Improved arachidonic acids production from the fungus Mortierella alpina by glutamate supplementation.

The effect of various concentrations of glutamate on arachidonic acid (AA) production from Mortierella alpina in shaker flask culture was studied. Glutamate supplementation promoted Mortierella growth, accelerated substrate metabolism, and increased AA production, and a concentration of 0.8 g/l glutamate resulted in the greatest AA yield (1.41 g/l). In 10 l airlift stirred fermenter culture, AA yield in the cultures exposed to 0.8 g/l glutamate was also greater than that in the control (0.56 g/l).

An inexpensive medium for production of arachidonic acid by Mortierella alpina.

The production of arachidonic acid was studied in the fungus Mortierella alpina using an inexpensive medium. Glucose derived from maize starch hydrolysate was the sole carbon source and defatted soybean meal and sodium nitrate were the nitrogen sources. Optimal arachidonic acid yield (1.47 g l(-1)) was observed at a glucose concentration of 100 g l(-1). Various treatments of defatted soybean meal to extract soluble nitrogen nutrients were evaluated. Alkali extract was the most effective for arachidonic acid production. A mixture of soybean alkali-extract protein and sodium nitrate was an excellent nitrogen source for fungal growth, lipid accumulation, and arachidonic acid production. A maximum yield of 1.87 g arachidonic acid l(-1) was obtained with a soybean protein concentration of 4.6 g l(-1) and a sodium nitrate concentration of 2.3 g l(-1).

Structure-activity relationship of tubeimosides in anti-inflammatory, antitumor, and antitumor-promoting effects.

AIM: To study structure-activity relationship of tubeimosides isolated from Bolbostemma paniculatum for their anti-inflammatory, antitumor, and antitumor-promoting effects. METHODS: Tubeimosides I, II, and III were isolated from tubers of Bolbostemma paniculatum (Maxim) Franquet (Cucurbitaceae), a Chinese folk medicine,"Tubeimu", and their anti-inflammatory, anti-tumor, anti-tumorigenic activities, and acute toxicity were studied in vivo. RESULTS: Tubeimosides I, II, and III are all natural analogues of oleanane type of triterpenoid saponins from the same medicinal plant, and all show anti-inflammatory, antitumor, and antitumor-promo ting effects. However, the anti-inflammatory, anti-tumor, and anti-tumorigenic activities of tubeimoside II are stronger than those of tubeimoside I, and the acute toxicity of tubeimoside II is lower than that of tubeimoside I; the anti-inflammatory, anti-tumor, and anti-tumorigenic activities of tubeimoside III are stronger than those of tubeimoside II, and the acute toxicity of tubeimoside III is also stronger than that of tubeimoside II. CONCLUSION: C-16 hydroxyl group of tubeimoside II plays an important role in enhancing biological activity of tubeimoside II and in decreasing its toxicity. The difference of chemical structure in B and/or C position between tubeimosides III and II plays an important role in enhancing biological activity and toxicity of tubeimoside III. Therefore tubeimosidre II may be the most promising agent for cancer chemoprevention and chemotherapy among tubeimosides I, II, and III.

P450 enzyme expression patterns in the NCI human tumor cell line panel.

Cytochrome P450 (P450) enzyme expression patterns were determined for a panel of 60 human tumor cell lines, representing nine tumor tissue types, used by the National Cancer Institute (NCI) Anticancer Drug Screening Program. All 60 tumor cell lines displayed significant P450 activity, as well as P450 reductase activity, as determined using the general P450 substrate 7-benzyloxyresorufin. Cell line-specific P450 enzyme patterns were observed using three other P450 substrates, 7-ethoxycoumarin, coumarin, and 7-ethoxyresorufin, each of which was metabolized at a low rate. Using a pattern-matching computer program, COMPARE, correlative relationships were investigated between the arrays of P450 activities and the patterns of cytotoxicity exhibited by a large group of anticancer agents of proven or potential clinical utility. Significant negative correlations between the patterns of P450-dependent 7-benzyloxyresorufin metabolism activity and cell line chemosensitivity were observed for 10 standard anticancer agents (including 6 alkylating agents) and 55 investigational compounds, suggesting a role for P450 metabolism in the inactivation of these agents. Negative correlations between 7-ethoxycoumarin O-deethylation and cell line chemosensitivity to a group of topoisomerase inhibitors were also seen, again suggesting P450-dependent drug inactivation. P450 enzyme profiling may thus aid in interpreting the patterns of drug sensitivity and resistance in the NCI tumor cell panel, and may facilitate the identification of anticancer agents whose activity can be altered via cytochrome P450 metabolism.

Effects of tubeimoside-1 on HIV core protein p24 and cytopathogenesis in vitro.

Tubeimoside-1 (Tub) is a triterpenoid saponin first isolated in China from Bolbostemma paniculatum (Maxim) Franquet, Cucurbitaceae. To find out whether Tub has any anti-infective activity on human immunodeficiency virus (HIV), we tested its effects on HIV core protein p24 (with an ELISA) and HIV-mediated cytopathogenesis (using a colorimetric assay). The results showed that Tub inhibited both p24 production and cytopathogenesis mediated by HTLV-IIIB, and the median effective concentrations (EC50) were 24.1 and 22.9 micrograms.ml-1, respectively. Tub also effectively neutralized the infection of 2 other isolates, HTLV-IIIRF and HTLV-IIIMN. It is concluded that Tub had an inhibitory action on the infection of HIV-1 isolates and would be a promising candidate for treatment of AIDS.

Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice.

Licochalcone A, 3-a,a-dimethylallyl-4,4'-dihydroxy-6-methoxychalcone, from the root of Glycyrrhiza inflata Beta (Leguminosae) (Xin-jiang liquorice) showed anti-inflammatory action towards mouse ear edema induced by arachidonic acid (AA) and 12-O-tetradecanoylphorbol 13-acetate (TPA) by topical application. Anti-tumour promoting action of licochalcone A was also observed in vivo for mouse skin papilloma initiated by dimethylbenz[a]anthracene (DMBA) and promoted by TPA. It inhibited in vitro 32Pi-incorporation to phospholipids in HeLa cells promoted by TPA. A competitive interaction of licochalcone A with the TPA-receptors in the cell membrane has been suggested.