Effects of traditional Chinese herbal medicine San-HuangXie-Xin-Tang on gastrointestinal motility in mice

AIM: To investigate the effects of San-Huang-Xie-XinTang(SHXXT), a herbal product used in traditional Chinese medicine, on gastrointestinal(GI) motility in mice.METHODS: The in vivo effects of SHXXT on GI motility were investigated by measuring the intestinal transit rates(ITRs) using Evans blue in normal mice and in mice with experimentally induced GI motility dysfunction(GMD).RESULTS: In normal ICR mice, ITRs were significantly and dose-dependently increased by SHXXT(0.1-1 g/kg). GMD was induced by injecting acetic acid or streptozotocin intraperitoneally. The ITRs of GMD mice were significantly reduced compared to normal mice, and these reductions were significantly and dose-dependently inhibited by SHXXT(0.1-1 g/kg).CONCLUSION: These results suggest that SHXXT is a novel candidate for the development of a prokinetic agent that may prevent or alleviate GMD.

Clinical application of traditional herbal medicine in five countries and regions: Japan;South Korea;China's Mainland;Hong Kong, China;Taiwan, China

Objective:To study the characteristics of the clinical application of traditional herbal medicine in five countries and regions where traditional medicine(TM)is widely used:Japan;South Korea;China's Mainland;Hong Kong,China;Taiwan,China.And to analyze,from multiple angles,the variations in the methods of TM used in each countries and regions.Methods:Fifty commonly used traditional herbs(TOP50)from classical formulae were selected,and descriptive statistics,correlation analyses,and Friedman test were used to compare methods of clinical application and dosages in the countries and regions of interest based on a retrospective review of randomly-selected medical records.Results:There were significant differences in sequencing TOP50 among the five countries and regions(P<.01).The adherence to the classical formulae,from strong to weak was Japan;China's Mainland;Taiwan,China;Hong Kong,China;South Korea.There were also significant differences in TOP50 dosing regimens(P<.01).Overall dosages of TOP50 from high to low were:China's Mainland;Hong Kong,China;Taiwan,China;South Korea;Japan.Finally,there were significant differences in the dosage intervals(P<.01),with dosage intervals from maximum to minimum as follows:China's Mainland;Taiwan,China;Hong Kong,China;South Korea;Japan.Conclusions:The clinical dosages of traditional herbal medicine used in the China's Mainland are relatively large compared with those prescribed in the other four countries and regions,and the range of dosages in China's Mainland is more flexible.On the other hand,clinical dosages of TOP50 are the lowest in Japan,where the dosage range is also the narrowest,supporting the idea that Doctors of Kampo medicine are highly cautious and are likely to adhere strictly to classical formulae,while Hong Kong,China and Taiwan,China are in the middle.The dosage of TOP50 in South Korea is significantly lower than that used in the China's Mainland;Hong Kong,China and Taiwan,China where the adherence to the classical formulae was the lowest,albeit slightly higher than that in Japan.The methods of clinical application of traditional herbal medicine in the five countries and regions were affected by multiple factors,including history,geography,climate,and culture.

Effects of Lizhong Tang on gastrointestinal motility in mice

AIM To investigate the effects of Lizhong Tang,a traditional Chinese medicine formula,on gastrointestinal motility in mice.METHODS The in vivo effects of Lizhong Tang on GI motility were investigated by measuring the intestinal transit rates(ITRs) and gastric emptying(GE) values in normal mice and in mice with experimentally induced GI motility dysfunction(GMD).RESULTS In normal ICR mice,the ITR and GE values were significantly and dose-dependently increased by Lizhong Tang(ITR values: 54.4% ± 1.9% vs 65.2% ± 1.8%,P < 0.01 with 0.1 g/kg Lizhong Tang and 54.4% ± 1.9% vs 83.8% ± 1.9%,P < 0.01 with 1 g/kg Lizhong Tang; GE values: 60.7% ± 1.9% vs 66.8% ± 2.1%,P < 0.05 with 0.1 g/kg Lizhong Tang and 60.7% ± 1.9% vs 72.5% ± 1.7%,P < 0.01 with 1 g/kg Lizhong Tang). The ITRs of the GMD mice were significantly reduced compared with those of the normal mice,which were significantly and dose-dependently reversed by Lizhong Tang. Additionally,in loperamide- and cisplatin-induced models of GE delay,Lizhong Tang administration reversed the GE deficits.CONCLUSION These results suggest that Lizhong Tang may be a novel candidate for development as a prokinetic treatment for the GI tract.

Korean red ginseng promotes hippocampal neurogenesis in mice

Neurogenesis in the adult hippocampus plays a major role in cognitive ability of animals including learning and memory.Korean red ginseng (KRG) has long been known as a medicinal herb with the potential to improve learning and memory;however,the mechanisms are still elusive.Therefore,we evaluated whether KRG can promote cognitive function and enhance neurogenesis in the hippocampus.Eight-week-old male C57BL/6 mice received 50 mg/kg of 5-bromo-2′-deoxyuridine (BrdU) intraperitoneally and 100 mg/kg of KRG or vehicle orally once a day for 14 days.Pole,Rotarod and Morris water maze tests were performed and the brains were collected after the last behavioral test.Changes in the numbers of BrdU- and BrdU/ doublecortin (DCX;a marker for neuronal precursor cells and immature neurons)-positive cells in the dentate gyrus and the gene expression of proliferating cell nuclear antigen (a marker for cell differentiation),cerebral dopamine neurotrophic factor and ciliary neurotrophic factor in the hippocampus were then investigated.KRG-treated mice came down the pole significantly faster and stood on the rotarod longer than vehicle-treated mice.The Morris water maze test showed that KRG administration enhanced the learning and memory abilities significantly.KRG also significantly increased BrdU- and BrdU/DCX-positive cells in the dentate gyrus as well as the proliferating cell nuclear antigen,cerebral dopamine neurotrophic factor and ciliary neurotrophic factor mRNA expression levels in the hippocampus compared to vehicle.Administration of KRG promotes learning and memory abilities,possibly by enhancing hippocampal neurogenesis.This study was approved by the Pusan National University Institutional Animal Care and Use Committee (approval No.PNU-2016-1071) on January 19,2016.

Hwangryunhaedok-tang induces the depolarization of pacemaker potentials through 5-HT3 and 5-HT4 receptors in cultured murine small intestine interstitial cells of Cajal

AIM To investigate the effects of a water extract of Hwangryunhaedok-tang(HHTE) on the pacemaker potentials of mouse interstitial cells of Cajal(ICCs).METHODS We dissociated ICCs from small intestines and cultured. ICCs were immunologically identified using an antic-kit antibody. We used the whole-cell patch-clamp configuration to record the pacemaker potentials generated by cultured ICCs under the current clamp mode(I = 0). All experiments were performed at 30 ℃-32 ℃RESULTS HHTE dose-dependently depolarized ICC pacemaker potentials. Pretreatment with a 5-HT_3 receptor anta-gonist(Y25130) or a 5-HT_4 receptor antagonist(RS39604) blocked HHTE-induced pacemaker potential depolarizations, whereas pretreatment with a 5-HT7 receptor antagonist(SB269970) did not. Intracellular GDPβS inhibited HHTE-induced pacemaker potential depolarization and pretreatment with a Ca^(2+)-free solution or thapsigargin abolished the pacemaker potentials. In the presence of a Ca^(2+)-free solution or thapsigargin, HHTE did not depolarize ICC pacemaker potentials. In addition, HHTE-induced pacemaker potential depolarization was unaffected by a PKC inhibitor(calphostin C) or a Rho kinase inhibitor(Y27632). Of the four ingredients of HHT, Coptidis Rhizoma and Gardeniae Fructus more effectively inhibited pacemaker potential depolarization.CONCLUSION These results suggest that HHTE dose-dependently depolarizes ICC pacemaker potentials through 5-HT_3 and 5-HT_4 receptors via external and internal Ca^(2+) regulation and via G protein-, PKC-and Rho kinase-independent pathways.

Effects of Lizhong Tang on cultured mouse small intestine interstitial cells of Cajal

AIM:To investigate the effects of Lizhong Tang,an herbal product used in traditional Chinese medicine,on mouse small intestine interstitial cells of Cajal(ICCs).METHODS:Enzymatic digestions were used to dissociate ICCs from mouse small intestine tissues.The ICCs were morphologically distinct from other cell types in culture and were identified using phase contrast microscopy after verification with anti c-kit antibody.A whole-cell patch-clamp configuration was used to record potentials(current clamp) from cultured ICCs.All of the experiments were performed at 30-32 ℃.RESULTS:ICCs generated pacemaker potentials,and Lizhong Tang produced membrane depolarization in current-clamp mode.The application of flufenamic acid(a nonselective cation channel blocker) abolished the generation of pacemaker potentials by Lizhong Tang.Pretreatment with thapsigargin(a Ca 2+-ATPase inhibi-tor in the endoplasmic reticulum) also abolished the generation of pacemaker potentials by Lizhong Tang.However,pacemaker potentials were completely abolished in the presence of an external Ca 2+-free solution,and under this condition,Lizhong Tang induced membrane depolarizations.Furthermore,When GDPβ-S(1 mmol/L) was in the pipette solution,Lizhong Tang still induced membrane depolarizations.In addition,membrane depolarizations were not inhibited by chelerythrine or calphostin C,which are protein kinase C inhibitors,but were inhibited by U-73122,an active phospholipase C inhibitors.CONCLUSION:These results suggest that Lizhong Tang might affect gastrointestinal motility by modulating pacemaker activity in interstitial cells of Cajal.

Identification of TRPM7 channels in human intestinal interstitial cells of Cajal

AIM:To investigate the characteristics of slow elec-trical waves and the presence of transient receptor potential melastatin-type 7(TRPM7)in the human gas-trointestinal(GI)tract.METHODS:Conventional microelectrode techniques were used to record intracellular electrical responses from human GI smooth muscle tissue.Immunohisto-chemistry was used to identify TRPM7 channels in in-terstitial cells of Cajal(ICCs).RESULTS:The human GI tract generated slow electri-cal waves and had ICCs which functioned as pacemak-er cells.Flufenamic acid,a nonselective cation channel blocker,and 2-APB(2-aminoethoxydiphenyl borate)and La3+,TRPM7 channel blockers,inhibited the slowwaves.Also,TRPM7 channels were expressed in ICCs in human tissue.CONCLUSION:These results suggest that the human GI tract generates slow waves and that TRPM7 chan-nels expressed in the ICCs may be involved in the gen-eration of the slow waves.

Effects of Hwangryunhaedok-tang on gastrointestinal motility function in mice

AIM To investigate the effects of Hwangryunhaedok-tang(HHT) on gastrointestinal(GI) motility in mice.METHODS The effects of a boiling water extract of HHT(HHTE) on GI motility were investigated by calculating percent intestinal transit rates(ITR%) and gastric emptying(GE) values using Evans Blue and phenol red, respectively, in normal mice and in mice with experimentally induced GI motility dysfunction(GMD). In addition, the effects of the four components of HHT, that is, Gardeniae Fructus(GF), Scutellariae Radix(SR), Coptidis Rhizoma(CR), and Phellodendri Cortex(PC), on GI motility were also investigated.RESULTS In normal ICR mice, ITR% and GE values were significantly and dose-dependently increased by the intragastric administration of HHTE(0.1-1 g/kg). The ITR% values of GMD mice were significantly lower than those of normal mice, and these reductions were significantly and dose-dependently inhibited by HHTE(0.1-1 g/kg). Additionally, GF, CR, and PC dosedependently increased ITR% and GE values in normal and GMD mice.CONCLUSION These results suggest that HHT is a novel candidate for the development of a gastroprokinetic agent for the GI tract.

Effects of electroacupuncture on the functionality of NG2-expressing cells in perilesional brain tissue of mice following ischemic stroke

Neural/glial antigen 2(NG2)-expressing cells has multipotent stem cell activity under cerebral ischemia.Our study examined the effects of electroacupuncture(EA)therapy(2 Hz,1 or 3 mA,20 minutes)at the Sishencong acupoint on motor function after ischemic insult in the brain by investigating the rehabilitative potential of NG2-derived cells in a mouse model of ischemic stroke.EA stimulation alleviated motor deficits caused by ischemic stroke,and 1 mA EA stimulation was more efficacious than 3 mA EA stimulation or positive control treatment with edaravone,a free radical scavenger.The properties of NG2-expressing cells were altered with 1 mA EA stimulation,enhancing their survival in perilesional brain tissue via reduction of tumor necrosis factor alpha expression.EA stimulation robustly activated signaling pathways related to proliferation and survival of NG2-expressing cells and increased the expression of neurotrophic factors such as brain-derived neurotrophic factor,tumor growth factor beta,and neurotrophin 3.In the perilesional striatum,EA stimulation greatly increased the number of NG2-expressing cells double-positive for oligodendrocyte,endothelial cell,and microglia/macrophage markers(CC1,CD31,and CD68).EA therapy also greatly activated brain-derived neurotrophic factor/tropomyosin receptor kinase B and glycogen synthase kinase 3 beta signaling.Our results indicate that EA therapy may prevent functional loss at the perilesional site by enhancing survival and differentiation of NG2-expressing cells via the activation of brain-derived neurotrophic factor-induced signaling,subsequently ameliorating motor dysfunction.The animal experiments were approved by the Animal Ethics Committee of Pusan National University(approval Nos.PNU2019-2199 and PNU2019-2884)on April 8,2019 and June 19,2019.

Analysis of Herbal Medicine Prescriptions for Patients in An Academic Korean Medical Hospital:A Cross Sectional Study of Electronic Medical Records(2010–2013)

Objective： To obtain fundamental information for the standardization of herbal medicine in Korea. Methods： We analyzed the herbal medicine prescription data of patients at the Pusan National University Korean Medicine Hospital from March 2010 to February 2013. We used the Dongui-Bogam （Dong Yi Bao Jian） to classify prescribed herbal medicines. Results： The study revealed that the most frequently prescribed herbal medicine was ‘Liuwei Dihuang Pill （LWDHP, 六味地黄丸）＇ which was used for invigorating ‘Shen （Kidndy）-yin＇. ‘LWDHP＇ was most frequently prescribed to male patients aged 50-59, 60-69, 70-79 and 80-89 years, and ‘Xionggui Tiaoxue Decoction （XGTXD, 芎归调血饮）＇ was most frequently prescribed to female patients aged 30-39 and 40-49 years. According to the International Classification of Diseases （ICD） codes,‘Diseases of the musculoskeletal system and connective tissue＇ showed the highest prevalence. ‘LWDHP＇ and ＇XGTXD＇ was the most frequently prescribed in categories 5 and 3, respectively. Based on the percentage of prescriptions for each sex, ‘Ziyin Jianghuo Decoction （滋阴降火汤）＇ was prescribed to mainly male patients, and ‘XGTXD＇ with ‘Guima Geban Decoction （桂麻各半汤）＇ were prescribed to mainly female patients. Conclusion： This study analysis successfully determined the frequency of a variety of herbal medicines, and many restorative herbal medicines were identified and frequently administered.

Muscovite nanoparticles mitigate neuropathic pain by modulating the inflammatory response and neuroglial activation in the spinal cord

Despite numerous efforts to overcome neuropathic pain,various pharmacological drugs often fail to meet the needs and have many side effects.Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect,but the efficacy of muscovite for neuropathic pain has not been investigated.Here,we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain.The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain,in which one-third to onehalf of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side.Muscovite nanoparticles(4 mg/100μL)was given intramuscularly to evaluate its effects on neuropathic pain(3 days per week for 4 weeks).The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia.In the spinal cord,the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-α,interleiukin-6 and monocyte chemoattractant protein-1,which were upregulated in the partial sciatic nerve ligation model.Moreover,the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3,a neuronal injury marker,in the sciatic nerve.These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines.We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain.All experimental protocols in this study were approved by the Institutional Animal Ethics Committee(IACUC)at Dongguk University,South Korea(approval No.2017-022-1)on September 28,2017.

Randomized Clinical Trials on Eastern-Western Integrative Medicine for Health Care in Korean Literature:A Systematic Review

Objective：To summarize and critically evaluate the evidence for and against the effectiveness of Eastern-Western integrative medicine（EWIM） for health care compared to Eastern medicine（EM） or Western medicine（WM） alone.Methods：Systematic searches were conducted on five Korean medical databases.Manual searches were also conducted through nine major Korean medical journals.Prospective randomized clinical trials （RCTs） were included if EWIM was tested for any type of conditions compared to EM or WM.Results：There were one hundred forty-one possibly relevant studies were identified,and seven RCTs were included.The risk of bias was high in most studies.The EWIM methods were compared with EM or WM in patients with pain conditions in four studies.These studies showed favorable effects of EWIM on pain reduction in patients with shoulder pain and chronic headache compared with EM,while the other RCTs failed to do so in traffic injury patients.Two studies tested EWIM in patients with Bell＇s palsy compared with EM and found acute functional improvement.An RCT comparing EWIM with WM in patients with acne showed a significant difference.Conclusion：The results of our systematic review suggest that there is limited evidence for the superiority of EWIM over EM or WM in the treatment of pain and acute symptom improvement in patients with Bell＇s palsy.The evidence from our analysis was limited from the low number of RCTs included and the high risk of bias.Future RCTs appear to be warranted.

Effects of Banxia Xiexin Decoction (半夏泻心汤) on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells

Objective： To examinie the synergistic effects of Banxia Xiexin Decoction （半夏泻心汤, Known as Banhasasim-tang in Korean） extract （BXDE） on cisplatin-induced cytotoxicity in the A549 human lung cancer ceil lines. Methods： A549 cells were treated with varying concentrations （50-200μg/mL） of cisplatin and BXDE alone or in combination for 96 h. We used 1-（4,5-dimethylthiazol-2-yl）-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. Results： The exposure of cells to cispiatin and BXDE alone or in combination decreased ceil viability dose- and time-dependently （P〈0.05）, which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V^＋/propidium iodide stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyI-Val-Ala-Asp （OMe） fluoromethylketone （z-VAD-FMK）. Conclusions： BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

Scalp Acupuncture for Parkinson's Disease:A Systematic Review of Randomized Controlled Trials

Objective： To evaluate the effectiveness of scalp acupuncture （SA）, a modern acupuncture technique specialized to neurological disorders, in managing motor function and symptoms for Parkinson＇s disease （PD） patients. Methods： Two independent reviewers extracted data from all of the randomized clinical trials （RCTs） that assessed the efficacy of SA for PD compared with conventional therapies （CTs）. Sixteen electronic databases were searched. The risk of bias was appraised with the Cochrane Collaboration tool, and the reporting of the included studies was evaluated by the Consolidated Standards of Reporting Trials （CONSORT） 2010 checklist and the revised Standards for Reporting Interventions in Clinical Trials of Acupuncture （STRICTA） guidelines. Results： In total, 4 RCTs met the inclusion criteria. As assessed by the Unified PD Rating Scale （UPDRS）, 2 RCTs showed that SA combined with CTs proved superior to CTs alone [60 cases; weighted mean difference, -3.94; 95% confidence interval （CI）, -6.05 to -1.64, P=0.01; 12=0%]. Based on the Webster scale, however, 3 RCTs showed no superior effect of SA when combined with CTs with high heterogeneity （154 cases; risk ratio, 1.29; 95% CI, 0.79 to 2.12, P=0.30; 12=84%）. The Cochrane risk of bias, adherence to the CONSORT and the STRICTA checklist showed that the quality of all the included RCTs was generally low. Conclusions： The result of our systematic review and meta-analysis suggested that the effectiveness of SA for PD is promising, however, the evidence is not convincing. A sham-controlled RCT design that adheres to the CONSORT and STRICTA guidelines to overcome methodological weakness and that includes a large sample size is strongly recommended to confirm the precise effect of SA on PD.

The effect of acupuncture on mood and working memory in patients with depression and schizophrenia

BACKGROUND： In patients with depression, as well as in patients with schizophrenia, both mood and working memory performance are often impaired. Both issues can only be addressed and improved with medication to some extent. OBJECTIVE： This study investigates the mood and the working memory performance in patients with depression or schizophrenia and whether acupuncture can improve these. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS： A pragmatic clinical trial design was used The study was conducted in a psychiatric clinic. Fifty patients with depression and 50 with schizophrenia were randomly divided into an experimental and a waiting-list group. Additionally, 25 healthy control participants were included. Twelve weeks of individualized acupuncture treatment was used as the clinical intervention. MAIN OUTCOME MEASURES： All patients were tested before （T1） and after （T2） acupuncture treatment on a mood scale （Beck Depression Inventory-II, BDI-II）, a simple working memory task （digit span）, and a complex working memory task （letter-number sequencing）; the healthy controls were tested at T1 only. RESULTS： Patients with depression scored worse than the others on the BDI-II, and patients with schizophrenia scored worse than the healthy controls. On the digit span, patients with schizophrenia did not differ from healthy controls whereas they scored worse of all on the letter-number sequencing. With respect to the acupuncture findings, first, the present study showed that the use of acupuncture to treat patients with schizophrenia was both practical and safe. Moreover, acupuncture had a positive effect on the BDI-II for the depression group, but acupuncture had no effect on the digit span and on the letter- number sequencing performance for the two clinical groups. CONCLUSION： The clinical improvement in patients with depression after acupuncture treatment was not accompanied by any significant change in a simple working memory task or in a more complex working memory task; the same was true for the patients with schizophrenia.

Red Ginseng for Type 2 Diabetes Mellitus:A Systematic Review of Randomized Controlled Trials

Objective： Red ginseng （RG, Panax ginseng C.A. Meyer） is one of the widely used herbs for treating type 2 diabetes mellitus （DM）. However, no systematic review of the effectiveness of RG for type 2 DM is available. This systematic review aimed to evaluate the current evidence for the effectiveness of RG in patients with type 2 DM. Methods＂ Electronic searches of 14 electronic databases were conducted without language restrictions. All randomized clinical trials （RCTs） with RG as a treatment for type 2 DM were considered for inclusion. Their methodological quality was assessed using the Cochrane criteria. Results： Four RCTs met our inclusion criteria. Their methodological quality was variable. Three of the RCTs compared the effectiveness of RG with placebo. The meta-analysis of these data failed to favor RG over placebo for fasting plasma glucose （FPG） [n=76, weighted mean difference （WMD）： -0.43 mmol/L; 95% confidence interval （CI）： -1.16 to 0.30, P=0.25] and fasting plasma insulin （FPI） （n=76, WMD： -8.43 pmol/L; 95% Ch -19.54 to 2.68, P=0.14） for 12 weeks of treatment. One RCT compared the effects of RG with no treatment. The results did not suggest favorable effects of RG on FPG, hemoglobin Alo （HbAlc） or 2-h blood glucose after a meal （PP2h）. Conclusions： The evidence for the effectiveness of RG in controlling glucose in type 2 DM is not convincing. Few included studies with various treatment regimens prohibit definitive conclusions. More rigorous studies are needed to clarify the effects of RG on this condition.

Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells

Objective:Mitophagy is known to contribute towards progression of Parkinson’s disease.Korean red ginseng(KRG)is a widely used medicinal herb in East Asia,and recent studies have reported that KRG prevents 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced cell death.This study was undertaken to investigate whether KRG suppresses MPP^(+)-induced apoptosis and mitophagy.Methods:SH-SY5 Y cells were incubated with KRG for 24 h,and subsequently exposed to MPP^(+).The MPP^(+)-induced cell death was confirmed with the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay,and the terminal deoxynucleotidyl transferase-mediated d UTP nick end-labeling assay.Changes in the structure and function of mitochondria were confirmed using mitotracker,Mito SOX red mitochondrial superoxide indicator,parkin,and phosphatase and tensin homolog deleted on chromosome ten-induced putative kinase 1(PINK1)immunofluorescent staining.Western blotting was performed to evaluate the expression of apoptosis-related factors in whole cells,including Bax,Bcl-2 and cleaved caspase-3,and mitophagy-related factors in the mitochondrial fraction,including cytochrome c,parkin,PINK1,translocase of the outer membrane 20(TOM20),p62 and Beclin 1.Results:MPP^(+)induced cell death by cytochrome c release and caspase-3 activation;however,this effect was suppressed by KRG’s regulation of the expressions of Bcl-2 and Bax.Moreover,MPP^(+)exposure increased the mitochondrial expressions of parkin,PINK1,Beclin 1 and p62,and decreased TOM20,cytochrome c and Bcl-2 expressions.These MPP^(+)-induced changes in the mitochondrial fraction were attenuated by treatment with KRG.Conclusion:KRG effectively prevents MPP^(+)-induced SH-SY5 Y cell death by regulating cytochrome c release from mitochondria and PINK1/parkin-mediated mitophagy,through regulation of the Bcl-2 family.

Extracts from Paeonia lactiflora Pallas, Rehmannia Glutinosa var. Purpurea Makino, Perilla Frutescens var. Acuta Kudo may increase the endometrial receptivity through expression of leukemia inhibitory factor and adhesion molecules

OBJECTIVE: To find out the combination of the extracts from Paeonia lactiflora Pallas(PL), Rehmannia Glutinosa var. Purpurea Makino(RG), Perilla Frutescens var. Acuta Kudo(PF) to increase endometrial receptivity.METHODS: Herbal medicines were extracted with boiling water and polysaccharides were removed.We examined the effect of PL, RG, and PF(PRP), a most effective herbal formula deduced from constitutive ingredient herbs of Antai Yin which is composed of PRP, on the leukemia inhibitory factor(LIF) expression and endometrial receptivity.RESULTS: The combination of the extracts from PRP induced the LIF expression in Ishikawa cells and increased the adhesion between Ishikawa and JAr cells. In addition, PRP-induced attachment of JAr cells onto Ishikawa cells and expression of adhesion molecules, ITGAV, ITGB5, CD44 s, and Lselectin, are significantly reduced by knock-down of LIF expression.CONCLUSION: Induced by the combination of the PRP extracts, the adhesion between trophoblast and endometrial cells are mediated by expression of LIF and adhesion molecules. Thus, we suggest the combination of the PRP extracts may be a novel therapy for enhancing embryo implantation rate.

Combating Drug Resistance in Colorectal Cancer Using Herbal Medicines

Colorectal cancer(CRC)is one of the most prevalent and lethal cancer types around the world.Most of the CRC patients are treated with chemotherapeutic drugs alone or combined.However,up to 90%of metastatic cancer patients experience the failure of treatment mostly because of the acquired drug resistance,which can be led to multidrug resistance(MDR).In this study,we reviewed the recent literature which studied potential CRC MDR reversal agents among herbal medicines(HMs).Among abundant HMs,6 single herbs,Andrographis paniculata,Salvia miltiorrhiza,Hedyotis diffusa,Sophora flavescens,Curcuma longa,Bufo gargarizans,and 2 formulae,Pien Tze Huang and Zhi Zhen Fang,were found to overcome CRC MDR by two or more different mechanisms,which could be a promising candidate in the development of new drugs for adjuvant CRC chemotherapy.

Anti-inflammatory Effects of Sanguisorbae Radix on Contact Dermatitis Induced by Dinitrofluorobenzene in Mice

Objective:To investigate the anti-inflammatory effects of Sanguisorbae Radix on contact dermatitis(CD).Methods:Mice were sensitized by painting 30μL of 1-fluoro-2,4-dinitrofluorobenzene(DNFB)onto each ear for 3 days.Four days later,mice were challenged by painting with 50μL of DNFB onto the shaved dorsum every 2 days.Sanguisorbae Radix methanol extract(MESR)was applied onto the shaved dorsum every 2 days.The effects of MESR on skin thickness,skin weights,histopathological changes,skin lesions and cytokine production in DNFB-induced CD mice were investigated,as well as its effects on body weights and spleen/body weight ratio.Results:Topical application of MESR effectively inhibited enlargement of skin thickness and weight(P<0.05).MESR treatment also inhibited hyperplasia,spongiosis and immune cell infiltration induced by DNFB in inflamed tissues and improved lesions on dorsum skin in CD mice.Moreover,treatment with MESR suppressed the increase in the levels of tumor necrosis factor α(TNF-α,P<0.01)and interferonγ(IFN-γ,P<0.05),respectively.Finally,MESR had no effect on body weight gain or spleen/body weight ratio.Conclusion:These data suggest that MESR acts as an anti-inflammatory agent that decreases the production of TNF-α and IFN-γ,resulting in reductions of skin lesions and histopathological changes in inflamed skin tissues.