• The Korea Journal of Herbology
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• v.25 no.3
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• pp.43-51
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• 2010

Objectives : We investigated the repeated-dose toxicity of Wenpitang-Hab-Wulingsan(WHW), a Korean traditional medicine prescribed with twelve herbs, which has been used for the treatment of renal disease. Methods : WHW extract prepared by GLP company. WHW was supplemented by gavage at 0, 100, 500 and 1000 mg/kg/day for 13-week consecutive days. We recorded the clinical signs of toxicity, body weight, organ weights, hematology, gross and histological changes in target organs rats and clinical chemistry analysis for all rats. Results : WHW extract at all doses was shown no mortality or abnormal clinical signs in rats during at the observation period. Furthermore, there was no difference in body weight and food-take consumption, organ weight, gross pathological findings, and urine analysis among the groups of rats treated with different doses of WHW extract. The hematological analysis and clinical blood chemistry data were revealed no toxic effects from WHW-treated rats. Conclusions : The results suggest that WHW extract in rats is a wide margin of safety on a acute toxicity.

• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.161-166
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• 2009

This study is to specify the criteria and testing methods of WHW extract which has a potency as a therapeutic agent for chronic renal failure. The determination of specifications of WHW extract is mostly important because of the quality assurance. Three batches of WHW extract were obtained by the extraction at $98^{\circ}$C for 3 hr using water from mixture of 15 herbal medicines including Codonopsis Pilosulae Radix, Salviae Radix, Pinelliae Rhizoma, Coptidis Rhizoma, Evodiae Fructus, Epimedii Herba, Rhei Rhizoma, Perillae Herba, Glycyrrhizae Radix, Artemixiae capillaris Herba, Alimatis Rhizoma, Hoelen, Atractylodies Rhizoma alba, Polyporus and Cinnamomi Ramulus, subsequently, vaccum-dried for 15 hr. The yield of WHW extracts was 24.53% on the average. The identification of each herbal medicine of WHW extract was performed by modification of Korean Pharmacopeia IX (KP IX). The assay of WHW extract was performed using standard such as berberine, icariin, glycyrrhizin, and cinnamic acid of indicative herbal medicines by modification of KP IX, too. As well as, paticle size classification test was carried out to indicate the boundary of particle size of WHW extract and the particle size of WHW extract more than 50% showed the 140 ${\mu}$m. Taken together, WHW extract could be prepared reproducibly and assurable if follows the presented extraction and drying steps and its specifications were satisfied with the indicated criteria.

• The Korea Journal of Herbology
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• v.27 no.4
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• pp.45-51
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• 2012

Objectives : WHW is a polyherbal medicine for the treatment of chronic renal failure (CRF). WHW previously reported various biological property such as anti-inflammation, anti-oxidation and anti-renal fibrosis in CRF. This study aimed to investigate the anti-apoptotic effect of WHW on staurosporin(SSP)-induced apoptosis in canine kidney epithelial cells (MDCK). Methods : MDCK cells were treated with different concentrations of WHW (0.1, 0.2, 0.5 and $1mg/m{\ell}$) for 1 h, and then induced apoptosis by treatment of SSP ($1{\mu}M$) for 24 h. Cell viability was measured by WST-1 assay. The expression of apoptotic proteins such as caspase-3, Bax and Bcl-2 was determined by Western blot. Caspase-3 activity and ROS levels were also measured by their commercial available assay kits. Cell apoptosis was observed by Hoechst and DNA fragmentation. Results : WHW significantly increased the cell viability on SSP-treated MDCK cells. WHW inhibited SSP-induced expression of apoptotic proteins such as caspase-3 and Bax, and significantly decreased caspase-3 activity in MDCK cells. WHW significantly decreased SSP-induced production of ROS, and suppressed SSP-induced chromatin condensation and DNA fragmentation in MDCK cells. Conclusions : These results suggest that WHW has an anti-apoptotic effect in renal cells through suppressing the expression of apoptotic proteins, ROS production and DNA damages.

• The Korea Journal of Herbology
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• v.23 no.3
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• pp.85-91
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• 2008

Objectives : This study aimed to evaluate the anti-diabetic effect of Wen-Pi-Tang-Hab-Wu-Ling-San (WHW) extract in streptozotocin(STZ)-induced type-1 diabetic rats. Methods : Experimental diabetes were induced by intraperitoneal injection of streptozotocin (60 mg/kg). Two groups of STZ-induced diabetic rats were given the following treatments for 2 weeks by oral Administrations : (1) WHW 10 mg/kg, (2) WHW 100 mg/kg. In addition, vehicle-treated diabetic and nondiabetic controls were used in the experiment. The effects of WHW extract on STZ-induced diabetes were observed by measuring the changes of body weights and the levels of fasting blood glucose, insulin, urea nitrogen (BUN) and creatinine level in sera of rats, respectively. Results : In comparison control group, WHW-treated groups (100 mg/kg) were significantly decreased fasting blood glucose levels and increased serum insulin levels in STZ-induced diabetic rats. Moreover, WHW-treated groups (100 mg/kg) were reduced s-creatinie levels in STZ-induced diabetic rats. In addition, the changes related to diabetic nephropathy with body weight were significantly lower in WHW extract-dosing groups than in the diabetic control. Conclusions : The study thus showed that WHW extract enhanced the anti-diabetic effect in STZ-induced diabetic rats by improving the hypoglycemia. It also increased pancreatic insulin content in these rats.

• The Journal of Korean Medicine
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• v.30 no.5
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• pp.146-156
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• 2009

Objectives: The objective of this study was to investigate the antioxidant effects of manufactured Wen-pi-tang-Hab-Wu-ling-san (WHW$^{(R)}$) in vitro. Methods: WHW$^{(R)}$ was prepared by the pilot manufacture of WHW water extract from a GMP system appointed company. Antioxidative activities were determined by in vitro tests as follows: the scavenging activities of oxygen free radicals including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, superoxide anion, hydrogen peroxide and nitric oxide radicals, as well as ferrous ion chelating capacity and Trolox equivalent antioxidant capacity (TEAC). Results: WHW$^{(R)}$ significantly scavenged oxygen free radicals such as DPPH (IC$_{50}$=115.28 $\pm$ 0.25 $\mu$g/$m\ell$), superoxide anion (IC$_{50}$=8.56 $\pm$ 0.08 $\mu$g/$m\ell$), hydrogen peroxide (IC$_{50}$=240.36 $\pm$ 3.41 $\mu$g/$m\ell$) and nitric oxide (IC$_{50}$=162.28 $\pm$ 0.21 $\mu$g/$m\ell$) radicals. WHW$^{(R)}$ also showed ferrous ion chelating activity (IC$_{50}$=543.19 $\pm$ 4.85 $\mu$g/$m\ell$) and Trolox equivalent effects (IC$_{50}$=45.311 $\mu$g/$m\ell$) in TEAC and ORAC assay, respectively. Conclusion: This study demonstrates that WHW$^{(R)}$ has strong antioxidative properties through free radical scavenging activity. These data suggest that WHW$^{(R)}$ be used as an antioxidant agent.

• Journal of Pharmaceutical Investigation
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• v.39 no.4
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• pp.257-261
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• 2009

Effective therapeutics for renal failures have not yet been developed until now. Recently, there was a report showing that Wen-pi-tang-Hab-Wu-ling-san (WHW) prescriptions had the potential to prevent renal failures through the increased expression of HSP-27 and HSP-72 after ischemia/reperfusion. Therefore, formulation studies by pH-specific released systems were carried out to exhibit the optimal activity of WHW prescriptions in this study. WHW prescriptions were separately extracted using water into two parts of stomach-released (SR) and intestine-released (IR) extracts. Subsequently, the double-layered tablet was prepared using the SR extracts and pharmaceutical additives and enteric-coated IR tablet. Dissolution studies were carried out to figure out the release of cinnamic acid and icarrin from SR tablet, IR tablet and double-layered tablet, respectively. The complete release of cinnamic acid from SR tablet showed 90min after dissolution in pH 1.2 and insignificant drug released from IR tablet. As well as, icarrin from IR tablet completely released in pH 6.8 and 7.4 as enteric-coating film dissolved.