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Objective: To explore the potential molecular mechanism of tetrahydropalmatine (THP) on acute myocardial ischemia (AMI). Methods: First, the target genes of THP and AMI were collected from SymMap Database, Traditional Chinese Medicine Database and Analysis Platform, and Swiss Target Prediction, respectively. Then, the overlapping target genes between THP and AMI were evaluated for Grene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein-protein interaction network analysis. The binding affinity between the protein and THP was assessed by molecular docking. Finally, the protective effects of THP on AMI model and oxygen and glucose deprivation (OGD) model of H9C2 cardiomyocyte were explored and the expression levels of target genes were detected by RT-qPCR in vivo and in vitro. Results: MMP9, PPARG, PTGS2, SLC6A4, ESR1, JAK2, GSK3B, NOS2 and AR were recognized as hub genes. The KEGG enrichment analysis results revealed that the potential target genes of THP were involved in the regulation of PPAR and hormone pathways. THP improved the cardiac function, as well as alleviated myocardial cell damage. Furthermore, THP significantly decreased the RNA expression levels of MMP9, PTGS2, SLC6A4, GSK3B and ESR1 (P<0.05, P<0.01) after AMI. In vitro, THP significantly increased H9C2 cardiomyocyte viability (P<0.05, P<0.01) and inhibited the RNA expression levels of PPARG, ESR1 and AR (P<0.05, P<0.01) in OGD model. Conclusions: THP could improve cardiac function and alleviate myocardial injury in AMI. The underlying mechanism may be inhibition of inflammation, the improvement of energy metabolism and the regulation of hormones. [ABSTRACT FROM AUTHOR]

Triptolide (TP), a bioactive compound extracted the from traditional Chinese medicine Tripterygium wilfordii Hook F (TwHF), has been shown to be effective in treating several autoimmune diseases, and has suppressive effects in several key immune cells such as dendritic cells, T cells, and macrophages. However, it is unknown whether TP has an impact on natural killer (NK) cells. Here, we report that TP has suppressive effects on human NK cell activity and effector functions. The suppressive effects were observed in human peripheral blood mononuclear cell cultures and purified NK cells from healthy donors, as well as in purified NK cells from patients with rheumatoid arthritis. TP treatment induced downregulation of NK-activating receptor (CD54, CD69) expression and IFN-gamma secretion, in a dose-dependent manner. When exposed to K562 target cells, TP treatment induced inhibition of surface expression of CD107a and IFN-gamma synthesis in NK cells. Furthermore, TP treatment induced activation of inhibitory signaling (SHIP, JNK) and inhibition of MAPK signaling (p38). Thus, our findings demonstrate a previously unknown role for TP in NK cell functional suppression and reveal several key intracellular signaling that can be regulated by TP. Our findings also offer new insight into mechanisms of TP therapeutic treatment in autoimmune disease. [ABSTRACT FROM AUTHOR]

Background. To explore the rules of TCM medication in the treatment of constipation in network pharmacology. Methods. Collect and screen the clinical intervention literature on TCM for constipation from China's national knowledge infrastructure, Wanfang and VIP databases established a database of TCM for constipation, applied R software (3.3.1) to analyze the pattern of prescriptions for TCM for constipation, and summarized the core prescription. The effective active compounds and action targets in the core prescription were screened by Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Traditional Chinese Medicine Integrated Databases (TCMID), constipation-related targets were derived from the DisGeNET and GeneCards databases, Protein-protein interaction network (PPI) was drawn by STRING database, and enrichment analysis was conducted by the Clusterprofiler package in R software (3.3.1). Finally, molecular docking was used to validate the binding ability of candidate compounds to potential targets. Results. Two hundred sixteen target prescriptions were screened through data mining, involving 226 herbs. Association rule analysis results suggested that the "Angelicae sinensis-Radix-dried rehmanniae-Cistanche deserticola-Atractylodes macrocephala-Astragali Radix" was a strong affinity for medicine. Network pharmacology analysis of the core prescription resulted in the screening of 115 candidate compounds, such as quercetin, kaempferol, mangostin, eugenol A, and beta-sitosterol; 131 potential targets, such as PTGS2, PTGS1, and CHRM3; and 160 signaling pathways, such as lipid and atherosclerosis, proteoglycans in cancer, hepatitis B, Kaposi's sarcoma-associated herpesvirus infection, and PI3K/AKT pathways. Molecular docking showed that PTGS1-formononetin, PTGS2-kaempferol, and CHRM3-kaempferol were all well bound and well matched. Conclusions. This study provides a new method and ideas for clinical applications of integrated Chinese and western medicine in treating constipation. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) is a major cause of morbidity and mortality globally, and is characterized by widespread inflammation in the lungs. Increased production of reactive oxygen species is hypothesized to be associated with ALI. Matrine and lycopene are active products present in traditional Chinese medicine. Matrine is an effective inhibitor of inflammation, whereas lycopene decreases lipid peroxidation. Therefore, it was hypothesized that combinatorial treatment with matrine and lycopene may provide synergistic protection against ALI. In the present study, mice were treated with dexamethasone (DEX; 5 mg/kg), matrine (25 mg/kg), lycopene (100 mg/kg), and matrine (25 mg/kg) + lycopene (100 mg/kg) for 7 days prior to injury induction using lipopolysaccharide (LPS; 5 mg/kg) for 6 h. Lung tissues were collected following the sacrifice of the mice and hematoxylin and eosin staining was used for histological analysis. Malondialdehyde (MDA), glutathione (GSH) and myeloperoxidas (MPO) levels were examined by respective kits. The expressions of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The expressions of IκBα and NF-κB p65 were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The results indicated that the combined treatment exhibited a similar effect to DEX, both of which attenuated lung structural injuries, downregulated the expressions of IL-6, TNF-α, MPO and MDA, and upregulated that of GSH. Furthermore, the combined treatment and DEX inhibited NF-κB p65 activation. The present study revealed that combined treatment with matrine and lycopene exhibited protective effects on an LPS-induced mouse model of ALI, suggesting that they may serve as a potential alternative to glucocorticoid therapy for ALI. [ABSTRACT FROM AUTHOR]

Fear- and anxiety-related psychiatric disorders have been one of the major chronic diseases afflicting patients for decades, and new compounds for treating such disorders remain to be developed. (+)-Borneol, a bicyclic monoterpene found in several species of Artemisia and Dipterocarpaceae, is widely used for anxiety, pain and anesthesia in Chinese medicine. Meanwhile, it can potentiate GABA (γ-aminobutyric acid) activity directly in recombinant GABAA receptors. The present study was to investigate the effects of (+)-Borneol on both contextual and cued fear recall. Interestingly, microinjection of (+)-Borneol into the dorsal hippocampus inhibited 24 h and 7 d contextual fear, whereas its infusion into ventral hippocampus only reduced 24 h cued fear responses. Moreover, microinjection of (+)-Borneol into dorsal but not ventral hippocampus suppressed anxiety-like behaviors in the open field test, light/dark exploration and the elevated plus maze test. As selective GABA A receptor antagonist bicuculline reversed the effect of (+)-Borneol on contextual fear paradigm and the drug potentiated GABA-evoked currents in acute hippocampus slices, modulation of the GABAergic neurotransmission may explain the effects of (+)-Borneol. Our findings suggest that (+)-Borneol can serve as a new therapeutic in fear- and anxiety-related disorders. [ABSTRACT FROM AUTHOR]

Lung cancer poses a serious threat to human health. Although targeted therapies have led to breakthroughs in the treatment of lung cancer, drug resistance and side effects limit their clinical applications. Xihuang pill (XHW), a classical anti-cancer traditional Chinese medicine formula, has been clinically proven to be an effective complementary therapy in the treatment of various of cancers. However, the underlying mechanism for its use in combination with anti-cancer drugs remains unclear. Here, we explored the anti-lung cancer effect of XHW combined with anlotinib in mice bearing Lewis lung cancer (LLC). We used gut microbiota and transcriptomics to elucidate the regulatory properties of XHW in improving anti-lung cancer effect of anlotinib. The results showed that combination treatment of XHW with Anlotinib significantly inhibited tumor growth in LLC-bearing mice. We found that XHW played a key role in the regulation of gut microbiota using 16 s rRNA sequencing analysis. Specifically, XHW increased the proportion of the beneficial bacteria Bacteroides and g_norank_f_Muribaculaceae. Based on transcriptomic analysis of tumor tissues, differentially expressed genes in the combination therapy group were related to biological processes concerning angiogenesis, such as regulation of blood vessel diameter, regulation of tube diameter, and regulation of tube size. Our data suggest that XWH enhances the anticancer effect of anlotinib by regulating gut microbiota composition and tumor angiogenesis pathway. Combination therapy with anlotinib and XHW may be a novel therapeutic strategy for lung cancer patients. [Display omitted] • XHW improved the effects of anlotinib in the Lewis lung cancer (LLC) -incubated mouse model. • XWH enhances the antitumor effect of Anlotinib by modulating gut microbiota composition. • XHW potentiates the antitumor effect of Anlotinib by regulating tumor angiogenesis. • Combination therapy with XHW and Anlotinib offers a new therapeutic strategy for lung cancer patients. [ABSTRACT FROM AUTHOR]

Xiaojin Pills was first recorded during the Qing Dynasty and have a history of nearly 300 years. It is the first choice among Chinese patent medicines for the clinical treatment of diseases of the mammary glands in contemporary traditional Chinese medicine. It was also widely used in the treatment of breast cancer, lung cancer, thyroid cancer, and other malignant tumors. Its initial administration method was "taken orally after soaking with Chinese baijiu"; however, the method was changed to "taken orally with water" within the last 40 years. There is no scientific evidence for the difference in efficacy against breast cancer between the two methods of administration. In vitro and in vivo experiments were carried out to confirm the therapeutic advantages of the liquor extract of Xiaojin Pills to improve the efficacy against breast cancer, and the mechanism was explained in terms of metabolomics and molecular biology. In vitro , a cell counting kit-8 cell activity assay and flow cytometry were used to detect the activity and apoptosis of MCF-7 breast cancer cells. In vivo , pharmacodynamic evaluation was performed by constructing a heterotopic transplantation model of breast cancer in BALB/c-nu mice. TUNEL staining was used to observe the apoptosis of cells in tumor tissues. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/Akt pathway in BALB/c-nu mice tissue was investigated by metabolomics analysis, immunohistochemistry and western blotting. CCK-8 assay showed that the IC 50 of XJP-L for the inhibition of the activity of MCF-7 cells was less than that of XJP-W at different times. Flow cytometry assay suggested that the apoptosis rate in the XJP-L group was higher than that in the normal control group (p < 0.01). Animal experiment results indicated that both XJP-W group and XJP-L group reduced the volume and quality of the tumor after administration, and the reduction was more significant in the XJP-L group (p < 0.01). Metabolomics analysis results demonstrated that there are about 26 different metabolites have been screened in the serum metabolites between the liquor and water extract, mainly involved in glycerophospholipid, glutamic acid, aspartic acid, nitrogen and pyrimidine metabolism. In addition, immunohistochemistry and WB results showed that compared with the model group, the protein expression of PTEN, AKT, BAX and in tumor tissues of XJP-L and XJP-W groups both exhibited an upward trend, while the expression of BCL-2, p-PI3K and p-AKT exhibited a downward trend, which was much more obvious in XJP-L group. This study demonstrates that the liquor extract of Xiaojin Pills had a stronger anti-breast cancer effect than that of the water extract. The PI3K/Akt signaling pathway might play an important role in the mechanism of the liquor extract of Xiaojin Pills and thus improve the efficacy against breast cancer. [ABSTRACT FROM AUTHOR]

• DSC, synchrotron XRD and FTIR techniques have been employed in this study. • EVO and RUT affect liposome membrane in a concentration-dependent manner. • The effect of RUT on liposome membrane was stronger than that of EVO. Evodiamine and rutaecarpine, derived from the traditional chinese medicine Euodia rutaecarpa (Juss.) Benth, have many similar pharmacological effects, but their pharmacological mechanisms are not exactly the same. In this study, liposomes were used as the model of biomembrane. DSC, synchrotron XRD and FTIR techniques have been employed to investigate and compare the interaction of evodiamine and rutaecarpine with DPPC liposomes. The results show that evodiamine and rutaecarpine remarkably affect the DPPC in a concentration-dependent manner. But the concentration dependence of the two drugs is obviously different. The effect of rutaecarpine on liposome membrane was stronger than that of evodiamine, which might be related to the different pharmacological mechanism of evodiamine and rutaecarpine. This study will play an important role in the further investigation of interaction of drugs with biomimetic membranes and further investigation of pharmacological mechanisms of drugs. [ABSTRACT FROM AUTHOR]

Osthole, 7-methoxy-8-[3-methylpent-2-enyl]coumarin (1), was extracted from a Chinese herb Cnidium monnieri (L.) Cuss. It showed immunity strengthening, anti-tumor, anti-hepatitis, and anti-osteoporosis activities in previous studies. Our goals are to study the effects of 1 on cell proliferation and TGF-β of hypertrophic scar fibroblasts. Our results showed that 1 induced apoptosis and inhibited cell proliferation in hypertrophic scar fibroblasts. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that its IC50 value toward hypertrophic scar fibroblasts was 15.5 ± 2.2 μmol/l. Furthermore, the results of cell growth curve matched with the above results. Inducing apoptosis by 1 in hypertrophic scar fibroblasts was assessed by various morphological and biochemical characteristics, including cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies, and DNA ladder formation. A typical 'Sub-G1 peak' was also checked through flow cytometry. We used immunohistochemistry to observe the expression of TGF-β1. Also, we found that 1 could obviously inhibit the expression of TGF-β1 of fibroblasts derived from hypertrophic scar compared with the control group (P < 0.05). These results suggest that 1 inhibits the growth of hypertrophic scar fibroblasts through apoptosis and decreases the expression of TGF-β1. [ABSTRACT FROM AUTHOR]

• Potential habitat of four medicinal crops for diabetes treatment were determined. • A. membranaceus and R. glutinosa mainly located in northern China. • C. chinensis and S. ningpoensis are mainly located in South and Central China. • The four species planted in the concentrated regions will produce maximum products. • Concentrated region is an effective way for conservation and utilization of crops. Revealing the potential geographical distribution and regions that yield maximum harvest of products will be of great significance for evaluation and utilization of crops in medicinal industry. Diabetes has become a global health problem that threatens almost all nations in the world. The traditional Chinese medicine (TCM) has long been used for the treatment of diabetes in history. Specifically, four medicinal plants including huangqi (Astragalus membranaceus [Fisch.] Bunge.), huanglian (Coptis chinensis Franch.), shengdi (Rehmannia glutinosa [Gaetn.] Libosch. ex Fisch. et Mey.), and xuanshen (Scrophularia ningpoensis Hemsl.) have been confirmed effective in diabetes treatment with clear anti-diabetic mechanisms. In recent years, increasing demand of pharmaceutical industry as well as human activities lead to the degradation of habitat and drop in production of the four species. A pressing problem faced by scientists is how to propose effective conservation and utilization strategies of these medicinal crops. In this study, a comprehensive evaluation on the potential geographical distribution of the four medicinal crops was conducted based on the maximum entropy (Maxent) modeling. A total of 227, 426, 433, and 353 localities for A. membranaceus , C. chinensis , R. glutinosa , and S. ningpoensis , respectively, in China were used as the occurrence data. Ten bioclimatic variables were used as environmental factors. The results showed that the Maxent modeling generated high area under curve (AUC) values of 0.947, 0.966, 0.959, and 0.959, respectively. The areas of suitable distribution for the four species are 878,181 km2, 684,406 km2, 768,132 km2, 714,267 km2, respectively. The main decisive environmental factors that determine the potential distribution are bio12, bio12, bio6, and bio6, respectively. By further determining the core distribution regions and main producing provinces of the four species, it was found that A. membranaceus and R. glutinosa shared similar potential habitats which mainly located in northern China, while C. chinensis and S. ningpoensis shared similar potential habitats which mainly located in South and Central China. Furthermore, the former two species have similar suitable precipitation condition, while the latter two species have similar suitable precipitation condition. These results thus raised the possibility of conducting concentrated conservation and utilization of the four species in overlapping distribution regions to obtain the maximum products for pharmaceutical industry. Collectively, these results will provide valuable references for the conservation and utilization of the four medicinal crops as well as other endangered species. [ABSTRACT FROM AUTHOR]

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two. [ABSTRACT FROM AUTHOR]

Cornus officinalis Sieb. et Zucc. is a small tree that is recognized with notable medicinal, economic, and ecological values. It has been used as traditional Chinese medicine (TCM) for thousands of years in China. Modern pharmacological research has revealed that cornel iridoid glycosides (CIGs, e.g., loganin and morroniside) in dried pericarp of C. officinalis have significant medicinal activities for strengthening immune functions. However, little is known on the molecular processes responsible for the production of these compounds. This is partly due to the absence of genomic resources, such as sequences of key enzyme genes in the biosynthetic pathways. In the present study, the transcriptome of C. officinalis was analyzed by the RNA sequencing. A total of 54,827 unigenes were yielded by de novo assembly, of which 31,780 unigenes were successfully annotated. As potential molecular markers, 121, 118, 96, 89, and 82 transcription factors belonged to bHLH, MYB, PHD, WRKY, and AP2-ERF were obtained, respectively. Moreover, the results showing that geraniol 10-hydroxylase (G10H) and secologanin synthase (SLS) were differentially expressed in fruits and leaves during different growing stages were confirmed by qRT-PCR. Furthermore, we identified two distinct expression patterns of G10H and SLS in loganin synthesis of C. officinalis fruits. Collectively, the genomic information and gene expression results presented in this study will be helpful for future studies on gene discovery and molecular process of loganin synthesis in C. officinalis. [ABSTRACT FROM AUTHOR]

Reports on Chinese patent medicines preparations containing Epimedii Folium (EF) and Psoraleae Fructus (PF) resulting in idiosyncratic drug-induced liver injury (IDILI) have received widespread attention. Previous studies have shown that bavachin and epimedin B—two active ingredients derived from both EF and PF—are potential components associated with IDILI, but the underlying mechanism remains unclear. We evaluated bavachin and epimedin B-induced IDILI under TNF-α-mediated immunological stress conditions and generated liver lipid metabolism profiles using lipidomics and multivariate statistical analysis. We next applied transcriptomics to identify the differential gene expression on the transcription level. Our results showed that co-exposure to bavachin, epimedin B under immunological stress conditions resulted in obvious liver injury. The differential metabolites screened in our study were closely related to the immune homeostasis of the liver. Sixteen differentially expressed genes were found, Zc3h6 and R3hdml were upregulated, while Sumo2 , Cd74 , Banp , Oas3 , Oas2 , Gbp8 , Slfn8 , Gbp2b , Serpina3g , Zbtb40 , H2-Ab1 , Osgin1 , Tgtp1 and Hspa1b were all downregulated. These differentially expressed genes were associated with biological processes concerning metabolic process and immune system process. Further integrative analysis indicated that bavachin combined with epimedin B affected genes that were not only related to immune system processes, but also to lipid metabolism. Ultimately, this led to an imbalance in the immune microenvironment in the liver and may have contributed to the observed liver injury. [Display omitted] • Bavachin combined with epimedin B-induced IDILI was evaluated under immunological stress conditions. • Integrative lipidomics and transcriptomics approach was used to reveal differential genes and metabolites underlying IDILI. • This study provide fresh insights into unraveling the pathogenesis of IDILI associated with traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

• The best harvesting time for S. baicalensis was determined as 2–3 years. • The main medicinal active ingredients were higher in cortex than in stele. • The reduction of ingredients in fresh-cutting was lower than that in fresh-crushing. • The treatments of drying and cutting-drying were optimal for the yield of products. • Novel processing methods for industrial production of S. baicalensis was provided. Optimizing the processing technology is an effective way to improve the yield of active ingredients for the industrial production of medicinal crops. Baikal Skullcap (Scutellaria baicalensis Georgi) is a perennial herb in the Lamiaceae family and its dried root is used as a famous traditional Chinese medicine (TCM). Modern pharmacological studies have shown that the active ingredients of S. baicalensis have important pharmacological effects including anti-oxidation, anti-bacterial, anti-viral, anti-tumor, and anti-inflammation. Specifically, it is recently found that S. baicalensis has significant curative effects on the treatment of corona virus disease 2019 (COVID-19). In recent years, the market demand for the medicinal products of S. baicalensis is increasing because of its great medicinal values. However, the annual yield of active ingredients originated from the root of S. baicalensis is limited due to that little progress has been made on the traditional processing technology used in the extraction process. A pressing issue faced by both herbalists and scientists is how to improve the processing efficiency, thereby obtaining the maximum yield of products for S. baicalensis. In this study, a systematic analysis on the effects of growth years and post-harvest processing on the contents of medicinal active ingredients of S. baicalensis was conducted. The contents of eight active ingredients (baicalin, wogonoside, baicalein, wogonin, scutellarin, scutellarein, apigenin, and chrysin) in roots of S. baicalensis of different growth years (ranging from 1 year to 15 years) were estimated using high performance liquid chromatography (HPLC) and further analyzed to determine the optimal harvest period. In particular, the contents of six active ingredients in different parts (cortex and stele) of the root of S. baicalensis were estimated and compared. Meanwhile, the dynamic changes of the contents of active ingredients in fresh-crush and fresh-cut roots of S. baicalensis at room temperature were compared and analyzed to reveal the influence of post-harvest treatment on the contents of active ingredients. In addition, the effects of six different post-harvest treatments on the contents of active ingredients were systematically designed and compared to determine the best primary processing technology. The results showed that the best harvesting period for S. baicalensis should be determined as 2–3 years based on comprehensive evaluation of active ingredient content, annual yield increment, and land use efficiency. The contents of active ingredients including baicalin, wogonoside, baicalein, and wogonin in cortex were significantly higher than those in stele (P ≤ 0.05). The contents of baicalin, wogonoside, and scutellarin in fresh roots of S. baicalensis significantly reduced as the storage time increased, but the reduction of fresh-cutting was significantly lower than that of fresh-crushing. For the effects of different processing treatments, the contents of four main active ingredients (baicalin, wogonoside, baicalein, and wogonin) under drying (D) and cutting-drying (C–D) treatments were significantly higher than those of the other four treatments (P ≤ 0.05). Collectively, the above results will not only provide novel processing methods that will improve the yield of active ingredients for S. baicalensis , but also shed light on the optimization of processing technology for the industrial production of medicinal crops. [ABSTRACT FROM AUTHOR]

Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200–220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E 2 , P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients. [Display omitted] [ABSTRACT FROM AUTHOR]