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Isolation and characterization of cytotoxic saponin chloromaloside A from Chlorophytum malayense.

A cytotoxic steroidal glycoside was isolated from Chlorophytum malayense Ridley and its structure was characterized as a known compound, neohecogenin 3-O-beta-D-glucopyranosyl(1-->2)-[beta-D-xylopyranosyl(1-->3)]-beta-D- glucopyranosyl(1-->4)-beta-D-galactopyranoside (chloromaloside A). The structural identification was performed using 2D-NMR and LC/MS/MS analysis. The previous, erroneously assigned 1H-NMR spectral data were revised whereas the published 13C-NMR spectral assignments were confirmed. This compound showed in vitro cytotoxicity against several human cancer cell lines.

Antineoplastic Agents, Phytogenic↗

Anti-inflammatory activity of aqueous extracts and steroidal sapogenins of Agave americana.

Lyophilized aqueous extracts obtained from Agave americana L (Agavaceae) collected in the north of Sardinia were characterized with regard to their steroidal sapogenin content. Extracts of A. americana and genins isolated from them were evaluated for anti-inflammatory properties by testing their effects on carrageenin-induced edema. The effect of orally administered genins on gastric mucous membranes was also assessed. Lyophilized extracts administered by the intraperitoneal route at doses equivalent to 200 and 300 mg/kg of fresh plant starting material, showed good anti-inflammatory activity. Doses of genins (total steroidal sapogenins, hecogenin and tigogenin) equivalent to the amount in the lyophilized extracts produced an antiedentatous effect which was much stronger and more efficacious than that obtained with an i.p. administration of 5 mg/kg of indomethacin or dexamethasone 21-phosphate at a dose equivalent to the molar content of hecogenin administered. At the doses used to evaluate the anti-inflammatory activity, the genins did not have any harmful effect on the gastric mucous membranes. Lesions occurred when significantly higher doses of hecogenin were given, but gastric damage was still less than that caused by the drugs used for comparative purposes.

Animals↗

Antinociceptive effect of smilaxin B administered intracerebroventricularly in the mouse.

We examined the antinociceptive effect of smilaxin B administered intracerebroventricularly (i.c.v.) in ICR mice. The tail-flick test was used as an analgesic assay. Smilaxin B showed a strong antinociceptive effect in a dose-dependent manner. Sulfated cholecystokinin (CCK-8s, 0.5 ng), muscimol (50ng), or MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5, 10-imine maleate, 1 microgram] injected i.c.v. significantly reduced inhibition of the tail-flick response induced by smilaxin B administered i.c.v. However, naloxone (2 microgram), baclofen (10 ng), or CNQX (6-cyano-7- nitroquinoxaline-2,3-dione, 0.5 microgram) injected i.c.v. did not affect inhibition of the tail-flick response induced by similaxin B administered i.c.v. The intrathecal (i.t.) injection of yohimbine (20 micrograms), but not methysergide (20 micrograms) and naloxone (2 microgram), significantly attenuated inhibition of the tail-flick response. induced by smilaxin B administered i.c.v. Our results suggest that GABAA or NMDA receptors but not opioid, GABAB, and non-NMDA receptors located at the supraspinal level may play important roles in the production of antinociception induced by smilaxin B administered supraspinally. Furthermore, smilaxin B administered supraspinally. may produce its antinociception by activating descending noradrenergic- but not opioidergic- and serotonergic-neurons.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Antineoplastic agents; I. Three spirostanol glycosides from rhizomes of Dioscorea collettii var. hypoglauca.

By activity-guided fractionation, three known steroidal saponins, prosapogenin A of dioscin, dioscin and gracillin, were isolated from the total saponin fraction of Dioscorea coiletti var. hypoglauca as active compounds causing morphological abnormality of Pyricularia oryzae mycelia. The compounds also exhibited cytotoxic activity against the cancer cell line K562 in vitro. The structures of the compounds were elucidated on the basis of chemical evidence and IR, FAB-MS, 1H-NMR, 13C-NMR, and two-dimensional NMR (2D-NMR) analysis.

Antineoplastic Agents↗

Furostanoside from Asparagus filicinus.

A new furostanoside, named aspafilioside D (1), together with the five known compounds officinalisnin-II (2), Asp-IV' (3), (+)-4'-O-methyl-nyasol (4), (+)-nyasol (5) and tormentic acid (6), have been isolated from the roots of Asparagus filicinus. The structure of 1 has been elucidated on the basis of spectral data.

Asparagus Plant↗

Antiviral activity of constituents of Tamus communis.

The antiviral activity of the phenanthrene derivatives 1-6, of the spyrostane triglycosides dioscin (7) and gracillin (8), of the furostanol tetraglycosides methylprotodioscin (9), its (25S) epimer methylprotoneodioscin (10), and methylprotogracillin 11, have been tested towards two RNA viruses: vesicular stomatitis virus and human rhinovirus type 1B. All these products were extracted from the rizomes of Tamus communis L; compound 11 was isolated also from Asparagus cochinchinesis, together with pseudoprotodioscin (12), a 20 (22)-unsaturated furostanoside, which was also investigated for antiviral activity. The results were of some interest mainly for the phenanthrene derivatives.

Animals↗

Separation of mitochondrial membranes of Neurospora crassa. II. Submitochondrial localization of the isoleucine-valine biosynthetic pathway.

Separation of Neurospora mitochondrial outer membranes from the inner membrane/matrix fraction was effected by digitonin treatment and discontinuous density gradient centrifugation. The solubilization of four isoleucine-valine biosynthetic enzymes was studied as a function of digitonin concentration and time of incubation in the detergent. The kinetics of the appearance of valine biosynthetic function in fractions outside of the inner membrane/matrix fraction, coupled with enzyme solubilization patterns similar to that for the matrix marker, mitochondrial malate dehydrogenase, indicate that the four isoleucine-valine pathway enzymes are localized in the mitochondrial matrix.

Alcohol Oxidoreductases↗

Ruscogenin glycoside (Lm-3) isolated from Liriope muscari improves liver injury by dysfunctioning liver-infiltrating lymphocytes.

The effects of ruscogenin 1-O-[beta-D-glucopyranosyl(1 --> 2)] [beta-D-xylopyranosyl(1 --> 3)]-beta-D-fucopyranoside (Lm-3) and its aglycone, ruscogenin, on liver injury induced in mice by delayed-type hypersensitivity to picryl chloride have been investigated. Lm-3 and ruscogenin significantly decreased liver injury when given during the effector phase of the delayed-type hypersensitivity reaction. The pretreatment of nonparenchymal cells, but not hepatocytes, with Lm-3 or ruscogenin in-vitro caused a concentration- and time-dependent inhibition against the damage. Lm-3 showed a stronger inhibition against the damage than ruscogenin (IC50: Lm-3 6.3 x 10(-10) M, ruscogenin 3.9 x 10(-7) M). However, neither Lm-3 nor ruscogenin blocked the hepatotoxic potential of CCl4, when used to pretreat hepatocytes. Moreover, Lm-3 and ruscogenin inhibited concanavalin A-induced lymphocyte proliferation only at high concentrations. These results suggested that Lm-3 and ruscogenin improved the immunological liver injury by selectively causing dysfunction of the liver-infiltrating cells rather than by protecting hepatocyte membranes. Such characteristics would be significant for treating immunologically related liver diseases as well as for developing new drugs.

Animals↗

Ruscogenin glycoside (Lm-3) isolated from Liriope muscari inhibits lymphocyte adhesion to extracellular matrix.

We examined the effects of ruscogenin glycoside (Lm-3), isolated from Liriope muscari, on lymphocyte adhesion to extracellular matrix. Adhesion of Jurkat cells activated by anti-CD3 to type I collagen was inhibited by Lm-3 in a concentration- and time-dependent manner. Lm-3 also inhibited the cell attachment to fibronectin and laminin. However, the saponin did not influence anti-CD3-induced cell proliferation and Mn2+-induced adhesion. Protein kinase C activator, phorbol 12,13-dibutyrate, significantly enhanced, while its inhibitor, chlorpromazine, almost completely blocked, the adhesion of anti-CD3-activated Jurkat cells to collagen. Against phorbol 12,13-dibutyrate-activated Jurkat cells, Lm-3 treatment, either before or after activation, significantly inhibited the cell adhesion to collagen. Lm-3 also inhibited the adhesion activated by both anti-CD3 and phorbol 12,13-dibutyrate. Similar inhibition by Lm-3 of the phorbol 12,13-dibutyrate-induced adhesion to collagen was also observed in lymphocytes freshly isolated from mice with contact dermatitis. Furthermore, Lm-3 significantly decreased the leucocyte accumulation in an animal model of experimental pleurisy. These results suggest that the blockade of lymphocyte adhesion to extracellular matrix through interference with the protein kinase C pathway may be one of the mechanisms by which Lm-3 exerts anti-inflammatory activity.

Animals↗

Effects of steroidal glycosides on blood glucose in normal and diabetic mice.

Two steroidal glycosides, PO-1 and PO-2, were tested as a new hypoglycemic drug. PO-2 showed remarkable hypoglycemic activity on i.p. injection into normal mice. PO-1 slightly lowered the blood glucose in normal mice. Furthermore, PO-1 and PO-2 exhibited significant hypoglycemic effects in streptozotocin-induced diabetic mice. However, a steroid, diosgenin, did not affect the blood glucose level in either normal or streptozocin-induced diabetic mice, indicating that the branching glucose units are essential for the biological activity.

Animals↗