Study of dual-directional regulatory effect of Banxia （Pinellia ternata） and Huanglian （Coptis chinensis） drug pair on gastrointestinal movement of mice

Objective： To evaluate the regulatory effects of Banxia （Pinellia ternata, P） and Huanglian （Coptis chinensis, C） drugpair, derived from Banxiaxiexin soup, on the gastrointestinal movement of mice with functional dyspepsia. Methods：Mice were treated with different proportions of the P and C drug pair （1：1, 3：1, and 4：1） for 10 days, and subsequentlyinjected with atropine （ATR） or neostigmine （NEO）. The effects of the different proportions of P and C were evaluatedbased on the alvine advance rate. In addition, we used the same modeling method used in the first experiment andadministered P： C at ratio of 3：1 and at different doses respectively （4.68 g/L, 2.34 g/L, and 1.17 g/L）, and tested levelsof the gastrointestinal hormones, gastrin （GAS）, vasoactive intestinal polypeptide （VIP）, and somatostatin （SS） in thesmall intestinal tissue using an enzyme-linked immunosorbent assay. Results： In the groups of NEO-induced mice, P：Cat ratios of 1：1, 3：1, and 4：1 significantly reduced the alvine advance rate compared with the NEO model group （P =0.003, P = 0.012 and P = 0.021, respectively）. In the groups of ATR-induced mice, only P：1 at ratio of 3：1 significantlyincreased the alvine advance rate compared with the ATR model group （P = 0.007）. After exposure to P： C at ratio of 3：1and at different dose, the GAS level was lower in the low-, medium-, and high-dose NEO groups than that in the NEOmodel group （P = 0.001, P = 0.004, and P = 0.003, respectively）. The VIP levels were higher in the medium-andhigh-dose NEO groups than that in the NEO model group （P = 0.004 and P = 0.002, respectively）. In addition, the SSlevel increased in the NEO medium-dose group compared with that in the NEO model group （P = 0.002）. The GAS levelwas higher in the ATR medium- and high-dose groups than in the ATR model group （P = 0.007 and P = 0.021,respectively）. The VIP level was lower in the ATR low-, medium-, and high-dose than that in the ATR model group （P =0.001, P = 0.001, and P = 0.001, respectively）. Furthermore, the SS level was lower in the ATR medium- and high-dosegroups than that in the ATR model group （P = 0.001 and P = 0.006）. Conclusion： The PC drug pair bidirectionallyadjusted the NEO- and ATR-induced functional dyspepsia in mice by modulating GAS, VIP, and SS levels in theintestine.

Allotetraploidization event of Coptis chinensis shared by all Ranunculales

Coptis chinensis Franch.,also named Chinese goldthread is a member of Ranunculaceae in the order Ranunculales and represents an important lineage of early eudicots with traditional medicinal value.In our study,by using syntenic analysis combined with phylogenomic analysis of C.chinensis and four other representative genomes from basal and core eudicots,we confirmed that the WGD event in C.chinensis was shared by Aquilegia coerulea and Papaver somniferum L.and quickly occurred after Ranunculales diverged from other eudicots,likely a Ranunculales common tetraploidization(RCT).The synonymous nucleotide substitutions at synonymous sites distribution of syntenic blocks across these genomes showed that the evolutionary rate of the P.somniferum genome is faster than that of the C.chinensis genome by approximately 13.7%,possibly due to Papaveraceaes having an additional special tetraploidization event(PST).After Ks correction,the RCT dated to 115—130 million years ago(MYA),which was close to the divergence of Ranunculaceaes and Papaveraceaes approximately115.45—130.51 MYA.Moreover,we identified homologous genes related to polyploidization and speciation and constructed multiple sequence alignments with different reference genomes.Notably,the event-related subgenomes in the basal genomes all showed genomic fractionation bias,suggesting a likely allopolyploid nature of the RCT,PST and T-Alpha and T-Beta events in Tetracentron sinense.In addition,we detected that the sixteen P450 subfamilies were markedly expanded in the genomes of Ranunculales,and most of them were related to the RCT and PST events.We constructed a new platform for Early Eudicot Comparative Genomic Research(http://www.cgrpoee.top/index.html)to store more information.In summary,our findings support the WGD of C.chinensis shared by Ranunculales,which is likely an allotetraploidization event.This present effort offered new insights into the evolution of key polyploidization events and the genes related to secondary metabolites during the diversification of early eudicots.

Mechanism of Huanglian Detoxification Soup Relieving Postherpetic Neuralgia by Enhancing IL-2 Levels in Rats

[Objectives]To explore the mechanism of Huanglian detoxification soup improving pain behavior by affecting serum IL-2 levels in postherpetic neuralgia(post herpes neuralgia,PHN)model rats.[Methods]20 PHN rats were randomly divided into model group(PHN group)and detoxification decoction group(n=10).In the group,10%Huanglian detoxification soup(0.4 mL/0.1 kg)was given once in the morning and evening for 14 d.The PHN group was filled with an equal volume of 0.9%sodium chloride solution.Tail vein serum inflammatory factor interleukin-2(IL-2),IL-βand IL-6 levels were measured using ELISA kits at 7 and 21 d.[Results]IL-2 increased at 14 and 21 d in IL group,while IL-βand IL-6 decreased compared with the PHN group(P<0.05).[Conclusions]Huanglian detoxification soup may raise IL-2 levels after VZV infection to promote the differentiation of cells of the immune system,so as to relieve the pain caused by IL-βand IL-6 inflammatory factors.

Network pharmacology and molecular dynamics study of the effect of the Astragalus-Coptis drug pair on diabetic kidney disease

BACKGROUND Diabetic kidney disease(DKD)is the primary cause of end-stage renal disease.The Astragalus-Coptis drug pair is frequently employed in the management of DKD.However,the precise molecular mechanism underlying its therapeutic effect remains elusive.AIM To investigate the synergistic effects of multiple active ingredients in the Astragalus-Coptis drug pair on DKD through multiple targets and pathways.METHODS The ingredients of the Astragalus-Coptis drug pair were collected and screened using the TCMSP database and the SwissADME platform.The targets were predicted using the SwissTargetPrediction database,while the DKD differential gene expression analysis was obtained from the Gene Expression Omnibus database.DKD targets were acquired from the GeneCards,Online Mendelian Inheritance in Man database,and DisGeNET databases,with common targets identified through the Venny platform.The protein-protein interaction network and the“disease-active ingredient-target”network of the common targets were constructed utilizing the STRING database and Cytoscape software,followed by the analysis of the interaction relationships and further screening of key targets and core active ingredients.Gene Ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichments were performed using the DAVID database.The tissue and organ distributions of key targets were evaluated.PyMOL and AutoDock software validate the molecular docking between the core ingredients and key targets.Finally,molecular dynamics(MD)simulations were conducted to simulate the optimal complex formed by interactions between core ingredients and key target proteins.RESULTS A total of 27 active ingredients and 512 potential targets of the Astragalus-Coptis drug pair were identified.There were 273 common targets between DKD and the Astragalus-Coptis drug pair.Through protein-protein interaction network topology analysis,we identified 9 core active ingredients and 10 key targets.GO and KEGG pathway enrichment analyses revealed that Astragalus-Coptis drug pair treatment for DKD involves various biological processes,including protein phosphorylation,negative regulation of apoptosis,inflammatory response,and endoplasmic reticulum unfolded protein response.These pathways are mainly associated with the advanced glycation end products(AGE)-receptor for AGE products signaling pathway in diabetic complications,as well as the Lipid and atherosclerosis.Molecular docking and MD simulations demonstrated high affinity and stability between the core active ingredients and key targets.Notably,the quercetin-AKT serine/threonine kinase 1(AKT1)and quercetin-tumor necrosis factor(TNF)protein complexes exhibited exceptional stability.CONCLUSION This study demonstrated that DKD treatment with the Astragalus-Coptis drug pair involves multiple ingredients,targets,and signaling pathways.We propose a novel approach for investigating the molecular mechanism underlying the therapeutic effects of the Astragalus-Coptis drug pair on DKD.Furthermore,we suggest that quercetin is the most potent active ingredient and specifically targets AKT1 and TNF,providing a theoretical foundation for further exploration of pharmacologically active ingredients and elucidating their molecular mechanisms in DKD treatment.

The effect of Huanglian Jiedu Decoction on inflammatory factors and oxidative stress in patients with acute ischemic stroke

Objective:To study the clinical efficacy of Huanglian Jiedu decoction in treating acute ischemic stroke(AIS)and its effects on inflammatory factors and oxidative stress.Method:A total of 53 patients with AIS were recruited as the study subjects and randomly divided into a control group and a treatment group using a random number table method.The control group consisted of 26 patients and the treatment group consisted of 27 patients.The control group received conventional Western medicine treatment.The control group received routine Western medicine treatment,while the treatment group received Huanglian Jiedu decoction based on the control group,with 14 days as a course of treatment.The effects of Huanglian Jiedu decoction on neurological function and activities of daily living were evaluated using the National Institute of Health stroke scale(NIHSS)and activities of daily living(ADL)scores.The effects of Huanglian Jiedu decoction on inflammatory reactions and oxidative stress were evaluated by detecting interleukin-4(IL-4),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),transforming growth factorβ(TGF-β),total antioxidative capacity(T-AOC),malondialdehyde(MDA),superoxide dismutase(SOD),and catalase(CAT)levels.Results:After treatment with Huanglian Jiedu Decoction,the ALD scores of AIS patients in both groups increased,while the NISHH scores decreased,suggesting that Huanglian Jiedu Decoction has therapeutic effects on AIS patients.It also reduces the levels of serum IL-6,TNF-α,MDA in AIS patients and increases the levels of IL-4,TGF-β,CAT,SOD,T-AOC,suggesting that Huanglian Jiedu decoction can improve the anti-inflammatory and antioxidant abilities of AIS patients.Conclusion:Huanglian Jiedu decoction can help AIS patients recover their neurological function,increase their capacity for self-care in daily life,and strengthen the body’s anti-inflammatory and antioxidant defenses.

Clinical Efficacy of Huanglian Ointment in the Treatment of Chronic Eczema

Objective:To investigate and analyze the clinical efficacy of Huanglian ointment in the treatment of chronic eczema.Methods:114 cases of chronic eczema patients admitted to the Department of Dermatology of our hospital from January 2023 to January 2024 were selected as the study subjects.They were divided into a study group(n=57)and a reference group(n=57)using the double-blind method.The study group was treated with dialyzed Huanglian ointment,while the reference group was treated with conventional treatment.Symptom scores,inflammatory levels,treatment effects,and immune indexes of the two groups were similar before treatment.Results:After treatment,the symptom scores of the study group were significantly lower than those in the reference group(P<0.05).Besides,the interleukin-2(IL-2),tumor necrosis factor-a(TNF-a),interferon-(IFN-),and other inflammatory indicators of the study group were significantly better than those of the reference group(P<0.05).The total efficacy of treatment in the study group was significantly higher than that in the reference group(P<0.05).Furthermore,after treatment,the immunity indexes such as CD3+,CD4+,and CD8+of the study group were significantly better than those of the reference group,(P<0.05).Conclusion:Huanglian ointment is extremely effective for treating chronic eczema so this treatment program should be popularized.

黄连(Coptis chinensis)花形态特征与传粉昆虫的适应性

以黄连(Coptis chinensis)为研究对象,通过对其花部形态结构及主要传粉昆虫访花频率、访花行为、传粉效率、结籽贡献率等的观察分析,探究黄连花形态特征与传粉昆虫的适应性关系。结果显示:黄连花具有简单的浅槽状蜜腺结构,花蜜分泌量少;观察到的2种黄连主要传粉昆虫麻蝇和黑带食蚜蝇都是具有舐吸式口器的双翅目昆虫,它们在访花过程中都表现出舔食花蜜的行为,且身体都能够接触到雌蕊和雄蕊,从而导致胚珠成功发育;受黄连早春开花时间差异及气候不稳定等因素的影响,黄连传粉昆虫的访花频率有所波动,但传粉昆虫种类没有变化。上述结果表明黄连的浅槽状蜜腺结构适合具有舐吸式口器的麻蝇和黑带食蚜蝇作为传粉媒介,且形成较为稳定的传粉系统。

Correlation between Yield of Coptis chinensis Franch. and Soil Nutrients under Different Forests

[Objective] This study was conducted to investigate the correlation be- tween yield of Coptis chinensis Franch. and soil nutrients under different forests. [Method] The soil nutrients and yields of C. chinensis in fallow field, Cryptomeria japonica forest, Magnolia officinalis forest and Phellodendron chinense forest planted with C. chinensis were investigated. [Result] The contents of soil nitrogen （total ni- trogen, alkali-hydrolyzale nitrogen）, organic matter, potassium and phosphorous under the planting mode of C. chinensis under C. japonica forest were the highest; and the contents of organic matter and total nitrogen in the soils of M. officinalis and P. chinense forests were close to each other at the medium abundant level, and the phosphorous contents were more abundant than those in fallow field. [Conclusion] This study could provide a theoretical basis for scientific fertilization.

Study of Total Alkaloids from Rhizoma Coptis Chinensis on Experimental Gastric Ulcers

Objective： To study the effects of total alkaloids （TA） extracted from Rhizoma Coptis Chinensis on experimental gastric ulcer models. Methods： Four kinds of experimental ulcer models were established respectively by water-immersion stress, intragastric ethanol, acetic acid erosion, and pylorus ligation. The anti-ulcer effects of TA were evaluated, and compared with that of berberine （Bet） and cimetidine （Oim）. Results： TA showed significant inhibitory effects on ulcerative formation induced by water-immersion stress, intragastric ethanol, and pylorus l igation in dose-dependent manner, and showed therapeutic effect on acetic acid erosion-inducing ulcer, in comparison with the control group. The anti-ulcer activity of Bet was less than TA containing equal content of Bet. TA significantly reduced the free acidity, total acidity and total acid output, but didn＇t affect the gastric juice volume, gastric pepsin activity, adherent mucus quantity of stomach wall and free mucus dissolving in gastric juice. The suppressive activities of TA on gastric acid secretion didn＇t occur when it was administered into dodecadactylon at a dose of 360 mg/kg wt. Moreover, when compared with Oim, the inhibitory effect of TA on gastric acid secretion isn＇t proportional to the inhibitory effects on the formation of the 4 kinds of experimental ulcers. Conclusion： TA is a potent candidate in therapeutic drugs for treating gastric ulcer. Its anti-ulcer effective components and mechanism is not only related to Bet and inhibition of gastric acid, but also to other ingredients of TA and mechanism so far unknown.

Qualitative and Semi-quantitative Analysis of Quaternary Alkaloids in Coptis-scute Herb Couple by Electrospray Mass Spectrometry

A practical solution of qualitatively analyzing quaternary alkaloids in coptis-scute herb couple by electrospray ionization mass spectrometry（ES1-MS） was developed. Without the complicated pretreatment of sample, thc active ingredients including berberine, palmatine, coptisine, jatrorrhizine, epiberberine, and columbamine were identified and some relative content changing rules of alkaloids in coptis-scute couple were summarized in this article. The overall profiles of the complex extracts were obtained. After adding an internal standard（rutaecarpine）, semi-quantitative analysis was performed and the result indicates that the actual content of alkaloids was decreased by increasing the amount of scute. Based on the data obtained by high-performance capillary electrophoresis（HPCE）, the feasibility of semi-quantitative analysis by ES1-MS was further proved.

The chromosome-level reference genome of Coptis chinensis provides insights into genomic evolution and berberine biosynthesis

Coptis chinensis Franch, a perennial herb, is mainly distributed in southeastern China. The rhizome of C. chinensis hasbeen used as a traditional medicine for more than 2000 years in China and many other Asian countries. Thepharmacological activities of C. chinensis have been validated by research. Here, we present a de novo high-qualitygenome of C. chinensis with a chromosome-level genome of ~958.20 Mb, a contig N50 of 1.58 Mb, and a scaffold N50of 4.53 Mb. We found that the relatively large genome size of C. chinensis was caused by the amplification of longterminal repeat (LTR) retrotransposons. In addition, a whole-genome duplication event in ancestral Ranunculales wasdiscovered. Comparative genomic analysis revealed that the tyrosine decarboxylase (TYDC) and (S)-norcoclaurinesynthase (NCS) genes were expanded and that the aspartate aminotransferase gene (ASP5) was positively selected inthe berberine metabolic pathway. Expression level and HPLC analyses showed that the berberine content was highestin the roots of C. chinensis in the third and fourth years. The chromosome-level reference genome of C. chinensisprovides important genomic data for molecular-assisted breeding and active ingredient biosynthesis.

Determination of coptis chinensis’ quality by FT-NIR spectroscopy

As a kind of traditional Chinese medicinal materials coptis chinensis has a lot of medicinal value and closely related to human health, Widely used in clinical or disease prevention and treatment. So the quality of medicinal coptis chinensis rapid determination is very important. Calibration model for determination of Coptis chinensis’ quality was built by partial least squares and near infrared spectroscopy, and the method of spectral pretreatment was discussed. Berberine and moisture content were used as evaluation index of Coptis chinensis’ quality according to traditional Chinese medicine standard in this experiment. The first derivative and vector normalization were adopted for the spectral preprocessing. The performance of the final model was evaluated according to root mean squares error of cross-validation (RMSECV), root mean square error of prediction (RMSEP) and correlation coefficient (R). According to the model of calibration set, the R values were 0.9298 and 0.8898, RMSECV were 0.239% and 0.302%. The R values of prediction set were 0.9347 and 0.9146, RMSEP were 0.104% and 0.330%, and prediction results were accurate and reliable. This method could be applied in rapid analysis of Coptis chinensis. The method was suitable for production fields and research fields, and had a wide application prospect.

Coptis,Pinellia,and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection

BACKGROUND Helicobacter pylori(H.pylori)is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.AIM To identify efficient therapeutic agents or strategies that can treat H.pylori infection.METHODS We performed literature analysis,experimental validation,and network pharmacology.First,traditional Chinese medicine(TCM)prescriptions for the treatment of H.pylori infection were obtained from the China National Knowledge Infrastructure,China Biology Medicine,China Science and Technology Journal Database,and WanFang databases.In addition,we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com).Next,we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions.Then,an H.pylori-associated chronic mouse model of gastritis was established.The antibacterial properties and antiinflammatory potential of the core drug combination were evaluated by the rapid urease test,modified Warthin-Starry silver staining,histopathological analysis,and enzyme linked immunosorbent assay.Finally,the active compounds,hub targets,and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.RESULTS The TCM treatment of H.pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing,bitter descending,cold and warm drugs.The combination of Coptis,Pinellia,and Scutellaria(CPS)was identified as the core drug combination from 207 prescriptions and 168 herbs.This drug combination eradicated H.pylori,alleviated the gastric pathology induced by H.pylori infection,and reduced the expression levels of tumor necrosis factor-α(P=0.024)and interleukin-1β(P=0.001).Moreover,a total of 35 compounds and 2807 targets of CPS were identified using online databases.Nine key compounds(tenaxin I,neobaicalein,norwogonin,skullcapflavone II,baicalein,5,8,2'-trihydroxy-7-methoxyflavone,acacetin,panicolin,and wogonin)and nine hub target proteins(EGFR,PTGS2,STAT3,MAPK3,MAPK8,HSP90AA1,MAPK1,MMP9,and MTOR)were further explored.Seventy-seven signaling pathways were correlated with H.pylori-induced inflammation and carcinogenesis.CONCLUSION In summary,we showed that CPS is the core drug combination for treating H.pylori infection.Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa.Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multipathway regulatory mechanisms.Although the results derived from network pharmacology are not necessarily comprehensive,they still expand our understanding of CPS for treating H.pylori infection.

An Economical Method for Preparative Purification of Five Alkaloids from Coptis Chinensis Franch by High-Speed Counter-Current Chromatography Using Singled Prepared Solvent System by GC

Coptis chinensis Franch, a widely used Traditional Chinese Medicine, shows various kinds of bioactivity. The major active components of the herb are considered to be alkaloids. Thus, preparative separation of these alkaloids is critical important for further pharmacology and mechanism studies. In the paper, five alkaloids from C. chinensis were purified by HSCCC using the solvent system composed of chloro-form-metha- nol-water (2:1:1, v/v/v) single prepared. The content of each solvent in solvent system were determined by gas chromatography (GC), then according the ratios of solvents in each phase to prepare the mobile and stationary phase respectively. And a comparative study was carried out between together preparation and single preparation of the solvent system. The purities and recoveries of all the products were over 98.5% and 92%. However, 134 mL chloroform, 336 mL methanol and 452 mL water were saved when the two phase were singled by GC. Our research showed an economical method for separating alkaloids from C. chinensis by HSCCC using the solvent system single prepared by GC.

Structural and Histochemical Features of the Slow-Growing Perennial Coptis chinensis Franch.(Ranunculaceae)

Huanglian(Coptis chinensis Franch.)is a slow-growing perennial medicinal herb with considerable economic value.This study aimed to determine the structural characteristics and the levels of berberine deposits in the organs and tissues of Huanglian using light and epifluorescence microscopy.The adventitious roots are composed of primary and secondary structures with endodermis,exodermis,and phellem.The rhizome structures are composed of primary and secondary structures with cuticle and phellem.The leaves are composed of sclerenchymatous rings,isolateral mesophyll,and thin cuticles.We detected berberine in the xylem walls of the roots and rhizomes as well as in the sclerenchymatous rings of the petioles.We postulate that as the exodermis is developed,the deposition of berberine in the xylem closest to the root tips may affect water and nutrient absorption and transfer.Leaf blades had a thin cuticle and isolateral mesophyll,suggesting shade tolerance.These structural and histochemical features suggest that Huanglian is adapted to the slow growing nature of a shady environment.

Huanglian decoction suppresses the growth of hepatocellular carcinoma cells by reducing CCNB1 expression

BACKGROUND Hepatocellular carcinoma(HCC)is one of the most prevalent cancers in human populations worldwide.Huanglian decoction is one of the most important Chinese medicine formulas,with the potential to treat cancer.AIM To investigate the role and mechanism of Huanglian decoction on HCC cells.METHODS To identify differentially expressed genes(DEGs),we downloaded gene expression profile data from The Cancer Genome Atlas Liver Hepatocellular Carcinoma and Gene Expression Omnibus(GSE45436)databases.We obtained phytochemicals of the four herbs of Huanglian decoction from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform.We also established a regulatory network of DEGs and drug target genes and subsequently analyzed key genes using bioinformatics approaches.Furthermore,we conducted in vitro experiments to explore the effect of Huanglian decoction and to verify the predictions.In particular,the CCNB1 gene was knocked down to verify the primary target of this decoction.Through the identification of the expression levels of key proteins,we determined the primary mechanism of Huanglian decoction in HCC.RESULTS Based on the results of the network pharmacological analysis,we revealed 5 bioactive compounds in Huanglian decoction that act on HCC.In addition,a protein-protein interaction network analysis of the target genes of these five compounds as well as expression and prognosis analyses were performed in tumors.CCNB1 was confirmed to be the primary gene that may be highly expressed in tumors and was significantly associated with a worse prognosis.We also noted that CCNB1 may serve as an independent prognostic indicator in HCC.Moreover,in vitro experiments demonstrated that Huanglian decoction significantly inhibited the growth,migration,and invasiveness of HCC cells and induced cell apoptosis and G2/M phase arrest.Further analysis showed that the decoction may inhibit the growth of HCC cells by downregulating the CCNB1 expression level.After Huanglian decoction treatment,the expression levels of Bax,caspase 3,caspase 9,p21 and p53 in HCC cells were increased,while the expression of CDK1 and CCNB1 was significantly decreased.The p53 signaling pathway was also found to play an important role in this process.CONCLUSION Huanglian decoction has a significant inhibitory effect on HCC cells.CCNB1 is a potential therapeutic target in HCC.Further analysis showed that Huanglian decoction can inhibit HCC cell growth by downregulating the expression of CCNB1 to activate the p53 signaling pathway.

Meta-analysis of the efficacy and safety of Huanglian Wendan Decoction alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance

Objective To evaluate the efficacy and safety of Huanglian Wendan Decoction(黄连温胆汤,HLWDD)alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance in recent 10 years.Methods The randomized controlled trials of HLWDD alone or combined with western medicine in treating insomnia caused by phlegm-heat internal disturbance from January 1,2012 to April 1,2022 were searched in China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),Wanfang Database,China BioMedical Literature Database(CBM),PubMed,Web of Science,Embase,and Cochrane Library databases.After being screening,the included literature was analyzed to evaluate the effective rate,Pittsburgh Sleep Quality Index(PSQI)score,traditional Chinese medicine(TCM)syndrome score,and adverse reactions of HLWDD on insomnia caused by phlegm-heat internal disturbance.The subgroup analyzed the effect of HLWDD after different treatment courses,and compared the therapeutic effects of HLWDD alone and HLWDD combined with western medicine.Results Twenty-seven randomized controlled trials were finally included,with a total of 2395 patients.The results of the meta-analysis showed that the curative effect of HLWDD alone or combined with the western medicine group was better than that of the western medicine group[RR=1.14,95%CI(1.06,1.22),P=0.000].The PSQI score[SMD=-0.31,95%CI(-0.42,-0.20),P=0.000],TCM syndrome score[SMD=-0.40,95%CI(-0.67,-0.12),P=0.005],and adverse reaction rate[RR=0.21,95%CI(0.15,0.29),P=0.000]of HLWDD alone or combined with western medicine group were significantly reduced compared with the western medicine group.The subgroup’s analysis showed that the curative effect of HLWDD alone or combined with western medicine group of 4 weeks treatment course was better than that of the western medicine group[RR=1.14,95%CI(1.03,1.26),P<0.05].The TCM syndrome score of HLWDD alone or combined with the western medicine group of 4 weeks treatment course decreased more obviously than that of the western medicine group[SMD=-0.60,95%CI(-0.96,-0.25),P<0.05].There were no significant differences between HLWDD alone or combined with western medicine group and western medicine group with different treatment courses based on PSQI score and adverse reaction rate.Based on the effective rate,the comparison between the HLWDD alone group and the western medicine group[RR=1.09,95%CI(1.00,-1.20)P<0.05],and between the HLWDD combined with western medicine group and the western medicine group[RR=1.15,95%CI(1.03,1.29),P<0.05]was the same.PSQI score[SMD=-0.44,95%CI(-0.59,-0.30),P<0.05]and TCM syndrome score[SMD=-1.10,95%CI(-1.59,-0.61),P<0.05]of HLWDD combined with western medicine group were significantly lower than those of the western medicine group.There were no significant differences of adverse reaction rate between HLWDD alone group[RR=0.08,95%CI(0.04,0.17),P<0.05]and HLWDD combined with western medicine group[RR=0.36,95%CI(0.24,0.53),P<0.05].Conclusion HLWDD alone or combined with western medicine is an effective treatment for insomnia caused by phlegm-heat internal disturbance,which has a high effective rate,significantly reduced PSQI score and TCM syndrome score,and favorable safety.The best course of treatment is 4 weeks.

Modulation of gut microbiota by berberine and decocted Coptis chinensis Franch.in a high-fat diet-induced metabolic syndrome rat model

Objective:To investigate the effect of decocted Coptis chinensis Franch.(Huanglian Jianji,黄连煎剂,HLJJ) and berbenne on the gut microbiota of the rats with metabolic syndrome (MS) induced by high-fat diet (HFD).Methods:Sixty Sprague Dawley rats were randomly divided into normal diet (ND) group (n =15)and HFD group (n =45).After 8 weeks of feeding,the HFD group was further divided into three groups:a group provided with a combination of HLJJ and HFD for 4 weeks,a group provided with a combination of berberine and HFD for 4 weeks,and a group supplied only with HFD for 4 consecutive weeks.Epididymal fat weight,serum high-density lipoproteincholesterohC (HDL-C),lowdensity lipoproteincholesterol-C (LDL-C) and irisin levels were measured.In addition,the V3-V4 region of the cecum microbiota 16S rRNA gene amplicon was sequenced on the Illumina MiSeq platform.Results:MS was successfully induced in the rats with HFD for 8 weeks.After 12 weeks,serum irisin levels in the HFD + berberine group were significantly increased compared with those in the HFD group (P <.05).The high-quality tags were delineated into 1149 operational taxonomic units at a 97% similarity level.Furthermore,at the genus level,Akkermansia muciniphila (A.muciniphila),Bacteroides,and Ruminococcus were markedly increased,whereas Candidatus arthromitus,Prevotella,Phascolarctobacterium were in great decrease in the HLJJ group and the berberine group,compared with the HFD group.The abundance of A.muciniphila,Ruminococcus gnavus and Bacteroides was significantly higher in the berberine group,whereas,the abundance of Oscillospira was lower in the berberine group,compared with the HLJJ group.Conclusion:HLJJ and berberine changed the gut microbiota in rats with MS.The mechanism underlying the treatments of berberine and HLJJ on HFD-induced MS is partly different.

Cerebroprotective effect of Huanglian Jiedu decoction on amyloid protein precursor/presenilin-1 double transgenic mice

Huanglian Jiedu decoction （HLJDD） has been shown to improve cerebral blood flow, and reduce lipid peroxidation damage to the brain and its energy metabolism. The present study was designed to observe the cerebroprotective effect of HL.JDD on an Alzheimer＇s disease rodent model, presenilin-1/amyloid protein precursor double transgenic mice. HLJDD reduced serum interleukin-6 and interleukin-113 levels, decreased [3-amyloid precursor protein gene and senile plaque expression, resisted oxidation, and reduced free radical-induced injury, thereby improving the learning and memory of these mice. Moreover, HLJDD at 433 mg/kg per day exhibited better effects compared with that at 865 or 216 mg/kg per day, and donepezil hydrochloride at 30 mg/kg per day. Thus, these results suggest that HLJDD may have protective effects against Alzheimer＇s disease.

Effects of Huanglian Jiedu Decoction on Rat Gingivitis Induced by LPS

[Objectives] To evaluate the effects of Huanglian Jiedu Decoration( HLJD) on the treatment of rat gingivitis with excess internal heat through injecting lipopolysaccharide( LPS) in tooth-supporting tissues. [Methods]Gingival inflammation was established by LPS injection. Male SD rats were randomly divided into 7 groups: normal control group( no treatment group),solvent control group,model group( LPS injection),HLJD low dose group( 0. 25 g/kg),HLJD medium dose group( 0. 50 g/kg),HLJD high dose group( 1. 00 g/kg),and metronidazole and fenbufen capsule( MFC) group. Water intake and urine volume were observed through metabolic cage feeding; gingival tissue protein expressions were detected by LC-ESI-MS/MS method; oxidative stress-related molecules such as total superoxide dismutase( T-SOD) and hydrogen peroxidase catalase( CAT) were detected by the biochemical kit combined with a microplate reader; expressions of TSC related with energy metabolism-related signaling pathway were detected by western blotting. [Results]When rat gingivitis was injected by LPS,both water intake and urine volume were decreased,the levels of T-SOD and CAT were decreased,and the expressions of fructose-bisphosphate aldolase C,triosephosphate isomerase 1 and TSC2 were increased. Huanglian Jiedu Decoration can increase water intake and urine volume,increase the levels of T-SOD and CAT,reduce the expressions of fructose-bisphosphate aldolase C and triosephosphate isomerase 1,and inhibit the expression of energy metabolism-related pathway molecule TSC2. [Conclusions] Huanglian Jiedu Decoration can treat rat gingivitis through inhibiting energy metabolism and oxidative stress such as TSC signal pathway and glycolysis related molecules.