Frankincense ameliorates endometriosis via inducing apoptosis and reducing adhesion.

Background: Frankincense, a resin derived from trees of the Boswellia genus, has been used as an incense and a type of herbal medicine for treating inflammatory diseases such arthritis, chronic bowel illness, and asthma. While endometriosis is a well-known inflammatory gynecological illness caused by the ectopic attachment and development of uterine tissue over the menstrual cycle, the impact of frankincense on this illness is poorly understood. The purpose of this study was to explore the effects of frankincense on endometriosis. Methods: We used a network pharmacological assessment, in vitro and in vivo investigations with a human endometriotic cell line as well as a syngeneic uterine transfer mouse model. High-performance liquid chromatographic analysis was used to compare water-extracted frankincense (Fr) to its reference compounds and validate the sample. Results: A network pharmacological analysis suggested a positive effect of Fr on endometriosis. Fr relieved endometriosis by reducing ectopic endometrial adherence and development, according to both in vivo and in vitro models. We suggested that the ER stress/p53-apoptosis and chemokine-migration/adhesion pathways underlie Fr's anti-endometriotic action using RNA sequencing and bioinformatic analysis. Conclusion: This study revealed the potential effect of Fr on endometriosis using an experimental investigation. Fr may have the potential to be an effective and safe treatment for endometriosis.

Water-Extracted Prunella vulgaris Alleviates Endometriosis by Reducing Aerobic Glycolysis.

Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. Prunella vulgaris is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of P. vulgaris is well-established. Therefore, in this work, we evaluated water-extracted P. vulgaris (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an in vitro study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.

Topical Application of Galgeunhwanggeumhwangryeon-Tang Recovers Skin-Lipid Barrier and Ameliorates Inflammation via Filaggrin-Thymic Stromal Lymphopoietin-Interleukin 4 Pathway.

Background and objectives: The purpose of this study was to confirm the effect of Galgeunhwanggeumhwangryeon-tang (GGRT) on the skin barrier integrity and inflammation in an atopic dermatitis-like animal model. Materials and Methods: The model was established using lipid barrier elimination (LBE) in BALB/c mice. Ceramide 3B, a control drug, and GGRT were applied to the skin of LBE mice. Gross observation and histological examination were combined with measurement of skin score, trans-epidermal water loss, and pH. The expression of filaggrin, kallikrein-related peptidase 7 (KLK7), protease-activated receptor-2 (PAR-2), thymic stromal lymphopoietin (TSLP), and interleukin 4 (IL-4) was examined. Results: The effect of GGRT on atopic dermatitis was estimated in silico using two individual gene sets of human atopic dermatitis. In animal experiments, GGRT treatment reduced atopic dermatitis-like symptoms, as confirmed via gross and histological observations, skin score, pH change, and trans-epidermal water loss. The expression level of filaggrin increased in the skin of GGRT-treated mice compared to that in the LBE group. The expression levels of KLK7, PAR2, TSLP, and IL-4 were decreased in GGRT-treated mice skin compared to those in LBE mice. Conclusions: We demonstrated that GGRT restored the skin barrier and reduced inflammatory reactions in a murine model of atopic dermatitis.

Targeting Lactate Dehydrogenase A with Catechin Resensitizes SNU620/5FU Gastric Cancer Cells to 5-Fluorouracil.

Resistance to anticancer therapeutics occurs in virtually every type of cancer and becomes a major difficulty in cancer treatment. Although 5-fluorouracil (5FU) is the first-line choice of anticancer therapy for gastric cancer, its effectiveness is limited owing to drug resistance. Recently, altered cancer metabolism, including the Warburg effect, a preference for glycolysis rather than oxidative phosphorylation for energy production, has been accepted as a pivotal mechanism regulating resistance to chemotherapy. Thus, we investigated the detailed mechanism and possible usefulness of antiglycolytic agents in ameliorating 5FU resistance using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cell harboring resistance to 5FU, showed much higher lactate production and expression of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA), than those of the parent SNU620 cells. To limit glycolysis, we examined catechin and its derivatives, which are known anti-inflammatory and anticancer natural products because epigallocatechin gallate has been previously reported as a suppressor of LDHA expression. Catechin, the simplest compound among them, had the highest inhibitory effect on lactate production and LDHA activity. In addition, the combination of 5FU and catechin showed additional cytotoxicity and induced reactive oxygen species (ROS)-mediated apoptosis in SNU620/5FU cells. Thus, based on these results, we suggest catechin as a candidate for the development of a novel adjuvant drug that reduces chemoresistance to 5FU by restricting LDHA.

The Oral Administration of Sanguisorba officinalis Extract Improves Physical Performance through LDHA Modulation.

Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.

Toxic Animal-Based Medicinal Materials Can Be Effective in Treating Endometriosis: A Scoping Review.

Animal toxins and venoms have recently been developed as cancer treatments possessing tumor cell growth-inhibitory, antiangiogenesis, and proapoptotic effects. Endometriosis is a common benign gynecological disorder in reproductive-age women, and no definite treatment for this disorder is without severe side effects. As endometriosis and malignant tumors share similar characteristics (progressive, invasive, estrogen-dependent growth, and recurrence), animal toxins and venoms are thought to be effective against endometriosis. The objective of this study was to outline studies using toxic animal-based medicinal materials (TMM) as endometriosis treatment and to explore its clinical applicability. Preclinical and clinical studies using TMM were searched for in four databases from inception to October 2020. A total of 20 studies of TMM on endometriosis were included. In eight clinical studies, herbal medicines containing TMM were effective in relieving symptoms of endometriosis, with no side effects. In twelve experimental studies, the main therapeutic mechanisms of TMM against endometriosis were proapoptotic, antiangiogenesis, estrogen level-reducing, and possible anti-inflammatory effects. TMM are thus considered promising sources for the development of an effective treatment method for endometriosis. Further studies are needed to clarify the therapeutic mechanism of TMM against endometriosis and to provide sufficient grounds for clinical application.

Herbal formulation MIT ameliorates high-fat diet-induced non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases and is caused by obesity, diabetes, high blood pressure, and insulin resistance. Many studies have explored novel candidates to treat NAFLD using herbal medicines owing to their fewer side effects. In this study, we examined the effect of MIT, an herbal formula comprising Ephedra sinica, Panax ginseng, and Alisma orientale, on the murine model of NAFLD. METHODS: To evaluate the effect of MIT on NAFLD, we used the high-fat diet (HFD)-induced NAFLD mice model. The mice were divided into four groups: control, HFD, HFD with metformin administration, and HFD with MIT administration. Freeze-dried MIT was dissolved in phosphate buffered saline and orally administered for 8 weeks to MIT-treated mice (60 mg/kg) after feeding them with HFD for 16 weeks. RESULTS: MIT treatment significantly attenuated fat accumulation, serum glucose levels, and excessive cholesterol. It also reduced the activation of NF-κB, JNK, ERK, mammalian target of rapamycin, and peroxisome proliferator-activated receptor γ in the HFD-induced NAFLD mice. The expression level of enzymes involved in the synthesis and oxidation of fatty acids, acetyl-coA carboxylase and CYP2E1, were clearly reduced by MIT treatment. Reactive oxygen species (ROS) production and subsequent liver damage were effectively reduced by MIT treatment. CONCLUSION: We suggest that MIT is a potent herbal formula that can be used for the prevention and treatment of obesity-related NAFLD via regulating the levels of serum glucose and free fatty acids, inflammation, lipid accumulation, and ROS-mediated liver damage.

Electroacupuncture Therapy Ameliorates Motor Dysfunction via Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is characterized by dopaminergic neuron loss in the substantia nigra. However, specific sensory stimulation via electroacupuncture (EA) therapy may attenuate this loss by promoting the expression of endogenous neurotrophic factors in a manner similar to physical therapy. We investigated the potential protective effects of EA on dopaminergic neurons in a mouse model of PD and whether these effects are associated with the promotion of endogenous brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Mouse models of PD were generated using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine. Motor performance was assessed using behavioral tests, and Western blot experiments, enzyme-linked immunosorbent assays (ELISAs), and immunohistochemical assays were performed. In both mouse models, EA treatment ameliorated motor impairments and dopaminergic neuron loss; these changes were accompanied by increases in BDNF and GDNF. In the MPTP group, EA treatment improved motor dysfunction by attenuating dopaminergic neuron loss in the substantia nigra, similar to the effects of levodopa. EA treatment significantly upregulated BDNF and GDNF expression in both the substantia nigra and striatum. Moreover, EA treatment induced the expression of cAMP response element binding protein (CREB) as well as Akt and Pitx3 in dopaminergic neurons in the substantia nigra. However, levodopa treatment did not induce BDNF/GDNF activation or related signaling factors. Thus, EA therapy may exert protective effects on dopaminergic neurons by upregulating the expression of BDNF, GDNF, and related signaling factors, thereby improving motor function. Hence, EA may represent an effective adjuvant therapy for motor deficits in patients with PD.

Enhancement of Endometrial Receptivity by Cnidium officinale through Expressing LIF and Integrins.

Improvement of endometrial receptivity is necessary for successful embryo implantation, and its impairment is associated with female infertility. In this study, we investigated the effect of the roots of Cnidium officinale Makino (CoM) on endometrial receptivity in both in vitro and in vivo model of embryo implantation. We found that CoM enhanced the adhesion of JAr cells to Ishikawa cells by stimulating expression of leukemia inhibitory factor (LIF) and integrins. In addition, blocking of LIFR using hLA or neutralization of integrins αV, ß3, and ß5 using antibodies significantly reduced the enhanced adhesion between JAr cell and CoM-treated Ishikawa cells, indicating that LIF and integrin play an important role in trophoblast-endometrium adhesion for embryo implantation. Furthermore, we identified that CoM significantly improved the implantation rate of blastocysts in the mouse model of RU-induced implantation failure. By collecting these results, here, we suggest that CoM has a therapeutic potential against female infertility associated with decreased endometrial receptivity.

Weisheng-Tang Ameliorates Acute Ischemic Brain Damage in Mice by Maintaining Blood-Brain Barrier Integrity.

Stroke is one of the major causes of death and long-term disability worldwide; the associated breakdown of the blood-brain barrier (BBB) aggravates ischemic brain damage. Accordingly, many medicinal herbs and formulas have been used to treat stroke-related symptoms. In this study, we selected two Korean herbal medicine formulas, Weisheng-tang and Tongxuewan, through Dongeuibogam text-mining analysis, and evaluated their protective effect on BBB disruption and brain damage in stroke. Ischemic brain damage was induced in mice by photothrombotic cortical ischemia. The infarct volume, brain edema, neurological deficits, and motor function 24 h after ischemic injury were analyzed. We investigated BBB breakdown by measuring Evans blue extravasation in addition to endothelial cells, tight junction proteins, protease-activated receptor-1 (PAR-1), and matrix metalloproteinase-9 (MMP-9) using immunofluorescence staining and confocal microscopy. Pretreatment with Weisheng-tang significantly reduced infarct volume and edema and improved neurological and motor functions; however, Tongxuewan did not. In addition, Weisheng-tang decreased brain infarction and edema and recovered neurological and motor deficit in a dose-dependent manner (30, 100, and 300 mg/kg). Weisheng-tang pretreatment resulted in significantly less BBB damage and higher brain microvasculature after focal cerebral ischemia. Tight junction proteins, such as zonula occludens-1 (ZO-1) and claudin-5, were preserved in Weisheng-tang-pretreated mice. Moreover, the ischemic brain in these mice showed suppressed PAR-1 and MMP-9 expression. In conclusion, our findings show that Weisheng-tang, which was selected through literature analysis but has not previously been used as a stroke remedy, exerts protective effects against ischemic brain damage and suggest its possible application for potential stroke patients, especially in the elderly.

Esculentoside B inhibits inflammatory response through JNK and downstream NF-κB signaling pathway in LPS-triggered murine macrophage RAW 264.7 cells.

Natural compound esculentoside B (EsB), (2S,4aR,6aR,6aS,6bR,8aR,9R,10R,11S,12aR,14bS)-11-hydroxy-9-(hydroxymethyl)-2 methoxycarbonyl-2,6a,6b,9,12a-pentamethyl-10-[(2S,3R,4S,5R)-3,4,5-trihydroxyoxan-2-yl]oxy-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid with molecular weight of 664.833, isolated from roots of Phytolacca acinosa Roxb has been widely used as a constituent of traditional Chinese medicine (TCM). However, the anti-inflammatory capacity of EsB has not been reported yet. Therefore, the objective of this study was to investigate anti-inflammatory activities of EsB in LPS-treated macrophage RAW 264.7 cells. EsB could inhibit nitric oxide (NO) production. EsB also suppressed gene and protein expression levels of inducible isoform of NO synthase (NOS) and cyclooxygenase-2 in a dose-dependent manner. In addition, EsB decreased gene expression and protein secretion levels of pro-inflammatory cytokines such as IL-1ß, TNF-α, and IL-6. EsB remarkably suppressed nuclear translocation of nuclear factor kappa-B (NF-κB) from cytosolic space. Phosphorylation of IκB was also inhibited by EsB. Moreover, EsB specifically down-regulated phospho-c-Jun N-terminal kinase (p-JNK), but not p-p38 or phospho-extracellular signal-regulated kinase 1/2 (p-ERK1/2). Taken together, these results suggest that EsB has inhibitory effect on inflammatory response by inactivating NF-κB and p-JNK. It could be used as a new modulatory drug for effective treatment of inflammation-related diseases.

Isolinderalactone regulates the BCL-2/caspase-3/PARP pathway and suppresses tumor growth in a human glioblastoma multiforme xenograft mouse model.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor, which remains incurable. Plant extracts are a potential source of potent anticancer medicines. In this study, we investigated the effect of isolinderalactone from Lindera aggregata on tumor growth using U-87 human glioblastoma cells. Treatment with isolinderalactone inhibited cell viability and promoted apoptotic cell death. In addition, intraperitoneal injection of isolinderalactone significantly inhibited tumor growth in a human GBM xenograft mouse model. To identify the proteins involved in the induction of apoptosis in isolinderalactone-treated cells, we performed a human apoptosis proteome array analysis and western blotting. Isolinderalactone suppressed the expression of B-cell lymphoma 2 (BCL-2), as well as of survivin and X-linked inhibitor of apoptosis protein (XIAP), known as apoptosis inhibitors, and increased the level of cleaved caspase-3. In addition, isolinderalactone treatment increased cleaved poly(ADP-ribose) polymerase (PARP) and DNA damage. In xenograft tumor tissues, we observed high immunofluorescence of cleaved caspase-3 and TUNEL in isolinderalactone-treated group. Taken together, isolinderalactone enhances U-87 GBM cell apoptosis in vitro and in vivo and retards tumor growth, suggesting that isolinderalactone may be a potential candidate for anti-glioblastoma drug development.

Therapeutic Potential of a Combination of Electroacupuncture and TrkB-Expressing Mesenchymal Stem Cells for Ischemic Stroke.

We prepared and grafted tropomyosin receptor kinase B (TrkB) gene-transfected mesenchymal stem cells (TrkB-MSCs) into the ischemic penumbra and investigated whether electroacupuncture (EA) treatment could promote functional recovery from ischemic stroke. For the behavioral test, TrkB-MSCs+EA resulted in significantly improved motor function compared to that obtained with MSCs+EA or TrkB-MSCs alone. At 30 days after middle cerebral artery occlusion (MCAO), the largest number of grafted MSCs was detected in the TrkB-MSC+EA group. Some differentiation into immature neuroblasts and astrocytes was detected; however, only a few mature neuron-like cells were found. Compared to other treatments, TrkB-MSCs+EA upregulated the expression of mature brain-derived neurotrophic factor (BDNF) and neurotrophin-4/5 (NT4) and induced the activation of TrkB receptor and its transcription factor cAMP response element-binding protein (CREB). At 60 days after MCAO, EA highly promoted the differentiation of TrkB-MSCs into mature neuron-like cells compared to the effect in MSCs. A selective TrkB antagonist, ANA-12, reverted the effect of TrkB-MSCs+EA in motor function recovery and survival of grafted MSCs. Our results suggest that EA combined with grafted TrkB-MSCs promotes the expression of BDNF and NT4, induces the differentiation of TrkB-MSCs, and improves motor function. TrkB-MSCs could serve as effective therapeutic agents for ischemic stroke if used in combination with BDNF/NT4-inducing therapeutic approaches.

Water-extracted branch of Cinnamomum cassia promotes lung cancer cell apoptosis by inhibiting pyruvate dehydrogenase kinase activity.

Cinnamomum cassia Blume has been widely reported as the anti-tumor agent. However, the precise mechanism underlying its pro-apoptotic action is still not clear. Restraining aerobic glycolysis through suppression of pyruvate dehydrogenase kinase (PDHK) is a promising strategy for cancer inhibition. In this study, we performed to investigate the anti-tumor action of C. cassia is mediated by PDHK inhibition. The inhibition of water-extracted branch of C. cassia (WBCC) on the activity of PDHK using both in vitro and cell-based kinase assay were examined in several lung cancer cells. WBCC reduced viabilities of several lung cancer cells with minimal cytotoxicity on normal bronchial epithelial cells. WBCC decreased lactate production through inhibiting activity of PDHK. In consequence of PDHK inhibition, WBCC increased ROS production, which damage mitochondria membrane stability. In addition, WBCC induced ROS- and mitochondria-dependent apoptotic cell death. Among the components of WBCC, cinnamic acid was founded as a major inhibitor on PDHK activity. This is first report that WBCC induces apoptosis of lung cancer cells through inhibiting PDHK activity. Our findings suggest that WBCC and cinnamic acid can be potential candidates for developing novel anti-cancer drugs through glycolysis metabolism.

Panax notoginseng Inhibits Tumor Growth through Activating Macrophage to M1 Polarization.

Among the herbal ingredients of HangAmDan-B, a medicinal formula that redirects macrophages to become tumoricidal effectors, we found that Panax notoginseng (Burk.) F. H. Chen is the active component responsible for its macrophage-mediated antitumor activity. The water extracted roots of P. notoginseng (PN) did not affect the viability of RAW264.7 murine macrophage-like cells and murine Lewis lung carcinoma (LLC) cells up to a concentration of 100[Formula: see text][Formula: see text]g/mL. However, the transfer of culture media from PN-treated RAW264.7 cells suppressed the growth of LLC cells. The expression of classically activated (M1) markers, such as interleukin (IL)-1[Formula: see text], monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-[Formula: see text], and inducible nitric oxide synthase (iNOS), was increased by PN treatment. The expression of alternatively activated (M2) markers including CD206, IL-10, and [Formula: see text]-[Formula: see text]-acetylhexosaminidases (YM-1) was reduced by PN treatment in the presence of IL-4. Flow cytometry also revealed that PN drives M1 activation of RAW264.7 cells. The transfer of culture media from PN-treated RAW264.7 cells induced the apoptosis of LLC cells as measured by flow cytometry using Annexin-V staining and western blot analysis for caspase cascade-related proteins. In addition, the results from in vivo tumor allograft model demonstrated that PN reduced both tumor volume and weight. The activation of macrophages toward an M1 phenotype was confirmed in the tumor allograft tumor model. These results collectively show that PN can serve as a potent anticancer agent through reeducation of macrophages toward an M1 phenotype.

Sorbus commixta water extract induces apoptotic cell death via a ROS-dependent pathway.

The stembark of Sorbus commixta Hedl. has been used for treating asthma, bronchitis, gastritis and edema. However, the anticancer and proapoptotic effects of the water extract of the stembark of S. commixta (SCE) remain unknown. In the present study, it was shown that SCE inhibited the cell viability of the hepatocellular carcinoma cell lines Hep3B and HepG2, and of the colon carcinoma cell line HCT116. DNA content analysis indicated that SCE increased the sub-G1 population of HCT116 cells. In addition, degradation of nuclear DNA and levels of proapoptotic cascade components, including caspase-9, caspase-3 and poly ADP-ribose polymerase, were augmented by SCE treatment. Mitochondrial membrane potential and the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) were also reduced. Furthermore, SCE increased the expression of proapoptotic proteins, including p21, p27 and p53. Mouse double minute 2 homology, a negative regulator of p53, was cleaved by SCE treatment. Intracellular reactive oxygen species (ROS) production was also increased by SCE treatment. However, the SCE-induced cytotoxic effects and the increased expression of proapoptotic proteins, including p53 and p21, and reduced Bcl-2/Bax ratio, could be attenuated by N-acetyl cysteine, an ROS inhibitor. Taken together, these results indicate that SCE is a potent proapoptotic herbal medicine, which exerts its effects via the ROS-mediated mitochondrial pathway.

A randomized, open phase IV exploratory clinical trial to evaluate the efficacy and safety of acupuncture on the outcome of induction of ovulation in women with poor ovarian response: A study protocol for a randomized controlled trial.

INTRODUCTION: Women with infertility who have a poor ovarian responder (POR), characterized by a low number of retrieved oocytes after ovulation induction, often have a significantly reduced pregnancy rate after in vitro fertilization-embryo transfer (IVF-ET), due to the few transferred embryos. Acupuncture is a form of Korean Traditional Medicine. It involves the insertion of a microscopic needle at a specific point in the body, known as an acupuncture point or an acupoint. In this study, our purpose is to investigate how acupuncture affects the retrieval of mature oocytes after ovulation induction in patients with POR. METHODS AND ANALYSIS: This study will be a randomized clinical trial comprising an IVF-ET trial and an IVF-ET trial after acupuncture. Seventy patients will by enrolled and randomly assigned to either of the 2 groups. The study subjects will be required to be diagnosed as having POR. Participants will be divided into 2 groups: IVF-ET single treatment group, and acupuncture and IVF-ET combined treatment group. The study subjects will be required to participate in a 15-week trial involving 16 acupuncture treatments over a period of approximately 2 months before ovulation induction for oocyte retrieval. The primary assessment of all participants will be comparing the number of oocytes. RESULT: This treatment will be a therapeutic model for POR. DISCUSSION: Our results will provide patients with POR as well as complementary and alternative medicine professionals, such as Korean medicine doctors, about the potential role of acupuncture in the treatment of POR. This will improve the quality of life in women with infertility and provide an important treatment option for patients with POR. Further studies can be performed to determine the optimal treatment for POR.

Pretreatment with Shuanghe-Tang Extract Attenuates Postischemic Brain Injury and Edema in a Mouse Model of Stroke: An Analysis of Medicinal Herbs Listed in Dongui Bogam.

AIM: Although stroke is among the leading causes of death and long-term disability, there are few effective treatments for limiting the severity of neurological sequelae. We evaluated the effects of 29 medicinal herbs listed in the Pung chapter of the 17th century Korean medical text Dongui Bogam on stroke symptoms in a mouse model of cerebral ischemia. METHODS: Focal cerebral ischemia was induced via photothrombosis. Infarct volume, brain edema, and neurological deficits were evaluated. Immunofluorescence staining for tight junction proteins and aquaporin 4 (AQP4) was performed following ischemic injury. RESULTS: Based on our initial findings, we examined the effects of two prescriptions in which the candidate herbs comprised more than 60% of the total formula: Shuanghe-tang and Zengsunsiwu-tang. Pretreatment with Shuanghe-tang significantly reduced infarct volume, decreased blood-brain barrier (BBB) breakdown, attenuated edema, and improved neurological and motor functions in a dose-dependent manner (30, 100, and 300 mg/kg), while no such effects were observed in mice pretreated with Zengsunsiwu-tang. Immunohistochemical analysis revealed significant increases in ipsilateral occludin and zonula occludens 1 (ZO-1) expression in Shuanghe-tang-pretreated mice, as well as increased AQP4 immunofluorescence. CONCLUSIONS: These results indicate that Shuanghe-tang may protect against brain injury and promote recovery of neurological function following ischemia.

Acupuncture stimulation at GB34 suppresses 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced oxidative stress in the striatum of mice.

Recent studies have suggested that increased oxidative stress is a potential etiology in Parkinson's disease (PD). In this study, we investigated whether acupuncture regulates antioxidants in the striatum (ST) of a PD mouse model. Male C57BL/6 mice were administered 30 mg/kg of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intraperitoneally once a day for 5 days and given acupuncture stimulation at SI3 or GB34 (Yanglingquan) was for 12 consecutive days. Dopaminergic neuronal survival in the nigrostriatal pathway and DJ-1 expression in the ST was evaluated by immunostaining, and the activities of superoxide dismutase (SOD) and catalase (CAT) in the ST was by enzyme-linked immunosorbent assay. MPTP administration induced dopaminergic neuronal death in the nigrostriatal pathway, which was suppressed by acupuncture stimulation at GB34. MPTP administration also suppressed DJ-1 expression and SOD and CAT activities in the ST, which were restored by acupuncture stimulation at GB34. These results indicate that the neuroprotective effect of acupuncture stimulation is due to regulation of the antioxidants.

Water-extracted tubers of Cyperus rotundus L. enhance endometrial receptivity through leukemia inhibitory factor-mediated expression of integrin αVß3 and αVß5.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyperus rotundus L. (CR) has been traditionally used as an herbal medicine in Asian countries to treat diverse gynecological disorders. However, the potential therapeutic effect of CR on endometrial receptivity for successful embryo implantation to treat female infertility has not been fully studied. AIM OF STUDY: The aim of this study was to evaluate the effect of water-extracted CR on endometrial receptivity by investigating the expression of leukemia inhibitory factor (LIF) and integrins, cell adhesion, and embryo implantation using mifepristone (RU486; RU)-induced implantation failure model. MATERIALS AND METHODS: The water extract of CR was prepared and fingerprinted using high-performance liquid chromatography (HPLC). For the expression and regulation of LIF, reverse transcription polymerase chain reaction (RT-PCR) and western blotting were performed in CR-stimulated Ishikawa cells. To evaluate LIF-mediated integrin expression, knockdown of LIF by shRNA was performed in Ishikawa cells. The effect of CR on endometrial receptivity was determined by an in vitro adhesion assay between JAr cells and CR-induced Ishikawa cells. In vivo, C57BL/6 female mice (n = 7 per group) orally received CR (31.68mg/kg/day), a similar dose as used clinically. Seven days after CR treatment, all female mice were caged with male mice until pregnancy was verified. On day 4 of pregnancy, RU (4mg/kg) was injected subcutaneously to induce embryo implantation failure. RESULT: CR increased the expression of LIF through the phosphatidylinositol-3-kinase/ protein kinase B (PI-3K/AKT) signaling pathway in Ishikawa cells. In addition, CR enhanced adhesion of JAr cells onto Ishikawa cells by inducing the expression of LIF-dependent integrins αVß3 and αVß5. Furthermore, CR improved the number of implantation sites in pregnant mice despite RU injection. CONCLUSION: CR increased the expression of LIF-mediated integrins αVß3 and αVß5 on the surface of endometrial cells, which is associated with adhesion of trophoblastic cells to endometrial cells for blastocyst implantation. Our findings provide evidence that CR has therapeutic potential against poor endometrial receptivity.