Saikogenin A

Anti-inflammatory effect of saikogenin A

Saikogenin A, an anti-inflammatory drug, is present in the crude extract of a Chinese herbal plant called Tsai-Fu. Saikogenin A was less effective in adrenalectomized rats than in normal rats in reducing the carrageenin-induced edema. Serum corticosterone and ACTH were increased in the saikogenin A-treated rats, supporting the view that stimulation of hypothalamopituitary-adrenal system is responsible for the anti-inflammatory effect of saikogenin A. This is further supported by the findings that saikogenin A did not affect the spontaneous release of corticosterone but it facilitated the ACTH-induced release. In addition, cyclic AMP in isolated pituitary and adrenal glands was increased by saikogenin A. A role for cyclic AMP as the second messenger is thus considered. Otherwise, the direct action of saikogenin A on the process of inflammation cannot be ruled out because saikogenin A also functioned in the adrenalectomized rats and it inhibited the release of histamine induced by compound 48/80. Reduction of the vascular permeability was also observed in the saikogenin A-treated rats. These results suggest that the anti-inflammatory action of saikogenin A are due to an increase in corticosterone caused by the release of ACTH and a direct effect on the process of inflammation.

A new triterpenoid saponin from Clinopodium chinense (Benth.) O. Kuntze

A new triterpene saponin, 3β,16β,23α,28β,30β-pentahydroxyl-olean-11,13(18)-dien-3β-yl-[β-D-glucopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→3)]-β-D-fucopyranoside, was named Clinoposaponin D (1), together with six known triterpene saponins, buddlejasaponin IVb (2), buddlejasaponin IVa (3), buddlejasaponin IV (4), clinopodisides D (5), 11α,16β,23,28-Tetrahydroxyolean-12-en-3β-yl-[β-D-glucopyranosyl-(1→2)]-[β-D-glucopyranosyl-(1→3)]-β-D-fucopyranoside (6) and prosaikogenin A (7), and two known triterpenes, saikogenin A (8) and saikogenin F (9) were isolated from Clinopodium chinense (Benth.) O. Kuntze. Their structures were elucidated on the basis of 1D, 2D NMR and MS analysis. Meanwhile, the effects of all compounds on rabbit platelet aggregation and thrombin time (TT) were investigated in vitro. Compounds 4 and 7 had significant promoting effects on platelet aggregation with EC50 value at 53.4 and 12.2 μM, respectively. In addition, the highest concentration (200 μM) of compounds 2 and 9 shortened TT by 20.6 and 25.1%, respectively.

Protective effect of saikosaponin A, saikosaponin D and saikogenin D against Pseudomonas aeruginosa infection in mice

Effects of saikosaponins and their genins on nonspecific resistance against Pseudomonas aeruginosa and Listeria monocytogenes infections were investigated. When mice were administered intraperitoneally (i.p.) saikosaponins one day before i.p. infection with P. aeruginosa, saikosaponins a and d induced a marked enhancement of nonspecific resistance at a dose of 10 micrograms/mouse. Also, saikogenin D, a secondary metabolite of saikosaponin d, showed an enhancing effect. The most effective condition for enhancing the nonspecific resistance was i.p. administration of saikosaponin d one day before i.p. or intravenous (i.v.) infection with P. aeruginosa, when mice were treated i.p., i.v., or subcutaneously with saikosaponin d 1, 4 or 7 days previously. Effect of saikosaponin d was weaker than that of formalin-killed bacilli of Propionibacterium acnes and lipopolysaccharide. On the other hand, effect of saikosaponin d on enhancement of nonspecific resistance against L. monocytogenes was not seen. Effector cells participating in the enhanced protection induced by saikosaponin d may be macrophages, since macrophages were a major component in peritoneal cells obtained from mice administered i.p. saikosaponin d 1 day earlier and intracellular bactericidal activity of peritoneal macrophages against P. aeruginosa increased.

Corticosterone secretion-inducing activity of saikosaponin metabolites formed in the alimentary tract

The corticosterone secretion-inducing activities of saikosaponin a, saikosaponin c and saikosaponin d, isolated from the root of Bupleurum falcatum L., and 27 metabolites formed in the murine alimentary tract were studied in mice. Serum corticosterone was determined by high-performance liquid chromatography (HPLC). Intraperitoneal administration of saikosaponin a and its intestinal metabolite, prosaikogenin F, showed corticosterone secretion-inducing activity at a dose of 0.1 mmol/kg, and maximally increased it at a dose of 0.4 mmol/kg. On the other hand, the genuine sapogenin, saikogenin F, was inactive. Saikosaponin b1 and saikosaponin g, gastric metabolites of saikosaponin a, and their intestinal metabolites, prosaikogenin A, prosaikogenin H, saikogenin A and saikogenin H, were also inactive. Serum corticosterone was increased by the administration of saikosaponin d and its intestinal metabolite, prosaikogenin G, at a dose of 0.04 mmol/kg, and it reached the maximal level at the dose of 0.1 mmol/kg. Saikogenin G also showed a slight activity. A gastric metabolite of saikosaponin d, saikosaponin b2, and its intestinal metabolites, prosaikogenin D and saikogenin D, were inactive. In the experiments on saikosaponin c and its metabolites, saikosaponin c was inactive but its intestinal metabolites, especially prosaikogenin E-2, showed activity almost equal to that of saikosaponin a. Saikosaponin h and saikosaponin i, gastric metabolites of saikosaponin c, were also inactive, but their prosaikogenins showed slight activities. When these compounds were orally administered, their corticosterone secretion-inducing activities were similar to those obtained in the intraperitoneal experiment. These results suggest that a proper polar balance between the sugar moiety and the aglycone is important for the corticosterone secretion-inducing activity of saikosaponins and their metabolites.

Dual effect of saikogenin D: in vitro inhibition of prostaglandin E2 production and elevation of intracellular free Ca2+ concentration in C6 rat glioma cells

To clarify the pharmacological profile of saikogenin D, we examined the effect of saikogenin D on prostaglandin E2 (PGE2) production and intracellular free Ca2+ concentration ([Ca2+]i) in C6 rat glioma cells. Saikogenin D (1-20 microM) inhibited PGE2 production induced by the Ca2+ ionophore A23187 in a concentration-dependent manner with the IC50 of about 3 microM. Saikogenin D did not affect the conversion of arachidonic acid into PGE2 in microsomal preparations. On the other hand, saikogenin D elevated [Ca2+]i in a concentration-dependent manner (10-100 microM) with the EC50 value of about 35 microM in the presence or absence of extracellular Ca2+. These results suggest that saikogenin D possesses a dual effect: an inhibition of A23187-induced PGE2 production without a direct inhibition of cyclooxygenase activity; and an elevation of [Ca2+]i that is attributed to Ca2+ release from intracellular stores.