Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of...

Bioavailability of curcumin: problems and promises.

Curcumin as “Curecumin”: From kitchen to clinic

https://www.sunsaferx.com/research-files/haematococcus-astaxanthin-applications-human-health-nutrition.pdf

Haematococcus astaxanthin: applications for human health and nutrition

Pharmacology of oleanolic acid and ursolic acid

Fifty-four polyphenols isolated from tea leaves were evaluated for their inhibitory activities against pancreatic lipase, the key enzyme of lipid absorption in the gut. (-)-Epigallocatechin 3-O-gallate (EGCG), which is one of major polyphenols in green tea, showed lipase inhibition with an IC50 of 0.349 microM. Moreover, flavan-3-ol digallate esters, such as (-)-epigallocatechin-3,5-digallate, showed higher activities of inhibition on lipase with an IC50 of 0.098 microM. On the other hand, nonesterified flavan-3-ols, such as (+)-catechin, (-)-epicatechin, (+)-gallocatechin, and (-)-epigallocatechin, showed zero and/or the lowest activities against pancreatic lipase (IC50 > 20 microM). These data suggested that the presence of galloyl moieties within the structure was required for enhancement of pancreatic lipase inhibition. It is well-known that flavan-3-ols are polymerized by polyphenol oxidase and/or heating in a manufacturing process of oolong tea. Oolonghomobisflavans A and B and oolongtheanin 3'-O-gallate, which are typical in oolong tea leaves, showed strong inhibitory activities with IC50 values of 0.048, 0.108, and 0.068 microM, respectively, even higher than that of EGCG. The oolong tea polymerized polyphenols (OTPP) were prepared for the assay from oolong tea extract, from which the preparation effectively subtracted the zero and/or less-active monomeric flavan-3-ols by preparative high-performance liquid chromatography. The weight-average molecular weight (Mw) and number-average molecular-weight (Mn) values of OTPP were 2017 and 903, respectively, by using gel permeation choromatography. OTPP showed a 5-fold stronger inhibition against pancreatic lipase (IC50 = 0.28 microg/mL) by comparison with that of the tannase-treated OTPP (IC50 = 1.38 microg/mL). These data suggested that the presence of galloyl moieties within their chemical structures and/or the polymerization of flavan-3-ols were required for enhancement of pancreatic lipase inhibition.

Inhibitory Effects of Oolong Tea Polyphenols on Pancreatic Lipase in Vitro

An extract of the crude drug “ukon”, the rhizomes of CURCUMA LONGA, exhibited intense preventive activity against carbon tetrachloride-induced liver injury IN VIVO and IN VITRO. The extract was subjected to fractionation by monitoring the activity by the IN VITRO assay methods employing carbon tetrachloride- and galactosamine-produced cytotoxicity in primary cultured rat hepatocytes. Curcuminoids were shown to possess significant antihepatotoxic action. The liver protective effects of some analogues of ferulic acid and p-coumaric acid, probable metabolites of the curcuminoids, were also evaluated.

Antihepatotoxic principles of Curcuma longa rhizomes.

From the ethyl acetate-soluble fraction of the drug ECLIPTA ALBA (L.) Hassk. Asteraceae, besides a flavonoid and simple phenolcarboxylic acids, the coumestans wedelolactone and demethyl-wedelolactone were isolated as the main active principles. Both constituents exhibited antihepatotoxic activity in assays employing CCl 4 -, GalN-, and phalloidin-cytotoxicity in rat hepatocytes. They also showed a significant stimulatory effect on liver cell regeneration. A HPLC-method is described for qualitative and quantitative analysis of the coumestans, in the extracts of ECLIPTA ALBA and also WEDELIA CALENDULACEA Less., Asteraceae.

Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea.

The mechanism of antihepatotoxic action of atractylon, a main sesquiterpenic constituent of ATRACTYLODES rhizomes, was studied. Atractylon inhibited carbon tetrachloride (CCl 4 )-induced cytotoxicity in primary cultured rat hepatocytes and CCl 4 -induced lipid peroxidation by rat liver microsomes. However, atractylon increased the free radical generation by CCl 4 with rat liver microsomes in the presence of a radical trapping agent, phenyl T-butyl nitrone (PBN). In addition, atractylon generated free radical PER SE. Experiments using 13 CCl 4 instead of CCl 4 indicated that the increased free radicals consisted of those from 13 CCl 4 and from atractylon. Accumulated data support that although both CCl 4 and atractylon generate free radicals respectively by rat liver microsomes, free radical from CCl 4 conducts lipid peroxidation and produces liver lesion, while atractylon forms free radical which scavenges CCl 3 radical in the absence of PBN, inhibits lipid peroxidation by CCl 4 and suppresses CCl 4 -induced liver lesion.

Mechanism of antihepatotoxic activity of glycyrrhizin. I: Effect on free radical generation and lipid peroxidation.

Sesamin, a major lignan in sesame oil, is known to have many biological activities, especially protective effects against oxidative damage in the liver. As sesamin itself has no antioxidative properties in vitro, to elucidate the mechanism of its antioxidative effects, the reaction products of sesamin in rat liver homogenate were analyzed. The methylenedioxyphenyl moiety in the structure of sesamin was shown to be changed into a dihydrophenyl (catechol) moiety. The enzymatic reaction products in vitro were identified as (1R,2S,5R,6S)-6-(3,4-dihydroxyphenyl)-2-(3,4-methylenedioxyphenyl)-3,7-dioxabicyclo[3,3,0]octane and (1R,2S,5R,6S)-2,6-bis(3,4-dihydroxyphenyl)-3,7-dioxabicyclo[3,3,0]octane, which showed strong radical scavenging activities; the latter was a novel compound. The same metabolites were found as glucuronic acid and/or sulfic acid conjugates in substantial amounts in rat bile after oral administration of sesamin. It is suggested that sesamin is a prodrug and the metabolites containing the catechol moieties in their structures are responsible for the protective effects of sesamin against oxidative damage in the liver.

Yoshinobu Kiso

Papers

Inhibitory Effects of Oolong Tea Polyphenols on Pancreatic Lipase in Vitro

Antihepatotoxic principles of Curcuma longa rhizomes.

Coumestans as the main active principles of the liver drugs Eclipta alba and Wedelia calendulacea.

Mechanism of antihepatotoxic activity of glycyrrhizin. I: Effect on free radical generation and lipid peroxidation.

Novel antioxidative metabolites in rat liver with ingested sesamin.