Danggui Sini Decoction Research Articles

From complexity to clarity: development of CHM-FIEFP for predicting effective components in Chinese herbal formulas by using big data.

The presence of complex components in Chinese herbal medicine (CHM) hinders identification of the primary active substances and understanding of pharmacological principles. This study was aimed at developing a big-data-based, knowledge-driven in silico algorithm for predicting central components in complex CHM formulas. Network pharmacology (TCMSP) and clinical (GEO) databases were searched to retrieve gene targets corresponding to the formula ingredients, herbal components, and specific disease being treated. Intersections were determined to obtain disease-specific core targets, which underwent further GO and KEGG enrichment analyses to generate non-redundant biological processes and molecular targets for the formula and each component. The ratios of the numbers of biological and molecular events associated with a component were calculated with a formula, and entropy weighting was performed to obtain a fitting score to facilitate ranking and improve identification of the key components. The established method was tested on the traditional CHM formula Danggui Sini Decoction (DSD) for gastric cancer. Finally, the effects of the predicted critical component were experimentally validated in gastric cancer cells. An algorithm called Chinese Herb Medicine-Formula vs. Ingredients Efficacy Fitting & Prediction (CHM-FIEFP) was developed. Ferulic acid was identified as having the highest fitting score among all tested DSD components. The pharmacological effects of ferulic acid alone were similar to those of DSD. CHM-FIEFP is a promising in silico method for identifying pharmacological components of CHM formulas with activity against specific diseases. This approach may also be practical for solving other similarly complex problems. The algorithm is available at http://chm-fiefp.net/.

Exploring the mechanism of Danggui Sini Decoction in the treatment of myocardial infarction: A systematic review, network pharmacology, and molecular docking.

Myocardial infarction (MI) is one of the leading causes of death worldwide because of its high morbidity and mortality. Traditional Chinese Medicine compounds play a crucial role in preventing cardiovascular diseases. Danggui Sini Decoction (DSD) is widely used clinically for cardiovascular diseases. However, the mechanism, main components, and main targets of DSD in treating MI are still unclear. In this study, we utilized network pharmacology and molecular docking for exploration. MI-related genes were examined using the Genecards database, and the active ingredients of DSD were screened based on System Pharmacology Database and Analysis Platform of Traditional Chinese Medicine by oral bioavailability ≥ 30% and drug-likeness ≥ 0.18. The protein-protein interaction network diagram was generated using the STRING database. The DAVID web platform was used to carry out gene ontology and Kyoto encyclopedia of gene and genome signaling pathway analysis. DSD's screening study revealed 120 primary active ingredients and 561 putative active target genes. The main therapeutic targets were TP53, EGFR, AKT1, IL6, TNF, STAT3, IL1B, CTNNB1, SRC, MYC, JUN, and INS. Gene ontology and Kyoto encyclopedia of gene and genome analyses revealed that DSD treatment of MI mainly involves the positive regulation of the ERK1 and ERK2 cascades, positive regulation of cell proliferation, inflammatory responses, aging, and the MAPK cascade, along with other biological processes. The molecular docking results indicate that DSD drugs may interact with AKT1, EGFR, TP53, and TNF through formononetin, isorhamnetin, β-Sitosterol, and kaempferol, potentially contributing to the treatment of MI. By utilizing a multi-component, multi-pathway, and multi-target mode of action, DSD may have the potential to prevent MI.

Integrated metabolomics and lipidomics investigation of the mechanism of Danggui Sini Decoction on improving lipid homeostasis in primary dysmenorrhea

BackgroundDanggui Sini Decoction (DGSND) is a classic prescription for treating primary dysmenorrhea (PD), while, the ameliorating effects of DGSND on PD and its mechanisms are not yet fully understood. PurposeThe present study is devoted to investigate the protective effect of DGSND against PD and the possible mechanism from the perspective of metabolomics as well as lipidomics. MethodsDGSND was characterized by UPLC-Q-TOF/MS. The PD rat model was induced by estradiol benzoate and oxytocin, and traditional pharmacology, including writhing times, latency time, biochemical index, organ index, and histopathology were performed to evaluated the efficacy of DGSND on PD. Urine metabolomics strategy combined with functional analysis was adopted to delineate the therapeutic effect of DGSND on PD rats and anchor the crucial pathway, and lipidomics analysis was further performed with the uterine tissue as the research object to elucidate the protective mechanism of DGSND from the perspective of lipid homeostasis. Finally, western blot analysis was used to validate the expression of key metabolic enzymes in lipid metabolism. ResultsDGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F2α (PGF2α)/PGE2, uterus index, and morphological changes of PD rats. Metabolic signature of PD rats was primarily characterized by the disturbance of steroid hormone metabolism, amino acid metabolism, and lipid metabolism. Functional analysis revealed the urine biomarkers of PD were most related with lipid abnormality. Further lipidomics analysis indicated DGSND exerted anti-PD effects by remodeling lipid homeostasis, which might be due to the significant correlations between different kinds of lipids, especially the extremely high correlation of phosphatidylethanolamine, phosphatidylcholine, and fatty acids. Moreover, the key metabolic enzymes expression of CK, PLA2, LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. ConclusionOur findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.

Dang-Gui-Si-Ni decoction facilitates wound healing in diabetic foot ulcers by regulating expression of AGEs/RAGE/TGF-β/Smad2/3.

Diabetic foot ulcer (DFU) is a predominant complication of diabetes mellitus with poor prognosis accompanied by high amputation and mortality rates. Dang-Gui-Si-Ni decoction (DSD), as a classic formula with a long history in China, has been found to improve DFU symptoms. However, mechanism of DSD for DFU therapy remains unclear with no systematic elaboration. In vivo, following establishment of DFU rat model, DSD intervention with low, medium and high doses was done, with Metformin (DM) as a positive control group. With wound healing detection, pathological changes by HE staining, inflammatory factor expression by ELISA and qRT-PCR, oxidative stress levels by ELISA, and AGEs/RAGE/TGF-β/Smad2/3 expression by Western blot were performed. In vitro, intervention with LY2109761 (TGF-β pathway inhibitor) based on DSD treatment in human dermal fibroblast-adult (HDF-a) cells was made. Cell viability by CCK8, migration ability by cell scratch, apoptosis by flow cytometry, and AGEs/RAGE/TGF-β/Smad2/3 expression by Western blot were measured. DFU rats exhibited elevated AGEs/RAGE expression, whereas decreased TGF-β1 and p-Smad3/Smad3 protein expression, accompanied by higher IL-1β, IL-6, TNF-α levels, and oxidative stress. DSD intervention reversed above effects. Glucose induction caused lower cell viability, migration, TGF-β1 and p-Smad3/Smad3 protein expression, with increased apoptosis and AGEs/RAGE expression in HDF-a cells. These effects were reversed after DSD intervention, and further LY2109761 intervention inhibited DSD effects in cells. DSD intervention may facilitate wound healing in DFU by regulating expression of AGEs/RAGE/TGF-β/Smad2/3, providing scientific experimental evidence for DSD clinical application for DFU therapy.

Effects of modified Danggui Sini Decoction as adjuvant therapy for angina pectoris in coronary heart disease: a systematic review and meta-analysis based on randomised controlled trials.

This systematic review evaluates the efficacy of the Chinese herbal formula modified Danggui Sini Decoction as an adjunctive treatment for angina pectoris in patients with coronary heart disease. We conducted a comprehensive search for randomized controlled trials that investigated the effects of modified Danggui Sini Decoction in combination with conventional Western medication on angina pectoris in coronary artery disease, published up to July 2023 across eight databases, including China Knowledge International Literature screening and data extraction were performed by two researchers following predefined inclusion and exclusion criteria. The quality of included studies was assessed using the Cochrane Handbook version 5.1, and meta-analysis was executed via RevMan 5.4 software. Thirteen studies encompassing 1,232 participants were incorporated. The meta-analysis revealed that combining modified Danggui Sini Decoction with conventional Western medication significantly enhanced overall clinical efficacy, reduced the duration of angina attacks, decreased the Chinese medicine syndrome score, improved inflammatory markers and cardiac function, lowered serum NT-proBNP levels, and elevated the Seattle Angina Questionnaire scores compared to the control group. Modified Danggui Sini Decoction, when used alongside conventional Western medications, shows promise in treating coronary artery disease patients with angina pectoris and may serve as a beneficial adjunctive therapy in clinical settings. Nonetheless, due to the limited quantity and quality of the included studies, further high-caliber research is essential to substantiate these findings. https://inplasy.com/? s=202390078, identifier INPLASY 202390078.

Danggui Sini Decoction normalizes the intestinal microbiota and serum metabolite levels to treat sciatica

Ethnopharmacological relevanceDanggui Sini Decoction (DGSD), which is commonly used to treat sciatica, has been shown to have an analgesic effect, but the underlying mechanisms are unclear. Here, Danggui Sini Decoction was shown to normalize the intestinal microbiota and serum metabolite levels to exert an analgesic effect. Aim of the studyThis study aimed to elucidate the therapeutic effects of DGSD on sciatica and the underlying mechanisms involved. MethodsIn this study, we conducted chronic constriction injury (CCI) model. Mecobalamin and DGSD were administered to CCI rats. Behavioural tests were used to examine the therapeutic effects of the drugs. UHPLC was used to identify DGSD components. 16S rRNA gene sequencing analysis of the intestinal flora was used to analyse the effect of DGSD on the intestinal microbiota. UHPLC‒MS/MS was used to identify blood metabolites. KEGG pathway analysis of differentially abundant metabolites was subsequently conducted. ELISA was used to measure the serum inflammatory factor levels, and correlation analysis between the serum inflammatory factor levels and intestinal microbe abundance was conducted. PCR, western blotting, and immunohistochemical staining were used to validate the results of the KEGG pathway analysis. ResultsAfter CCI, the rats exhibited obvious thermal hyperalgesia; disruption of sciatic nerve structure; increased IL1α, SP, CCL5, and PGE2 levels; decreased IL10 levels in the blood; increased IL1β, IL6, COX2, MMP9, nNOS, and p-NF-κB levels; and decreased IL4 levels in the sciatic nerve. In addition, CCI led to increased abundances of Peptostreptococcaceae, Leuconostocaceae, Christensenellaceae, Akkermansiaceae, Staphylococcaceae, Romboutsia, Marvinbryantia, Turicibacter, Weissella, UCG-005, Christensenellaceae_R-7_group, Akkermansia, Staphylococcus, Romboutsia_ilealis, Weissella_paramesenteroides, and Akkermansia_muciniphila and decreased abundances of Lactobacillaceae, Lactobacillus, Lactobacillus_murinus, and Lactobacillus_johnsonii. Correlation analysis indicated that Turicibacter abundance was most strongly related to IL1α, PGE2, IL10, and CCL5 levels, while norank_o_Coriobacteriales abundance had the weakest relationship with SP levels. KEGG pathway analysis of the differentially abundant metabolites revealed that the ‘NF-kappa B signalling pathway’ was involved in sciatica. DGSD reduced the levels of inflammatory factors, including IL1α, SP, CCL5, PGE2, IL6, COX2, and MMP9, in the blood and sciatic nerve and inhibited nNOS and NF-κB phosphorylation. DGSD improved the abundance of probiotics, including Lactobacillus and Blautia, and lowered the abundance of harmful bacteria, including Romboutsia, Turicibacter, and Weissella. DGSD promoted the repair of the injured sciatic nerve. ConclusionsDGSD can treat sciatica by inhibiting intestinal microbiota disorders induced by CCI in rats, normalizing inflammatory factor levels, and promoting nerve repair.

Danggui Sini decoction alleviates oxaliplatin-induced peripheral neuropathy by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Danggui Sini decoction (DSD), a traditional Chinese medicine formula, has the function of nourishing blood, warming meridians, and unblocking collaterals. Our clinical and animal studies had shown that DSD can effectively protect against oxaliplatin (OXA)-induced peripheral neuropathy (OIPN), but the detailed mechanisms remain uncertain. Multiple studies have confirmed that gut microbiota plays a crucial role in the development of OIPN. In this study, the potential mechanism of protective effect of DSD against OIPN by regulating gut microbiota was investigated. The neuroprotective effects of DSD against OIPN were examined on a rat model of OIPN by determining mechanical allodynia, biological features of dorsal root ganglia (DRG) as well as proinflammatory indicators. Gut microbiota dysbiosis was characterized using 16S rDNA gene sequencing and metabolism disorders were evaluated using untargeted and targeted metabolomics. Moreover the gut microbiota mediated mechanisms were validated by antibiotic intervention and fecal microbiota transplantation. DSD treatment significantly alleviated OIPN symptoms by relieving mechanical allodynia, preserving DRG integrity and reducing proinflammatory indicators lipopolysaccharide (LPS), IL-6 and TNF-α. Besides, DSD restored OXA induced intestinal barrier disruption, gut microbiota dysbiosis as well as systemic metabolic disorders. Correlation analysis revealed that DSD increased bacterial genera such as Faecalibaculum, Allobaculum, Dubosiella and Rhodospirillales_unclassified were closely associated with neuroinflammation related metabolites, including positively with short-chain fatty acids (SCFAs) and sphingomyelin (d18:1/16:0), and negatively with pi-methylimidazoleacetic acid, L-glutamine and homovanillic acid. Meanwhile, antibiotic intervention apparently relieved OIPN symptoms. Furthermore, fecal microbiota transplantation further confirmed the mediated effects of gut microbiota. DSD alleviates OIPN by regulating gut microbiota and potentially relieving neuroinflammation related metabolic disorder.

Discussion on the mechanism of Danggui Sini decoction in treating diabetic foot based on network pharmacology and molecular docking and verification of the curative effect by meta-analysis.

The main active components and mechanism of Danggui Sini decoction (DSD) in treating diabetic foot (DF) were studied and verified by network pharmacology and molecular docking. Evidence-based medicine was used to prove its efficacy. The TCMSP systematic pharmacology platform screened out DSD's practical components and targets-screening disease targets in GeneCards database, using Cytoscape 3.7.2 to draw DSD-active ingredient-target network diagram, and drawing the protein interaction network diagram through STRING database. The Metascape platform was used to analyze the GO function enrichment and KEGG signal pathway. The molecular docking experiment was carried out by using Auto Dock vina 4.2. The related literature on DSD in treating DF in China Zhiwang, Wanfang, Weipu, and China Biomedical Literature Database was searched. The literature was screened, data was extracted, and quality was evaluated according to the inclusion and exclusion criteria. Then, a meta-analysis was performed using RevMan 5.3 software. A total of 256 targets of all effective components of DSD were obtained. Among 1,272 disease targets, there are 113 common targets. The GO analysis received 6,179 entries, and the KEGG pathway enrichment analysis found 251 related pathways. The molecular docking results of the main targets of diabetic foot and the active substances of DSD all showed a high docking activity. The meta-analysis included six literature, all of which were randomized controlled experiments. The quality grade of the literature was C, and the results showed that the total effective rate of clinical efficacy in the experimental group was significantly higher than that in the control group. DSD may treat DF by participating in biological processes such as cell proliferation regulation, inflammatory reaction, oxidative stress reaction, and promotion of angiogenesis. DSD treats DF through AKT1, TP53, IL6, TNF, VEGFA, and other targets. DSD plays a role in treating DF mainly through the AGE-RAGE signaling pathway and PI3K-AKT signaling pathway. The molecular docking results of AKT1, TP53, IL-6, TNF, and VEGFA with the active substances of DSD show that they all have a high docking activity; among them, VEGFA has a higher docking activity. Compared with conventional treatment, DSD has a high effective rate, short wound healing time, large wound healing area, and high ABI index.

Mechanism of Danggui Sini Decoction in improving kidney injury caused by blood stasis syndrome based on metabolomics and network pharmacology

This article analyzed the mechanism of Danggui Sini Decoction(DSD) in improving kidney injury caused by blood stasis syndrome(BSS) in rats. Firstly, 32 female SD rats were randomly divided into the following four groups: a normal group and a BSS group, both receiving an equal amount of distilled water by gavage; a normal+DSD group and a BSS+DSD group, both receiving 5.103 g·kg~(-1) DSD orally for a total of 14 days. Daily cold water bath was given to establish the BSS model, and on the 14th day, BSS rats were subcutaneously injected with 0.8 mg·kg~(-1) adrenaline. Normal rats were subjected to the water bath at 37 ℃ and injected with an equal volume of distilled water. After the experiment, 24-hour urine, serum, and kidney samples were collected for metabolomic analysis, biochemical measurements, and hematoxylin-eosin(HE) staining. The study then employed ~1H-NMR metabolomic technology to reveal the metabolic network regulated by DSD in improving BSS-induced kidney injury and used network pharmacology to preliminarily elucidate the key targets of the effectiveness of DSD. Pathological and biochemical analysis showed that DSD intervention significantly reduced inflammation and abnormal levels of blood creatinine, blood urea nitrogen, and urine protein in the kidneys. Metabolomic analysis indicated that DSD attenuated BSS-induced kidney injury primarily by regulating 10 differential metabolites and three major metabolic pathways(taurine and hypotaurine metabolism, citrate cycle, and acetaldehyde and dicarboxylic acid metabolism). Network pharmacology analysis suggested that the protective effect of DSD against BSS-induced kidney injury might be related to two key genes, ATP citrate lyase(ACLY) and nitric oxide synthase 2(NOS2), and two main metabolic pathways, i.e., arginine biosynthesis, and arginine and proline metabolism. This study, from the perspective of network regulation, provides initial insights and evidence into the mechanism of DSD in improving kidney injury induced by BSS, offering a basis for further investigation into the molecular mechanisms underlying its efficacy.

Combining Gut Microbiota Data with Network Pharmacology to Explore the Mechanism of Danggui Sini Decoction Action Against Blood Stasis Syndrome in Rats

Danggui Sini decoction is a traditional Chinese medicine preparation commonly used in the treatment of blood stasis syndrome through a mechanism yet to be defined. Therefore, we have explored its mechanism of action by combining pharmacology and gut microbiota analysis. To this end, female Sprague-Dawley rats were divided into 5 groups, including the control group, the acute blood stasis group, the Danshen tablet-treated group, the low-dose Danggui Sini decoction group, and the high-dose Danggui Sini decoction group. Danggui Sini decoction led to a significant reduction in the changes in the whole blood viscosity and plasma viscosity of rats with acute blood stasis syndrome, improved the coagulation function and cardiopulmonary pathological injury, upregulated the plasma 6-keto prostaglandin F1α and endothelial nitric oxide synthase, and downregulated thromboxane B2 and endothelin-1. The high throughput 16S rRNA gene sequencing results showed that Danggui Sini decoction reduced the number of pathogenic proteobacteria, significantly reduced erysipelas and suzericella, and increased the beneficial bacteria Roche, effectively improving the status of intestinal flora disorder in acute blood stasis rats. The Spearman correlation analyses showed that there was a close correlation between intestinal flora distribution and changes in blood stasis-related biochemical indices. In addition, network pharmacological analysis showed that the epidermal growth factor receptor, tumor protein p53, signal transducer and activator of transcription 3, vascular endothelial growth factor A, and hypoxia-inducible factor 1-alpha were the core targets of Danggui Sini decoction in alleviation of blood stasis. Further genetic ontological and pathway enrichment analyses suggested that the therapeutic effect of Danggui Sini decoction on blood stasis involved the lipid and atherosclerosis pathways, advanced glycation end-product-receptor for advanced glycation end-product signaling pathways in diabetic complications, fluid shear stress and atherosclerosis pathways, and hypoxia-inducible factors, 1-alpha signaling pathway, phosphatidylinositol 3-kinase- protein kinase B signaling, and other pathways. These results are helpful in understanding the mechanism by which Danggui Sini decoction improves blood stasis and provide a reference for further research.

Efficacy and safety of Chinese herbal medicine Danggui Sini decoction for knee osteoarthritis: A protocol for systematic review and meta-analysis.

Knee osteoarthritis (KOA) often causes joint pain, weakness and mobility disorders, which seriously affects people's daily life and makes them unable to work and study normally. Traditional Chinese medicine (TCM) prescription Danggui Sini Decoction (DGSND) has been widely used in clinical practice and achieved good results. But there is no high-level evidence to support this result. The aim of this study is to evaluate DGSND's efficacy and safety in the management of KOA. We will search 7 electronic databases including Chinese National Knowledge Infrastructure (CNKI), Wanfang Data (WF), Chinese Scientific Journals Database (VIP), Chinese databases SinoMed (CBM), PubMed, Embase, and Cochrane Library databases. All the publications, with no time restrictions, will be searched without any restriction of language and status, the time from the establishment of the database to September 2022. Two reviewers will independently assess the quality of the selected studies, NoteExpress and Excel software will be used to extract data, and the content will be stored in an electronic chart. Different researchers will separately screen the titles and abstracts of records acquired potential eligibility which comes from the electronic databases. Full-text screening and data extraction will be conducted afterward independently. Statistical analysis will be conducted using RevMan 5.4 software. This study will compare the effects of DGSND and any other different methods on patients with KOA to provide high-quality, evidence-based clinical recommendations. The study provides a trustable clinical foundation for DGSND in the treatment of KOA.

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA’s metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

Quality control of substance benchmarks for Danggui Sini Decoction

A comprehensive quality control method was established to provide references for quality control and evaluation of substance benchmarks of Danggui Sini Decoction(DSD). The HPLC separation was performed on a Kromasil 100 C-8 column(4.6 mm×250 mm, 5 μm) with acetonitrile(A)-0.05% phosphoric acid in water(B) as mobile phase in a gradient elution mode at the flow rate of 1 mL·min~(-1). The column temperature was 25 ℃ and the detection wavelength was set at 275 nm. Under these conditions, the content of seven components, including paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate, ligustilide, and asarinin was simultaneously determined. Under the same chromatographic conditions, the HPLC fingerprint method for analysis of 15 batches of DSD was established. The content determination of aristolochic acid I, using the same test solution as the content determination item, was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 μm) with methanol(A)-water(including 0.1% formic acid and 5 mmol·L~(-1) ammonium formate)(B) as the mobile phase in a gradient elution mode at the flow rate of 0.4 mL·min~(-1) and the column temperature of 40 ℃ by LC-MS/MS. The MS conditions included electrospray ionization(ESI) as an ion source, positive ion ionization, selective reaction monitoring(SRM), the parent ion of 359.3, and the daughter ion of 297.8. The results of the methodological investigation all met the requirements of content determination/fingerprint determination. As a result, the content ranges of paeoniflorin, liquiritin, cinnamic acid, cinnamaldehyde, ammonium glycyrrhetate, ligustilide, and asarinin were 5.419 8-11.267 3, 1.023-3.669 8, 0.145 6-0.444 1, 0.099 1-0.321 9, 3.159 1-7.731 9, 0.146 4-0.471 7, and 0.237 3-0.401 0 mg·g~(-1), respectively. Twenty-two common peaks were selected and 10 of them were identified by the comparison with the reference substances. The fingerprint similarity of 15 batches of DSD was in the range of 0.91-0.996 and the content of aristolochic acid I in DSD was 300.03-638.13 ng·g~(-1). The method established in this study is reliable and easy to operate and has great practical value, which can be used for overall quality control of substance benchmarks for DSD.

Study on the Effect and Safety of Danggui Sini Decoction in Treating Cold Syndrome of Blood Stasis and Blood Stasis Syndrome of Diabetes

Study on the Effect and Safety of Danggui Sini Decoction in Treating Cold Syndrome of Blood Stasis and Blood Stasis Syndrome of Diabetes

Preventive Efficacy and Safety of Yiqi-Wenjing-Fang Granules on Oxaliplatin-Induced Peripheral Neuropathy: A Protocol for a Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

Background. Oxaliplatin-induced peripheral neuropathy (OIPN) is one of the most common side effects of oxaliplatin, which can cause reduction and cessation of oxaliplatin-based chemotherapy and significantly affect patients' quality of life. However, no drug has got recognition to prevent or treat OIPN. Yiqi-Wenjing-Fang (YWF) is a joint name of Chinese medicine prescriptions with similar effects of tonifying qi and warming meridians, represented by Huangqi Guizhi Wuwu decoction (HGWD) and Danggui Sini decoction (DSD), both from “Treatise on Cold Pathogenic and Miscellaneous Diseases.” YWF granules, including HGWD granules and DSD granules, have been, respectively, demonstrated to be effective in preventing OIPN in previous small-sample observations. The purpose of this study is to enlarge the sample size for further evaluation of the preventive efficacy and safety of YWF granules on OIPN. Methods and Analysis. This study is a randomized, double-blind, placebo-controlled, and multicenter clinical trial. 360 postoperative patients with stage IIa-IIIc colorectal cancer will be randomly assigned into placebo-control group, intervention group I, and intervention group II, taking the mimetic granules of YWF as placebo, HGWD granules and DSD granules, respectively. All subjects will receive oxaliplatin-based chemotherapy regimen at the same time. EORTC QLQ-CIPN20 will be used to assess the degree of OIPN as the primary outcome measure. The grades of OIPN, quality of life, chemotherapeutic efficacy, and the number of completed chemotherapy cycles are selected as the secondary outcome measures. Discussion. Based on the condition of no recognized effective drugs in preventing OIPN, evidence-based medical study will be conducted for seeking a breakthrough in the field of Chinese herb medicine. This protocol could provide reliable and systemic research basis about the efficacy of YWF granules and the differentiation of two classical prescriptions of YWF on preventing OIPN objectively. Trial Registration. This study was registered at ClinicalTrials.gov on 26 December 2020 (ID: https://clinicaltrials.gov/ct2/show/NCT04690283).

Mechanism of Modified Danggui Sini Decoction for Knee Osteoarthritis Based on Network Pharmacology and Molecular Docking.

Objective This study aimed to explore the mechanism of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis via a combination of network pharmacology and molecular docking. Methods The main chemical components and corresponding targets of Modified Danggui Sini Decoction were searched and screened in TCMSP database. The disease targets of knee osteoarthritis were summarized in GeneCards, OMIM, PharmGkb, TTD, and DrugBank databases. The visual interactive network of “drugs-active components-disease targets” was drawn by Cytoscape 3.8.1 software. The protein-protein interaction network was constructed by STRING database. Then, GO function and KEGG pathway enrichment were analyzed by Bioconductor/R, and the pathway of the highest degree of correlation with knee osteoarthritis was selected for specific analysis. Finally, molecular docking was used to screen and verify core genes by AutoDockTools software. Results Seventy-one main components of Modified Danggui Sini Decoction and 116 potential therapeutic targets of knee osteoarthritis were selected. The KEGG pathway and the GO function enrichment analysis showed that the targets of Modified Danggui Sini Decoction in the treatment of knee osteoarthritis were mainly concentrated on PI3K-Akt signaling pathway, TNF signaling pathway, IL-17 signaling pathway, apoptosis signaling pathway, Toll-like receptor signaling pathway, Th17 cell differentiation signaling pathway, HIF-1 signaling pathway, and NF-κB signaling pathway. It mainly involved inflammatory reaction, regulation of apoptotic signaling pathway, cellular response to regulation of inflammatory response, cellular response to oxidative stress, and other biological processes. The molecular docking results showed that ESR1-wogonin, MAPK1-quercetin, RELA-wogonin, RELA-baicalein, TP53-baicalein, TP53-quercetin, and RELA-quercetin have strong docking activities. Conclusion Modified Danggui Sini Decoction has the hierarchical network characteristics of “multicomponent, multitarget, multifunction, and multipathway” in the treatment of knee osteoarthritis. It mainly regulates the proliferation and apoptosis of chondrocytes by regulating the PI3K-Akt signaling pathway and establishes cross-talk with many downstream inflammatory-related pathways to reduce the overall inflammatory response. Meanwhile, HIF-1 expression was used to ensure the normal function and metabolism of knee joint under hypoxia condition, and the above processes play a key role in the treatment of knee osteoarthritis.

Mechanism of Danggui Sini Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.

A Mechanism of Action Study on Danggui Sini Decoction to Discover Its Therapeutic Effect on Gastric Cancer.

Danggui Sini Decoction (DSD), a classic Chinese herb medicine (CHM) formula, has been used to treat various diseases in China for centuries. However, it remains challenging to reveal its mechanism of action through conventional pharmacological methods. Here, we first explored the mechanism of action of DSD with the assistance of network pharmacology and bioinformatic analysis tools, and found a potential therapeutic effect of DSD on cancer. Indeed, our in vivo experiment demonstrated that oral administration of DSD could significantly inhibit the growth of xenografted gastric cancer (GC) on mice. The subsequent enrichment analyses for 123 candidate core targets evacuated from the drug/disease-target protein-protein interaction network showed that DSD could affect the key biological processes involving the survival and growth of GC cells, such as apoptosis and cell cycle, and the disturbance of these biological processes is likely attributed to the simultaneous inhibition of multiple signaling pathways, including PI3K/Akt, MAPK, and p53 pathways. Notably, these in silico results were further validated by a series of cellular functional and molecular biological assays in vitro. Moreover, molecular docking analysis suggested an important role of MCM2 in delivering the pharmacological activity of DSD against GC. Together, these results indicate that our network pharmacology and bioinformatics-guided approach is feasible and useful in exploring not only the mechanism of action, but also the “new use” of the old CHM formula.

Uncovering the Complexity Mechanism of Different Formulas Treatment for Rheumatoid Arthritis Based on a Novel Network Pharmacology Model.

Traditional Chinese medicine (TCM) with the characteristics of “multi-component-multi-target-multi-pathway” has obvious advantages in the prevention and treatment of complex diseases, especially in the aspects of “treating the same disease with different treatments”. However, there are still some problems such as unclear substance basis and molecular mechanism of the effectiveness of formula. Network pharmacology is a new strategy based on system biology and poly-pharmacology, which could observe the intervention of drugs on disease networks at systematical and comprehensive level, and especially suitable for study of complex TCM systems. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease, causing articular and extra articular dysfunctions among patients, it could lead to irreversible joint damage or disability if left untreated. TCM formulas, Danggui-Sini-decoction (DSD), Guizhi-Fuzi-decoction (GFD), and Huangqi-Guizhi-Wuwu-Decoction (HGWD), et al., have been found successful in controlling RA in clinical applications. Here, a network pharmacology-based approach was established. With this model, key gene network motif with significant (KNMS) of three formulas were predicted, and the molecular mechanism of different formula in the treatment of rheumatoid arthritis (RA) was inferred based on these KNMSs. The results show that the KNMSs predicted by the model kept a high consistency with the corresponding C-T network in coverage of RA pathogenic genes, coverage of functional pathways and cumulative contribution of key nodes, which confirmed the reliability and accuracy of our proposed KNMS prediction strategy. All validated KNMSs of each RA therapy-related formula were employed to decode the mechanisms of different formulas treat the same disease. Finally, the key components in KNMSs of each formula were evaluated by in vitro experiments. Our proposed KNMS prediction and validation strategy provides methodological reference for interpreting the optimization of core components group and inference of molecular mechanism of formula in the treatment of complex diseases in TCM.

Danggui Sini decoction for treating diabetic peripheral neuropathy: A protocol of systematic review and meta-analysis of randomized controlled trials.

Background:Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetic patients, which seriously affects the quality of life of patients. At present, mainstream drugs have problems such as poor efficacy and side effects. Traditional Chinese medicine (TCM) has extensive clinical experience in the prevention and treatment of diabetes and chronic complications, and it also shows clear advantages in the treatment of DPN. Clinical studies have confirmed that Danggui Sini decoction (DSD), a TCM decoction, can improve the clinical symptoms and signs of DPN patients. Therefore, we will conduct a systematic review to clarify the effectiveness and safety of DSD for DPN.Methods:We will search every database from the built-in to October 2020. Chinese literature comes from CNKI, Wanfang, VIP, and CBM databases. English literature mainly searches Cochrane Library, PubMed, Web of Science, and EMBASE. At the same time, we will also search for clinical registration tests and gray literatures. This study only screened clinical randomized controlled trials (RCT) for DSD for DPN. The two researchers independently conducted literature selection, data extraction and quality assessment. Dichotomous data is represented by relative risk (RR), continuous data is represented by mean difference (MD) or standard mean deviation (SMD), and the final data is fixed effect model (FEM) or random effect model (REM), depending on whether it exists Heterogeneity. The main result is clinical efficacy and nerve conduction velocity. Fasting blood glucose, 2 hours postprandial blood glucose, blood lipid, hemorheology, and adverse events are secondary results. Finally, a meta-analysis was conducted through Review Manager software version 5.3.Results:This study will conduct a comprehensive analysis based on the currently released DSD data for the treatment of DPN and provide high-quality evidence of clinical efficacy and safety.Conclusion:This systematic review aims to provide new options for DSD treatment of DPN in terms of its efficacy and safety.Ethics and dissemination:The review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines, or peer-reviewed journals.INPLASY registration number:INPLASY202040157.