SUB-ACUTE TOXICITY OF A STEROIDAL GLYCOSIDE FROM THE FLOWERS OF ALANGIUM SALVIIFOLIUM WANG

The current study was carried out to investigate the sub-acute toxicity of 3-O--D-glucopyranosyl-(24)-ethylcholesta-5,22,25-triene, a steroidal glycoside isolated from the flowers of Alangium salviifolium Wang on Long Evan’s rat. After intra-peritoneal administration of the compound at a dose of 300 μg/rat/day for 14 consecutive days, no mortality or significant changes in body weight or behavior were observed. The blood samples of the rats were examined for hematological and biochemical parameters which were statistically insignificant when compared to that of the control group. All the vital organs showed normal histopathological architecture (heart, lungs, liver and kidney) in comparison to the control group. This preliminary investigation demonstrate that the compound is safe at dose of 300 μg/rat/day for 14 consecutive days. But acute, sub-chronic and chronic toxicity evaluations as well as clinical trials need to be done.

Quantum chemical, experimental exploration of biological activity and inhibitory potential of new cytotoxic kochiosides from Kochia prostrata (L.) Schrad

New cytotoxic steroidal glycoside of methanol extract from Kochia prostrata ([Formula: see text]) Schrad was investigated in this study. Bio-guided isolation from ethylacetate fraction of whole plant afforded steroidal glycosides named as 5-ene-dimethylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 1A1), 5-ene-methylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 2A1) and 4-ene-dimethylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 3A1). Their structures were assigned by physical and spectroscopic methods. Kochiosides 1A1–3A1 showed inhibitory potential against brine shrimp lethality bioassay with etoposide standard drug. The new steroidal glycoside kochiosides 1A1–3A1 showed inhibition values of 8.3201, 8.8205 and 8.2310[Formula: see text][Formula: see text]g/mL, respectively with [Formula: see text] compared to standard etoposide [Formula: see text] (7.4625[Formula: see text][Formula: see text]g/mL) drug. Moreover, six new derivatives were designed by substituting the –NH2 and –OCH3 at R1, R2 and R3 positions in the isolated compounds. Herein, various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential and molecular electrostatic potential (MEP) were carried out to understand the active sites and biological active nature of the new cytotoxic steroidal glycoside kochiosides. The effect of electron donating groups (–NH2 and –OCH3) was also investigated on the structural parameters and electronic properties in gas and solvent (DMSO) phases. The energy gap, MEP and reactivity descriptors values demonstrate that the kochioside 3A1 retains good reactivity, which is in good agreement with current experimental studies.

A C21-Steroidal Glycoside from Cynanchum atratum Attenuates Concanavalin A-Induced Liver Injury in Mice

Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1β and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1–10 μM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1β and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 μM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis.

A New Steroidal Glycoside Granulatoside C from the Starfish Choriaster granulatus, Unexpectedly Combining Structural Features of Polar Steroids from Several Different Marine Invertebrate Phyla

A new unique steroidal glycoside, granulatoside C (1), was isolated from the ethanol extract of the starfish Choriaster granulatus. The structure of 1 was elucidated by extensive NMR and ESI-MS techniques as (20 R)-16,21- O-di-(P-D-fucopyranosyl)-24-methyl-cholesta-5,24(28)-diene-3p,7a,16a,21-tetraol (1). This glycoside is unusual one, because combines some characteristic structural peculiarities of steroids from several different phyla of marine invertebrates, it has a range of structural features that not previously found in starfish polyhydroxysteroidal glycosides, such as Δ5-3β,7α,16α-trihydroxysteroidal nucleus, Δ24(28)-21-hydroxy-24-methyl-cholestane side chain and 16,21-diglycosylation by D-fucopyranosyl residues, but also characteristic of sponges, ophiuroids and soft corals, respectively.

New Steroidal Glycoside and Flavonoid Constituents from Ophiopogon japonicus

Chromatographic separations of a methanolic extract of Ophiopogon japonicus tubers resulted in the isolation of a new steroidal glycoside, (25 R)-ruscogenin 1- O-(4- O-sulfo)-β-D-fucopyranoside (1), a new C-methylflavonol, 3,4′-dimethoxy-3′,5,5′,7-tetrahydroxy-8-methylflavone (2), and a known flavonol, 3,4′-dimethoxy-3′,5,5′,7-tetrahydroxyflavone (3). The C-methylflavonol was reported for the first time from the genus Ophiopogon. Compound 1 showed moderate cytotoxicity against SK-Mel-2 and KB cells with IC50 values of 24.3 and 28.8 μM, respectively. Compound 2 was active on SK-Mel-2 cells (IC50 20.3 μM).