Xiexin Decoction Research Articles

Banxia Xiexin Decoction () Treats Diabetic Gastroparesis through PLC-IP3-Ca2+/NO-cGMP-PKG Signal Pathway.

To test the effect of Banxia Xiexin Decoction (, BXD) on the contraction and relaxation of gastric smooth muscle (SM) in diabetic gastroparesis (DGP) model rats, and to explore the mechanism of BXD in the prevention and treatment of DGP through experiments of signal pathway both in vivo and in vitro. Sixty Sprague-Dawley rats were divided into 6 groups according to a random number table: control group, model group, high-, medium- and low-dose BXD groups (9.2, 4.6 and 1.8 g/(kg·d), respectively), and domperidone group (10 mg/(kg·d)), 10 rats per group. DGP model was established initially by a single intraperitoneal injection of streptozotocin (STZ), and was confirmed by recording gastric emptying, intestinal transport velocity and gastric myoelectric activity of rats after 2 months. Each group was treated with a corresponding drug for 4 weeks. The mRNA and protein expressions of phospholipase C (PLC), inositol triphosphate (IP3), neuronal nitric oxide synthase (nNOS), and cyclic guanosine monophosphate (cGMP) dependent protein kinase G (PKG) were detected by reverse transcription-polymerase chain reaction and Western blot, respectively, while nitric oxide (NO) and cGMP expressions were detected by enzyme-linked immunosorbent assay. Gastric tissues were obtained from rats for primary cell culture preparation. Gastric SM cells were treated with 0.8 µmol/L of STZ or STZ plus 1,000, 500 and 200 µg/mL of BXD or STZ plus 2.5 µmol/mL of domperidone for 24, 48, 72 or 96 h, respectively. The length of gastric SM cells and intracellular Ca2+ concentration ([Ca2+]i) before and after BXD treatment was measured. Compared with the model group, high- and medium-dose BXD and domperidone significantly increased the expressions of PLC, IP3, NO, nNOS, cGMP and PKG in rat's gastric tissue (P<0.01). Gastric SM cells treated with BXD showed a time- and dose-dependent increase in cell viability (P<0.01). The treatment with high- and medium-dose BXD and domperidone inhibited the increase in gastric SM cells length and increased [Ca2+]i compared with the model cells (P<0.01). Treatment with high- and medium-dose BXD significantly attenuated STZ-induced experimental DGP in rats. The therapeutic effect of BXD on DGP rats might be associated with the PLC-IP3-Ca2+/NO-cGMP-PKG signal pathway.

Efficacy and safety of Shengjiang Xiexin decoction in prophylaxis of chemotherapy-related diarrhea in small cell lung cancer patients: study protocol for a multicenter randomized controlled trial

BackgroundDiarrhea is a common adverse reaction in patients with cancer receiving chemotherapy, for which there is currently no effective method of treatment. Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medicine (TCM) formula, has shown efficacy in alleviating irinotecan-induced diarrhea in preliminary clinical studies. The current study is designed to assess the efficacy and safety of SXD for prophylaxis against irinotecan-induced diarrhea. Additionally, we employ a new approach to analyze and evaluate the data based on the patients’ uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype, which predicts the risk of diarrhea.Methods and designA prospective, double-blind, randomized, placebo-controlled trial will be conducted in patients with small cell lung cancer (SCLC) from five hospitals in China. For this study, 100 irinotecan-naïve patients will be randomly allocated to either the SXD or placebo arms in a 1:1 ratio. Stratified randomization will be used to divide subjects by UGT1A1 genotype into groups with differing risk of diarrhea. The trial will consist of two cycles of chemotherapy with 14 days of oral administration of SXD or placebo administered beginning between 3 days before and up to 11 days after initiation of each chemotherapy cycle. The primary study outcome is the incidence of diarrhea. Secondary outcomes include the degree of diarrhea, the degree of neutropenia, the rate of alterations in chemotherapy regimens, the amount of antidiarrheal drug taken, the rate of hospitalization, and evaluation of chemotherapy efficacy.DiscussionThis study is the first to use the UGT1A1 genotype to stratify patients into groups based on their risk of diarrhea, and to provide a complete assessment of chemotherapy-related diarrhea (CRD), including records of diarrhea duration, grading the severity of diarrhea, and evaluating concomitant symptoms. Study results will provide high-level clinical evidence on the use of SXD as prophylaxis for CRD.Trial registrationChinese Clinical Trial Register: ChiCTR1800018490. Registered on 20 September 2018. Retrospectively registered. http://www.chictr.org.cn/edit.aspx?pid=25250&htm=4c

Banxia Xiexin Decoction Ameliorates t-BHP-Induced Apoptosis in Pancreatic Beta Cells by Activating the PI3K/AKT/FOXO1 Signaling Pathway.

Background Banxia Xiexin Decoction (BXXD) reportedly regulates glycolipid metabolism and inhibits pancreatic β-cell apoptosis. This study is aimed at investigating the protective effect of BXXD on tert-butyl hydroperoxide- (t-BHP-) induced apoptosis in MIN6 cells and the underlying mechanisms. Methods MIN6 cells were preincubated with BXXD or liraglutide (Li) with or without PI3K inhibitor LY294002 (LY) for 12 h, following which t-BHP was added to induce MIN6 cell apoptosis. The protective effects of BXXD on MIN6 cells were evaluated by detecting cell viability and proliferation and glucose-stimulated insulin secretion (GSIS). The antiapoptotic effects were evaluated by Hoechst 33342 staining and terminal deoxynucleotidyl transferase dUTP nick end labeling assay (TUNEL). Malondialdehyde and glutathione peroxidase content and superoxide dismutase activity were measured using commercial kits. The expression of PI3K/AKT/FOXO1 signaling pathway-related signal molecules, and that of apoptotic indicators Bax, P27, and Caspase-3, was quantified using western blotting. Results Preincubation with BXXD significantly improved t-BHP-induced proliferation inhibition and apoptosis and enhanced GSIS. t-BHP induced the generation of reactive oxygen species and inhibited the activities of antioxidant enzymes, which could be neutralized by pretreatment with BXXD. BXXD promoted the phosphorylation of AKT and FOXO1 in t-BHP-induced MIN6 cells. Moreover, BXXD attenuated the expression of related apoptotic indicators Bax, P27, and Caspase-3. LY abolished these effects of BXXD. Conclusion BXXD protected MIN6 cells against t-BHP-induced apoptosis and improved insulin secretory function through modulation of the PI3K/AKT pathway and the downstream FOXO1, thus suggesting a novel therapeutic approach for type 2 diabetes mellitus (T2DM).

Efficacy and Safety of Banxia XieXin Decoction, a Blended Traditional Chinese Medicine, as Monotherapy for Patients With Advanced Hepatocellular Carcinoma.

Purpose:To explore a new therapeutic option for patients with hepatocellular carcinoma (HCC), the efficacy and safety of a group of traditional Chinese medicines (Banxia XieXin recipe) as monotherapy for patients with advanced HCC was studied.Materials and Methods:The study included 68 patients with advanced HCC from August 16,2016 to August 15,2019 for analysis. These eligible patients received treatment with Banxia XieXin recipe for at least 1 month. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary efficacy endpoints included objective response rate (ORR) and disease control rate (DCR). In addition, safety was also assessed.Results:The median treatment duration of these 68 patients was 10.3 months (range = 1.6-33.5 months), and follow-up is still ongoing. The median PFS was 6.07 months (95% confidence interval [CI] = 3.748-8.392 months), and the median OS was 12.60 months (95% CI = 8.019-17.181 months). The ORR was 10.3% and the DCR was 41.2%. In the subgroup analysis, the median OS in the transcatheter arterial chemoembolization (TACE) group was not reached, and the median OS in the NO TACE group was 11.30 months (95% CI = 3.219-19.381 months). In addition, no drug-related serious adverse events were observed during the study.Conclusion:This is the first clinical analysis of traditional Chinese medicine as a single treatment for advanced HCC. The obtained results are encouraging as they suggest that this panel of Chinese herbs is safe and it may be effective for patients with advanced HCC in a real-world clinical setting.

Modeling rapid and selective capture of nNOS–PSD-95 uncouplers from Sanhuang Xiexin decoction by novel molecularly imprinted polymers based on metal–organic frameworks

Novel and highly selective molecularly imprinted polymers based on the surface of metal–organic frameworks, NH2-MIL-101(Cr) (MIL@MIPS), were successfully fabricated to capture neuronal nitric oxide synthase–postsynaptic density protein-95 (nNOS–PSD-95) uncouplers from Sanhuang Xiexin Decoction (SXD) for stroke treatment. The resultant polymers were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffraction. The performance tests revealed that MIL@MIPs had a large binding capacity, fast kinetics, and excellent selectivity. Then the obtained polymers were satisfactorily applied to solid-phase extraction coupled with high-performance liquid chromatography to selectively capture nNOS–PSD-95 uncouplers from SXD. Furthermore, the biological activities of components obtained from SXD were evaluated in vivo and in vitro. As a consequence, the components showed a potent neuroprotective effect from the MTS assay and uncoupling activity from the co-immunoprecipitation experiment. In addition, the anti-ischemic stroke assay in vivo was further investigated to determine the effect of reducing infarct size and ameliorating neurological deficit by the active components. Therefore, this present study contributes a valuable new method and new tendency to selectively capture active components for stroke treatment from SXD and other natural medicines.

Medication regularity of combination of traditional Chinese medicine and Western medicine in treating Helicobacter pylori-related gastropathy based on literatures

The medication rules of combination of traditional Chinese medicine( TCM) and Western medicine in treating Helicobacter pylori-related gastropathy are analyzed to provide reference for clinical Helicobacter pylori-related gastropathy. Relevant literatures on integrated traditional Chinese and Western medicine in the treatment of Helicobacter pylori-related gastropathy were collected in CNKI,Wan Fang,VIP and CBM. Excel software and traditional Chinese medicine inheritance support system were used to establish a prescription database for data mining and analysis of the medication rules. A total of 178 literatures were selected,77 of them indicated TCM syndromes,and the syndrome of dampness-heat in the spleen and stomach had the highest frequency. A total of 207 prescriptions were used,including 100 classic prescriptions,and Banxia Xiexin Decoction had the highest frequency. Traditional Chinese medicine materials were used for 3 027 times,involving 207 herbs,and the top three mostly frequently used herbs were Glycyrrhiza uralensis,Coptis chinensis,and Pinellia ternata. The herbs mostly featured cold and warm properties in four natures,and bitterness and pungent in five flavors,and enter spleen,stomach and liver meridians. Totally 21 core drug combinations and 12 new prescriptions were obtained. According to data mining,the treatment of Helicobacter pylori-related gastropathy gives priority to " dispelling evil" " tonifying deficiency" and regulating Qi. The medication rules were the combination of cold and warm herbs and the compatibility of acrid opening and bitter down-bearing herbs. This provides a certain reference for optimizing clinical prescriptions,improving efficacy,and developing new drugs.

Banxia Xiexin decoction, a traditional Chinese medicine, alleviates colon cancer in nude mice.

Banxia Xiexin decoction (BXD) is widely used in the treatment of acute and chronic gastritis, peptic ulcer, dyspepsia, gastrointestinal dysfunction, chronic hepatitis, oral ulcer and other diseases, but there are few reports on its treatment of colon cancer. The current study was designed to investigate the effect of BXD on colon cancer and its possible molecular mechanisms. Fifty SPF BALB/c nude mice were selected to establish an animal model of colon cancer bearing nude mice. Establishment of nude mice intestinal cancer model by subcutaneous injection of intestinal cancer cells. Serum superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by commercial kits. Pro-inflammatory cytokines in serum were detected. Western blotting was used to demonstrate the expression levels of related apoptosis proteins, inflammation and oxidative stress proteins. Our results showed that BXD could decrease SOD and increased MDA in nude mice bearing tumors. BXD increased pro-inflammatory cytokines in serum in nude mice bearing tumors. Western blotting revealed that the protein expressions of Bax, Caspase-3, Caspase-9 were increased by different concentrations of BXD, while Bcl-2 was decreased. BXD also decreased Nrf-2 and HO-1, and increased the levels of MAPK/NF-κB pathway in tumor tissue. BXD has an obvious tumor inhibiting effect on SW 480 colon cancer transplanted tumor in nude mice via apoptotic pathway and MAPK/NF-κB pathway.

Banxia Xiexin Decoction for patients with peptic ulcer or chronic gastritis infected with Helicobacter pylori

Abstract Objective To compare the effectiveness and safety of Banxia Xiexin Decoction (BXD) as alternative therapy versus standard triple therapy or quadruple therapy for patients with peptic ulcer or chronic gastritis infected with Helicobacter pylori (H. pylori). Methods Databases including China National Knowledge Infrastructure, Chongqing VIP, Wanfang Database, PubMed, the Cochrane Library and clinicaltrials.gov were searched in December 2018 for relevant randomized controlled trials (RCTs). Two authors independently screened and selected studies, extracted data and checked data extraction. Methodological quality was evaluated using the Cochrane Risk of Bias tool. Meta-analysis was performed by using RevMan 5.3.5 software. Results Fourteen RCTs were included in our analysis involving 1300 patients. Thirteen RCTs compared the effects of BXD alone versus standard therapy, 11 involving triple therapy and 2 in quadruple therapy. The cure rate for both diseases were higher in the BXD alone group than in the standard therapy group (RR and 95% CI: 1.85 [1.07, 3.17] and 1.48 [1.24, 1.75], respectively). And also, the same result with effectiveness rate (RR and 95% CI: 1.18 [1.08, 1.29] and 1.14 [1.08, 1.20], respectively). However, there was no significant difference in the clearance of H. pylori one month after treatment, neither compared with quadruple therapy nor triple therapy (RR and 95% CI: 1.10 [1.00, 1.22] and 1.04 [0.97, 1.12], respectively). Adverse events appeared in 3 participants in the BXD group and 26 participants in the conventional therapy group. The quality of the trials included in this review was not very good. Conclusion BXD has a superior effect to standard conventional therapy in improving clinical symptoms and repair of the mucosal lesion, and a similar effect to standard conventional therapy in clearing H. pylori. We still need good quality trials, especially placebo-controlled trials, in the future to confirm this result.

A meta-analysis of Banxia Xiexin decoction versus omeprazole in the treatment of gastroesophageal reflux disease

A meta-analysis of Banxia Xiexin decoction versus omeprazole in the treatment of gastroesophageal reflux disease

Exploring the multicomponent synergy mechanism of Banxia Xiexin Decoction on irritable bowel syndrome by a systems pharmacology strategy

Ethnopharmacological relevanceBanxia Xiexin Decoction (BXD) is a representative prescription to regulate spleen and stomach in “Treatise on Febrile Diseases”, which has been proven effective for the clinical treatment of irritable bowel syndrome (IBS) in the past decades. However, the active principles and molecular mechanisms involved in BXD against IBS are vague yet. Aim of the studyTo unfold multicomponent synergy mechanism of BXD on irritable bowel syndrome, this work explored active principles, drug targets and crucial pathways using a systems pharmacology strategy. Materials and methodsIn this study, a systems pharmacology based strategy was applied by the procedures integrating compound database construction, ADME evaluation, target identification, functional annotation, pathway enrichment analysis, network analysis, and molecular docking verification. The 158 compounds from BXD were selected for the screening. The Compound-Target network (C-T) and the Target-Pathway network (T-P) were constructed. The bioinformatics and network topology were employed to systematically reveal multicomponent-target interactions of BXD. The affinity between important ingredients and the kernel targets was validated using molecular mechanics simulation. ResultsThe 35 potential important ingredients and the 16 associated kernel targets were identified. 27 crucial pathways, in which the kernel targets participated, could regulate the biological processes, such as synthesis of inflammatory mediators, smooth muscle relaxation and synaptic plasticity, closely related to pathological mechanism of IBS. The cross-talk interactions were revealed between TNF signaling pathway, Dopaminergic synapse and cGMP-PKG signaling pathway, which would exert the synergistic influences on the occurrence and treatment of the IBS. PTGS2, CALM, NOS2, SCN5A, and PRSS1 might become novel drug targets for IBS. ConclusionsThe study demonstrated that the synergy molecular mechanisms of BXD mainly involved three therapeutic modules including inhibiting inflammatory reaction, maintaining intestinal function and improving psychological regulation via the multicomponent-target interaction networks. It may also provide the promising drug targets and therapeutic agents for the development of new medicines.

Sanhuang Xiexin decoction promotes good functional outcome in acute ischemic stroke.

ObjectivesTo explore the efficiency and safety of Sanhuang Xiexin decoction in the treatment of acute ischemic stroke (AIS) patients after endovascular intervention examination.MethodsIn this prospective observational study, 121 AIS patients admitted in our hospital were enrolled from January 2012 to December 2015. They were randomly divided into two groups, 61 patients received Sanhuang Xiexin decoction + basic treatment (SX group) and 60 patients received basic treatment (control group). The prescription of Sanhuang Xiexin decoction was taken in the SX group, with one dose (100 ml), twice a day for 7 days orally. For all patients, blood samples were drawn on the first morning and sixth morning after endovascular intervention examination under fasting state for Fib (fibrinogen), PAgT (platelet aggregation test), CRP (C‐reactive protein), and TMAO (trimethylamine oxide) tested. Estimate the changes in plasma Fib, PAgT, CRP, and TMAO levels and the syndrome of fire‐heat scores.ResultsThe plasma Fib, PAgT, CRP, and TMAO levels in the SX group were significantly lower than those in the control group (PFib < 0.01, PPAgT < 0.01, PCRP = 0.02, PTMAO < 0.01). The syndrome of fire‐heat scores in the SX group was significantly lower than that in the control group (p < 0.01). The incidences of ischemic cerebrovascular events within 3 and 6 months after endovascular intervention treatment in the SX group were lower than those in the control group (P3 month = 0.04, P6month = 0.03).ConclusionsThe prescription of Sanhuang Xiexin is efficient and safe in the treatment of AIS patients after endovascular intervention examination through reducing the inflammatory factors.

Chinese Herbal Medicines Facilitate the Control of Chemotherapy-Induced Side Effects in Colorectal Cancer: Progress and Perspective.

Side effects, including nausea, vomiting, mucositis, peripheral neuropathy, and diarrhea, have been frequently reported in colorectal cancer (CRC) patients undergoing chemotherapy. Chinese Herbal Medicines (CHMs) display distinct clinical outcomes, as a result, they have been increasingly used as an adjuvant therapy to manage chemotherapy-induced side effects. In this review, we aim to intensively explore the molecular mechanisms of CHMs, underline the significance of CHMs in mitigating the side effects induced by chemotherapy, and examine the necessary studies required to understand the role of CHMs in alleviating chemotherapy-induced side effects. Specifically, ginger, Astragali Radix, and Liujunzi Decoction have been verified to ameliorate nausea and vomiting. Banxia Xiexin Decoction and Huangqin Decoction have been confirmed to be beneficial to mucositis and delayed-onset of diarrhea. Moreover, Niuche Shenqi Wan, Guilong Tongluo Decoction, Huangqi Guizhi Wuwu Decoction, and tumeric have been found to display potential therapeutic effects for preventing the genesis and development of peripheral neurotoxicity. These findings have further emphasized the pivotal role of CHMs in improving the outcomes of chemotherapy-induced side effects in CRC. Nonetheless, more molecular evidence is required to comprehensively understand and more appropriately apply CHMs in routine clinical practice for CRC.

Banxia Xiexin Decoction Is Effective to Prevent and Control Irinotecan-Induced Delayed Diarrhea in Recurrent Small Cell Lung Cancer.

Background: Irinotecan (CPT-11) can be used as a first-line therapeutic drug against extensive-stage small cell lung cancer (SCLC); it can also be used in second-line treatment for SCLC. CPT-11-induced delayed diarrhea restricts its clinical application. This study aimed to confirm whether Banxia Xiexin decoction was effective in preventing and controlling CPT-11-induced delayed diarrhea. Methods: A total of 27 patients with recurrent SCLC undergoing chemotherapy regimens including CPT-11 were enrolled for the study. UGT1A1*28, UGTlAl*6, ABCB1*2, and SLCO1B1*15 gene polymorphisms were detected. If delayed diarrhea occurred in the first cycle of chemotherapy, Banxia Xiexin decoction was orally administered for 5 consecutive days starting 1 day before the second cycle of chemotherapy to prevent and control the delayed diarrhea. The objective response, overall survival, and toxicity were recorded. Results: Complete response, partial response, and stable disease were observed in none, 6, and 10 patients, respectively. Delayed diarrhea occurred in 6 patients, and 4 of 5 patients were relieved or controlled using Banxia Xiexin decoction. The median overall survival was 6 months. Conclusion: Banxia Xiexin decoction appeared to prevent and control delayed diarrhea induced by CPT-11 in this small observational study, and further study with a larger sample size, including potentially randomized trials, is suggested.

Herbal medicine (Gancao Xiexin decoction) for Behcet disease: A systematic review protocol.

Background:Behcet disease (BD) is a systemic vasculitis that causes blood vessel inflammation throughout body and no cure exists. The purpose of this review is to evaluate the safety and efficacy of Gancao Xiexin Decoction (GCXX) in the treatment of BD and provide a clinical reference for the treatment of the refractory disease.Methods:First, the researcher will retrieve the following database based on the established search strategy: MEDLINE (PubMed), the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Allied and Complementary Medicine Database (AMED), China National Knowledge Infrastructure, Wanfang, VIP (Journal Integration Platform). The quality of the literature will be evaluated according to Cochrane's handbook and review inclusion criteria. Data will be extracted and data of sufficient homogeneity was combined using Review Manager (RevMan) software V5.3.5.Results:This study will provide a high quality synthesis of herbal medicine (Gancao Xiexin decoction) for Behcet disease.Conclusions:The conclusion of our systematic review will provide evidence to judge whether herbal medicine (Gancao Xiexin decoction) for Behcet disease is an effective intervention for patient with menopausal women.Trial registration number:PROSPERO CRD 42018104099.

Research Progress of Different Acupuncture and Moxibustion Methods in the Treatment of GERD (Gastro Esophageal Reflux Disease)

Over the past decade, there have been many clinical reports on acupuncture and moxibustion in the treatment of gastro esophageal reflux disease, which has been an increasing trend year by year. The authors use "acupuncture", "acupuncture and moxibustion" or "electric acupuncture" and "GERD" or "gastro esophageal reflux disease" as key words for retrieval. Through the clinical articles on acupuncture and moxibustion methods in the treatment of GERD indexed by China CNKI academic literature database, VPCS database and Wanfang database from 2006 to 2016, we find that: acupuncture and moxibustion methods in the treatment of GERD has definite curative effect and outstanding advantages. It can better improve the symptoms of patients and can effectively improve their quality of life. At present, in clinical applications, there are treatment ideas such as the method of acupuncture on governor vessel back segment, the old ten needles, and compatibility of five meridians in the aspect of acupoint selection; there are treatment ideas such as fire acupuncture, thread-embedding, and electric acupuncture in the aspect of method of needling and moxibustion; there are treatment ideas such as acupuncture and moxibustion combined with pinellia ternate Xiexin Decoction, Chinese herb bath, deanxit (flupentixol and melitracen tablets) in the aspect of acupuncture and medicinal treatment. This paper comb integration of the current variety of therapies, in order to allow readers to obtain a more comprehensive clinical diagnosis and treatment ideas of gastro esophageal reflux disease.

Effect of Banxia Xiexin decoction on Helicobacter pylori-related peptic ulcers and its possible mechanism via the TGF-β/Smad signaling pathway

OBJECTIVETo investigate the effect of Banxia Xiexin decoction (BXD) on Helicobacter pylori (Hp)-related peptic ulcers (PUs) and the possible mechanism underlying BXD actions via the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) signaling pathway. METHODSPU patients with cold-heat complex syndrome were randomly assigned to groups that received Chinese or Western medicines with 20 patients in each group. Serum was collected after 7 d of treatment. The healthy group included 20 individuals. Gastric mucosal epithelial cell line GES-1 was cultured in vitro and randomly divided into the following seven groups: control, model, healthy, Western Medicine, prior treatment, low dosage, and high dosage. After 72 h of treatment with the corresponding serum, the mRNA and protein expression levels of TGF-β1, Smad3, and Smad7 were measured by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. RESULTSThe mRNA expression levels of TGF-β1 and Smad3 in GES-1 cells were increased after Hp introduction, and these increased levels were reduced by the BXD-containing serum. The protein levels of p-Smad3, but not TGF-β1 or Smad3, were significantly increased in Hp-treated GES-1 cells, and treatment with the BXD-containing serum markedly decreased the protein levels. Smad7 expression was significantly enhanced following treatment with the BXD-containing serum at transcriptional and protein levels in a dose-dependent manner. CONCLUSIONBXD regulates the TGF-β/Smad signaling pathway by inhibiting the expression of TGF-β1 and Smad3, and increasing the expression of Smad7.

Effects of Banxia Xiexin Decoction (半夏泻心汤) on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells

To examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines. A549 cells were treated with varying concentrations (50-200 μg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. The exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V+/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK). BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

Banxia Xiexin decoction ameliorated cognition via the regulation of insulin pathways and glucose transporters in the hippocampus of APPswe/PS1dE9 mice.

Reduced glucose utilization and deficient energy metabolism that occur in the early stages of Alzheimer’s disease correlate with impaired cognition, and this information is evidence that Alzheimer’s disease is a metabolic disease that is associated with brain insulin/insulin-like growth factor resistance. This research aimed to investigate the effects of Banxia Xiexin decoction (BXD) on cognitive deficits in APPswe/PS1dE9 double transgenic mice and verify the hypothesis that BXD treatment improves cognitive function via improving insulin signalling, glucose metabolism and synaptic plasticity in the hippocampus of APPswe/PS1dE9 double transgenic mice. We used 3-month-old APPswe/PS1dE9 double transgenic mice as the case groups and wild-type littermates of the double transgenic mice from the same colony as the control group. Forty-five APPswe/PS1dE9 double transgenic mice were randomly divided into the model group, donepezil group and BXD group. The mice in the control and model groups were administered 0.5% carboxymethyl cellulose orally. The Morris water maze and step-down test were conducted to evaluate the cognitive performance of APPswe/PS1dE9 double transgenic mice after BXD treatment. Ultrastructure of synapses was observed in the hippocampal CA1 area. Proteins involved in insulin signalling pathways and glucose transports in the hippocampus were assessed through immunohistochemical staining and western blot. After 3 months intervention, we found that BXD treatment improved cognitive performance and the synaptic quantity and ultrastructure, restored insulin signalling and increased the expression of glucose transporter 1 (GLUT1) and GLUT3 levels. These findings suggest that the beneficial effect of BXD on cognition may be due to the improvement of insulin signalling, glucose metabolism and synaptic plasticity.

Experimental research of hypotensive and hypolipidemic effects with Modified Sanhuang Xiexin Decoction ().

To investigate the hypotensive and hypolipidemic effects of Modified Sanhuang Xiexin Decoction (, HVC1), a herbal prescription for the vascular diseases in Chinese medicine and evaluate the acute and subchronic oral toxicities. Fifty-six spontaneous hypertensive rats (SHRs) were used to investigate the hypotensive and hypolipidemic effect of HVC1. Rats in the normal group (n=8) were fed with normal diet. The rats in the other groups (n=48) were fed with high fat and cholesterol diet for inducing hyperlipidemia models. Forty-eight rats were randomly divided into 6 groups [model, positive control (amlodipine, simvastain), 50, 250, and 1,000 mg/(kg•d) HVC1 groups] with 8 animals in each group. Normal and model groups were treated with distilled water [1 mL/(kg•d)], the positive control group was treated with amlodipine [5 mg/(kg•d)] or simvastatin [10 mg/(kg•d)], and the HVC1 groups were treated with HVC1 [50, 250, or 1,000 mg/(kg•d)] for 8 weeks, respectively. Blood pressure (BP) of the rats was measured using a non-invasive tail cuff system. On the last day of the experiment, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels were measured. To investigate the safety of HVC1, acute and subchronic toxicity studies were conducted on Sprague-Dawley rats. In toxicity studies, the body weight, food and water consumption of rats were measured and clinical signs observation, ophthalmologic examinations, urinalysis, hematological analysis, and serum biochemical analysis were performed. A dose of 50 and 250 mg/(kg•d) HVC1 lowered systolic and diastolic BP (P<0.05). HVC1 at 1,000 mg/(kg•d) decreased TC, LDL-C and TG levels, respectively (P<0.01 or P<0.05) and 250 mg/(kg•d) HVC1 decreased TG levels on hyperlipidemic SHRs (P<0.05). In the acute toxicity study, oral administration of HVC1 did not show any toxicity effect, and the median lethal dose value of HVC1 was greater than 5,000 mg/kg. In the subchronic toxicity study, oral administration of HVC1 for 4 weeks also did not show any toxicity effect, and the no-observedadverse-effect-level of HVC1 was established as 2,000 mg/(kg•d). These results could be used as preclinical data for clinical trials that develop HVC1 as a herbal medicine for treating or preventing hypertension and hyperlipidemia.

Shengjiang Xiexin Decoction Alters Pharmacokinetics of Irinotecan by Regulating Metabolic Enzymes and Transporters: A Multi-Target Therapy for Alleviating the Gastrointestinal Toxicity.

Shengjiang Xiexin decoction (SXD), a classic traditional Chinese medical formula chronicled in Shang Han Lun, is used in modern clinical practice to decrease gastrointestinal toxicity induced by the chemotherapeutic drug irinotecan (CPT-11). In this study, the effect of SXD on the pharmacokinetics of CPT-11 and its active metabolites (SN-38 and SN-38G), and the underlying mechanisms were further examined. An ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous quantification of CPT-11, SN-38, and SN-38G in the plasma, bile, liver, intestine, and intestinal contents of control and SXD-pre-treated rats after intravenous administration of CPT-11. SXD pretreatment increased the area under the curve (AUC) and the initial plasma concentration (C0) of CPT-11 but decreased the plasma clearance (CL). The AUC and the maximum plasma concentration (Cmax) of SN-38 decreased, whereas the Cmax of SN-38G increased. Compared with that of the control group, the biliary excretion of CPT-11, SN-38, and SN-38G was inhibited. The CPT-11, SN-38, and SN-38G concentrations in the liver, intestine, and intestinal contents were different between the two groups. Furthermore, the hepatic expression of multidrug resistance-associated protein-2 (Mrp-2), P-glycoprotein (P-gp), and carboxylesterase 2 (CES2) was significantly down-regulated by SXD, while the hepatic and jejunal uridine diphosphate (UDP)-glucuronosyltransferase 1A1 (UGT1A1) expression was elevated. The hydrolysis of CPT-11 to SN-38 by CES and the glucuronidation of SN-38 to SN-38G by UGT were affected by liver and jejunum S9 fractions from rats pre-treated with SXD. Therefore, this study demonstrated for the first time that SXD could alter the pharmacokinetics of CPT-11 and its metabolites to alleviate CPT-11-induced diarrhea. And the underlying mechanism of drug interaction between CPT-11 and SXD involves decreasing hepatic Mrp-2 and P-gp expression and altering the activities of CES and UGT.