Stamineus
(OS), Syzygium polyanthum (SZ), Curcuma xantorrizza (CX), Cinnamomum zeylanicum (CZ)
and Andrographis paniculata (AP) and is standardized against phytochemical markers of rosmarinic
acid, gallic acid, curcumin, catechin and andrographolide respectively. This herbal medicine has been
used as health supplement for diabetes. SynacinnTM
is recommended to be consumed as supplement to
the diabetic drugs. However, herb-drug interaction of SynacinnTM
polyherbal with present drugs is unknown.
Methods: This study was designed to investigate the effect of SynacinnTM and its individual
biomarkers on drug metabolizing enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19,
CYP2D6, CYP3A4 (Midazolam), CYP3A4 (Testosteron)), to assess its herb-drug interaction potential
through cytochrome P450 inhibition assay. This study was conducted using liquid chromatography-
tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes
against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and
CYP3A4 (Testosteron).
Results: Result showed that SynacinnTM at maximum concentration (5000 g/ml) 100% inhibit
CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4 (Midazolam) and CYP3A4
(Testosteron). IC50 values determined were 0.23, 0.60, 0.47, 0.78, 1.23, 0.99, 1.01, and 0.91 mg/ml
for CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4 (midazolam) and 3A4 (testosterone), respectively.
Meanwhile, all individual biomarkers showed no, less or moderate inhibitory effect towards all the
tested CYP450 except for curcumin that showed inhibition of CYP2C8 (91%), CYP2C9 (81%) and
CYP2C19 (72%) at 10µM.
Conclusion: Curcumin was found to be an active constituent that might contribute to the inhibition
of SynacinnTM against CYP2C8, CYP2C9 and CYP2C19. It can be suggested that SynacinnTM can
be consumed separately from a drug known to be metabolized by all tested CYP450 enzymes.
