Platycodin D-induced apoptosis through nuclear factor-kappaB activation in immortalized keratinocytes.

Platycodi Radix is the root of Platycodon grandiflorum and it is widely used in the traditional Oriental medicine as an expectorant for pulmonary diseases and a remedy for respiratory disorders. Platycodin D is the major constituent of triterpene saponins in the root. This study investigates apoptosis by platycodin D in immortalized human keratinocytes (HaCaT). Platycodin D-induced apoptosis in HaCaT cells was confirmed by DNA fragmentation, caspase-3 activation, and caspase-8 activation. Platycodin D could activate inhibitor of nuclear factor-kappaB kinase (IKK)-beta in the nuclear factor-kappaB (NF-kappaB) activation of upstream level, but not IKK-alpha. Pretreated-N-tosyl-l-phenylalanine chloromethyl ketone (TPCK), a potent NF-kappaB inhibitor, could suppress the induction of apoptosis and activation of NF-kappaB of HaCaT cells by platycodin D. We also demonstrated that platycodin D-mediated apoptosis of HaCaT cells upregulates Fas receptor and Fas ligand (FasL) expression, but did not exhibit p53 activation. HaCaT cells were also transfected with pFLF1, which preserves the promoter region of Fas receptor gene containing NF-kappaB binding site. On incubation with platycodin D, the NF-kappaB activity related to Fas receptor increased in a dose-dependent manner. Among the major transcription elements on Fas receptor and FasL promoter, NF-kappaB activation was shown to have an essential role in the expression of the death receptor such as FasL. These results suggest that platycodin D has the ability to induce apoptosis in HaCaT cells through the upregulation of Fas receptor and FasL expression via to NF-kappaB activation in the transcriptional level. These results demonstrate that the NF-kappaB activation plays a crucial role in the induction of apoptosis in human HaCaT cells on treatment with platycodin D.

Araloside A, an antiulcer constituent from the root bark of Aralia elata.

Araloside A, a potent inhibitor of gastric lesion and ulcer formation in rats, was isolated from the root bark of Aralia elata through a bioassay-guided separation procedure. The compound exhibited significant reduction of HCl.ethanol-induced gastric lesions and aspirin-induced gastric ulcers at oral doses of 50 and 100 mg/kg, respectively. These activities are comparable to those of cimetidine.

Therapeutic effect of DA-9601 on chronic reflux gastritis induced by sodium taurocholate in rats.

AIM: To investigate the therapeutic effects of DA-9601 on sodium taurocholate (TCA)-induced chronic reflux gastritis in SD rats. METHODS: In this study, we have investigated the therapeutic effects of DA-9601 on chronic erosive and atrophic gastritis induced by 6 mo of TCA administration (5 mmol/L in drinking water) in SD rats. RESULTS: Four weeks of DA-9601 administration (0.065%, 0.216% in rat chow), following the withdrawal of TCA treatment, resulted in a significant decrease in total length of erosions in rats in a dose-dependent manner. Furthermore, the indicators of atrophic gastritis, such as reduced mucosal thickness and reduction in the number of parietal cells, were improved by the administration of DA-9601 in a dose-related manner. DA-9601 also attenuated inflammatory cell infiltration and the proliferation of collagenous fiber in the gastric mucosa. The improvement in the reduction of the gastric mucus was observed in the rats receiving a high dose of DA-9601 (0.216%). The therapeutic effect of DA-9601 on experimental chronic erosive gastritis was superior to that of rebamipide (1.08% in rat chow). Biochemical analyses showed increased mucosal prostaglandin E2 and reduced glutathione levels by DA-9601 treatment. CONCLUSION: We suggest that DA-9601 is a promising agent for the treatment of chronic erosive and atrophic gastritis with an etiological factor of bile reflux. Increased mucosal prostaglandin E2 and reduced glutathione by DA-9601 treatment may be therapeutic mechanisms for chronic erosive and atrophic gastritis.

Comparison of green tea extract and epigallocatechin gallate on blood pressure and contractile responses of vascular smooth muscle of rats.

The present study was conducted to investigate the effects of green tea extract (GTE) on arteral blood pressure and contractile responses of isolated aortic strips of the normotensive rats and to establish the mechanism of action. The phenylephrine (10(-8) approximately 10(-5) M)-induced contractile responses were greatly inhibited in the presence of GTE (0.3 approximately 1.2 mg/mL) in a dose-dependent fashion. Also, high potassium (3.5 x 10(-2) approximately 5.6 x 10(-2) M)-induced contractile responses were depressed in the presence of 0.6 approximately 1.2 mg/mL of GTE, but not affected in low concentration of GTE (0.3 mg/mL). However, epigallocatechin gallate (EGCG, 4 approximately 12 microg/mL) did not affect the contractile responses evoked by phenylephrine and high K+. GTE (5 approximately 20 mg/kg) given into a femoral vein of the normotensive rat produced a dose-dependent depressor response, which is transient. Interestingly, the infusion of a moderate dose of GTE (10 mg/kg/30 min) made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study demonstrate that intravenous GTE causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of adrenergic alpha1-receptors. GTE also causes the relaxation in the isolated aortic strips of the rat via the blockade of adrenergic alpha1-receptors, in addition to the unknown direct mechanism. It seems that there is a big difference in the vascular effect between GTE and EGCG.

Antiinflammatory activity of alpha-hederin methyl ester from the alkaline hydrolysate of the butanol fraction of Kalopanax pictus bark extract.

Three antiinflammatory saponin components were isolated from the alkaline hydrolysate of a butanol-soluble portion of Kalopanax pictus bark extract through an in vivo activity-guided fractionation procedure. The hydrolysate showed inhibition of adjuvant induced arthritis in rats. After further fractionation, the ethyl acetate fraction exhibited antiarthritic activity, which resulted in the isolation of alpha-hederin, alpha-hederin methyl ester, and kalopanaxsaponin I. All compounds showed inhibition of vascular permeability in mice, but only alpha-hederin methyl ester showed anticarrageenan activity in rats and antiarthritic activity in rats and mice.

Effects of Opuntia ficus-indica var. Saboten stem on gastric damages in rats.

The effects of the dried stem powder of Opuntia ficus-indica var. saboten (OF-s) were investigated on gastric lesion and ulcer models in rats. It showed significant inhibition in HCl ethanol-induced gastric lesion at the doses of 200 and 600 mg/kg p.o. and in HCl.aspirin-induced gastric lesion at 600 mg/kg p.o. OF-s also showed significant inhibition in indomethacin-induced gastric lesion at the doses of 200 and 600 mg/kg, p.o. However, it did not affect both the aspirin-induced and Shay ulcers in rats. It also did not affect gastric juice secretion, acid output and pH. These data indicate that OF-s only possesses pronounced inhibitory action on gastric lesion without antiulcer activity in rats.

Platycodin D and D3 increase airway mucin release in vivo and in vitro in rats and hamsters.

The root of Platycodon grandiflorum has been widely used for the treatment of various chronic inflammatory diseases including airway disease in oriental medicine. The root extract of the plant has been known to be effective in the expectoration of sputum or mucus, thereby improving airway respiratory function and preventing secondary airway inflammation. In this study, we investigated the effect of platycodin D and D3, the saponin components that are anti-inflammatory components in Platycodon grandiflorum. Platycodin D and D3 increased mucin release from rat and hamster tracheal surface epithelial cell culture and also from intact rat trachea upon nebulization. The effect of platycodin D3 was stronger than that of ATP, a potent mucin secretagogue and also of ambroxole, a mucolytic drug. The results from the present study suggest that platycodin D and D3 are useful as expectorant agents in the treatment of various airway diseases.