In-Bae Song

Platycodin D, a triterpenoid sapoinin from Platycodon grandiflorum, ameliorates cisplatin-induced nephrotoxicity in mice

Platycodin D (PD) is well known as a potent triterpenoid saponin having various pharmacological activities isolated from the root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae). We aimed to evaluate protective effect of PD on cisplatin (CDDP)-induced nephrotoxicity. Male ICR mice were allocated into five groups as follows: Negative control, CDDP alone and CDDP with PD (0.1, 1 and 5 mg/kg) treated group. PD was given for three consecutive days before CDDP injection. Increased blood urea nitrogen (BUN) and creatinine (CRE) levels in CDDP alone treated mice were decreased to normal range by pretreatment with PD. It also decreased nitric oxide (NO) and lipid peroxidation with increased antioxidant enzymes such as glutathione (GSH), glutathione peroxidase (GPx) and superoxide dismutase (SOD) in PD pretreated mice. In histopathological examination, pretreatment with PD showed ameliorated renal injury such as intraluminal cast formation and epithelial desquamation. Furthermore, over-expression of nuclear factor-kappa B p65 and apoptotic cells were suppressed by PD pretreatment. Taken together, PD pretreatment might be beneficial to CDDP-induced nephrotoxicity.

Protective Effects of Platycodon grandiflorum AqueousExtract on Thioacetamide-induced Fulminant HepaticFailure in Mice

The aim of the present study was to evaluate the protective activity of aqueous extract from Platycodon grandiflorum (BC703) on thioacetamide (TA)-induced hepatotoxicity in mice. We found that BC703 significantly decreased mortality and the change in serum transaminase following TA administration. The group treated with BC703 at doses of 1, 5, and 10 mg/kg produced significant hepatoprotective effects against TA-induced liver damage by decreasing the activities of serum enzymes, nitric oxide and lipid peroxidation in dose-dependent manners. Histopathological studies further substantiated the protective effect of BC703. These results show the hepatoprotective activity of aqueous extract from Platycodon grandiflorum on thioacetamide-induced fulminant hepatic failure.

Platycodin D attenuates bile duct ligation-induced hepatic injury and fibrosis in mice.

Platycodin D (PD) is the major triterpene saponin in the root of Platycodon grandiflorum. The aim of the present study was to evaluate the protective effects of PD on bile duct ligation (BDL)-induced cholestasis in mice. Mice were allocated to five groups: sham, BDL alone, and BDL with PD treatment at 1, 2, and 4mg/kg. PD was administered to the mice for 28 consecutive days after the BDL operation. PD treatment of BDL-operated mice decreased serum alanine aminotransferase, serum aspartate aminotransferase, and total bilirubin levels by up to 37%, 31%, and 41%, respectively, in comparison with the levels in mice that underwent BDL alone. PD treatment attenuated oxidative stress, as evidenced by an increase in anti-oxidative enzyme levels glutathione and superoxide dismutase together with a decrease in lipid peroxidation and oxidative stress indices levels of malondialdehyde and nitric oxide. Histopathological studies further confirmed the protective effects of PD on cholestasis-induced hepatic injury and liver fibrosis in mice. In addition, nuclear factor-kappa B and inducible nitric oxide synthase levels significantly decreased after PD treatment, as did the levels of hepatocyte apoptosis. Taken together, these results suggest that PD treatment might be beneficial in cholestasis-induced hepatotoxicity.

Plasma disposition of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, in rabbits after oral administration.

The objective of this study was to evaluate the pharmacokinetic profiles of toltrazuril (TZR), and its major metabolites toltrazuril sulfoxide (TZR x SO) and toltrazuril sulfone (TZR x SO(2)) in rabbits after oral administrations. Rabbits were dosed once with 10 and 20mg/kg TZR via stomach tube with manual restraint. The plasma concentrations of TZR, TZR x SO and TZR x SO(2) were determined by liquid chromatography/mass spectrometry. Plasma concentration-time data after single oral administration were analyzed by a non-compartmental analysis. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 30.2+/-1.5microg/mL at 20.0+/-6.9h, 8.9+/-1.3microg/mL at 20.0+/-6.9h and 14.7+/-3.9microg/mL at 96.0+/-0.0h after oral administration of TZR with 10mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 10mg/kg were 52.7+/-3.6, 56.1+/-10.7 and 76.7+/-7.5h, respectively. Plasma peak concentrations of TZR, TZR x SO and TZR x SO(2) were 39.4+/-1.2microg/mL at 28.0+/-6.9h, 12.5+/-3.9microg/mL at 20.0+/-6.9h and 24.9+/-8.74microg/mL at 112.0+/-6.9h after oral administration of TZR with 20mg/kg bw, respectively. The terminal elimination half-lives for TZR, TZR x SO and TZR x SO(2) after oral dose of 20mg/kg were 56.7+/-1.9, 68.8+/-12.5 and 82.3+/-12.6h, respectively. In conclusion, TZR was very well-absorbed through the gastrointestinal tract and rapidly metabolized to TZR x SO and TZR x SO(2) in rabbits after oral administration. TZR x SO(2) was actually more slowly eliminated than TZR and TZR x SO.

Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the β-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhlers method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. β-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.

Protective effect of the aqueous extract from the root of Platycodon grandiflorum on cholestasis-induced hepatic injury in mice

Context: The root of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae) has been widely studied for its hepatoprotective effects against various hepatotoxicants. Objective: The present study evaluated the protective effect of the standardized aqueous extract of P. grandiflorum (BC703) on cholestasis-induced hepatic injury in mice. Materials and methods: BC703 is a standardized aqueous extract of P. grandiflorum in reference to platycodin D (at least 0.8%). The mice were allocated into five groups as follows: Sham-operated, bile duct ligation (BDL) alone, and BDL with BC703 (1, 5, and 10 mg/kg BW) treated group. BC703 was given for 3 consecutive days before BDL operation. The animals were sacrificed by CO2 anesthesia post-24 h of BDL operations. Results and discussion: Serum alanine aminotransferase and serum aspartate aminotransferase increased to 395.2 ± 90.0 and 266.0 ± 45.6 Unit/L in the BDL alone group and decreased with BC703 in a dose-dependent manner. Especially the 10 mg/kg of BC703-treated mice showed a 77% decrease of serum alanine aminotransferase and 56% of aspartate aminotransferase as compared with BDL alone. Decreased antioxidant enzyme levels in BDL alone group were elevated in BC703-treated groups ranging from 7 to 29% for glutathione and from 13 to 25% for superoxide dismutase. BC703 treatment also attenuated malondialdehyde (from 3 to 32%) and nitric oxide levels (from 32 to 50%) as compared with BDL alone. Histopathological studies further confirmed the hepatoprotective effect of BC703 in BDL-induced cholestesis. Conclusion: BC703 could attenuate liver injury by BDL in mice, and test results indicate that BC703 might be useful in cholestatic liver injury.

Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation-induced hepatic fibrosis in rats

The aim of the present study was to evaluate the protective effect of aqueous extract from Platycodon grandiflorum (BC703) on bile duct ligation (BDL)-induced hepatic fibrosis in rats. BDL rats were divided into three groups, which orally received distilled water or BC703 (10 or 50 mg/kg/day) for consecutive 28 days. Antifibrotic effects of BC703 on BDL-induced hepatic fibrosis in rats were estimated by assessing serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), blood urea nitrogen (BUN), transforming growth factor-beta 1 (TGF-β1) and hepatic levels of malondialdehyde (MDA), glutathione (GSH), total superoxide dismutase (SOD) and nitric oxide (NO). The biochemical observations were supplemented by histopathological examination of liver samples stained with hematoxylin and eosin and Masson’s trichrome stain. ALT, AST, TBIL and BUN were elevated in the group treated with BDL alone than in the sham-operated group. These elevations were significantly decreased by BC703 treatment. Hepatic GSH and SOD levels, depressed by BDL, were also increased in the BC703 group. In addition, increases in hepatic MDA and NO levels in the BDL-induced cholestasis were attenuated by BC703 treatment. Furthermore, BC703 treatment significantly reduced the serum level of fibrogenic cytokine, TGF-β1. Histopathological studies further substantiated the protective effect of BC703 on BDL-induced hepatic fibrosis in rat. BC703 may have beneficial effects not only on hepatic fibrosis by cholestasis but also on hepatic fibrosis development in patients with chronic hepatic disease.