sapogenins and Edema

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Biomarkers; Carrageenan; Cytokines; Diosgenin; Edema; Humans; Methotrexate; Oxidative Stress; Rats; Rats, Wistar; Sapogenins

Epidemiological studies have demonstrated that ginseng intake decreases the risk of cancer. Ginseng saponins (ginsenosides) have been regarded as principal components responsible for the majority of pharmacological activities exerted by ginseng. IH-901 [20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol], an intestinal bacterial metabolite derived from protopanaxadiol-type saponins of Panax ginseng C.A. Meyer, has been reported to possess antitumor effects, including inhibition of invasion, metastasis and angiogenesis and induction of tumor cell apoptosis. Tumor promotion often accompanies an elevated ornithine decarboxylase (ODC) activity, acute inflammation and induction of cyclooxygenase-2 (COX-2) activity. Here we examined the effects of IH-901 on tumor promotion and related molecular events in mouse skin in vivo. Mouse ear edema induced by the prototype tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was repressed by IH-901 pre-treatment in a dose-dependent manner. Topical application of IH-901 onto shaven backs of female ICR mice led to the inhibition of TPA-induced expression of COX-2 and production of prostaglandin E(2). The eukaryotic transcription factor NF-kappaB has been involved in intracellular signaling pathways associated with inflammation and carcinogenesis. IH-901 pre-treatment inhibited TPA-induced epidermal NF-kappaB DNA binding in mouse skin, which appeared to be mediated by blocking phosphorylation and subsequent degradation of IkappaBalpha. In an attempt to elucidate the molecular mechanisms by which IH-901 inactivates NF-kappaB, its effects on activation of upstream signaling kinases were explored. IH-901 also inhibited the activation of ERK1/2 and Akt signaling. When IH-901 was treated topically prior to TPA, expression and activity of ODC were inhibited dose-dependently. In addition, IH-901 given prior to each topical dose of TPA markedly lowered the number of papillomas in mouse skin induced by 7,12-dimethylbenz[a]anthracene. Taken together, these findings suggest that IH-901 exerts anti-inflammatory effects by inhibiting TPA-induced COX-2 expression, which may contribute to its antitumor-promoting effects on mouse skin carcinogenesis.

Topics: Animals; Antineoplastic Agents; Bacteria; Benz(a)Anthracenes; Carcinogens; Cyclooxygenase 2; Dinoprostone; Edema; Extracellular Signal-Regulated MAP Kinases; Female; Ginsenosides; Mice; Mice, Inbred ICR; NF-kappaB-Inducing Kinase; Ornithine Decarboxylase; Papilloma; Prostaglandin-Endoperoxide Synthases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Sapogenins; Skin; Tetradecanoylphorbol Acetate

MeOH extract of Kochia scoparia was fractionated into CHCl3-, EtOAc- and BuOH extracts and the last fraction were hydrolyzed by 3%-NaOH (MeOH-H2O) to compare the bioactivities on antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH fraction afforded a large amount of 3-O-beta-D-xylopyranosyl (1-->3)-beta-D-glucuronopyranosyl oleanolic acid (momordin lc, 4) and that of acid hydrolysate of BuOH fraction gave 3-O-beta-D-glucuronopyranosyl oleanolic acid (momordin lb, 3), its 6'-O-methyl ester (2) and oleanolic acid (1). Silica gel column chromatography of alkaline hydrolysate afforded a large amount of 4. MeOH extract and both EtOAc- and BuOH fractions were active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas CHCl3 fraction was inactive. Compound 1 and 4 showed significant activities in the same assay but oleanolic acid 3-O-glucuronopyranoside (3) showed no activity. These fashions were also observed in carrageenan-induced edema of the rat and in the antinociceptive activity tests undertaken in hot plate- and writhing methods. These results suggest that momordin lc and its aglycone, oleanolic acid, could be active principles for rheumatoid arthritis.

Topics: Acetic Acid; Animals; Arthritis, Experimental; Carrageenan; Chenopodiaceae; Edema; Fruit; Hydrolysis; Male; Mice; Mice, Inbred ICR; Oleanolic Acid; Pain Measurement; Plant Extracts; Rats; Rats, Sprague-Dawley; Sapogenins; Structure-Activity Relationship

Buddlejasaponin I and saikosaponin 1 and 2, biologically active compounds from Scrophularia scorodonia and Bupleurum rigidum respectively, exert potent in vivo antiinflammatory effects on mouse ear edema induced by phorbol myristate acetate (PMA). The effects of these compounds on swelling and other inflammatory parameters are described. In screening for in vitro effects of saikosaponins on cellular systems generating cyclooxygenase (COX) and lipoxygenase (LOX) metabolites, we observed that most saikosaponins showed a significant effect. The action is more marked on LOX metabolite LTC4. Our data support the inhibition of arachidonic acid metabolism as one of the biochemical mechanisms that might be the rationale for the putative antiphlogistic activity of these saikosaponins.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Carbohydrate Sequence; Cell Survival; Cells, Cultured; Dinoprostone; Ear, External; Edema; Female; Humans; Leukotriene C4; Macrophages, Peritoneal; Male; Mice; Molecular Sequence Data; Oleanolic Acid; Plant Extracts; Plants, Medicinal; Sapogenins; Saponins; Tetradecanoylphorbol Acetate

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.

Topics: Animals; Anti-Inflammatory Agents; Carrageenan; Edema; Gastric Mucosa; Inflammation; Italy; Male; Plant Extracts; Plant Leaves; Plants, Medicinal; Rats; Rats, Wistar; Sapogenins; Spirostans; Stomach Ulcer; Water

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.

Topics: Adrenocorticotropic Hormone; Animals; Anti-Inflammatory Agents; Capillary Permeability; Carrageenan; Corticosterone; Cyclic AMP; Edema; Female; Histamine Release; Indomethacin; Male; Oleanolic Acid; Rats; Rats, Inbred Strains; Sapogenins

Topics: Animals; Anti-Inflammatory Agents; Cell Migration Inhibition; Edema; Granuloma; Histamine Release; Oleanolic Acid; Rats; Sapogenins; Saponins

Topics: Animals; Anti-Inflammatory Agents; Arthritis, Experimental; Capillary Permeability; Edema; Female; Granuloma; Oleanolic Acid; Plants; Rats; Sapogenins; Saponins