Drug-drug interactions of plant alkaloids derived from herbal medicines on the phase II UGT enzymes: an introductory review.

Herbal medicines are widely used as alternative or complementary therapies to treat and prevent chronic diseases. However, these can lead to drug-drug interactions (DDIs) that affect the glucuronidation reaction of UDP glucuronosyltransferases (UGTs), which convert drugs into metabolites. Plant extracts derived from medicinal herbs contain a diverse array of compounds categorized into different functional groups.

Inhibition of UGT2B7 Enzyme Activity in Human and Rat Liver Microsomes by Herbal Constituents.

The co-use of conventional drug and herbal medicines may lead to herb-drug interaction via modulation of drug-metabolizing enzymes (DMEs) by herbal constituents. UDP-glucuronosyltransferases (UGTs) catalyzing glucuronidation are the major metabolic enzymes of Phase II DMEs. The in vitro inhibitory effect of several herbal constituents on one of the most important UGT isoforms, UGT2B7, in human liver microsomes (HLM) and rat liver microsomes (RLM) was investigated.

Mechanism of Action of Isolated Caffeic Acid and Epicatechin 3-gallate from against .

Background: The escalating dominance of resistant strains as infectious pathogen had urged the researchers to look for alternative and complementary drugs.

Objective: The objective of this study is to address the biological targets and probable mechanisms of action underlying the potent antibacterial effect of the isolated compounds from (L.) against .

Inhibitory Effects of , , , and Extracts and Constituents on Human Liver Glucuronidation Activity.

Background: , , and are commonly consumed as herbal medicines. However their effects on human liver glucuronidation activity are not yet evaluated.

Objective: In this study, we evaluate the inhibitory Effects of Andrographis paniculata, Gynura procumbens, Ficus deltoidea and Curcuma xanthorrhiza extracts and their constituents on human liver glucuronidation activity.

The Inhibition of Hepatic and Renal Glucuronidation of -Nitrophenol and 4-Methylumbelliferone by Oil Palm Empty Fruit Bunch Lignin and Its Main Oxidation Compounds.

Background: In order to develop oil palm empty fruit bunch (EFB) lignin as a nutraceutical and health supplement, the investigation of its potential in interacting with other drugs via inhibition of drug-metabolizing enzymes (DMEs) would ensure product safety.

Objective: The study was aimed to investigate the effect of oil palm EFB lignin and its main oxidation compounds on phase II DME UDP-glucuronosyltransferases (UGTs) in rat liver and kidney microsomes.

Materials And Methods: The -nitrophenol (-NP) and 4-methylumbelliferone (4-MU) were employed as probe substrates in glucuronidation assays.

Effects of Extracts and Their Constituents on Phase II Drug-metabolizing Enzymes Activity.

Background: is a native Indonesian plant and traditionally utilized for a range of illness including liver damage, hypertension, diabetes, and cancer.

Objective: The study determined the effects of extracts (ethanol and aqueous) and their constituents (curcumene and xanthorrhizol) on UDP-glucuronosyltransferase (UGT) and glutathione transferase (GST) activities.

Materials And Methods: The inhibition studies were evaluated both in rat liver microsomes and in human recombinant UGT1A1 and UGT2B7 enzymes.

Effects of mitragynine and 7-hydroxymitragynine (the alkaloids of Mitragyna speciosa Korth) on 4-methylumbelliferone glucuronidation in rat and human liver microsomes and recombinant human uridine 5'-diphospho-glucuronosyltransferase isoforms.

Background: Glucuronidation catalyzed by uridine 5'- diphospho-glucuronosyltransferase (UGT) is a major phase II drug metabolism reaction which facilitates drug elimination. Inhibition of UGT activity can cause drug-drug interaction. Therefore, it is important to determine the inhibitory potentials of drugs on glucuronidation.

Investigation of antioxidant and hepatoprotective activity of standardized Curcuma xanthorrhiza rhizome in carbon tetrachloride-induced hepatic damaged rats.

Curcuma xanthorrhiza (CX) has been used for centuries in traditional system of medicine to treat several diseases such as hepatitis, liver complaints, and diabetes. It has been consumed as food supplement and "jamu" as a remedy for hepatitis. Hence, CX was further explored for its potential as a functional food for liver related diseases.

Mitragyna speciosa Korth leaves extracts induced the CYP450 catalyzed aminopyrine-N-demethylase (APND) and UDP-glucuronosyl transferase (UGT) activities in male Sprague-Dawley rat livers.

Background: Mitragyna speciosa leaves have been abused by drug addicts as some of the alkaloids (mainly mitragynine) from the plant possess opiate and cocaine-like effects. These bring to its prohibition in Malaysia in 2004 as consumption of M. speciosa leaves has been perceived to lead to the abuse of other drugs such as cannabis and heroin.

Review on pharmacological activities of Cinnamomum iners Reinw. ex Blume.

This review describes the morphological, phytochemical and pharmacological properties of Cinnamomum iners Reinw. ex Blume (Lauraceae). The plant grows wild in the lowland of Malaysia, India, Myanmar, Indonesia, Thailand, Singapore, Brunei and Philippines.

Chemical composition, antioxidant and cytotoxicity activities of the essential oils of Myristica fragrans and Morinda citrifolia.

Background: In this study the chemical composition, antioxidant activities and cytotoxic effect of the essential oils of Myristica fragrans (nutmeg) and Morinda citrifolia (mengkudu) were determined.

Results: Thirty-eight compounds in nutmeg oil and six compounds in mengkudu oil were identified by gas chromatography–mass spectrometry. The free radical scavenging activity of nutmeg oil was superior of that mengkudu oil.

Brine shrimp lethality and acute oral toxicity studies on Swietenia mahagoni (Linn.) Jacq. seed methanolic extract.

Background: The seeds of Swietenia mahagoni have been applied in folk medicine for the treatment of hypertension, diabetes, malaria, amoebiasis, cough, chest pain, and intestinal parasitism. Here we are the first to report on the toxicity of the Swietenia mahagoni crude methanolic (SMCM) seed extract.

Methods: SMCM seed extract has been studied for its brine shrimp lethality and acute oral toxicity, in mice.

An antimicrobial compound isolated from Cinnamomum iners leaves with activity against methicillin-resistant Staphylococcus aureus.

This study was designed to investigate the antimicrobial activity of Cinnamomum iners standardized leave methanolic extract (CSLE), its fractions and isolated compounds. CSLE and fractions were subjected to disc diffusion, minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests using different Gram positive and Gram negative bacteria and yeast. Within the series of fractions tested, the ethyl acetate fraction was the most active, particularly against methicillin resistant Staphylococcus aureus (MRSA) and Escherichia coli, with MIC values of 100 and 200 µg/mL, respectively.

Effects of Andrographis paniculata and Orthosiphon stamineus extracts on the glucuronidation of 4-methylumbelliferone in human UGT isoforms.

The effects of Andrographis paniculata and Orthosiphon stamineus extracts on the in vitro glucuronidation of 4-methylumbelliferone (4MU) by recombinant human UGTs, UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7 and UGT2B15 were determined. The potential inhibitory effects of both of the extracts on the activity of each of the UGT isoforms were investigated using 4MU as the substrate. Incubations contained UDP-glucuronic acid (UDPGA) as the cofactor, MgCl(2), cell lysate of respective isoform, and 4MU at the approximate apparent K(m) or S(50) value of each isoform.

Determination of mitragynine in plasma with solid-phase extraction and rapid HPLC-UV analysis, and its application to a pharmacokinetic study in rat.

A new solid phase extraction method for rapid high performance liquid chromatography-UV determination of mitragynine in plasma has been developed. Optimal separation was achieved with an isocratic mobile phase consisting of acetonitrile-ammonium acetate buffer, 50 mM at pH 5.0 (50:50, v/v).

Evaluation of the antinociceptive activity and acute oral toxicity of standardized ethanolic extract of the rhizome of Curcuma xanthorrhiza Roxb.

Ethanolic extract of Curcuma xanthorrhiza was used to evaluate the analgesic and toxicity effects in vivo. The extract was standardized using GC-MS, which showed that 1 mg of Curcuma xanthorrhiza ethanolic extract contains 0.1238 mg of xanthorrhizol.

In vitro and in vivo effects of three different Mitragyna speciosa korth leaf extracts on phase II drug metabolizing enzymes--glutathione transferases (GSTs).

In the present study, we investigate the effects of three different Mitragyna speciosa extracts, namely methanolic, aqueous and total alkaloid extracts, on glutathione transferase-specific activity in male Sprague Dawley rat liver cytosol in vitro and in vivo. In the in vitro study, the effect of Mitragyna speciosa extracts (0.01 to 750 microg/mL) against the specific activity of glutathione transferases was examined in rat liver cytosolic fraction from untreated rats.

Activity of Eurycoma longifolia root extract against Plasmodium falciparum in vitro.

The habitats of Eurycoma longifolia Jack, a slender tree, are jungles in Malaysia and Indonesia. It belongs to the family Simaroubaceae and is a source of quassinoids with anabolic, antimalarial and cytostatic activity. In this study, conducted during 2008 in Mae Sot, Thailand, a standardized extract of E.

In Vitro antioxidant and xanthine oxidase inhibitory activities of methanolic Swietenia mahagoni seed extracts.

This study examines the in vitro antioxidant activities of the methanol extract of Swietenia mahagoni seeds (SMCM seed extract). The extract was screened for possible antioxidant activities by free radical scavenging activity (DPPH), xanthine oxidase inhibition (XOI), hydrogen peroxide scavenging activity (HPSA) and ferric-reducing antioxidant power (FRAP) assays. The total phenolic and flavonoid contents were also determined.

Evaluation of antioxidant and antibacterial activities of aqueous, methanolic and alkaloid extracts from Mitragyna speciosa (Rubiaceae family) leaves.

Studies on the antioxidant and antimicrobial activities of Mitragyna speciosa leaf extracts are lacking. In this study the antioxidant properties of water, methanolic and alkaloid M. speciosa leaf extracts were evaluated using the DPPH (2,2-diphenyl-1- picrylhydrazyl) radical scavenging method.