Traditional Oriental Herbal Medicine Research Articles

Anti-Neuroinflammatory Effects of Arecae pericarpium on LPS-Stimulated BV2 Cells.

Arecae pericarpium (AP), the fruit peel of the betel palm, is a traditional Oriental herbal medicine. AP is used to treat various diseases and conditions, such as ascites, edema, and urinary retention, in traditional Korean medicine. Recent studies have demonstrated its anti-obesity and antibacterial effects; however, its anti-neuroinflammatory effects have not yet been reported. Therefore, we investigated the anti-neuroinflammatory effects of AP on lipopolysaccharide (LPS)-stimulated mouse microglia in this study. To determine the anti-neuroinflammatory effects of AP on BV2 microglial cells, we examined the production of nitric oxide (NO) using Griess assay and assessed the mRNA expression levels of inflammatory mediators, such as inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, and pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, using a real-time reverse transcription-polymerase chain reaction. Furthermore, we determined the levels of mitogen-activated protein kinases and IκBα via Western blotting to understand the regulating mechanisms of AP. AP treatment decreased NO production in LPS-stimulated BV2 cells. Additionally, AP suppressed the expression of iNOS and COX-2 and the production of pro-inflammatory cytokines. AP also inhibited the activation of p38 and nuclear factor-kappa B (NF-κB) in LPS-stimulated BV2 cells. Therefore, AP exerts anti-neuroinflammatory effects via inactivation of the p38 and NF-κB pathways.

Aconitum Alkaloid Songorine Exerts Potent Gamma-Aminobutyric Acid-A Receptor Agonist Action In Vivo and Effectively Decreases Anxiety without Adverse Sedative or Psychomotor Effects in the Rat.

Songorine (SON) is a diterpenoid alkaloid from Aconitum plants. Preparations of Aconitum roots have been employed in traditional oriental herbal medicine, however, their mechanisms of action are still unclear. Since GABA-receptors are possible brain targets of SON, we investigated which subtypes of GABA-receptors contribute to the effects of SON, and how SON affects anxiety-like trait behavior and psychomotor cognitive performance of rats. First, we investigated the effects of microiontophoretically applied SON alone and combined with GABA-receptor agents picrotoxin and saclofen on neuronal firing activity in various brain areas. Next, putative anxiolytic effects of SON (1.0–3.0 mg/kg) were tested against the GABA-receptor positive allosteric modulator reference compound diazepam (1.0–5.0 mg/kg) in the elevated zero maze (EOM). Furthermore, basic cognitive effects were assessed in a rodent version of the psychomotor vigilance task (PVT). Local application of SON predominantly inhibited the firing activity of neurons. This inhibitory effect of SON was successfully blocked by GABA(A)-receptor antagonist picrotoxin but not by GABA(B)-receptor antagonist saclofen. Similar to GABA(A)-receptor positive allosteric modulator diazepam, SON increased the time spent by animals in the open quadrants of the EOM without any signs of adverse psychomotor and cognitive effects observed in the PVT. We showed that, under in vivo conditions, SON acts as a potent GABA(A)-receptor agonist and effectively decreases anxiety without observable side effects. The present findings facilitate the deeper understanding of the mechanism of action and the widespread pharmacological use of diterpene alkaloids in various CNS indications.

Developmental toxicity of Zishen Guchong Pill on the early life stages of Zebrafish

Background: Zishen Guchong Pill (ZGP), a traditional oriental herbal medicine, has been applied broadly in the treatment of threatened or recurrent miscarriages in clinics, but little is known about its developmental toxicity.Aim of the study: This study aimed to investigate the potential toxicity of ZGP and its mechanisms.methods: We investigated the developmental toxicity of ZGP using a zebrafish model. Zebrafish embryos at 4 hours post-fertilization (hpf) were exposed to 25, 50, 100, and 200 µg/mL ZGP until 120 hpf. The zebrafish morphology, organ development, reactive oxygen species (ROS) content, oxidative stress-related enzyme activity, and mRNA levels of oxidative stress and apoptosis-related genes were measured.Results: Our results demonstrated that ZGP had no toxicity at 50 µg/mL ZGP but induced phenotypic defects and decreased the hatching rate and body length at more than 50 µg/mL ZGP (high dose). High doses of ZGP caused severe heart failure, including a significant increase in the sinus venosus (SV) and bulbus arteriosus (BA) distance and pericardial area, and reduced heart rate and numbers of red blood cells. In addition, high doses of ZGP caused liver atrophy and decreased the length of dopamine ganglia and neurovascular. High doses of ZGP elicited the generation of ROS and elevated malondialdehyde levels, but reduced the activity of superoxide dismutase (SOD) and catalase (CAT). Real-time PCR data showed the downregulation of oxidative stress-related genes (sod and cat) and the activation of Nrf2 (nrf2, keap1, ho-1, nqo1, gclc, and gclm) and P53 (p53, bcl-2, and bax) signal pathway genes after high ZGP exposure.Conclusions: Taken together, our results indicate that ZGP has no developmental toxicity under 50 µg/mL ZGP but induced developmental toxicity in zebrafish embryos at more than 50 µg/mL ZGP, and oxidative stress contributed to the toxic response.•ZGP is safe and reliable in clinical use.•ZGP (high does) caused an increase in ROS, which induced oxidative stress, leading to apoptosis and developmental toxicity.•The Nrf2 signaling pathway is impaired during the early stages of ZGP-induced developmental toxicity.

Icariin Attenuates Diabetic Cardiomyopathy and Downregulates Extracellular Matrix Proteins in Heart Tissue of Type 2 Diabetic Rats

Objective: Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM), resulting in unfavorable prognosis. Icariin (ICA) is a major flavonoid isolated from the traditional oriental herbal medicine Epimedium that has been recently proved to show potential therapeutic efficacy on T2DM. The aim of this study was to investigate the underlying mechanism of how ICA improved DCM in rat models. Methods: To corroborate myocardial improvement by ICA, we managed to establish the T2DM rat model by streptozotocin (STZ) administration and high-glucose-high-fat diet. Results: The rats with T2DM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, and fibrosis compared with the control group. All these pathological symptoms were ameliorated by the treatment of ICA. The levels of extracellular matrix proteins of heart tissue significantly declined in ICA-treated rats. Conclusion: ICA may exert as a protector in T2DM-induced DCM by reducing extracellular matrix proteins in the heart tissue, implicating its potential role for the treatment of human DCM.

Icariin treatment reduces blood glucose levels in type 2 diabetic rats and protects pancreatic function.

Icariin, a flavonoid isolated from traditional oriental herbal medicines, has been demonstrated to exhibit several health benefits in animal models and in humans. The aim of the present study was to investigate the effect of Icariin on hyperglycemia in type 2 diabetes mellitus (T2DM) in rats. A model of diabetes was established in 50 Sprague Dawley rats using a high-sugar and high-fat diet and peritoneal injection of streptozotocin. Diabetic rats were divided into five groups: Diabetic control; metformin; and rats treated with three different doses of Icariin, 5, 10 and 20 mg/kg. Body weight and blood glucose levels were measured, and serum adiponectin levels, expression of phospho-AMP mediated protein kinase (p-AMPK) and glucose transporter isoform 4 (GLUT-4) were measured using ELISA, Realtime PCR and western blotting, respectively. Diabetic rats without drug treatment exhibited reduced body weight, increased blood glucose levels and decreased the number of islets. In T2DM rats treated with 10 or 20 mg/kg Icariin, the blood glucose levels were reduced, whereas serum adiponectin levels were not affected. Additionally, the mRNA and protein expression levels of p-AMPK and GLUT-4 protein were increased in the T2DM rats treated with Icariin. In conclusion, in the diabetes rat model, Icariin alleviated the severity of diabetes, and the effects may be associated with reduction of hyperglycemia by activating an AMPK/GLUT-4 pathway.

Positive effects of α-asarone on transplanted neural progenitor cells in a murine model of ischemic stroke

BackgroundSome traditional Oriental herbal medicines, such as Acorus tatarinowii and Acorus gramineus, produce beneficial effects for cognition enhancement. An active compound in rhizomes and the bark of these plants is α-asarone. PurposeThis study investigated the effects of α-asarone on the proliferation and differentiation of neural progenitor cells (NPCs) in a primary culture and a murine model of ischemic stroke. MethodsNPCs were isolated from mouse fetal cerebral cortices on embryonic day 15, and all experiments were performed using passage 3 NPCs. We utilized a cell counting kit-8 assay, flow cytometry, western blot, and immunohistochemical analysis to assess proliferation and differentiation of NPCs and employed α-asarone in NPC transplanted ischemic stroke mice to evaluate stroke-related functional recovery using behavioral and immunohistochemical analysis. ResultTreatment with 1 µM, 3 µM, or 10 μM α-asarone induced significant NPC proliferation compared to vehicle treatment. Induced NPCs expressed the neuronal marker neuronal nuclei (NeuN) or the astrocyte marker S100 calcium-binding protein B (S100β). Both immunohistochemistry and flow cytometry revealed that treatment with α-asarone increased the number of NeuN-immunoreactive cells and decreased the number of S100β-immunoreactive cells. Treatment with α-asarone also increased the expression of β-catenin, cyclin D1, and phosphorylated extracellular signal-regulated kinase (ERK) compared to vehicle treatment. In a murine model of ischemic stroke, treatment with α-asarone and transplanted NPCs alleviated stroke-related functional impairments. The corner and rotarod test results revealed that treatment with α-asarone in the NPC transplanted group had greater-than-additive effects on sensorimotor function and motor balance. Moreover, α-asarone treatment promoted the differentiation of transplanted NPCs into NeuN-, glial fibrillary acidic protein (GFAP)-, platelet-derived growth factor-α (PDGFR-α)-, and 2′, 3′-cyclic nucleotide 3′-phosphodiesterase (CNPase)-immunoreactive cells. Conclusionα-asarone may promote NPC proliferation and differentiation into neuron-lineage cells by activating β-catenin, cyclin D1, and ERK. Moreover, α-asarone treatment facilitated neurofunctional recovery after NPC transplantation in a murine model of ischemic stroke. Therefore, α-asarone is a potential adjunct treatment to NPC therapy for functional restoration after brain injuries such as ischemic stroke.

Anti-ulcer effect of Gallarhois extract with anti-oxidant activity in an ICR model of ethanol/hydrochloride acid-induced gastric injury

Gallarhois (GR) is a traditional oriental herbal medicine with various pharmacological effects; however, its effect on gastric ulcer has not been previously explored. We firstly investigated the component and antioxidant activity of GR extract (EtGR) by HPLC analysis and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results showed that EtGR consisted of gallotannin (68.7%), gallic acid (27.2%) and methyl gallate (4.1%) and that it had a high antioxidant value (IC50 value; 1.93 μg/mL). To evaluate the possible anti-gastric ulcer potential of EtGR, we investigated the effects of EtGR in the model of ethanol/hydrochloric acid (EtOH/HCl)-induced gastric ulcer. Gross and histological gastric lesions, biochemical and gene expression parameters were taken into consideration. The results showed that EtOH/HCl treatment produced mucosal injuries with morphological and histological damage, whereas EtGR co-treatment reduced the gastric injuries. EtGR treatment also decreased the contents of malonaldehyde (MDA) activity relative to the vehicle group. Moreover, EtGR decreased the levels of interleukin-1β (IL-1β), interleukin-6 (IL-6) and cyclo-oxygenase-2 (COX-2) expression. Finally, EtGR did not induce any specific toxicity in the livers or kidneys of the EtOH/HCl-induced gastric ulcer model. These results suggest that EtGR had stronger antioxidant activity and could be a new useful natural drug for gastroprotection against gastric ulcer. Moreover, these findings provide a scientific basis for the development of drugs from traditional oriental herbal medicines.

Daikenchuto (Da-Jian-Zhong-Tang) ameliorates intestinal fibrosis by activating myofibroblast transient receptor potential ankyrin 1 channel.

AIMTo investigate the anti-fibrotic effects of the traditional oriental herbal medicine Daikenchuto (DKT) associated with transient receptor potential ankyrin 1 (TRPA1) channels in intestinal myofibroblasts.METHODSInflammatory and fibrotic changes were detected in a 2,4,6-trinitrobenzenesulfonic acid (TNBS) chronic colitis model of wild-type and TRPA1-knockout (TRPA1-KO) mice via pathological staining and immunoblotting analysis. Ca2+ imaging experiments examined the effects of DKT and its components/ingredients on intestinal myofibroblast (InMyoFib) cell TRPA1 channel function. Pro-fibrotic factors and transforming growth factor (TGF)-β1-associated signaling were tested in an InMyoFib cell line by qPCR and immunoblotting experiments. Samples from non-stenotic and stenotic regions of the intestines of patients with Crohn’s disease (CD) were used for pathological analysis.RESULTSChronic treatment with TNBS caused more severe inflammation and fibrotic changes in TRPA1-KO than in wild-type mice. A one-week enema administration of DKT reduced fibrotic lesions in wild-type but not in TRPA1-KO mice. The active ingredients of DKT, i.e., hydroxy α-sanshool and 6-shogaol, induced Ca2+ influxes in InMyoFib, and this was antagonized by co-treatment with a selective TRPA1 channel blocker, HC-030031. DKT counteracted TGF-β1-induced expression of Type I collagen and α-smooth muscle actin (α-SMA), which were accompanied by a reduction in the phosphorylation of Smad-2 and p38-mitogen-activated protein kinase (p38-MAPK) and the expression of myocardin. Importantly, 24-h incubation with a DKT active component Japanese Pepper increased the mRNA and protein expression levels of TRPA1 in InMyoFibs, which in turn negatively regulated collagen synthesis. In the stenotic regions of the intestines of CD patients, TRPA1 expression was significantly enhanced.CONCLUSIONThe effects of DKT on the expression and activation of the TRPA1 channel could be advantageous for suppressing intestinal fibrosis, and benefit inflammatory bowel disease treatment.

Effect of Sipjeondaebo-Tang on the Pharmacokinetics of S-1, an Anticancer Agent, in Rats Evaluated by Population Pharmacokinetic Modeling.

S-1 (TS-1®) is an oral fluoropyrimidine anticancer agent containing tegafur, oteracil, and gimeracil. Sipjeondaebo-tang (SDT) is a traditional oriental herbal medicine that has potential to alleviate chemotherapy-related adverse effects. The aim of the present study was to evaluate the effect of SDT on the pharmacokinetics of S-1. Sprague-Dawley rats were pretreated with a single dose or repeated doses of SDT for seven consecutive days (1200 mg/kg/day). After the completion of pretreatment with SDT, S-1 was orally administered and plasma concentrations of tegafur, its active metabolite 5-FU, and gimeracil were determined by liquid chromatography-tandem mass spectrometry (LC/MS/MS). A population pharmacokinetic model was developed to evaluate the effect of SDT on pharmacokinetics of tegafur and 5-FU. Although a single dose of SDT did not have any significant effect, the absorption rate of tegafur decreased, and the plasma levels of 5-FU reduced significantly in rats pretreated with SDT for seven days in parallel to the decreased gimeracil concentrations. Population pharmacokinetic modeling also showed the enhanced elimination of 5-FU in the SDT-pretreated group. Repeated doses of SDT may inhibit the absorption of gimeracil, an inhibitor of 5-FU metabolism, resulting in enhanced elimination of 5-FU and decrease its plasma level.

The Effect of Traditional Oriental Herbal Medicine for Anorexia in Cancer Patients: A Systematic Review

Objectives Traditional oriental herbal medicine is used in cancer care to alleviate symptoms. Anorexia is a symptom which is frequently observed in patients with cancer and impairs their quality of life. The objective of this systematic review is to summarize current available evidence to evaluate the effect of traditional oriental herbal medicine on anorexia in cancer patients. Methods The review evaluated randomized controlled trials (RCTs) measuring the effect of any types of herbal medicine on anorexia in cancer patients within 4 electronic databases and manual search up to December 2015. The Cochrane risk of bias tool (ROB) was used to assess the quality of RCTs. Results In total, 11 RCTs met the inclusion criteria. All of the studies reported the rate or severity of anorexia improved after treatment in herbal-conventional medicine combined group compared to conventional medicine group. 7 of 11 studies showed between-group statistical differences. The methodological quality of RCTs was insufficient with unclear and high ROB. Conclusions Traditional oriental herbal medicine may have a potential to improve anorexia in patients with cancer. To confirm the clinical recommendation, further researches with rigorous study design are required to support the effects of herbal medicine. Keywords: Herbal medicine, Anorexia, Neoplasms, Quality of life, Korean medicine

Traditional Oriental Herbal Medicine and Natural Killer Cells for Cancer Patients: A Systematic Review and Meta-analysis.

Traditional oriental herbal medicine (HM) is used by cancer patients to improve immunity. Natural killer (NK) cells are associated with development and progression of tumor and survival of cancer patients. This literature review examined randomized controlled trials (RCTs) in four electronic databases until October 2015 to evaluate the effects of oral HM on NK cells in cancer patients. Data were pooled and computed in a meta-analysis. The methodological quality was assessed according to the Cochrane risk of bias tool. Sixteen RCTs involving 1326 cancer patients were identified. Combination of HM and conventional treatment was associated with significantly higher level of NK cells compared with conventional cancer treatments (standardized mean difference, 1.218; 95% confidence interval 0.719-1.717; p<0.001). Eight RCTs reported statistically significant improvements in the proportions or activity of NK cells in patient groups who received both HM and conventional treatment compared with patients who received conventional treatment alone, while eight RCTs reported no statistically significant differences between the two groups. Studies (n=16) included in this review had insufficient quality of evidence with unclear (n=1) and high (n=15) values of the risk of bias. Although traditional oriental HM may have the positive effects on preserving the level of NK cells in cancer patients receiving conventional treatments, current evidence is inconclusive because of lack of high-quality evidence. Copyright © 2017 John Wiley & Sons, Ltd.

Metabolites of Scutellariae Radix Inhibit Injury of Endothelial Cells in Hypoxia Device

The effects of the metabolites of Scutellariae Radix (SR), a traditional anti-inflammatory oriental herbal medicine, on hypoxia/reoxygenation (H/R)-induced inflammation and apoptosis of human umbilical vein endothelial cells (HUVECs) were investigated. SR metabolites (SRMs) were prepared from the sulfatase/β-glucuronidase-added serum of SR-decoction-fed rats and examined using high-performance liquid chromatography. HUVECs were put into a mechanical device conditioned with hypoxia (94 % N2, 5 % CO2, and 1 % O2) for 4 h (H4), and then reoxygenation (room air with 5 % CO2) for 4 h (R4), alone or in the presence of SRMs or vitamin C. Cell adhesion and apoptosis were detected using the enzyme-linked immunosorbent assay. Intercellular adhesion molecule-1 (ICAM-1), cyclooxygenase-2 (COX-2), caspase-3, and heme oxygenase-1 (HO-1) were evaluated using western blotting. COX-2 small hairpin RNA (shRNA) and HO-1 shRNA were used to evaluate the relationship of COX-2 and HO-1 to cell apoptosis. THP-1 adhesion, and ICAM-1 and COX-2 expression increased at H4 and H4/R4, but decreased at H8, and could be ameliorated by SRMs in a dose-dependent manner. Notedly, SRMs effectively attenuated COX-2-mediated cell apoptosis, which was enhanced by HO-1 shRNA, especially at H4/R4 injury. In conclusion, in a hypoxia chamber that mimics the hypoxic condition in acute coronary syndrome, SRMs protected H/R-induced inflammation and the death of endothelial cells via oxidative stress reduction.

HOX-7 suppresses body weight gain and adipogenesis-related gene expression in high-fat-diet-induced obese mice.

BackgroundHOX-7 is a newly developed dietary formula composed of traditional oriental herbal medicines. The formula was developed with the aim of improving weight control. We investigated the anti-obesity effect of HOX-7 on high-fat-diet (HFD)-induced obesity in C57BL/6 mice.MethodsThe mice were divided into four groups and were fed a normal diet (ND), HFD, or HFD with oral administration of HOX-7 at 100 or 200 mg/kg/day for 12 weeks. Body and fat weight, histological changes of fat tissue, and the expression of key adipogenic transcription factors were investigated.ResultsThe body weight of mice fed the HFD with HOX-7 was significantly decreased compared to the HFD group. There were no obvious differences in weekly food intake among the 4 groups. The weight of the epididymal and total fat pads was reduced in mice fed the HFD with HOX-7. Treatment with HOX-7 also substantially attenuated the expression of key adipogenic transcription factors, including peroxisome proliferatoractivated receptor γ, CCAAT/enhancer binding protein α, sterol regulatory element binding protein 1c, adipocyte P2, liver X receptor, and lipoprotein lipase in the epididymal adipose tissue.ConclusionOverall, this study highlighted the anti-obesity effects of HOX-7, a finding that could contribute to the development of natural anti-obesity herbal medicines.

Review of tumor dormancy therapy using traditional oriental herbal medicine.

Objective:Standard cancer therapy prolongs survival, but can be detrimental to the quality of life, compromise the immune system, and leave residual disease that can cause recurrence years or decades in the future. Tumor dormancy therapy is a novel therapeutic approach that may improve these shortcomings, promote quality of life, and prolong survival. The aim of this study was to analyze studies on dormancy therapy, especially studies using traditional Oriental herbal medicine, so as to evaluate the efficacy of dormancy therapy with traditional oriental herbal medicine.Methods:We conducted a systematic literature review using Scientific and Technical Information Integration Services (NDSL), PubMed, and RISS. We searched for clinical reports, papers, and books related to tumor metastasis, recurrence, immunotherapy, tumor dormancy, and traditional oriental herbal medicine with anticancer effects. Seventy-nine (79) experimental and clinical articles in both Korean and English were reviewed. This study was conducted from March 1, 2012 to May 31, 2012.Results:This approach, Tumor dormancy therapy, rather than seeking to remove the tumor, includes combination of low-dose chemotherapy, immunotherapy, immunosurveillance, and other methods to stabilize tumor growth and to enhance the host is immunity against disseminated tumor cells and thus to manage cancer as a chronic disease while maintaining quality of life. In particular, integrative use of Oriental herbal medicine has been shown to induce or maintain tumor dormancy, increase the effectiveness of conventional chemotherapy, improve quality of life, and prolong survival.Conclusion:Tumor dormancy therapy is a promising novel therapeutic approach that may be especially effective with Oriental herbal medicine. Further research is needed to determine its potential mechanisms and therapeutic applications.

In vitro pharmacological investigations of Biophytum sensitivum callus extract: Lack of potent activities

Objective: Biophytum sensitivum is an important medicinal plant extensively used in traditional oriental herbal medicines. Though medicinal use of this plant is known, the active principles responsible such property is not known. Pharmacological screening of this plant may lead to discovery of new activity with new mode of treatment. Hence, screening for in-vitro pharmacological activities of methanolic callus extracts of Biophytum sensitivum has been carried out. Experiments were designed according to the standard methods and processes. Materials and Methods: Leaf cutting derived callus on MS medium supplemented with BA (Benzyl adenine) 1.0 mg/l + NAA (1-naphthaleneacetic acid) 1.0 mg/l is used as a source, and compounds were extracted from dried callus using methanol solvent with Soxhlet apparatus. Results: The callus extract has shown antioxidant activity, in-vitro inhibition of enzyme activities like α-glycosidase, acetyl cholesterase, and tyrosinase, but potency was found to be low. The Graph pad Prism Version-5 software is used to analyze data in the form of Figures. Conclusion: For the first time, we are reporting in-vitro pharmacological screening of methanolic callus extracts of Biophytum sensitivum .

Hair Growth Activity of Crataegus pinnatifida on C57BL/6 Mouse Model

Crataegus pinnatifida has a long history of use in traditional oriental herbal medicine to stimulating digestion and improving blood circulation. Based on nutrition of hair, the present study was conducted to assess the effect of C. pinnatifida extract on hair growth using mouse model and its mechanisms of action. The C. pinnatifida extract containing the contents of total polyphenol of 5.88□0.82 g gallic acid/100 g extract and proanthocyanidin of 9.15□1.58 mg cyaniding chloride/100 g extract was orally administered daily at a dosage of 50 mg/kg weight to the 7-week-old C57BL/6 mice in telogen. The C. pinnatifida extract promoted hair growth by inducing anagen phase in mice in telogen, reflected by color of skin, thickness of hair shaft, and density of hair. The ratio of anagento telogen was determined by shape of hair follicles in vertically sectioned slide and increased by oral administration of C. pinnatifida extract. The number and the size of hair follicles were also enlarged, indicating anagen phase induction. The proliferation of human dermal papilla cells (hDPC) was accelerated by addition of C. pinnatifida extract, which activated the signaling of mitogen-activated protein kinases (Erk, p-38, and JNK) and Akt. Moreover, the ratio of Bcl-2/Bax as the determinant of cell fate was also raised in skin. These results suggest that the C. pinnatifida extract promotes hair growth by inducing anagen phase, which might be mediated by the activation of cellular signalings that enhance the survival of cultured hDPC and the increase of the ratio of Bcl-2 to Bax that protects cells against cell death.

Traditional Oriental Herbal Medicine for Children and Adolescents with ADHD: A Systematic Review

Objective. To evaluate the efficacy of traditional Oriental herbal medicines (TOHM) for children and adolescents with ADHD. Methods. Randomized clinical trials published from January 1, 1990, to December 31, 2010, in English, Chinese, Japanese, or Korean language which evaluated the use of TOHM on ADHD subjects of 18 years old or below, diagnosed based on DSM-IV, were searched from MEDLINE, EMBASE, PsyINFO, Cochrane Library, and 10 other databases. Results. Twelve studies involving 1189 subjects met the inclusion criteria. In general, the included studies claimed that TOHM has similar efficacy to methylphenidate and at the same time has fewer side effects compared to methylphenidate. Some studies also suggested that the effect of TOHM sustained better than methylphenidate. However, solid conclusions could not be drawn because the included studies were not of high quality. Risk of bias issues such as randomization, allocation, concealment and blinding were not addressed in most of the studies, and the risk of publication bias could not be ruled out. Conclusion. Currently, there is not strong evidence to say that TOHM is effective in treating the core symptoms of ADHD.

Toxicological evaluation of Gumiganghwaltang aqueous extract in Crl:CD (SD) rats: 13 weeks oral gavage studies

Gumiganghwaltang is a traditional oriental herbal medicine that has been commonly used to treat colds and inflammatory diseases. Aqueous extract of Gumiganghwaltang (GMGHT) was administrated daily by oral gavage to male and female rats for 13weeks. A dose of 2000mg/kg/day was selected as a maximum, and doses of 1000 and 500mg/kg/day were determined as medium and low doses, respectively. No treatment-related clinical signs or mortality were observed in the treatment group. We observed no clear treatment-related effects with regard to body weight, food consumption, ophthalmology, hematology, or urinalysis data. The serum biochemistry values for sodium and chloride in the treated male and female groups (1000mg/kg/day) were lower than in those treated with the vehicle control. However, these changes lacked dose dependence, and no abnormalities were found in corresponding pathological findings. Our results indicated that the no-observed-adverse-effect-level (NOAEL) for GMGHT was determined to be a dietary dose of over 2000mg/kg/day for both sexes under the present experimental conditions.

Decursin and decursinol angelate from Angelica gigas Nakai induce apoptosis via induction of TRAIL expression on cervical cancer cells

Aim of the studyThe root of Angelica gigas Nakai (Korean “Dang-Gui”) has been used to treat female afflictions and anemia in traditional oriental herbal medicine since ancient times in Korea. The objective of this study is to identify the anti-cancer mechanism induced by A. gigas extract including decursin and decursinol angelate in human cervical cancer cells for scientific evidence regarding herbal therapy. Materials and methodsThe extract of A. gigas, decursin, and decursinol angelate was used to evaluate the anti-cancer effects on HeLa cells. Cell viability was evaluated by MTT assay and cell cycle regulation was analysed by FACS program. The expression of apoptotic proteins was confirmed by Western blot analysis and proteome profiler array. ResultsThe extract of A. gigas containing decursin and decursinol angelate exhibited anti-cancer effect on HeLa cells through the significant activation of caspases and the cleavage of PARP. Expression of TRAIL and TRAIL receptors was also increased by two active components of A. gigas, respectively. In particular, two components regulated the expression of apoptosis-related proteins such as Bcl-2, Bcl-x, survivin, cIAP-1, -2, XIAP, etc. ConclusionsThese results suggest that TRAIL expression induced by extract of A. gigas stimulates the extrinsic and intrinsic apoptosis pathway by activating caspase-8 and caspase-9, respectively. Thus, extract of A. gigas including decursin and decursinol angelate takes a role in inhibition of cell-proliferation and activation of apoptosis in cervical cancer and could be developed as therapeutic anti-cancer agent against cervical cancer.

Assessment and comparison of immunoregulatory activity of four hydrosoluble fractions of Angelica sinensisin vitro on the peritoneal macrophages in ICR mice

Angelica sinensis (Oliv) Diels, a traditional oriental herbal medicine, is known to have immunostimulatory and antitumor effects. In this paper, four hydrosoluble fractions were obtained and purified from A. sinensis including: Angelica polysaccharide, oligosaccharides (Angelica oligosaccharide and Angelica sucrose) and Angelica total amino acid, named APS, AOS, AS, and TAA, respectively. Moreover, the immunomodulatory activity of these four fractions on murine peritoneal macrophages were assessed and compared from various aspects including cell proliferation, phagocytic activity, nitric oxide (NO) and hydrogen peroxide (H 2O 2) release, induced nitric oxide synthetase (iNOS) and lysozyme (LZM) activity, intracellular adhesion molecule-1 (ICAM-1) expression on cell surface and Toll-like receptor 4 (TLR4) gene expression. Although APS exhibited the most obvious growth facilitative activity, AOS did better in activation of H 2O 2 release; TAA exerted the best activation of phagocytic activity, production of NO and ICAM-1 expression. Furthermore, we found that the action mode of the four fractions was similar to that of LPS and the mechanism may be related to the upregulation of TLR4 mRNA. These results demonstrated that oligosaccharide and amino acid fractions, as well as polysaccharide fraction of Radix A. sinensis, could serve as immunomodulator and TLR4 as one of the immune receptors may play important role for this action.