From the ethyl acetate-soluble fraction of the drug Ed/pta a/ba (L.) Hassk. Asteraceae, besides a flavonoid and simple phenolcarboxylic acids, the coumestans wedelolactone and demethylwedelolactone were isolated as the main active principles. Both constituents exhibited antihepatotoxic activity in assays employing CC!4-, GaiN-, 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 a/ba and also Wedelia ca/endulacea Less., Asteraceae.

An extract of the crude drug "ukon", the rhizomes of Curcuma longa, exhibited intense preventive activity against carbon tetrachioride-induced liver injury in vivo and in vitro. The extract was subjected to frac-Part 8 in Liver-protective drugs. This paper also constitutes Part 53in the series on the validity of the Oriental medicines. Table I tionation by monitoring the activity by the in vitro assay methods employing carbon tetrachioride-and galactosamine-produced cytotoxicity in primary cultured rat hepatocytes. Curcuminoids were shown to possess significant antihepatotoxic action. The liverprotective effects of some analogues of ferulic acid and p-coumaric acid, probable metabolites of the curcuminoids, were also evaluated.

Ephedrine (EP), pseudoephedrine (PEP), ephedroxane (EX) and pseudoephedroxane (PEX) inhibited carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice. Hind-paw edema induced by histamine, serotonin, bradykinin and prostaglandin E (1) was suppressed by these alkaloids, showing that they exert the antiinflammatory activity at the early exudative stage of inflammation. Although tolazoline and propranolol had no effects on the inhibitory activity of EX and PEX, treatment with tolazoline decreased the antiinflammatory activity of EP and PEP on carrageenin-induced hind-paw edema. Antiinflammatory activity of PEP was reduced by previous treatment with reserpine, indicating the antiinflammatory activity of EP and PEP to be partly concerned with the sympathetic nervous system. Although these alkaloids injected I.C.V. elicited no antiinflammatory actions on carrageenin-induced hind-paw edema and the inhibitory activity of morphine on carrageenin-induced hind-paw edema was potentiated by the concurrent administration of PEP and EX, demonstrating that the mechanism of antiinflammatory activity does not involve the central nervous system. Further, these alkaloids inhibited prostaglandin E (2) biosynthesis.

Glycyrrhizin and its analogues were screened for antihepatotoxic activity by in vitro assay methods using carbon tetrachloride (CC!4)-and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. Structure-activity relationship in these substances is discussed. The mechanism of inhibitory activity of glycyrrhizin and glycyrrhetinic acid in CCI4-produced liver damage was investigated by determining the effects of these substances on the initial steps in the sequence of events leading to liver lesion, revealing that anti-oxidative action plays an important part in the antihepatotoxic activity. Liver-protective drugs, Part 14. Also Part 65 in the Tohoku University series on the validity of Oriental medicines.

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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 silymonm in carbon tetrachloride-treated cultures, and silydianin and silymonm were effective in preventing galactosamine-produced cell lesions. Possible structure-activity relationships are discussed.

The antihepatotoxic effects of twenty-three lignans, twentytwo from the fruits of Schizandra chinensis and one from the fruits of Kadsura japonica, were investigated utilizing carbon tetrachloride (Cd4)-and galactosamine (Ga1N)-induced cytotoxicity in primary cultured rat hepatocytes as model systems. Prominent protective actions were found with wuweizisu C and schisantherin D in CC14-treated cultures, and deoxygomisin A, gomisin N, wuweizisu C, gomisin C and schisantherin D were effective in preventing GaIN-induced cell damage. Structure-activity relationship suggests that the methylenedioxy group of the dibenzocyclooctane skeleton may play an important role in antihepatotoxic activity.

Extracts of various samples of the crude drug prepared from Atractylodes rhizomes exhibited antihepatotoxic activity by in vitro assay methods using carbon tetrachloride- and galactosamine-induced cytotoxicity in primary cultured rat hepatocytes. The main sesquiterpenoid components were subjected to screening by these methods to reveal that atractylon, beta-eudesmol, and hinesol exerted significant liver-protective effects. Some analogs were also assayed.