Displaying publications 41 - 60 of 127 in total

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  1. Gan CY, Etoh T, Hayashi M, Komiyama K, Kam TS
    J Nat Prod, 2010 Jun 25;73(6):1107-11.
    PMID: 20515042 DOI: 10.1021/np1001187
    Four new bisindole alkaloids of the Strychnos-Strychnos type, leucoridines A-D (1-4), were isolated from the stem-bark extract of Leuconotis griffithii. Alkaloids 1-4 showed moderate cytotoxicity against drug-sensitive and vincristine-resistant human KB cells.
    Matched MeSH terms: Indole Alkaloids/pharmacology*
  2. Ismail IS, Nagakura Y, Hirasawa Y, Hosoya T, Lazim MI, Lajis NH, et al.
    J Nat Prod, 2009 Oct;72(10):1879-83.
    PMID: 19757855 DOI: 10.1021/np9003849
    Four new chromone alkaloids, chrotacumines A-D (1-4), consisting of a 5,7-dihydroxy-2-methylchromone, an N-Me piperidine ring, and an ester side chain were isolated from Dysoxylum acutangulum, and their structures including absolute configurations were elucidated on the basis of spectroscopic data interpretation including 2D NMR, CD spectra, and X-ray analysis. The known compound rohitukine (5) showed moderate cytotoxicity against human HL-60 promyelocytic leukemia and HCT-116 colon cancer cells.
    Matched MeSH terms: Alkaloids/pharmacology
  3. 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: Alkaloids/pharmacology*
  4. Shaari K, Ling KC, Rashid ZM, Jean TP, Abas F, Raof SM, et al.
    Mar Drugs, 2009;7(1):1-8.
    PMID: 19370166 DOI: 10.3390/md7010001
    In a preliminary screen, Aaptos aaptos showed significant cytotoxic activity towards a panel of cell lines and was thus subjected to bioassay-guided isolation of the bioactive constituents. In addition to the known aaptamine, two new derivatives of the alkaloid were isolated from the bioactive chloroform fraction of the crude methanolic extract. Detailed analysis by NMR and mass spectroscopy enabled their identification to be 3-(phenethylamino)demethyl(oxy)aaptamine and 3-(isopentylamino)demethyl(oxy) aaptamine. The cytotoxic activities of the three alkaloids were further evaluated against CEM-SS cells.
    Matched MeSH terms: Alkaloids/pharmacology
  5. Nugroho AE, Hirasawa Y, Kawahara N, Goda Y, Awang K, Hadi AH, et al.
    J Nat Prod, 2009 Aug;72(8):1502-6.
    PMID: 19388660 DOI: 10.1021/np900115q
    A new bisindole alkaloid, bisnicalaterine A (1), consisting of two vobasine-type skeletons, and 3-epivobasinol (2) and 3-O-methylepivobasinol (3), with vobasine-type skeletons, were isolated from the leaves of Hunteria zeylanica, and their structures were elucidated on the basis of spectroscopic data and chemical correlation. Bisnicalaterine A showed moderate cytotoxicity against various human cancer cell lines.
    Matched MeSH terms: Indole Alkaloids/pharmacology
  6. Awang K, Mukhtar MR, Mustafa MR, Litaudon M, Shaari K, Mohamad K, et al.
    Nat Prod Res, 2007 Jul 10;21(8):704-9.
    PMID: 17616898
    The leaves of the Phoebe scortechinii (Gamb.) Kochummen Comb. Nov. (Lauraceae), afforded one new proaporphine-tryptamine dimer; (-)-phoebescortechiniine (1), along with two known ones; phoebegrandine A and phoebegrandine B. The proaporphine, tetrahydropronuciferine (2), was isolated for the first time as a natural product. The alkaloids were elucidated primarily by means of high field NMR and HRMS.
    Matched MeSH terms: Alkaloids/pharmacology
  7. Lim KH, Hiraku O, Komiyama K, Koyano T, Hayashi M, Kam TS
    J Nat Prod, 2007 Aug;70(8):1302-7.
    PMID: 17665953
    Nine new indole alkaloids, rhazinoline (1), 19(S)-methoxytubotaiwine (2), 19(R)-methoxytubotaiwine (3), kopsamidine A (4), kopsamidine B (5), kopsinidine A (6), kopsinidine B (7), paucidactine C (8), and pericine N-oxide (9), in addition to several recently reported novel indoles and 34 other known ones, were obtained from the stem-bark extract of the Malayan Kopsia arborea. The structures were determined using NMR and MS analysis. Valparicine (12) showed pronounced cytotoxic effects against KB and Jurkat cells (IC(50) 13.0 and 0.91 microM, respectively).
    Matched MeSH terms: Indole Alkaloids/pharmacology*
  8. Awang K, Mukhtar MR, Hadi AH, Litaudon M, Latip J, Abdullah NR
    Nat Prod Res, 2006 May 20;20(6):567-72.
    PMID: 16835089
    The alkaloidal extract of the leaves of Phoebe grandis (nees) merr. have provided two new minor alkaloids; phoebegrandine D (1), a proaporphine-tryptamine dimer, and phoebegrandine E (2), an indoloquinolizidine. This is the first report on the occurrence of an indoloquinolizidine in the Phoebe species. The crude extract also exhibited antiplasmodial activity (IC50<8 microg mL-1). The structures of the novel compounds were elucidated by spectroscopic methods, notably 2D NMR and HRMS.
    Matched MeSH terms: Alkaloids/pharmacology
  9. Singh D, Müller CP, Vicknasingam BK, Mansor SM
    J Psychoactive Drugs, 2015 5 8;47(2):125-31.
    PMID: 25950592 DOI: 10.1080/02791072.2015.1012610
    Kratom (Mitragyna speciosa) is an indigenous plant known for its traditional medicinal use, and for its addiction potential, in Southeast Asia. In recent years, kratom and its major alkaloid, mitragynine, spread worldwide with largely unknown effects on behavior and mental health. Recent studies show that kratom use can lead to dependence and that mitragynine works as an addictive drug in animal studies. Nevertheless, kratom preparations were also suggested as a less harmful substitute in opiate withdrawal. Potential side-effects of prolonged kratom use, however, are currently unclear. The aim of this study was to investigate the social functioning of regular kratom users in Malaysia. A cross-sectional survey was carried out in three northern states of Peninsular Malaysia investigating 293 regular kratom consumers using the Addiction Severity Index in a snowball sampling technique. Findings showed that regular kratom users do not experience major impairments in their social functioning, despite being dependent on kratom for prolonged periods. Our findings suggest that chronic kratom administration does not significantly impair social functioning of users in a natural context in Malaysia.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
  10. Mok SL, Yoganathan K, Lim TM, Kam TS
    J Nat Prod, 1998 Mar;61(3):328-32.
    PMID: 9544563
    Intravenous injection of the aspidofractinine alkaloid, kopsingine (1, 0.2-10.0 mg/kg) from Kopsia teoi, produced dose-related decreases in the mean arterial blood pressure and heart rate in anesthetized spontaneously hypertensive rats, which were similar to those seen in normotensive controls. Minor modifications in the molecular structure of kopsingine, as in kopsaporine (2, the 12-demethoxy derivative of kopsingine) and 14,15-dihydrokopsingine (4), did not significantly alter the hypotensive responses, whereas a more drastic change in the structure, as in the heptacyclic kopsidine A (3) and the 3-to-17 oxo-bridged compound 5, resulted in an increase in blood pressure. The antihypertensive effects of kopsingine (1) and its congeners (2 and 4) along with the pressor effects produced by the heptacyclic oxo-bridged compounds (5 and 3) could be ascribed to central as well as peripheral actions.
    Matched MeSH terms: Alkaloids/pharmacology
  11. Mok JS, Chang P, Lee KH, Kam TS, Goh SH
    J Ethnopharmacol, 1992 Jun;36(3):219-23.
    PMID: 1434680
    Among several alkaloids, including dimeric indoles, isolated from Uncaria callophylla, gambirine which is an alkaloid unique to this plant, has been found to be another hypotensive principle from the plant. Intravenous injections of gambirine in the dose range of 0.2 to 10.0 mg/kg caused a dose-related fall in both systolic and diastolic blood pressures as well as heart rate. At all doses gambirine showed a prompt onset of action and at the higher doses (5.0-10 mg/kg), marked persistence of hypotension accompanied by severe bradycardia were observed. In addition, higher doses of gambirine produced a more marked decrease in diastolic than systolic pressure while at lower doses both decreased equally. It is suggested that the hypotensive effect of gambirine may be peripheral in origin and is associated, at least in part, with a cardiac action.
    Matched MeSH terms: Alkaloids/pharmacology*
  12. Obeng S, Kamble SH, Reeves ME, Restrepo LF, Patel A, Behnke M, et al.
    J Med Chem, 2020 01 09;63(1):433-439.
    PMID: 31834797 DOI: 10.1021/acs.jmedchem.9b01465
    Selected indole-based kratom alkaloids were evaluated for their opioid and adrenergic receptor binding and functional effects, in vivo antinociceptive effects, plasma protein binding, and metabolic stability. Mitragynine, the major alkaloid in Mitragyna speciosa (kratom), had higher affinity at opioid receptors than at adrenergic receptors while the vice versa was observed for corynantheidine. The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology*
  13. Taha H, Hadi AH, Nordin N, Najmuldeen IA, Mohamad K, Shirota O, et al.
    Chem Pharm Bull (Tokyo), 2011;59(7):896-7.
    PMID: 21720044
    Pseuduvarines A (1) and B (2), two new dioxoaporphine alkaloids with an amino moiety, were isolated from the stem bark of Pseuduvaria rugosa and their structures were elucidated by combination of 2D-NMR spectroscopic analysis. Pseuduvarines A (1) and B (2) showed cytotoxicity against MCF7, HepG2, and HL-60 (1: IC₅₀, 0.9, 21.7, and >50.0 µM, respectively, 2: IC₅₀ >50.0, 15.7, and 12.4 µM, respectively).
    Matched MeSH terms: Alkaloids/pharmacology
  14. Morita H, Nugroho AE, Nagakura Y, Hirasawa Y, Yoshida H, Kaneda T, et al.
    Bioorg Med Chem Lett, 2014 Jun 1;24(11):2437-9.
    PMID: 24767841 DOI: 10.1016/j.bmcl.2014.04.020
    Four new chromone alkaloids, chrotacumines G-J (1-4), have been isolated from the barks of Dysoxylum acutangulum. Their structures and absolute configurations were elucidated on the basis of NMR and CD data. Chrotacumines G and J (1 and 4) showed osteoclast differentiation inhibitory activity in a dose dependent manner.
    Matched MeSH terms: Alkaloids/pharmacology*
  15. Ahmad H, Ahmad S, Shah SAA, Latif A, Ali M, Khan FA, et al.
    Bioorg Med Chem, 2017 07 01;25(13):3368-3376.
    PMID: 28457693 DOI: 10.1016/j.bmc.2017.04.022
    Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6β-Methoxy, 9β-dihydroxylheteratisine (1), 1α,11,13β-trihydroxylhetisine (2), 6,15β-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.
    Matched MeSH terms: Alkaloids/pharmacology*
  16. Ahmad H, Ahmad S, Ali M, Latif A, Shah SAA, Naz H, et al.
    Bioorg Chem, 2018 08;78:427-435.
    PMID: 29698893 DOI: 10.1016/j.bioorg.2018.04.008
    Three new norditerpenoids alkaloids, 1β-hydroxy,14β-acetyl condelphine (1), jadwarine-A (2), jadwarine-B (3) along with two known alkaloids isotalatizidine hydrate (4) and dihydropentagynine (5) were isolated from medicinal plant Delphinium denudatum. The structures of natural products 1-5 were established on the basis of HR-EIMS, 1H and 13C NMR (1D & 2D) spectroscopic data as well as by comparison from literature data. The structures of compound 1 and 4 were also confirmed by single crystal X-ray diffraction studies. In-vitro AChE and BChE enzyme inhibitory activities of compounds 1-5 and molecular docking studies were performed to investigate the possible molecular inhibitory mechanism of the isolated natural products. Compound 2, 4 and 5 showed competitive inhibitory effects by inhibiting AChE and BChE, respectively, while 1 and 3 showed non-competitive inhibition. This work is the first report that provides a supporting evidence about the use of constituents of Delphinium denudatum in cerebral dementia and Alzheimer diseases.
    Matched MeSH terms: Alkaloids/pharmacology*
  17. Shipton FN, Khoo TJ, Hossan MS, Wiart C
    J Ethnopharmacol, 2017 Feb 23;198:91-97.
    PMID: 28049063 DOI: 10.1016/j.jep.2016.12.045
    ETHNOPHARMACOLOGICAL RELEVANCE: Pericampylus glaucus is a climbing plant found across Asia and used in traditional medicine to treat a number of conditions including splenomegaly, fever, cough, laryngitis, pulmonary disease, asthma, headache, hair loss, snake bite, boar bite, factures, boils, tumours, tetanus, rheumatic pain, itches and eclampsia.

    AIM OF THE STUDY: To test extracts of P. glaucus in a number of bioassays and determine the legitimacy of its traditional use.

    MATERIALS AND METHODS: The stems, leaves, roots and fruits of P. glaucus were collected and extracted sequentially with hexane, chloroform and ethanol, respectively. The anti-inflammatory activity was assessed by testing the ability of the extracts to inhibit heat induced protein denaturation, stabilise human red blood cells under hypotonic stress and by testing the inhibitory activity of the extracts against cyclooxygenases 1 and 2. Cytotoxicity was tested using the human lung epithelial cell line MRC-5 and nasopharangeal carcinoma cell line HK1 in the MTT assay.

    RESULTS: Many of the samples showed an ability to prevent heat induced protein denaturation, as well as prevent lysis of red blood cells. Most of the extracts demonstrated inhibitory activity towards both of the COX enzymes. The ethanol extracts tended to demonstrate greater toxicity than other extracts, with some of the other extracts significantly enhancing growth and metabolism of the cells.

    CONCLUSION: The benefit of P. glaucus for the treatment of diseases related to inflammation and cancer was supported by the in vitro assays adopted in this study.

    Matched MeSH terms: Alkaloids/pharmacology*
  18. 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: Alkaloids/pharmacology*
  19. Prozialeck WC, Avery BA, Boyer EW, Grundmann O, Henningfield JE, Kruegel AC, et al.
    Int J Drug Policy, 2019 08;70:70-77.
    PMID: 31103778 DOI: 10.1016/j.drugpo.2019.05.003
    Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.
    Matched MeSH terms: Secologanin Tryptamine Alkaloids/pharmacology
  20. Domnic G, Jeng-Yeou Chear N, Abdul Rahman SF, Ramanathan S, Lo KW, Singh D, et al.
    J Ethnopharmacol, 2021 Oct 28;279:114391.
    PMID: 34224811 DOI: 10.1016/j.jep.2021.114391
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) or kratom is a medicinal plant indigenous to Southeast Asia. The leaf of M. speciosa is used as a remedy in pain management including cancer related pain, in a similar way as opioids and cannabis. Despite its well-known analgesic effect, there is a scarce of information on the cancer-suppressing potential of M. speciosa and its active constituents.

    AIM OF THE STUDY: To assess the potential applicability of M. speciosa alkaloids (mitragynine, speciociliatine or paynantheine) as chemosensitizers for cisplatin in Nasopharyngeal carcinoma (NPC) cell lines.

    MATERIALS AND METHODS: The cytotoxic effects of the extracts, fractions and compounds were determined by conducting in vitro cytotoxicity assays. Based on the cytotoxic screening, the alkaloid extract of M. speciosa exhibited potent inhibitory effect on the NPC cell line NPC/HK1, and therefore, was chosen for further fractionation and purification. NPC cell lines NPC/HK1 and C666-1 were treated with combinations of cisplatin and M. speciosa alkaloids combinations in 2D monolayer culture. The effect of cisplatin and mitragynine as a combination on cell migration was tested using in vitro wound healing and spheroid invasion assays.

    RESULTS: In our bioassay guided isolation, both methanolic and alkaloid extracts showed mild to moderate cytotoxic effect against the NPC/HK1 cell line. Both NPC cell lines (NPC/HK1 and C666-1) were insensitive to single agent and combination treatments of the M. speciosa alkaloids. However, mitragynine and speciociliatine sensitized the NPC/HK1 and C666-1 cells to cisplatin at ~4- and >5-fold, respectively in 2D monolayer culture. The combination of mitragynine and cisplatin also significantly inhibited cell migration of the NPC cell lines. Similarly, the combination also of mitragynine and cisplatin inhibited growth and invasion of NPC/HK1 spheroids in a dose-dependent manner. In addition, the spheroids did not rapidly develop resistance to the drug combinations at higher concentrations over 10 days.

    CONCLUSION: Our data indicate that both mitragynine and speciociliatine could be potential chemosensitizers for cisplatin. Further elucidation focusing on the drug mechanistic studies and in vivo studies are necessary to support delineate the therapeutic applicability of M. speciosa alkaloids for NPC treatment.

    Matched MeSH terms: Indole Alkaloids/pharmacology*
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