Analgesic effects and metabolome analyses of laser- and electro-acupuncture combined therapies in paclitaxel-induced neuropathic pain model.

Introduction: Allodynia, which can be induced by paclitaxel administration, is the presence of pain as a result of a stimulus that does not usually provoke pain. Many studies have investigated the analgesic efficacy of acupuncture, including laser acupuncture (LA) and electroacupuncture (EA). Although pain-related diseases are relatively common, few studies have analyzed the analgesic effects and mechanisms of LA combined with EA. The purpose of this study was to investigate the therapeutic effect and mechanism of manual acupuncture (MA), EA, LA, and combined therapy (LA + EA) in a paclitaxel-induced allodynia rat model. Methods: A total of 56 rats were classified into eight groups: a normal (Nor, n = 7), a control (Con, n = 7), an MA (n = 7), an EA (n = 7), a 650-nm LA (650LA, n = 7), an 830-nm LA (830LA, n = 7), a 650-nm LA combined with EA (650LA + EA, n = 7), and an 830-nm LA combined with EA group (830LA + EA, n = 7). Allodynia was induced by intraperitoneal injection of 2 mg/kg of paclitaxel every other day for a total of four times except the Nor group. Acupuncture treatments were conducted at the points of Jungwan (CV12) and Joksamni (ST36) once every other day for 6 min, for a total of nine times. Withdrawal response reaction times and force intensity of the foot were measured before the start of the experiment, after the 4th paclitaxel administration (day 8), and after the 9th and last treatment (day 15). On the 16th day, mRNA and protein expression in the spinal nerves was assessed, and a metabolome analysis of the animals' feces was performed. Results and discussion: Our analyses show that 650LA + EA treatment resulted in an upregulation of protein expression related to pain relief and nerve regeneration, whereas 830LA + EA treatment led to significant changes in metabolomes. This study demonstrates that a combination treatment of EA and LA can suppress allodynia and promote upregulation of protein expression related to nerve regeneration and is effective in changing the intestinal microbiome. Further large-scale research is required to assess the exact mechanism underlying the therapeutic effect of this combination treatment in pain-related diseases.

Grifola frondosa Extract Containing Bioactive Components Blocks Skin Fibroblastic Inflammation and Cytotoxicity Caused by Endocrine Disrupting Chemical, Bisphenol A.

Grifola frondosa (GF), a species of Basidiomycotina, is widely distributed across Asia and has been used as an immunomodulatory, anti-bacterial, and anti-cancer agent. In the present study, the pharmacological activity of the GF extract against an ecotoxicological industrial chemical, bisphenol A (BPA) in normal human dermal fibroblasts (NHDFs), was investigated. GF extract containing naringin, hesperidin, chlorogenic acid, and kaempferol showed an inhibitory effect on cell death and inflammation induced by BPA in the NHDFs. For the cell death caused by BPA, GF extract inhibited the production of reactive oxygen species responsible for the unique activation of the extracellular signal-regulated kinase. In addition, GF extract attenuated the expression of apoptosis-related proteins (Bax, Bcl-2, and cleaved caspase-3) and the pro-inflammatory cytokine IL-1ß by the suppression of the redox-sensitive transcription factor, nuclear factor-kappa B (NF-κB) in BPA-treated NHDFs. For the inflammation triggered by BPA, GF extract blocked the inflammasome-mediated caspase-1 activation that leads to the secretion of IL-1ß protein. These results indicate that the GF extract is a functional antioxidant that prevents skin fibroblastic pyroptosis induced by BPA.

Metabolomic Approach for Discrimination of Cultivation Age and Ripening Stage in Ginseng Berry Using Gas Chromatography-Mass Spectrometry.

The purpose of this study was to analyze metabolic differences of ginseng berries according to cultivation age and ripening stage using gas chromatography-mass spectrometry (GC-MS)-based metabolomics method. Ginseng berries were harvested every week during five different ripening stages of three-year-old and four-year-old ginseng. Using identified metabolites, a random forest machine learning approach was applied to obtain predictive models for the classification of cultivation age or ripening stage. Principal component analysis (PCA) score plot showed a clear separation by ripening stage, indicating that continuous metabolic changes occurred until the fifth ripening stage. Three-year-old ginseng berries had higher levels of valine, glutamic acid, and tryptophan, but lower levels of lactic acid and galactose than four-year-old ginseng berries at fully ripened stage. Metabolic pathways affected by different cultivation age were involved in amino acid metabolism pathways. A random forest machine learning approach extracted some important metabolites for predicting cultivation age or ripening stage with low error rate. This study demonstrates that different cultivation ages or ripening stages of ginseng berry can be successfully discriminated using a GC-MS-based metabolomic approach together with random forest analysis.

Korean Traditional Medicine (Jakyakgamcho-tang) Ameliorates Colitis by Regulating Gut Microbiota.

The objective of this study was to examine the anti-colitis activity of Jakyakgamcho-tang (JGT) in dextran sulfate sodium (DSS)-induced colitis and explore changes of the gut microbial community using 16S rRNA amplicon sequencing and metabolomics approaches. It was found that treatment with JGT or 5-aminosalicylic acid (5-ASA) alleviated the severity of colitis symptoms by suppressing inflammatory cytokine levels of IL-6, IL-12, and IFN-γ. The non-metric multidimensional scaling analysis of gut microbiome revealed that JGT groups were clearly separated from the DSS group, suggesting that JGT administration altered gut microbiota. The operational taxonomic units (OTUs) that were decreased by DSS but increased by JGT include Akkermansia and Allobaculum. On the other hand, OTUs that were increased by DSS but decreased by 5-ASA or JGT treatments include Bacteroidales S24-7, Ruminococcaceae, and Rikenellaceae, and the genera Bacteroides, Parabacteroides, Oscillospira, and Coprobacillus. After JGT administration, the metabolites, including most amino acids and lactic acid that were altered by colitis induction, became similar to those of the control group. This study demonstrates that JGT might have potential to effectively treat colitis by restoring dysbiosis of gut microbiota and host metabolites.

Metabolite Markers for Characterizing Sasang Constitution Type through GC-MS and 1H NMR-Based Metabolomics Study.

Sasang constitutional medicine classifies human beings into four types based on their physical and psychological characteristics. Despite its potential value in achieving personalized medicine, the diagnosis of sasang constitution (SC) type is complex and subjective. In this study, gas chromatography-mass spectrometry and 1H nuclear magnetic resonance-based metabolic analyses were conducted to find maker metabolites in serum and urine according to different SC types. Although some samples were overlapped on orthogonal projection to latent structure discriminant analysis score plots, serum samples showed separation between different SC types. Levels of lactate, glutamate, triglyceride, and fatty acids in serum and glycolic acid in urine of Tae-Eum type were higher than those of So-Eum and So-Yang type. Fatty acids, triglyceride, and lactate levels were found to be metabolites related to body mass index, indicating that marker metabolites for the diagnosis of SC type could be associated with obese. However, Tae-Eum type showed higher lactate levels in serum than So-Yang type for both normal weight and overweight groups, suggesting that the contents of serum lactate might be dependent on the SC type regardless of body weight. These results suggest that metabolomics analysis could be used to determine SC type.

GC/MS-Based Metabolomics Approach to Evaluate the Effect of Jackyakgamcho-Tang on Acute Colitis.

The objective of this study was to examine the effects of Jackyakgamcho-tang (JGT) on acute colitis. GC/MS-based metabolomics and NGS-based metagenomics were applied to investigate the alteration of metabolites and microbiota in an acute colitis model. The severity of acute colitis symptoms was alleviated by JGT treatment. Induction of colitis and JGT treatment changed compositions of gut microbiota and inflammatory cytokine levels (TNF-α and IL-6). They also substantially change metabolites (i.e., lactic acid, linoleic acid, monostearin, and palmitoylglycerol). In addition, some clear correlations were observed among metabolites, cytokine, and microbiota. This study highlights the applicability of metabolomics and metagenomics study for evaluating anti-inflammatory effects of a new functional herbal medicine as a therapeutic agent for acute colitis.

GC/MS-Based Metabolomics Reveals Biomarkers in Asthma Murine Model Modulated by Opuntia humifusa.

GC/MS coupled with multivariate statistical analysis was performed to identify marker metabolites in serum of mice after healing ovalbumin- (OVA-) induced asthma using Opuntia humifusa. Principal component analysis (PCA) score plot showed separation among groups, with metabolite profiles of serum showing differences according to various treatments for the asthma murine model. Levels of stearic acid and arachidic acid were significantly lower in the serum from OVA-induced group than those from the control group. Dexamethasone treatment group was characterized by higher serum levels of urea, myristic acid, and palmitic acid along with lower levels of aspartic acid compared to OVA-induced group. O. humifusa treatment mice groups showed dose-proportional higher levels of urea and glycerol than OVA-induced group. These results highlight that GC/MS-based metabolomics is a powerful technique for identifying molecular markers of asthma.

Intramuscular hematoma with motor weakness after trigger point injection: A case report.

RATIONALE: Although trigger point injection is known as an easy and low-risk procedure, it is contraindicated to patients with hemorrhagic disorders or who regularly take anticoagulants/antiplatelets. However, taking clopidogrel is not a defined contraindication to this low-risk procedure. PATIENT CONCERNS: The chief complaint of a 76-year old woman regularly taking clopidogrel was low back and left buttock pain which prolonged for several years. DIAGNOSES: The patient was diagnosed with L4-5 and L5-S1 spinal stenosis at the orthopedics department and was referred for lumbar spinal epidural steroid injection. INTERVENTION: She was treated with trigger point injection. OUTCOMES: Three hours after the injection, she complained motor weakness and pain in the injection area. A hematoma on left gluteus medium muscle was detected with ultrasonography and ultrasound-guided needle aspiration was accomplished to relieve the symptom. LESSONS: Trigger point injection for patients taking clopidogrel should be done with a caution to prevent such complication.

Saponins from the roots of Platycodon grandiflorum ameliorate high fat diet-induced non-alcoholic steatohepatitis.

Platycodon grandiflorum has been healthy effects due to its various nutritious compounds and is considered as a functional food. Platycodon grandiflorum root-derived saponins (CKS) have been reported to show a variety of effects including anti-inflammatory and anti-oxidative activity. Although CKS have been studied on various bioactivities, the inhibitory effect of CKS on non-alcoholic steatohepatitis (NASH) is not examined. In this study, the inhibitory effects on HFD-induced NASH by CKS were determined. CKS suppressed HFD-induced hepatic lipid peroxidation level, collagen deposition, pro-fibrogenic and pro-inflammatory cytokines expression. CKS treatment suppressed HFD-induced COX-2 expression via inhibition of NF-κB p65 nuclear translocation and IκBα degradation. CKS treatment restored HFD-reduced Nrf2-mediated antioxidant enzymes expression. Furthermore, CKS treatment reinstated HFD-reduced peroxisomal proliferator-activated receptor alpha (PPARα)-regulated acyl-coA oxidase and carnitine-palmitoyl-coA transferase-1 expression. These findings suggest that CKS reduces HFD-induced NASH by up-regulation of Nrf2-mediated anti-oxidant enzymes and PPARα-regulated fatty acid oxidation.

Renoprotective effect of Alpiniae oxyphyllae Fructus on ischemia/reperfusion-induced acute renal failure.

The present study was designed to examine whether water extract of Alpiniae oxyphyllae Fructus (AAO) has an effect on renal functional parameters in association with the expression of water channels and sodium potassium pump in ischemia/reperfusion-induced acute renal failure (ARF). Polyuria caused by down-regulation of renal AQP-2, 3 in the ischemia/reperfusion-induced ARF rats was markedly restored by administration of AAO (200 mg/kg/day p.o.) with restoring expression of AQP-2, 3 in the kidney. The expression of Na,K-ATPase α1 subunit was also restored in the ischemia/reperfusion-induced ARF rat by administration of AAO. The renal functional parameters including urinary sodium excretion, urinary osmolality, and solute-free reabsorption were also markedly restored in ischemia-ARF rats by administration of AAO. In histopathologic study, administration of AAO improved tubular damage such as necrosis of tubular segment. Ischemia/reperfusion-induced ARF decreased the expressions of AQP-2, 3, and Na,K-ATPase in renal medulla. However, administration of AAO markedly restored the expression levels of AQP-2, 3 and Na,K-ATPase. Taken together, the present study suggested that A. oxyphyllae ameliorates the urine concentration and renal functions in ischemia/reperfusion-induced ARF, through the restoring of AQP-2, 3 and Na,K-ATPase.

Reactivity of Fe/FeS nanoparticles: electrolyte composition effects on corrosion electrochemistry.

Zerovalent iron nanoparticles (Fe(0) NPs or nZVI) synthesized by reductive precipitation in aqueous solution (Fe/FeO) differ in composition and reactivity from the NPs obtained by reductive precipitation in the presence of a S-source such as dithionite (Fe/FeS). To compare the redox properties of these types of NPs under a range of environmentally relevant solution conditions, stationary powder disk electrodes (PDEs) made from Fe/FeO and Fe/FeS were characterized using a series of complementary electrochemical techniques: open-circuit chronopotentiometry (CP), linear polarization resistance (LPR), electrochemical impedance spectroscopy (EIS), and linear sweep voltammetry (LSV). The passive films on these materials equilibrate within minutes of first immersion and do not show further breakdown until >1 day of exposure. During this period, the potentials and currents measured by LPR and LSV suggest that Fe/FeS undergoes more rapid corrosion and is more strongly influence by solution chemical conditions than Fe/FeO. Chloride containing media were strongly activating and natural organic matter (NOM) was mildly passivating for both materials. These effects were also seen in the impedance data obtained by EIS, and equivalent circuit modeling of the electrodes composed of these powders suggested that the higher reactivity of Fe/FeS is due to greater abundance of defects in its passive film.

Berberine inhibits human colon cancer cell migration via AMP-activated protein kinase-mediated downregulation of integrin ß1 signaling.

Colon cancer is associated with a poor prognosis, motivating strategies to prevent its development. An encouraging preventative strategy is the use of nutraceuticals; however, scientific verification of therapeutic functions and mechanisms of biological activity are necessary for the acceptance of dietary supplements in cancer treatment. Berberine is a benzylisoquinoline alkaloid extracted from many kinds of medicinal plants that has been extensively used as a Chinese traditional medicine. Recently, berberine has been reported to possess antitumoral activities. Among the various cellular targets of berberine is AMP-activated protein kinase (AMPK), which regulates tumor progression and metastasis. However, the specific role of berberine-induced AMPK activation and its effects on the metastatic potential of colon cancer remain largely unknown. The present study investigated berberine-induced activation of AMPK and its effects on colon cancer cell migration. Berberine decreased the migration of SW480 and HCT116 cells. We found that berberine activated AMPK in human colon cancer cell lines. Notably, berberine-induced activation of AMPK reduced the integrin ß1 protein levels and decreased the phosphorylation of integrin ß1 signaling targets. Knockdown of AMPKα1 subunits using small interfering RNA significantly attenuated berberine-induced downregulation of integrin ß1 and inhibition of tumor cell migration. Collectively, our results suggest that berberine-induced AMPK activation inhibits the metastatic potential of colon cancer cells by decreasing integrin ß1 protein levels and downstream signaling.

Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced acute renal failure rats.

The kidneys play a central role in regulating water, ion composition and excretion of metabolic waste products in the urine. Cuscuta chinensis has been known as an important traditional Oriental medicine for the treatment of liver and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta chinensis (ACC) seeds has an effect on renal function parameters in ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of 250 mg/kg/day ACC showed that renal functional parameters including urinary excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free water reabsorption were significantly recovered in ischemia/reperfusion-induced ARF. Periodic acid Schiff staining showed that administration of ACC improved tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and immunohistological examinations, ischemia/reperfusion-induced ARF decreased the expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in the renal medulla. However, administration of ACC markedly incremented AQP 2, 3 and Na,K-ATPase expressions. Therefore, these data indicate that administration of ACC ameliorates regulation of the urine concentration and renal functions in rats with ischemia/reperfusion-induced ARF.

Hypotensive, hypolipidemic, and vascular protective effects of Morus alba L. in rats fed an atherogenic diet.

Morus alba L. has been used in traditional Chinese medicine and almost all parts of this plant are useful in cardiovascular, liver and spleen disorders. The present study was designed to investigate the inhibitory effect of a water extract from Morus alba L. (WMA) on vascular dysfunction in rat models fed a high fat and high cholesterol diet. Male rats were fed an atherogenic diet consisting of food with 7.5% cocoa butter and 1.25% cholesterol, with or without 100 or 200 mg/day/kg WMA, for 14 weeks. Chronic treatment with low (100 mg/kg/day) or high (200 mg/day/kg) doses of WMA markedly attenuated hypertension and the impairments of acetylcholine-induced relaxation of aortic rings in rats fed an atherogenic diet. WMA reduced intima/media thickness in rats fed an atherogenic diet. WMA improved plasma levels of triglyceride (TG) and augmented plasma levels of high-density lipoprotein (HDL) and plasma low-density lipoprotein (LDL), but did not affect blood glucose levels. Interestingly, WMA suppressed increased cell adhesion molecules such as E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) expression in the aorta. Taken together, these results suggested that Morus alba L. could improve an atherogenic diet-induced hypertension, hyperlipidemia, and vascular dysfunction through inhibition of cell adhesion molecules expression and induction of vascular relaxation.

Use of grape seed and its natural polyphenol extracts as a natural organic coagulant for removal of cationic dyes.

Natural organic coagulants (NOCs) such as chitosan and Moringa oleifera seeds have been extensively characterized for potential application in water treatment as an alternative to metal-based coagulants. However, the action of both chitosan and M. oleifera seeds is mainly restricted to anionic organic pollutants because of their cationic functional groups affording poor cationic pollutant coagulation by electrostatic repulsion. In this study, we employed ethanolic grape seed extract (GSE) and grape seed-derived polyphenols such as tannic acid and catechin in an effort to find novel NOCs showing stable anionic forms for removal of cationic organic pollutants. The target substances tested were malachite green (MG) and crystal violet (CV), both mutagenic cationic dyes. Polyphenol treatment induced fast decolorization followed by gradual floc formation concomitant with red or blue shifts in maximum absorbance wavelengths of the cationic dyes. Liquid chromatography analysis of flocs formed by polyphenols directly showed that initial supramolecular complexes attributed mainly to electrostatic attraction between polyphenol hydroxyphenyl groups and cationic dyes further progressed into stronger aggregates, leading to precipitation of dye-polyphenol complexes. Consistent with the results obtained using catechin and tannic acid, use of GSE also resulted in effective decolorization and coagulation of soluble MG and CV in aqueous solutions. Screening of several organic GSE components for NOC activity strongly suggested that natural polyphenols are the main organic ingredients causing MG and CV removal via gradual floc formation. The treatment by natural polyphenols and GSE decreased toxicity of MG- or CV-contaminated water.

The effect of sativan from Viola verecunda A. Gray on the expressions of matrix metalloproteinase-1 caused by ultraviolet irradiated cultured primary human skin fibroblasts.

Matrix metalloproteinases (MMPs) are a family of enzymes whose main function is degradation of the extracellular matrix. Matrix metalloproteinase-1 (MMP-1) degrades type I procollagen constituting the major structural component of the basement membrane and extra cellular membrane. The enzymatic activity is found to be elevated in photoaging. With the aim of finding novel MMP-1 inhibitors from natural products, 15 extracts of the Viola taxa, which are used as prescriptions for skin eruption treatment in traditional medicine, were screened for their inhibitory activities towards MMP-1. Among the 15 tested materials, the methanol extracts of Viola hondoensis W. BECKER et H. BOISS, Viola ibukiana MAKINO, Viola lactiflora NAKAI and Viola verecunda A. GRAY were potential inhibitory to MMP-1, and other Viola taxa showed a weak inhibitory effect at a concentration of 100 microg/ml. We investigated the effect of MMP-1 inhibitory of the solvent fractions of the same plants (Viola hondoensis, Viola ibukiana and Viola verecunda). Therefore, a strong inhibition was found in the ethylacetate fractions of Viola verecunda with inhibitory activity (>90%) at a concentration of 10 microg/ml. Here we investigated the effect of sativan isolated from the ethylacetate fractions of Viola verecunda on the expression of MMPs in UV-irradiated human skin fibroblasts in vitro. Sativan markedly reduced UV-induced MMP-1 expression at the protein levels in a dose-dependent manner. Our report is the first description for the ability of sativan to regulate UV-induced MMP-1 expression.