Cancer Biology & Medicine
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2024
·Vol. 21
·期 11
·1067
·
IF 5.6
Boyu Pan,Han Zhu,Jiaqi Yang,Liangjiao Wang,Zizhen Chen,Jian Ma,Bo Zhang,Zhanyu Pan,Guoguang Ying,Shao Li,Liren Liu
Objective: 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. Methods: 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. Results: 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. Conclusions: 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/ .
研究领域:
中药学
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生物信息学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yun Li,Teng-Teng Ren,Shan-Shan Liu,Ling Zhang,Hong Yi,Chun Li,Liang-Mian Chen,Hui-Min Gao,Li-Hua Yan,Xiao-Qian Liu,Zhi-Min Wang
Ethnopharmacological relevance Dang-Gui-Si-Ni (DGSN) decoction is a classic prescription in the clinical practice of traditional Chinese Medicine (TCM). DGSN decoction is often used to relieve symptoms of cold coagulation and blood stasis recorded by Treatise on Febrile Diseases ( Shang Han Lun ) and treat Raynaud's disease, dysmenorrhea, arthritis, migraine in TCM clinic. Accumulated evidences have suggested that this diseases are related to microcirculation disturbance. However, the anticoagulant activity and underlying mechanisms of DGSN decoction responsible for the therapeutic not well understood. Aim of the study The fingerprint and anticoagulant activity in vivo-in vitro of DGSN decoction were evaluated to strengthen the quality control and activity study of formulas. Materials and methods The chemical components of DGSN decoction were analyzed by HPLC and its fingerprint similarity were evaluated by “Chinese Medicine Chromatographic Fingerprint Similarity Evaluation Software (2012 Edition)". The anticoagulant activity of DGSN decoction was assessed by measuring four coagulation factors (PT, TT, APTT, FIB) in vitro . Zebrafish thrombosis model induced by punatinib was established to evaluate the activity of improving microvascular hemodynamics in vivo . Quantitative real-time polymerase chain reaction (q-PCR) were adopted to compare the changes in the RNA expression levels of coagulation factor II (FII), VII (FVII), IX (FIX) and X (FX) in zebrafish thrombosis model. Results The fingerprint similarity evaluation method of DGSN decoction was established. The results showed that 18 samples had higher similarity (S1–S18 > 0.878). Pharmacodynamic results showed that DGSN decoction could extend PT, TT and APTT, and reduce FIB content in vitro . Meanwhile, it markedly enhanced the cardiac output and blood flow velocity at low dosage (500 μg mL −1 ) in vivo . q-PCR data demonstrated that DGSN decoction (500 μg mL −1 ) could downregulate the RNA expression of FII, FVII, FIX and FX. Interestingly, there were a bidirectional regulation of FII, FIX and FX in a certain concentration range. In general, DGSN decoction can significantly improve hemodynamics and downregulate coagulation factors, and the results were consistent both in vitro - in vivo . Conclusion The fingerprint study provide a new perspective for improving the quality control of DGSN decoction. DGSN decoction possess anticoagulant activity by regulating multiple coagulation factors simultaneously. Thus, it has the potential to develop into the novel raw material of anticoagulant drugs.
研究领域:
中药学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Qian Zhou,Ping Meng,Ya Zhang,Peng Chen,Haibo Wang,Guangguo Tan
Ethnopharmacological relevance Sini decoction (SND) is a famous Traditional Chinese Medicine (TCM) formula composed of Acontium carmichaeli , Zingiber officinale and Glycyrrhiza uralensis , which is considered as an efficient formula against doxorubicin (DOX)-induced heart failure. But the compatibility mechanism of SND remains unclear. Aim of the study The present study aimed to investigate the compatibility mechanism of SND against DOX-induced heart failure in rats. Materials and methods Mass spectrometry-based serum metabolomics were performed. The relative distance values (RDVs) of SND, A. carmichaeli -free decoction (ACFD), Z. officinale -free decoction (ZOFD) and G. uralensis -free decoction (GUFD) treated groups from the control/DOX groups in multidimensional space were calculated to provide a measure of compatibility effect of SND. SND, ACFD, ZOFD, GUFD-targeted metabolic pathways were identified and compared to investigate the synergistic mechanism of SND by computational systems analysis. Real-time quantitative PCR was further employed to validate the key metabolic pathways at the level of the gene. Results The RDVs combined with the hemodynamic and biochemical analysis showed that the protection effects were sorted as SND > GUFD > ZOFD > ACFD. It revealed that DOX-induced heart failure perturbed 16 metabolic pathways, and SND, GUFD, ZOFD and ACFD-treated groups could significantly reversed 12, 10, 7 and 6 metabolic pathways of these 16 metabolic pathways, respectively. Metabolic pathway and RT-PCR analysis indicated that both SND and GUFD could protect DOX-induced heart failure mainly by regulating PLA2-COX pathway and PLA2-CYP pathway. Conclusion It can be concluded that A. carmichaeli played an essential role in attenuation of DOX-induced heart failure among the three herb constituents of SND and the constituent herbs mutually reinforced each other. This work demonstrated that metabolomics combined with computational systems analysis was a promising tool for uncovering the compatibility effects of TCM.
研究领域:
药理学
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中医药学
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代谢组学
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系统生物学
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DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
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2014
·Vol. 71
·期 2
·945-950
·
IF 2.38
Chen Qing-quan,Han Xuesong,Wang Wan-ming,Zhao Liangyu,Chen Aimin
Danggui Sini decoction (DSD), a famous Chinese medicine, has been used therapeutically in various diseases. In this study, we tried to investigate whether and how DSD could ameliorate myelosuppression in an animal model, in which myelosuppression is induced by cyclophosphamide treatment. The myelosuppression model was established by intraperitoneal injection of 100 mg/kg cyclophosphamide in mice. Flow cytometry was used to assess cell numbers and evaluate the bone marrow cell cycle distribution. Spleen samples were collected, and the mRNA expression levels of thrombopoietin (TPO) and c - Mpl were analyzed by RT-PCR. Our results demonstrated that DSD could significantly elevate the level of bone marrow hematopoietic stem progenitor cells in myelosuppression mice model. DSD also accelerated cell proliferation by switching cell cycles from G0/G1 phase to S and G2/M phase. Moreover, DSD significantly elevated the mRNA expression level of TPO , but not c - Mpl in spleen. Overall, the present results indicated that DSD is a promising Chinese medicine that is highly potent to ameliorate myelosuppression induced by chemotherapy by upregulating TPO expression.
研究领域:
药理学
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血液学
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肿瘤学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Zhang Di,Chen Zhenni,Zhuang Zifeng,Jing Bei,Cao Yong,Li Yixuan,Pan Yuwei,Gao Li,Chen Jiaxu,Zhao Guoping
Ethnopharmacological relevance Danggui 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 study This study aimed to elucidate the therapeutic effects of DGSD on sciatica and the underlying mechanisms involved. Methods In 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. Results After 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. Conclusions DGSD can treat sciatica by inhibiting intestinal microbiota disorders induced by CCI in rats, normalizing inflammatory factor levels, and promoting nerve repair.
研究领域:
药理学
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神经科学
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微生物学
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代谢组学
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民族药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yanru Liu,Hui Chen,Gongjun Yang,Fang Feng
Ethnopharmacological relevance Yin-Chen-Si-Ni Decoction is a classical traditional Chinese medicine (TCM) prescription that is used clinically for treating cholestatic liver injury (CLI) and other hepatic diseases. However, the material basis and underlying mechanisms of YCSND are not clear. Aim of the study : To investigate effective components and mechanisms of YCSND in the treatment of CLI using serum pharmacochemistry, metabolomics, and network pharmacology. Materials and methods Biochemical indicators, liver index, and histopathology analysis were adopted to evaluate the protective effect of YCSND on ANIT-induced CLI rats. Then, a UPLC-Q-Exactive Orbitrap MS/MS analysis of the migrant components in serum and liver including prototype and metabolic components was performed in YCSND. In addition, a study of the endogenous metabolites using serum and liver metabolomics was performed to discover potential biomarkers, metabolic pathways, and associated mechanisms. Further, the network pharmacology oriented by in vivo migrant components was also used to pinpoint the active ingredients, core targets, and signaling pathways of YCSND. Finally, molecular docking and molecular dynamics simulation (MDS) were used to predict the binding ability between components and core targets, and a real-time qPCR (RT-qPCR) experiment was used to measure the mRNA expression of the core target genes. Results Pharmacodynamic studies suggest that YCSND could exert obvious hepatoprotective effects on CLI rats. Furthermore, 68 compounds, comprising 32 prototype components and 36 metabolic components from YCSND, were found by serum pharmacochemistry analysis. Network pharmacology combining molecular docking and MDS showed that apigenin, naringenin, 18β-glycyrrhetinic acid, and isoformononetin have better binding ability to 6 core targets (EGFR, AKT1, IL6, MMP9, CASP3, PPARG). Additionally, PI3K, TNF-α, MAPK3, and six core target genes in liver tissues were validated with RT-qPCR. Metabolomics revealed the anti-CLI effects of YCSND by regulating four metabolic pathways of primary bile acid and biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, taurine and hypotaurine metabolism, and arachidonic acid metabolism. Integrating metabolomics and network pharmacology identified four pathways related to CLI, including the PI3K-Akt, HIF-1, MAPK, and TNF signaling pathway, which revealed multiple mechanisms of YCSND against CLI that might involve anti-inflammatory and apoptosis. Conclusion The research based on serum pharmacochemistry, network pharmacology, and metabolomics demonstrates the beneficial hepatoprotective effects of YCSND on CLI rats by regulating multiple components, multiple targets, and multiple pathways, and provides a potent means of illuminating the material basis and mechanisms of TCM prescriptions.
研究领域:
药理学
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中医药学
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分子生物学
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代谢研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2018
·
IF 3.115
Min Zhang,Ying Peng,Mengyue Wang,Beibei Gao,Lijuan Zhao,Xiaobo Li
Ethnopharmacological relevance In traditional Chinese medicine , processed aconite root (lateral root of Aconitum carmichaelii Debx.) is used as the principle herb of the Si-Ni decoction (SND) formula due to its cardiotonic effect, while its cardiotoxicity and neurotoxicity caused by diester and monoester diterpenoid alkaloids are reduced by compatibility of dried ginger and honey-processed liquorice in SND. Aim of the study To investigate the detoxification of processed aconite root by compatibility of SND from the perspective of intestinal absorption with metabolism in intestinal bacteria . Materials and methods Decoctions of processed aconite root (AD), processed aconite root and honey-processed liquorice (ALD), and SND with the same amount of each herb were prepared, then were incubated in human intestinal bacteria juice (IBJ) in vitro for different durations. Bidirectional transmembrane transports of these decoctions and their IBJ-incubated decoctions were conducted on Caco-2 monolayers. Correlation between efflux ratios changes of benzoylmesaconine, benzoylaconine, benzoylhypaconine (monoester-diterpenoid alkaloids, MDAs) and hypaconitine (diester-diterpenoid alkaloids) from processed aconite root, and metabolic trends of compounds from honey-processed liquorice and dried ginger were also performed. Results The absorption of MDAs from processed aconite root was increased by combination with honey-processed liquorice in ALD, but they were decreased significantly by the addition of dried ginger in SND. Take benzoylhypaconine for example, the P app, AP to BL soared from ( 3.13 ± 0.18) × 10 −7 cm/s in AD to (23.32 ± 3.51) × 10 −7 cm/s in ALD, while it dropped to (1.12 ± 0.17) × 10 −7 cm/s in SND. When herb combined decoctions metabolised by intestinal bacteria for 12 h, the efflux ratio of benzoylhypaconine were both increased from 0.56 to 1.21 in ALD and from 1.10 to 2.61 in SND, which was correlative with the generation of davidigenin and glycyrrhetic acid (the metabolites of chalcones and pentacyclic triterpenoids from liquorice) in ALD and with the metabolism of [6]-gingerol (the major compound from dried ginger) in SND, respectively. Conclusions Compatibility of SND altered the intestinal absorption of toxic MDAs and hypaconitine from processed aconite root. In SND, dried ginger rather than honey-processed liquorice played the role of detoxification of these toxic compounds in the intestinal absorption. The intestinal detoxification of SND was significantly and strongly correlative with metabolism of dried ginger and honey-processed liquorice by intestinal bacteria, simultaneously.
研究领域:
药理学
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民族药理学
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微生物学
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毒理学
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中医药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2024
·
IF 4.7
Cuiping Long,Qian Zhou,Min Xu,Xin Ding,Xingxing Zhang,Ya Zhang,Yuping Tang,Guangguo Tan
Objective Myocardial inflammation during myocardial infarction (MI) could be inhibited by regulating arachidonic acid (AA) metabolism. Recent studies demonstrated that Sini Decoction (SND) was identified to be an effective prescription for treating heart failure (HF) caused by MI. But the anti-inflammatory mechanism of SND remained unclear. The work was designed to investigate the anti-inflammatory mechanism of SND through the AA metabolism pathway in vitro and in vivo experiments. Methods An inflammatory injury model of H9c2 cells was established by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM). The animal MI model was built by the ligation of left anterior descending (LAD) branch of coronary artery in rat. Meanwhile, the rats were divided into five groups: sham group, MI group, MI + Celecoxib group, MI + low-dose SND group (SND-L) and MI + high-dose SND group (SND-H). Cardiac function, histopathological changes and serum cytokines were examined four weeks later. Western blot analysis was conducted to verify the key enzymes levels in the AA metabolic pathway, including phospholipase A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs). Results These in vivo results demonstrated that SND could improve the cardiac function and pathological changes of rats with MI, and regulate the key inflammatory molecules in the AA metabolism pathway, including sPLA2, COX-1, COX-2, 5-LOX and 15-LOX. In vitro , SND could decrease the release of pro-inflammatory cytokines including TNF-α and IL-6 and inhibit cell apoptosis in CM-induced H9c2 cells. Moreover, SND could protect H9c2 cells from the damage of CM by regulating nuclear factor kappa-B (NF-κB) signal pathway and the expression of COX-2. Conclusion SND may be a drug candidate for anti-inflammatory treatment during MI by regulating the multiple targets in the AA metabolism pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Junling Ren,Xia Wang,Yuran Sun,Le Yang,Hui Sun,Ye Sun,Ling Kong,Guangli Yan,Ying Han,Xijun Wang
Background Danggui 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. Purpose The 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. Methods DGSND 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. Results DGSND was effective in ameliorating writhing times, latency time, the value of prostaglandin F 2α (PGF 2α )/PGE 2 , 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, PLA 2 , LPCAT3, COX-2, and 5-LOX can be greatly downregulated by DGSND. Conclusion Our findings demonstrated a novel protective mechanism of DGSND against PD by regulating lipid homeostasis.
研究领域:
药理学
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代谢组学
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脂质组学
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中医
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动物模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）