Displaying publications 81 - 100 of 139 in total

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  1. Wong SK, Wong SP, Sim KS, Lim SH, Low YY, Kam TS
    J Nat Prod, 2019 07 26;82(7):1902-1907.
    PMID: 31241923 DOI: 10.1021/acs.jnatprod.9b00255
    Three new alkaloids were isolated from the bark extract of the Malayan Kopsia arborea, viz., arbophyllidine (1), an unusual pentacyclic, monoterpenoid indole characterized by an absence of oxygen atoms and incorporating a new carbon-nitrogen skeleton, and arbophyllinines A (2) and B (3), two pentacyclic corynanthean alkaloids incorporating a hydroxyethyl-substituted tetrahydrofuranone ring. The structures of the alkaloids were deduced based on analysis of the MS and NMR data and confirmed by X-ray diffraction analyses. The absolute configuration of arbophyllidine (1) was established based on experimental and calculated ECD data, while that of arbophyllinine A was based on X-ray diffraction analysis (Cu Kα). A reasonable biosynthetic route to arbophyllidine (1) from a pericine precursor is presented. Arbophyllidine (1) showed pronounced in vitro growth inhibitory activity against the HT-29 human cancer cell line with IC50 6.2 μM.
  2. Subermaniam K, Yow YY, Lim SH, Koh OH, Wong KH
    Saudi J Biol Sci, 2020 Jun;27(6):1435-1445.
    PMID: 32489279 DOI: 10.1016/j.sjbs.2020.04.042
    Oxidative damage has been associated with the pathophysiology of depression. Macroalgae are equipped with antioxidant defense system to counteract the effects of free radicals. We explored the use of Malaysian Padina australis to attenuate high dose corticosterone-mediated oxidative damage in a cellular model mimicking depression. Fresh specimen of P. australis was freeze-dried and extracted sequentially with hexanes, ethyl acetate and ethanol. The extracts were screened for their phytochemical contents and antioxidant activities. Ethanol extract demonstrated the most potent antioxidant capacity and was selected for subsequent assays against high dose corticosterone of 600 µM-mediated oxidative damage in the rat pheochromocytoma (PC12) cells. The corticosterone reduced the cell viability, glutathione (GSH) level, aconitase activity, and mitochondrial membrane potential (MMP); and increased the lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) level and apoptosis. However, the extent of oxidative damage was reversed by 0.25-0.5 mg/mL ethanol extract suggesting a possible role of P. australis-based antioxidants in the mitochondrial defense against constant ROS generation and regulation of antioxidant pathway. The effects were similar to that of desipramine, a tricyclic antidepressant. Our findings indicate that P. australis can be developed as a mitochondria-targeted antioxidant to mitigate antidepressant-like effects.
  3. Yeap JS, Tan CH, Yong KT, Lim KH, Lim SH, Low YY, et al.
    Phytochemistry, 2020 Aug;176:112391.
    PMID: 32387883 DOI: 10.1016/j.phytochem.2020.112391
    Fourteen previously undescribed alkaloids comprising two N-1-hydroxymethylmacroline alkaloids, one talpinine-type oxindole acetal, a pair of equilibrating talpinine-type oxindole hemiacetals, eight oxidized derivatives of sarpagine- and akuammiline-type indole alkaloids, in addition to alstochalotine a diastereomer of gelsochalotine recently isolated from Gelsemium elegans, were isolated from the leaf and stem-bark extracts of Alstonia penangiana. The structures and relative configurations of these alkaloids were established using NMR, MS, and in one instance, confirmed by X-ray diffraction analysis. An NMR-based method is described as a useful chemotaxonomic tool for differentiating between A. penangiana and A. macrophylla. Several of the alkaloids isolated showed appreciable growth inhibitory effects when tested against a number of human cancer cell lines.
  4. Galka JM, Wang M, Azwa I, Gibson B, Lim SH, Shrestha R, et al.
    Transgend Health, 2020 Dec;5(4):258-266.
    PMID: 33644315 DOI: 10.1089/trgh.2020.0003
    Introduction: Transgender women (TW) face one of the highest HIV burdens worldwide. In Malaysia, 12.4% of TW are HIV infected, ∼30-fold higher than in the Malaysian adult population. Pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy, however, little is known about TW's willingness to use PrEP or their preferences for receiving PrEP. This study examined the correlates of Malaysian TW's willingness to use PrEP and their attitudes and preferences related to delivery of PrEP and PrEP-related care. Methods: Between June and August 2017, 361 TW in Malaysia completed an online survey about their knowledge of and willingness to use PrEP for HIV prevention. Results: Only 20.2% of participants had ever previously heard of PrEP and none were currently taking PrEP. The majority (82.5%) expressed high willingness to take PrEP and most participants met the World Health Organization (WHO) indication for PrEP (82.3%). In the multivariate model, lifetime hormone use, prior postexposure prophylaxis use, and having completed a high school education were associated with higher willingness to use PrEP, while injection drug use, older age, and Chinese ethnicity were associated with lower PrEP willingness. Conclusion: TW in Malaysia are highly willing to use PrEP for HIV prevention. Differences in willingness to use PrEP identified by education, ethnicity, substance abuse, and age suggest different strategies may be needed to scale-up PrEP for this diverse community of TW.
  5. Alcantara VS, Lim GH, Lim SH, Sultana R, Lee JA
    J Surg Oncol, 2017 Apr;115(5):523-537.
    PMID: 28168712 DOI: 10.1002/jso.24559
    BACKGROUND AND OBJECTIVES: Triple negative breast cancer (TNBC) carries a worse prognosis compared to the other subtypes. There have been conflicting studies that race may impact the prognosis of TNBC patients. We aim to determine the incidence and prognosis of TNBC among the different ethnic races in Singapore, and to determine its associated risk factors for prognosis.

    METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS).

    RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients.

    CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.

  6. Chong KW, Yeap JS, Lim SH, Weber JF, Low YY, Kam TS
    J Nat Prod, 2017 11 22;80(11):3014-3024.
    PMID: 29087707 DOI: 10.1021/acs.jnatprod.7b00621
    Reexamination of the absolute configuration of recently isolated eburnane alkaloids from Malaysian Kopsia and Leuconotis species by X-ray diffraction analysis and ECD/TDDFT has revealed the existence of biosynthetic enantiodivergence. Three different scenarios are discerned with respect to the composition of the enantiomeric eburnane alkaloids in these plants: first, where the new eburnane congeners possess the same C-20, C-21 absolute configurations as the common eburnane alkaloids (eburnamonine, eburnamine, isoeburnamine, eburnamenine) occurring in the same plant; second, where the new eburnane congeners possess opposite or enantiomeric C-20, C-21 absolute configurations compared to the common eburnane alkaloids found in the same plant; and, third, where the four common eburnane alkaloids were isolated as racemic or scalemic mixtures, while the new eburnane congeners were isolated as pure enantiomers with a common C-20, C-21 configuration (20α, 21α). Additionally, the same Kopsia species (K. pauciflora) found in two different geographical locations (Peninsular Malaysia and Malaysian Borneo) showed different patterns in the composition of the enantiomeric eburnane alkaloids. Revision of the absolute configurations of a number of new eburnane congeners (previously assigned based on the assumption of a common biogenetic origin to that of the known eburnane alkaloids co-occurring in the same plant) is required based on the present results.
  7. Ezeoke MC, Krishnan P, Sim DS, Lim SH, Low YY, Chong KW, et al.
    Phytochemistry, 2018 Feb;146:75-81.
    PMID: 29247894 DOI: 10.1016/j.phytochem.2017.12.003
    From the leaves of Elaeocarpus tectorius (Lour.) Poir. four previously undescribed phenethylamine-containing alkaloids were isolated, namely, tectoricine, possessing an unprecedented isoquinuclidinone ring system incorporating a phenethylamine moiety, tectoraline, representing a rare alkamide incorporating two phenethylamine moieties, and tectoramidines A and B, representing the first naturally occurring trimeric and dimeric phenethylamine alkaloids incorporating an amidine function. The structures of these alkaloids were established by detailed spectroscopic analysis. The absolute configuration of tectoricine was determined by comparison of the experimental and calculated ECD spectra. Plausible biosynthetic pathways to the four alkaloids are proposed.
  8. Lim SH, Nowak-Sliwinska P, Kamarulzaman FA, van den Bergh H, Wagnières G, Lee HB
    Photochem Photobiol, 2010 Mar-Apr;86(2):397-402.
    PMID: 20074086 DOI: 10.1111/j.1751-1097.2009.00684.x
    In this study, the photodynamic therapy (PDT) induced efficacy of a semi-synthesized analogue 15(1)-hydroxypurpurin-7-lactone dimethyl ester or G2, in terms of chick chorioallantoic membrane blood vessel occlusion was evaluated in reference to verteporfin. Early formulation studies showed that G2 prepared in a system of cremophor EL 2.5% and ethanol 2.5% in saline was biocompatible up to 20 microL volume of injection. Following injection, G2 accumulation peaked within the first minute and its extravasation from intra- to extra-vascular occurred somewhat slower as compared with verteporfin. In the PDT study, closure of capillaries and small neovessels was observed with 4 microg per embryo of G2 and a light dose of 20 J cm(-2) at a fluence rate of 40 mW cm(-2) filtered at 400-440 nm-a result that may be considered optimum for the treatment of age-related macular degeneration (AMD). Also, partial occlusion of the large vessels was observed using the same dose of G2 and light-an effect which is desirable for cancer treatment. From this study, we conclude that G2 has the potential to be developed as a therapeutic agent for photodynamic treatment for AMD and cancer.
  9. Tang SY, Tan CH, Sim KS, Yong KT, Lim KH, Low YY, et al.
    Phytochemistry, 2023 Apr;208:113587.
    PMID: 36646163 DOI: 10.1016/j.phytochem.2023.113587
    Eight undescribed iboga alkaloids, polyneurines A-H, were isolated from the bark of Tabernaemontana polyneura. The structures of these alkaloids were established by interpretation of the MS and NMR data, while the configurations were determined using GIAO NMR calculations and DP4+ probability analysis, TDDFT-ECD method, or X-ray diffraction analysis. Polyneurine A possesses a γ-lactone unit embedded within the iboga skeleton, while polyneurines D and E incorporate a formylmethyl moiety at C-3 of the iboga skeleton. Biosynthetic pathways towards the formation of polyneurines A, C, D, and E were proposed.
  10. Lim SH, Chin NL, Sulaiman A, Tay CH, Wong TH
    Foods, 2023 Jan 31;12(3).
    PMID: 36766121 DOI: 10.3390/foods12030592
    The safety, shelf life, and quality of fresh cow milk treated using industrial High-Pressure Processing (HPP) treatment at 600 MPa for 10 min was studied to identify the novelty of this non-thermal technology in milk processing. Changes in microbiological and physicochemical properties, including nutritional values of vitamins and amino acid profiles, were measured for a 60-day storage period at 6 °C +/- 1 °C. The HPP treatment produced milk that met all microbial safety requirements and exhibited a shelf life beyond 60 days in a hot and humid region. High physicochemical stability was achieved, with consistent pH and undetectable titratable acidity. The HPP treatment successfully retained all vitamins and minerals, including calcium (99.3%), phosphorus (99.4%), and magnesium (99.1%). However, the 60-day storage caused some degradation of Vitamin A (25%), B3 (91%), B5 (35%), B6 (80%), and C (85%), and minerals, including potassium (5%) and zinc (18%) when compared with fresh milk. This research has shown that the adoption of advanced treatment with HPP is very beneficial to the dairy industry in preserving milk quality in terms of its physicochemical and nutritional properties and extending its storage shelf life beyond 60 days.
  11. Subermaniam K, Lew SY, Yow YY, Lim SH, Yu WS, Lim LW, et al.
    Iran J Basic Med Sci, 2023;26(6):669-679.
    PMID: 37275754 DOI: 10.22038/IJBMS.2023.67835.14842
    OBJECTIVES: Neuroinflammation and microglial activation are pathological features in central nervous system disorders. Excess levels of reactive oxygen species (ROS) and pro-inflammatory cytokines have been implicated in exacerbation of neuronal damage during chronic activation of microglial cells. Padina australis, a brown macroalga, has been demonstrated to have various pharmacological properties such as anti-neuroinflammatory activity. However, the underlying mechanism mediating the anti-neuroinflammatory potential of P. australis remains poorly understood. We explored the use of Malaysian P. australis in attenuating lipopolysaccharide (LPS)-stimulated neuroinflammation in BV2 microglial cells.

    MATERIALS AND METHODS: Fresh specimens of P. australis were freeze-dried and subjected to ethanol extraction. The ethanol extract (PAEE) was evaluated for its protective effects against 1 µg/ml LPS-stimulated neuroinflammation in BV2 microglial cells.

    RESULTS: LPS reduced the viability of BV2 microglia cells and increased the levels of nitric oxide (NO), prostaglandin E2 (PGE2), intracellular reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). However, the neuroinflammatory response was reversed by 0.5-2.0 mg/ml PAEE in a dose-dependent manner. Analysis of liquid chromatography-mass spectrometry (LC-MS) of PAEE subfractions revealed five compounds; methyl α-eleostearate, ethyl α-eleostearate, niacinamide, stearamide, and linoleic acid.

    CONCLUSION: The protective effects of PAEE against LPS-stimulated neuroinflammation in BV2 microglial cells were found to be mediated by the suppression of excess levels of intracellular ROS and pro-inflammatory mediators and cytokines, denoting the protective role of P. australis in combating continuous neuroinflammation. Our findings support the use of P. australis as a possible therapeutic for neuroinflammatory and neurodegenerative diseases.

  12. Lim SH, Tan TL, Ngo PW, Lee LY, Ting SY, Tan HJ
    Med J Malaysia, 2023 Mar;78(2):241-249.
    PMID: 36988537
    INTRODUCTION: Time is the greatest challenge in stroke management. This study aimed to examine factors contributing to prehospital delay and decision delay among stroke patients.

    MATERIALS AND METHODS: A cross-sectional study involving acute stroke patients admitted to Seri Manjung Hospital was conducted between August 2019 and October 2020 via faceto- face interview. Prehospital delay was defined as more than 120 minutes taken from recognition of stroke symptoms till arrival in hospital, while decision delay was defined as more than 60 minutes taken from recognition of stroke symptoms till decision was made to seek treatment.

    RESULTS: The median prehospital delay of 102 enrolled patients was 364 minutes (IQR 151.5, 1134.3) while the median for decision delay was 120 minutes (IQR 30.0, 675.0). No history of stroke (adj. OR 4.15; 95% CI 1.21, 14.25; p=0.024) and unaware of thrombolysis service (adj. OR 17.12; 95% CI 1.28, 229.17; p=0.032) were associated with higher odds of prehospital delay, while Indian ethnicity (adj. OR 0.09; 95% CI 0.02, 0.52; p=0.007) was associated with lower odds of prehospital delay as compared to Malay ethnicity. On the other hand, higher National Institutes of Health Stroke Scale (NIHSS) score (adj. OR 0.86; 95% CI 0.78, 0.95; p=0.002) was associated with lower odds of decision delay.

    CONCLUSION: Public awareness is crucial to shorten prehosital delay and decision delay for better patients' outcomes in stroke. Various public health campaigns are needed to improve the awareness for stroke.

  13. Mburu G, Igbinedion E, Lim SH, Paing AZ, Yi S, Elbe S, et al.
    BMJ Open, 2020 Jan 08;10(1):e031844.
    PMID: 31919124 DOI: 10.1136/bmjopen-2019-031844
    INTRODUCTION: Private sector provision of HIV treatment is increasing in low-income and middle-income countries (LMIC). However, there is limited documentation of its outcomes. This protocol reports a proposed systematic review that will synthesise clinical outcomes of private sector HIV treatment in LMIC.

    METHODS AND ANALYSIS: This review will be conducted in accordance with the preferred reporting items for systematic review and meta-analyses protocols. Primary outcomes will include: (1) proportion of eligible patients initiating antiretroviral therapy (ART); (2) proportion of those on ART with <1000 copies/mL; (3) rate of all-cause mortality among ART recipients. Secondary outcomes will include: (1) proportion receiving Pneumocystis jiroveci pneumonia prophylaxis; (2) proportion with >90% ART adherence (based on any measure reported); (3) proportion screened for non-communicable diseases (specifically cervical cancer, diabetes, hypertension and mental ill health); (iv) proportion screened for tuberculosis. A search of five electronic bibliographical databases (Embase, Medline, PsychINFO, Web of Science and CINAHL) and reference lists of included articles will be conducted to identify relevant articles reporting HIV clinical outcomes. Searches will be limited to LMIC. No age, publication date, study-design or language limits will be applied. Authors of relevant studies will be contacted for clarification. Two reviewers will independently screen citations and abstracts, identify full text articles for inclusion, extract data and appraise the quality and bias of included studies. Outcome data will be pooled to generate aggregative proportions of primary and secondary outcomes. Descriptive statistics and a narrative synthesis will be presented. Heterogeneity and sensitivity assessments will be conducted to aid interpretation of results.

    ETHICS AND DISSEMINATION: The results of this review will be disseminated through a peer-reviewed scientific manuscript and at international scientific conferences. Results will inform quality improvement strategies, replication of identified good practices, potential policy changes, and future research.

    PROSPERO REGISTRATION NUMBER: CRD42016040053.

  14. Ooi DJ, Dzulkurnain A, Othman RY, Lim SH, Harikrishna JA
    J Virol Methods, 2006 Sep;136(1-2):160-5.
    PMID: 16781785
    A modified method for the rapid isolation of specific ligands to whole virus particles is described. Biopanning against cymbidium mosaic virus was carried out with a commercial 12-mer random peptide display library. A solution phase panning method was devised using streptavidin-coated superparamagnetic beads. The solution based panning method was more efficient than conventional immobilized target panning when using whole viral particles of cymbidium mosaic virus as a target. Enzyme-linked immunosorbent assay of cymbidium mosaic virus-binding peptides isolated from the library identified seven peptides with affinity for cymbidium mosaic virus and one peptide which was specific to cymbidium mosaic virus and had no significant binding to odontoglossum ringspot virus. This method should have broad application for the screening of whole viral particles towards the rapid development of diagnostic reagents without the requirement for cloning and expression of single antigens.
  15. Tan YS, Wong SK, Yong KT, Lim KH, Lim SH, Low YY
    J Nat Prod, 2023 Jan 27;86(1):232-236.
    PMID: 36651825 DOI: 10.1021/acs.jnatprod.2c00731
    Eugeniifoline (1), a pentacyclic indole alkaloid with a five-membered ring E, was isolated for the first time as a natural product from the stem-bark extract of Leuconotis eugeniifolia. Eugeniifoline (1) was previously reported as a synthetic product from a diversity-enhanced extract, but with the configuration at C-21 reported as S (1a). The configuration at C-21 was revised to R as shown in 1, based on the NOE data, GIAO NMR calculations, and DP4+ probability analysis, as well as the TDDFT-ECD method.
  16. Cheung DH, Samoh N, Jonas K, Lim SH, Kongjareon Y, Guadamuz TE
    Sex Transm Dis, 2024 May 01;51(5):352-358.
    PMID: 38301623 DOI: 10.1097/OLQ.0000000000001937
    BACKGROUND: Human immunodeficiency virus (HIV) testing for Thai men who have sex with men (MSM) is suboptimal, which undermines their linkage to care and subsequent HIV preexposure prophylaxis (PrEP) uptake.

    METHODS: We analyzed a cross-sectional survey conducted in 2021 among Thai MSM who attended any private sex parties or circuit parties in the past 3 years ("sexualized parties").

    RESULTS: Of the 424 men included in our analysis, 47.6% had been recently tested for HIV in the past 1 year, 30.2% had not recently been tested, and 22.2% had never been tested. In our multivariable analysis, relative to participants who had recently tested for HIV, those who have never tested were more likely to have lower education or to live outside of Bangkok, and to have attended both circuit and private sex parties (vs. private sex party only) but were less likely to report any sexually transmitted infection diagnosis or to have heard of PrEP. Participants who had an HIV test more than a year ago were more likely to have attended both circuit and private sex parties (vs. private sex parties only) but were less likely to have any sexually transmitted infection diagnosis, meet sexual partners online, or have heard of PrEP. Rates of condomless anal sex and willingness to use PrEP were similar across groups.

    CONCLUSIONS: Despite the high rates of sexual risk-taking, sexualized party attendees reported suboptimal HIV testing uptake. The joint promotion of HIV testing and PrEP is warranted-especially on-premise HIV testing at circuit parties and outreach at online platforms to reach sexualized party attendees.

  17. Voon SH, Kiew LV, Lee HB, Lim SH, Noordin MI, Kamkaew A, et al.
    Small, 2014 Dec 29;10(24):4993-5013.
    PMID: 25164105 DOI: 10.1002/smll.201401416
    Animal models, particularly rodents, are major translational models for evaluating novel anticancer therapeutics. In this review, different types of nanostructure-based photosensitizers that have advanced into the in vivo evaluation stage for the photodynamic therapy (PDT) of cancer are described. This article focuses on the in vivo efficacies of the nanostructures as delivery agents and as energy transducers for photosensitizers in animal models. These materials are useful in overcoming solubility issues, lack of tumor specificity, and access to tumors deep in healthy tissue. At the end of this article, the opportunities made possible by these multiplexed nanostructure-based systems are summarized, as well as the considerable challenges associated with obtaining regulatory approval for such materials. The following questions are also addressed: (1) Is there a pressing demand for more nanoparticle materials? (2) What is the prognosis for regulatory approval of nanoparticles to be used in the clinic?
  18. Lim SH, Thivierge C, Nowak-Sliwinska P, Han J, van den Bergh H, Wagnières G, et al.
    J Med Chem, 2010 Apr 8;53(7):2865-74.
    PMID: 20199028 DOI: 10.1021/jm901823u
    To understand the effects of substitution patterns on photosensitizing the ability of boron dipyrromethene (BODIPY), two structural variations that either investigate the effectiveness of various iodinated derivatives to maximize the "heavy atom effect" or focus on the effect of extended conjugation at the 4-pyrrolic position to red-shift their activation wavelengths were investigated. Compounds with conjugation at the 4-pyrrolic position were less photocytotoxic than the parent unconjugated compound, while those with an iodinated BODIPY core presented better photocytotoxicity than compounds with iodoaryl groups at the meso-positions. The potency of the derivatives generally correlated well with their singlet oxygen generation level. Further studies of compound 5 on HSC-2 cells showed almost exclusive localization to mitochondria, induction of G(2)/M-phase cell cycle block, and onset of apoptosis. Compound 5 also extensively occluded the vasculature of the chick chorioallantoic membrane. Iodinated BODIPY structures such as compound 5 may have potential as new photodynamic therapy agents for cancer.
  19. Lim JL, Sim KS, Yong KT, Loong BJ, Ting KN, Lim SH, et al.
    Phytochemistry, 2015 Sep;117:317-24.
    PMID: 26125941 DOI: 10.1016/j.phytochem.2015.06.024
    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.
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