Mee Young Lee

Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats

BackgroundYukmijihwang-tang, a traditional herbal formula, has been used for treating disorder, diabetic mellitus and neurosis in China (Liu-wei-di-huang-tang in Chinese), Japan (Lokumijio-to in Japanese) and Korea for many years. In this study, we investigated the effects of Yukmijihwang-tang water extract (YJT) on the development of benign prostatic hyperplasia (BPH) using a rat model of testosterone propionate (TP)-induced BPH.MethodsA total of 30 rats were divided into five groups. One group was used as a control and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. YJT (200 or 400 mg/kg) was administered daily for 4 weeks to two groups by oral gavage concurrently with the TP. The animals were euthanized, the prostate and body weights were recorded, and tissues were subjected to hormone assays and histomorphology. In addition, we investigated proliferating cell nuclear antigen (PCNA) expression in the prostate using immunoblotting.ResultsAnimals with BPH showed significantly increased absolute and relative prostate weights, increased dihydrotestosterone levels in the serum or prostate and increased PCNA expression in the prostate; however, YJT-treated animals showed significant reductions compared with the animals with TP-induced BPH. Histomorphology also showed that YJT inhibited TP-induced prostatic hyperplasia.ConclusionsThese findings indicate that YJT effectively inhibited the development of BPH and might be a useful drug clinically.

An Extract of Crataegus pinnatifida Fruit Attenuates Airway Inflammation by Modulation of Matrix Metalloproteinase-9 in Ovalbumin Induced Asthma

Background Crataegus pinnatifida (Chinese hawthorn) has long been used as a herbal medicine in Asia and Europe. It has been used for the treatment of various cardiovascular diseases such as myocardial weakness, tachycardia, hypertension and arteriosclerosis. In this study, we investigated the anti-inflammatory effects of Crataegus pinnatifida ethanolic extracts (CPEE) on Th2-type cytokines, eosinophil infiltration, expression of matrix metalloproteinase (MMP)-9, and other factors, using an ovalbumin (OVA)-induced murine asthma model. Methods/Principal Finding Airways of OVA-sensitized mice exposed to OVA challenge developed eosinophilia, mucus hypersecretion and increased cytokine levels. CPEE was applied 1 h prior to OVA challenge. Mice were administered CPEE orally at doses of 100 and 200 mg/kg once daily on days 18–23. Bronchoalveolar lavage fluid (BALF) was collected 48 h after the final OVA challenge. Levels of interleukin (IL)-4 and IL-5 in BALF were measured using enzyme-linked immunosorbent (ELISA) assays. Lung tissue sections 4 µm in thickness were stained with Mayer’s hematoxylin and eosin for assessment of cell infiltration and mucus production with PAS staining, in conjunction with ELISA, and Western blot analyses for the expression of MMP-9, intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 protein expression. CPEE significantly decreased the Th2 cytokines including IL-4 and IL-5 levels, reduced the number of inflammatory cells in BALF and airway hyperresponsiveness, suppressed the infiltration of eosinophil-rich inflammatory cells and mucus hypersecretion and reduced the expression of ICAM-1, VCAM-1 and MMP-9 and the activity of MMP-9 in lung tissue of OVA-challenged mice. Conclusions These results showed that CPEE can protect against allergic airway inflammation and can act as an MMP-9 modulator to induce a reduction in ICAM-1 and VCAM-1 expression. In conclusion, we strongly suggest the feasibility of CPEE as a therapeutic drug for allergic asthma.

A water extract of Samchulkunbi-tang attenuates airway inflammation by inhibiting inos and MMP-9 activities in an ovalbumin-induced murine asthma model

BackgroundIn this study, we investigated the effect of Samchulkunbi-tang water extract (SCTE) in an established mouse model of ovalbumin (OVA)-induced allergic asthma. The effects of SCTE on the production of Th1 and Th2 cytokines, eotaxin, and total and OVA-specific immunoglobulin E, inducible nitric oxide synthase expression, and matrix metalloproteinase-9 activity were measured.MethodsMice were sensitized on days 0 and 14 with an intraperitoneal injection of 20 μg ovalbumin (OVA) emulsified in 2 mg aluminum hydroxide in 200 μL PBS buffer. On days 21, 22, and 23, mice received an airway exposure to OVA (1%, w/v, in PBS) for 1 h. SCTE was administered orally to mice at doses of 200 and 400 mg/kg per day from days 18 to 23.ResultsSCTE reduced the number of inflammatory cells, cytokines, and chemokines in bronchoalveolar lavage fluids and iNOS expression and MMP-9 activity in mouse lung tissue. Histological studies using hematoxylin & eosin and periodic acid-schiff staining showed that SCTE substantially inhibited OVA-induced inflammatory cell infiltration in lung tissue and goblet cell hyperplasia in the airway. SCTE also reduced IL-4 and IL-13 expression in concanavalin-A-stimulated splenocytes. These results were similar to those obtained with montelukast as a positive control.ConclusionsCollectively, these results suggest that SCTE may be an effective oral treatment for allergic airway inflammation by virtue of its anti-inflammatory activity.

Genotoxicity assessment of Pyungwi-san (PWS), a traditional herbal prescription.

ETHNOPHARMACOLOGICAL RELEVANCE Pyungwi-san (PWS, Heii-san in Japanese) is a mixture of six herbs and is traditionally used in Northeast Asia (especially Korea and Japan) for the treatment of gastrointestinal disorder, such as dyspepsia and inappetance induced by gastric dilatation and gastrointestinal catarrh. AIM OF THE STUDY Although PWS is a widely used herbal prescription in Korea and Japan, little information is available in the literature on the safety and toxicity of PWS. As part of a safety evaluation of PWS, the present study evaluated the potential genotoxicity of PWS using a standard battery of test. MATERIALS AND METHODS We prepared PWS using a water extraction method and simultaneously extracted three compounds from PWS using high performance liquid chromatography. The PWS extract that was obtained was assayed for genotoxicity using the standard three tests recommended by the Korea Food and Drug Administration. These tests included the bacterial reverse mutation test (Ames test), the chromosomal aberration test using China hamster lung cells, and the micronucleus test using ICR mice. RESULTS The Ames test showed that the PWS extract did not induce an increase in the number of revertant colonies compared with vehicle control at any dose in all of tester strains. In the micronucleus test, no significant increase was observed in micronucleated polychromatic erythrocytes (MNPCEs) at any dose of PWS extract compared with vehicle control. Conversely, chromosomal aberration test showed that the PWS extract at a dosage of 4500 μg/mL induced an increase in the number of chromosomal aberrations in the 6 h group with metabolic activation compared with the vehicle control. CONCLUSION PWS extract exhibits genotoxicity, based on the results of the chromosomal aberration test. Thus, further detailed experiments will be needed to identify the ingredient responsible for inducing this genotoxicity and to determine its mechanism.

Subacute toxicity and stability of Soshiho-tang, a traditional herbal formula, in Sprague–Dawley rats

BackgroudSoshiho-tang (SST, Xiao-chai-hu-tang in Chinese and Sho-saiko-to in Japanese), an oriental herbal formula, is used for treatment of chronic liver diseases. Although many researchers have studied the pharmacological properties of SST, information about its safety and toxicity is limited. Therefore, we evaluated the potential safety of SST in Sprague–Dawley rats over a period of 4-weeks.MethodsThe SST was administered once daily by gavage to male and female rats at doses of 0, 500, 1000 and 2000 mg/kg/day for 4 weeks. We measured the body weight, mortality, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights and histopathology. In addition, we analyzed the component of SST and measured the stability of its component in SST according to study periods using high performance liquid chromatography.ResultsThe SST treatment did not result in any toxicologically significant changes in mortality, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights and histopathology, except for salivation and reduction in body weight in the 2000 mg/kg/day male group. These findings in the 2000 mg/kg/day male group are considered toxicologically insignificant because they are not accompanied by other pathological findings, including in hematology, serum biochemistry and histopatholgy, and they do not exhibit a dose–response relationship. SST is detected three components including liquiritin, baicalin, and glycyrrhizin. In addition, there were not observed the significant differences among the contents of three components in SST according to storage periods.ConclusionThese results indicate that SST may be a safe material. Based on these results, the no-observed-adverse-effect level was more than 2000 mg/kg for both genders.

Effects of montelukast on subepithelial/peribronchial fibrosis in a murine model of ovalbumin induced chronic asthma.

Montelukast, a leukotriene receptor antagonist, is used commercially as a maintenance treatment for asthma and to relieve allergic symptoms. In this study, we evaluated the protective effects of montelukast against the airway inflammation and fibrosis using a murine model of ovalbumin (OVA) induced chronic asthma. The animals received OVA challenge three times a week for 4 weeks. Montelukast (30 mg/kg) was administrated orally once a day for 4 weeks. The administration of montelukast caused a reduction in elevated interleukin (IL)-4, IL-13, eotaxin, immunoglobulin (Ig), inflammatory cell infiltration into the airways, and mucus production after repeated OVA challenges. To investigate the antifibrotic mechanism of montelukast, we examined the expression of profibrotic mediators, including vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, and Smad3 proteins in the lung tissue using western blotting and immunohistochemistry. The administration of montelukast reduced the overexpression of profibrotic proteins in the lung tissue, which was confirmed by immnunohistochemistry. These results are consistent with a histopathological examination of lung tissue with Massons trichrome stain. In conclusion, the administration of montelukast reduced airway inflammation and pulmonary fibrosis by reducing the release of Th2 cytokines and the expression of VEGF, TGF-β1/Smad3 in the lung tissue.

Ojeok-san, a traditional Korean herbal medicine attenuates airway inflammation and pulmonary fibrosis induced by repeated ovalbumin challenge

ETHNOPHARMACOLOGICAL EVIDENCE Ojeok-san, a traditional Korean herbal medicine, is widely used in China, Japan and Korea for treatment of the common cold, pain and fever. AIM OF THE STUDY In this study, we investigated the protective effects of Ojeok-san aqueous extract (OJS) against pulmonary fibrosis using a chronic asthma murine model. METHODS Mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed 1 weeks later by an airway challenge with OVA delivered three times a week for 4 weeks. OJS (50mg/kg or 100mg/kg) was also administered by oral gavage once a day for 4 weeks. RESULTS OJS significantly reduced interleukin (IL)-4, IL-13, eotaxin, immunoglobulin E and the number of inflammatory cells in bronchoalveolar lavage fluid; in addition, it reduced inflammatory cell infiltration and mucus production in the respiratory tract. We found that OJS also attenuated the OVA-induced increase in vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1 and Smad3 protein in lung tissue, as determined by Western analysis and immunohistochemistry. These inhibitory effects of OJS were accompanied by a reduction in pulmonary fibrosis, consistent with the histopathology of lung tissue stained with Massons trichrome. CONCLUSION Administration of OJS reduced the airway inflammation and pulmonary fibrosis, as well as the level of T helper type 2 cytokines and VEGF and TGF-β1/Smad3 expressions in lung tissue. These results suggest that OJS might represent a useful new oral therapy for the treatment of chronic asthma.

Safety assessment of So-cheong-ryong-tang: subchronic toxicity study in Crl:CD Sprague Dawley rats.

So-cheong-ryong-tang, an oriental herbal formula, is used in Korea for treating pulmonary disorders, including asthma, bronchitis and allergic diseases. The objective of the present study was to investigate the potential adverse effects, if any, of subchronic administration of So-cheong-ryong-tang aqueous extract (SCRT) in male and female rats. In the present study, 0, 1,000, 2,000 and 5,000 mg/kg/day of SCRT was administered to Crl:CD Sprague Dawley rats (10/gender/group) for 13 weeks via oral gavage. Administration of the SCRT did not result in any mortality. There were no clinical or ophthalmological signs, changes in urinalysis, body weight, food consumption, gross findings, hematology, serum biochemistry, organ weight or histopathology attributable to the administration of SCRT. Any alterations noted were incidental and consistent with those historically observed in the age and strain of rats used in the present study. Based on the results of the present study, the no observed adverse effect level for SCRT under the present experimental conditions was determined to be 5,000 mg/kg/day, the highest dose assessed, for both genders.

Jaeumganghwa-tang, a traditional herbal formula inhibits the development of benign prostatic hyperplasia in rats

Benign prostate hyperplasia (BPH) is the most common proliferative disorder affecting older men and results in prostate enlargement and lowered urinary tract symptoms. Jaeumganghwa-tang (JGT), an oriental traditional herbal formula, has been used in China (Zi-yin-jiang-huo-tang in Chinese), Japan (Jiin-koka-to in Japanese), and Korea for many years. Effects of JGT on prostate dihydrotestosterone (DHT) level and prostatic hyperplasia were investigated using a rat model, in which BPH was induced using testosterone propionate (TP). Rats were divided into five groups. One group was used as a normal, and four groups received subcutaneous injections of TP for 4 weeks to induce BPH. JGT (200 or 400 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with TP injections, and rats were sacrificed at scheduled times. Prostates were weighed, and histopathologic examination was conducted. DHT levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) protein was investigated using Western blotting. BPH animals showed increases in absolute and relative weights of the prostate, levels of DHT in serum and the prostate, and expression of PCNA in the prostate, whereas JGTtreated animals showed significant reductions in these indices compared with the BPH animals. Administration of JGT attenuated TP-induced epithelial hyperplasia. These findings indicate that JGT inhibits the development of BPH, an effect closely associated with a reduction in DHT level.

α-Spinasterol from Melandrium firmum attenuates benign prostatic hyperplasia in a rat model.

Spinasterol, a biologically active compound, exhibits a number of pharmacological activities, including antitumor, antiulcerogenic and anticarcinogenic activity, and originates from the aerial parts of Aster scaber Thunb (Asteraceae). The present study investigated whether α-spinasterol isolated from Melandrium firmum Rohrbach could prevent benign prostatic hyperplasia (BPH) induced by testosterone propionate (TP) in rats. Male Wistar rats were randomly divided into four groups of eight rats following castration. A negative control group received subcutaneous injections of corn oil. Treatments were administered orally 1 h prior to TP injection. All the rats were sacrificed at the scheduled termination time and their prostates were removed, cleaned and weighed. The prostate size ratio (prostate weight/rat body weight) was then calculated. Additional histopathological examinations were conducted, and the levels of TP and dihydrotestosterone (DHT) in the serum and prostate were measured. TP significantly increased the prostate size ratio (P<0.01), and DHT and testosterone levels in the serum and prostate. The TP-induced increase was significantly inhibited in α-spinasterol-treated rats when compared with the negative controls (P<0.05). In addition, histopathological examination demonstrated that α-spinasterol treatment suppressed TP-induced prostatic hyperplasia. It is concluded that α-spinasterol can prevent TP-induced prostatic hyperplasia and may be beneficial in the management of BPH.