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

Pharmacology of oleanolic acid and ursolic acid

Antidiabetic plants and their active constituents.

Turmeric (Curcuma longa) is extensively used as a spice, food preservative and colouring material in India, China and South East Asia. It has been used in traditional medicine as a household remedy for various diseases, including biliary disorders, anorexia, cough, diabetic wounds, hepatic disorders, rheumatism and sinusitis. For the last few decades, extensive work has been done to establish the biological activities and pharmacological actions of turmeric and its extracts. Curcumin (diferuloylmethane), the main yellow bioactive component of turmeric has been shown to have a wide spectrum of biological actions. These include its antiinflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. Its anticancer effect is mainly mediated through induction of apoptosis. Its antiinflammatory, anticancer and antioxidant roles may be clinically exploited to control rheumatism, carcinogenesis and oxidative stress-related pathogenesis. Clinically, curcumin has already been used to reduce post-operative inflammation. Safety evaluation studies indicate that both turmeric and curcumin are well tolerated at a very high dose without any toxic effects. Thus, both turmeric and curcumin have the potential for the development of modern medicine for the treatment of various diseases.

Turmeric and curcumin: Biological actions and medicinal applications

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.

A water extract of the Oriental crude drug "reishi", the fruit bodies of GANODERMA LUCIDUM, significantly decreased plasma sugar level in mice. Fractionation of the extract by monitoring the hypoglycemic activity afforded two glycans, ganoderans A and B. These glycans elicited remarkable hypoglycemic actions in normal and alloxan-induced hyperglycemic mice.

Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies.

The antihepatatoxic effects of flavonolignans and related constituents from SILYBUM MARIANUM were examined using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes as model systems. Remarkable inhibitory actions were observed with silandrin, 3-deoxysilychristin, silybin and silymonin in carbon tetrachloride-treated cultures, and silydianin and silymonin were effective in preventing galactosamine-produced cell lesions. Possible structure-activity relationships are discussed.

Hiroshi Hikino

Papers

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.

Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies.

Antihepatotoxic actions of flavonolignans from Silybum marianum fruits.