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Sishen pill (SSP) is an old Chinese medicine used to treat colitis with spleen-kidney-yang deficiency (SKYD) syndromes. However, its exact mechanism of action has not yet been fully elucidated. The aim of this study was to evaluate the effects and potential mechanisms of SSP on colitis with SKYD syndromes in mice. Colitis with SKYD syndromes was induced by rhubarb, hydrocortisone, and dextran sulfate sodium (DSS), and treatment was provided with SSP. Flow cytometry was performed to examine the inflammatory dendritic cell (infDC) regulations of SSP. The changes in the gut microbiota (GM) and fecal metabolites post-SSP treatment were investigated using the combination of 16S rRNA sequencing and untargeted metabolomics. Additionally, we also examined whether SSPs could regulate the infDCs by modifying TLR4/NF-κB signaling pathways. Compared with the DSS group, the disease activity index, colonic weight, index of colonic weight, and colonic injury scores, as well as the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-12p70 decreased significantly in the DSS + SSP group, while free triiodothyronine (FT3), free tetraiodothyronine (FT4), testosterone (TESTO), body weight change, colonic length, and the levels of IL-10 increased. Also, SSP decreased the amounts of CD103+CD11c+iNOS+, CD103+CD11c+TNF-α+, CD11c+CD103+CD324+, CD103+CD11c+MHC-II+, and CD103+CD11c+CD115+. Interestingly, 16S rRNA sequencing and untargeted metabolomics showed that SSP treatment restored the dysbiosis of GM and improved the dysfunction in fecal metabolism in colitis mice with SKYD syndromes. Correlation analysis indicated that the modulatory effects of SSP on FT3, FT4, IL-10, colonic weight index, CD103+CD11c+TNF-α+, CD103+CD11c+MHC-II+, and 13 common differential metabolites were related to alterations in the abundance of Parvibacter, Aerococcus, norank_f_Lachnospiraceae, Lachnospiraceae_UCG-006, Akkermansia, and Rhodococcus in the GM. In addition, SSP markedly inhibited the activation of the TLR4, MyD88, TRAF6, TAB2, and NF-κBp65 proteins and activated IκB. These results indicate that SSP can effectively alleviate colitis mice with SKYD syndrome by regulating infDCs, GM, fecal metabolites, and TLR4/NF-κB signaling pathways. [ABSTRACT FROM AUTHOR]

Objective: To explore the prescription patterns of different dosage forms of Chinese herbal medicines (CHMs) for the treatment of rheumatoid arthritis (RA) and their effects on immune-inflammatory indices. Methods: Clinical data were collected from patients with RA in 4 hospitals (3 Class A comprehensive hospitals and 1 Class B comprehensive hospital) in Anhui Province, China, from August 2012 to June 2018 via the electronic medical record gathering system. Following extraction of prescription information, each prescribed herb was quantified and standardized according to the knowledge base to establish a database of RA treatment formulae. The medical records were divided into the granules group and decoction pieces group. Core herbs and their combination patterns were obtained from the two groups of cases using Liquorice software. Changes in immune-inflammatory and hepatic and renal function indices were compared between the two groups using SPSS 23.0 software. The Aprior module of SPSS Clementine 11.1 software was applied to analyse the correlation between CHMs and improvement in indices. Finally, the ORACLE 10 g tool was used to evaluate the random walk model of the immune-inflammatory indices between the two groups. Results: (1) We retrospectively analysed 35,898 prescriptions for 6,829 patients with RA who received CHM treatment. There were 3,816 patients in the granules group and 3,013 in the decoction pieces group. (2) The core herbs were Pi (Spleen)-strengthening and dampness-resolving drugs, blood-activating and stasis-resolving drugs, wind/dampness-dispelling drugs and heat-clearing and detoxifying drugs. (3) Both dosage forms could improve immune-inflammatory indices in RA patients, with similar efficacy and no influence on hepatic or renal function. (4) Herba Siegesbeckiae and Oldenlandia had a stronger association with immune-inflammatory indices in the two groups. (5) The immune-inflammatory indices showed obvious improvement after treatment with granules and decoction pieces of CHMs, and there were long range correlations between the comprehensive evaluation indices and interventions. Conclusions: The principal CHM treatment methods for RA in four hospitals in Anhui Province are strengthening Pi and resolving dampness, activating blood and resolving stasis, dispelling wind/dampness and clearing heat. Granules and decoction pieces of CHMs have similar efficacy in improving immune-inflammatory indices in RA patients and could be used as treatment options for RA. [ABSTRACT FROM AUTHOR]

Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1β levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier. [ABSTRACT FROM AUTHOR]

Objective: To investigate the synergistic effect of Naoxintong Capsule (NXTC, 脑心通胶囊) and Guhong Injection (GHI, 谷红注射液) on cerebral ischemia-reperfusion (I/R) injury. Methods: Forty-eight Sprague-Dawley rats were divided into 6 groups: control group, oxygen and glucose deprivation (OGD) group, nimodipine group (9.375 mg/kg), NXTC group (0.5 g/kg), GHI group (5 mL/kg) and NXTC+GHI group (0.5 g/kg NXTC+5 mL/kg GHI), after the onset of reperfusion and once per day for the following 7 days. Blood was collected 1 h after final administration, and the sera were collected. Cultured primary rat brain microvascular endothelial cells (rBMECs) were subjected to OGD to establish a cell injury model. Untreated rBMECs were used as blank control. The cell counting kit-8 assay was used to assess cell viability using the sera. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed using an enzyme-linked immunosorbent assay. Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry. JC-1 staining was performed to assess changes in mitochondrial membrane potential. Results: Statistical analysis indicated that more than 95% of the cells were rBMECs. Compared with the OGD group, the cellular morphology of the all drug delivery groups improved. In particular, the combined drug group had the most significant effect. Compared with the OGD group, all drug intervention groups induced a decrease in the apoptotic rate of rBMECs, increased the SOD levels, and decreased the MDA levels (all P<0.01). Compared with the mono-therapy groups, the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs (P<0.01). All drug intervention groups showed different degrees of increase in membrane potential, and the NXTC+GHI group was higher than the NXTC or GHI group (P<0.01). Conclusion: The combinationa application of NXTC and GHI on cerebral I/R injury clearly resulted in protective benefits. [ABSTRACT FROM AUTHOR]

Objective: To obtain the subtypes of the clinical hypertension population based on symptoms and to explore the relationship between hypertension and comorbidities. Methods: The data set was collected from the Chinese medicine (CM) electronic medical records of 33,458 hypertension inpatients in the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between July 2014 and May 2017. Then, a hypertension disease comorbidity network (HDCN) was built to investigate the complicated associations between hypertension and their comorbidities. Moreover, a hypertension patient similarity network (HPSN) was constructed with patients' shared symptoms, and 7 main hypertension patient subgroups were identified from HPSN with a community detection method to exhibit the characteristics of clinical phenotypes and molecular mechanisms. In addition, the significant symptoms, diseases, CM syndromes and pathways of each main patient subgroup were obtained by enrichment analysis. Results: The significant symptoms and diseases of these patient subgroups were associated with different damaged target organs of hypertension. Additionally, the specific phenotypic features (symptoms, diseases, and CM syndromes) were consistent with specific molecular features (pathways) in the same patient subgroup. Conclusion: The utility and comprehensiveness of disease classification based on community detection of patient networks using shared CM symptom phenotypes showed the importance of hypertension patient subgroups. [ABSTRACT FROM AUTHOR]

Sishen Pill (SSP) is a typical prescription in the pharmacopeia of traditional Chinese medicine (TCM), and is usually used to treat inflammatory bowel disease (IBD). It is known that inflammatory dendritic cells (DCs) and imbalance of gut microbiota play significant roles in the pathogenesis of IBD. However, it is not clear whether SSP can treat IBD by regulating interaction of DCs and gut microbiota. In the present study, the levels of inflammatory DCs and gut microbiota were analyzed by flow cytometry and 16S rDNA analysis. SSP relieved the pathological damage to the colon of mice with colitis induced by dextran sodium sulfate (DSS). As typical indicators of inflammatory DCs, the levels of CD11c+CD103+E-cadherin+ cells and pro-inflammatory cytokines [interleukin (IL)-1β, -4, -9, and -17A] were decreased in mice with colitis treated by SSP for 10 days. Simultaneously, the gut microbiota composition was regulated, and beneficial bacteria were increased and pathogenic bacteria were reduced. The results indicated that SSP regulated the interaction between inflammatory DCs and gut microbiota to treat DSS-induced colitis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Tongxiening Granules (痛泻宁颗粒, TXNG) in the treatment of irritable bowel syndrome with predominant diarrhea (IBS-D). Methods: A randomized, double-blind, double-dummy, and positive parallel controlled clinical trial was conducted from October 2014 to March 2016. Totally 342 patients from 13 clinical centers were enrolled and randomly assigned (at the ratio of 1:1) to a treatment group (171 cases) and a control group (171 cases) by a random coding table. The patients in the treatment group were administered orally with TXNG (5 g per time) combined with pinaverium bromide Tablet simulator (50 mg per time), 3 times per day. The patients in the control group were given TXNG simulator (5 g per time) combined with pinaverium bromide Tablets (50 mg per time), 3 times per day. The treatment course lasted for 6 weeks. The improvement of Irritable Bowel Syndrome Symptom Severity Score (IBS-SSS) was used to evaluate the primary outcome. Secondary outcomes included adequate relief (AR) rate, Irritable Bowel Syndrome-Quality of Life Questionnaire (IBS-QOL), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), and the recurrence rate at follow-ups. Safety indices including the adverse events (AEs) and related laboratory tests were evaluated. Results: Primary outcome: IBS-SSS at baseline, weeks 2, 4, 6 showed no statistical significance in both full analysis set (FAS) and per protocol set (PPS, P>0.05). After 6 weeks of treatment, the total effective rate of IBS-SSS scores in the treatment group (147/171,86.0%) was higher than the control group (143/171, 83.6%) by FAS (P>0.05). In regard to secondary outcomes, after 6-week treatment, there was no significant difference in AR rate, total score of IBS-QOL, improvement of HAMD and HAMA total scores between the two groups (P>0.05). The recurrence rate at 8-week follow-up was 12.35% (10/18) in treatment group and 15.79% (12/76) in control group, respectively (P>0.05). A total of 21 AEs occurred in 15 cases, of which 11 occurred in 8 cases in the treatment group and 10 AEs in 7 cases in the control group. The incidence of AEs had no statistical significance between the two goups (P>0.05). Conclusion: Tongxiening Granules could relieve the symptoms of patients with IBS-D and the treatment effect was comparable to pinaverium bromide. (No. ChiCTR-IPR-15006415) [ABSTRACT FROM AUTHOR]

The nuclear factor (NF)-κB signaling pathway plays an important role in the initialization and development phase of inflammatory injuries, including inflammatory bowel disease (IBD). Sishen Wan (SSW) is a classic Chinese patent medicine listed in the Chinese Pharmacopoeia, which is usually used to treat chronic colitis; however, it is unclear whether SSW can treat IBD via the NF-κB signaling pathway. In the present study, the therapeutic effect of SSW was demonstrated by the decreased index of colonic weight, macroscopic and microscopic score, and pathological observation in chronic colitis induced by trinitrobenzene sulfonic acid. In colonic mucosa of rats with chronic colitis, SSW reduced the levels of calprotectin and eliminated oxidative lesions; downregulated expression of interferon-γ, interleukin (IL)-1β and IL-17; increased expression of IL-4; and suppressed expression of NF-κB p65, and NF-κB essential modulator (NEMO)-like kinase (NLK). Furthermore, SSW inhibited ubiquitinated NEMO, ubiquitin-activated enzyme, and E2i activation, and phosphorylation of downstream proteins (cylindromatosis protein, transforming growth factor-β-activated kinase and P38). These results show that the therapeutic effects of SSW in chronic colitis were mediated by inhibiting the NEMO/NLK signaling pathway to suppress NF-κB activation. [ABSTRACT FROM AUTHOR]

Objectives: To explore the effects of acupoint application therapy (AAT) with TianGui Powder (TGP) on the expressions of the transforming growth factor β1 (TGF‐β1) and Smad‐2/3 signaling pathway in ovariectomized osteoporosis rats. Methods: Sixty rats were randomly divided into four groups: normal group (group A), model group (group B), TGP group (group C), and Western medicine group (group D). Group A had only the corresponding amount of adipose tissue around the ovary removed; rats in the other groups had bilateral ovariectomies. After 1 week, groups A and B were given 1 mL/100 mg normal saline solution by gavage, group C was treated with AAT with TGP on ShenQue acupoint (0.2 piece/rat, 6 h/time, 1 time/d) and group D was given calcium carbonate vitamin D3 (36 mg/kg/d) and alfacalcidol (0.05 μg/kg/d) tablet suspension. In this study, the bone mineral density (BMD) , the levels of BALP, TRAP‐5b, and BGP in serum and the changes in bone histomorphology was detected. For acquiring lumbar experimental data, the expression of TGF‐β1, Smad‐2/3 proteins and mRNA of TGF‐β1and Smad‐2/3 were assessed. After 12 weeks, the data were collected for analysis. Results: Compared with group A, the bone trabecula was thinner and significantly reduced in other groups. The result of BMD improved significantly in both groups C and D compared to group B after intervention (P < 0.05). In contrast, compared to group B, the levels of BALP, TRAP‐5b, and BGP significantly declined in both groups C and D. In group C, the results of protein expressions in TGF‐β1, Smad‐2/3 were 2.870 ± 0.270, 1.552 ± 0.111, and 1.420 ± 0.079, respectively. In groups C and D, those indications significantly declined compared to group B (P < 0.01). In group C, the level of mRNA expressions of TGF‐β1, Smad‐2/3 were 1.872 ± 0.177, 1.672 ± 0.086, and 1.790 ± 0.136, respectively. Compared with group B, those indications had significant difference in groups C and D (P < 0.05). Conclusion: Acupoint application therapy with TGP could significantly improve the BMD. The TGF‐β1 and Smad‐2/3 signaling pathway could be a therapeutic target of TGP in postmenopausal osteoporosis rats. [ABSTRACT FROM AUTHOR]

Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM). In this study, we found that herb medium could increase the IDO expression at appropriate concentrations. As an inhibitor of IDO, 1-MT could impair the inhibitory function of trophoblasts on NK cells. Furthermore, Bu-Shen-Yi-Qi formula could enhance the inhibitory function of trophoblasts on NK cells. In conclusion, Bu-Shen-Yi-Qi formula can inhibit NK cytotoxicity by up-regulating IDO expression in trophoblasts and play a role in the treatment of URSA patients. [ABSTRACT FROM AUTHOR]

Engineering artificial implantable tissues require rapid induction of angiogenesis to meet the significant oxygen and nutrient demands of the cell during tissue repair. In this study, we investigated the role of a Chinese medicine, scutellarin (1), in the tissue engineering scaffold of balb/c mice model. The trial groups of balb/c mice were given an intraperitoneal injection of 1 at 20, 60, and 100 mg/kg per ml, respectively. The implanted samples were retrieved at 1 week and 1 month post transplantation. Angiogenesis response in polyglycolic acid (PGA) scaffold was evaluated by histopathological and immunohistochemical methods. The expression levels of vascular endothelial growth factor (VEGF) were determined by RT-PCR. The results showed that the density of neocapillaries in the PGA was enhanced by basic fibroblast growth factor (bFGF) and 1 at 1 week. At 1 month, only 60 and 100 mg/kg per ml 1 groups continuingly kept significant neocapillaries. The inflammatory cells were significantly less in the 100 mg/kg per ml 1 group in comparison with bFGF group and negative group at 1 week and 1 month. Our results indicated that 1 not only promoted angiogenesis in the PGA scaffold, but also inhibited the host inflammatory response to the xenogenic materials. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of Traditional Chinese Medicine(TCM) on the growth and invasion of human first trimester cytotrophoblasts in vitro. Methods: Serum contained drug was collected from rats adiministered with herbs intragastricly. Serum collected from rats administered with saline was used as the control. Isolated from first trimester placental tissues, human cytotrophoblast cultured in media with 5%, 10%, 20% drug-containing serum for a 24 h, 48 h or 72 h period. Then cell morphology was measured by scanning electric microscope, cell viability by MTT assay, cell DNA content by flow cytomester, and cell invasion by transwell assay. Results: After a 48 h- and 72 h-culture period in media with drug-containing rat serum, cytotrophoblast showed more and longer cell pseudopodia than control cells. In addition, cytotrophoblast exhibited more cell microvillous than control cells after a 72 h culture with drug-containing serum. Cell viability cultured with drug-containing serum was higher than control cells. Cells cultured with drug-containing serum in S phase were more, by contrast, in sub-G1 and G2/M phase were less than the control. Cells cultured with drug-containing serum for 72 h showed significantly greater invasive ability than control cells. Conclusion: TCM had a beneficial role in the growth and invasion of human first trimester cytotrophoblast in vitro. [Copyright &y& Elsevier]

• G. biloba nut is a kind of seed with bioactive components and toxicity. • Summarize the detoxification process of Ginkgo biloba seeds. • Summarize the bioactivities of G. biloba seeds especially neuroprotective effects. Ginkgo biloba leaves and seeds have been used as a food and traditional herbal remedies for thousands of years. Extracts from G. biloba leaves , especially EGb761, have been investigated extensively to determine their chemical components and pharmacological effects, specifically on degenerative nerve diseases, such as Alzheimer's disease. G. biloba seeds, another important part of Ginkgo biloba, have been consumed as a food and medicinal nuts for thousands of years. The seeds are rich in carbohydrates, protein, fat and phytochemicals and have been used in traditional Chinese medicine to treat asthma, cough, enuresis, pyogenic skin infections and intestinal tract worm infections. Recently, G. biloba seeds have also been reported to have neuroprotective effects. Therefore, it is important to promote the intake of G. biloba seeds. However, there are few reports that comprehensively summarize G. biloba seeds. To develop a full understanding of G. biloba seeds and provide a scientific basis for the development of this edible seed, this review summarizes the major components of G. biloba seeds and their bioactivities, processing methods and updated information on the pharmacological functions. Additionally, side effects, such as allergies, haemorrhaging or excessive bleeding, that occurred in people with allergies also have been discussed. [ABSTRACT FROM AUTHOR]

As a classic prescription and commercial Chinese patent medicine, Zuojin Pill (ZJP) has been used to treat ulcerative colitis (UC) effectively for many years. However, its mechanism of action remains unclear. Aim of the study: Mice with dextran-sulfate-sodium-induced colitis were treated with ZJP for 7 d. In the present study, the therapeutic effect of ZJP was evaluated by macroscopic and microscopic observation; regulatory T (Treg) cells and their subsets were analyzed by flow cytometry; and the composition of gut microbiota was tested by 16S rRNA analysis. Activation of the phosphoinostide 3-kinase (PI3K)/Akt signaling pathway was observed by western blotting. The pathological damage was attenuated and expression of proinflammatory cytokines was decreased. While the diversity of intestinal microflora was regulated, the relative abundance of Actinobacteria , and Sphingobacteriia was modified. Meanwhile, the level of CD4+CD25+Foxp3+ and PD-L1+ Treg cells improved. These changes maintained a positive correlation which was analyzed statistically. Our results also showed that ZJP inhibited activation of the PI3K/Akt signaling pathway. ZJP regulates crosstalk between intestinal microflora and Treg cells to attenuate experimental colitis via the PI3K/Akt signaling pathway. Image 1 [ABSTRACT FROM AUTHOR]