Caragana sinica (Buc'hoz) Rehd. (jin ji er) polysaccharide regulates the immune function and intestinal microbiota of cyclophosphamide (CTX) induced immunosuppressed mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Caragana sinica (Buc'hoz) Rehd. is a plant widely grown in Yunnan, China, for both medicinal and edible purposes. The "National Compilation of Chinese Herbal Medicine" describes its nature as "slightly temperate and sweet". Caragana sinica is usually medicated with whole herbs, the main function is to replenish the kidneys and stop bleeding. Caragana sinica was used in folk medicine in Chuxiong, Yunnan, to treat deficiency colds, fatigue, fever, cough, hypertension, and other diseases. AIM OF THE STUDY: This article investigates the structural characteristics of Caragana sinica polysaccharide (CSP) and explores its immune-regulatory activity and molecular biological mechanisms in cyclophosphamide-induced immunosuppressed mice, as well as its effects on intestinal bacteria. METHODS: With the water-extraction and alcohol-precipitation method, Caragana sinica polysaccharide were extracted, obtaining CSP by purification. A variety of methods and techniques have been used to analyze the chemical properties and structural characteristics of CSP. Immunosuppressive mice model was established through intraperitoneal injection of cyclophosphamide (CTX) to study the immune-regulatory effects and mechanisms of CSP. RESULTS: The data indicated that CSP is a neutral heteropolysaccharide mainly composed of arabinose and galactose. This article uses immunosuppressive mice induced by cyclophosphamide (CTX) as the model. The results showed that CSP can promote the immune function of CTX treated immunosuppressed mice and regulate the diversity and composition of intestinal microbiota. CSP can increase macrophage phagocytosis, NK cell killing activity, and lymphocyte proliferation activity. It can also repair the index and morphological damage of the thymus and spleen. And by binding to the TLR4 receptor, MyD88 was activated and interacted with TRAF6 to promote the transfer of NF-κB into the nucleus. Thereby promoting cytokine release and increasing the production of IL-1ß, IL-6, IL-10, TNF-α, IgA, and IgG in the serum. CSP also effectively alleviated the liver damage caused by CTX through antioxidant activity. Furthermore, CSP can dramatically affect the intestinal microbiota and the body's immunity by boosting the relative presence of Bacteroides and Verrucamicrobiota. CONCLUSIONS: Research results indicated that CSP can regulate the immune function of mice, providing a basis for developing CSP as a potential immune modulator and functional food.

Acupuncture modulates the functional connectivity among the subcortical nucleus and fronto-parietal network in adolescents with internet addiction.

BACKGROUND: Internet addiction (IA), recognized as a behavioral addiction, is emerging as a global public health problem. Acupuncture has been demonstrated to be effective in alleviating IA; however, the mechanism is not yet clear. To fill this knowledge gap, our study aimed to investigate the modulatory effects of acupuncture on the functional interactions among the addiction-related networks in adolescents with IA. METHODS: Thirty individuals with IA and thirty age- and sex-matched healthy control subjects (HCs) were recruited. Subjects with IA were given a 40-day acupuncture treatment, and resting-state functional magnetic resonance imaging (fMRI) data were collected before and after acupuncture sessions. HCs received no treatment and underwent one fMRI scan after enrollment. The intergroup differences in functional connectivity (FC) among the subcortical nucleus (SN) and fronto-parietal network (FPN) were compared between HCs and subjects with IA at baseline. Then, the intragroup FC differences between the pre- and post-treatment were analyzed in the IA group. A multiple linear regression model was further employed to fit the FC changes to symptom relief in the IA group. RESULTS: In comparison to HCs, subjects with IA exhibited significantly heightened FC within and between the SN and FPN at baseline. After 40 days of acupuncture treatment, the FC within the FPN and between the SN and FPN were significantly decreased in individuals with IA. Symptom improvement in subjects with IA was well fitted by the decrease in FC between the left midbrain and ventral prefrontal cortex and between the left thalamus and ventral anterior prefrontal cortex. CONCLUSION: These findings confirmed the modulatory effects of acupuncture on the aberrant functional interactions among the SN and FPN, which may partly reflect the neurophysiological mechanism of acupuncture for IA.

The potential mechanism of qinghua quyu jianpi decoction in the treatment of ulcerative colitis based on network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic and recurrent inflammation of the gastrointestinal tract. Following the idea of herbal property and compatibility, a traditional Chinese medicine (TCM) formula consists of a number of TCM herbs. Qinghua Quyu Jianpi Decoction (QQJD) has been clinically proven to be effective in treating UC, however, its therapeutic mechanism has not been fully elucidated. AIM OF STUDY: Here, we used network pharmacology analysis and ultra-performance liquid chromatography-tandem mass spectrometry to predict the mechanism of action of QQJD, and then validated our predictions through in vivo and in vitro experiments. MATERIALS AND METHODS: First, based on a number of datasets, relationship network diagrams between QQJD and UC were created. The target network for the QQJD-UC intersection genes was then built, and KEGG analysis was carried out to identify a potential pharmacological mechanism. Finally, the results of the previous prediction were validated in dextran sulfate sodium salt (DSS) induced UC mice and a cellular inflammatory model. RESULTS: Network pharmacology results suggested that QQJD may play a role in repairing intestinal mucosa by activating Wnt pathway. In vivo experiments have shown that QQJD can significantly reduce weight loss, disease activity index (DAI) score, improve colon length, and effectively repair the tissue morphology of UC mice. In addition, we also found that QQJD can activate the Wnt pathway to promote epithelial cell renewal, reduce apoptosis, and repair the mucosal barrier. To further understand how QQJD promotes cell proliferation in DSS-induced Caco-2 cells, we performed a study in vitro experiment. We were surprised to find that QQJD activated the Wnt pathway by inducing nuclear translocation of ß-catenin, accelerating the cell cycle and promoting cell proliferation in vitro. CONCLUSION: Taken together, network pharmacology and experiments showed that QQJD achieves mucosal healing and restores the colonic epithelium barrier by activating Wnt/ß-catenin signaling, regulating cell cycle progression, and promoting the proliferation of epithelial cells.

Antibacterial and antibiofilm potential of Lacticaseibacillus rhamnosus YT and its cell-surface extract.

BACKGROUND: Foodborne pathogens and spoilage bacteria survived in the biofilm pose a serious threat to food safety and human health. It is urgent to find safe and effective methods to control the planktonic bacteria as well as the biofilm formation. Substances with antibacterial and antibiofilm activity found in lactic acid bacteria were mainly metabolites secreted in the cell-free supernatant. Previously, Lacticaseibacillus rhamnosus YT was isolated because its cell pellets displayed distinguished antibacterial activity under neutral conditions. This study aimed to investigate the antibacterial and antibiofilm properties of the L. rhamnosus YT cells and its crude cell-surface extract. RESULTS: The antibacterial activity of the L. rhamnosus YT cells constantly increased with cells growth and reached the peak value after the cells grew into stationary phase. After cocultivation with the L. rhamnosus YT cells, the biofilm formation of B. subtilis and S. enterica was reduced. The antibacterial activity of the L. rhamnosus YT cells was varied along with various culture conditions (carbon sources, nitrogen sources, medium pH and cultural temperatures) and the antibacterial intensity (antibacterial activity per cell) was disproportional to the biomass. Furthermore, the cell-surface extract was isolated and displayed broad antimicrobial spectrum with a bacteriostatic mode of action. The antibiofilm activity of the extract was concentration-dependent. In addition, the extract was stable to physicochemical treatments (heat, pH and protease). The extract performed favorable emulsifying property which could reduce the water surface tension from 72.708 mN/m to 51.011 mN/m and the critical micelle concentration (CMC) value was 6.88 mg/mL. Besides, the extract was also able to emulsify hydrocarbon substrates with the emulsification, index (E24) ranged from 38.55% (for n-hexane) to 53.78% (for xylene). The E24 for xylene/extract emulsion was merely decreased by 5.77% after standing for 120 h. The main components of the extract were polysaccharide (684.63 µg/mL) and protein (120.79 µg/mL). CONCLUSION: The properties of the extract indicated that it might be a kind of biosurfactant. These data suggested that L. rhamnosus YT and the cell-surface extract could be used as an alternative antimicrobial and antibiofilm agent against foodborne pathogens and spoilage bacteria in food industry.

Preparation and characterization of antioxidant and pH-sensitive films based on arrowhead (Sagittaria sagittifolia) starch, κ-carrageenan and black chokeberry (Aronia melanocarpa) extract for monitoring spoilage of chicken wings.

In this study, we firstly developed an antioxidant and pH-sensitive film based on arrowhead starch (AS), κ-carrageenan (KC) and black chokeberry extract (BCE) and its physical and structural properties were investigated. We found BCE showed different colors in different pH solutions and incorporation with KC and BCE could significantly decrease light transmittance, increase thickness, elongation at break and pH-sensitive property of AS film. The results of structural property assay indicated that there were some intermolecular interactions between BCE and AS/KC in AS-KC-BCE films. Secondly, we investigated the rheological property of AS, AS-KC and AS-KC-BCE suspensions and found the suspensions showed an obvious shear-thinning behavior with high apparent viscosity. Finally, the functional properties of AS-KC-BCE films were investigated and AS-KC-BCE films showed strong scavenging activity on DPPH free radical and presented visible colour changes in response to the changes of the chicken wing qualities. The results suggest that AS-KC-BCE films can be used in active and intelligent packaging of food industry.

Transcriptome-phenotype matching analysis of how nitrogen sources influence Lacticaseibacillus rhamnosus tolerance to heat stress and oxidative stress.

BACKGROUND: Spray drying is the most cost-effective production method for lactic acid bacteria starters, but heat and oxidative stresses result in low survival rates. The heat stress and oxidative stress tolerance of Lacticaseibacillus rhamnosus cultured in tryptone-free MRS (NP-MRS) broth was much stronger than that in MRS or tryptone-free MRS broth supplemented with phenylalanine (Phe-MRS). Here, multiple transcriptome-phenotype matching was performed on cells cultured in NP-MRS, MRS and Phe-MRS broths to reveal the mechanism by which nitrogen sources influence L. rhamnosus tolerance to heat stress and oxidative stress. RESULTS: Compared with cells cultured in NP-MRS broth, 83 overlapping differentially expressed genes (DEGs) were downregulated by either tryptone or phenylalanine. The overlapping DEGs were mainly classified into carbohydrate metabolism and membrane transport pathways, which are often repressed by glucose during carbon catabolite repression (CCR). In the presence of glucose, the heat stress or oxidative stress tolerance of L. rhamnosus hsryfm 1301 was not strengthened by supplementation with secondary carbohydrates. Replacing glucose with mannose, fructose or ribose improved the heat stress and oxidative stress tolerance of L. rhamnosus hsryfm 1301 (5 to 46-fold). CONCLUSIONS: Alleviation of CCR might be a reason for the resistance of L. rhamnosus hsryfm 1301 to heat stress and oxidative stress in a low-nitrogen environment. The survival rate of L. rhamnosus during spray drying will hopefully be improved by relieving CCR. It is a new discovery that nitrogen sources influence CCR in L. rhamnosus.

Oligostilbenes from the seeds of Paeonia lactiflora as potent GLP-1 secretagogues targeting TGR5 receptor.

One unusual stilbene trimer-flavonoid hybrid, paeonilactiflobenoid (1), together with six known stilbenes (2-7) were isolated from the seeds of Paeonia lactiflora. The structure of 1 was elucidated with the aid of HRESIMS, 1D and 2D NMR, [α]D spectroscopic data and ECD calculation. Compounds 2-7 showed stimulative effects on GLP-1 secretion with promoting rates of 79.8%-880.4% (25 µM) and 217.6%-1089.4% (50 µM), more potent than the positive control, oleoylethanolamide (250.2% at 50 µM). Moreover, compounds 4 and 6 exhibited agonistic activity on the G protein-coupled receptor (GPCR) TGR5 with stimulative ratios of 40.2% and 40.5% at 50 µM, and 54.2% and 49.1% at 100 µM, respectively. Docking study manifested that 6 well located in the catalytic pocket of TGR5 by hydrogen-bond and hydrophobic interactions. The GLP-1 promotion of 6 could be attenuated by IP3, Ca2+/CaMKII and MEK/ERK pathway inhibitors, suggesting that these pathways played important roles in GLP-1 secretion. Thus, stilbenes in peony seeds maybe regarded as potential GLP-1 secretagogues through TGR5-IP3-Ca2+/CaMKII-MEK/ERK pathways.

Influence of nitrogen sources on the tolerance of Lacticaseibacillus rhamnosus to heat stress and oxidative stress.

It has been found that 32 genes related to nitrogen source metabolism in Lacticaseibacillus rhamnosus are downregulated under both heat stress and oxidative stress. In this study, the influence of different nitrogen sources within the growth medium on the tolerance of L. rhamnosus to heat stress and oxidative stress was investigated. Tryptone-free MRS was found to enhance the tolerance of L. rhamnosus hsryfm 1301 to heat stress and oxidative stress during the whole growth period, and this result was universal for all L. rhamnosus species analyzed. The strongest strengthening effect occurred when the OD600 value reached 2.0, at which the survival rates under heat stress and oxidative stress increased 130-fold and 40-fold, respectively. After supplementing phenylalanine, isoleucine, glutamate, valine, histidine, or tryptophan into the tryptone-free MRS, the tolerance of L. rhamnosus to heat stress and oxidative stress exhibited a sharp drop. The spray drying survival rate of L. rhamnosus hsryfm 1301 cultured in the tryptone-free MRS rose to 75% (from 30%), and the spray dried powder also performed better in the experimentally simulated gastrointestinal digestion. These results showed that decreasing the intake of amino acids is an important mechanism for L. rhamnosus to tolerate heat stress and oxidative stress. When L. rhamnosus is cultured for spray drying, the concentration of the nitrogen source's components should be an important consideration.

The modulation of mRNA levels of MAOA by electroacupuncture and psychotherapy in patients with pathological internet use.

Objective: The aim of this study was to observe the efficacy of electroacupuncture (EA) and psychotherapy (PT) effect on the mental status, sleep quality and impulsive trait in patients with pathological internet use, and to observe the changes of Monoamine oxidase type A (MAOA) messenger Ribonucleic acid (mRNA) levels in each group. Methods: A total of 60 PIU patients were included for the present study. These patients were randomly divided into two groups: EA group and PT group. Baihui, Sishencong, Hegu, Neiguan, Shenmen, Taichong, Sanyinjiao and Xuanzhong were selected for acupuncture in the EA group, while group psychotherapy combined with individual psychotherapy was used for intervention in patients in the PT group. Young's Internet addiction Test (IAT), Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Barratt Impulse Scale (BIS-11) and Pittsburgh Sleep Quality Index (PSQI) were used to observe the severity of Internet addiction, mental status, sleep quality and impulsive trait of all patients at baseline and 40th days of treatment; and MAOA mRNA data were collected at baseline and 40th days of treatment. Results: Electroacupuncture and psychological intervention effectively reduced IAT, SAS, SDS, Y-BOCS, BIS and PSQI scores of PIU patients. After 40 days treatment, the MAOA expression of the PT group was increased, and there was no significant change in EA group. The correlation analysis indicated that IAT scores were positively correlated with SAS, SDS, Y-BOCS, BIS and PSQI at baseline. In addition, after treatment the EA group showed that the change in IAT scores was positively correlated with the change in Y-BOCS and BIS scores, and the PT group showed that the change in IAT scores was positively correlated with the change in SDS, BIS and PSQI scores. Conclusion: The present study showed that electroacupuncture and psychological intervention can improve severity of Internet addiction, mental status, sleep quality and impulsive trait of PIU patients. Simultaneously, neurobiological changes may be the underlying mechanisms of psychotherapy for internet additcion.

The Modulation of Reward and Habit Systems by Acupuncture in Adolescents with Internet Addiction.

Purpose: Acupuncture is an effective therapy for Internet addiction (IA). However, the underlying mechanisms of acupuncture in relieving compulsive Internet use remain unknown. Neuroimaging studies have demonstrated the role of the ventral striatum (VS) in the progress of IA; hence, the aim of this study was to explore the effects of acupuncture on the resting-state functional connectivity (rsFC) and relevant network of VS in IA. Methods: Twenty-seven IA individuals and 30 demographically matched healthy control subjects (HCs) were recruited in this study. We acquired the functional magnetic resonance imaging (fMRI) data in IA subjects before and after 40 days of acupuncture treatment. Seed-to-voxel and ROI-to-ROI analyses were applied to detect the rsFC alterations of the VS and related network in IA subjects and to investigate the modulation effect of acupuncture on the rsFC. Results: Compared with HCs, IA subjects exhibited enhanced rsFC of the right ventral rostral putamen (VRP) with the left orbitofrontal cortex (OFC), premotor cortex (PMC), cerebellum, and right ventromedial prefrontal cortex (vmPFC). In the network including these five ROIs, IA also showed increased ROI-to-ROI rsFC. Using a paired t-test in IA subjects before and after 40 days of acupuncture, the increased ROI-to-ROI rsFC was decreased (normalized to HC) with acupuncture, including the rsFC of the right VRP with the left OFC, PMC, and cerebellum, and the rsFC of the left cerebellum with the left OFC, PMC, and right vmPFC. Furthermore, the change in rsFC strength between the right VRP and left cerebellum in IA individuals was found positively correlated with the Internet craving alleviation after acupuncture. Conclusions: These findings verified the modulation effect of acupuncture on functional connectivity of reward and habit systems related to the VS in IA individuals, which might partly represent the underlying mechanisms of acupuncture on IA.

Antidiabetic Stilbenes from Peony Seeds with PTP1B, α-Glucosidase, and DPPIV Inhibitory Activities.

One unusual resveratrol tetramer, paeonilactiflorol (1), and 14 known compounds (2-15) were isolated from peony seeds ( Paeonia lactiflora) under the guidance of bioassay. Paeonilactiflorol (1) was determined by extensive HRESIMS, UV, IR, 1D and 2D NMR spectroscopic analyses. Most of the stilbenes showed obvious inhibition on PTP1B and α-glucosidase, superior to the monoterpene glycosides. Especially, the stilbene tetramer (1) and trimer (8) exhibited high activity inhibiting both PTP1B with IC50 values of 27.23 and 27.81 µM and α-glucosidase with IC50 values of 13.57 and 14.39 µM. Two trans-dimers (4 and 5) also showed dipeptidyl peptidase-4 (DPPIV) inhibitory activity (55.35% and 61.26%, 500 µM) in addition to PTP1B and α-glucosidase. Enzyme kinetic study indicated that the types of inhibition on PTP1B were noncompetitive for 3 and 5 and mixed for 8 and 10. Quantitative analysis suggested that the stilbene trimers 8 (23.17 ± 0.36 mg/g) and 10 (15.24 ± 0.25 mg/g) were the main contents in peony seeds and should be responsible for the antidiabetic effects. This investigation supports the therapeutic potential of peony seeds in the treatment of diabetes with stilbenes as the active constituents.

The triplet state of tanshinone I and its synergic effect on the phototherapy of cancer cells with curcumin.

The excited triplet state of tanshinone I (Tan I) extracted from the traditional Chinese medicine Salvia miltiorrhiza Bunge was characterized by laser flash photolysis. The synergic effect of Tan I on the phototherapy of cancer cells with curcumin (Cur) was also investigated by MTT assay because the excited energy transfer from the triplet state of Tan I ((3)Tan I(∗)) to Cur occurred. At the same time, the characteristic absorption spectra of (3)Tan I(∗) were recorded, and its molar absorption coefficient and rate constants for several excited energy transfers were obtained. The photo-therapeutic effect of Cur is enhanced by combination with Tan I.

Simultaneous determination of four alkaloids in Solanum lyratum Thunb by UPLC-MS/MS method.

Four alkaloids, strychnine, soladulcidine, solamargine and (3-O-beta-D-glucopyranosyl-(1 --> 2)beta-D-glucopyranosyl-(1 --> 4)-beta-D-galactopyranoside-(25xi)-solanidan-3beta,23beta-diol)(abbreviation, glycoalkaloid A) were isolated from Solanum lyratum Thunb. The structures were elucidated by NMR and measuring physicochemical properties. Then a novel and rapid method using an ultra-performance liquid chromatography coupled with mass spectrometry was developed and validated for the simultaneous determination of these compounds. An acquit UPLC BEH C18 column (2.1 mm x 50 mm, 1.7 microm) was used. Acetonitrile and 0.1% formic acid were adopted as mobile phase. Detection was performed on a Waters Micromass Quattro Premier tandem quadrupole mass spectrometer in the positive ion mode using an electrospray source. The multiple reaction monitoring (MRM) mode was used to detect the target compounds. The established method showed a good linearity (R2 > 0.999 0) over the investigated concentration ranges, good inter-day and intra-day precisions (less than 2%) and good recoveries (from 99.8% to 100.1%) for all four target compounds. Compared to previous methods employing conventional high performance liquid chromatography (HPLC) separation, the ultra-high-pressure liquid chromatography-tandem mass spectrometry achieved preferable chromatographic parameters and significantly increased sample throughput.

[Mitochondrial dysfunction induced by excessive ROS/RNS-metabolic cardiovascular disease and traditional Chinese medicines intervention].

Metabolic cardiovascular disease is a type of disease which almost caused by body carbohydrate and lipid metabolism dysfunction. Type 2 diabetes mellitus is a typical metabolic disease. It not only lead to the insulin resistance but also related to atherosclerosis. Oxidative stress is produced by the reactive oxygen/nitrogen species (ROS/RNS). Oxidative stress and its consequence events play important roles in atherosclerosis (AS). Mitochondria are both sources and targets of reactive oxygen and/or nitrogen species (ROS/RNS), and there is growing evidence that mitochondrial dysfunction may be relevant intermediate mechanism by which cardiovascular risk factors lead to the formation of vascular lesions. Several cardiovascular risk factors are demonstrated causes of mitochondrial damage. This review starts with excessive ROS/RNS-induced mitochondrial dysfunction. The authors emphasize the relationship among axis of excessive ROS/RNS-mitochondrial dysfunction-apoptosis-atherosclerosis. They also introduce several traditional Chinese medicines such as Ophiopogon japonicus, butin, Panax ginseng, Pueraria lobata, Solanum lyratum and so on in the treatment of relevant diseases through anti-ROS/RNS mechanism. Moreover, the TCMs also can anti-cancer and anti-fatigue,which show the speciality of TCMs different from the single effect of classical western medicines.