Structures of withanosides I, II, III, IV, V, VI, and VII, new withanolide glycosides, from the roots of Indian Withania somnifera Dunal. and inhibitory activity for tachyphylaxis to clonidine in isolated guinea-pig ileum

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Abstract

Seven new withanolide glycosides called withanosides I, II, III, IV, V, VI, and VII were isolated from an Indian natural medicine, Ashwagandha, the roots of Indian Withania somnifera Dunal. (Solanaceae), together with four known compounds, withaferin A, 5α,20αF(R)-dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide, physagulin D, and coagulin Q. The structures of withanosides I, II, III, IV, V, VI, and VII were determined based on chemical and physicochemical evidence. Principal constituents, withanoside VI (10 and 30 μM) and withaferin A (10 μM), attenuated the tachyphylaxis to clonidine on electrically stimulated guinea-pig ileum in vitro.

Seven new withanolide glycosides called withanosides I, II, III, IV, V, VI, and VII were isolated from an Indian natural medicine, Ashwagandha, the roots of Indian Withania somnifera (Solanaceae), together with four known compounds, withaferin A, 5α,20αF(R)-dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide, physagulin D, and coagulin Q. The structures of withanosides I–VII were determined based on chemical and physicochemical evidence. Principal constituents, withanoside VI (10 and 30 μM) and withaferin A (10 μM), attenuated the tachyphylaxis to clonidine on electrically stimulated guinea-pig ileum in vitro.

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Structures of withanosides I (1), II (2), III (3), IV (4), V (5), VI (6), and VII (7)

In the positive-ion FAB–MS of withanolide I (1), a quasimolecular ion peak was observed at m/z 659 (M+Na)+, and high-resolution MS analysis revealed the molecular formula of 1 to be C34H52O11. The IR spectrum of 1 showed absorption bands at 1705 and 1655 cm–1 assignable to α,β-unsaturated δ-lactone and carbonyl functions and broad bands at 3432, 2942, and 1034 cm–1 suggestive of an oligoglycosidic structure. The UV spectrum of 1 showed absorption maxima at 227 nm (log ε 3.7), which suggested the

Effects of Withanoside VI (6) and Withaferin A (8) on the Tachyphylaxis to Clonidine

Clonidine (0.3 to 100 nM) produced a concentration-dependent inhibition of twitch responses on electrically stimulated guinea-pig ileum. The EC50 value of clonidine was 4.2 nM. After 90-min incubation with clonidine (10 nM) that gave an initial reduction in twitch height of 69±11% (n=5), their effective concentrations in the first treatment were less effective to the twitch responses. Namely, EC50 value shifted to 15 nM (Table 2).

Withanoside VI (6, 10 and 30 μM) and withaferin A (8, 10 μM), when

Experimental


The following instruments were used to obtain physical data:specific rotations, Horiba SEPA-300 digital polarimeter (l=5 cm); UV spectra, Shimadzu UV-1200 spectrometer; CD spectra; J-720WI spectropolarimeter; IR spectra, Shimadzu FTIR-8100 spectrometer; 1H NMR spectra, JEOL EX-270 (270 MHz) and JNM-LA500 (500 MHz) spectrometers; 13C NMR spectra, JEOL EX-270 (68 MHz) and JNM-LA500 (125 MHz) spectrometers with tetramethylsilane as an internal standard; MS and high-resolution MS, JEOL JMS-SX 102A mass

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