Neuroprotective effects of methanolic extract from Chuanxiong Rhizoma in mice with middle cerebral artery occlusion-induced ischemic stroke: suppression of astrocyte- and microglia-related inflammatory response.

BACKGROUND: In traditional Asian medicine, dried rhizomes of Ligusticum chuanxiong Hort. (Chuanxiong Rhizoma [CR]) have long been used to treat pain disorders that affect the head and face such as headaches. Furthermore, they have been used primarily for blood circulation improvement or as an analgesic and anti-inflammatory medicine. This study aimed to investigate the neuroprotective effects of a methanol extract of CR (CRex) on ischemic stroke in mice caused by middle cerebral artery occlusion (MCAO). METHODS: C57BL/6 mice were given a 1.5-h transient MCAO (MCAO control and CRex groups); CRex was administered in the mice of the CRex group at 1,000-3,000 mg/kg either once (single dose) or twice (twice dose) before MCAO. The mechanism behind the neuroprotective effects of CRex was examined using the following techniques: brain infarction volume, edema, neurological deficit, novel object recognition test (NORT), forepaw grip strength, and immuno-fluorescence staining. RESULTS: Pretreating the mice with CRex once at 1,000 or 3,000 mg/kg and twice at 1,000 mg/kg 1 h before MCAO, brought about a significantly decrease in the infarction volumes. Furthermore, pretreating mice with CRex once at 3,000 mg/kg 1 h before MCAO significantly suppressed the reduction of forepaw grip strength of MCAO-induced mice. In the MCAO-induced group, preadministration of CRex inhibited the reduction in the discrimination ratio brought on by MCAO in a similar manner. CRex exhibited these effects by suppressing the activation of astrocytes and microglia, which regulated the inflammatory response. CONCLUSIONS: This study proposes a novel development for the treatment of ischemic stroke and provides evidence favoring the use of L. chuanxiong rhizomes against ischemic stroke.

Methanol extract of Ligusticum chuanxiong Hort. Rhizome ameliorates bilateral common carotid artery stenosis-induced cognitive deficit in mice by altering microglia and astrocyte activation.

In traditional Asian medicine, Ligusticum chuanxiong Hort also known as Conioselinum anthriscoides "Chuanxiong", is mainly used for improving blood circulation or for analgesic and anti-inflammatory purposes, but they also have a long history of use for pain disorders in the head and face, such as headache. Despite the possibility that the plant is effective for diseases such as cerebral infarction and vascular dementia (VaD), the mechanism of action is not well understood. To determine if the dried rhizomes of L. chuanxiong (Chuanxiong Rhizoma, CR) methanol extract (CRex) has activity in a VaD mice model. Through network analysis, we confirm that CR is effective in cerebrovascular diseases. In mice, we induce cognitive impairment, similar to VaD in humans, by chronically reducing the cerebral blood flow by performing bilateral common carotid artery stenosis (BCAS) and administering CRex for 6 weeks. We measure behavioral changes due to cognitive function impairment and use immunofluorescence staining to confirm if CRex can inhibit the activation of astrocytes and microglia involved in the inflammatory response in the brain. We quantify proteins involved in the mechanism, such as mitogen-activated protein kinases (MAPK), in the hippocampus and surrounding white matter, and analyze gene expression and protein interaction networks through RNA sequencing to interpret the results of the study. CRex administration rescued cognitive impairment relating to a novel object and inhibited the activation of astrocytes and microglia. Western blotting analysis revealed that CRex regulated the changes in protein expression involved in MAPK signaling such as extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38). The administration of CRex suppressed approximately 44% of the pathological changes in gene expression caused by BCAS. CRex extract effectively inhibited cognitive impairment caused by BCAS, and the mechanism through which this occurred is inhibited activation of astrocytes and microglia.

Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial.

BACKGROUND: Electroacupuncture (EA) may reduce the severity of acute pancreatitis (AP) and provide additional pain relief in patients with chronic pancreatitis. However, the ability of EA to relieve pain in patients with AP has not been well documented. OBJECTIVE: This study was undertaken to compare the pain-relieving effects of EA and conventional treatment in patients with AP. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was conducted using a randomized, controlled, three-arm, parallel-group and multi-center design. Patients diagnosed with AP were randomly and equally assigned to EA1, EA2 or control groups. All participants received conventional standard-of-care therapy for AP. Local EA alone was administered in EA1, and local plus distal EA was given in EA2. Local EA included two abdominal acupoints, while distal EA included twelve peripheral acupoints. EA groups underwent one session of EA daily for 4 days (days 1-4), or until pain was resolved or discharged. MAIN OUTCOME MEASURES: The primary outcome measure was the change in the visual analogue scale (VAS; 0-100) pain score between baseline and day 5. RESULTS: Eighty-nine participants were randomized into EA1, EA2 and control groups, and 88 (EA1, 30; EA2, 29; control, 29) were included in the full-analysis set. VAS score change (median [interquartile range]) on day 5 was (12.3 ± 22.5) in the EA1 group, (10.3 ± 21.5) in the EA2 group, and (8.9 ± 15.2) in the control group. There were not significant differences in the change in VAS score among treatments (P = 0.983). However, time to food intake was significantly shorter in the EA group (EA1 + EA2) than in the control group (median 2.0 days vs 3.0 days), with a hazard ratio of 0.581 (P = 0.022; 95% CI, 0.366-0.924). No significant adverse events occurred. CONCLUSION: EA treatment did not significantly reduce pain after 4 days of treatment in patients with AP-associated abdominal pain but significantly reduced time to first food intake. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03173222. Please cite this article as: Jang DK, Lee JK, Jung CY, Kim KH, Kang HR, Lee YS, Yoon JH, Joo KR, Chae MK, Baek YH, Seo BK, Lee SH, Lim C. Electroacupuncture for abdominal pain relief in patients with acute pancreatitis: A three-arm randomized controlled trial. J Integr Med. 2023; 21(6): 537-542.

Efficacy and Safety of Woohwangchungsimwon Combined with Donepezil in Behavioral and Psychological Symptoms of Dementia in Patients with Probable Alzheimer's Disease: Study Protocol for a Randomized Controlled Trial.

Behavioral and psychological symptoms of dementia are a major factor in the burden of care and medical expenses. Conventional pharmacological treatments do not exert a distinct effect on the benefits versus the risks. The herbal medicine woohwangchungsimwon is frequently prescribed for neuropsychiatric disorders. An effect of woohwangchungsimwon on behavioral and psychological symptoms of dementia has been previously reported; however, no clinical studies have been conducted. We aim to evaluate the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating these symptoms in probable Alzheimer's disease. In this randomized, assessor-blinded, parallel-group clinical trial, 74 participants with probable Alzheimer's disease will be divided via block randomization into a woohwangchungsimwon + donepezil combination group (n = 37) or a donepezil single group (n = 37). Participants will include patients under donepezil treatment for at least a month. We will perform the study for 24 weeks. The Neuro-Psychiatric Inventory subscale scores will be the primary outcome. Secondary outcomes will include cognitive function, dementia severity, physical function, quality of life, depression, anxiety, and insomnia. For safety evaluation, we will assess adverse reactions, measure vital signs, and conduct laboratory tests. This is the first trial aiming to confirm the efficacy and safety of woohwangchungsimwon combined with donepezil for alleviating behavioral and psychological symptoms of dementia. Its findings could provide a basis for their co-administration to control these symptoms in probable Alzheimer's disease.

Tooth-Cutting-Induced Maxillary Malocclusion Exacerbates Cognitive Deficit in a Mouse Model of Vascular Dementia.

Treatments to restore the balance of the temporomandibular joint (TMJ) are performed in the field of complementary and alternative medicine; however, evidence supporting this approach remains weak. Therefore, this study attempted to establish such evidence. Bilateral common carotid artery stenosis (BCAS) operation, which is commonly used for the establishment of a mouse model of vascular dementia, was performed, followed by tooth cutting (TEX) for maxillary malocclusion to promote the imbalance of the TMJ. Behavioural changes, changes in nerve cells and changes in gene expression were assessed in these mice. The TEX-induced imbalance of the TMJ caused a more severe cognitive deficit in mice with BCAS, as indicated by behavioural changes in the Y-maze test and novel object recognition test. Moreover, inflammatory responses were induced via astrocyte activation in the hippocampal region of the brain, and the proteins involved in inflammatory responses were found to be involved in these changes. These results indirectly show that therapies that restore the balance of the TMJ can be effectively used for the management of cognitive-deficit-related brain diseases associated with inflammation.

Systemic Analgesic Effects of Electroacupuncture in Healthy Individuals: Thermal Threshhold, Acupuncture Sensation Intensity and De-qi on Quantitative Sensory Test.

Background: Electroacupuncture (EA) has been known to exert analgesic effects according to several reports, but studies investigating the analgesic effect of EA using the quantitative sensory test (QST) are rare. Primary Study Objective: To investigate the analgesic effects of electroacupuncture through changes in thermal thresholds measured using the QST. Design: Pilot, randomized, single-blind, parallel design. Setting: The study was conducted at Dongguk University Bundang Oriental Hospital (DUBOH) in South Korea. Participants: We included 40 healthy participants age 20 to 40 years. Intervention: The EA group received EA for 30 minutes at 6 acupuncture points (LI4, PC6, LI10, LI11, ST36, and SP6) and the control group just rested. Outcome measures: The primary outcome measure was 4 thermal thresholds including warm detection (WDT), cold detection (CDT), hot pain (HPT), and cold pain (CPT) measured using QST at baseline and after 15, 30 and 60 minutes. The secondary outcomes were the intensity of acupuncture sensation (visual analogue scale [VAS]) and De-qi (Massachusetts General Hospital Acupuncture Sensation Scale [MASS]). Results: The EA group showed significant changes in HPT (P < .001) and CPT (P = .049) compared with the control group, whereas WDT and CDT did not significantly differ. Furthermore, the changes in thermal thresholds were more pronounced in the higher intensity acupuncture sensation group (VAS ≥40) than in the lower intensity group (VAS < 40), although not significantly. The high De-qi group presented greater changes in WDT, CDT, HPT and CPT than the low De-qi group, as measured using MASS. It was especially statistically significant at HPT a feeling of "heaviness" and "dull pain" and at CDT of "tingling." We observed no adverse events related to the study. Conclusion: The change in thermal pain thresholds effected by EA supports the analgesic effect of EA reported in previous studies. The underlying mechanisms need to be holistically considered, and further studies are needed for definitive evidence.

Amelioration of Brain Damage after Treatment with the Methanolic Extract of Glycyrrhizae Radix et Rhizoma in Mice.

Glycyrrhizae Radix et Rhizoma (GR) is a traditional herbal medicine widely used in Asian countries. GR was the most frequently used medicine among stroke patients in Donguibogam, the most representative book in Korean medicine. In the present study, we investigated the neuroprotective effects of the GR methanolic extract (GRex) on an ischemic stroke mice model. Ischemic stroke was induced by a 90 min transient middle cerebral artery occlusion (MCAO), and GRex was administered to mice with oral gavage after reperfusion of MCA blood flow. The MCAO-induced edema and infarction volume was measured, and behavioral changes were evaluated by a novel object recognition test (NORT). Immunofluorescence stains and Western blotting identified underlying mechanisms of the protective effects of GRex. GRex post-treatment in mice with MCAO showed potent effects in reducing cerebral edema and infarction at 125 mg/kg but no effects when the dosage was much lower or higher than 125 mg/kg. GRex inhibited the decrease of spontaneous motor activity and novel object recognition functions. The neuroprotective effects of GRex on ischemic stroke were due to its regulation of inflammation-related neuronal cells, such as microglia and astrocytes.

Effects of Daehwang-Hwanglyoun-Sasim-Tang on brain injury and cognitive function in mice caused by bilateral common carotid artery stenosis.

Among geriatric diseases, cerebrovascular disease ranks fourth according to the Causes of Death Statistics in 2019, Korea, and is the most common cause of acquired disorders in adults. Daehwang-Hwanglyoun-Sasim-Tang (DHST), a herbal prescription consisting of two herbal medicines, Rhei Rhizoma and Coptidis Rhizoma, has been reported to have anti-inflammatory, antioxidant, and anticancer effects. This study was conducted to confirm the anti-inflammatory mechanism of DHST treatment in ischemic brain injury and to confirm the role of DHST in cognitive function improvement. C57BL/6 male mice were randomly divided into four groups (sham operation, bilateral common carotid artery stenosis (BCAS) control, experimental group administered 5 mL/kg DHST, experimental group administered 50 mL/kg DHST), with each group containing five mice. After 1 week, DHST was orally administered for 4 weeks, 5 days a week, and then behavioral evaluation of learning and memory was performed. In addition, morphological changes in the neurons in the CA1 region of the hippocampus were observed. Inflammation-related factors were evaluated using western blot analysis. In the 50 mL/kg DHST (H-DHST) group, the expression of apoptosis-related proteins was reduced and neuronal damage was suppressed in the hippocampal CA1 region. However, cognitive improvement was observed in the H-DHST group that was attributable to anti-inflammatory and antiapoptotic pathways. In the 5 mL/kg DHST group, no significant effect was observed compared with the control group.

Effectiveness and safety of electric heating moxibustion for perennial allergic rhinitis: A pilot, randomized, assessor-blind trial.

BACKGROUND: The prevalence of allergic rhinitis (AR), an inflammatory disease, is gradually increasing. Studies have reported that moxibustion is effective for treating AR. Electric heating moxibustion (EM) was developed to offer adaptable heat stimulation without the generation of smoke. OBJECTIVES: The objective of this study was to examine the possibility of EM in treating perennial allergic rhinitis (PAR) and to assess the feasibility of using this technique on a larger scale by comparing EM with acupuncture (AC). DESIGN: A randomized pilot study was conducted on 40 patients with PAR. Patients were randomly assigned to one of two treatment groups: EM or AC. The primary outcome measure was the change in the total nasal symptom score (TNSS) between before and after treatment. The secondary outcome measures were the changes in the rhinoconjunctivitis quality of life questionnaire (RQLQ), nasal endoscopy index for pattern identification, pattern identification questionnaire for AR, total serum immunoglobulin E (IgE), eosinophil count, and adverse effects (AEs). RESULTS: The results showed a statistically significant improvement in mean TNSS and RQLQ scores in both groups (p < 0.05), but no significant difference between the two groups. However, mean changes in itching and sneezing TNSS were significantly higher in the AC group. There was no significant difference in total serum IgE or eosinophil count before versus after treatment, nor was there any significant difference of three pattern subgroups between the two groups in the mean TNSS change. While the AC group reported two treatment-related AEs, there were no treatment-related AEs in the EM group. CONCLUSION: This trial provides evidence that EM isa safe alternative treatment for patients with PAR. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03342105. Registered on 14 November 2017.

Effectiveness and safety of Korean medicine for treating women with unexplained infertility: A multi-center observational study.

BACKGROUND: This study was conducted to demonstrate the effectiveness and safety of herbal medicine and acupuncture treatment in unexplained infertile females. METHODS: One hundred patients were recruited from 3 Korean Medicine hospitals in Korea and they voluntarily signed informed consent agreements. Participants took the Onkyeong-tang (120cc) twice daily between menstrual cycle day (MCD) 3 and 12, and herbal medicine for ovulation and implantation (120cc) twice daily between MCD 13 and 28. They also received acupuncture and moxibustion treatment during 4 menstrual cycles. After the 4 menstrual cycle treatment period, there were 3 menstrual cycle observation periods. The primary outcome is signified by clinical pregnancy rates (CPR) and the secondary outcomes were implantation rates (IR), ongoing pregnancy rates (OPR), and live birth rates. RESULTS: 90 patients completed the study. 13 of the 90 subjects became pregnant. The CPR and IR was 14.44%. 7 of 13 pregnant subjects had continuing pregnancy for over 12 weeks, so that the OPR was 53.85%. The birth rate was 7.78%. All 7 pregnant patients gave birth to their babies and all the babies were live singletons and healthy. There were no serious adverse events. CONCLUSIONS: The findings of this study may provide the possibility of effectiveness and safety of Korea medicine treatment for unexplained infertile women. Further study is required due to lack of control and small sample size in this study.

Angelica gigas root ameliorates ischaemic stroke-induced brain injury in mice by activating the PI3K/AKT/mTOR and MAPK pathways.

CONTEXT: Traditionally, the root of Angelica gigas Nakai (Umbelliferae), has long been used to treat ischaemic diseases and is considered safe in humans. OBJECTIVE: To investigate the neuroprotective effects of a methanol extract of A. gigas root (AGmex) on the middle cerebral artery occlusion (MCAO)-induced brain injury in mice, and the underlying mechanisms. MATERIALS AND METHODS: Two hours of transient MCAO (tMCAO) was induced in C57BL/6 mice (MCAO control group and AGmex groups), AGmex was administered to the AGmex group at 300-3,000 mg/kg bw at 1, 1, and 24 h before tMCAO or at 1000 mg/kg bw at 1 h before and after tMCAO. Infarction volumes, tissue staining, and western blotting were used to investigate the mechanism underlying the neuroprotective effects of AGmex. RESULTS: The median effective dose (ED50) could not be measured because the AGmex treatment did not reduce the infarction volume caused by 2 h of tMCAO to within 50%; however, pre-treatment with AGmex twice at 1,000 mg/kg bw before tMCAO significantly reduced the infarction volumes. The proteins related to cell growth, differentiation, and death were upregulated by this treatment, and the major recovery mechanisms appeared to involve the attenuation of the mitochondrial function of Bcl-2/Bax and activation of the PI3K/AKT/mTOR and MAPK signalling pathways in ischaemic neurons. CONCLUSIONS: This study provides evidence supporting the use of A. gigas root against ischaemic stroke and suggests a novel developmental starting point for the treatment of ischaemic stroke.

Effects of the methanol fraction of modified Seonghyangjeongki-san water extract on transient ischaemic brain injury in mice.

CONTEXT: Recently in Korean medicine, the antioxidant and anti-inflammatory activities of Seonghyangjeongki-san (SHJKS) were reported. However, studies on the specific mechanisms of action of SHJKS for the treatment of ischaemic stroke are still lacking. OBJECTIVE: This study investigates the mechanism of action of the water extract methanol fraction of modified SHJKS (SHJKSmex) on cerebral ischaemic injury. MATERIALS AND METHODS: C57BL/6 male mice were orally administered SHJKSmex (30, 100, or 300 mg/kg) for 3 consecutive days (2 days, 1 day, and 1 h, respectively) before middle cerebral artery occlusion (MCAO). Twenty-four hours after MCAO, the infarct volumes were measured, brain edoema indices were calculated, and neurological deficit scores were determined. Inflammation-related substances in the ipsilateral hemisphere were determined by western blotting, dichlorofluorescin diacetate, thiobarbituric acid-reactive substances assay, and enzyme-linked immunosorbent assay. RESULTS: SHJKSmex pre-treatment at 300 mg/kg decreased infarct volume by 87% and mean brain water content by 90% of the MCAO control group. Moreover, SHJKSmex effectively suppressed the expression of inducible nitric oxide synthase, reactive oxygen species, interleukin 1, and caspases-8 and -9 and increased the B-cell lymphoma 2/Bcl-2-associated X protein ratio (Bcl-2/Bax) in ischaemic mouse brain. The hippocampal pyramidal cell densities were significantly increased in the 300 mg/kg SHJKSmex-administered group compared to the MCAO control group. DISCUSSION AND CONCLUSIONS: SHJKSmex protected the brain from ischaemic stroke in mice through its antioxidant, anti-inflammatory, and antiapoptotic activities. Our findings suggest that SHJKSmex is a promising therapeutic candidate for the development of a new formulation for ischaemia-induced brain damage.

Artemisia kruhsiana leaf extract induces autophagic cell death in human prostate cancer cells.

Some species of Artemisia have been reported to induce apoptosis and autophagy, but little is known of the apoptotic and autophagic effects of the stems and leaves of Artemisia kruhsiana Bess. (AkB). This study was conducted to investigate the antioxidant and anti-autophagic effects of the methanol extracts of the stems (EAkBs) and leaves (EAkBl) of AkB on human prostate cancer PC-3 cells. The antioxidant effects of EAkBs and EAkBl were measured using in vitro total flavonoid and total phenolic assays and a free radical scavenging assay. The effects of EAkBl on cell viability, apoptosis, autophagy, intracellular reactive oxygen species (ROS) generation and protein expression levels were also investigated. EAkBl was found to induce apoptosis, autophagy, and intracellular ROS generation in PC-3 cells. In terms of protein levels, EAkBl reduced phospho (p)-protein kinase B (AKT)/AKT, p-mammalian target of rapamycin (mTOR)/mTOR, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratios, and the activations of beclin 1/ß-actin and microtubule-associated protein 1A/1B-light chain 3 (LC3) II/LC3 I ratios in PC-3 cells. The results of this study indicate EAkBl has antioxidant and anticancer effects on prostate cancer cells, and that these effects are associated with suppressions of p-AKT, p-mTOR, Bcl-2, and Bax, and the activations of beclin 1 and LC3. Our results indicate EAkBl has potential as a treatment for prostate cancer.

Dracocephalum palmatum Stephan extract induces apoptosis in human prostate cancer cells via the caspase-8-mediated extrinsic pathway.

Dracocephalum palmatum Stephan is a medicinal plant traditionally used by nomadic people in Eastern Russia; however, research on this plant is currently limited. Recently, although studies have been conducted on the constituents of this plant and their antioxidant effects, data on its various pharmacological activities are still lacking. Thus, this study examined the anticancer potential of the dried leaves of D. palmatum S. (DpL) using human prostate cancer PC-3 cells. The antioxidant potential of DpL was evaluated by estimating the total flavonoid and total phenolic content (TFC and TPC, respectively). Additionally, we investigated the effects of the DpL ethyl acetate fraction (DpLE) on cell proliferation, intracellular reactive oxygen species (ROS) generation, apoptosis, and cell cycle arrest in this cell line. The expression levels of superoxide dismutase (SOD)-1, SOD-2, B-cell lymphoma 2 (Bcl-2) and Bcl-2 associated X (Bax) ratio, phospho-protein kinase B (p-AKT), cleaved caspase-8, poly adenosine diphosphate (ADP) ribose polymerase (PARP), and cleaved-PARP were evaluated by western blotting. The results indicated that DpLE causes apoptosis and exerts intracellular ROS-independent anticancer effects on prostate cancer cells, associated with increased SOD-2, cleaved caspase-8, and cleaved-PARP expression and inhibited p-AKT signaling. Thus, DpLE may be a potential resource for the development of promising chemotherapeutic agents for prostate cancer.

Neuroprotective effect of Angelica gigas root in a mouse model of ischemic brain injury through MAPK signaling pathway regulation.

BACKGROUND: The root of Angelica gigas Nakai (Apiaceae) has been traditionally used as an important herbal medicine to treat blood-deficiency-related disorders in Eastern Asian countries, and recently, it has been recognized as a potential candidate for improving cardiovascular diseases. METHODS: In this study, the neuroprotective effect of a methanol extract of A. gigas root (RAGE) was investigated in a mouse stroke model induced by a 90 min transient middle cerebral artery occlusion (tMCAO). Infarction volumes and morphological changes in brain tissues were measured using TTC, cresyl violet, and H&E staining. The neuroprotective mechanism of RAGE was elucidated through investigation of protein expression levels using western blotting, IHC, and ELISA assays. The plasma concentrations of decursin, a major compound in RAGE, were measured after oral administration of RAGE to SD rats. RESULTS: The infarction volumes in brain tissues were significantly reduced and the morphological deteriorations in the brain neuron cells were improved in tMCAO mice when pre-treated with RAGE at 1000 mg/(kg bw·d) for two consecutive days. The neuroprotective mechanism of RAGE was confirmed to attenuate ERK-related MAPK signaling pathways in the ipsilateral hippocampus hemisphere in mice. The concentrations of decursin in rat plasma samples showed peak absorption and elimination in vivo after oral administration of RAGE at 100 mg/rat. CONCLUSION: Mice administered RAGE before the tMCAO operation had less neuronal cell death than those that were not administered RAGE prior to the operation, and this study provides preclinical evidence for use of A. gigas in ischemic stroke.

Refined Deep Seawater Improves Serum Lipid Profile in Hypercholesterolemia: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial.

Deep seawater (DSW) has been investigated for its lipid-lowering effects, but clinical evidence is still far from conclusive. Therefore, this study was conducted to examine the effects of refined DSW (RDSW) on hypercholesterolemia. In this randomized, double-blind, placebo-controlled trial, 78 Korean participants were randomized to either an RDSW group that drank RDSW for 8 weeks or a placebo group. Clinical laboratory information was collected from all subjects at 0, 4, and 8 weeks. Both groups showed a significant reduction in total cholesterol (TC), whereas only the RDSW group demonstrated a significant decrease in low-density lipoprotein cholesterol (LDL-c) during the study. Stratified analysis of both groups revealed a significant reduction of TC in the moderately high TC subgroup. However, only the RDSW exhibited a significant decline of LDL-c in the high LDL-c subgroup. In addition, lipoprotein(a) decreased significantly in the RDSW group, but not in the placebo. RDSW did not affect other lipid profiles, including high-density lipoprotein cholesterol (HDL-c), triglyceride, free fatty acid, apolipoproteins, and other markers including inflammation marker, hematological parameters, blood and urine chemistry, and vital signs. RDSW improved lipid profiles by decreasing TC and LDL-c while maintaining HDL-c levels in people with hypercholesterolemia.

Effect of Ephedrae Herba methanol extract on high-fat diet-induced hyperlipidaemic mice.

Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up- or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.

Gentiana scabra Bunge roots alleviates skin lesions of contact dermatitis in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots and rhizomes of Gentiana scabra Bunge in the family Gentianaceae comprise a major herbal medicine for skin diseases caused by wind-heat or dampness-heat in China, Japan and Korea. This treatment can clear away heat and dry dampness and purge fire from the liver and gallbladder. AIM OF THE STUDY: This study was designed to investigate the therapeutic potential and anti-inflammatory effects of G. scabra, roots and rhizomes. MATERIALS AND METHODS: Thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) revealed the presence of gentiopicrin in the roots and rhizomes of G. scabra. We then investigated the effects of ethanol extract of G. scabra, roots and rhizomes (EEGS) on skin lesions and thickness, erythema and melanin index, histopathological abnormalities, and cytokine and chemokine production in mice with contact dermatitis (CD) induced by 1-fluoro-2,4-dinitrofluorobenzene (DNFB). Moreover, the effects of EEGS on body weights and spleen body weight ratio were evaluated. RESULTS: Topical application of EEGS alleviated skin lesions such as surface roughness, excoriations and scabs on the skin of CD mice, as well as prevented skin enlargement, and lowered the erythema and melanin index. In addition, EEGS prevented hyperkeratosis, epidermal hyperplasia and immune cell infiltration, and inhibited TNF-α, IFN-γ, IL-6 and MCP-1 production in inflamed tissues. EEGS did not affect changes in body weights and spleen body weight ratio in contrast to dexamethasone. CONCLUSIONS: These data indicate that the roots and rhizomes of G. scabra can be used as anti-inflammatory agents for CD with relative safety and that its therapeutic mechanisms are related to regulation of pro-inflammatory cytokines such as TNF-α and IFN-γ.

Assessing Neuroprotective Effects of Glycyrrhizae Radix et Rhizoma Extract Using a Transient Middle Cerebral Artery Occlusion Mouse Model.

Ischemia followed by reperfusion of cerebral blood flow after a stroke leads to the death of nerve cells and loss of brain tissue. The most commonly used animal model for studying stroke is the middle cerebral artery occlusion (MCAO) model. Previous research studies have reported different infarct sizes even when the same experimental animal species was used under similar MCAO conditions. Therefore, we developed an improved experimental method to address this discrepancy. Mice were subjected to MCAO using a filament as the occlusion material to mimic human stroke conditions and filament thickness was optimized to establish more reproducible infarction volume. Mice treated with a methanol extract of Glycyrrhizae Radix et Rhizome (GRex) following stroke induction showed a significantly decreased total infarction volume and increased number of surviving cells relative to the untreated control group. This modified experimental protocol successfully and reproducibly demonstrated the beneficial effect of GRex on ischemic stroke.

Electroacupuncture to treat with Overactive Bladder in Postmenopausal Women: study protocol for a multicenter, randomized, controlled, parallel clinical trial.

BACKGROUND: Electroacupuncture has been used for treatment in patients with overactive bladder. This study was conducted to evaluate the efficacy and safety of electroacupuncture for treating overactive bladder of postmenopausal women. METHODS/DESIGN: This is a multicenter, randomized controlled, parallel clinical trial. Two hundred ninety participants with overactive bladder syndrome will be recruited from Dongguk University Bundang Oriental Hospital and Cheonan Korean Medicine Hospital of Daejeon University and randomly allocated into one of two groups in a 1:1 ratio. One group will receive electroacupuncture (EA) and the other acupuncture (AC). The allocation will be concealed from both participants and assessors. The study period will be about 10 weeks, including 6 weeks of electroacupuncture or acupuncture treatment and a four week follow-up period. Both EA group and AT group will undergo acupuncture at 7 fixed points, and the EA group will undergo electronic stimulation at 6 points. The primary outcome will be the average number of micturitions per 24 h based on a 3-day bladder diary. The secondary outcome will comprise the 3-day bladder diary, the overactive bladder symptom score and the results of the King's health questionnaire. DISCUSSION: The results of this trial will provide information regarding the efficacy and safety of electroacupuncture for treating overactive bladder in postmenopausal women. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03260907 . Registered on 24 August 2017.