To increase the bioavailability of curcumin different formulations have been made . Among them, nanoglobules based. How do you increase the bioavailability of curcumin naturally into your body? We have taken a closer look at it and here are a few simple ways. The prospect of improving the bioavailability of curcumin and the subsequent enhancement of its bioactivity could monumentally alter the.
the Curcumin of Increasing Bioavailability
These studies suggest the role of route of administration on achievable serum levels of curcumin and also the comparison of serum level in rodents and humans. To increase the bioavailability of curcumin different formulations have been made. Among them, nanoglobules based nanoemulsion formulation has been prepared to evaluate the potential for the solubility enhancement of curcumin Fig.
During ex vivo study, the release of curcumin from nanoemulsion was found much higher than curcumin suspension. This indicated the enhancement of solubility of curcumin in aqueous solution [ 70 ]. Another study showed an encapsulating the curcumin into the hydrogel nanoparticles yielded a homogenous curcumin dispersion in aqueous solution compared to the free form of curcumin.
In contrast, intracellular soluble curcumin sol-curcumin reaches a maximum at 2 hours followed by its complete elimination by 4 hours [ ]. The colloidal nanoparticles, named as 'theracurmin' showed AUC after the oral administration more than fold higher than that of curcumin powder in rats. In healthy human volunteers, theracurmin 30 mg when administered orally resulted fold higher AUC than that of curcumin powder [ ].
The nanoparticle of curcumin prepared by Cheng et al. Thus, nanocurcumin enhances bioavailability of curcumin in animals as well as in humans. To improve the pharmacokinetics of curcumin with enhancing its bioavailability other effective formulation PLGA encapsulated curcumin was prepared. In vitro study showed that PLGA-curcumin has very rapid and more efficient cellular uptake than curcumin.
Intravenous administration of either curcumin or PLGA-curcumin 2. Thus these formulations are potential carriers for the oral delivery of curcumin [ ]. Other study showed that curcumin encapsulated in low and high molecular weight PLGA have relatively different oral bioavailability of curcumin. It has been found that the relative bioavailability of high molecular weight PLGA conjugated curcumin has 1. In support of previous study, it has been found that after oral administration of curcumin-PLGA-nanoparticles, the relative bioavailability was increased 5.
This improved oral bioavailability of curcumin found to be associated with improved water solubility, higher release rate in the intestinal juice, enhanced absorption by improved permeability, inhibition of P-glycoprotein-mediated efflux, and increased residence time in the intestinal cavity [ ].
It has been also observed that PLGA-curcumin enhances two and six fold increases in the cellular uptake performed in cisplatin resistant ACP ovarian and metastatic MDA-MB breast cancer cells, respectively, compared to free curcumin [ ]. Another formulation designed for improvement of bioavailability of curcumin is liposomal curcumin. Liposomes are considered as effective drug carriers because of their ability to solubilize hydrophobic compounds and to alter their pharmacokinetic properties.
In rat oral administration of liposome-encapsulated curcumin LEC showed high bioavailability of curcumin. In addition, a faster rate and better absorption of curcumin were observed as compared to the other forms. Another study showed that curcumin incorporated into N-trimethyl chitosan chloride TMC -coated liposomes exhibited different pharmacokinetic parameters and enhanced bioavailability, compared with curcumin encapsulated by uncoated liposomes and curcumin suspension.
Uncoated curcumin liposomes and TMC-coated curcumin liposomes showed a similar in vitro release profile [ 62 ].
In order to facilitate the intracellular delivery of curcumin, a new type of liposomes-propylene glycol liposomes PGL were prepared. It has been observed from cell experiment in vitro , PGL exhibited the highest uptake of curcumin compared with that of conventional liposomes and free curcumin solution [ 63 ].
These studies indicate that liposome conjugated curcumin increases the bioavailabllity of curcumin.
CD, cyclic oligosaccharides, has been also used in order to improve curcumin's delivery and bioavailability via its encapsulation with CD. It has been found that CD encapsulated curcumin CDC had a greater cellular uptake and longer half-life in the cancer cells compared with free curcumin indicating CDC has superior attributes compared with free curcumin for cellular uptake [ 86 ]. In addition, the improvement of CUR permeability acrossed animal skin tissue was observed in CD encapsulated curcumin and was about 1.
Thus, these studies suggest that CDC has improved in vitro and in vivo bioavailability and chemotherapeutic efficacy compared to curcumin alone. Besides these natural compounds have been also used to increase the bioavailability of curcumin. One of them is piperine, a major component of black pepper, known as inhibitor of hepatic and intestinal glucuronidation and is also shown to increase the bioavailability of curcumin.
This effect of piperine on the pharmacokinetics of curcumin has been shown to be much greater in humans than in rats. The study shows that in the dosages used, piperine enhances the serum concentration, extent of absorption and bioavailability of curcumin in both rats and humans with no adverse effects [ 95 ].
Enhanced bioavailability of curcumin was also evidenced by other researcher when curcumin was administered orally concomitant with piperine. Intestinal absorption of curcumin was also found relatively higher when administered concomitantly with piperine, and it stayed significantly longer in the body tissues [ ].
In view of these findings, curcumin-piperine Cu-Pi nanoparticles has been prepared by various methods [ ]. The bioavailability, cellular uptake and biological effects of this nanoparticles are being tested.
Accumulating data evident that most, if not all, formulated curcumin have better bioavailability and biological activities than unformulated curcumin. Nanosuspension of curcumin also induces more cytotoxicity in Hela and MCF-7 cells than curcumin [ 44 ]. Curcumin liposomes of dimyristoyl phosphatidyl choline and cholesterol inhibit proliferation of prostate cancer cell 10 times more than curcumin [ 67 ].
Beside these, PLGA encapsulated curcumin has shown more potent than curcumin in inducing apoptosis of leukemic cells and in suppressing proliferation of various tumor cell lines. PLGA nanocapsulated curcumin found to eliminate diethylnitrosamine-induced hepatocellular carcinoma in rat [ 72 ].
Doxorubicin and curcumin in a single PLGA nanoparticle formulation, curcumin facilitates the retention of doxorubicin in nucleus for a longer period of time. It also inhibits the development of drug resistance for the enhancement of antiproliferative activity of doxorubicin in K cells [ ]. CDC is another formulation of curcumin having anti-inflammatory and antiproliferative effects. CD entrapped curcuminoid also induces autophagic cell death in lung cancer cells and inhibits tumor growth in nude rats [ ].
Besides these, other formulations such as dipeptide nanoparticles, phosphatidylcholine encapsulated curcumin, etc. Dipeptide nanoparticle of curcumin inhibits tumor growth in mice [ 87 ]. Phosphatidylcholine encapsulated curcumin exhibits antimalarial activity [ 88 ], inhibits vaginal inflammation [ ] and induce cytotoxicity of cancer cells [ 81 ]. There are several other cucrumin formulation are synthesized having more biological activities than curcumin.
Uptake and distribution of curcumin in body tissues is obviously important for its biological activity. Most of curcumin get metabolized in liver and intestine however, a small quantity is still remains detectable in the organs Fig. Intravenous injection of [ 18 F]-curcumin in mice found to persistently accumulated in the liver and spleen while lung uptake was found to decrease with time.
Brain uptake of [ 18 F]-curcumin was at 2 minutes postinjection, and its radioactivity was rapidly washed out from the brain at 30 minutes [ ]. These studies indicate that curcumin is bioavailable in several organs and its availability decreases with time depend on the organs. Biodistribution of [ 18 F]-curcumin A and of [ 18 F]-curcumin co-injected with piperine B in mice. Adopted from Ryu et al. Another study showed distribution of curcumin in the intestines, spleen, liver, and kidneys, which was In comparison with dietary administration, when curcumin given intragastric resulted more curcumin in the plasma but much less in the colon mucosa, indicating mode of administration play a role in distribution of curcumin [ ].
In contrast, curcumin was poorly detected in patients of colorectal cancer. In a study of 12 patients with hepatic metastases from colorectal cancer, treatment of , mg of curcumin daily, for 1 week prior to surgery, poor availability of curcumin was observed in the peripheral or portal circulation following oral administration.
While curcumin was not found in liver tissue, trace levels of products of its metabolic reduction were detected [ ]. Using ultra performance liquid chromatography by Marczylo et al. Curcumin was found in plasma Another study evaluated the tissue distribution of curcumin using tritium-labeled drug. They found that radioactivity was detectable in blood, liver, and kidney following doses of , 80, or 10 mg of [ 3 H] curcumin.
With mg, considerable amount of radio labeled products were present in tissues 12 days after dosing. Numerous studies evaluated that curcumin undergoes metabolism in different components after oral administration in animals. Because of its metabolism, curcumin has demonstrated poorly bioavailable after p. Curcumin bioavailability may also be poor in humans, as indicated by a pilot study of a standardized curcuma extract in colorectal cancer patients [ ].
Reduced curcumin also subjected to glucuronidation into curcumin glucuronide, dihydro-curcumin-glucuronide, tetrahydrocurcumin-glucuronide, and curcumin sulfate [ ]. A minor biliary metabolite was dihydroferulic acid together with traces of ferulic acid.
Numerous studies have revealed that curcumin metabolites have antioxidative, anti-inflammatory and anticancer activities. Tetrahydrocurcumin THC inhibits radiation-induced lipid peroxidation [ ] and induced antioxidant enzymes in vitro [ ]. In rats, dietary administration of THC reduces aberrant crypt foci and polyps formation in azoxymethane-induced colon carcinogenesis [ ].
Hexahydrocurcumin, another metabolite, has reduced ability to inhibit COX-2 expression compared to curcumin [ ]. Hexahydrocurcumin also induce cell cycle arrest in human colorectal cancer SW cells [ ]. However, the free radical scavenging activity of octahydrocurcumin is higher than curcumin [ ]. Beside these, we have recently showed that none of curcumin mono- or di-glucurnoid showed biological activity such as anti-inflammatory or antiproliferative activity compared to curcumin [ ].
The curcumin metabolite, curcumin sulfate has shown to have less biological activities compared to curcumin. Curcumin sulfate inhibits prostaglandin E2 activity very poor than curcumin [ ]. Thus these studies indicate that after metabolism of curcumin in different components, shows biological activities differ from parent curcumin. Since ancient times, curcumin has been used in Asian countries against human ailments. Modern science has delineated the molecular basis for the pharmaceutical uses of curcumin.
Multiple studies over the past decade have indicated the safety and efficacy of this polyphenol and have provided a solid basis for evaluating its efficacy in human clinical trials. Despite its efficacy and safety, limited curcumin bioavailability continues to be highlighted as a major concern.
However in attempts to improve the bioavailability of curcumin, several strategies have been explored such as modulation of route and medium of curcumin administration, blocking of metabolic pathways by concomitant administration with other agents, and conjugation and structural modifications of curcumin. Evidence from literatures indicated its increased bioavailability and efficacy in different experimental models with these strategies. In spite of these, improvements in curcumin bioavailability enhancement and efficacy have not gained significant attention in human.
Therefore, further exploration in attempts to enhance the bioavailability, medicinal value, and application of this interesting molecule from Mother Nature are needed for human use. Aggarwal is the Ransom Horne, Jr. Conflict of interest relevant to this article was not reported.
National Center for Biotechnology Information , U. Journal List Cancer Res Treat v. Published online Jan Tyagi , PhD, and Bharat B. Find articles by Sahdeo Prasad. Find articles by Amit K. Find articles by Bharat B. Author information Article notes Copyright and License information Disclaimer. Received Dec 25; Accepted Dec This article has been cited by other articles in PMC.
Abstract Curcumin diferuloylmethane is a yellow pigment present in the spice turmeric Curcuma longa that has been associated with antioxidant, anti-inflammatory, anticancer, antiviral, and antibacterial activities as indicated by over 6, citations.
Curcumin, Nano-formulation, Biological availability, Metabolism, Anticancer. Introduction Curcumin is the major active component of turmeric, a yellow compound originally isolated from the plant Curcuma longa.
Open in a separate window. Delivery of Curcumin 1. Oral delivery In most of studies curcumin has been delivered orally whether subject is human or animals. Subcutaneous delivery Subcutaneous treatment of curcumin in animals has been used to provide effective and sustained tissue concentrations.
Intraperitoneal IP delivery IP injection is the injection of a substance into the peritoneum body cavity. Intravenous Delivery Numerous reports have been shown that intravenous injection of curcumin exhibits anticancer property in animal model. Topical delivery A topical treatment is a medication that is applied to body surfaces such as the skin or mucous membranes to treat ailments. Nasal delivery To increase the bioavailability and also direct nose-to-brain drug transport, nasal delivery of curcumin has been used.
Bioavailability of Curcumin Evidence from numerous literatures revealed that curcumin has poor absorption, biodistribution, metabolism, and bioavailability. Table 1 Reformulation of curcumin for enhanced bioavailability. Unformulated curcumin The pharmacological studies revealed that curcumin is safe and effective which makes it a potential compound for treatment and prevention of a wide variety of human diseases.
Nanocurcumin To increase the bioavailability of curcumin different formulations have been made. Polylactic-co-glycolic acid PLGA To improve the pharmacokinetics of curcumin with enhancing its bioavailability other effective formulation PLGA encapsulated curcumin was prepared. Liposomal encapsulation Another formulation designed for improvement of bioavailability of curcumin is liposomal curcumin.
Cyclodextrin CD CD, cyclic oligosaccharides, has been also used in order to improve curcumin's delivery and bioavailability via its encapsulation with CD. Piperine Besides these natural compounds have been also used to increase the bioavailability of curcumin. Biological Activities of Formulated Curcumin Accumulating data evident that most, if not all, formulated curcumin have better bioavailability and biological activities than unformulated curcumin.
Absorption of Curcumin in Blood, Liver, Brain, Kidney, and Other Organs Uptake and distribution of curcumin in body tissues is obviously important for its biological activity. Metabolism of Curcumin Numerous studies evaluated that curcumin undergoes metabolism in different components after oral administration in animals.
Conclusion Since ancient times, curcumin has been used in Asian countries against human ailments. Footnotes Conflict of interest relevant to this article was not reported.
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Intranasal curcumin and its evaluation in murine model of asthma. Turmeric is indeed a constituent of indian food and home cooks use it sparingly. These days when i get a sore throat or a bacterial infection, I just take a teaspoonful with water, gargle and gulp it down. Works for my throat. Along with salt water gargling and , eucalyptus oil inhalation for sinuses. Shall we invest mUSD in clinical trials so skeptics will be satisfied? Again this is for turmeric not curcumin which probably has all non-drug like properties but is a good anti-oxidant etc.
I am tired of this all negative posts. We are intelligent enough to figure out what is nonsense. No need to repeat it ad nauseum or or snigger at home remedies that may be placebos but worked anecdotally or as placebos before modern industrial medicine appeared, just this last century.
Most folk try out home remedies because there are no good alternatives. Have anyone found a great oral drug cure for sinuses lately?
IOr repeated infections in polluted countries like ours that makes taking antibiotics each time a non-option? And as I quoted curcumin or not, turmeric works in throat and sinus infections. Why not write a post that points out those positive points and then say that curcumin is probably not what makes it work and other compounds should be investigated? And speculate which ones? Why not compare the reasonable looking symmetric structure and reason in which of the myriad claimed indications, it could work from a medchem viewpoint?
Our ancestors had to make do with what nature gave them since organic chemistry and understanding of drug mechanisms is a very recent development relatively. Why not think about what your expertise could do to make it work? Thus the talk about the badge. Being scientific is not beating the drum that every layperson has always been wrong. If you ask a question, you ought to be willing to listen to the answer.
Not liking the answer is not relevant. As a side note, if the lead is claimed to have both an activity and its converse, it ought to make one start questioning what is happening with the lead.
The question is whether curcumin does not work outside of gastrointestinal inflammatory diseases perhaps because of its low bioavailability or it does not work for other reasons.
If the answer is the former, then the compound should continue to be studied. What can be done or has been done to increase it bioavailability? Does the combination of curcumin with piperine make a difference? Do the other compounds in turmeric make a difference?
And are similar compounds with greater bioavailability effective in the treatment of diseases caused by oxidation and inflammation? The intent of studies like this seems to be as conversation enders. Instead, they should be conversation starters. If you know of some reliable clinical data on turmeric helping viral infections, etc. I have never seen a structure like this turn into an actual drug.
Everything you need to know about Curcumin can be summed up as follows: Unfortunately, the myth of curcumin lives on in part because the US Office of Research Integrity has yet to release findings of an investigation into Aggarwal, after more than 4 years. Including Type 2 diabetes, for which the effect disappears as reliably as it does for every other condition when the proper double-blind trial is conducted.
Studies listed from their website:. Subjects were randomly assigned to either curcumin or placebo rice flour and supplemented 2 days before to 4 days after EMID. Curcumin supplement improves vascular endothelial function in middle-aged and older adults. Santos-Parker JR et al. Nahar PP et al. Centre for Human Psychopharmacology, Swinburne University.
J Psychopharmacol May Vol 29 No 5: Nahar et al, J Med Food. Cox et al , J Psychpharm. Ma et al, J Biol Chem. The Ohio State University. Ma et al For the uninformed, how does curcumin resemble ibrutinib?
To my untrained eye, ibrutinib looks like a typical kinase inhibitor with a reactive group at one end. Is it even that terribly reactive? I mean the alkene is in that nice conjugated system with the amide. Curcumin is just one of hundreds of small molecules in turmeric.
Curcumin is rapidly metabolized. It is conjugated to form glucuronide and sulfate secondary metabolites. No free curcumin is detectable in the circulation The same is true for resveratrol, green tea catechins and most every polyphenol.
So, if there is indeed something beneficial in turmeric or wine, tea and dark chocolate it has not yet been identified.
Ibrutinib was intentionally designed with a Michael acceptor to target a catalytic cysteine residue based on the co-crystal structure of the initial pyrazolpyrimidine scaffold. Such a covalent mechanism is attractive for anticancer agents that are given in very low doses and where the therapeutic index and hence safety profile is also low.
If this compound were found as a hit in a HTS assay, then non-specific covalent inhibition would certainly be probable and most chemists would want some evidence that it possesses some useful level of selectivity before working on the scaffold. Among Michael acceptors, acrylamides are relatively weak compared to the corresponding vinylketones, vinylsulfones, vinylsulfoxides, and vinyl sulfonamides. In the case of ibrutinib, the selectivity is due to specific recognition with the target, which places the Michael acceptor proximal to a conserved non-catalytic, but sufficiently reactive cysteine.
These factors together provide the selectivity. In India turmeric used in curries as a spice. The procedure of cooking is adding turmeric and other spices to the boiling oil and mix thoroughly. Generally it is cooked in any cooking oil, and curcumin is readily soluble in almost all cooking oils. So the heat, and the presence of oil will increase the solubility of turmeric and hence it will increase the bioavailability. Turmeric also used in the dishes of chicken, meat, or fish, and the fat contained in it also increases the solubility of turmeric.
In my experience, it is very difficult to remove the yellow color of turmeric from my hand after eating the turmeric contained food cooked in oil. Science is not myth, we want strong evidence, and proof to believe. So more research is needed on the efficacy of curcumin.
In my opinion, the laboratory and real situation is entirely different. In real life we consume turmeric along with other spices, oils, fats, etc. For example the presence of piperine will increase the bioavailability of curcumin. In the lab, curcumin will precipitate or aggregate very fast. This can overcome by dissolving curcumin in any organic solvent and dilute to the desired concentration by adding few microleters of concentrate curcumin in to the buffer solution in step wise and stir simultaneously.
Like Haris, I use turmeric as a food, not curcumin as a drug. Consumed with an oil or fat, to allow better absorption, and with freshly ground pepper to inhibit glucoronidation, it is indeed effective. The supplement industry jumped on the first few positive reports about curcuminoids and have used it as a cash cow ever since. That includes subsidizing university research that used their products both Meriva and Longvida have been guilty of that.
What does anyone expect when profit takes precedence over science? It was the low incidence of colon cancer and dementia in India that attracted western researchers to begin with. If you take root powder it works. By most measures life expectancy; general overall health indicators [incidence of various diseases]; quality of health care system; etc.
What is a learning med-chemist to think? I assume that you also tested it by actually trying it out for a longer period of time? Or maybe not… proving the article you wrote. Including me a massive diaphragm-bil-stomach-duodenum inflamation. Just took a big dose of turmeric and the whole thing healed. It healed without strong chemical medication. For me, curcumin is a life safer. From little things that totaly stress me out because im so burned out from my anxiety to a normal feeling of being able to do things.
All within 30mins after taking a capsule. We are all different and what works for one, might be useless for another. In that regard, such generalized articles might be of little help for anyone trying to gather information.
But, I was otherwise asymptomatic. I had a full course of blood work done nearly every month for 6 months. My low D rose, my high D1,25 dropped significantly. I had just previously had a liver ultrasound that showed pretty severe NAFLD, that 6 months later totally disappeared. The results were hard to refute. I even went short periods where I would lower the dose, or stop entirely, and retest, and the markers rose quickly. Yes, it can cause upset stomach for some, but it was never a problem for me.
A lot of my initial research was from papers by B. Aggarwal, and I know what happened to him. It is a terrible stain on the research community and MD Anderson specifically. Or, many times the doses were very small, or for short periods. Randomized human trials are, of course, the only way to really understand the efficacy of a product in humans, but one must remember that in any statistical analysis, the results are only related to what you test, all other things being equal. Thank you for pointing out that many studies from others than the infamous Aggarwal have concluded that curcumin s with something else that makes them bioavailable work in human studies.
I just went to Examine. It takes a month or more to start, but stuff works — curcumin, Boswellia, Ashwagandha, and so on. I am going to attempt a course of Curcumin but would like to know the specific preparation that you took because clearly there are absorption and bioavailability issues.
Novel Drug Delivery Systems to Improve Bioavailability of Curcumin
Heat is said to increase the solubility of curcumin (the primary active constituent in turmeric) by 12 times, which may also increase its bioavailability in the body. Turmeric is poorly absorbed in the body. Here are some simple tips to improve its absorption in the body. “The CW8 formulation showed a fold increase in relative bioavailability compared with unformulated standard curcumin,” commented.