Herbal medicine (Taohong Siwu Tang) for the treatment of primary dysmenorrhea: A systematic review and meta-analysis.

OBJECTIVES: This systematic review aimed to evaluate the efficacy and safety of Tao-Hong Siwu Tang (TST) for the treatment of primary dysmenorrhea. METHODS: We searched four English databases (MEDLINE, EMBASE, Allied and Complementary Medicine Database, and Cochrane Central Register of Controlled Trials [CENTRAL, Cochrane Library]), three Chinese databases (China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Periodical Database), two Korean databases (Oriental Medicine Advanced Searching Integrated System and Korean traditional Knowledge Portal), and one Japanese database (Citation Information by NII). All randomized controlled trials (RCTs) using TST or modified TST (MTST) were included. Three independent reviewers extracted the data, assessed the risk of bias according to the Cochrane criteria, and performed a meta-analysis. RESULTS: A total of 85 possibly relevant articles were identified, and five trials met our inclusion criteria. The meta-analysis showed a favorable effect of MTST compared to non-steroidal anti-inflammatory drugs (NSAIDs) (n = 486, risk ratio [RR] = 1.53, 95% confidence interval [95% CI] = 1.37-1.72, I2 = 39%). Among the included trials, one RCT showed superior effects of MTST on primary dysmenorrhea recurrence rate compared to NSAIDs (n = 246, RR = 0.31, 95% CI = 0.15-0.63, P = 0.001). Another RCT revealed a beneficial impact of oral contraceptives (OCs) used in combination with TST compared to OCs alone (n = 60, RR = 1.35, 95% CI = 1.02-1.79, P = 0.04). CONCLUSION: This systematic review and meta-analysis provides moderate quality evidence for the superiority of MTST over NSAIDs as well as that of TST plus OCs over OCs in the treatment of primary dysmenorrhea.

Apoptotic effect of Gyejibokryunghwan on uterine sarcoma cells (SK-UT-1B).

BACKGROUND: Diagnosis of uterine sarcomais is a challenging task for clinicians because its position is not easily accessible by current conventional techniques. In addition, standardized treatment for uterine sarcoma has not yet been established due to its rarity and heterogeneity. HYPOTHESIS/PURPOSE: We investigated the apoptotic cell death of uterine sarcoma cells (SK-UT-1B) induced by Gyejibokryunghwan (GBH). GBH, an herbal medicine, has been widely used for gynecological diseases in Koean medicine. METHODS: SK-UT-1B cells were treated with GBH of varying concentrations from 0 to 500 µg/ml. The mechanism of cell death was investigated through multiple analysis methods, including flow cytometry, cell cycle, and western blotting. RESULTS: Flow cytometric analysis revealed that the number of apoptotic cells increased in a GBH dose-dependent manner. The cell populations of sub-G1 and G0/G1 phases were increased by GBH treatment, indicating apoptosisand cell arrest, while the population of S and G2/M phases decreased. With GBH, the expression levels of cleaved caspase-3, -6, and -9 were upregulated, while the expression levels of pro-caspase-3, -6, and -9 were down-regulated in SK-UT-1B cells. CONCLUSION: These results are the first observation of uterine sarcoma cell death induced by GBH and confirmation of the mechanism of cell death, which occurred through the intrinsic apoptotic pathway. Clinically, uterine sarcoma has a poor prognosis with no appropriate treatment. GBH may become a new treatment modality for uterine sarcoma.

Characteristics of heart rate variability in women with polycystic ovary syndrome: A retrospective cross-sectional study.

We aimed to compare the modulation of the autonomic nervous system (ANS) in women with polycystic ovary syndrome (PCOS) with that in healthy ovulatory women on the basis of heart rate variability (HRV), and to analyze the characteristics of the ANS in PCOS.In a retrospective chart review, HRV, body mass index, and physical examination data in women with PCOS and those with regular menstrual cycles were collected. Approval from the institutional review board (IRB) was obtained (IRB No. 2017-05-007-001) for this study. The mean outcomes were the values of HRV in the time [standard deviation of all normal R-R intervals (SDNN), the square root of the sum of the squares of the differences between the adjacent normal R-R intervals (rMSSD), and the mean heart rate turbulence (mean HRT)] and frequency [total power (TP), very-low-frequency power (VLF), low-frequency power (LF), normalized low-frequency power (LF norm), high-frequency power (HF), normalized high-frequency power (HF norm), and LF/HF ratio] domains. Differences between the 2 groups were analyzed by Mann-Whitney U test, using SPSS for Windows (version 22.0).There was no significant difference in the values of the time domain (SDNN, rMSSD, and mean HRT) between the groups. In the frequency domain, women with PCOS showed significantly higher LF (598.63 ±â€Š94.38 vs 459.13 ±â€Š163.64, P = .028), LF norm (48.64 ±â€Š3.39 vs 36.49 ±â€Š2.82, P = .009), and LF/HF ratio (1.49 ±â€Š0.31 vs 0.73 ±â€Š0.13, P = .009) than the control group. HF norm was significantly lower in the women with PCOS than in the controls (51.38 ±â€Š3.39 vs 63.51 ±â€Š2.82, P = .009). The TP, VLF, and HF showed no significant difference between the groups.The results of the present study indicated that PCOS is related to increased sympathetic modulation in HRV.

A review of in vitro and in vivo studies on the efficacy of herbal medicines for primary dysmenorrhea.

Purpose. Primary dysmenorrhea (PD) is a common gynecological complaint among adolescent girls and women of reproductive age. This study aims to review the findings of published articles on the in vitro and in vivo efficacy of herbal medicines for PD. Methods. In vitro and in vivo studies of herbal compounds, individual herbal extracts, or herbal formula decoctions published from their inception to April 2014 were included in this review. Results. A total of 18 studies involving herbal medicines exhibited their inhibitory effect on PD. The majority of in vitro studies investigated the inhibition of uterine contractions. In vivo studies suggest that herbal medicines exert a peripheral analgesic effect and a possible anti-inflammatory activity via the inhibition of prostaglandin (PG) synthesis. The mechanisms of herbal medicines for PD are associated with PG level reduction, suppression of cyclooxygenase-2 expression, superoxide dismutase activation and malondialdehyde reduction, nitric oxide, inducible nitric oxide synthase, and nuclear factor-kappa B reduction, stimulation of somatostatin receptor, intracellular Ca(2+) reduction, and recovery of phospholipid metabolism. Conclusions. Herbal medicines are thought to be promising sources for the development of effective therapeutic agents for PD. Further investigations on the appropriate herbal formula and their constituents are recommended.

Effect of Korean red ginseng on cold hypersensitivity in the hands and feet: study protocol for a randomized controlled trial.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is one of the most common complaints among Asians, especially in women. Korean red ginseng (KRG), which is a steamed form of Panax ginseng, has vasodilating action in the peripheral vessels and increases blood flow under cold stress. However, few studies have evaluated the effect of KRG on cold hypersensitivity. METHODS/DESIGN: This trial is a randomized, double-blind, placebo-controlled trial in 80 CHHF patients. The trial will be implemented at Kyung Hee University Hospital at Gangdong in Seoul, Korea. The participants will take KRG or a placebo for eight weeks, after which they will be followed-up for four weeks. During the administration period, six capsules of 500 mg KRG or placebo will be provided twice a day. The primary outcome is change of skin temperature in the hands between baseline and after treatment. The secondary outcomes include the visual analogue scale scores of cold hypersensitivity in the hands, change of skin temperature and the VAS scores of cold hypersensitivity in the feet, the recovery rate of the skin temperature by the cold stress test of the hands, the distal-dorsal difference of the hands, power variables of heart rate variability, and the 36-item short form health survey. DISCUSSION: This study is the first trial to evaluate the efficacy of KRG on CHHF by using infrared thermography. Our study will provide basic evidence regarding CHHF. TRIAL REGISTRATION: CliniacalTrials.gov NCT01664156.

Dangguijakyak-San Protects against 1-Methyl-4-phenyl-1,2,3,6,-tetrahydropyridine-Induced Neuronal Damage via Anti-Inflammatory Action.

Dangguijakyak-san (DJS), a famous traditional Korean multiherbal medicine, has been used to treat gynecological and neuro-associated disease. Recent studies demonstrated that DJS has multiple bioactivities including neuroprotection. In the present study, we were to investigate the effect of DJS and its mechanism in an in vitro and in vivo model of Parkinson's disease (PD). In primary mesencephalic culture system, DJS attenuated the dopaminergic cell damage induced by 1-methyl-4-phenylpyridine toxicity, and it inhibited production of inflammatory factors such as tumor necrosis factor α (TNF- α ), nitric oxide (NO), and activation of microglial cells. Then, we confirmed the effect of DJS in a mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In the pole test, DJS at 50 mg/kg/day for 5 days showed increase of motor activity showing shortened time to turn and locomotor activity compared with the MPTP only treated mice. In addition, DJS significantly protected nigrostriatal dopaminergic neuron from MPTP stress. Moreover, DJS showed inhibition of gliosis in the substantia nigra pars compacta. These results have therapeutic implications for DJS in the treatment of PD via anti-inflammatory effects.

Safflower seed extract inhibits osteoclast differentiation by suppression of the p38 mitogen-activated protein kinase and IκB kinase activity.

Safflower seed has been reported to have a protective effect against bone loss diseases. However, the precise molecular mechanisms underlying the inhibitory effect of safflower seed in osteoclast differentiation remain unclear. In this study, we investigated the inhibitory action of safflower seed extract (SSE) on the receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis in cultured mouse-derived bone marrow macrophages (BMMs). We found that SSE significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells in BMMs without cytotoxicity. The gene expressions of nuclear factor of activated T-cells (NFATc1) and TRAP, which are genetic markers of osteoclast differentiation, were substantially decreased by SSE in a dose-dependent manner. Also, SSE diminished RANKL-mediated intracellular reactive oxygen species (ROS) generation on osteoclastogenesis in a dose-dependent manner. The SSE thereafter suppressed RANKL-induced p38 mitogen-activated protein kinase and IκBα kinase signalling activities which were activated by ROS generation for osteoclastogenesis. Additionally, SSE was found to decrease RANKL-induced actin ring formation, which is required for bone resorption activity. Taken together, our results suggest that SSE acts as a RANKL-induced osteoclastogenesis inhibitor by suppression of ROS generation. This induces a remarkable suppression of the p38 and IκBα kinase pathways, thereby suppressing the gene expression of NFATc1 in osteoclast precursors.

Dangguijakyak-san, a medicinal herbal formula, protects dopaminergic neurons from 6-hydroxydopamine-induced neurotoxicity.

AIM OF THE STUDY: Dangguijakyak-san (DJS) is a multi-herbal formula that has long been widely used in traditional Oriental medicine to treat gynecologic disorders, including neurological symptoms. Recent clinical and experimental studies have reported aging and anti-neurodegenerative effects of DJS. In this study, we evaluated the neuroprotective effects of DJS on dopaminergic (DA) neurons damaged by 6-hydroxydopamine (6-OHDA). MATERIALS AND METHODS: To evaluate the protective effects of DJS, we analyzed viability in SH-SY5Y neuroblastoma cells and tyrosine hydroxylase (TH) staining in primary DA cells. To explore the possible mechanism(s) of neuroprotection, we assessed anti-oxidant activity by measuring reactive oxygen species (ROS) and glutathione (GSH) levels. To determine mitochondria-mediated apoptotic activity, we examined mitochondrial membrane potential, cytochrome c release, and caspase-3 activation. RESULTS: DJS at 0.05-5 µg/mL significantly protected SH-SY5Y cells from 6-OHDA toxicity, dose-dependently, and attenuated 6-OHDA damage in primary DA cells. DJS reduced 6-OHDA-induced intracellular ROS production and GSH depletion and inhibited mitochondrial membrane instability, cytosolic cytochrome c release, and caspase-3 activation. CONCLUSIONS: These results demonstrate that DJS has neuroprotective effects in DA neurons against 6-OHDA-induced toxicity through anti-oxidant and anti-mitochondrial-mediated apoptotic activities.

Protective effect of Cyperi rhizoma against 6-hydroxydopamine-induced neuronal damage.

Cyperi rhizoma, the rhizome of Cyperus rotundus L. (Family Cyperaceae), is a well-known functional food and traditional herbal medicine in Korea. It has been reported that Cyperi rhizoma has antioxidant and free radical scavenging activities that play a major role in protection of neurodegenerative disorders, such as Parkinson's disease (PD). In the present study, the neuroprotective effects of a water extract of Cyperi rhizoma (CRE) against 6-hydroxydopamine (6-OHDA)-induced neuronal damage were evaluated in an experimental model of PD. In PC12 cells, CRE showed a significant protective effect on cell viability at 50 and 100 microg/mL. CRE inhibited generation of reactive oxygen species and nitric oxide, reduction of mitochondrial membrane potential, and caspase-3 activity, which were induced by 6-OHDA. CRE also showed a significant protective effect against damage to dopaminergic neurons in primary mesencephalic culture. These results suggest that CRE has neuroprotective effects against 6-OHDA-induced toxicity through antioxidant and anti-apoptotic activities in an in vitro PD model.

Therapeutic effects of Chiljehyangbuhwan on primary dysmenorrhea: a randomized, double blind, placebo-controlled study.

OBJECTIVE: This clinical study was conducted to investigate the efficacy and safety of an oriental herbal medicine native to Korea, Chiljehyangbuhwan, in treating primary dysmenorrhea. DESIGN AND SETTING: A total of 100 primary dysmenorrhea patients who visited Kyung Hee University Korean Oriental Medicine Hospital between July 19 2004 and August 27 2004 were recruited. Secondary or drug-related dysmenorrhea was screened out through interviews and examination. The patients were grouped by fixed blocked randomization and administered either Chiljehyangbuhwan or placebo for one menstrual period in a double blind model. Visual Analogue Scale (VAS), Verbal Rating Scale (VRS), and Multidimensional Verbal Rating Scale (MVRS) were used to evaluate dysmenorrhea severity. A total of 71 patients who passed the screening test and remained to the last were divided into either placebo or Chiljehyangbuhwan group, and each were further split into smaller subsets (indication, non-indication, and unspecified group) according to Korean Oriental medical diagnosis. RESULTS: In the non-indication group, the placebo and Chiljehyangbuhwan group did not show significant difference in VAS, VRS, and MVRS scores before medication (1st VAS, 1st VRS, 1st MVRS), after medication (2nd VAS, 2nd VRS, 2nd MVRS), and in changes in scores before and after (DeltaVAS, DeltaVRS, DeltaMVRS). In the indication group, the placebo and Chiljehyangbuhwan group showed significant difference in change in VAS and MVRS scores (DeltaVAS and DeltaMVRS). No evidence of toxicity could be found, and no serious adverse reactions to Chiljehyangbuhwan were reported. CONCLUSION: The results suggest that Chiljehyangbuhwan is effective and safe in treating primary dysmenorrhea when prescribed appropriately under Korean Oriental medical diagnosis.

Inhibition of the PI3K-Akt/PKB survival pathway enhanced an ethanol extract of Rhus verniciflua Stokes-induced apoptosis via a mitochondrial pathway in AGS gastric cancer cell lines.

Rhus verniciflua Stokes (RVS) has been used in traditional Eastern Asia medicine for the treatment of gastritis and stomach cancer, although the mechanism for its biological activity remains to be elucidated. We previously established that an ethanol extract of RVS-induced G(1)-cell cycle arrest via accumulation of p27(Kip1) controlled by Skp2 reduction and apoptosis in AGS human gastric cancer cells. Here, we showed that an ethanol extract of RVS-induced apoptosis via caspase-9 activation (mitochondrial death pathway) is mediated by the loss of mitochondrial membrane potential (MMP, Deltapsi(m)) and the release of cytochrome C from the mitochondrial intermembrane space. In addition, an ethanol extract of RVS inactivated PI3K-Akt/PKB kinase in a time-dependent manner. Moreover, combined treatment of an ethanol extract of RVS and LY294002 (a PI3K inhibitor) markedly increased apoptosis compared to treatment with an ethanol extract of RVS alone. The role of PI3K-Akt/PKB in this process was confirmed by constitutive expression of inactive mutants of this kinase in AGS cells. Finally, siRNA-mediated knockdown of Akt/PKB expression resulted in a significant reduction in AGS cell proliferation. Taken together, these results suggest that an ethanol extract of RVS induces apoptosis via a mitochondrial death pathway in human gastric cancer cells, but not in normal cells, and inhibition of the PI3K-Akt/PKB pathway enhanced the mitochondrial death pathway.