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  1. Fulltext Camellia sinensis solvent extract, epigallocatechin gallate and caffeine confer trophocidal and cysticidal effects against Acanthamoeba castellanii
    Fakae LB, Harun MSR, Ting DSJ, Dua HS, Cave GWV, Zhu XQ, et al.
    Acta Trop, 2023 Jan;237:106729.
    PMID: 36280206 DOI: 10.1016/j.actatropica.2022.106729
    We examined the anti-acanthamoebic efficacy of green tea Camellia sinensis solvent extract (SE) or its chemical constituents against Acanthamoeba castellanii by using anti-trophozoite, anti-encystation, and anti-excystation assays. C. sinensis SE (625-5000 µg/mL) inhibited trophozoite replication within 24-72 h. C. sinensis SE exhibited a dose-dependent inhibition of encystation, with a marked cysticidal activity at 2500-5000 µg/mL. Two constituents of C. sinensis, namely epigallocatechin-3-gallate and caffeine, at 100 μM and 200 μM respectively, significantly inhibited both trophozoite replication and encystation. Cytotoxicity analysis showed that 156.25-2500 µg/mL of SE was not toxic to human corneal epithelial cells, while up to 625 µg/mL was not toxic to Madin-Darby canine kidney cells. This study shows the anti-acanthamoebic potential of C. sinensis SE against A. castellanii trophozoites and cysts. Pre-clinical studies are required to elucidate the in vivo efficacy and safety of C. sinensis SE.
    Matched MeSH terms: Caffeine/pharmacology
  2. Caffeine-Supplemented Diet Prevents Fatigue-Like Behavior in Tumor-Bearing Mice
    Ferdaos N, Harada A, Masuda E, Kasai S, Horaguchi T, Yoshizawa K
    Nutr Cancer, 2023;75(3):1005-1013.
    PMID: 36714982 DOI: 10.1080/01635581.2022.2163669
    Caffeine is a widely consumed stimulant, known for its positive effects on physical and mental performance. These effects are potentially beneficial for ameliorating cancer-related fatigue, which affects the quality of life of patients with cancer. This study aimed to determine the anti-fatigue and antitumor effects of caffeine in tumor-bearing mice. BALB/c mice were intravenously injected with C26 colon carcinoma cells and fed with normal or 0.05% caffeine-supplemented diet. Fatigue-like behavior was assessed by running performance using a treadmill test. Lung, blood, liver, muscle, and epididymal adipose tissue samples were collected on day 13 and examined. The antitumor effect of caffeine was assessed using subcutaneous tumor-bearing mice fed with 0.05% caffeine-supplemented diet, and the tumor volume was measured. C26 tumor-bearing mice showed fatigue-like behavior associated with hypoglycemia, depleted liver glycogen and non-esterified fatty acid (NEFA) levels. C26 tumor-bearing mice fed with 0.05% caffeine-supplemented diet showed improved running performance associated with restored NEFA levels. However, exacerbated hypoglycemia and liver glycogen levels after caffeine consumption may be due to tumor-induced catabolic signals, as the tumor volume was not affected. Collectively, caffeine may exert anti-fatigue effects through enhanced lipolysis leading to restored NEFA levels, which can be used as an alternative energy source.
    Matched MeSH terms: Caffeine/pharmacology
  3. Fulltext Caffeine as a potential quorum sensing inhibitor
    Norizan SN, Yin WF, Chan KG
    Sensors (Basel), 2013;13(4):5117-29.
    PMID: 23598500 DOI: 10.3390/s130405117
    Quorum sensing enables bacteria to control the gene expression in response to the cell density. It regulates a variety of bacterial physiological functions such as biofilm formation, bioluminescence, virulence factors and swarming which has been shown contribute to bacterial pathogenesis. The use of quorum sensing inhibitor would be of particular interest in treating bacterial pathogenicity and infections. In this work, we have tested caffeine as quorum sensing inhibitor by using Chromobacterium violaceum CV026 as a biosensor. We verified that caffeine did not degrade the N-acyl homoserine lactones tested. In this work, it is shown that caffeine could inhibit N-acyl homoserine lactone production and swarming of a human opportunistic pathogen, namely Pseudomonas aeruginosa PA01. To the best of our knowledge, this is the first documentation providing evidence on the presence of anti-quorum sensing activity in caffeine. Our work will allow caffeine to be explored as anti-infective drugs.
    Matched MeSH terms: Caffeine/pharmacology*
  4. Effects of restricted caffeine intake by mother on fetal, neonatal and pregnancy outcome
    Jahanfar S, Sharifah H
    Cochrane Database Syst Rev, 2009 April 15.
    PMID: 19370665 DOI: 10.1002/14651858.CD006965.pub2
    BACKGROUND: Maternal caffeine consumption during pregnancy may have adverse effects on fetal, neonatal and maternal outcomes.
    OBJECTIVES: This review investigates the effects of restricting caffeine intake by mothers on fetal, neonatal and pregnancy outcomes.
    SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2008), scanned bibliographies of published studies and corresponded with investigators.
    SELECTION CRITERIA: Randomised controlled trials including quasi-randomised controlled trials (RCTs) investigating the effect of caffeine and/or supplementary caffeine versus restricted caffeine intake or placebo on pregnancy outcome.
    DATA COLLECTION AND ANALYSIS: The two review authors independently assessed trial quality and extracted data.
    MAIN RESULTS: One study met the inclusion criteria. Caffeinated instant coffee (568 women) was compared with decaffeinated instant coffee (629 women) and it was found that reducing the caffeine intake of regular coffee drinkers (3+ cups/day) during the second and third trimester by an average of 182 mg/day did not affect birthweight or length of gestation.
    AUTHORS' CONCLUSIONS: There is insufficient evidence to confirm or refute the effectiveness of caffeine avoidance on birthweight or other pregnancy outcomes. There is a need to conduct high-quality, double-blinded RCTs to determine whether caffeine has any effect on pregnancy outcome.
    Matched MeSH terms: Caffeine/pharmacology*
  5. Confounding effects of caffeine on neuroplasticity induced by transcranial alternating current stimulation and paired associative stimulation
    Zulkifly MFM, Merkohitaj O, Brockmöller J, Paulus W
    Clin Neurophysiol, 2021 06;132(6):1367-1379.
    PMID: 33762129 DOI: 10.1016/j.clinph.2021.01.024
    OBJECTIVE: We examined the effects of caffeine, time of day, and alertness fluctuation on plasticity effects after transcranial alternating current stimulation (tACS) or 25 ms paired associative stimulation (PAS25) in caffeine-naïve and caffeine-adapted subjects.

    METHODS: In two randomised, double-blinded, cross-over or placebo-controlled (caffeine) studies, we measured sixty subjects in eight sessions (n = 30, Male: Female = 1:1 in each study).

    RESULTS: We found caffeine increased motor cortex excitability in caffeine naïve subjects. The aftereffects in caffeine naïve subjects were enhanced and prolonged when combined with PAS 25. Caffeine also increased alertness and the motor evoked potentials (MEPs) were reduced under light deprivation in caffeine consumers both with and without caffeine. In caffeine consumers, the time of day had no effect on tACS-induced plasticity.

    CONCLUSIONS: We conclude that caffeine should be avoided or controlled as confounding factor for brain stimulation protocols. It is also important to keep the brightness constant in all sessions and study groups should not be mixed with caffeine-naïve and caffeine consuming participants.

    SIGNIFICANCE: Caffeine is one of the confounding factors in the plasticity induction studies and it induces different excitability effects in caffeine-naïve and caffeine-adapted subjects. This study was registered in the ClinicalTrials.gov with these registration IDs: 1) NCT03720665 https://clinicaltrials.gov/ct2/results?cond=NCT03720665&term=&cntry=&state=&city=&dist= 2) NCT04011670 https://clinicaltrials.gov/ct2/results?cond=&term=NCT04011670&cntry=&state=&city=&dist=.

    Matched MeSH terms: Caffeine/pharmacology*
  6. Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy
    Tripathi M, Singh BK, Liehn EA, Lim SY, Tikno K, Castano-Mayan D, et al.
    Autophagy, 2022 Sep;18(9):2150-2160.
    PMID: 35012409 DOI: 10.1080/15548627.2021.2021494
    Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.
    Matched MeSH terms: Caffeine/pharmacology
  7. Fulltext Effects of acute supplementation of caffeine and Panax ginseng on endurance running performance in a hot and humid environment
    Bandyopadhyay A, Ping FW, Keong CC
    J Hum Ergol (Tokyo), 2011 Dec;40(1-2):63-72.
    PMID: 25665208 DOI: 10.11183/jhe.40.63
    Acute supplementation of Panax ginseng (PG) is known not to impose any significant effect on endurance performance of recreational Malaysian runners, while caffeine augments the ergogenic property of some herbs. The present study was aimed to examine the effects of acute supplementation of caffeine and PG on endurance running performance in a hot and humid condition. Nine heat adapted Malaysian recreational runners (age : 25.4 ± 6.9 years, body mass : 57.6 ± 8.4 kg; body height : 168.3 ± 7.6 cm) ingested either placebo or combined dose of 5 mg x kg(-1) of body weight of caffeine and 200 mg of PG one hour before the running on treadmill at 70% of VO2(max) in this placebo-controlled double blind randomised study in a laboratory environment of 31 degrees C and 70% relative humidity. They drank 3 ml x kg(-1) of body weight of cool water every 20 minutes during the exercise to prevent dehydration. Blood samples were withdrawn and oxygen uptake was recorded every 20 minutes while heart rate, core body temperature, skin temperature and ratings of perceived exertion (RPE) were recorded every 10 minutes during the trials. Endurance time was significantly different (P < 0.05) between experimental and placebo trials. Heart rate, skin temperature, core body temperature, oxygen uptake, RPE, plasma insulin, glucose, free fatty acid and lactate levels during the endurance exercise did not show any significant difference between the trials. Thus, we conclude that combined and acute supplementation of caffeine and PG in the said doses improved the endurance running performance of the heat-adapted male recreational runners.
    Matched MeSH terms: Caffeine/pharmacology*
  8. Fulltext Up Regulation of cystathione γ lyase and Hydrogen Sulphide in the Myocardium Inhibits the Progression of Isoproterenol-Caffeine Induced Left Ventricular Hypertrophy in Wistar Kyoto Rats
    Ahmad A, Sattar MA, Rathore HA, Abdulla MH, Khan SA, Azam M, et al.
    PLoS One, 2016;11(3):e0150137.
    PMID: 26963622 DOI: 10.1371/journal.pone.0150137
    Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56μM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05) in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05) in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05) plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II) and noradrenaline (NA) but attenuates oxidative stress and improves pulse wave velocity which helps to suppress LVH. Exogenous administration of H2S augmented the reduced renal cortical blood perfusion in the LVH state.
    Matched MeSH terms: Caffeine/pharmacology
  9. Effects of acute supplementation of caffeine on cardiorespiratory responses during endurance running in a hot & humid climate
    Ping WC, Keong CC, Bandyopadhyay A
    Indian J Med Res, 2010 Jul;132:36-41.
    PMID: 20693587
    Athletes in Malaysia need to perform in a hot and humid climate. Chronic supplementation of caffeine on endurance performance have been studied extensively in different populations. However, concurrent research on the effects of acute supplementation of caffeine on cardiorespiratory responses during endurance exercise in the Malaysian context especially in a hot and humid environment is unavailable.
    Matched MeSH terms: Caffeine/pharmacology*
  10. Investigation of optimum roasting conditions to obtain possible health benefit supplement, antioxidants from coffee beans
    Sulaiman SF, Moon JK, Shibamoto T
    J Diet Suppl, 2011 Sep;8(3):293-310.
    PMID: 22432728 DOI: 10.3109/19390211.2011.593618
    In order to investigate the role of roasting conditions in antioxidant formation, methanol and hot water extracts from Robusta coffee beans roasted for various lengths of time and at various temperatures were analyzed for total phenolic acid, chlorogenic acid, and caffeine content, as well as for their antioxidant activities using 1,1-diphenyl-2-picryhydrazyl (DPPH), thiobarbituric acid (TBA), and malonaldehyde/gas chromatography (MA/GC) assays. The amount of total phenolics in methanol extracts decreased linearly over the roasting temperature from 63.51 ± 0.77 mg chlorogenic acid equivalent (CAE)/g coffee beans (roasted at 200°C) to 42.56 ± 0.33 mg CAE/g coffee beans (roasted at 240°C). The total chlorogenic acid content decreased when the roasting time was increased from 78.33 ± 1.41 mg/g (green coffee beans) to 4.31 ± 0.23 mg/g (roasted for 16 min at 250°C). All methanol extracts from roasted coffee beans possessed over 90% antioxidant activities in the DPPH assay. The antioxidant activity of methanol extracts ranged from 41.38 ± 1.77% (roasted at 250°C for 10 min) to 98.20 ± 1.49% (roasted at 230°C for 16 min) as tested by the TBA assay. The antioxidant activity of methanol extracts of green coffee beans and roasted coffee beans ranged from 93.01% (green coffee beans) to 98.62 ± 1.32% (roasted at 250°C for 14 min) in the MA/GC assays. All hot water extracts exhibited moderate pro-oxidant activities in TBA and MA/GC assays. The results indicated that roasting conditions of coffee beans play an important role in the formation of antioxidants in brewed coffee, which can be dietary supplements having beneficial effect to human health.
    Matched MeSH terms: Caffeine/pharmacology
  11. Fulltext Triterpene composition and bioactivities of Centella asiatica
    Hashim P, Sidek H, Helan MH, Sabery A, Palanisamy UD, Ilham M
    Molecules, 2011;16(2):1310-22.
    PMID: 21278681 DOI: 10.3390/molecules16021310
    Leaves of Centella asiatica (Centella) were analysed for their triterpene composition and bioactivity such as collagen enhancement, antioxidant, anticellulite and UV protection capacity properties. Triterpenes of Centella were measured using HPLC-PAD on an Excil ODS 5 mm (C18) column for the simultaneous determination of asiatic acid, madecassic acid, asiaticoside and madecassoside. Centella was found to contain significant amounts of madecassoside (3.10 ± 4.58 mg/mL) and asiaticoside (1.97 ± 2.65 mg/mL), but was low in asiatic and madecassic acid. The highest collagen synthesis was found at 50 mg/mL of Centella extracts. The antioxidant activity of Centella (84%) was compared to grape seed extract (83%) and Vitamin C (88%). Its lipolytic activity was observed by the release of glycerol (115.9 µmol/L) at 0.02% concentration. Centella extracts exhibited similar UV protection effect to OMC at 10% concentration. In view of these results, the potential application of Centella in food and pharmaceutical industries is now widely open.
    Matched MeSH terms: Caffeine/pharmacology
  12. Fulltext Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound
    Muchtaridi M, Lestari D, Khairul Ikram NK, Gazzali AM, Hariono M, Wahab HA
    Molecules, 2021 Jun 04;26(11).
    PMID: 34199752 DOI: 10.3390/molecules26113402
    Coffee has been studied for its health benefits, including prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson's, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. However, the presence of caffeine in coffee beans may also cause insomnia and stomach irritation, and increase heart rate and respiration rate. These unwanted effects may be reduced by decaffeination of green bean Arabica coffee (GBAC) by treatment with dichloromethane, followed by solid-phase extraction using methanol. In this study, the caffeine and chlorogenic acid (CGA) level in the coffee bean from three different areas in West Java, before and after decaffeination, was determined and validated using HPLC. The results showed that the levels of caffeine were reduced significantly, with an order as follows: Tasikmalaya (2.28% to 0.097% (97 ppm), Pangalengan (1.57% to 0.049% (495 ppm), and Garut (1.45% to 0.00002% (0.2 ppm). The CGA levels in the GBAC were also reduced as follows: Tasikmalaya (0.54% to 0.001% (118 ppm), Pangalengan (0.97% to 0.0047% (388 ppm)), and Garut (0.81% to 0.029% (282 ppm). The decaffeinated samples were then subjected to the H5N1 neuraminidase (NA) binding assay to determine its bioactivity as an anti-influenza agent. The results show that samples from Tasikmalaya, Pangalengan, and Garut possess NA inhibitory activity with IC50 of 69.70, 75.23, and 55.74 μg/mL, respectively. The low level of caffeine with a higher level of CGA correlates with their higher levels of NA inhibitory, as shown in the Garut samples. Therefore, the level of caffeine and CGA influenced the level of NA inhibitory activity. This is supported by the validation of CGA-NA binding interaction via molecular docking and pharmacophore modeling; hence, CGA could potentially serve as a bioactive compound for neuraminidase activity in GBAC.
    Matched MeSH terms: Caffeine/pharmacology
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