Balanitoside, a furostanol glycoside, and 6-methyldiosgenin from Balanites aegyptiaca.

In addition to a known spirostanol glycoside, balanitin-3, and a new sapogenol, 6-methyldiosgenin, a new furostanol saponin, balanitoside has been isolated from the fruits (mesocarp) of Balanites aegyptiaca. The structure of the glycoside has been determined as 26-O-beta-D-glucopyranosyl-3 beta, 22,26-trihydroxy-furost-5-ene 3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D- glucopyranosyl-(1-->4)-beta-D-glucopyranoside, on the basis of spectroscopic and chemical evidence.     

Aldose reductase inhibitory effect by tectorigenin derivatives from Viola hondoensis

Aldose reductase (AR), the key enzyme of the polyol pathway, is known to play important roles in the diabetic complication. The inhibitors of AR, therefore, would be potential agents for the prevention of diabetic complication. The AR inhibition activity of several isoflavonoids was evaluated in vitro against rat lens. Tectoridin-4'-O-beta-D-glucoside exhibited strong AR inhibition activity on rat lens with an IC50 of 0.54 microM. Similar activities were recorded for the natural tectorigenin and tectoridin. In contrast, tectoridin-4'-O-beta-D-glucoside showed a stronger inhibitory activity than tectorigenin and tectoridin. Our results indicate that glucose conjugation position in this type of isoflavonoids may be required for the activity.     

Aldose reductase inhibition prevents metaplasia of airway epithelial cells

Background

Goblet cell metaplasia that causes mucus hypersecretion and obstruction in the airway lumen could be life threatening in asthma and chronic obstructive pulmonary disease patients. Inflammatory cytokines such as IL-13 mediate the transformation of airway ciliary epithelial cells to mucin-secreting goblet cells in acute as well as chronic airway inflammatory diseases. However, no effective and specific pharmacologic treatment is currently available. Here, we investigated the mechanisms by which aldose reductase (AR) regulates the mucus cell metaplasia in vitro and in vivo.

Methodology/Findings

Metaplasia in primary human small airway epithelial cells (SAEC) was induced by a Th2 cytokine, IL-13, without or with AR inhibitor, fidarestat. After 48 h of incubation with IL-13 a large number of SAEC were transformed into goblet cells as determined by periodic acid-schiff (PAS)-staining and immunohistochemistry using antibodies against Mucin5AC. Further, IL-13 significantly increased the expression of Mucin5AC at mRNA and protein levels. These changes were significantly prevented by treatment of the SAEC with AR inhibitor. AR inhibition also decreased IL-13-induced expression of Muc5AC, Muc5B, and SPDEF, and phosphorylation of JAK-1, ERK1/2 and STAT-6. In a mouse model of ragweed pollen extract (RWE)-induced allergic asthma treatment with fidarestat prevented the expression of IL-13, phosphorylation of STAT-6 and transformation of epithelial cells to goblet cells in the lung. Additionally, while the AR-null mice were resistant, wild-type mice showed goblet cell metaplasia after challenge with RWE.

Conclusions

The results show that exposure of SAEC to IL-13 caused goblet cell metaplasia, which was significantly prevented by AR inhibition. Administration of fidarestat to mice prevented RWE-induced goblet cell metaplasia and AR null mice were largely resistant to allergen induced changes in the lung. Thus our results indicate that AR inhibitors such as fidarestat could be developed as therapeutic agents to prevent goblet cell metaplasia in asthma and related pathologies.     

Larvicidal activity of saponins from Balanites aegyptiaca callus against Aedes aegypti mosquito

Seeking an alternative approach for producing a larvicidal product from Balanites aegyptiaca plants, callus was produced from in vitro cultures of root explants and its larvicidal activity against Aedes aegypti mosquito larvae was evaluated. Concentrations of 0, 50, 100, 500, 1000, and 1500 ppm of saponins from the root-derived callus of B. aegyptiaca were used to determine larvicidal effects and consequent effect on adult emergence. A dose-dependent effect was observed. In a chronic mortality assessment (after 7 days of exposure), concentrations of 500 ppm or greater killed 100% of the test larvae population. Fifty parts per million showed no difference in larval mortality compared to the control (0 ppm); however, this concentration allowed one-fourth of the adult emergence of the control treatment. These results suggest that saponins from in vitro cultures of the root explant of B. aegyptiaca can be used as a larvicidal agent against A. aegypti larvae.     

Aldose reductase inhibitory compounds from extracts of Dipsacus asper

Amethanolic extract of Dipsacus asper, having anti-diabetic activity, was examined as a possible aldose reductase (ALR2) inhibitor, a key enzyme involved in diabetic complications. Bioactivity guided fractionation led to the isolation of ten compounds, ursolic acid (1), oleanolic acid-3-O-α-L-arabinopyranoside (2), daucosterol (3), hederagenin-3-O-α-L-arabinopyranoside (4), sweroside(5), caffeic acid (6), esculetin (7), protocatechualdehyde (8), loganin (9), and vanilic acid (10) from the ethyl acetate fraction of D. asper methanol extract. Among them, compounds 4, 6, 7, and 8 exhibited inhibitory effects on aldose reductase, with IC₅₀ values of 23.70, 16.71, 34.36, and 21.81 μM, respectively. This is the first report on the isolation of these compounds from D. asper, and the ALR2 inhibitory activity of hederagenin-3-O-α-L-arabinopyranoside. These results suggest the successful use of the extract of D. asper for ameliorating diabetic complications.     

Two new triterpene saponins from the anti-inflammatory saponin fraction of Ilex pubescens root

The saponin fraction from the ethanolic extracts of the root of Ilex pubescens Hook. et Arn. (Ilexaceae) was found to exhibit potent anti-inflammatory effects on carrageenan-induced paw edema in rats. Two novel triterpene saponins, pubescenosides C and D (1 and 2, resp.), together with five known saponins were isolated from this saponin fraction. The structures of 1 and 2 were elucidated as (20beta)-3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa-12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, and (20beta)-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->2)-beta-D-xylopyranosyl]ursa- 12,18-dien-28-oic acid 28-O-beta-D-glucopyranosyl ester, respectively, on the basis of chemical and spectroscopic data. Five known saponins isolated from the saponin fraction were identified as ilexsaponin B(1), B(2), B(3), A(1), and chikusetsusaponin IV(a).     

Aldose reductase inhibitors from the fruits of Caesalpinia ferrea Mart.

Aldose reductase inhibitors were isolated from an extract of the dry fruits of Caesalpinia ferrea Mart. (Leguminosae). Compound 2 was identified as ellagic acid by comparison with a reference sample. The structure of compound 1 was elucidated as 2-(2,3,6-trihydroxy-4-carboxyphenyl) ellagic acid on the basis of spectral evidence, especially 2D-NMR data (HMQC, HMBC and NOESY). These two compounds inhibited aldose reductase in a non-competitive manner.     

Aldose reductase inhibition prevents lipopolysaccharide-induced glucose uptake and glucose transporter 3 expression in RAW264.7 macrophages

Macrophages which play a central role in the injury, infection and sepsis, use glucose as their primary source of metabolic energy. Increased glucose uptake in inflammatory cells is well known to be one of the responsible processes that cause inflammatory response and cytotoxicity. We have shown recently that the inhibition of aldose reductase (AR) prevents bacterial endotoxin, lipopolysaccharide (LPS)-induced cytotoxicity and inflammatory response in macrophages. However, it is not known how AR inhibition prevents LPS-induced inflammation. Here in, we examined the effect of AR inhibition on LPS-induced glucose uptake and the expression of glucose transporter 3 (GLUT-3) in RAW264.7 murine macrophages. Stimulation of macrophages with LPS-increased glucose uptake as measured by using C¹⁴ labeled methyl-d-glucose and inhibition of AR prevented it. Similarly, ablation of AR by using AR-siRNA also prevented the LPS-induced glucose uptake in macrophages. Further, AR inhibition also prevented the LPS-induced up-regulation of GLUT-3 expression, cyclic adenosine monophosphate (cAMP) accumulation and protein kinase A (PKA) activation in RAW264.7 cells. Moreover, LPS-induced down-regulation of cAMP response element modulator (CREM), phosphorylation of cAMP response element-binding protein (CREB) and DNA-binding of CREB were also prevented by AR inhibition. Further, inhibition of AR or PKA also prevented the LPS-induced levels of GLUT-3 protein as well as mRNA in macrophages. These results indicate that AR mediates LPS-induced glucose uptake and expression of glucose transporter-3 via cAMP/PKA/CREB pathway and thus represents a novel mechanism by which AR regulates LPS-induced inflammation.     

Seven new benzeneacetic acid derivatives and their quinone reductase activity from Eurycorymbus cavaleriei

From the twigs of Eurycorymbus cavaleriei, seven new benzeneacetic acid derivatives cavaol A–G (1–7) were isolated. The structures were elucidated on the basis of the results of spectroscopic (NMR, IR, UV and MS) analysis. In the present study, the quinone reductase (QR) induction activities of compounds 1–7 were assayed. Compounds 3 and 4 showed moderate QR induction with concentrations to double the enzyme activity (CD) of 9.9 ± 0.3 and 7.9 ± 0.5 μg/mL, respectively. LC-MS-MS analysis revealed that the quinone reductase induction activity of compounds 3 and 4 was not due to alkylating the sulfhydryl groups of Keap1. There must be some other pathways for compounds 3 and 4 to induce quinone reductase.     

Isolation and characterization of a furostanol glycoside from fenugreek

From the seed of fenugreek, a new glycoside has been isolated and shown to have the structure, (25S)-22-O- methyl-5α-furostan-3β,22,26-triol 3-O-α-rhamnopyranosyl(1→2)[-β-d-glucopyranosyl (1→3)]-β-d- glucopyranoside-26-O-β-d-glucopyranoside.     

Lack of inhibition of glutathione reductase by unnitrated derivatives of nitrofurantoin

Nitrofurantoin produced greater than 70% inhibition of glutathione reductase (EC 1.6.4.2) from human blood, rat blood and yeast. In contrast, identical concentrations of unnitrated derivatives produced less than 10% inhibition of the enzyme. Both nitrofurantoin and the unnitrated derivatives are equally effective in causing depletion of erythrocyte ATP and reduced glutathione levels. These data suggest that the drug-induced red cell toxicity may not be mediated solely by inhibition of glutathione reductase.     

Rivularinin,a new saponin from Anemone rivularis

A new saponin, rivularinin, has been isolated from the ethanolic extract of Anemone rivularis (Ranunculaceae). The saponin was shown to be [α-l-arabinofuranosyl(1→2)-α-l-rhamnopyranosyl (1→4)-β-d-glucopyranosyl(1→4)-β-d-glucuronopyranosyl(1→3)]-3β-hydroxy-olean-12-en-28-oic acid.     

Anti-inflammatory activity of a new triterpenoid saponin from carthamus tinctorius linn

A new bioactive triterpenoid saponin 3beta-O-[beta-D-xylopyranosyl(1 --> 3)-O-beta-D-galactopyranosyl]-lup-12-ene-28 oic acid-28-O-alpha-L-rhamnopyranosyl ester compound (A), was isolated from the methanolic fraction of the roots of this plant by various colour reactions, chemical degradations and spectral analysis. Compound (A) showed anti-inflammatory activity.     

Anti-inflammatory activity of a new triterpenoid saponin from carthamus tinctorius linn

A new bioactive triterpenoid saponin 3β-O-[β-D-xylopyranosyl(1 → 3)-O-β-D-galactopyranosyl]-lup-12-ene-28 oic acid-28-O-α-L-rhamnopyranosyl ester compound (A), was isolated from the methanolic fraction of the roots of this plant by various colour reactions, chemical degradations and spectral analysis. Compound (A) showed anti-inflammatory activity.