ginsenoside-m1 and Edema

The present study aimed to evaluate the anti-inflammatory and analgesic activities of the ginsenoside metabolite compound K (CK) and its mechanisms.. Mice model of xylene-induced ear swelling and rat model of carrageenan-induced paw swelling were used to evaluate the effect of CK on acute inflammation. The analgesic effect of CK was evaluated on heat-, acetic acid-, and carrageenan-induced hyperalgesia. The levels of prostaglandin E2 (PGE2), cyclooxygenase-1 (COX-1), and COX-2 in carrageenan-induced rat paw swelling and gastric mucosa were detected by enzyme-linked immunosorbent assay (ELISA). COX-1 and COX-2 expressions in carrageenan-induced rat paw swelling and gastric mucosa were detected by western blotting. In vitro effect of CK (10. CK at doses of 7, 14, 28, 56, 112, and 224 mg/kg alleviated xylene-induced ear oedema, whereas CK at 40, 80, and 160 mg/kg alleviated carrageenan-induced paw oedema. CK at 224 mg/kg showed an analgesic effect against acetic acid-induced pain. CK at 40, 80, and 160 mg/kg significantly increased rat inflammatory pain threshold, but had no effect on heat-induced pain threshold. CK at 10, 20, 40, 80, and 160 mg/kg reduced PGE2 level in the paw tissue, but showed no effect on that in the gastric mucosa. CK at 20, 40, 80, and 160 mg/kg decreased COX-2 expression in the paw tissue and gastric mucosa, but exhibited no effect on COX-1 expression or on COX-1 and COX-2 activities.. CK exerted anti-inflammatory and analgesic effects, possibly by reducing the catalytic synthesis of PGE2 via downregulation of COX-2 expression.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Down-Regulation; Edema; Female; Ginsenosides; Hyperalgesia; Inflammation; Male; Mice; Pain; Pain Threshold; Rats; Rats, Sprague-Dawley

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