Electroacupuncture alleviates intestinal inflammation via a distinct neuro-immune signal pathway in the treatment of postoperative ileus.

BACKGROUND: The induction of intestinal inflammation as a result of abdominal surgery is an essential factor in postoperative ileus (POI) development. Electroacupuncture (EA) at ST36 has been demonstrated to relieve intestinal inflammation and restore gastrointestinal dysmotility in POI. This study aims to elucidate the neuroimmune pathway involved in the anti-inflammatory properties of EA in POI. METHODS: After intestinal manipulation (IM) was performed to induce POI, intestinal inflammation and motility were assessed 24 h post-IM, by evaluating gastrointestinal transit (GIT), cytokines expression, and leukocyte infiltration. Experimental surgery, pharmacological intervention, and genetic knockout mice were used to elucidate the neuroimmune mechanisms of EA. RESULTS: EA at ST36 significantly improved GIT and reduced the expression of pro-inflammatory cytokines and leukocyte infiltration in the intestinal muscularis following IM in mice. The anti-inflammatory effectiveness of EA treatment was abolished by sub-diaphragmatic vagotomy, whereas splenectomy did not hinder the anti-inflammatory benefits of EA treatment. The hexamethonium chloride (HEX) administration contributes to a notable reduction in the EA capacity to suppress inflammation and enhance motility dysfunction, and EA is ineffective in α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. CONCLUSIONS: EA at ST36 prevents intestinal inflammation and dysmotility through a neural circuit that requires vagal innervation but is independent of the spleen. Further findings revealed that the process involves enteric neurons mediating the vagal signal and requires the presence of α7nAChR. These findings suggest that utilizing EA at ST36 may represent a possible therapeutic approach for POI and other immune-related gastrointestinal diseases.

Inhibitory effects and mechanisms of insoluble humic acids on internal phosphorus release from the sediments.

Release of phosphorus (P) from the sediments plays a critical role in the eutrophication of aquatic environments. Humic acids (HA), as the main form of carbon storage in the sediments, has essential impacts on the biogeochemical cycle of phosphorus in aquatic systems. Nevertheless, previous studies mainly concentrated on the competitive adsorption of HA solution and P on metal oxides and soils, with little attention paid to the effects of insoluble humic acids (IHA) on P sorption by and release from the sediments. Herein, an investigation on the rivers and lakes in Sichuan Province, China, found that there was a significantly positive correlation between the maximum P adsorption capacity (Qmax) of sediments and IHA contents (p < 0.01), but a significantly negative correlation between the zero equilibrium P concentration (EPC0) and IHA concentrations (p < 0.01). This indicated that IHA might have an inhibitory effect on the release of P from the sediments, which was verified by batch adsorption experiments and static incubation experiments. Adsorption experiments indicated that IHA can promote P adsorption by sediments. With the increase of IHA addition (from 0 to 20 mg/g) in the sediments, Qmax of sediments increased (from 0.516 to 0.911 mg/g), while EPC0 decreased greatly (from 0.264 to 0.005 mg/L). Increases in Fe (Ⅲ) bound-P, Al bound-P and humic bound-P caused by IHA were responsible for this promoting effect. Incubation experiments illustrated that IHA addition can efficiently inhibit P release from the sediments. After 32 days incubation, P concentration in the overlying water of control group (without IHA addition) was 0.651 mg/L, which was 13.29-40.69 times higher than those (0.016-0.049 mg/L) in the test groups (with 5 %-20 % IHA addition). The analysis of P species in sediments showed that transformation from loosely adsorbed-P and Fe (Ⅲ) bound-P to Al bound-P and humic bound-P was responsible for this inhibition of P release by IHA. This study demonstrated that IHA, differing from readily degradable or dissolved organic matter, have great inhibitory effects on internal P release, which provided a novel insight into the association between carbon burial and internal P release and even the management of water eutrophication.

Network pharmacology: a bright guiding light on the way to explore the personalized precise medication of traditional Chinese medicine.

Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using "TCM network pharmacology" and "network pharmacology" as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.

Disruption of serotonin biosynthesis increases resistance to striped stem borer without changing innate defense response in rice.

Striped stem borer (SSB) is one of the most damaging pests in rice production worldwide. Previously, we preliminarily demonstrated that indica rice Jiazhe LM, an OsT5H (encoding tryptamine-5-hydroxylase) knockout mutant deficient in serotonin, had increased resistance to SSB as compared with its wildtype parent Jiazhe B. However, the full scenario of SSB resistance and the underlying mechanism remain unknown. In this study, we first demonstrated that the OsT5H knockout could generally increase rice resistance to SSB and then proved that the OsT5H knockout does not disrupt the innate defense response of rice plants to SSB infestation, that is, OsT5H knockout mutations neither had significant effect on the transcriptional response of defense genes upon SSB infestation, nor the profile of defense related metabolites and plant hormones, such as lignin, salicylic acid, jasmonic acid, and abscisic acid, nor the activity of reactive oxygen species (ROS) scavenging enzymes and the ROS contents. We then demonstrated that supplementation of serotonin promoted SSB growth and performance in artificial diet feeding experiments. We observed that SSB larvae feeding on Jiazhe B had serotonin 1.72- to 2.30-fold that of those feeding on Jiazhe LM at the whole body level, and more than 3.31 and 1.84 times in the hemolymph and head, respectively. Further studies showed that the expression of genes involved in serotonin biosynthesis and transport was ~88.1% greater in SSB larvae feeding on Jiahze LM than those feeding on Jiazhe B. These observations indicated that SSB increases serotonin synthesis when feeding on serotonin deficient rice but is unable to fully compensate the dietary serotonin deficiency. Put together, the present study strongly suggests that it is the deficiency of serotonin, not the secondary effect of OsT5H knockout on innate defense response confers the SSB resistance in rice, which implies that reducing serotonin level, particularly through inhibition of its inductive synthesis upon SSB damage, could be an efficient strategy for breeding SSB resistant varieties.

Wild vs. Cultivated Zingiber striolatum Diels: Nutritional and Biological Activity Differences.

Compositional, functional, and nutritional properties are important for the use-value assessments of wild and cultivated edible plants. The aim of this study was to compare the nutritional composition, bioactive compounds, volatile compounds, and potential biological activities of cultivated and wild Zingiber striolatum. Various substances, such as soluble sugars, mineral elements, vitamins, total phenolics, total flavonoids, and volatiles, were measured and analyzed using UV spectrophotometry, ICP-OES, HPLC, and GC-MS methods. The antioxidant capacity of a methanol extract of Z. striolatum, as well as the hypoglycemic abilities of its ethanol and water extracts, were tested. The results showed that the contents of soluble sugar, soluble protein, and total saponin in the cultivated samples were higher, while the wild samples contained higher amounts of K, Na, Se, vitamin C, and total amino acids. The cultivated Z. striolatum also showed a higher antioxidant potential, while the wild Z. striolatum exhibited a better hypoglycemic activity. Thirty-three volatile compounds were identified using GC-MS in two plants, with esters and hydrocarbons being the main volatile compounds. This study demonstrated that both cultivated and wild Z. striolatum have a good nutritional value and biological activity, and can be used as a source of nutritional supplementation or even in medication.

Taraxasterol alleviates fatty acid-induced lipid deposition in calf hepatocytes by decreasing ROS production and endoplasmic reticulum stress.

Increased concentrations of free fatty acids (FFAs) induce reactive oxygen species (ROSs) generation and endoplasmic reticulum (ER) stress, thus, increasing the risk of fatty liver in dairy cows during the periparturient period. In non-ruminants, Taraxasterol (Tara; a pentacyclic triterpenoid found in medicinal plants) plays an important role in anti-inflammatory and antioxidant reactions. Whether Tara can alleviate or prevent fatty liver in ruminants is unknown. We addressed whether Tara supply could dampen lipid accumulation, ROSs production, and ER stress caused by FFAs in calf hepatocytes. Primary calf hepatocytes were isolated from five healthy calves (1 d old, female, 30-40 kg, fasting, rectal temperature 38.7-39.7 °C). In the first experiment, hepatocytes were incubated with various concentrations of Tara (2.5, 5, and 10 µg/mL) for 12 h prior to the 1.2-mM FFAs challenge. Results indicated that the level of ROSs was lowest with 5 µg/mL Tara. Thus, to further characterize the molecular mechanisms whereby Tara protects from FFAs-induced lipid deposition in calf hepatocytes, we performed incubations with 5 µg/mL Tara for 12 h prior to a 1.2-mM FFAs challenge for an additional 12 h. Results indicated that 1.2-mM FFAs challenge increased mitochondrial membrane potential (MMP), enhanced expression of proteins and mRNA associated with ER stress (PERK, IRE1, GRP78, ATF6, and CHOP) and fatty acid synthesis (FASN, ACC1, and SREBP-1c), and ultimately led to increased lipid droplet synthesis. In contrast, Tara treatment alleviated these negative effects after 1.2-mM FFAs challenge. To determine whether Tara protects against FFAs-induced lipid droplet synthesis by alleviating oxidative stress, hepatocytes were treated with 5 µg/mL Tara for 22 h prior to H2O2 (440 µM) challenge for 2 h. Compared with H2O2 treatment alone, results revealed a marked decrease in ROSs, MMP, and protein abundance of ER stress (GRP78, ATF6, and CHOP) and lipid droplet synthesis in response to Tara prior to H2O2 challenge. Data suggested that the increase in mitochondrial ROSs production contributes to lipid accumulation in calf hepatocytes. Collectively, our in vitro data indicate that Tara alleviates fatty acid-induced lipid deposition. Further research is warranted to ascertain that Tara can be helpful in the therapeutic management of early lactating cows to control or alleviate excessive hepatic lipid deposition.

Fatty liver is a common occurrence in the early postpartum period, partly due to the large influx of fatty acids into the liver during adipose tissue lipolysis. Because there is a linkage between fatty acid metabolism, oxidative stress, and lipid deposition in hepatocytes of nonruminant animals, we evaluated the potential therapeutic roles of Taraxasterol on reactive oxygen species and endoplasmic reticulum (ER) stress in vitro. This compound found in medicinal plants alleviated oxidative and ER stress and reduced lipid accumulation. Thus, it may represent a novel therapeutic tool for the management of dairy cows around parturition.

Exploring the Mechanisms and Molecular Targets of Taohong Siwu Decoction for the Treatment of Androgenetic Alopecia Based on Network Analysis and Molecular Docking.

Purpose: Taohong Siwu decoction (THSWD) is traditionally used to treat androgenic alopecia (AGA) in clinical practice of traditional Chinese medicine. This study used a network pharmacology approach to elucidate the molecular mechanism governing the effect of THSWD on AGA. Materials and Methods: The major active components and their corresponding targets of THSWD were screened. AGA-related targets were obtained by analyzing the differentially expressed genes between AGA patients and healthy individuals. The protein-protein interaction networks of putative targets of THSWD and AGA-related targets were visualized and merged to identify the candidate targets for THSWD against AGA. Gene ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for core targets were performed. Finally, the key effective components and core targets screened were verified by molecular docking. Results: In this study, 69 compounds and 202 compound targets of THSWD, as well as 1158 disease targets, were screened. Forty-five interactive targets were identified for constructing the "ingredient-targets" network. The functional annotations of target genes were found to be related to oxidative stress, reactive oxygen species, and hydrogen peroxide. Pathways involved in the treatment of AGA included apoptosis and PI3K-AKT signaling pathways. The luteolin, quercetin, kaempferol, baicalein, and beta-carotene were identified as the vital active compounds, and AKT1, TP53, JUN, CASP3 and MYC were considered as the core targets. Assessment of molecular docking revealed that these active compounds and targets had good-binding interactions. Conclusion: The results indicated that the effects of THSWD against AGA may be related to anti-inflammation and anti-oxidation properties of the compounds through the specific biological processes and the related pathways.

Protective Effects of Facilitated Removal of Blood Alcohol and Acetaldehyde Against Liver Injury in Animal Models Fed Alcohol and Anti-HIV Drugs.

BACKGROUND: We previously developed enzyme nanoparticles (ENP) of alcohol metabolism. This study was to evaluate protective effects of facilitated removal of blood alcohol and/or acetaldehyde on anti-HIV drugs and alcohol-induced liver injuries. METHODS: ENP were prepared for degrading alcohol completely (ENP1) or partially into acetaldehyde (ENP2), which were applied to mice of acute binge or chronic-binge alcohol feeding in the presence of antivirals (ritonavir and lopinavir). Liver pathologies were examined to assess the protective effects of ENP. RESULTS: In the acute model, ENP1 and ENP2 reduced the blood alcohol concentration (BAC) by 41 and 32%, respectively, within 4 hr, whereas in control without ENP, BAC was reduced only by 15%. Blood acetaldehyde concentration (BADC) was increased by 39% in alcohol-fed mice treated with ENP2 comparing to control. No significant effects of the anti-HIV drugs on BAC or BADC were observed. Plasma alanine aminotransferase (ALT) and expression of liver TNF-α were both significantly increased in the alcohol-fed mice, which were normalized by ENP1. In the presence of the antivirals, ALT was partially reduced by ENP1 or ENP2. In the chronic model, inflammation, fatty liver, and ALT were increased, which were deteriorated by the antivirals. ENP1 partially reduced BAC, BADC, ALT, and expression of inflammation markers of TNF-α, F4/80, and IL-6 and lipogenic factors of ACC, LXRα, and SREBP1. ENP2 reduced BAC without significant effects on ALT, inflammation, or lipogenesis. Antivirals and alcohol synergistically increased expression of organelle stress markers of CHOP, sXBP-1, ATF6, and GCP60. ENP1 reduced BAC, CHOP, and sXbp-1. However, no effects of ENP1 were found on ATF6 or GCP60. CONCLUSIONS: Removal of blood alcohol and acetaldehyde by the ENP protects the liver against alcoholic injuries, and the protection is less effective in chronic alcohol and antiviral feeding due to additional drug-induced organelle stresses.

Anxiolytic-like behavioural effects of head electroacupuncture in rats susceptible to stress.

AIM: To evaluate the behavioural effects of head electroacupuncture (EA) using the Holtzman rat model, a genetic strain showing susceptibility to stress-evoked helplessness. METHODS: Putative anxiolytic and antidepressant behavioural effects of head EA were investigated using the light-dark and forced swim tests, respectively. The open field test was used to investigate motor activity. A total of 28 rats were used in two experiments, each with two groups (n=7 rats each). Rats were restrained and randomised to handling only (control) or 2Hz EA on the midline head anteriorly (at Yintang) and posteriorly (at GV20) for 3 days (experiment 1) or 4 days (experiment 2). RESULTS: One day of EA did not modify behaviour in any of the tests (p>0.1); however, 2 days of 2 Hz EA treatment to the head had anxiolytic-like effects, as indicated by an improvement in ambulatory time and average velocity in the light-dark test (experiment 2). Relative to the control group, the EA group demonstrated greater ambulatory time (37.0±3.7 vs 25.2±3.6 s, p<0.05) and lower average velocity (2.73±0.06 vs 3.08±0.13 cm/s, p<0.05). However, EA treatment had no significant effects on the open field and forced swim tests in either experiment. CONCLUSIONS: Two days of EA treatment using 2 Hz pulsating electrical current at midline anterior and posterior acupuncture points on the head induces behavioural effects suggestive of anxiolysis.

Scalp acupuncture treatment protocol for anxiety disorders: a case report.

Anxiety disorders are among the most common psychiatric illnesses, and acupuncture treatment is widely accepted in the clinic without the side effects seen from various medications. We designed a scalp acupuncture treatment protocol by locating two new stimulation areas. The area one is between Yintang (M-HN-3) and Shangxing (DU-23) and Shenting (DU-24), and the area two is between Taiyang (M-HN-9) and Tianchong (GB-9) and Shuaigu (GB-8). By stimulating these two areas with high-frequency continuous electric waves, remarkable immediate and long-term effects for anxiety disorders have been observed in our practice. The first case was a 70-year-old male with general anxiety disorder (GAD) and panic attacks at night. The scalp acupuncture treatment protocol was applied with electric stimulation for 45 minutes once every week. After four sessions of acupuncture treatments, the patient reported that he did not have panic attacks at night and he had no feelings of anxiety during the day. Follow-up 4 weeks later confirmed that he did not have any episodes of panic attacks and he had no anxiety during the day since his last acupuncture treatment. The second case was a 35-year-old male who was diagnosed with posttraumatic stress disorder (PTSD) with a history of providing frontline trauma care as a Combat Medics from the Iraq combat field. He also had 21 broken bones and multiple concussions from his time in the battlefield. He had symptoms of severe anxiety, insomnia, nightmares with flashbacks, irritability, and bad temper. He also had chest pain, back pain, and joint pain due to injuries. The above treatment protocol was performed with 30 minutes of electric stimulation each time in combination with body acupuncture for pain management. After weekly acupuncture treatment for the first two visits, the patient reported that he felt less anxious and that his sleep was getting better with fewer nightmares. After six sessions of acupuncture treatments, the patient completely recovered from PTSD, went back to work, and now lives a healthy and happy family life. The above cases and clinical observation show that the scalp acupuncture treatment protocol with electric stimulation has a significant clinic outcome for GAD, panic disorder and PTSD. The possible mechanism of action of scalp acupuncture on anxiety disorder may be related to overlapping modulatory effects on the cortical structures (orbitofrontal cortex [OFC]) and medial prefrontal cortex [mPFC]) and subcortical/limbic regions (amygdala and hippocampus), and biochemical effect of acupuncture through immunohistochemistry (norepinephrine, serotonin) performed directly to the brain tissue for anxiety disorders.

Cytotoxic triterpenesaponins from Ilex pubescens.

Two new triterpenesaponins, ilexsaponins G and H (1 and 2), together with six known triterpenesaponins (3-8), were isolated from the roots of Ilex pubescens. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Those compounds showed inhibitory activities against two human colorectal cancer cell lines HCT 116 and HT-29.

Study on intestinal absorption and pharmacokinetic characterization of diester diterpenoid alkaloids in precipitation derived from fuzi-gancao herb-pair decoction for its potential interaction mechanism investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconitum carmichaelii Debx. (Fuzi in Chinese) has been widely clinically used to treat heart failure and rheumatism. Whereas its serious toxicity, Radix et Rhizoma Glycyrrhizae (Gancao in Chinese) was combined with it as traditional Chinese medicine (TCM) herb-pair for toxicity reduction and pharmacological effect improvement. Though some previous viewpoints about that has been reported, the underlying interaction mechanism of two herbs remain unknown and definitely worthy of investigating. AIM OF STUDY: In present study, we focus on Fuzi-Gancao herb-pair precipitation (FGP), considering it related to the compatibility mechanism of Fuzi-Gancao herb-pair. The intestinal absorption and pharmacokinetic characters of 3 diester diterpenoid alkaloids in the precipitation were investigated. MATERIALS AND METHODS: Both everted gut sac model and in situ single-pass intestinal perfusion model were used to investigate rat small intestinal permeability and transport mechanism of aconitine, hypaconitine and mesaconitine. Moreover, by means of determination of the plasma concentration, the pharmacokinetic characters of 3 alkaloid compounds in rats have been developed. RESULTS: In everted gut sac permeability experiment, the permeability of hypaconitine appeared best in ileum. Furthermore, their uptakes were increased in the presence of P-glycoprotein (P-gp) inhibitors. In situ single-pass intestinal perfusion uptake experiment, results revealed that the transport mechanism may fit the active transport mechanism. And 3 alkaloids in FPG could be absorbed well in rats, fitting 2-compartment model with 1(st) order absorption and lag time. CONCLUSIONS: Our results in present study indicated that 3 diester diterpenoid alkaloids in FGP could be dissolved out in gastrointestinal tract firstly and then absorbed in blood after oral administration, which could result in prolonging their mean residence time and adding their absorbed doses, avoiding dose dumping. The current study has significant enlightenments for further investigation on the interaction mechanisms of other acid-base herb-pairs as well as Fuzi-Gancao herb-pair.

Three new triterpenoid saponins from Ilex pubescens.

Three new triterpene saponins, ilexsaponins D-F (1-3), were isolated from the roots of Ilex pubescens. Their structures were elucidated as 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinopyranosyl urs-12,18-diene-24,28-dioic acid 28-O-ß-D-glucopyranoside (1), 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinopyranosyl urs-12,18-diene-24,28-dioic acid (2), and 3-O-ß-D-glucopyranosyl(1 → 3)-α-L-arabinoyranosyl-30-hydroxyurs-12,19-diene-24,28-dioic acid 28-O-ß-D-glucopyranoside (3) on the basis of the chemical and spectroscopic evidence.

Cytotoxic triterpene saponins from Clematis mandshurica.

Two new triterpene saponins, mandshunosides A and B (1 and 2), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis products. Compounds 1 and 2 showed inhibitory activities against two colorectal human cancer cells HCT 116 (IC50 2.1 µM for 1 and 2.5 µM for 2) and HT-29 (IC50 3.7 µM for 1 and 3.3 µM for 2).

[Studies on the chemical constituents of the flowers of Bupleurum chinese].

OBJECTIVE: To study the chemical constituents of the flowers of Bupleurum chinese. METHODS: The compounds were separated by column chromatography with silica gel. Their structures were identified by spectral methods and chemical analysis. RESULTS: Five compounds were isolated and identified as 8-(3',6'-dimethoxy)-4,5-cyclohexadiene-(delta11,12-dioxide-methylene) -dense-dihydrogen-isocoumarin(I), quercetin(II), rutin(III), calcifenol (IV), isorhamnetin (V). CONCLUSION: Compounds I and IV are obtained from the genus for the first time. Compound I is a new compound.