See also polyphenols, generally
Introduction Definitions:
Curcuminoids: may be obtained form or found in a turmeric extract or may be syntehsized. Curcuminoids include curcumin (see below), tetrahydrocurcuminoids (see below), hexahydrocurcuminoids and octahydrocurcuminoids.
Curcuminoids such as curcuin, demethoxycurcumin and bisdemethoxycurcumin are components of the spice turmeric and have been recommended for a number o medical applications. Research has suggested that curcuminoids can suppress the production of TNF-alpha from macropahges.
Curcuminoids are linear diarylheptanoids that are tumeric extracts used as food coloring agents as yellow pignments and as traditional drugs. (Singh, US 2016/0058713)
Types of Curcuminoids:
Curcumin (diferuloylmethane) (1.7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) is a phenolic natural product isolated from the rhizome of Curcuma longa (turmeric). Curcumin, the active component of tumeric, has been shwon to exhibit anti-inflammatory and antimutagenic and anticarcinogenic activity. Studies report that curcumin stronlgy inhibits the initiation and promotion of chemical carcinogen-induced tumor formation in mice and the proliferation of various cultured tumor cells. Thes activities may be attributed to the inhibition of certain signal transduction pathways critical to tumor cell growth, such as AP0-1, NF-kB and protein kinase c.
Curcumin is a golden pigment from turmeric which has been linked with antioxidant, anti-inflammatory, anticancer, antiiral, antibacterial, and antidiabetic properties. Most of these activities have been assigned to methoxy, hydroxyl, alpha,beta-unsaturated carbonyl moiety or to diketone groups present in curcumin. (Prasad, “Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular resposnes” Molcules 2015, 20, 185-205).
Curcumin, a diarylheptanoid present in turmeric, has shown promise as an antioxidant and anti-inflammatory agent in animal models of kideny failure. However, as curcumin is composed of several phenols and some of these compoudns may exert paradoxical pro-inflammatory effects.
There are practical problems associated with using curcumin for boosting the immune system. Curcumin is insoluble in water under acidic or neutral conditions. It is unstable by underoging rapid hydrolytic degradation in neutral or alkaline conditions. US Patent Publication No. 2021/0353583A1 to DuBourdieu, assigned to Probioticssmart, LLC, published November 18, 2021) discloses a tetrahydrocurcuminoid-metal complex that incldues at least one tetrahydrocurcuminoid chelated to a metal.
US Patent No. 9393,198B2, to Helson, assigned to Signpath Phamra Inc., published July 19, 2016) discloses liposomal curminfor neruopathic applications.
–Curcumin in combination with Probiotics: U.S. Patent Application Publication No. 2023/0190835 discloses therapeutic compositions comprising curcumin in combination with selected probiotic bacteria for the treatment of amyloidosis. The disclosed probiotic bacteria include, for example, Enterococcus faecium, Bifidobacterium longum, Streptococcus thermophilus, Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, and Pseudomonas fluorescens. The publication does not disclose or suggest the use of Lactobacillus gasseri for conversion of curcumin to tetrahydrocurcumin or enhancement of such conversion.
–Curcumin Metabolism:
So far, two pahses of curcumin metabolism in the livers and intestines of rats and humans, and plasma of mice, have been reported. Phase I metabolism includes the reduction of the four double bonds of the heptadiene-3,5-dione strcuture: namely, curcumin-DHC-THC-hexahydrocurcumin-octahydrocurcumin. During pahse II, curumin and its reduced metabolites are conjguated with a monoglucuronide, a monosulfate and a mixed sulfate-glucuronide; namely, conjugated curcumin-conjugated DHA-conjugated THC-conjugated hexahydrocurcumin-conjugated octahydrocurcumin. Hassaninasab “Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism” PNAS, 2011, 108 (16))
–Curcumin-Converting Microorganisms:
—-E. coli: Hassaninasab “Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism” PNAS, 2011, 108 (16))discloses microorganisms with curcumin-converting ability that were isoalted form feces. The intestinal microorganism exhibiting the highest specific activity as to curcumin conversion was selected. A 16S rRNA sequence of the slected microorganisms exhibited the highest similarity to those of E coli H10407 strain. The ioslated microorganism was then cultured on MacConkey and Levine EMB agar to examine the lactose fermentation reaction and to observe the colony morphology. On MacConkey agar, it produced red colonies depending upon the ability to ferment lactose; fermentation of this sugar causes the medium pH to drop, leading to darkening of the medium. Growth of the microrganisms on Levine EMB agar produced black colonies iwth a greenish-black metallic sheen because of lactose fermentation; These findings strongly supported that the isolated microrgnaism was E. coli. The curcumin converting enzyme was also purified and cloned. During enzyme purification, the curcumin converting enzyme activity was lost on dialysis. However, the addition of NADPH increased the activity, but the addition of NADH did not. These findings suggest that the enzyme catalyzes NADPH dependent conversion of curcumin. The products derived from curcumin conversion were anlayzed by LC-ESI-MS and fast atom bombarment (FAB)-MS showing one peak at 280 nm with a retnetion time agreeing with tetrahydrocurcumin (THC). This peak was collected and also anlayzed by LC-ESI-MS, the product exhibting a mz vlaue of 395, corresonding with the (M+Na]+ ion of THC (372 MW). Next, the reaction was carried out for 10 min at 28C using a low concentraiton of the purified enzyme and suprisingly, another peak with a retention time of 14.43 min was detected with a HPLC method. The new peak was not detected when the reaction was coarried out compeltely, suggesting that the new peak is that of an intermediate product. It was collecte and also anlayzed by LC-ESI-MS and exhibiting a m/z vlaue of 393, consistent with the [M+Na]+ ion of dihydrocurcumin (DHC) (370 MW).
Tetrahydrocurcumin (THC): One of the major metabolites of curcumin is tetrahydrocurcumin (THC), which lacks alpha, beta-unsaturated carbonyl moiety and is white in color. The yellow component of turmeric, is metabolized to white THC and these two compound exhibit distinct activities. Studies have shown that curcumin given intraperitoneally is first biottransformed to dihydrocurcumin and then to THC. THC, one of the major metabolites of curcumin, was very stable in 0.1 M phospahte buffers at various pH values and was more stable than curcumin in 0.1 M phosphate buffer at pH 7.2 (37C). (Prasad, “Curcumin differs from tetrahydrocurcumin for molecular targets, signaling pathways and cellular responses” Molecules 2015, 20, 185-205).
Tetrahydrocurcumin is a major metabolite of the curcuminoid, curcumin and can be used for its anti-fibrotic and anti-oxidant activities. Tetrahydrocurcumin is a strong anti-oxidative molecule. It can be used as an anti-oxidant in oxidative stress diseases. Tetrahydrocurcumin can also be used to treat renal damage, hepatotoxicity and hepatic damage. Although it is relatively safe at high dosasges (80 mgs/kg body weight), one of the major disadvantages is its low solubility. (US 2016/0058713 to Singh, assigned to Bhupinder Singh, published March 3, 2016, which discloses a deuterated form of tetrahydrocurcumin)
Okada investigated the protective effects of curcumin and its derivative tetrahydrocurcum against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage in mice. The results suggested that THC is more easily absorbed from the gastrointestinal tract and that it induced antioxidant enzymes, such as glutathione peroxidase, glutathione S-transferase and NADPH: quinone reducatse, as well as or betterhn than curcumin and scavenged Fe-NTA-induced free radials in vitro better than curcumin. The resutls suggested that curcumin is converted to tetrahydrocurcumin in viov and that THC is a more promising chemopreventive agent. (Okada, et al. “Curcumin and especially tetrahydrocurcuin ameliorate oxidative stress-induced renal injury in mice” Biochemical and Molecular Aciton of Nutrients, 2001)
US Patent No. 5,266,344 to Mimura discloses tetrahydrocurcumin which a substance containing the same which are produced form curcumin or a substance containing it as a material. Mimura discloses that antioxidative activity is much more enhanced in tetrahydrocurcumin with no double bonds in its molecule than in curcumin with double bonds. It is considered that the covalent double bonds in the curcumin molecule may suppress its antioxidative activity.
Use in Treatment Methods:
Psoriasis:
Clapp (US 10,835,584, Nuvothera) discloses treating psoriasis which includes applying a anti-microbial gel which includes turmeric or curcumin, a mosturizer such as bromelain and an anti-microbial, such as benzalkonium chloride and sodium chlorite. In some embodiments the composition also includes cortisones, vitamins, green tea catechins, salicylic acid, coal tar, lidocaine and other pain-killers or anti-finlammatory molecuels.
Neurological Disorders:
–in combination Probiotic bacterium:
Van de Wiel (US 2023/0190835) discloses probiotic bacteria in particular combination with herbal active agents such as a curcuminoid and/or a cannabinoid to treat or prevent Alzheimer’s disease. In one embodiment the probiotic bacterium is selected form the genus of Lactobacillus bacteria.
Doses:
US Patent No. 10,835,584B2, to Clapp, assigned to Nuvothera, Inc., published November 17, 2020 discloses the use of curcumin at a final concentration of less than 0.1% whereas the prior art has indicated the use of curcuminoids at a final concentration of great than 0.1%.