Regulatory effect of a Chinese herbal medicine formula on nonalcoholic fatty liver disease

BACKGROUND Non-alcoholic fatty liver disease(NAFLD)has become a major cause of chronic liver disease.The Chinese herbal medicine(CHM)Dachaihu decoction(DCHD)has been proved to treat NAFLD with good efficacy in previous studies.Based on the TCM principle of formula formation,we divided DCHD into soothing liver part,invigorating spleen part,and dredging intestine part.Marshall officially proposed the concept of“intestinal-hepatic axis”,which systematically explains the interactions between the intestine and liver.We hypothesized that the effect of CHM on NAFLD is achieved by regulating the liver and intestine.Thus,we aimed to investigate the possible effect of a CHM formula on NAFLD in a rat model.AIM To investigate the effects of a CHM formula(a decoction of Chinese thorowax root,scutellaria root,and white peony root)on NAFLD and its regulatory effect on the“intestinal-liver”axis.METHODS Sixty rats were randomly divided into control,model,pioglitazone hydrochloride(PH),and CHM(a decoction of Chinese thorowax root,scutellaria root,and white peony root)groups.An NAFLD rat model was established using a high-fat highfructose diet for 16 wk.From the 13th week,rats were administered with PH or a decoction of Chinese thorowax,scutellaria,and white peony root(CHM group)for 4 wk.Rats in the control group and model group were administered with an equal volume of distilled water.At the end of the study,blood was collected via the abdominal aorta.Liver tissues were harvested and any morphological changes were observed by hematoxylin-eosin(HE)staining,Oil red O staining,and Masson staining.In addition,blood lipids,liver function markers,and triglyceride(TG)in liver tissues were analyzed.The levels of transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),Toll-like receptor-4(TLR4),and nuclear factor-kappa B(NF-кB)in liver tissues and secreted immunoglobulin A(sIgA)in intestinal tissues were analyzed by ELISA,and protein and mRNA expression of occludin and zonula occludens-1(ZO-1)in the intestine were measured using Western blot and reverse transcriptionquantitative polymerase chain reaction,respectively.The endotoxin level in plasma was detected by endpoint chromogenic assay.RESULTS Compared to the normal control group,the liver coefficient,serum TG,total cholesterol(TC),low density lipoprotein(LDL),aspartate aminotransferase(AST),and alanine aminotransferase(ALT),blood glucose,plasma endotoxin,and the levels of TG,TNF-α,TGF-β,NF-kB,and TLR4 in liver tissues increased significantly in the model group,while serum high density lipoprotein(HDL),intestinal sIgA,and protein and mRNA expression of occludin and ZO-1 decreased significantly in the model group(P<0.01).PH and CHM attenuated the elevated liver coefficient,serum TG,TC,LDL,AST,and ALT,blood glucose,plasma endotoxin,and the levels of TG,TNF-α,TGF-β,NF-kB,and TLR4 in liver tissues and increased serum HDL levels compared to the model group(P<0.01).Intestinal sIgA and the protein and mRNA expression of intestinal occludin and ZO-1 were significantly increased in the PH group compared to the model and CHM groups(P<0.01).CONCLUSION The decoction of Chinese thorowax root,scutellaria root,and white peony root is beneficial in regulating lipid metabolism and liver function,which indicates that it has a good effect on the liver.To a certain extent,this CHM formula can affect both the liver and intestine,while its effect on the liver is superior to that on the intestine.

Suspended moxibustion relieves chronic visceral hyperalgesia and decreases hypothalamic corticotropin-releasing hormone levels

AIM:To evaluate the effect of suspended moxibustion(SM) on rectal sensory thresholds and to analyze the possible mechanisms involved in SM treatment of chronic visceral hypersensitivity(CVH) in rats.METHODS:SM was administered once daily to 37-dold CVH rats for 7 d.The two pairs of acupoints(ST25 and ST37,bilateral) were simultaneously treated with SM.Each treatment lasted for 30 min.Rats undergoing treatment with SM were not anesthetized.Untreated CVH rats and normal rats were used as controls.The abdominal withdrawal reflex was determined 30-90 min after the seven treatments.The hypothalamic corticotropin-releasing hormone(CRH) mRNA level was measured using real-time quantitative reverse transcriptionpolymerase chain reaction.RESULTS:We found that SM treatment significantly decreased visceral sensitivity to colorectal distention in this rat model.In treated animals,SM also decreased the relative hypothalamic CRH mRNA expression level to control levels.CONCLUSION:Lower hypothalamic CRH levels may mediate the beneficial effects of SM in this rat irritable bowel syndrome model.

Overcoming chemoresistance in non-angiogenic colorectal cancer by metformin via inhibiting endothelial apoptosis and vascular immaturity

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed independently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endothelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Temperature effects on atmospheric continuous-variable quantum key distribution

Compared with the fiber channel,the atmospheric channel offers the possibility of a broader geographical coverage and more flexible transmission for continuous-variable quantum key distribution(CVQKD).However,the fluctuation of atmospheric conditions will lead to the loss of performance in atmospheric quantum communication.In this paper,we study how temperature affects atmospheric CVQKD.We mainly consider the temperature effects on the transmittance and interruption probability.From the numerical simulation analysis,it can be shown that the performance of atmospheric CVQKD is improved as temperature increases,with the other factors fixed.Moreover,the results in this work can be used to evaluate the feasibility of the experimental implementation of the atmospheric CVQKD protocols.

Performance analysis of continuous-variable measurement-device-independent quantum key distribution under diverse weather conditions

The effects of weather conditions are ubiquitous in practical wireless quantum communication links.Here in this work,the performances of atmospheric continuous-variable measurement-device-independent quantum key distribution(CV-MDI-QKD)under diverse weather conditions are analyzed quantitatively.According to the Mie scattering theory and atmospheric CV-MDI-QKD model,we numerically simulate the relationship between performance of CV-MDI-QKD and the rainy and foggy conditions,aiming to get close to the actual combat environment in the future.The results show that both rain and fog will degrade the performance of the CV-MDI-QKD protocol.Under the rainy condition,the larger the raindrop diameter,the more obvious the extinction effect is and the lower the secret key rate accordingly.In addition,we find that the secret key rate decreases with the increase of spot deflection distance and the fluctuation of deflection.Under the foggy condition,the results illustrate that the transmittance decreases with the increase of droplet radius or deflection distance,which eventually yields the decrease in the secret key rate.Besides,in both weather conditions,the increase of transmission distance also leads the secret key rate to deteriorate.Our work can provide a foundation for evaluating the performance evaluation and successfully implementing the atmospheric CV-MDI-QKD in the future field operation environment under different weather conditions.

Exploring the mechanism of action of DHI on myeloproliferative neoplasms based on network pharmacology

Objective:The aim of this study is to explore the active ingredients and mechanism of action of danhong injection(DHI)in treating myeloproliferative neoplasms using network pharmacology.Methods:The TCMSP platform and relevant literature were used to search for the active ingredients and targets of Radix Salviae and Carthami Flos in DHI.Disease targets related to myeloproliferative neoplasms were obtained from the GEO database,GeneCards,and DisGeNET database.The queried component targets were normalized using the UniProt database.Potential targets were identified by constructing protein-protein interactions networks using STRING 11.5 and visualized and analyzed using Cytoscape 3.9.1.GO and KEGG analysis were performed using the Metascape platform,and visualization was done using the built-in plug-in CluoGO or SangerBox platforms with Cytoscape 3.9.1.Results:The active ingredients of DHI for treating myeloproliferative neoplasms mainly consist of flavonoids and o-benzoquinones,including quercetin,luteolin,kaempferol,stigmasterol,tanshinone iia,cryptotanshinone,beta-carotene,2-isopropyl-8-methylphenanthrene-3,4-dione,and neocryptotanshinone ii.The potential targets are JUN,TP53,STAT3,AKT1,MAPK1,RELA,TNF,MAPK14,IL6,and FOS.The relevant signaling pathways involved are mainly TNFαsignaling pathway,PI3K-Akt signaling pathway,apoptosis,IL-17 signaling pathway,cellular senescence,MAPK signaling pathway,p53 signaling pathway,JAK-STAT signaling pathway,and NF-kappa B signaling.Conclusions:DHI acts mainly through flavonoids and o-benzoquinones to treat myeloproliferative neoplasms in a multi-targeted and multi-pathway manner.

Effects of Dachaihu Decoction and Its “Prescription Elements” on Intestinal Flora of Nonalcoholic Fatty Liver Disease Model Rats

Objective:The study objective was to observe the effect of Dachaihu decoction and its "prescription elements" on intestinal flora of model rats with nonalcoholic fatty liver disease (NAFLD). Materials and Methods:Healthy male Sprague-Dawley rats were randomly divided into the following seven groups (n=105):normal, model, pioglitazone hydrochloride (PH), Shuganlidan, Jianpihuatan, Tongfuxiezhuo, and dachaihu decoction (DD). 16SrRNA high-throughput IIlumina sequencing platform was used for sequencing, and bioinformatics analysis of rat intestinal flora was done. Results:Compared with the normal group, rats in the model, PH, Shuganlidan, Jianpihuatan, Tongfuxiezhuo,and DD groups showed significant differences in the intestinal microflora structure. The microorganisms that play an important role in the normal group are Ruminococcaceae, Oscillospira, Lactobacillales, Lactobacillaceae, Lactobacillus, bacilli, Ruminococcus, TM7, Spirochaetes,Clostridium, Elusimicrobia, Elusimicrobiaceae, Elusimicrobiales, Lactobacillus helveticus, Lactobacillus reuteri, Elusimicrobium, RF39, and Christensenellaceae;in the model group are Ruminococcus gnavus;in the PH group are Prevotella, Paraprevotellaceae, and Blautia;in the Jianpihuatan group are Bacteroidetes, Bacteroidia, Bacteroidales, Roseburia, Rikenellaceae, and?Stridium methylpentosum;in the TongfuXiezhuo group are Bacteroidaceae, Bacteroides, Porphyromonadaceae, Parabacteroide, 4C0d2, Cyanobacteria, YS2, Parabacteroides distasonis,Bacteroides uniformis, Verrucomicrobiaceae, Verrucomicrobiae, Verrucomicrobiales, Akkermansia, Akkermansia muciniphila, Coprobacillus,Parabacteroides gordonii, Blautia producta, and Ruminococcus torques;and in the DD group are Erysipelotrichales, Erysipelotrichi, and Erysipelothrichaceae. Conclusion:The Tongfuxiezhuo prescription elements of the DD significantly improved the intestinal flora of rats with NAFLD, improving the relative abundance of beneficial bacteria in the intestinal flora of NAFLD rats such as Bacteroides, Sartre genus,Vibrio pseudobutyrate bacteria, and Akkermansia muciniphila. This subsequently improved the glucose and lipid metabolism in NAFLD rats,reducing fat deposition in the liver, inhibiting intestinal inflammatory reaction, and maintaining the integrity of intestinal mucosal barrier. The action target is the intestinal axis of "intestinal–hepatic axis."