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Background: Silicosis is an important occupational disease caused by inhalation of free silica and is characterized by persistent pulmonary inflammation, subsequent fibrosis and lung dysfunction. Until now, there has been no effective treatment for the disease due to the complexity of pathogenesis. Fermented cordyceps powder (FCP) has a similar effect to natural cordyceps in tonifying the lung and kidney. It has started to be used in the adjuvant treatment of silicosis. This work aimed to verify the protective effects of FCP against silicosis, and to explore the related mechanism. Methods: Wistar rats were randomly divided into four groups including the saline-instilled group, the silica-exposed group, the silica + FCP (300 mg/kg) group and the silica + FCP (600 mg/kg) group. Silicosis rat models were constructed by intratracheal instillation of silica (50 mg). Rats in the FCP intervention groups received the corresponding dose of FCP daily by intragastric gavage. Rats were sacrificed on days 7, 28 and 56 after treatment, then samples were collected for further analysis. Results: FCP intervention reduced the infiltration of inflammatory cells and the concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) at days 7, 28, 56, and decreased the expression of collagen, α-smooth muscle actin (α-SMA) and fibronectin (FN) at days 28 and 56 in the lung of silicosis rats. FCP also decreased the immune response of Th1 and Th17 at days 7, 28, 56 and inhibited the enhancement of the Th2 response at day 56. Conclusions: FCP intervention could alleviate silica-induced pulmonary inflammation and fibrosis, the protective effect may be achieved by reducing Th1 and Th17 immune responses and inhibiting the enhancement of the Th2 response. [ABSTRACT FROM AUTHOR]

Background: Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs).Methods: Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab.Results: For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone.Conclusions: The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN.Clinical Trial Registration: NCT01527877. [ABSTRACT FROM AUTHOR]

Numerous studies have reported that autophagy plays an important role in chronic wound healing, and enhancement of autophagic activity impairs cutaneous wound healing. The autophagy inhibitor Bafilomycin A1 (Baf A1) inhibits autophagy by preventing the formation of autophagosomes. This study aimed at elucidating the effect of Bafilomycin A1 on chronic refractory wound healing in diabetic mice. A total of 40 diabetic (db/db) mice and 20 nondiabetic (db/m) mice were used in this study. Full-thickness skin defects were generated in the db/db mice models, which were then divided into the following two groups: the nontreated (db/db group) and Baf A1-treated groups (Baf A1 group). The same skin defects were generated in db/m mice (db/m group) to serve as a control. We demonstrated that Baf A1 treatment significantly accelerated wound healing in db/db mice and exerted good healing effects. Moreover, Baf A1 inhibited autophagy in the newly generated epidermis and had minor effects on metabolism in db/db mice. PCNA expression, as detected by immunohistochemistry, and collagen thickness, as detected by Masson's trichrome staining on the 14th day, were higher in the db/m and Baf A1 groups than in the db/db group. In addition, the expression of the proinflammatory cytokine TNF-α in the db/m and Baf A1 groups increased significantly on day 6, and the expression of the anti-inflammatory cytokine IL-10 also increased significantly on day 9. However, there were no significant changes in the expression levels of TNF-α and IL-10 in the db/db group. Therefore, Baf A1 may accelerate diabetic chronic refractory wound healing by promoting cell proliferation, collagen production, and regulating the inflammatory balance. [ABSTRACT FROM AUTHOR]

Chronic ulcers are a significant cause of morbidity in diabetic patients, which can greatly affect a patient's quality of life. While numerous methods have been developed to promote and enhance wound healing in diabetic patients, a convenient, effective treatment for diabetic ulcers has yet to be established. Here, we demonstrate the promotion of wound healing using a low-fluence (2 mJ/spot) ablative fractional laser (AFL) treatment in diabetic mice. Treatment was shown to confer increases in mRNA expression and in protein abundance of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), along with decreases in mRNA expression and protein abundance of transforming growth factor beta (TGF-β). Taken together, these results suggest that low-fluence AFL treatment can be used to promote healing in chronic diabetic wounds. [ABSTRACT FROM AUTHOR]

Schisandra chinensis (SC) and its main constituent, schizandrin (SCH) exhibit anti-inflammatory and anti-allergic activities. Allergic and inflammatory reactions are aggravated via caspase-1 signaling pathway. However, the regulatory effects of SC and SCH on caspase-1 activation have not been clarified yet. In this study, we aimed to clarify the anti-allergic effects of SC and SCH using an ovalbumin (OVA)-sensitized mice and anti-CD3 and anti-CD28 antibodies-stimulated splenocytes. SC or SCH significantly inhibited the levels of immunoglobulin (Ig)E, IgG1, or interleukin (IL)-4 in serum of OVA-sensitized mice. SC or SCH significantly inhibited the levels of IL-6, tumor necrosis factor (TNF)-, and IL-1 in spleen of the OVA-sensitized mice. SC or SCH significantly suppressed the expression of caspase-1 and receptor-interacting protein (RIP)-2 in spleen of the OVA-sensitized mice. In activated splenocytes, SC or SCH significantly decreased the expression of caspase-1 and RIP-2 as well as the production of IL-6 and TNF-. We suggest that SC and SCH exert an anti-allergic effect by down-regulating caspase-1 signaling. [ABSTRACT FROM AUTHOR]

Some amino acids are considered alternative therapies for improving menopausal symptoms. Glutamic acid (GA), which is abundant in meats, fish, and protein-rich plant foods, is known to be a neurotransmitter or precursor of γ -aminobutyric acid. Although it is unclear if GA functions in menopausal symptoms, we hypothesized that GA would attenuate estrogen deficiency–induced menopausal symptoms. The objective to test our hypothesis was to examine an estrogenic effect of GA in ovariectomized (OVX) mice, estrogen receptor (ER)–positive human osteoblast–like MG-63 cells, and ER-positive human breast cancer MCF-7 cells. The results demonstrated that administration with GA to mice suppressed body weight gain and vaginal atrophy when compared with the OVX mice. A microcomputed tomographic analysis of the trabecular bone showed increases in bone mineral density, trabecular number, and connectivity density as well as a significant decrease in total porosity of the OVX mice treated with GA. In addition, GA increased serum levels of alkaline phosphatase and estrogen compared with the OVX mice. Furthermore, GA induced proliferation and increased ER- β messenger RNA (mRNA) expression, estrogen response element (ERE) activity, extracellular signal–regulated kinase phosphorylation, and alkaline phosphatase activity in MG-63 cells. In MCF-7 cells, GA also increased proliferation, Ki-67 mRNA expression, ER- β mRNA expression, and ERE activity. Estrogen response element activity increased by GA was inhibited by an estrogen antagonist. Taken together, our data demonstrated that GA has estrogenic and osteogenic activities in OVX mice, MG-63 cells, and MCF-7 cells. [ABSTRACT FROM AUTHOR]

Background and purpose - Metaphyseal fractures heal in a rapid fashion that is different from the bone shaft healing process. Animal studies have focused on diaphyseal fractures. We investigated the metaphyseal fracture-healing process in rabbits. Animals and methods - 60 rabbits (divided into 12 groups) underwent proximal tibial osteotomy, anatomical reduction, and fixation with screws. After surgery, the proximal tibiae were harvested at different time points for histology. Results - No obvious osteonecrosis or bone resorption were found 2 weeks after surgery. From day 5 to week 5, woven bone or new trabeculae formed. From week 2, remodeling into lamellar bone started and reached a peak at week 6. These 3 stages overlapped. Histomorphometry showed that the structure changed as a unimodal curve. Interpretation - The healing process of metaphyseal fractures appears to differ from the commonly studied healing process in diaphyseal fractures. It is rapid, and can be divided into 4 histological stages: cellular activation and differentiation, formation of woven bone, transformation of woven bone into lamellar bone, and further remodeling. [ABSTRACT FROM AUTHOR]

BiRyuChe-bang (BRC) is a Korean prescription medicine, which has been used to treat allergic rhinitis at Kyung Hee Medical Center. In this work, we investigated the effects of BRC on mast cell-mediated allergic reactions and inflammatory cytokines production, and identified the active component of BRC. Histamine release was measured from rat peritoneal mast cells (RPMCs). Ear swelling and passive cutaneous anaphylaxis (PCA) were examined in mouse models. Phorbol 12-myristate 13-acetate (PMA) plus A23187-induced inflammatory cytokines production was measured using enzyme-linked immunosorbent assay. Reverse transcriptase-polymerase chain reaction was used for the expressions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8. Activation of nuclear factor (NF)-κB was analyzed by Western blotting. BRC significantly inhibited the compound 48/80-induced ear swelling response, histamine release from RPMCs, PCA activated by anti-dinitrophenyl IgE, and PMA plus A23187-induced inflammatory cytokines production (p < 0.05). In addition, BRC dose-dependently inhibited the mRNA expressions of TNF-α, IL-6, and IL-8 as well as the activation of NF-κB in a human mast cell line, HMC-1 cells. BRC inhibited the levels of TNF-α and IL-6 in mice induced with PCA. Several components of BRC, such as 1,8-Cineole, Linalool, Linalyl acetate, α-Pinene, and α-Terpineol, significantly inhibited the release of histamine from RPMCs (p < 0.05). Among these components, Linalyl acetate was the most effective for inhibiting histamine release. These results indicate that BRC has a potential regulatory effect on allergic and inflammatory reactions mediated by mast cells. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Sunqingwan watered pill (SWP) is a Chinese medicine compound, traditionally used in the treating UC symptoms like diarrhea, bloody and purulent stool, abdominal pain, etc. The present study aim to examine the effects of SWP on ulcerative colitis using the modern pharmacological models. Materials and methods: To address this question, we used two experimental models of colitis, mice induced by dextran sulfate sodium (DSS) as well as rats induced by 2,4-dinitrochlorobenzene (DNCB). For the mice with DSS-induced colitis, the disease activity index (DAI) and colon histological injuries were observed. For the rat models with DNCB-induced colitis, DAI, levels of nitric oxide (NO) in serum, macroscopic and histological colon injury were investigated. Besides, we also introduced a usually used model of ear swelling induced by xylene in mice to reveal the effect of SWP on acute inflammation. Result: In the mice with DSS-induced colitis and the rats with DNCB-induced colitis, SWP could significantly decreased the DAI scores, which meant the body weights of animals were recovered and the gross rectal bleeding reduced. Under the microscope, the histology of colon was obviously changed in SWP administration groups. In the rat models with DNCB-induced colitis, SWP also significantly attenuated macroscopic and colon histological injury. The colon scores in SWP groups in rats was obviously lower than those in the control and similarly the serum levels of NO in the treatment groups were significantly lower than that of control group except for low dosage group of SWP. SWP with the dosages of 1.755 and 3.510g/kg could inhibit the degree of ear swelling significantly compared with the blank control group (p <0.01), showing it owned good anti-inflammatory activity after 14 days administration. Conclusion: SWP is effective on treating UC, especially at the high dose and the mechanism may be related with adjusting the serum level of NO, inhibiting colonic mucosa damage and promoting ulcer repair. [Copyright &y& Elsevier]

Aim of study: To evaluate the potential expectorant and antitussive activity of a traditional Chinese medicine. Materials and methods: The water extract and four fractions of the aerial part of Reineckia carnea were orally administrated to coughing mice induced by ammonium hydroxide and mice injected with phenol red, respectively, to investigate their medification effect on coughing and mucus scretion. Results and discussion: 90% Ethanol fraction significantly lengthened the latent period of cough and decreased cough frequency caused by ammonium hydroxide at the dose of 0.372g/kg (p <0.05). Sixty percent ethanol fraction reduced the cough frequency as well as the mucus secretion from mouse tracheas obviously at the dose of 0.570g/kg (p <0.05) by measuring the tracheal output of phenol red in mice. The medication effects in multiple doses of the active fractions were then performed and it has been proved that the 60% ethanol and 90% ethanol fraction were curatively effective on expectoration and coughing, respectively both at the high and middle dose, which supplied proofs for the further research on chemical constituents in both of two effective fractions. [Copyright &y& Elsevier]

Background and Purpose: 5-HT4 receptor agonists have been shown to be effective at treating various gastrointestinal tract disorders. However, a lack of selectivity against off-targets has been a limiting factor for their clinical use.Experimental Approach: The binding affinity and selectivity of YH12852 for human 5-HT4(a) receptor in CHO-K1 cells were evaluated using radioligand binding assays, and agonistic activity was assessed using a β-lactamase reporter system. Contractile activity and propulsive motility were measured in the guinea pig isolated distal colon. Its prokinetic effect on the gastrointestinal tract was evaluated in guinea pigs, dogs and monkeys. Its tissue distribution was evaluated in rats.Key Results: YH12852 exhibited high affinity and potency for human recombinant 5-HT4(a) receptor with high selectivity over other 5-HT and non-5-HT receptors, ion channels, enzymes and transporters. YH12852 induced contractions and increased propulsive motility in guinea pig isolated colon. These effects were abolished by the 5-HT4 receptor antagonist GR113808. YH12852 increased defecation more effectively than prucalopride in guinea pigs and dogs and improved gastric emptying more effectively than mosapride in guinea pigs, dogs and monkeys. YH12852 was highly distributed to the gastrointestinal tract as the target organ.Conclusion and Implications: The high in vitro potency and selectivity of YH12852 for 5-HT4 receptor translated into potent in vivo efficacy with good tolerability. YH12852 significantly improved both upper and lower bowel motility in the animal models tested and has the potential to address considerable unmet needs in patients with functional constipation, gastroparesis or both. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Astilboides tabularis has a long history of usage as the functional food with the effect of adjunctive therapy of diabetic in northeast of China. The present study was undertaken to assess anti-diabetic activity of the aqueous extract of leaves of A. tabularis and provided experimental evidence for the clinical usage of A. tabularis in the treatment of diabetes mellitus. Materials and methods The aqueous extracts of leaves of A. tabularis (EAT) were orally administered at 300 and 600 mg/kg dose to epinephrine-induced and alloxan-induced diabetes mice. Hypoglycemic effects, change in body weight, water intake, food intake, lipid profile and lipid peroxidant were assessed. Furthermore, the main chemical components of EAT were isolated and high performance liquid chromatography (HPLC) analysis was employed to identify the phytochemical composition of the plant extract. The finally, total flavonoids content and total phenolic content were quantified by colorimetric assay. Results EAT showed a significant reduction in blood glucose level at both 300 and 600 mg/kg (ig). In addition, EAT also exhibited a profound antioxidant effect for increasing SOD and GSH-px activity and decreasing TBARS activity at both low and high dose. Furthermore, EAT also could significantly decrease the contents of TC and TG. The 8 main constituents of EAT are also isolated and characterized and the content of total flavonoid and total phenolic are 22% and 25% in EAT respectively. Conclusion The present investigation revealed that EAT possess potent anti-diabetic activity and polyphenol compounds may be the main active ingredients. [ABSTRACT FROM AUTHOR]

The traditional Chinese medicine (TCM) Xiaoer-Feire-Qing granules (XEFRQ) has been used to treat pyretic pulmonary syndrome (PPS) in children for many years. The function of the lungs is considered to be closely related to the large intestine in TCM. Purpose: We aimed to investigate the effects of XEFRQ on PPS and the underlying mechanisms via network pharmacology and animal experiments. The TCMSP platform was used to identify the ingredients and potential targets of XEFRQ. The GeneCards, OMIM, and TTD databases were used to predict PPS-associated targets. Cytoscape 3.9.1 was employed to construct the protein–protein interaction network, and target prediction was performed by GO and KEGG analyses. For the animal experiment, a PPS model was constructed by three cycles of nasal drip of Streptococcus pneumoniae (STP; 0.5 mL/kg). The animals were randomly divided into the following four groups according to their weight (n = 10 rats per group): the blank group, the model group, the XEFRQ-L (16.3 g/kg) group, and the XEFRQ-H (56.6 g/kg) group. Rats in the blank group and the model group were given 0.5% CMC-Na by gavage. The general conditions of the rats were observed, and their food-intake, body weight, and body temperature were recorded for 14 days. After the intervention of 14 days, serum was collected to detect inflammatory cytokines (TNF-α, IL-1β, and PGE2) and neurotransmitters (5-HT, SP, and VIP). H&E staining was used to observe the pathological morphology of lung and colon tissue. AQP3 expression was detected by Western blot. In addition, the gut microbiota in cecal content samples were analyzed by 16S rDNA high-throughput sequencing. Our network analysis revealed that XEFRQ may alleviate PPS injury by affecting the levels of inflammatory cytokines and neurotransmitters and mitigating STP-induced PPS. In vivo validation experiments revealed that XEFRQ improved STP-induced PPS and reduced the expression of inflammatory cytokines and neurotransmitters. Notably, XEFRQ significantly decreased the protein expression levels of AQP3, which was associated with dry stool. Our gut microbiota analysis revealed that the relative abundance of [Eubacterium]_ruminantium_group , Colidextribacter , Romboutsia , and Oscillibacter was decreased, which means XEFRQ exerts therapeutic effects against PPS associated with these bacteria. Our results demonstrate that XEFRQ alleviates PPS by affecting the lungs and intestines, further guiding its clinical application. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Hong Yao aerosol (HYA) is a new dosage form developed from Hong Yao, a traditional Chinese medicine preparation, which has the efficacy of promoting soft tissue contusion repair, anti-inflammation, and analgesia. Aim: To evaluate the soft tissue contusion repairing, anti-inflammatory and analgesic effects of HYA formulations with different penetration enhancers (PE) and to quantify the transdermal absorption of HYA component. Materials and methods: Three preparations of HYA with different PEs were made: DMSO preparation (5% DMSO as additional PE), Azone preparation (3% azone as additional PE), and NAPE preparation (no additional PE). Four in vivo rodent models were employed to evaluate the pharmacodynamic effects of the HYAs: mouse soft tissue contusion model, rat paw edema model, mouse ear swelling model, and mouse analgesia model of electric-stimulated foot. In vitro skin penetration experiment was applied to evaluate the transdermal absorption of HYA components. Results: All HYA preparations showed effects on soft tissue contusion repairing, anti-inflammation, and analgesia compared with the blank control (p<0.05). There was no significant difference among the three preparations. Pathological variation of mice skin and the pain response time (PRT) reduction phenomena indicated that DMSO preparation induced skin irritation. In vitro skin penetration experiment showed no significant difference between DMSO and NAPE on absorption enhancement of ferulic acid from HYA. Conclusions: NAPE preparation was considered as best and Menthol/borneol (6.3%, W/W, 4:1.75) in HYA might be a good PE combination. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: DBXX is a derived prescription from “Banxiaxiexin Tang” in “Shanghan Lun”, the representative prescription to regulate spleen and stomach. Aim of the study: To determine the pharmacodynamics effects of DBXX granules on anti-ulcer and anti-side effect on digestive system induced by chemotherapeutic drugs. Materials and methods: Chronic gastric ulcer was induced by an injection of 100% glacial acetic acid into the submucosal layer of the glandular stomach, then the area of all ulcers was added together as the ulcer index and inhibition rate of ulcer was calculated. While S180 tumor-bearing mice were treated with cyclophosphamide as the chemotherapeutic drug, the weight of food-intake after chemotherapy, the loss body weight, tumor weight and spleen index were weighed and calculated. Results: In the gastric ulcer bearing mice, DBXX granules showed a dose-dependent reduction of ulcer at the dose 4.87 and 9.73g/kg. In the S180 tumor-bearing mice, low dose of DBXX granules could significantly improve every investigated index compared with that of control group (p <0.05). Conclusions: It proved that DBXX granules showed good healing effect on the chronic gastric ulcer mice and significant effect on decreasing the side effect of chemotherapy of S180 tumor-bearing mice. [Copyright &y& Elsevier]

Massa Medicata Fermentata ("Shenqu") has long been applied in the treatment of indigestion in China; in fact, it is the active ingredient in the medicine Shenqu xiaoshi oral solution (SQXSOS). Based on robust clinical evidence, SQXSOS has shown efficacy in treating infantile anorexia (IFA). To investigate the underlying mechanisms by which SQXSOS treats IFA. The pharmacodynamic efficacy of SQXSOS was validated through a high-fat diet (HFD)-induced IFA model of juvenile rats, which share physiological similarities to two-year-old humans. Ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UHPLC-TOF MS) was utilized to analyze the blood-dissolved components of SQXSOS in rats. After identification of the blood-dissolved components, the key components and target genes were predicted through network pharmacology analysis. To further validate the predicted key targets of the blood-dissolved components, RT-PCR and Western blotting were employed to measure the changes in their concentrations. Meanwhile, the efficacy of SQXSOS on the structure of gastrointestinal microbiota (GM) in IFA rats was investigated. SQXSOS, when administered to the IFA rats at a dosage equivalent to its clinical dose in humans (3.78 mL/kg/day), induced a significant increase in the gastric emptying rate (+1.9-fold) and small intestine advancement rate (+0.5-fold) compared to the IFA rats. Additionally, SQXSOS reversed the pathological changes observed in the serum levels of digestive functioning biochemicals (−32.4%～+250% compared to the model group, p < 0.05). A total of 40 blood-dissolved components were identified by UHPLC-TOF MS. Berberine, oleanolic acid, ganolucidic acid A, slicyluric acid, and glycyrrhetinic acid were identified as the key components of SQXSOS, while AKT1, STAT3, TP53, JUN, and MAPK1 were identified as the key targets enabling the therapeutic efficacy of SQXSOS in treating IFA. In a target validation study, the mRNA transcript levels of the abovementioned target genes were found to be significantly higher in the gastric antrum of IFA rats. However, SQXSOS administration (3.78 and 7.56 mL/kg/day) reduced the elevated mRNA transcript levels of the abovementioned target genes (41.1–77.3% compared to model group, p < 0.05). GM analysis revealed a significant increase in the Firmicutes/Bacteroidota ratio (F/B ratio, +214.2%) in the IFA fecal samples compared to normal rats, but the high dosage of SQXSOS induced a marked decrease in the F/B ratio (−44.1%) compared to IFA rats. Furthermore, the therapeutic efficacy of SQXSOS against IFA might be attributed to the increase in Muribaculaceae abundance and the decrease in Prevotellaceae_UCG_003 abundance. Mechanistic investigations indicated that the efficacy of SQXSOS in treating IFA could be manifested by regulating the transcription and expression levels of AKT1, MAPK1, STAT3, and TP53 genes in the gastric antrum as well as modulating the abundance of Muribaculaceae and Prevotellaceae_UCG_003 family. Furthermore, there are still some limitations: the contents of the key biochemicals remained to be determined, similar STAT3 transcription levels were observed in both normal rats and IFA rats, and it is crucial to further validate the potential target GM when transitioning from animal populations to humans. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Suqingwan (SQW), a traditional Chinese medicine used for treating ulcerative colitis (UC), is composed of 13 kinds of Traditional Chinese medicines (TCMs). According to TCM theory, we investigated whether a simplified prescription composed of the herbs with some functions, would have similar effects to SQW and examined its potential treatment mechanism of action. Materials and methods We categorized the herbs in SQW into four groups according to their traditional functions and used an orthogonal experimental design to obtain nine separated prescriptions (SPs) of SQW. A dextran sulfate sodium (DSS)-induced UC mouse model was used to evaluate the anti-ulcer colitis effects of the nine SPs and the calculated prescription (CP) was obtained based on the orthogonal t values of the disease activity index (DAI) of the nine SPs. The effect of the CP and SP8 were verified in the DSS-induced UC model, and the DAI and histopathology of the UC mice were examined. Myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF)-α, interleukin (IL)−1β, IL-6, IL-4 and IL-10 of the mice in SP8 were investigated to explore the mechanism of action of the optimized prescription with regard to anti-inflammatory and anti-oxidation effects. Results Among the 9 SPs, separate prescription 6, 7 and 8 (SP6, SP7 and SP8) and the SQW formulation all significantly reduced the DAI of the UC mice and, in particular, SP8 had an effect similar to SQW, which consists of Sanguisorba officinalis L., Rehmannia glutinosa Libosch. and four other herbal medicines. In a further investigation, SP8 was found to improve the ulcerative colitis in mice in terms of both clinical symptoms and histopathology. The mortality of mice in the SP8 group was 33.3%, better than CP based on the orthogonal t values (83.3%). SP8 could also reduce the levels of TNF-α, IL-1β, IL-6, MPO and MDA and increase the levels of IL-4 and IL-10 in colon tissue of UC mice in comparison with those of the model group ( p <0.05). Conclusions An optimized prescription (SP8) from SQW was obtained based on an orthogonal experimental design, which involved 6 herbal medicines, with significantly fewer herbs than in the original prescription. SP8 displayed a similar anti-ulcerative colitis activity to SQW, and its in vivo mechanism of action is related to up-regulation of anti-inflammatory cytokines and down-regulation of pro-inflammatory and oxidative factors. [ABSTRACT FROM AUTHOR]

Chinese patent medicine Zhixiong Capsule (ZXC) is the equal mixture of the extract of leech, Ligusticum chuanxiong Hort., Salvia miltiorrhiza Bunge, Leonurus japonicus Houtt., and Pueraria lobate (Willd.) Ohwi, which have been long used against inflammation, hyperlipidemia or blood stasis. In our previous study, ZXC showed good efficacy in preventing atherosclerosis (AS) plaque formation in rabbits. In actual clinic practice, patients are more likely to receive treatments after AS plaque formation. Therefore, the efficacy of ZXC on formed AS plaques and the underlying mechanisms were further investigated in this study. Simvastatin (positive control) and ZXC (420 mg/kg and 840 mg/kg) were administrated to rats which first received long-term high fat diet administration (12 weeks). The blood lipid profiles of rats were monitored during the whole experiment, and the thoracic arteries were collected at the end of experiment for AS assessment (18th week). The blood-dissolved ZXC components were determined using an UPLC-QTOF-MS method, and the attained components were then used for network pharmacology analysis to predict the key ZXC components and targets. At last, the predicted targets were validated by ELISA and western blot methods. ZXC administration showed good blood lipid-lowering effect by significantly reduced LDL-C and TC levels in rats while significantly increased HDL-C level. Compared with model group, simvastatin, low- and high-dose of ZXC administration decreased the ratio of intimal area and medial area by 81.1%, 71.1% and 71.4%, respectively (p < 0.01), and significantly alleviated collagen deposition and mineralization in rat arteries. It was found by network pharmacology analysis that leech and four components (namely daidzein, 4-methylenemiltirone, isorhamnetin and 2-isopropyl-8-methylphenanthrene-3,4-dione) are vital components for the anti-AS efficacy of ZXC. Combing the results from biochemical validation, IL-4, IL-13, MAPK1, MAPK14, JUN and P53 were confirmed as key targets of ZXC. It could be concluded that ZXC has value as an anti-AS agent in clinical treatment against formed AS plaque at the current application dosage. Image 1 [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine Celastrus orbiculatus Thunb (C. orbiculatus) with peel and seeds is mainly composed of flavonoids, sesquiterpenes and tripenes. According to the Traditional Chinese medicine standard of Liaoning province (2009), it has been long used to invigorate blood circulation. To identify the antithrombus fraction and components of C. orbiculatus , and to investigate the underlying mechanisms. The antithrombus effects of C. orbiculatus fractions were evaluated in vitro by plasma recalcification time (PRT). The antithrombus effect of NST-50, the most effective fraction, was further investigated in acute pulmonary embolism (APE) mice and FeCl 3 -induced carotid arterial thrombus rats. Bleeding assessment was also carried out to assess the side effects of NST-50. In addition, the content of total flavonoids and active components of NST-50 was also quantified. Nine flavonoids were detected in NST-50 as main components with the content of 44.70%. Next, NST-50 was found with significant anticoagulation activity by prolonging the plasma recalcification time (PRT), activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) and decreasing the content of fibrinogen (FIB). Furthermore, NST-50 administration markedly suppressed the level of TXB 2 and PAI-1, while significantly up-regulated the level of 6-keto-PGF 1a and t-PA (p < 0.05). The results demonstrated that NST-50 could be valuable in clinical application against acute coronary syndrome, venous thromboembolisms and cerebrovascular thrombosis. It was possible that the anticoagulation action of NST-50 could be related to the regulation of TXA 2 - PGI 2 and t-PA - PAI-1 pairs. Image 1 [ABSTRACT FROM AUTHOR]