Displaying publications 1 - 20 of 31 in total

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  1. Chee JW, Amirul AA, Majid MI, Mansor SM
    Int J Pharm, 2008 Sep 1;361(1-2):1-6.
    PMID: 18584978 DOI: 10.1016/j.ijpharm.2008.05.007
    Copolyesters of 3-hydroxybutyrate (3HB) and 4-hydroxybutyrate (4HB) were produced by Cupriavidus sp. (USMAA2-4) (DSM 19379) from carbon sources of 1,4-butanediol and gamma-butyrolactone. The composition of copolyesters produced varied from 0 to 45 mol% 4HB, depending on the combination of carbon sources supplied. The P(3HB-co-4HB) films containing Mitragyna speciosa crude extract were prepared with the ratio varying from 10 to 40% (w/w). The in vitro crude extract release of the films was studied in 0.1M phosphate buffer (pH 7.4) at 37 degrees C. Although the release rate was slow, it was maintained at a constant rate. This suggests that the crude extract release was due to the polymer degradation because the amount of crude extract released was consistent. The amount of degradation was based on the films' dry weight loss, decrease in molecular weight and surface morphology changes. The degradation rate increased with the 4HB content. This showed that the polymer degradation is dependant on the molecular weight, crystallinity, thermal properties and water permeability. The different drug loading ratio which led to surface morphology changes also gave an effect on polymer degradation.
    Matched MeSH terms: Mitragyna/chemistry*
  2. Kong WM, Chik Z, Ramachandra M, Subramaniam U, Aziddin RE, Mohamed Z
    Molecules, 2011 Aug 29;16(9):7344-56.
    PMID: 21876481 DOI: 10.3390/molecules16097344
    The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC(50)) values of 0.78 µg/mL and 0.636 µg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC(50) of 39 µg/mL, and weak inhibition was detected for CYP2C19. The IC(50) of CYP2C19 could not be determined, however, because inhibition was <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were ACCESSused as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.
    Matched MeSH terms: Mitragyna/chemistry*
  3. Chan KB, Pakiam C, Rahim RA
    Bull Narc, 2005;57(1-2):249-56.
    PMID: 21338025
    Recently, the abuse of ketum, an indigenous psychoactive plant, has received a lot of attention in Malaysia. To help national law enforcement agencies control its abuse, the laboratory of the Forensic Division has developed a procedure for its positive identification. Botanical identification may not be practical or conclusive, owing to the wide range of ketum materials available on the market, including dry macerated leaves, powdered leaves and drinks. In order to confirm that a substance is, in fact, ketum or that a preparation is derived from ketum, gas chromatography-mass spectrometry is used to definitively identify the presence of the psychoactive principle mnitragynine.
    Matched MeSH terms: Mitragyna/chemistry*
  4. Parthasarathy S, Ramanathan S, Murugaiyah V, Hamdan MR, Said MI, Lai CS, et al.
    Forensic Sci Int, 2013 Mar 10;226(1-3):183-7.
    PMID: 23385139 DOI: 10.1016/j.forsciint.2013.01.014
    Mitragyna speciosa, a native plant of Thailand and Malaysia known as 'ketum', is a plant of considerable interest. It exhibits strong antinociceptive effect and yet, acts like a psychostimulant. Due to the affordability and its ease of availability, the abuse of this plant as a substitute for other banned narcotics has become a major concern in many societies. In countries such as Thailand, Myanmar, Australia and Malaysia, the use of ketum is illegal. However, for a person to be charged for possessing or selling ketum, a reliable analytical method is needed in order to detect and identify the plant and its products. Mitragynine is the major alkaloid of ketum. This compound manifests its antinociceptive effects by acting on the opioid receptors. Since M. speciosa contain large quantity of mitragynine and it is exclusive to the species, the present analytical method is developed and validated for the purpose of screening ketum products based on this unique compound as the analytical marker. The method uses a HPLC-DAD system with Inertsil C8 (4.6 mm × 150 mm, 5 μm) as the column and a mixture of acetonitrile and formic acid, 50:50 (v/v), as the mobile phase. This method not only detects mitragynine, it can also be used to quantify the amount of mitragynine in the sample. The limit of detection is 0.25 μg/ml, while the limit of quantification is 0.50 μg/ml. The method is quick, simple and reliable with an accuracy of 97.27-101.74% and coefficient of variations of between 0.91 and 3.96%. The method has been tested and found suitable for the identification and quantification of mitragynine in dried plants, a variety of ketum extracts, as well as ketum drink obtained from the market.
    Matched MeSH terms: Mitragyna/chemistry*
  5. Ramanathan S, Parthasarathy S, Murugaiyah V, Magosso E, Tan SC, Mansor SM
    Molecules, 2015 Mar 18;20(3):4915-27.
    PMID: 25793541 DOI: 10.3390/molecules20034915
    Varied pharmacological responses have been reported for mitragynine in the literature, but no supportive scientific explanations have been given for this. These studies have been undertaken without a sufficient understanding of the physicochemical properties of mitragynine. In this work a UV spectrophotometer approach and HPLC-UV method were employed to ascertain the physicochemical properties of mitragynine. The pKa of mitragynine measured by conventional UV (8.11 ± 0.11) was in agreement with the microplate reader determination (8.08 ± 0.04). Mitragynine is a lipophilic alkaloid, as indicated by a logP value of 1.73. Mitragynine had poor solubility in water and basic media, and conversely in acidic environments, but it is acid labile. In an in vitro dissolution the total drug release was higher for the simulated gastric fluid but was prolonged and incomplete for the simulated intestinal fluid. The hydrophobicity, poor water solubility, high variability of drug release in simulated biological fluids and acid degradable characteristics of mitragynine probably explain the large variability of its pharmacological responses reported in the literature. The determined physicochemical properties of mitragynine will provide a basis for developing a suitable formulation to further improve its solubility, stability and oral absorption for better assessment of this compound in preclinical studies.
    Matched MeSH terms: Mitragyna/chemistry*
  6. Sharma A, Kamble SH, León F, Chear NJ, King TI, Berthold EC, et al.
    Drug Test Anal, 2019 Aug;11(8):1162-1171.
    PMID: 30997725 DOI: 10.1002/dta.2604
    Kratom (Mitragyna speciosa) is a psychoactive plant popular in the United States for the self-treatment of pain and opioid addiction. For standardization and quality control of raw and commercial kratom products, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantification of ten key alkaloids, namely: corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine, mitragynine, mitraphylline, paynantheine, speciociliatine, and speciogynine. Chromatographic separation of diastereomers, or alkaloids sharing same ion transitions, was achieved on an Acquity BEH C18 column with a gradient elution using a mobile phase containing acetonitrile and aqueous ammonium acetate buffer (10mM, pH 3.5). The developed method was linear over a concentration range of 1-200 ng/mL for each alkaloid. The total analysis time per sample was 22.5 minutes. The analytical method was validated for accuracy, precision, robustness, and stability. After successful validation, the method was applied for the quantification of kratom alkaloids in alkaloid-rich fractions, ethanolic extracts, lyophilized teas, and commercial products. Mitragynine (0.7%-38.7% w/w), paynantheine (0.3%-12.8% w/w), speciociliatine (0.4%-12.3% w/w), and speciogynine (0.1%-5.3% w/w) were the major alkaloids in the analyzed kratom products/extracts. Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.
    Matched MeSH terms: Mitragyna/chemistry*
  7. Saref A, Suraya S, Singh D, Grundmann O, Narayanan S, Swogger MT, et al.
    J Ethnopharmacol, 2019 Jun 28;238:111876.
    PMID: 31014959 DOI: 10.1016/j.jep.2019.111876
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) is a traditional medicinal plant widely used in Southeast Asia for its opioid-like effects. Although kratom produces analgesia through binding of mitragynine and other alkaloids at the mu-opioid receptor (MOR), the association of long-term kratom use with adverse opioid-like effects remains unknown.

    AIM OF THE STUDY: To determine the self-reported prevalence and severity of opioid-related adverse effects after kratom initiation in a cohort of illicit opioid users.

    MATERIALS AND METHODS: A total of 163 illicit opioid users with current kratom use history were recruited through convenience sampling from the northern states of Peninsular Malaysia. Face-to-face interviews were conducted using a semi-structured questionnaire.

    RESULTS: Respondents were all males, majority Malays (94%, n = 154/163), with a mean age of 37.10 years (SD = 10.9). Most were single (65%, n = 106/163), had 11 years of education (52%, n = 85/163) and employed (88%, n = 144/163). Half reported using kratom for over >6 years (50%, n = 81/163), and 41% consumed >3 glasses of kratom daily (n = 67/163). Results from Chi-square analysis showed kratom initiation was associated with decreased prevalence of respiratory depression, constipation, physical pain, insomnia, depression, loss of appetite, craving, decreased sexual performance, weight loss and fatigue.

    CONCLUSIONS: Our findings indicate that kratom initiation (approximately 214.29 mg of mitragynine) was associated with significant decreases in the prevalence and severity of opioid adverse effects.

    Matched MeSH terms: Mitragyna/chemistry*
  8. Singh D, Narayanan S, Vicknasingam B
    Brain Res Bull, 2016 09;126(Pt 1):41-46.
    PMID: 27178014 DOI: 10.1016/j.brainresbull.2016.05.004
    INTRODUCTION: The objective of the paper was to highlight the differences in the traditional and non-traditional users of kratom in the South East Asian and Western contexts.

    METHOD: A literature survey of published kratom studies among humans was conducted. Forty published studies relevant to the objective were reviewed.

    RESULTS: Apart from the differences in the sources of supply, patterns of use and social acceptability of kratom within these two regions, the most interesting finding is its evolution to a recreational drug in both settings and the severity of the adverse effects of kratom use reported in the West. While several cases of toxicity and death have emerged in the West, such reports have been non-existent in South East Asia where kratom has had a longer history of use. We highlight the possible reasons for this as discussed in the literature. More importantly, it should be borne in mind that the individual clinical case-reports emerging from the West that link kratom use to adverse reactions or fatalities frequently pertained to kratom used together with other substances. Therefore, there is a danger of these reports being used to strengthen the case for legal sanction against kratom. This would be unfortunate since the experiences from South East Asia suggest considerable potential for therapeutic use among people who use drugs.

    CONCLUSION: Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.

    Matched MeSH terms: Mitragyna/chemistry
  9. Suhaimi FW, Yusoff NH, Hassan R, Mansor SM, Navaratnam V, Müller CP, et al.
    Brain Res Bull, 2016 09;126(Pt 1):29-40.
    PMID: 27018165 DOI: 10.1016/j.brainresbull.2016.03.015
    Kratom or its main alkaloid, mitragynine is derived from the plant Mitragyna speciosa Korth which is indigenous to Southeast Asian countries. This substance has become widely available in other countries like Europe and United States due to its opium- and coca-like effects. In this article, we have reviewed available reports on mitragynine and other M. speciosa extracts. M. speciosa has been proven to have a rewarding effect and is effective in alleviating the morphine and ethanol withdrawal effects. However, studies in human revealed that prolonged consumption of this plant led to dependence and tolerance while cessation caused a series of aversive withdrawal symptoms. Findings also showed that M. speciosa extracts possess antinociceptive, anti-inflammatory, anti-depressant, and muscle relaxant properties. Available evidence further supports the adverse effects of M. speciosa preparations, mitragynine on cognition. Pharmacological activities are mainly mediated via opioid receptors as well as neuronal Ca2+ channels, expression of cAMP and CREB protein and via descending monoaminergic system. Physicochemical properties of mitragynine have been documented which may further explain the variation in pharmacological responses. In summary, current researchs on its main indole alkaloid, mitragynine suggest both therapeutic and addictive potential but further research on its molecular effects is needed.
    Matched MeSH terms: Mitragyna/chemistry*
  10. Goh YS, Karunakaran T, Murugaiyah V, Santhanam R, Abu Bakar MH, Ramanathan S
    Molecules, 2021 Jun 17;26(12).
    PMID: 34204457 DOI: 10.3390/molecules26123704
    Mitragyna speciosa Korth (kratom) is known for its psychoactive and analgesic properties. Mitragynine is the primary constituent present in kratom leaves. This study highlights the utilisation of the green accelerated solvent extraction technique to produce a better, non-toxic and antinociceptive active botanical extract of kratom. ASE M. speciosa extract had a dry yield (0.53-2.91 g) and showed a constant mitragynine content (6.53-7.19%) when extracted with organic solvents of different polarities. It only requires a shorter extraction time (5 min) and a reduced amount of solvents (less than 100 mL). A substantial amount of total phenolic (407.83 ± 2.50 GAE mg/g and flavonoids (194.00 ± 5.00 QE mg/g) were found in ASE kratom ethanol extract. The MTT test indicated that the ASE kratom ethanolic leaf extract is non-cytotoxic towards HEK-293 and HeLa Chang liver cells. In mice, ASE kratom ethanolic extract (200 mg/kg) demonstrated a better antinociceptive effect compared to methanol and ethyl acetate leaf extracts. The presence of bioactive indole alkaloids and flavonols such as mitragynine, paynantheine, quercetin, and rutin in ASE kratom ethanolic leaf extract was detected using UHPLC-ESI-QTOF-MS/MS analysis supports its antinociceptive properties. ASE ethanolic leaf extract offers a better, safe, and cost-effective choice of test botanical extract for further preclinical studies.
    Matched MeSH terms: Mitragyna/chemistry*
  11. Chear NJ, León F, Sharma A, Kanumuri SRR, Zwolinski G, Abboud KA, et al.
    J Nat Prod, 2021 04 23;84(4):1034-1043.
    PMID: 33635670 DOI: 10.1021/acs.jnatprod.0c01055
    Ten indole and oxindole alkaloids (1-10) were isolated from the freshly collected leaves of Malaysian Mitragyna speciosa (Kratom). The chemical structures of these compounds were established on the basis of extensive 1D and 2D NMR and HRMS data analysis. The spectroscopic data of mitragynine oxindole B (4) are reported herein for the first time. The spatial configuration of mitragynine oxindole B (4) was confirmed by single-crystal X-ray diffraction. Simultaneous quantification of the isolated alkaloids in the M. speciosa leaf specimens collected from different locations in the northern region of Peninsular Malaysia was also performed using UPLC-MS/MS. The oxindole alkaloids (1-4) and the indole alkaloid (10) were assessed for binding affinity at opioid receptors. Corynoxine (1) showed high binding affinity to μ-opioid receptors with a Ki value of 16.4 nM. Further, corynoxine (1) was 1.8-fold more potent than morphine in rats subjected to a nociceptive hot plate assay. These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity of M. speciosa.
    Matched MeSH terms: Mitragyna/chemistry*
  12. Orio L, Alexandru L, Cravotto G, Mantegna S, Barge A
    Ultrason Sonochem, 2012 May;19(3):591-5.
    PMID: 22054912 DOI: 10.1016/j.ultsonch.2011.10.001
    Mitragyna speciosa, a tropical plant indigenous to Southeast Asia, is well known for its psychoactive properties. Its leaves are traditionally chewed by Thai and Malaysian farmers and manual labourers as it causes a numbing, stimulating effect. The present study aims to evaluate alkaloid yield and composition in the leaf extracts. For this purpose we have compared several non-conventional extraction techniques with classic procedures (room temperature or under heating). Dried M. speciosa leaves belonging to three batches of different origin (from Thailand, Malaysia and Indonesia) were extracted using ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and supercritical carbon dioxide extraction SFE-CO(2), using methanol, ethanol, water and binary mixtures. The extracts were compared using an HPLC/ESI-MS analysis of mitragynine and four other related alkaloids which were present in the alkaloid fraction. The extraction technique influences both the raw product yield and the relative alkaloid content of M. speciosa leaves. Of the several methods tested, MAE in a closed vessel at 110 °C (60 W, methanol/water 1:1) gave the highest alkaloid fraction amount, while UAE with an immersion horn at 25 °C (21.4 kHz, 50 W, methanol) showed the best yield for mitragynine. This work may prove to be a useful contribution to forensic, toxicological and pharmacognosy studies. Although the potential applications of M. speciosa alkaloids clearly need further investigation, these results may facilitate the scaling-up of their extraction.
    Matched MeSH terms: Mitragyna/chemistry*
  13. Apryani E, Hidayat MT, Moklas MA, Fakurazi S, Idayu NF
    J Ethnopharmacol, 2010 Jun 16;129(3):357-60.
    PMID: 20371280 DOI: 10.1016/j.jep.2010.03.036
    AIM OF THE STUDY: Mitragyna speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. However there is no scientific information about the effect of mitragynine on the cognitive performances. This study is designed to examine the working memory effects of mitragynine which is extracted from Mitragyna speciosa mature leaves.

    MATERIALS AND METHODS: The cognitive effect was studied using object location task and the motor activity in open-field test. Mitragynine 5, 10 and 15 mg/kg and were administered by intraperitoneal (IP) for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the control positive drug.

    RESULTS: In this study there is prominent effects on horizontal locomotor activity was observed. Mitragynine significantly reduced locomotor activity in open-field test compared with vehicle. In object location task mitragynine (5, 10 and 15 mg/kg) did not showed any significances discrimination between the object that had changed position than the object that had remain in a constant position.

    CONCLUSION: Our results suggest that chronic administration of mitragynine can altered the cognitive behavioral function in mice.

    Matched MeSH terms: Mitragyna/chemistry*
  14. Parthasarathy S, Bin Azizi J, Ramanathan S, Ismail S, Sasidharan S, Said MI, et al.
    Molecules, 2009;14(10):3964-74.
    PMID: 19924042 DOI: 10.3390/molecules14103964
    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. The amount of total phenolics and flavanoid contents were also estimated. The DPPH IC(50) values of the aqueous, alkaloid and methanolic extracts were 213.4, 104.81 and 37.08 microg/mL, respectively. The total phenolic content of the aqueous, alkaloid and methanolic extracts were 66.0 mg, 88.4, 105.6 mg GAE/g, respectively, while the total flavanoid were 28.2, 20.0 and 91.1 mg CAE/g respectively. The antioxidant activities were correlated with the total phenolic content. This result suggests that the relatively high antioxidant activity of the methanolic extract compared to aqueous and alkaloid extract could be possibly be due to its high phenolic content. The aqueous, alkaloid and methanolic extracts were screened for antimicrobial activity. The extracts showed antimicrobial activity against Salmonella typhi and Bacillus subtilis. The minimum inhibitory concentrations (MICs) of extracts determined by the broth dilution method ranged from 3.12 to 6.25 mg/mL. The alkaloid extract was found to be most effective against all of the tested organisms.
    Matched MeSH terms: Mitragyna/chemistry*
  15. Azizi J, Ismail S, Mordi MN, Ramanathan S, Said MI, Mansor SM
    Molecules, 2010 Jan 20;15(1):432-41.
    PMID: 20110902 DOI: 10.3390/molecules15010432
    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. Our data show concentration dependent inhibition of cytosolic GSTs when Mitragyna speciosa extract was added into the reaction mixture. At the highest concentration used, the methanolic extract showed the highest GSTs specific activity inhibition (61%), followed by aqueous (50%) and total alkaloid extract (43%), respectively. In in vivo study, three different dosages; 50, 100 and 200 mg/kg for methanolic and aqueous extracts and 5, 10 and 20 mg/kg for total alkaloid extract were given orally for 14 days. An increase in GST specific activity was generally observed. However, only Mitragyna speciosa aqueous extract with a dosage of 100 mg/kg showed significant results: 129% compared to control.
    Matched MeSH terms: Mitragyna/chemistry*
  16. Philipp AA, Wissenbach DK, Weber AA, Zapp J, Maurer HH
    Anal Bioanal Chem, 2011 Mar;399(8):2747-53.
    PMID: 21249338 DOI: 10.1007/s00216-011-4660-9
    Mitragyna speciosa (Kratom) is currently used as a drug of abuse. When monitoring its abuse in urine, several alkaloids and their metabolites must be considered. In former studies, mitragynine (MG), its diastereomer speciogynine (SG), and paynantheine and their metabolites could be identified in rat and human urine using LC-MS(n). In Kratom users' urines, besides MG and SG, further isomeric compounds were detected. To elucidate whether the MG and SG diastereomer speciociliatine (SC) and its metabolites represent further compounds, the phase I and II metabolites of SC were identified first in rat urine after the administration of the pure alkaloid. Then, the identified rat metabolites were screened for in the urine of Kratom users using the above-mentioned LC-MS(n) procedure. Considering the mass spectra and retention times, it could be confirmed that SC and its metabolites are so far the unidentified isomers in human urine. In conclusion, SC and its metabolites can be used as further markers for Kratom use, especially by consumption of raw material or products that contain a high amount of fruits of the Malaysian plant M. speciosa.
    Matched MeSH terms: Mitragyna/chemistry*
  17. Ismail I, Wahab S, Sidi H, Das S, Lin LJ, Razali R
    Curr Drug Targets, 2019;20(2):166-172.
    PMID: 28443503 DOI: 10.2174/1389450118666170425154120
    Kratom (Mitragyna speciosa), a naturally existing plant found in South-East Asia, is traditionally used as a herb to help elevate a person's energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (µ) and kappa (κ). The role of neural reward pathways linked to µ-opioid receptors and both dopaminergic and gamma-Aminobutyric acid (GABA)-ergic interneurons that express µ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of adverse effects and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, unique 'herbs" as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction.
    Matched MeSH terms: Mitragyna/chemistry*
  18. Smith LC, Lin L, Hwang CS, Zhou B, Kubitz DM, Wang H, et al.
    Chem Res Toxicol, 2019 01 22;32(1):113-121.
    PMID: 30380840 DOI: 10.1021/acs.chemrestox.8b00218
    The leaves of the Mitragynine speciosia tree (also known as Kratom) have long been chewed, smoked, or brewed into a tea by people in Southeastern Asian countries, such as Malaysia and Thailand. Just this past year, the plant Kratom gained popularity in the United States as a "legal opioid" and scheduling it as a drug of abuse is currently pending. The primary alkaloid found in Kratom is a μ-opioid receptor agonist, mitragynine, whose structure contains a promising scaffold for immunopharmacological use. Although Kratom is regarded as a safe opioid alternative, here we report the LD50 values determined for its two main psychoactive alkaloids, mitragynine and 7-hydroxymitragynine, as comparable to heroin in mice when administered intravenously. Given Kratom's recent emergence in the U.S., there is currently no diagnostic test available for law enforcement or health professionals, so we sought to design such an assay. Mitragynine was used as a starting point for hapten design, resulting in a hapten with an ether linker extending from the C9 position of the alkaloid. Bacterial flagellin (FliC) was chosen as a carrier protein for active immunization in mice, yielding 32 potential monoclonal antibodies (mAbs) for assay development. Antimitragynine mAbs in the range of micro- to nanomolar affinities were uncovered and their utility in producing a convenient lateral flow detection assay of human fluid samples was examined. Antibodies were screened for binding to mitragynine, 7-hydroxymitragynine, and performance in lateral flow assays. Two monoclonal antibodies were subcloned and further purified with 93 and 362 nM affinity to mitragynine. Test strip assays were optimized with a detection cut off of 0.5 μg/mL for mitragynine in buffer and urine (reflecting projected clinically relevant levels of drug in urine), which could be beneficial to law enforcement agencies and health professionals as the opioid epidemic in America continues to evolve.
    Matched MeSH terms: Mitragyna/chemistry*
  19. Hassan Z, Suhaimi FW, Ramanathan S, Ling KH, Effendy MA, Müller CP, et al.
    J. Psychopharmacol. (Oxford), 2019 07;33(7):908-918.
    PMID: 31081443 DOI: 10.1177/0269881119844186
    BACKGROUND: Mitragynine is the major alkaloid of Mitragyna speciosa (Korth.) or Kratom, a psychoactive plant widely abused in Southeast Asia. While addictive effects of the substance are emerging, adverse cognitive effects of this drug and neuropharmacological actions are insufficiently understood.

    AIMS: In the present study, we investigated the effects of mitragynine on spatial learning and synaptic transmission in the CA1 region of the hippocampus.

    METHODS: Male Sprague Dawley rats received daily (for 12 days) training sessions in the Morris water maze, with each session followed by treatment either with mitragynine (1, 5, or 10 mg/kg; intraperitoneally), morphine (5 mg/kg; intraperitoneally) or a vehicle. In the second experiment, we recorded field excitatory postsynaptic potentials in the hippocampal CA1 area in anesthetized rats and assessed the effects of mitragynine on baseline synaptic transmission, paired-pulse facilitation, and long-term potentiation. Gene expression of major memory- and addiction-related genes was investigated and the effects of mitragynine on Ca2+ influx was also examined in cultured primary neurons from E16-E18 rats.

    RESULTS/OUTCOMES: Escape latency results indicate that animals treated with mitragynine displayed a slower rate of acquisition as compared to their control counterparts. Further, mitragynine treatment significantly reduced the amplitude of baseline (i.e. non-potentiated) field excitatory postsynaptic potentials and resulted in a minor suppression of long-term potentiation in CA1. Bdnf and αCaMKII mRNA expressions in the brain were not affected and Ca2+ influx elicited by glutamate application was inhibited in neurons pre-treated with mitragynine.

    CONCLUSIONS/INTERPRETATION: These data suggest that high doses of mitragynine (5 and 10 mg/kg) cause memory deficits, possibly via inhibition of Ca2+ influx and disruption of hippocampal synaptic transmission and long-term potentiation induction.

    Matched MeSH terms: Mitragyna/chemistry
  20. Leong Bin Abdullah MFI, Tan KL, Mohd Isa S, Yusoff NS, Chear NJY, Singh D
    PLoS One, 2020;15(6):e0234639.
    PMID: 32525924 DOI: 10.1371/journal.pone.0234639
    BACKGROUND AND AIM: Kratom, or Mitragyna speciosa Korth., is a tropical plant that has been reported to exhibit opioid-like effects. Although opioids have been demonstrated to alter the lipid profile of regular users, data on the lipid-altering effects of kratom are scarce. This study aimed to compare the fasting lipid profile of regular kratom users to that of healthy subjects who do not use kratom. It also determined the association between various characteristics of kratom users and the serum triglycerides, total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels of regular kratom users.

    METHODS: A total of 200 participants (n = 100 kratom users and n = 100 healthy subjects who do not use kratom) were recruited for this analytical cross-sectional study. Data on sociodemographic status, kratom use characteristics, cigarette smoking, physical activity, body mass index (BMI), fasting serum lipid profile, and liver function were collected from all participants.

    RESULTS: The liver parameters of the study participants were within normal range. The serum total cholesterol and LDL of kratom users were significantly lower than those of healthy subjects who do not use kratom. There were no significant differences in the serum triglyceride and HDL levels. However, higher average daily frequency of kratom use and increasing age were associated with increased serum total cholesterol among kratom users. Other kratom use characteristics such as age of first kratom intake, duration of kratom use, and quantity of daily kratom intake were not associated with increased serum triglyceride, total cholesterol, LDL, and HDL levels.

    CONCLUSIONS: Our findings suggest regular kratom consumption was not linked to elevated serum lipids, except when there is a higher frequency of daily kratom intake. However, the study was limited by the small sample size, and hence a more comprehensive study with larger sample size is warranted to confirm the findings.

    Matched MeSH terms: Mitragyna/chemistry*
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