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Effect of different curcumin dosages on human gall bladder
Abstract
Our previous study demonstrated that curcumin, an active compound of Curcuma xanthorrhiza and C. domestica, produces a positive cholekinetic effect. A 20 mg amount of curcumin is capable of contracting the gall bladder by up to 29% within an observation time of 2 h. The aim of the current study was to define the dosage of curcumin capable of producing a 50% contraction of the gall bladder, and to determine if there is a linear relationship between doubling the curcumin dosage and the doubling of gall bladder contraction. A randomised, single-blind, three-phase, crossover-designed examination was carried out on 12 healthy volunteers. Ultrasonography was carried out serially to measure the gall bladder volume. The data obtained was analysed by analysis of variance (ANOVA). The fasting volumes of gall bladders were similar (P > 0.50), with 17.28 +/- 5.47 mL for 20 mg curcumin, 18.34 +/- 3.75 mL for 40 mg and 18.24 +/- 3.72 mL for 80 mg. The percentage decrease in gall bladder volume 2 h after administration of 20, 40 and 80 mg was 34.10 +/- 10.16, 51.15 +/- 8.08 and 72.25 +/- 8.22, respectively, which was significantly different (P < 0.01). On the basis of the present findings, it appears that the dosage of cucumin capable of producing a 50% contraction of the bladder was 40 mg. This study did not show any linear relationship between doubling curcumin dosage and the doubling of gall bladder contraction.
... > Het kan ook nuttig zijn voor de voeding van het maag-darmkanaal als preventief middel tegen galblaaspijn bij mensen met galstenen (en mogelijk galblaaskanker, zie hieronder) als preventief middel tegen galstenen te werken als een cholecystokinetisch middel, hetgeen betekent dat het de pompwerking van de galblaas vergemakkelijkt dat helpt te voorkomen dat de gal stagneerde, zoals in deze dubbelblinde placebo-gecontroleerde cross-over studie waarin ze mensen een kleine dosis curcumine gaven van ongeveer de hoeveelheid gevonden in ¼ (een kwart) theelepel kurkuma, waarna ze met behulp van echografie als reactie de galblaas naar beneden konden zien knijpen met een gemiddelde verandering in volume van ongeveer 29 [%] [100]. In een optimaler geval zou je het echter het liefst in tweeën willen knijpen hetgeen reden gaf voor herhalen van het experiment met verschillende dosissen [101], hetgeen resulteerde in de wetenschap dat het ongeveer 40 [milligram] kostte om een contractie van 50 [%] te krijgen, wat per dag ongeveer 1/3 (een derde) van een theelepel kurkuma is. Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. ...
... Kurkuma curcumine kan galstenen helpen voorkomen door als preventief middel tegen galstenen te werken als een cholecystokinetisch middel, hetgeen betekent dat het de pompwerking van de galblaas vergemakkelijkt dat helpt te voorkomen dat de gal stagneerde, zoals in deze dubbelblinde placebo-gecontroleerde cross-over studie waarin ze mensen een kleine dosis curcumine gaven van ongeveer de hoeveelheid gevonden in ¼ (een kwart) theelepel kurkuma, waarna ze met behulp van echografie als reactie de galblaas naar beneden konden zien knijpen met een gemiddelde verandering in volume van ongeveer 29 [%] [100]. In een optimaler geval zou je het echter het liefst in tweeën willen knijpen hetgeen reden gaf voor herhalen van het experiment met verschillende dosissen [101], hetgeen resulteerde in de wetenschap dat het ongeveer 40 [milligram] kostte om een contractie van 50 [%] te krijgen, wat per dag ongeveer 1/3 (een derde) van een theelepel kurkuma is. Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. ...
... Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. Patiënten met galwegobstructie moeten dus voorzichtig zijn met het consumeren van curcumine [30], maar voor alle anderen suggereren deze resultaten dat curcumine de galblaas effectief kan laten legen en daardoor het risico op galsteenvorming in de eerste plaats en uiteindelijk misschien zelfs de kans op galblaaskanker kan verminderen [101]. ...
De prikkelende, bittere, neus-samentrekkend ruikende fel geeloranje gouden (de alleppey kurkuma ook wel de Indiase kurkuma exemplaren genoemd hebben een diepgele tot oranjegele kleur) of (exclusief of) bruin (de Chinese kurkuma exemplaren hebben een typisch bruinachtige kleur) of (exclusief of) rood (welke rode kleur ontstaat door gedroogde kurkuma te combineren met calciumhydroxide poeder en wanneer het rood is wordt het ook wel het "kunkum" en "kumkuma" genoemd) kruidenpoeder van de gedroogde gemberachtige groente maar aan de binnenkant gekleurde wortelstelen en de wortelstokken van de meerjarige bloeiende kruidenplant die leeft in gebieden met tropisch warme temperaturen en veel regen nodig heeft om te gedijen welke gewoonlijk kurkuma genoemd met de soortnaam curcuma longa linnaeus (ookmeritorious earth", "Indiase saffraan" en "Indian saffron" omdat Marco Polo schreef dat het een groente is die alle eigenschappen heeft die echte saffraan ook heeft, waaronder de geur en de kleur, maar toch niet gelijk is aan echte saffraan) categoriseerbaar in het plantengeslacht curcuma (ook kurkuma genoemd, waarvan de naam kan zijn afgeleid van het Sanskriet "kuṅkuma" dat verwijst naar zowel kurkuma als saffraan) in de gemberfamilie zingiberaceae (en dus een relatief naaste verwant van gember) mogelijk omdat het de niet-steroïde polyfenolische (vanwege de meerdere chemisch gedefinieerde aromatische fenolringen) en de meervoudige hydroxylgroep (welke chemisch gedefinieerde aromatische fenolringen en meerdere hydroxylgroepen het zijn antioxiderende eigenschap geven) bevat het polair gemakkelijk in water oplosbaar potentieel krachtige antioxidant curcuminoïde diferuloylmethaan biologisch actieve verbinding molecuul kurkuma curcumine (ook wel "curcumine", "kurkumine" en "kurkumin" genoemd) dat aanwezig is en dus kan worden gevonden in kurkuma, aangezien het ongeveer 5 [%] van zijn massa uitmaakt [105] (waarvoor een handige nuttige pragmatische kanttekening zou zijn dat de biologische beschikbaarheid van curcumine in het bloedserum door verhoogde absorptie in de dikke darm synergetisch potentieel kan worden versterkt en dus verhoogd tot 2'000 [%] bij menselijke dieren bij gepaarde consumptie samen met de zwarte peper piper nigrum die de verbinding peperine [1] bevat die verantwoordelijk is voor ongeveer 5 [%] van zijn massa [106] en tevens ook verantwoordelijk is voor de scherpe smaak van peper en het remt inhibiterend ook het metabolische vermogen van de lever om stoffen in water oplosbaar te maken zodat ze gemakkelijker kunnen worden uitgescheiden hetgeen leidt tot verhoging van het biologisch beschikbare niveau van curcumine in de bloedbaan omdat wanneer het mechanisme niet wordt onderdrukt de lever actief probeert om er vanaf te komen en je dus maar een relatief kleine piek in bloodbuis niveau van crucumine ziet terwijl vergeleken met wanneer gepaard ook peperine wordt geconsumeerd met dezelfde hoeveelheid curcumine de biologische beschikbaarheid omhoog schiet tot wel 2000 [%] [ 1], waarvoor niet veel zwarte peper nodig is, aangezien een klein snuifje van 1/20 van een theelepel genoeg is om het niveau aanzienlijk te verhogen [107], een combinatie die bijvoorbeeld uitstekend zou werken in een curryrecept, omdat de biologische beschikbaarheid van curcumine normaal gesproken erg laag is en daarom is de voedingswaarde lager als het niet wordt geconsumeerd met zwarte peper, aangezien er slechts een klein beetje in onze bloedbaan komt na het eten van een lekkere curry, tenzij we wat zwarte peper toevoegen [1]; en een andere manier om de opname van curcumine te stimuleren, is door het in de vorm van kurkumawortel te consumeren (relatief vers of gedroogd als poeder) in vergelijking met een extract, omdat natuurlijke oliën in kurkumawortel en kurkumapoeder de biologische beschikbaarheid van curcumine kunnen verbeteren met een verschil van (zeven) tot 8 (acht) keer hogere biologische beschikbaarheid [107]; en wanneer het samen gegeten
... > Het kan ook nuttig zijn voor de voeding van het maag-darmkanaal als preventief middel tegen galblaaspijn bij mensen met galstenen (en mogelijk galblaaskanker, zie hieronder) als preventief middel tegen galstenen te werken als een cholecystokinetisch middel, hetgeen betekent dat het de pompwerking van de galblaas vergemakkelijkt dat helpt te voorkomen dat de gal stagneerde, zoals in deze dubbelblinde placebo-gecontroleerde cross-over studie waarin ze mensen een kleine dosis curcumine gaven van ongeveer de hoeveelheid gevonden in ¼ (een kwart) theelepel kurkuma, waarna ze met behulp van echografie als reactie de galblaas naar beneden konden zien knijpen met een gemiddelde verandering in volume van ongeveer 29 [%] [100]. In een optimaler geval zou je het echter het liefst in tweeën willen knijpen hetgeen reden gaf voor herhalen van het experiment met verschillende dosissen [101], hetgeen resulteerde in de wetenschap dat het ongeveer 40 [milligram] kostte om een contractie van 50 [%] te krijgen, wat per dag ongeveer 1/3 (een derde) van een theelepel kurkuma is. Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. ...
... Kurkuma curcumine kan galstenen helpen voorkomen door als preventief middel tegen galstenen te werken als een cholecystokinetisch middel, hetgeen betekent dat het de pompwerking van de galblaas vergemakkelijkt dat helpt te voorkomen dat de gal stagneerde, zoals in deze dubbelblinde placebo-gecontroleerde cross-over studie waarin ze mensen een kleine dosis curcumine gaven van ongeveer de hoeveelheid gevonden in ¼ (een kwart) theelepel kurkuma, waarna ze met behulp van echografie als reactie de galblaas naar beneden konden zien knijpen met een gemiddelde verandering in volume van ongeveer 29 [%] [100]. In een optimaler geval zou je het echter het liefst in tweeën willen knijpen hetgeen reden gaf voor herhalen van het experiment met verschillende dosissen [101], hetgeen resulteerde in de wetenschap dat het ongeveer 40 [milligram] kostte om een contractie van 50 [%] te krijgen, wat per dag ongeveer 1/3 (een derde) van een theelepel kurkuma is. Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. ...
... Maar als je al een galblaasobstructie hebt, zoals een galsteen die je galkanaal blokkeert en je eet kurkuma, dan knijpt je galblaas harder naar beneden, hetgeen veel pijn kan doen en dat dit waarschijnlijk het mechanisme is dat achter de melding van het onderzoek schuilgaat waarbij werd gezegd dat mogelijk galblaaspijn zou kunnen veroorzaken bij mensen met galstenen [97]. Patiënten met galwegobstructie moeten dus voorzichtig zijn met het consumeren van curcumine [30], maar voor alle anderen suggereren deze resultaten dat curcumine de galblaas effectief kan laten legen en daardoor het risico op galsteenvorming in de eerste plaats en uiteindelijk misschien zelfs de kans op galblaaskanker kan verminderen [101]. ...
Website link: www.nutritionfactsnederlands.nl/videoscript/2022/1/17/kurkuma-alomvattend-artikel [Turmeric-SOURCES BELOW] The pungent, bitter, astringent smelling brightly yellow-orange golden (the alleppey turmeric also called the Indian turmeric exemplars have a deep yellow to orange-yellow color) or (exclusive or) brown (the Chinese turmeric exemplars have typically a brownish color) or (exclusive or) red (which red color is created by combining dried turmeric with calcium hydroxide powder and when red it is also called "kunkum" and "kumkuma") spice powder from the dried ginger-like vegetable but colored on the inside root stalks and the rhizomes of the perennial flowering herb plant living in tropical warm temperature areas and needing plenty of rainfalls to thrive commonly named turmeric which species name is curcuma longa linnaeus (alsoIndiase saffraan" and "Indian saffron" since Marco Polo wrote a that it is a vegetable that has all the properties of true saffron as well as the smell and the color but yet it is not really saffron) categorizable in the plant genus curcuma (also called kurkuma which name may be derived from the Sanskrit "kuṅkuma" which is referring to both turmeric and saffron) in the ginger family zingiberaceae (and thus a relatively close relative of ginger) possibly because it contains the non-steroidal polyphenolic (because of the multiple chemically defined aromatic phenol rings) and multiple hydroxyl group (which aromatic phenol rings and hydroxyl groups give it its antioxidant property) containing the polar readily in water soluble potentially powerful antioxidant curcuminoid diferuloylmethane biologically active compound molecule turmeric curcumin (also called "curcumine", "kurkumine" and "kurkumin") that is contained and thus can be found in turmeric as it makes up of approximately 5 [%] of its mass [105] (for which a convenient useful pragmatic sidenote would be that curcumin's blood serum level bioavailability by increased absorption in the colon can be synergistically potentially boosted thus increased up to 2'000 [%] in human animals when consuming it together with the black pepper piper nigrum that contains the compound peperine [1] which is responsible for about 5 [%] of its mass [106] and which is also responsible for the pungent flavor of pepper and also inhibits the livers metabolism mechanism to make substances water-soluble so they can be more easily excreted suppressing this mechanism leading to higher blood levels of bioavailability of curcumin as within an hour you can see a little bump in the level in the bloodstream of curcumin when the mechanism is unsuppressed because the liver is actively trying to get rid of it while compared to when also consuming peperine with the same amount of curcumin consumed the bioavailability shoots up to 2'000 [%] [1], which does not take much black pepper since a little pinch of 1/20 of a teaspoon is enough to considerably boost levels [107], which concomitant combination would work great in a curry recipe for example since the bioavailability of curcumin is normally very low and thus the nutritional value is poorer when not consumed with black pepper since just a tiny bit gets into our bloodstream after eating a nice curry unless we add some black pepper [1]; and another way to boost the absorption of curcumin is to consume it in the whole food turmeric root form (relatively fresh or dried as a powder) as compared to an extract because natural oils found in turmeric root and turmeric powder can enhance the bioavailability of curcumin 7 (seven) to 8 (eight) fold [107]; and when eaten together with a relatively large amount of fatty acid containing foods such as nuts, e.g. walnuts, almonds or pecans, also ensures increased bioavailability as curcumin can be directly absorbed into the bloodstream through the lymphatic system and thus thereby in part bypassing the liver [107]) which curcumin pigment also gives turmeric its brightly deep yellow to orange-yellow golden color which turmeric is possibly usable as
... An Indonesian study by (Rasyid et al., 2002) was conducted to determine a dosage capable of producing an increase in gallbladder contraction by 50% and to define whether there is any linear relationship between the doubling of curcumin dosages and the doubling of gallbladder contraction. According to the authors, curcumin may be useful in preventing gallstone formation due to its ability to cause gallbladder contraction.The randomised, singleblind, three-phase, crossover design study included healthy adults volunteers (n=12; eight males, four females) ages 20-50 years, who were given either curcumin (Merck Schudchardt, Munich, Germany) or the placebo amylum (Shangi, Java, Indonesia). ...
... The dosage capable of producing an increase in gallbladder contraction by 50% was 40 mg curcumin. A linear relationship between doubling curcumin dosage and doubling of contraction was not proven (Rasyid et al., 2002). ...
... An Indonesian study by (Rasyid et al., 2002) was conducted to determine a dosage capable of producing an increase in gallbladder contraction by 50% and to define whether there is any linear relationship between the doubling of curcumin dosages and the doubling of gallbladder contraction. According to the authors, curcumin may be useful in preventing gallstone formation due to its ability to cause gallbladder contraction.The randomised, singleblind, three-phase, crossover design study included healthy adults volunteers (n=12; eight males, four females) ages 20-50 years, who were given either curcumin (Merck Schudchardt, Munich, Germany) or the placebo amylum (Shangi, Java, Indonesia). ...
... The dosage capable of producing an increase in gallbladder contraction by 50% was 40 mg curcumin. A linear relationship between doubling curcumin dosage and doubling of contraction was not proven (Rasyid et al., 2002). ...
... These traits can possibly be attributed to the methoxy, hydroxyl, α, β-unsaturated carbonyl moiety or diketone groups present in curcumin . Besides its safety and tolerability, cost-effectiveness is an added advantage of this compound (Shoba et al., 1998;Rasyid and Lelo, 1999;Rasyid et al., 2002;Lao et al., 2006;Tuntipopipat et al., 2006;Juan et al., 2007;Vareed et al., 2008;Shimouchi et al., 2009;Dominiak et al., 2010;Cuomo et al., 2011;Pungcharoenkul and Thongnopnua, 2011;Sasaki et al., 2011;DiSilvestro et al., 2012;Kusuhara et al., 2012;Sugawara et Klickovic et al., 2014). Because of its amazing properties, curcumin is being marketed in several countries of the world in various forms (Prasad et al., 2014b). ...
... Furthermore, curcumin was found to exhibit positive cholekinetic effect as it induced a significant contraction of the human gall-bladder (Rasyid and Lelo, 1999). At the dosage of 40 mg, curcumin evoked a 50% contraction of the gall bladder (Rasyid et al., 2002). A dose-response study was undertaken to detect the maximum tolerated dose and safety of a single dose of standardized powder extract; uniformlymilled curcumin was administered to healthy volunteers at doses ranging from 500 to 12 000 mg and it was found to be profoundly well tolerated (Lao et al., 2006). ...
Curcumin, a yellow pigment in the Indian spice Turmeric (Curcuma longa), which is chemically known as diferuloylmethane, was first isolated exactly two centuries ago in 1815 by two German Scientists, Vogel and Pelletier. However, according to the pubmed database, the first study on its biological activity as an antibacterial agent was published in 1949 in Nature and the first clinical trial was reported in The Lancet in 1937. Although the current database indicates almost 9000 publications on curcumin, until 1990 there were less than 100 papers published on this nutraceutical. At the molecular level, this multitargeted agent has been shown to exhibit anti-inflammatory activity through the suppression of numerous cell signalling pathways including NF-κB, STAT3, Nrf2, ROS and COX-2. Numerous studies have indicated that curcumin is a highly potent antimicrobial agent and has been shown to be active against various chronic diseases including various types of cancers, diabetes, obesity, cardiovascular, pulmonary, neurological and autoimmune diseases. Furthermore, this compound has also been shown to be synergistic with other nutraceuticals such as resveratrol, piperine, catechins, quercetin and genistein. To date, over 100 different clinical trials have been completed with curcumin, which clearly show its safety, tolerability and its effectiveness against various chronic diseases in humans. However, more clinical trials in different populations are necessary to prove its potential against different chronic diseases in humans. This review's primary focus is on lessons learnt about curcumin from clinical trials.
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This article is part of a themed section on Principles of Pharmacological Research of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.11/issuetoc.
... Testing of enhanced bioavailability products was also less common (21%). Most studies focused on the intestines (69%, n = 27), including disorders of the foregut (n = 13) [249][250][251][252][253][254][255][256][257][258][259][260][261], small intestine (n = 4) [262][263][264][265], and colon (n = 10) [266][267][268][269][270][271][272][273][274][275]; additional citations focused on gallbladder (n = 6) [276][277][278][279][280][281] and liver (n = 6) [282][283][284][285][286][287]. When considered by disease pathogenesis, foregut conditions related to disordered gastric secretion, including peptic ulcer disease and Barrett's esophagitis, were the most frequently studied (33%, n = 13) [249][250][251][252][253][254][255][256][257][258][259][260][261], followed by inflammatory bowel disease (IBD; 26%, n = 10), including Crohn's disease or ulcerative colitis [262,263,[268][269][270][271][272][273][274][275]. ...
Medicinal properties of turmeric (Curcuma longa L.), a plant used for centuries as an anti-inflammatory, are attributed to its polyphenolic curcuminoids, where curcumin predominates. Although “curcumin” supplements are a top-selling botanical with promising pre-clinical effects, questions remain regarding biological activity in humans. To address this, a scoping review was conducted to assess human clinical trials reporting oral curcumin effects on disease outcomes. Eight databases were searched using established guidelines, yielding 389 citations (from 9528 initial) that met inclusion criteria. Half focused on obesity-associated metabolic disorders (29%) or musculoskeletal disorders (17%), where inflammation is a key driver, and beneficial effects on clinical outcomes and/or biomarkers were reported for most citations (75%) in studies that were primarily double-blind, randomized, and placebo-controlled trials (77%, D-RCT). Citations for the next most studied disease categories (neurocognitive [11%] or gastrointestinal disorders [10%], or cancer [9%]), were far fewer in number and yielded mixed results depending on study quality and condition studied. Although additional research is needed, including systematic evaluation of diverse curcumin formulations and doses in larger D-RCT studies, the preponderance of current evidence for several highly studied diseases (e.g., metabolic syndrome, osteoarthritis), which are also clinically common, are suggestive of clinical benefits.
... This may be due to an overdose of this substance. Curcumin exerts pro-oxidant activity (Aggeli et al. 2013) and promotes gall bladder contraction (Rasyid et al. 2002) to release bile, as well as having an influence on bile flow (Wang et al. 2016) despite obstructions where adult O. viverrini occur, leading to increased bile duct proliferation. This suggests that dosage of CNCs should be considered carefully in diseases associated with biliary obstruction. ...
Background
Curcumin-loaded nanocomplexes (CNCs) previously demonstrated lower toxicity and extended release better than is the case for free curcumin. Here, we evaluated the efficacy of CNCs against opisthorchiasis-associated cholangiocarcinoma (CCA) in hamsters.
Method
Dose optimization (dose and frequency) was performed over a 1-month period using hamsters, a model that is widely used for study of opisthorchiasis-associated cholangiocarcinoma. In the main experimental study, CCA was induced by a combination of fluke, Opisthorchis viverrini (OV), infection and N-nitrosodimethylamine (NDMA) treatment. Either blank (empty) nanocomplexes (BNCs) or different concentrations of CNCs (equivalent to 10 and 20 mg cur/kg bw) were given to hamsters thrice a week for 5 months. The histopathological changes, biochemical parameters, and the expression of inflammatory/oncogenic transcription factors were investigated. In addition, the role of CNCs in attenuating CCA genesis, as seen in an animal model, was also confirmed in vitro using CCA cell lines.
Results
The optimization study revealed that treatment with CNCs at a dose equivalent to 10 mg cur/kg bw, thrice a week for 1 month, led to a greater reduction of inflammation and liver injury induced in hamsters by OV + NDMA than did treatments at other dose rates. Oral administration with CNCs (10 mg cur/kg bw), thrice a week for 5 months, significantly increased survival rate, reduced CCA incidence, extent of tumor development, cholangitis, bile duct injury and cholangiofibroma. In addition, this treatment decreased serum ALP and ALT activities and suppressed expression of NF-κB, FOXM1, HMGB1, PCNA and formation of 8-nitroguanine. Treatment of CCA cell lines with CNCs also reduced cell proliferation and colony formation, similar to those treated with NF-κB and/or FOXM1 inhibitors.
Conclusion
CNCs (10 mg cur/kg bw) attenuate the progression of fluke-related CCA in hamsters partly via a NF-κB and FOXM1-mediated pathway.
... Holt et al. (95) investigated this disease through the use of curcumin, manifesting that there are significant reduction in symptoms as well as inflammatory indices in all patients. In the case of gallbladder contraction, the use of curcumin could also impact to gallbladder through the studies of Rasyid et al. (96,97). As a result, the gallbladder sizes lowered through an appropriately used curcumin dose (20.0-80.0 ...
Turmeric (Curcuma longa L.) is widely utilized as a spice, food colorant, and preservative in India, China, and SouthEast Asia. With containing potential turmeric extracts and compounds, it has been utilized in traditional medicine for various diseases counting diabetes, hepatitis, hemorrhoids, hysteria, indigestion, skin disease, inflammation, anorexia, hepatic disorders, cough, and sinusitis, etc. So far, a large number of work has been conducted to find and prove biological activities and pharmacological applications of turmeric and its extracts in both animals and humans. In particular, curcumin (diferuloylmethane), a characteristic component with major yellow bioactive turmeric feature, has been found to possess numerous biological actions. Nonetheless, the polyphenol compound in curcumin has been limited for human disease treatments even though adequate studies are utilized in animal trials. Plenty of ongoing studies are also contributing significantly to this promising molecule that to the forefront of human therapeutics as well as its activities in health benefits. Thus, curcumin and some turmeric extracts are considered as non-toxic and highly promising compounds with a lot of potentially biological functions based on an appropriately used dose. It is expected that curcumin and some turmeric extracts can be explored in novel medical applications in the future to effectively against or treat various diseases. Here, we hope that it is likely a good and right approach for using and encouraging this product, and its chemical components and effective clinical applications will be briefly summarized in disease treatments. Cite this: Vo TS, Vo TTBC, Vo TTTN, Lai TNH. Turmeric (Curcuma longa L.): Chemical components and Their Effective Clinical Applications. JOTCSA. 2021;8(3):883-98.
... Curcumin is reported to be effective, safe, and tolerable against various chronic diseases in human trials (Kunnumakkara et al., 2017). Clinical trials involving healthy human subjects revealed that curcumin induced a 50% contraction of the gall bladder at the dosage of 40 mg/day (Rasyid, Rahman, Jaalam, & Lelo, 2002). Despite this, JECFA (The Joint FAO/WHO Expert Committee on Food Additives) and EFSA (European Food Safety Authority) established an ADI of up to 3 mg/kg b.w. for curcumin which is equivalent to 210 mg/day for a 70-kg adult (Kocaadam & Şanlier, 2017). ...
The outbreak of mysterious pneumonia at the end of 2019 is associated with widespread research interest worldwide. The coronavirus disease-19 (COVID-19) targets multiple organs through inflammatory, immune, and redox mechanisms, and no effective drug for its prophylaxis or treatment has been identified until now. The use of dietary bioactive compounds, such as phenolic compounds (PC), has emerged as a putative nutritional or therapeutic adjunct approach for COVID-19. In the present study, scientific data on the mechanisms underlying the bioactivity of PC and their usefulness in COVID-19 mitigation are reviewed. In addition, antioxidant, antiviral, anti-inflammatory, and immunomodulatory effects of dietary PC are studied. Moreover, the implications of digestion on the putative benefits of dietary PC against COVID-19 are presented by addressing the bioavailability and biotransformation of PC by the gut microbiota. Lastly, safety issues and possible drug interactions of PC and their implications in COVID-19 therapeutics are discussed.
... We had previously observed that turmeric, which has cholekinetic properties (Rasyid and Lelo, 1999;Rasyid et al., 2002;Marciani et al., 2013), could be administered to mice in order to stimulate bile secretion and thereby elicit bile acid-mediated microbiome-dependent physiologic responses (Dey et al., 2015). Consistent with our prior experience, we found that gnotobiotic Swiss Webster mice colonized with the BSH-high-1 consortium experienced significantly faster whole gut transit times compared to age-matched mice harboring the BSH-low-1 consortium when fed a turmeric-containing diet (n = 4 mice/group; 2.2 G 0.1 vs 2.9 G 0.1 hr, p< 0.02, two-tailed t-test; Figures 2B and S1B), but this difference was not significant in the same mice in the setting of a bland diet (Table S3). ...
Gut motility is regulated by the microbiome via mechanisms that include bile acid metabolism. To localize the effects of microbiome-generated bile acids, we colonized gnotobiotic mice with different synthetic gut bacterial communities that were metabolically phenotyped using a functional in vitro screen. Using two different marker-based assays of gut transit, we inferred that bile acids exert effects on colonic transit. We validated this using an intra-colonic bile acid infusion assay and determined that these effects were dependent upon signaling via the bile acid receptor TGR5. The intra-colonic bile acid infusion experiments further revealed sex-biased bile acid-specific effects on colonic transit, with lithocholic acid having the largest pro-motility effect. Transcriptional responses of the enteric nervous system (ENS) were stereotypic, regional, and observed in response to different microbiota, their associated bile acid profiles, and even to a single diet ingredient, evidencing exquisite sensitivity of the ENS to environmental perturbations.
... It is significantly different from placebo [136]. A subsequent study by the same group showed that curcumin supplementation (40 and 80 mg) resulted in a 50 and 72% reduction in the gallbladder size, respectively [137]. Anemia often comes across in patients with IBD, compromising life and deteriorating the prognosis of the disease. ...
Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disorder of the small intestine and colon. IBD includes ulcerative colitis (UC) and Crohn’s disease (CD), and it is a major factor for the development of colon cancer, referred to as colitis-associated cancer (CAC). The current treatment of IBD mainly includes the use of synthetic drugs and monoclonal antibodies. However, these drugs have side effects over long-term use, and the high relapse rate restricts their application. In the recent past, many studies had witnessed a surge in applying plant-derived products to manage various diseases, including IBD. Curcumin is a bioactive component derived from a rhizome of turmeric (Curcuma longa). Numerous in vitro and in vivo studies show that curcumin may interact with many cellular targets (NF-κB, JAKs/STATs, MAPKs, TNF-γ, IL-6, PPARγ, and TRPV1) and effectively reduce the progression of IBD with promising results. Thus, curcumin is a potential therapeutic agent for patients with IBD once it significantly decreases clinical relapse in patients with quiescent IBD. This review aims to summarize recent advances and provide a comprehensive picture of curcumin’s effectiveness in IBD and offer our view on future research on curcumin in IBD treatment.
... The chemical components responsible for choleretic activity are curcuminoids and sesquiterpenes (α-turmerone and β-turmerone) [12]. Human studies report an increased contraction of the gallbladder with various dosages of curcumin (from 20 to 80 mg) [13][14][15]. Turmeric is used as powdered herbal substance (posology is 0.5-1 g 2-3 times daily), herbal tea (0.5-1.0 g as an infusion 2-3 times daily), tincture (the dilution is 1:10 or 1:5 and the posology is respectively 0.5-1 ml 3 times daily and 10 ml once daily or 5 ml 3 times daily), and dry extract [11]. ...
Introduction:
Turmeric is the common name for the rhizome of Curcuma longa L. In the recent years, food supplements containing turmeric have been marketed and widely used by an increasing number of consumers. Spontaneous reports of suspected adverse reactions to food supplements are collected within the Phytovigilance system.
Methods:
An ad hoc multidisciplinary group investigated the suspected cases of hepatotoxicity reported to the Italian Phytovigilance system associated with the assumption of turmeric food supplements with the methodology specific to pharmacovigilance as well as for the evaluation of the quality and safety of food supplements.
Results:
A cluster of 28 spontaneous reports of acute hepatitis, mostly with cholestasis, associated with turmeric products were sent to the Italian Phytovigilance system in the first six months of 2019. In all cases, except one, the causality assessment was at least possible. The suspected products were collected and analysed for the presence of drugs, heavy metals, aflatoxins, pesticides, synthetic dyes and pyrrolizidine alkaloids.
Conclusion:
On the basis of the results of all the activities performed by multidisciplinary group, regulatory intervention was taken. This study highlights the importance of developing an integrated evaluation approach for the evaluation of the adverse effects associated with the use of food supplements.
... C. domestica contains the major diarylheptanoids, curcuminoids (curcumin, monodemethyoxycurcumin, and bisdemethyoxycurcumin) in the range of 2.9-9.1% (dry weight) (Lechtenberg et al., 2004;Dairam et al., 2007). Curcuminoids have been shown to possess many pharmacological properties including anti-inflammatory and hepatoprotective activities (Srimal and Dhawan, 1973;Hänsel, 1997;Lukita-Atmadja et al., 2002), antioxidant and cholekinetic activities (Masuda et al., 1992(Masuda et al., , 1999Hänsel, 1997;Rasyid et al., 2002), and anti-protease activity (Nishigaki et al., 1992;Sui et al., 1993). In addition, they have been shown to induce apoptosis in human cancer cells (Choudhuri et al., 2002) and act as a chemopreventive agents for major cancer targets, including the breast, prostate, lung, stomach, duodenal and colon cancers, as well as leukemias (Kim et al., 1998;Kelloff et al., 2000;Shao et al., 2002;Duvoix et al., 2005), and display neuroprotective effects (Lee et al., 2007). ...
The metabolic profile of polar (methanol) and non-polar (hexane) extracts of Curcuma domestica, a widely used medicinal plant, was established using various different analytical techniques, including GC-FID, GC-MS, HR-GC-MS and analytical HPLC-ESI-MS/MS by means of LTQ-Orbitrap technology. The major non-volatile curcuminoids curcumin, demethoxycurcumin and bisdemethoxycurcumin were identified when their chromatographic and precursor ion masses were compared with those of authentic standard compounds. In this paper we describe for the first time a GC/MS-based method for metabolic profiling of the hydrophilic extract. We also identified 61 polar metabolites as TMS derivatives.
... Therefore, people with liver diseases such as cirrhosis, gallstones, gallbladder and biliary tract obstruction, acute biliary colic and obstructive jaundice, or those who use drugs for liver problems are contraindicated in curcumin treatment because curcumin may stimulate bile secretion [162]. In fact, a dose of up to 20-40 mg of curcumin a day can increase gallbladder contractions in healthy people [163,164]. Similarly, alcoholics or heavy drinkers cannot use curcumin. In addition, curcumin is not recommended for people taking blood thinners, reserpine, or nonsteroid anti-inflammatory drugs, as it may interact with these drugs [102,158,159]. ...
Currently available pharmacological treatment of post-ischemia-reperfusion brain injury has limited effectiveness. This review provides an assessment of the current state of neurodegeneration treatment due to ischemia-reperfusion brain injury and focuses on the role of curcumin in the diet. The purpose of this review was to provide a comprehensive overview of what was published about the benefits of curcumin influence on post-ischemic brain damage. Some data on the clinical benefits of curcumin treatment of post-ischemic brain in terms of clinical symptoms and adverse reactions have been reviewed. The data in this review contributes to a better understanding of the potential benefits of curcumin in the treatment of neurodegenerative changes after ischemia and informs scientists, clinicians, and patients, as well as their families and caregivers about the possibilities of such treatment. Due to the pleotropic properties of curcumin, including anti-amyloid, anti-tau protein hyperphosphorylation, anti-inflammatory, anti-apoptotic, and neuroprotective action, as well as increasing neuronal lifespan and promoting neurogenesis, curcumin is a promising candidate for the treatment of post-ischemic neurodegeneration with misfolded proteins accumulation. In this way, it may gain interest as a potential therapy to prevent the development of neurodegenerative changes after cerebral ischemia. In addition, it is a safe substance and inexpensive, easily accessible, and can effectively penetrate the blood–brain barrier and neuronal membranes. In conclusion, the evidence available in a review of the literature on the therapeutic potential of curcumin provides helpful insight into the potential clinical utility of curcumin in the treatment of neurological neurodegenerative diseases with misfolded proteins. Therefore, curcumin may be a promising supplementary agent against development of neurodegeneration after brain ischemia in the future. Indeed, there is a rational scientific basis for the use of curcumin for the prophylaxis and treatment of post-ischemic neurodegeneration.
... The first clinical trial to evaluate the effect of curcumin or its preparations 'Curcumen' or 'Curcunat' in human diseases was reported in 1937 and it was found to benefit patients with chronic cholecystitis by inducing rapid gall bladder emptying [212]. A set of studies also indicated the role of curcumin in the prevention of gall-bladder stone formation [213,214]. In 1999, Niederau and Gopfert evinced the positive impact of curcumin in biliary dyskinesia patients [215]. Not only this, but curcumin was also found to improve airway obstruction and hematological parameters in patients with BA [216]. ...
Introduction: Since ancient times, turmeric has been used in several folklore remedies against various ailments. The principle component of turmeric is curcumin and its efficacy has been advocated in in vitro, in vivo and clinical studies for different chronic diseases. However, some studies suggest that curcumin bioavailability is a major problem.
Areas covered: This article discusses over 200 clinical studies with curcumin that have demonstrated pronounced protective role of this compound against cardiovascular diseases, inflammatory diseases, metabolic diseases, neurological diseases, skin diseases, liver diseases, various types of cancer, etc. The review also describes the combination of curcumin with many natural and synthetic compounds as well as various formulations of curcumin that have shown efficacy in multiple clinical studies.
Expert opinion: The therapeutic potential of curcumin as demonstrated by clinical trials has overpowered the myth that poor bioavailability of curcumin poses a problem. Low curcumin bioavailabilty in certain studies has been addressed by using higher concentrations of curcumin within nontoxic limits. Moreover, curcumin in combination with other compounds or as formulations have shown enhanced bioavailability. Hence, bioavailability is not a problem in curcumin mediated treatment of chronic diseases. Therefore, this golden nutraceutical presents a safe, low-cost and effective treatment modality for different chronic diseases.
... The curcumin effects on gall bladder were investigated in two different studies enrolling healthy subjects, where 20e80 mg curcumin were given as a single dose; afterwards gall bladders were measured by an ultrasound technique. It has been found that up to 2 h after single curcumin dose administration, gall bladder dimensions reduced in a dose dependent manner [95,96]. In patients with biliary dyskinesia, a faster reduction in dumpy and colicky pain was stated in group receiving Cholagogum F, when compared with placebo group [97]. ...
... Among enzymes of CYP 450 system, CYP 2E1 is mainly involved in formation of reactive metabolite NAPQI through metabolism in case when glutathione stores get depleted. (Aggarwal et al., 2004), breast cancer (Kakarala et al., 2010), colorectal cancer (Li et al., 2007), lung cancer (Chen et al., 2008), multiple myeloma (Bharti et al., 2003), pancreatic cancer (Dhillon et al., 2008); CVS disorders: Acute coronary syndrome (Shamsara et al., 2009), atherosclerosis (Olszanecki et al., 2005); Neurologic disorders: Alzheimer's disease (Baum et al., 2008), Parkinson's disease (B Mythri and M Srinivas Bharath, 2012), stroke (Kalani et al., 2015); Skin disorders: Psoriasis (Sun et al., 2013), vitiligo (Becatti et al., 2010); Inflammatory disorders: Osteoarthritis (Volpe, 2018), Rheumatoid arthritis (Chandran and Goel, 2012), ulcerative colitis (Lang et al., 2015), peptic ulcers (Khonche et al., 2016), inflammatory bowel disease (Holt et al., 2005), uveitis (Allegri et al., 2010), postoperative inflammation (Jurenka, 2009), H. Pylori infection (Di Mario et al., 2007); Metabolic disorders: Diabetes (Meng et al., 2013), obesity (Shehzad et al., 2011); Infectious diseases: Viral infections , bacterial infections (Rudrappa and Bais, 2008), fungal infections (Martins et al., 2008); Other diseases: Alcohol intoxication , hepatoprotection , recurrent respiratory tract infections (Zuccotti et al., 2009), renal transplantation (Shoskes et al., 2005), chronic arsenic exposure (Biswas et al., 2010), gall bladder contraction (Rasyid et al., 2002). Alcohol intake induces CYP 2E1 and can enhance formation of NAPQI resulting in early hepatic damage. ...
The liver is the most essential organ of the body performing vital functions. Hepatic disorders affect the physiological and biochemical functions of the body. These disorders include hepatitis B, hepatitis C, alcoholic liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), liver cirrhosis, hepatic failure and hepatocellular carcinoma (HCC). Drugs related hepatotoxicity is one of the major challenges facing by clinicians as it is a leading cause of liver failure. During post-marketing surveillance studies, detection and reporting of drug-induced hepatotoxicity may lead to drug withdrawal or warnings. Several mechanisms are involved in hepatotoxicity such as cell membrane disruption, initiating an immune response, alteration of cellular pathways of drug metabolism, accumulation of reactive oxygen species (ROS), lipid peroxidation and cell death. Curcumin, the active ingredient of turmeric and exhibits therapeutic potential for the treatment of diabetes, cardiovascular disorders and various types of cancers. Curcumin is strong anti-oxidant and anti-inflammatory effects and thus it possesses hepatoprotective properties. Despite its low bioavailability, its hepatoprotective effects have been studied in various protocols of hepatotoxicity including acetaminophen, alcohol, lindane, carbon tetrachloride (CCL4), diethylnitrosamine and heavy metals induced hepatotoxicities. This report reviews the hepatoprotective effects of curcumin with a focus on its mechanistic insights in various hepatotoxic protocols.
... Therefore, a person with liver diseases, such as cirrhosis, biliary tract obstruction, gallstones, obstructive jaundice and acute biliary colic, or those are under prescribed medication for hepatic problems are counter-indicated for Cur therapy, because Cur can stimulate bile secretion [74]. In fact, supplementation of even 20-40 mg of Cur per day can increase the gallbladder contractions in healthy people [195,196]. Similarly, alcoholics or heavy drinkers may not receive the benefits of this therapy. Furthermore, the individual taking any blood thinning agents, non-steroidal anti-inflammatory (NSAIDs) drugs, or reserpine are recommended not to take Cur, because, it can interact with these drugs [10,33,126]. ...
Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur) has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.
... The dose of 6 g (corresponding to 120 mg of curcumin) was chosen because it appeared as the maximal dose that the volunteers could ingest (12 pills of 500 mg) without risk of vomiting, and because it was close to the maximum daily intake recommended by the FDA (180 mg curcumin). Moreover, previous studies showed that pharmacodynamic effects were observed with doses of curcumin starting at 20 mg [21]. ...
Hepcidin, secreted by hepatocytes, controls iron metabolism by limiting iron egress in plasma. Hepcidin is up-regulated during inflammation through the activation of the signal transducer and activator of transcription 3 (STAT3) transduction pathway, which decreases iron bioavailability and may explain the anemia of chronic inflammatory disease. In vitro, it has been shown that curcumin can decrease hepcidin synthesis by decreasing STAT3 activity. We conducted a proof-of-concept study to assess the effect of curcuma on hepcidin synthesis in human. This was a placebo-controlled, randomized, double-blind, cross-over, two-period study performed in 18 healthy male volunteers. Subjects received a single oral dose of 6g curcuma containing 2% of curcumin or placebo. Serum hepcidin, and iron parameters were assessed repeatedly until 48h after dosing. When compared with a placebo curcuma decreased hepcidin levels significantly at 6h (-19%, p=0.004), 8h (-17%, p=0.009), and 12h (-17%, p=0.007), and tended to decrease hepcidin at 24h (-15%, p=0.076). Curcuma also significantly increased serum ferritin levels at 6h and 8h (+7% for both times, p=0.018, p=0.030, respectively) and had no effects on serum iron, transferrin and transferrin saturation. This pilot study showed that curcuma decreases serum hepcidin levels in human and supports the idea that curcuma could be useful in treating hepcidin over-production during inflammatory processes. Confirmatory studies in patients with chronic inflammation are now required to determine the optimal dose and therapeutic scheme of curcuma. This article is protected by copyright. All rights reserved.
... Curcumin is the principal polyphenol of the curcuminoid class of the Indian spice Curcuma Longa Linn., a plant typically grown and used in Southeast Asia ( Figure 10) [113]. Curcumin lowers cholesterol, reduces platelet aggregation, inhibits the proliferation of cancer cells and improves digestion by increasing the flow of bile from the gallbladder [114]. Moreover, it has immunomodulatory, antiangiogenic and neuroprotective actions, antioxidant and anti-inflammatory abilities and the capacity to modulate the activity of several key transcription factors, cytokines, growth factors, kinases and other enzymes [115]. ...
Natural polyphenols are valuable compounds present in plants, fruits, legumes, chocolate, tea, wine and marine
organisms possessing scavenging properties towards radical oxygen species. These abilities make polyphenols
interesting either for the treatment of various diseases like inflammation and cancer or for anti-ageing purposes
in cosmetic formulations. Unfortunately, such compounds lack in long-term stability, are very sensitive to light,
and often present a low water solubility and poor bioavailability. To overcome these limitations and enhance
polyphenols therapeutic applications, nanotechnology-based delivery systems have been developed, and among all,
nanoencapsulation represented a promising strategy. This review described a recent overview of physicochemical
nanoencapsulated polyphenols focusing on the most representative molecules such as resveratrol, quercetin,
epigallocatechin-3-gallate, and curcumin.
... Curcumin is the principal polyphenol of the curcuminoid class of the Indian spice Curcuma Longa Linn., a plant typically grown and used in Southeast Asia ( Figure 10) [113]. Curcumin lowers cholesterol, reduces platelet aggregation, inhibits the proliferation of cancer cells and improves digestion by increasing the flow of bile from the gallbladder [114]. Moreover, it has immunomodulatory, antiangiogenic and neuroprotective actions, antioxidant and anti-inflammatory abilities and the capacity to modulate the activity of several key transcription factors, cytokines, growth factors, kinases and other enzymes [115]. ...
Natural polyphenols are valuable compounds present in plants, fruits, legumes, chocolate, tea, wine and marine organisms possessing scavenging properties towards radical oxygen species. These abilities make polyphenols interesting either for the treatment of various diseases like inflammation and cancer or for anti-ageing purposes in cosmetic formulations. Unfortunately, such compounds lack in long-term stability, are very sensitive to light, and often present a low water solubility and poor bioavailability. To overcome these limitations and enhance polyphenols therapeutic applications, nanotechnology-based delivery systems have been developed, and among all, nanoencapsulation represented a promising strategy. This review described a recent overview of physicochemical nanoencapsulated polyphenols focusing on the most representative molecules such as resveratrol, quercetin, epigallocatechin-3-gallate, and curcumin.
... 3) Consumption of high doses of tea preparations is associated with gastrointestinal irritation, and chromosomal translocation [195, 196]. 4) Supplementation of curcumin (20-40 mg) has been reported to increase gallbladder contractions [197]. Thus, high doses of dietary flavonoids should be considered with caution, and the adverse effects of phytochemicals may be explained by the relatively low bioavailability and rapid metabolism and elimination of most flavonoids. ...
... Instead a concentration-dependent relaxation of CCK-and KCl-induced tension was obtained using curcumin. In humans it was reported that 20 mg of curcumin swallowed with 100 mL of water was capable of contracting the human gallbladder (of both sexes) 29% within an observation time of 2 h [17,18]. The concentration of curcumin used in the current study may not be considered physiologic; however, it has been argued that the shortterm application of high concentrations of factors can mimic low (physiologic) levels applied over a long period of time. ...
Background
Curcumin (diferuloymethane) is the active ingredient of the dietary spice turmeric. Curcumin modulates various signalling molecules, including inflammatory agents, transcription factors, protein kinases and cell cycle regulatory proteins. The purpose of this study was to determine if curcumin had an effect on gallbladder motility.
Methods
A pharmacologic in vitro technique was used. Since curcumin relaxed both cholecystokinin octapeptide- (CCK) and KCl-induced tension of guinea pig gallbladder strips in a concentration dependent manner, an in vitro technique was used to determine which second messenger system(s) mediated the observed relaxation. Paired t-tests, t-tests and analysis of variance were used for statistical analysis. Differences between mean values of P < 0.05 were considered significant.
Results
To determine if protein kinase A (PKA) mediated the curcumin-induced relaxation, PKA inhibitor 14-22 amide myristolated (PKA-IM) was used. PKA-IM had no significant effect on the amount of curcumin-induced relaxation. When the protein kinase C (PKC) inhibitors bisindolymaleimide IV and chelerythrine Cl⁻ were used together, a significant (P < 0.01) reduction in the curcumin-induced relaxation was observed. The use of tetraethylammonium chloride (TEA) caused a significant (P < 0.01) decrease in the amount of curcumin-induced relaxation. Adding curcumin prior to the KCl caused a significant (P < 0.001) decrease in the amount of KCl-induced tension.
Conclusions
The results suggested that the curcumin-induced relaxation is mediated by multiple signaling pathways including the PKC second messenger system, inhibiting extracellular Ca²⁺ entry and K+ channels.
... Moreover, at high doses curcumin induces chromosome aberrations and astrocyte cell death [114,115]. In addition, curcumin induces human gallbladder contraction and therefore it is not recommended for gallstones patients [116]. Despite to this, there is a lack of scientific information about systematic toxicity of curcumin and, therefore, it can be suggested that future studies should be performed to fully address the toxicity of curcumin. ...
Curcumin is the yellow-colored bioactive constituent of the perennial plant, Curcuma longa L., which possesses a wide range of physiological and pharmacological properties such as antioxidant, anti-inflammatory, anticancer, neuroprotective and anti-diabetic activities. Anti-diabetic activity of curcumin may be due to its potent ability to suppress oxidative stress and inflammation. Moreover, it shows a beneficial role on the diabetes-induced endothelial dysfunction and induces a down-regulation of nuclear factor-kappa B. Curcumin possesses a protective role against advanced glycation as well as collagen crosslinking and through this way, mitigates advanced glycation end products-induced complications of diabetes. Curcumin also reduces blood glucose, and the levels of glycosylated hemoglobin in diabetic rat through the regulation of polyol pathway. It also suppresses increased bone resorption through he inhibition of osteoclastogenesis and expression of the AP-1 transcription factors, c-fos and c-jun, in diabetic animals. Overall, scientific literature shows that curcumin possesses anti-diabetic effects and mitigates diabetes complications. Here we report a systematical discussion on the beneficial role of curcumin on diabetes and its complications with emphasis on its molecular mechanisms of actions.
... Cheng et al. [54] reported that no treatment-related toxicity was observed up to 8 g daily in phase I clinical trials, but beyond this dose, the bulk volume of the drug was unacceptable to the patients. Similarly, several other clinical trials have reported use of curcumin on various disease conditions viz, cancer [55], familial adenomatous polyposis [56], tropical pancreatic cancer [57], inflammatory bowel disease [58,59], gall bladder function [60], psoriasis [61] and helicobacter pylori infection [62]. ...
The present study was proposed to elucidate the prophylactic role of curcumin in the prevention of hypoxia-induced cerebral edema (HACE).
Rats were exposed to simulated hypobaric hypoxia at 7620 m for 24 h at 25 ± 1 °C. Transvascular leakage, expression of transcriptional factors (nuclear factor-kappa B (NF-κB) and hypoxia inducible factor 1 alpha (Hif-1α) and also the genes regulated by these transcriptional factors, sodium potassium-adenosine triphosphatase (Na(+)/K(+)-ATPase) and endothelial sodium channel (ENaC) levels and brain tight junction (TJ) proteins like ZO-1, junctional adhesion molecule C (JAMC), claudin 4 and claudin 5 levels were determined in the brain of rats under hypoxia by Western blotting, electro mobility shift assay, ELISA, immunohistochemistry, and histopathology along with haematological parameters. Simultaneously, to rule out the fact that inflammation causes impaired Na(+)/K(+)-ATPase and ENaC functions and disturbing the TJ integrity leading to cerebral edema, the rats were pre-treated with curcumin (100 mg/kg body weight) 1 h prior to 24-h hypoxia.
Curcumin administration to rats, under hypoxia showed a significant decrease (p < 0.001) in brain water content (3.53 ± 0.58 wet-to-dry-weight (W/D) ratio) and transvascular leakage (136.2 ± 13.24 relative fluorescence units per gram (r.f.u./g)) in the brain of rats compared to control (24-h hypoxia) (7.1 ± 1.0 W/D ratio and 262.42 ± 24.67 r.f.u./g, respectively). Curcumin prophylaxis significantly attenuated the upregulation of NF-κB (p < 0.001), thereby leading to concomitant downregulation of pro-inflammatory cytokine levels (↓IL-1, IL-2, IL-18 and TNF-α), cell adhesion molecules (↓P-selectin and E-selectin) and increased anti-inflammatory cytokine (↑IL-10). Curcumin stabilized the brain HIF-1α levels followed by maintaining VEGF levels along with upregulated Na(+)/K(+)-ATPase and ENaC levels (p < 0.001) under hypoxia. Curcumin restored the brain ZO-1, JAMC, claudin 4 and claudin 5 levels (p < 0.001) under hypoxia. Histopathological observations revealed the absence of edema and inflammation in the brain of rats supplemented with curcumin.
These results indicate that curcumin is a potent drug in amelioration of HACE as it effectively attenuated inflammation as well as fluid influx by maintaining the tight junction protein integrity with increased ion channel expression in the brain of rats under hypoxia.
... However, curcumin may have adverse effect in the following situations: (a) curcumin increases contraction in the gallbladder and potentially could increase the risk of symptoms in people with gallstone [331,332]; (b) curcumin can increase the risk of bleeding in subjects taking anticoagulant medicines because it can inhibit platelet aggregation [333,334]; and (c) curcumin also increases acid output in the stomach and can interfere with acid suppressing drugs in patients with duodenal ulcers [335]. ...
Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Ayurvedic Medicine, or Ayurveda, is a traditional Indian health care system. Research into the medicinal plants utilised in Ayurveda is becoming a global endeavour, and large pharmaceutical companies are investing in novel drug discovery from Ayurvedic sources as a number of clinical studies have demonstrated efficacy of natural products from Ayurvedic plant extracts against common ailments such as arthritis and diabetes.
Ayurvedic medicine and its components have been well described in the past, but this book represents a comprehensive source on the biochemistry and mechanisms of the pharmacological effects of natural products from Ayurvedic sources.
This book is a valuable resource for researchers in natural products and alternative sources of bioactive compounds in drug discovery, as well as pharmaceutical experts and those in industry.
Two turmeric food powders (C1 and C2) were studied for curcuminoid content and their effects on the guinea pig intestinal tract in vitro. C1 contained a higher curcuminoid content than C2 (5.22% vs 2.31%). C1 and C2 increased gallbladder (∼10%) and biliary smooth muscle tone (∼15%), without affecting the sphincter of Oddi smooth muscle contractility. C2 was more effective than C1 in lowering ileum tone (–22% vs −37%), whereas the reverse occurred in the colon (-50% vs −20%). Standard Fast Fourier transforms and absolute powers analysis of the frequency bands highlighted that, in the bile duct, C2 induced contractions of higher variability and ampler oscillations of low-frequency waves. At the Oddi sphincter, C1 had a biphasic effect, increasing and then drastically decreasing the oscillations. The same occurred with C2 in the ileum, while both samples reduced the fluctuations in the colon.
Background: Curcumin-loaded nanocomplexes (CNCs) previously demonstrated lower toxicity and extended release better than is the case for free curcumin. Here, we evaluated the efficacy of CNCs against opisthorchiasis-associated cholangiocarcinoma (CCA) in hamsters.
Method: Dose optimization (dose and frequency) was performed over a one-month period using hamsters, a model that is widely used for study of opisthorchiasis-associated cholangiocarcinoma. In the main experimental study, CCA was induced by a combination of fluke, Opisthorchis viverrini (OV), infection and N-nitrosodimethylamine (NDMA) treatment. Either blank (empty) nanocomplexes (BNCs) or different concentrations of CNCs (equivalent to 10 and 20 mg cur/kg bw) were given to hamsters thrice a week for five months. The histopathological changes, biochemical parameters, and the expression of inflammatory/ oncogenic transcription factors were investigated.
Results: The optimization study revealed that treatment with CNCs at a dose equivalent to 10 mg cur/kg bw, thrice a week for one month, led to a greater reduction of inflammation and liver injury induced in hamsters by OV+NDMA than did treatments at other dose rates. Oral administration with CNCs (10 mg cur/kg bw), thrice a week for five months, significantly increased survival rate, reduced CCA incidence, extent of tumor development, cholangitis, bile-duct injury and cholangiofibroma. In addition, this treatment decreased serum ALP and ALT levels and suppressed expression of oncogenic transcription factors including NF- κB and FOXM1.
Conclusion: CNCs (10 mg cur/kg bw) attenuate the progression of fluke-related CCA in hamsters.
The last decade has seen an unprecedented rise in the prevalence of chronic diseases worldwide. Different mono-targeted approaches have been devised to treat these multigenic diseases, still most of them suffer from limited success due to the off-target debilitating side effects and their inability to target multiple pathways. Hence a safe, efficacious, and multi-targeted approach is the need for the hour to circumvent these challenging chronic diseases. Curcumin, a natural compound extracted from the rhizomes of Curcuma longa, has been under intense scrutiny for its wide medicinal and biological properties. Curcumin is known to manifest antibacterial, antiinflammatory, antioxidant, antifungal, antineoplastic, antifungal, and proapoptotic effects. A plethora of literature has already established the immense promise of curcuminoids in the treatment and clinical management of various chronic diseases like cancer, cardiovascular, metabolic, neurological, inflammatory, and infectious diseases. To date, more than 230 clinical trials have opened investigations to understand the pharmacological aspects of curcumin in human systems. Still, further randomized clinical studies in different ethnic populations warrant its transition to a marketed drug. This review summarizes the results from different clinical trials of curcumin-based therapeutics in the prevention and treatment of various chronic diseases.
Background
Curcumin is a natural polyphenol and the main compound from the rhizome of Turmeric (Curcuma longa) and other Curcuma species. It has been widely used for different medical purposes, such as improvement of pain and inflammatory conditions in various diseases.
Purpose
This systematic review was aimed to assess all studies regarding the efficacy of the pure form of curcumin (unformulated curcumin) on rheumatoid arthritis (RA).
Methods
The comprehensive search of the literature was done until September 2020 on the MEDLINE, Embase, Scopus, and Web of Knowledge databases. Out of 2079 initial records, 51 articles (13 in vitro and 37 animal and one human) were met our inclusion criteria.
Results
Most studies have shown the curative effects of curcumin on clinical and inflammatory parameters of RA and reported different mechanisms; inhibition of mitogen‐activated protein kinase family (MAPK), extracellular signal‐regulated protein kinase (ERK1/2), activator protein‐1 (AP‐1), and nuclear factor kappa B (NF‐kB) are the main mechanisms associated with the anti‐inflammatory function of curcumin in RA. The results of the only human study showed that curcumin significantly improved morning stiffness, walking time, and joint swelling.
Conclusion
In conclusion, curcumin seems to be useful and it is recommended that more human studies be performed to approve the cellular and animal results and determine the effective and optimal doses of curcumin on RA patients.
The novel coronavirus outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was recognized in late 2019 in Wuhan, China. Subsequently, the World Health Organization declared coronavirus disease 2019 (COVID-19) as a pandemic on 11 March 2020. The proportion of potentially fatal coronavirus infections may vary by location, age, and underlying risk factors. However, acute respiratory distress syndrome (ARDS) is the most frequent complication and leading cause of death in critically ill patients. Immunomodulatory and anti-inflammatory agents have received great attention as therapeutic strategies against COVID-19. Here, we review potential mechanisms and special clinical considerations of supplementation with curcumin as an anti-inflammatory and antioxidant compound in the setting of COVID-19 clinical research.
Curcumin, an essential ingredient of a well-known Indian spice Turmeric, has been proven to protect from numerous diseases including liver diseases. Despite its remarkable therapeutic efficacy, a few limitations such as low water solubility, low bioavailability, and short systemic circulation impeded its success. To overcome these challenges and offer significant therapeutic efficacy of curcumin, a wealth of research studies used multifarious drug delivery systems that significantly enhanced the therapeutic efficacy of curcumin. However, they also showed a few demerits such as nonspecific drug delivery, drug dripping from the delivery system, etc. This chapter has primarily focused on various nanotechnological methods used to overcome challenges associated with curcumin.
Curcumin faces challenges such as poor aqueous solubility and limited bioaccessibility which limits its oral therapeutic applications. This work evaluated the complexation of curcumin using pea protein isolate (PPI, leguminous protein) vis-à-vis whey protein isolate (WPI, animal protein) to overcome these limitations. Thermodynamic parameters (ΔH and ΔS) indicated the interaction to be hydrophobic in nature. While WPI-curcumin complex showed better aqueous solubility for curcumin than PPI-curcumin complex at varying pH (3, 5 & 7), the PPI-curcumin complex showed better solubility at higher temperature of 80 °C. The solubility of curcumin in WPI-curcumin and PPI-curcumin complex at pH 7 was 1.16 mg/g and 1.02 mg/g, respectively. The protein curcumin solutions were further spray dried and characterized for surface hydrophobicity, crystallinity, thermal properties, and surface morphology. Both the proteins showed a similar score for bioaccessibility of curcumin from their respective complexes. Thus PPI can be a good non-dairy protein alternative for curcumin delivery.
Polyphenols are potent micronutrients that can be found in large quantities in various food sources and spices. These compounds, also known as phenolics due to their phenolic structure, play a vital nutrient-based role in the prevention of various diseases such as diabetes, cardiovascular diseases, neurodegenerative diseases, liver disease, and cancers. However, the function of polyphenols in disease prevention and therapy depends on their dietary consumption and biological properties. According to American Cancer Society statistics, there will be an expected rise of 23.6 million new cancer cases by 2030. Due to the severity of the increased risk, it is important to evaluate various preventive measures associated with cancer. Relatively recently, numerous studies have indicated that various dietary polyphenols and phytochemicals possess properties of modifying epigenetic mechanisms that modulate gene expression resulting in regulation of cancer. These polyphenols and phytochemicals, when administrated in a dose-dependent and combinatorial-based manner, can have an enhanced effect on epigenetic changes, which play a crucial role in cancer prevention and therapy. Hence, this review will focus on the mechanisms of combined polyphenols and phytochemicals that can impact various epigenetic modifications such as DNA methylation and histone modifications as well as regulation of non-coding miRNAs expression for treatment and prevention of various types of cancer.
Le curcuma provient du rhizome séché et broyé d'une plante de la famille des Zingiberaceae. Cette plante herbacée, Curcuma longa, est cultivée en Inde et en Asie du Sud-est. L'Inde est le plus grand producteur et le plus grand consommateur de curcuma au monde.Par contre, en Occident, en dehors de ses usages médicinaux et tinctoriaux, son emploi n'a jamais été très répandu. Son emploi, en Asie, en Afrique et au Proche et Moyen-Orient, remonte à plus de 4000 ans. Dès cette époque, le curcuma est utilisé en tant qu'épice, mais aussi comme agent de coloration de plusieurs aliments, tel que le curry, de même que dans la production de cosmétiques, de teintures et de médicaments.La couleur jaune du curcuma provient d'un mélange de pigments phénoliques, les curcuminoïdes. La teneur en curcuminoïdes dans la poudre de curcuma est d'environ 5%. Ce mélange de composés phénoliques se compose de 70 à 75% de curcumine, de 15 à 20% de diméthoxycurcumine et de 3 à 5% de bisdiméthoxycurcumine. De ces trois curcuminoïdes, c'est la curcumine qui présente les propriétés pharmacologiques les plus intéressantes.Dans la médecine indienne traditionnelle, le curcuma est employé comme remède contre la toux, les désordres biliaires, l'anorexie, les plaies des diabétiques, les désordres hépatiques, les rhumatismes et les sinusites.Plus récemment, des études, effectuées in vitro et in vivo, ont montré que la curcumine possédait des activités biologiques intéressantes pour la santé humaine incluant un effet antioxydant, anti-inflammatoire et anti-cancer.Depuis ces dix dernières années, le nombre d'études sur le curcuma et surtout sur son constituant majeur, la curcumine, n'a cessé d'augmenter afin de comprendre ses mécanismes d'actions et dans l'espoir de traiter de nombreuses maladies. Des siècles d'utilisation ont montré son innocuité et les premières études cliniques n'ont rapporté aucun effet secondaire. Enfin, de fil en aiguille, les recherchessont passées des laboratoires à la clinique, et la curcumine devrait trouver une application en tant que nouveau médicament dans un futur proche pour contrôler des maladies variées, notamment les désordres inflammatoires, le cancer, et lespathologies causées par le stress oxydatif.
Periodontitis is a chronic infl ammatory disease in the oral cavity caused by bacterial
biofi lm attached to tooth surfaces. The periodontal pathogenic microorganisms trigger
the disease process; however, the destruction of the periodontium is mostly caused by
the host’s immune response to the bacterial insults.
The main thrust of periodontal therapy has been centered traditionally on reducing the
microbial load by mechanical and antimicrobial means. This approach has been reported
to be effective for the majority of patients and sites. However, modulating the host response
by anti-infl ammatory agents could provide another viable pathway to managing poorly responding periodontal patients. The overall objective of this paper is to review current data pertinent to curcumin and its dual anti-inflammatory and antimicrobial properties and to explore its potential in managing patients with periodontal diseases.
Curcumin has a wide biological spectrum that could provide clinicians with an alternative
anti-infl ammatory and antimicrobial agent for managing a variety of maladies including
periodontal diseases. However, large-scale longitudinal randomized clinical trials are
needed to prove efficacy and effectiveness of curcumin in managing periodontitis. Furthermore,
its structure requires modification in order to improve its bioavailability and its clinical
effectiveness. Further research aiming at improving its delivery and formulation will
enhance its dual potential as an important anti-inflammatory and anti-microbial
agent in periodontology.
Periodontitis is a chronic infl ammatory disease in the oral cavity caused by bacterial
biofi lm attached to tooth surfaces. The periodontal pathogenic microorganisms trigger
the disease process; however, the destruction of the periodontium is mostly caused by
the host’s immune response to the bacterial insults.
The main thrust of periodontal therapy has been centered traditionally on reducing the
microbial load by mechanical and antimicrobial means. This approach has been reported
to be effective for the majority of patients and sites. However, modulating the host response
by anti-inflammatory agents could provide another viable pathway to managing poorly responding periodontal
patients.
The overall objective of this paper is to review current data pertinent to curcumin and its dual anti-inflammatory and antimicrobial properties and to explore its potential in managing patients with periodontal diseases.
Curcumin has a wide biological spectrum that could provide clinicians with an alternative
anti-inflammatory and antimicrobial agent for managing a variety of maladies including
periodontal diseases. However, large-scale longitudinal randomized clinical trials are
needed to prove efficacy and effectiveness of curcumin in managing periodontitis. Furthermore,
its structure requires modification in order to improve its bioavailability and its clinical effectiveness.
Further research aiming at improving its delivery and formulation will enhance its dual potential as an important anti-infl ammatory and anti-microbial agent in periodontology
Alzheimer's disease (AD) is the most common form of dementia, and it has only a limited treatment choice in modern therapeutics. Hence, newer and alternate treatment options with high efficacy and good safety profiles are being explored. Turmeric possesses multiple medicinal uses in a variety of diseases, including AD. Curcuminoids, a mixture of curcumin, demethoxycurcumin, and bisdemethoxycurcumin, are vital constituents of turmeric that are well known for their promising pharmacological profile, particularly in AD. It is generally believed that curcumin is the most important constituent of the curcuminoid mixture. However, a careful literature study reveals that significant evidence exists for the effectiveness of the other two constituents in AD. In this chapter, we highlight the critical and distinctive role of each, concluding that curcuminoid mixture - being a mixture of all three constituents - has multiple targets and serves as a potential therapeutic candidate for AD.
Globally, millions of people are getting affected with a chronic metabolic disorder, diabetes mellitus. Experimental and clinical approaches suggest that cellular stress (oxidative stress, nitrosative stress, and endoplasmic reticulum stress) plays a fundamental role in the pathogenesis of this silent pandemic and its related complications. Although some achievement has been made in diabetes management and drug discovery, both the patients and physicians are still facing problems with severe diabetic complications due to the adverse effects of these medications. Use of natural antioxidants, therefore, could be an apparent substitute as the interplay between reactive species (ROS, RNS, etc.) and antioxidants are important in maintaining individual's health. In this regard, new strategies with the natural antioxidants should be implemented for the treatment of diabetes mellitus in the world of biomedical sciences. This particular chapter begins with the extraction and identification of various naturally occurring antioxidants present in food, plants, and dietary supplements, then moves on to the discussion of their detailed beneficial role, cellular and molecular mechanism of action on various stress-induced diabetes and its related complications (organ damage), and ends up with the discussion of their clinical trials and harmful effects. This book chapter would be an effective guide for the readers to gain the up-to-date knowledge on the extraction, identification, and the journey of natural antioxidants as effective antidiabetic agents.
Curcuma xanthorhiza Roxb, is an original medicinal plant from Indonesia. Almost of Indonesian Jamu consist of it, and the people made it in the various methods such as decoction, homemade jamu. Nowadays, it is used in the formal therapy, such as in vitamins. It contains curcuminoid which one is curcumin that has various activities. The objective of the research is to evaluate the curcumin concentrations in two different preparation methods, fresh and decoction of dried rhizome. The rhizome was screened of the phytochemical constituents. Fresh rhizome was scraped and was kneaded with 50 ml of boiled water, dried rhizome was boiled in 50 ml water at 90°C in 30 minutes, volume to be kept at constant. Both were filtered and the supernatants were evaporated on the water bath. Curcumin were isolated with 50 ml methanol. Concentrations of curcumin were measured with spectrophotometer at wavelength 418 nm. Phytochemicals screening showed of positive results for the presence of alkaloid, saponin, quinon, and steroid/triterfenoid. From 20 g fresh of Curcuma xanthorhiza rhizome and 5.87 g decoction of dried Curcuma xanthorhiza rhizome could be isolated 37.9 mg and 12.95 mg curcumin respectively. In conclusion curcumin concentration that could be isolated from fresh Curcuma xanthorhiza rhizome is higher than decoction of dried Curcuma xanthorhiza rhizome, those are 37.9 mg and 12.95 mg curcumin respectively. Curcumin has positive effects on health, hence both fresh and decoction of dried Curcuma xanthorrhiza rhizome can promote the consumers health.
Background: Turmeric has a long history for food additive and medicinal uses. In Asian traditional medical systems turmeric has been expected to be a therapeutic or preventive agent for several human diseases including: gastrointestinal symptoms, liver disease, kidney stone, rheumatic and menstrual disorders. Due to its current uses as well as its pharmacological effects further information needs for future clinical studies. Objective: The aim of this review was to provide an update overview of research studies focused on the pharmacological effects of turmeric and its active component curcumin. Methods: A computerized search of published articles was performed using the electronic database such as MEDLINE from 1980 to 2009. Results: The large numbers of articles published on pharmacological effects of turmeric over recent three decade. Turmeric and its active component curcumin exert several pharmacological effects including anti-inflammatory, anti-oxidant, anti-cancer, hypoglycemic, hypolipidemic and immunomudulator as observed in experimental and some clinical studies. Conclusion: The present scientific-based evidence provide good information about pharmacological effects of turmeric. These information may be useful to researcher for induction of clinical trial for this herbal medicine in treatment of traditionally recognized application such as cancer, liver, gastrointestinal and cardiovascular disease, Alzheimer, rheumatoid arthritis, diabetes.
Summary To understand how different diets, the consumers' gut microbiota, and the enteric nervous system (ENS) interact to regulate gut motility, we developed a gnotobiotic mouse model that mimics short-term dietary changes that happen when humans are traveling to places with different culinary traditions. Studying animals transplanted with the microbiota from humans representing diverse culinary traditions and fed a sequence of diets representing those of all donors, we found that correlations between bacterial species abundances and transit times are diet dependent. However, the levels of unconjugated bile acids - generated by bacterial bile salt hydrolases (BSH) - correlated with faster transit, including during consumption of a Bangladeshi diet. Mice harboring a consortium of sequenced cultured bacterial strains from the Bangladeshi donor's microbiota and fed a Bangladeshi diet revealed that the commonly used cholekinetic spice, turmeric, affects gut motility through a mechanism that reflects bacterial BSH activity and Ret signaling in the ENS. These results demonstrate how a single food ingredient interacts with a functional microbiota trait to regulate host physiology.
It has been recently shown that erythromycin, a macrolide antibiotic, exhibits prokinetic properties, by enhancing gastric emptying in health and disease and by inducing gallbladder contraction. The aim of the study was to further investigate the effect of intravenous erythromycin on gallbladder motility during fasting and postprandial states. In 10 healthy male subjects gallbladder emptying was assessed by ultrasonography on three different occasions, each in a random sequence, as follows: (1) after giving 300 ml of fresh milk and infusing normal saline as placebo (postprandial emptying), (2) after infusing 200 mg of erythromycin during the fasting state, and (3) after infusing 200 mg of erythromycin along with ingestion of 300 ml of fresh milk. Infusion of erythromycin and placebo lasted 10 min. From the emptying curves, the duration of the lag phase of emptying, the ejection fraction of emptying, and the time by which maximal emptying was achieved were calculated. Infusion of erythromycin induced an immediate contraction [lag phase (+/-SD): 1.3+/-2.6 SD min] of the gallbladder by 42.1+/-22% of its initial volume. Infusion of erythromycin during the postprandial state significantly decreased the duration of the lag phase (1.3+/-3.5 min after erythromycin plus test meal versus 3.6+/-4.2 min after test meal only, P < 0.04) and significantly increased the ejection fraction (78+/-8.5% after erythromycin plus test meal versus 60.6+/-8.5% after test meal only, P < 0.0008). It is concluded that intravenously given erythromycin induces contraction of the gallbladder during the fasting state and enhances postprandial gallbladder emptying by accelerating the initiation and increasing the extent of emptying.
Impaired gallbladder emptying is implicated in gallstone disease. Ultrasonography and scintigraphy have shown conflicting results because the former is influenced by postprandial refilling, whereas the latter is not influenced by refilling. The aim of this study was to measure postprandial refilling and turnover of bile by combining the two techniques.
Simultaneous scintigraphy and ultrasonography were used in 14 patients with gallstones and 11 healthy controls. Measurements were performed while the patients were fasting and at 10-minute intervals after a standard meal for 90 minutes, and the measurements were used to calculate postprandial refilling, turnover of bile (in milliliters), and turnover index.
Ultrasonography and scintigraphy provided different gallbladder emptying patterns. Compared with controls, patients with gallstones had impaired emptying by both scintigraphy (P < 0.0001) and ultrasonography (P < 0.01). Postprandial refilling and turnover were both reduced between 60 and 90 minutes (P < 0.05), and the turnover index was markedly reduced (1.8 vs. 3.5; P < 0.001).
Simultaneous scintigraphy and ultrasonography provide a new model of gallbladder motor function showing that refilling begins immediately postprandially. In healthy controls, the gallbladder postprandially handles up to six times its basal volume within a period of 90 minutes, but this turnover of bile is markedly reduced in cholelithiasis causing a reduced washout effect of the gallbladder contents, including cholesterol crystals.
The extract of medicinal plants containing curcumin is traditionally believed to have a positive contraction effect on the human gall-bladder.
To compare the effect of 20 mg curcumin or placebo on the gall-bladder volume of healthy volunteers.
A randomized, double blind and crossover design study was carried out in 12 healthy volunteers (seven males and five females). Ultrasonography examination was carried out serially to measure the gall-bladder volume. The data obtained was analysed by paired Student's t-test.
The fasting gall-bladder volumes of 15.74 +/- 4.29 mL on curcumin and 15.98 +/- 4.08 mL on placebo were similar (P > 0.20). The gall-bladder volume was reduced within the period after curcumin administration. The percentage of gall-bladder volume reduction at 0.5, 1.0, 1.5 and 2.0 h after 20 mg curcumin administration were 11.8 +/- 6.9, 16.8 +/- 7.4, 22.0 +/- 8.5 and 29. 3 +/- 8.3%, respectively, which was statistically significant compared to placebo.
On the basis of the present findings, it appears that curcumin induces contraction of the human gall-bladder.
Cholekinetic effect of an agent on human gallbladder could be investigated by monitoring and measuring the changes of its volume before and after drug administration. The pharmaco-sonography study is based on such phenomena. Ellipsoid method is a simple and accurate ultrasonography method in measuring gallbladder volume. However, it could be applied only for gallbladder with an ellipsoid form. The present study aimed to define the distribution of gallbladder forms in a population (n = 300 persons, 145 males and 155 females). This study demonstrated that the common shape of gallbladder was elliptical form (67%), followed by simple folded form (15%), multiple folded form (6%), double folded form (5%), phrygian cap form (5%), and angulated form (3%). Furthermore, the distribution of gallbladder forms was not different (p < 0.05) between genders. It was concluded that the ellipsoid method could be applied in measuring human gallbladder volume in 2 out of 3 people, at least in Indonesian citizens.
To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double-blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects.
The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects.
Gallbladder contractility can be quantified radiologically, but it is not known whether the degree of contraction exhibited by a person's gallbladder varies from day to day. Thirty healthy volunteers were studied with sonography on three separate occasions to determine the variation of individual gallbladder contractility. Using the ellipsoid method, we measured gallbladder volume after an overnight fast (fasting gallbladder volume) and between 45 and 60 min after a standard fatty meal (residual gallbladder volume). Percentage gallbladder contraction was calculated by dividing the difference between the fasting and residual gallbladder volumes by the fasting gallbladder volume and multiplying by 100. The 90 studies in 30 subjects exhibited a wide range of values: fasting gallbladder volume from 1.9 to 45.5 ml, residual gallbladder volume from 0.1 to 21.0 ml, and percentage gallbladder contraction from -10% to 99%. Within each subject, fasting gallbladder volume measurements varied from 1.5 to 26.2 ml (mean +/- two standard deviations, 10.3 +/- 5.1 ml) and residual gallbladder volume from 0.3 to 15.4 ml (5.1 +/- 3.8 ml). Percentage gallbladder contraction varied from 6% to 87% (28% +/- 18%). In 60% of the subjects, percentage gallbladder contraction values varied by more than 20%, and in 20% of the subjects it varied by more than 40%. These data show that a wide variation exists within a normal person in the degree of gallbladder contraction exhibited from one day to another, and a single test for gallbladder contraction can be misleading.
Curcuma domestica Val. is a medicinal plant. It has been claimed to be effective for dyspepsia. The studies done so far showed no toxicity due to consuming Curcuma domestica Val. The plant has been found to contain volatile oil and curcuminoids which are believed to be the active ingredients. The objective of the study was to test the efficacy of Curcuma domestica Val. rhizome for treatment of dyspepsia compared with a placebo and flatulence in a multicenter, randomized, double-blind trial carried out in one provincial and 5 community hospitals. One hundred and sixteen adult patients who had acid dyspepsia, flatulent dyspepsia, or atonic dyspepsia were included in the study. Forty-one (41) patients were in the placebo group, 36 and 39 were in the flatulence and Curcuma domestica Val. groups respectively. Each patient received 2 capsules of placebo or study drugs 4 times a day for 7 days. Each patient was then assessed for symptoms response, side effects and satisfaction. Ten patients did not participate in the follow-up. The baseline characteristics of the patients among the three groups were not significantly different. Fifty-three (53) per cent of the patients receiving placebo responded to the treatment whereas 83 per cent of the patients receiving flatulence and 87 per cent of patients receiving Curcuma domestica Val. responded to the treatment. The differences in efficacy between placebo and active drugs were statistically significant and clinically important. Mild and self-limited side effects were observed at similar frequency in the three groups. About 50 per cent of the patients in each group were satisfied with the treatment they received.(ABSTRACT TRUNCATED AT 250 WORDS)
Dose-response curves for cholecystokinin (CCK), cerulein (CRL), and the effect of atropine on peptide-induced gallbladder evacuation, were evaluated in 13 normal subjects. Gallbladder volume was monitored by means of real-time ultrasonography. After an overnight fast, CCK was infused in six subjects iv, with increasing doses from 0.002 IDU/kg/min for 15 min, and CRL in seven subjects from 0.5 ng/kg/min for 5 min, until maximum gallbladder evacuation (greater than 70% of the fasting volume) was achieved. Forty-eight hours after the first study, CCK and CRL were readministered at the maximum contracting dose in each subject with and without a pretreatment with atropine (1 mg iv as bolus). The results showed maximum gallbladder evacuation at 0.016 IDU for CCK, and at 4 ng for CRL. Atropine significantly blunted the gallbladder response both to CCK and to CRL. It is therefore suggested that the cholinergic system is involved in the gallbladder response to CCK and to CRL.
Methods for investigating the physiology of the gallbladder in intact man are generally limited by their inconvenience and hazards, which include repeated exposure of the patient to radiation, nasoduodenal intubation, and complicated or time-consuming chemical techniques. We have carefully evaluated real-time ultrasonography for measuring gallbladder volume and contraction. We determined the validity and accuracy of ultrasound in assessing gallbladder volume and emptying in response to a stimulus. Gallbladder volume, calculated from sonography by a method which assumes gallbladder volume is equal to the sum of a series of cylinders, was 0.95 (SD = 0.01) times the true volume of bile instilled into a human gallbladder in vitro. With a rubber balloon model, containing small volumes (3-17 ml), the true volumes were overestimated by ~17% (0.5-3.1 ml). The intra- and interobserver variation in measurement of gallbladder size was usually within 10%. In 16 subjects we compared the fasting gallbladder volumes and response to a standard liquid meal on 2 successive days. The coefficients of variation in fasting volume, maximum percent emptied after meal-stimulated contraction, residual volume, and rate constant of emptying were 15.0, 12.8, 25.3, and 23.8%, respectively. In 15 consecutive subjects gallbladder volume was determined simultaneously by oral cholecystography and by real-time ultrasonography. Using the sum of cylinders technique, ultrasound volumes were 1.03 (SD = 0.11) times the cholecystogram volumes. We conclude that real-time ultrasonography is a simple, accurate, noninvasive and potentially valuable means of studying gallbladder size and emptying in intact man.
Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187 +/- 27; mean +/- SEM) and maximal (> 85% of fasting volume) gallbladder contraction (3172 +/- 361; AUC) as compared to the other two meals (P < 0.05). The mixed and the fat-free meal caused similarly low (< 50% of fasting volume) gallbladder contraction (6052 +/- 342 and 6134 +/- 500, respectively), although they induced markedly different CCK levels (157 +/- 12 and 87 +/- 13, respectively; P < 0.05). Gastric emptying rates were similar for all meals (18,500 +/- 3300, 18,600 +/- 2700 and 19,800 +/- 3100, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Patients receiving total intravenous nutrition have inert gallbladders; gallbladder sludge and gallstones often develop, but are preventable if gallbladder emptying can be improved. We measured the effect of giving rapid intravenous infusions of aminoacid solutions in eight normal subjects. Four regimens were tested (250 mL over 30 min, 250 mL over 10 min, 125 mL over 5 min, and 50 mL over 5 min). Gallbladder emptying, as measured by ultrasound and cholecystokinin release, depended on both the amount and the rate of aminoacid infusion. Rapid infusion of 125 mL of an aminoacid mixture (Synthamin 14 without electrolytes) over 5 min (2.1 g per min) produced a 64% reduction in gallbladder volume within 30 min, whereas a 50 mL infusion over 5 min produced only a 22% reduction. Intermittent rapid infusion of small amounts of aminoacids may prevent gallstones in patients receiving intravenous nutrition.
To evaluate the effects of a single oral dose of erythromycin on gastric and gallbladder emptying, 10 volunteers, without a known history of gastrointestinal disease, were investigated. Erythromycin stearate (500 mg) or placebo was given on separate mornings 30 min before a standard solid meal in a randomized, double-blind, crossover study. Gastric and gallbladder emptying rates were simultaneously evaluated by means of real-time ultrasonography. Gastric antral area and gallbladder volume were determined before the meal and 30, 60, 120, 180, 240, and 300 min after commencing eating. Erythromycin, compared to placebo, significantly accelerates and increases the degree of both gastric and gallbladder emptying. As previously reported for intravenous and chronic oral assumption, also a single dose of oral erythromycin is able to accelerate gastric and gallbladder emptying in normal human subjects.
Fifty two diabetic patients and 15 healthy control subjects were prospectively studied for their gall bladder function by ultrasound examination. The fasting gall bladder volume (FGBV) was calculated by using ellipse formula from the dimension of gall bladder shadow seen on ultrasound screen in two different cuts. The contractility of gall bladder was measured by calculating post prandial ejection fraction (EF) of the gall bladder. The mean FGBV and EF in 52 diabetic patients was found to be 20.7 +/- 10.7 cc and 47.5 +/- 20.1%, which was not significantly different from that in normal controls. Age, sex, obesity, diabetic control and presence of dyspeptic symptoms had no impact in FGBV and EF. Diabetic symptoms had no impact in FGBV and EF. However, diabetics with longer duration of disease had poorer gall bladder contractility (p < 0.05). Patients with autonomic neuropathy (AN) had significantly larger FGBV but normal contractility. Our results suggest that (a) long standing diabetics may have poor gall bladder emptying predisposing to gall stone formation (b) patients with autonomic neuropathy have reduced tone of fasting gall bladder but normal contractility.
To study the action of intravenously administered erythromycin lactobionate on human gallbladder volume, as a possible preventive method against gallbladder stone formation, in high risk patients such as those in sepsis, long standing fasting periods or those receiving prolonged total parenteral nutrition or octreotide.
Twenty-two volunteers randomized to receive intravenously either erythromycin lactobionate 7 mg per kg (study group) or normal saline (controls). We measured ultrasonographically the gallbladder volume before and at 5, 15, 35, 55, 90, 120 and 180 min after the infusion.
Erythromycin induced a biphasic gallbladder contraction, with maximum contractility at 15 min (10.2%) and between 120 and 180 min (22.6%), compared to normal saline controls. Late contractility was correlated to body mass index (BMI).
Erythromycin activity on gallbladder contraction is proved. Its biphasic action needs further investigation to find the involved mechanism(s). Long term administration is also necessary to test its efficacy in preventing gallbladder dilatation.
Orlistat (tetrahydrolipstatin) is a potent inhibitor of gastric and pancreatic lipase activity causing a diminution of free fatty acids in the intestinal lumen. The release of cholecystokinin (CCK) critically depends on the presence of free fatty acids in the small intestine. Postprandial CCK release and gallbladder contraction might be decreased by orlistat, potentially resulting in an increased risk of gallstone formation. In this double-blind, placebo-controlled, six-way crossover study, six healthy volunteers ingested in a randomized order three isocaloric test meals (250 ml) of identical osmolality with either orlistat (200 mg) or placebo: (a) a pure-fat meal (25 g triglycerides), (b) a mixed meal containing fat (8 g; 29% of caloric content), protein (10 g; 17%), and dextrose (32 g; 54%), and (c) a fat-free meal containing albumin (25 g; 46%) and dextrose (32 g; 54%). Gallbladder volumes were determined by ultrasonography, and plasma CCK, pancreatic polypeptide and gastrin levels by RIA. Gall-bladder contraction (AUC, % x 90 min; difference of means +/- 95% CI) in subjects receiving orlistat or placebo did not significantly differ after intake of the pure-fat meal (443+/-1174), the mixed meal (313+/-1170), or the fat-free-meal (-760+/-1180). The release of CCK (AUC; pM x 90 min; difference of means +/- 95% CI) was not different between orlistat and placebo after ingestion of the pure-fat meal (-18+/-64), the mixed meal (-45+/-62), and the fat-free meal (27+/-63). Likewise, the release of pancreatic polypeptide and gastrin was similar after intake of the meals with either orlistat or placebo. A single dose of orlistat did not reduce gallbladder motility after ingestion of meals with differing fat contents. The safety of long-term treatment with orlistat with respect to gallstone formation remains to be determined.
To date, the intraindividual reproducibility of fasting and postprandial gallbladder (GB) volumes has not been established satisfactorily. Hence we examined the variability of postprandial GB motility, using the biplane Simpson method as a new sonographic tool for GB volume determination.
The biplane Simpson method was validated in vitro and in vivo and compared with the sum-of-cylinders method. Thereafter, postprandial GB emptying after a defined test meal was examined in 10 healthy volunteers over 108 min on days 1, 31, and 61.
The results of the biplane Simpson method correlated with real volumes (r = 0.99) and provided a intra- and inter-observer variation of less than 5%. Intraindividually, differences in fasting GB volume ranged from 1.9 to 24.0 ml within the observation period. The patterns of GB emptying also showed fluctuations characterized by a rather large interindividual and intraindividual variability.
The biplane Simpson method is a reliable tool for measuring GB volumes. The fasting and the postprandial GB volumes vary considerably within individuals when measured over a period of 2 months.
Plants with hepatoprotective effect. Symposium on Hep-atitis and the Use of Medicinal Plants as Hepatoprotectors
- S Sidik
Sidik S. [Plants with hepatoprotective effect. Symposium on Hep-atitis and the Use of Medicinal Plants as Hepatoprotectors.] Band-ung, Indonesia, 22nd October 1988. Jakarta: Department Kesehatan (Indonesian).
An ultrasonographic measurement used for studying agents acting on human gallbladder
- A Rasyid
- A Lelo
Rasyid A, Lelo A. An ultrasonographic measurement used for
studying agents acting on human gallbladder. Asian Oceanian J
Radiol 1998; 3: 70-74.
- S Sidik
Sidik S. [Plants with hepatoprotective effect. Symposium on Hepatitis and the Use of Medicinal Plants as Hepatoprotectors.] Bandung, Indonesia, 22nd October 1988. Jakarta: Department
Kesehatan (Indonesian).