Effects of electroacupuncture on the PI3K/Akt/CREB signaling pathway and hippocampal neuronal apoptosis in diabetic cognitive impairment rats. / ç”µé’ˆå¯¹ç³–å°¿ç— è®¤çŸ¥åŠŸèƒ½éšœç¢å¤§é¼ PI3K/Akt/CREBä¿¡å·é€šè·¯å’Œæµ·é©¬ç¥žç»å ƒå‡‹äº¡çš„å½±å“.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/cAMP response element binding protein (CREB) signaling pathway-related proteins and hippocampal neuron apoptosis in diabetic cognitive impairment (DCI) rats, and to explore the mechanisms of EA in treating DCI. METHODS: Adult male SD rats were randomly divided into normal, model, and EA groups, with 12 rats in each group. The animal model of DCI was replicated using a high-fat, high-sugar diet combined with low-dose streptozotocin. The EA group received EA stimulation at "Yishu" (EX-B6), "Zusanli" (ST36), "Baihui" (GV20), and "Dazhui" (GV14). Blood glucose contents of the rats in each group were measured. The Morris water maze test was used to assess the learning and memory abilities of rats. Transmission electron microscopy was used to observe the ultrastructure of hippocampal CA1 neurons. Nissl staining was used to observe the pathological changes in hippocampal CA1 neurons. TUNEL staining was used to detect the apoptosis in hippocampal CA1 neurons. Western blot was used to detect the protein expression levels of p-PI3K/PI3K and p-Akt/Akt, as well as CREB, p-CREB, cysteine aspartate pro-tease (Caspase)-3, B-cell lymphoma-2 (Bcl-2), and Bcl-2 related X protein (Bax) in the hippocampal tissue of rats. RESULTS: Compared with the normal group, the rats' random blood glucose contents were significantly increased (P<0.01), the escape latency prolonged (P<0.01), and the original platform crossing counts reduced (P<0.01) in the model group. Significant damage to hippocampal CA1 neurons, a significantly increased neuronal apoptosis index (P<0.01), decreased ratio of p-PI3K/PI3K and p-Akt/Akt and expression of CREB, p-CREB and Bcl-2 proteins, increased expression of Caspase-3 and Bax proteins (P<0.01) were observed in the hippocampal tissue of rats in the model group. Compared with the model group, the rats in the EA group showed decreased random blood glucose content (P<0.01), shortened escape latency (P<0.01), increased original platform crossing counts (P<0.01), improved quantity and pathological morphology and ultrastructure of hippocampal CA1 neurons, reduced neuronal apoptosis index (P<0.01), increased ratio of p-PI3K/PI3K and p-Akt/Akt, and expression of CREB, p-CREB and Bcl-2 proteins (P<0.05, P<0.01) in the hippocampal tissue, and decreased expression of Caspase-3 and Bax proteins (P<0.01). CONCLUSIONS: EA can improve the learning and memory abilities of rats with DCI, and the mechanism may be related to the regulation of the expression of PI3K/Akt/CREB signaling pathway-related proteins, which attenuates the neuronal apoptosis in the hippocampus of rats, and improves the neural function.

Polyamine-mediated ferroptosis amplification acts as a targetable vulnerability in cancer.

Targeting ferroptosis, an iron-dependent form of regulated cell death triggered by the lethal overload of lipid peroxides, in cancer therapy is impeded by our limited understanding of the intersection of tumour's metabolic feature and ferroptosis vulnerability. In the present study, arginine is identified as a ferroptotic promoter using a metabolites library. This effect is mainly achieved through arginine's conversion to polyamines, which exerts their potent ferroptosis-promoting property in an H2O2-dependent manner. Notably, the expression of ornithine decarboxylase 1 (ODC1), the critical enzyme catalysing polyamine synthesis, is significantly activated by the ferroptosis signal--iron overload--through WNT/MYC signalling, as well as the subsequent elevated polyamine synthesis, thus forming a ferroptosis-iron overload-WNT/MYC-ODC1-polyamine-H2O2 positive feedback loop that amplifies ferroptosis. Meanwhile, we notice that ferroptotic cells release enhanced polyamine-containing extracellular vesicles into the microenvironment, thereby further sensitizing neighbouring cells to ferroptosis and accelerating the "spread" of ferroptosis in the tumour region. Besides, polyamine supplementation also sensitizes cancer cells or xenograft tumours to radiotherapy or chemotherapy through inducing ferroptosis. Considering that cancer cells are often characterized by elevated intracellular polyamine pools, our results indicate that polyamine metabolism exposes a targetable vulnerability to ferroptosis and represents an exciting opportunity for therapeutic strategies for cancer.

Efficient and fast screening and separation based on computer-aided screening and complex chromatography methods for lipoxygenase inhibitors from Ganoderma lucidum.

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.

A polysaccharide from Alhagi honey protects the intestinal barrier and regulates the Nrf2/HO-1-TLR4/MAPK signaling pathway to treat alcoholic liver disease in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of traditional Chinese medicine, the main factors related to alcoholic liver disease (ALD) are qi stagnation and blood stasis of the five viscera. Previously, we showed that the bioactive components of Alhagi honey have various pharmacological effects in treating liver diseases, but the influence of Alhagi honey on ALD (and its mechanism of action) is not known. AIM OF THE STUDY: To determine the efficacy of the main active component of Alhagi honey, the polysaccharide AHPN80, in ALD and to explore the potential mechanism of action. MATERIALS AND METHODS: AHPN80 was isolated from dried Alhagi honey and identified by transmission electron microscopy, Fourier-transform infrared spectroscopy, and gas chromatography. Venous blood, liver tissue, and colon tissue were collected in a mouse model of alcohol-induced acute liver injury. Histology, staining (Oil Red O, Alcian Blue-Periodic Acid Schiff) and measurement of reactive oxygen species (ROS) levels were used to detect histopathologic and lipid-accumulation changes in the liver and colon. Lipopolysaccharide (LPS) levels and the content of proinflammatory cytokines in serum were measured by enzyme-linked immunosorbent assays. Commercial kits were employed to detect biochemistry parameters in serum and the liver. A terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining kit was used to identify hepatocyte apoptosis. Expression of tight junction-associated proteins in colon tissues and nuclear factor erythroid 2-related factor 2/heme oxygenase-1/toll-like receptor-4/mitogen-activated protein kinase (Nrf2/HO-1/TLR4/MAPK) pathway-related proteins in liver tissues and HepG2 cells were analyzed by immunofluorescence or western blotting. RESULTS: In a mouse model of alcohol-induced acute liver injury, AHPN80 therapy: significantly improved liver parameters (cytochrome P450 2E1, alcohol dehydrogenase, aldehyde dehydrogenase, superoxide dismutase, malondialdehyde, glutathione peroxidase, catalase, total cholesterol, triglycerides, alanine transaminase, aspartate transaminase); reduced serum levels of LPS, interleukin (IL)-1ß, IL-6, and tumor necrosis faction-α; increased levels of IL-10 and interferon-gamma. AHPN80 reduced ALD-induced lipid accumulation and ROS production, improved alcohol-induced inflammatory damage to hepatocytes, and inhibited hepatocyte apoptosis. Immunofluorescence staining and western blotting suggested that AHPN80 might eliminate hepatic oxidative stress by activating the Nrf2/HO-1 signaling pathway, repair the intestinal barrier, inhibit the LPS/TLR4/MAPK signaling pathway, and reduce liver inflammation. CONCLUSIONS: AHPN80 may activate the Nrf2/HO-1 pathway to eliminate oxidative stress, protect the intestinal barrier, and regulate the TLR4/MAPK pathway to treat ALD in mice. AHPN80 could be a functional food and natural medicine to prevent ALD and its complications.

Rapid screening, isolation, and activity evaluation of potential xanthine oxidase inhibitors in Polyporus umbellatus and mechanism of action in the treatment of gout.

INTRODUCTION: Studies show that Polyporus umbellatus has some pharmacological effects in enhancing immunity and against gout. OBJECTIVES: We aimed to establish new techniques for extraction, biological activity screening, and preparation of xanthine oxidase inhibitors (XODIs) from P. umbellatus. METHODS: First, the extraction of P. umbellatus was investigated using the back propagation (BP) neural network genetic algorithm mathematical regression model, and the extraction variables were optimised to maximise P. umbellatus yield. Second, XODIs were rapidly screened using ultrafiltration, and the change of XOD activity was tested by enzymatic reaction kinetics experiment to reflect the inhibitory effect of active compounds on XOD. Meanwhile, the potential anti-gout effects of the obtained active substances were verified using molecular docking, molecular dynamics simulations, and network pharmacology analysis. Finally, with activity screening as guide, a high-speed countercurrent chromatography (HSCCC) method combined with consecutive injection and two-phase solvent system preparation using the UNIFAC mathematical model was successfully developed for separation and purification of XODIs, and the XODIs were identified using MS and NMR. RESULTS: The results verified that polyporusterone A, polyporusterone B, ergosta-4,6,8(14),22-tetraen-3-one, and ergosta-7,22-dien-3-one of P. umbellatus exhibited high biological affinity towards XOD. Their structures have been further identified by NMR, indicating that the method is effective and applicable for rapid screening and identification of XODIs. CONCLUSION: This study provides new ideas for the search for natural XODIs active ingredients, and the study provide valuable support for the further development of functional foods with potential therapeutic benefits.

PLK1 regulating chemoradiotherapy sensitivity of esophageal squamous cell carcinoma through pentose phosphate pathway/ferroptosis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China, accounting for more than 90 %. Most patients were diagnosed with advanced-stage ESCC, for whom new adjuvant therapy is recommended. Therefore, it is urgent to explore new therapeutic targets for ESCC. Ferroptosis, a newly discovered iron-dependent programmed cell death, has been shown to play an important role in carcinogenesis by many studies. This study explored the effect of Polo like kinase 1 (PLK1) on chemoradiotherapy sensitivity of ESCC through ferroptosis METHODS: In this study, we knocked out the expression of PLK1 (PLK1-KO) in ESCC cell lines (KYSE150 and ECA109) with CRISPR/CAS9. The effects of PLK1-knock out on G6PD, the rate-limiting enzyme of pentose phosphate pathway (PPP), and downstream NADPH and GSH were explored. The lipid peroxidation was observed by flow cytometry, and the changes in mitochondria were observed by transmission electron microscopy. Next, through the CCK-8 assay and clone formation assay, the sensitivity to cobalt 60 rays, paclitaxel, and cisplatin were assessed after PLK1-knock out, and the nude mouse tumorigenesis experiment further verified it. The regulation of transcription factor YY1 on PLK1 was evaluated by dual luciferase reporter assay. The expression and correlation of PLK1 and YY1, and their impact on prognosis were analyzed in more than 300 ESCC cases from the GEO database and our center. Finally, the above results were further proved by single-cell sequencing. RESULTS: After PLK1 knockout, the expression of G6PD dimer and the level of NADPH and GSH in KYSE150 and ECA109 cells significantly decreased. Accordingly, lipid peroxidation increased, mitochondria became smaller, membrane density increased, and ferroptosis was more likely to occur. However, with the stimulation of exogenous GSH (10 mM), there was no significant difference in lipid peroxidation and ferroptosis between the PLK1-KO group and the control group. After ionizing radiation, the PLK1-KO group had higher lipid peroxidation ratio, more cell death, and was more sensitive to radiation, while exogenous GSH (10 mM) could eliminate this difference. Similar results could also be observed when receiving paclitaxel combined with cisplatin and chemoradiotherapy. The expression of PLK1, G6PD dimer, and the level of NADPH and GSH in KYSE150, ECA109, and 293 T cells stably transfected with YY1-shRNAs significantly decreased, and the cells were more sensitive to radiotherapy and chemotherapy. ESCC patients from the GEO database and our center, YY1 and PLK1 expression were significantly positively-correlated, and the survival of patients with high expression of PLK1 was significantly shorter. Further analysis of single-cell sequencing specimens of ESCC in our center confirmed the above results. CONCLUSION: In ESCC, down-regulation of PLK1 can inhibit PPP, and reduce the level of NADPH and GSH, thereby promoting ferroptosis and improving their sensitivity to radiotherapy and chemotherapy. Transcription factor YY1 has a positive regulatory effect on PLK1, and their expressions were positively correlated. PLK1 may be a target for predicting and enhancing the chemoradiotherapy sensitivity of ESCC.

Generation of Meaty Aroma from Onion (Allium cepa L.) with Polyporus umbellatus: Fermentation System, Sensory Profile, and Aroma Characterization.

One of the main reasons for consumer rejection of plant-based meat alternatives is the lack of meaty flavor after cooking. In this study, a platform was developed to generate meaty flavors solely from Allium substrates (chives, leeks, ramsons, and onions) using basidiomycete-mediated submerged fermentations. Polyporus umbellatus-mediated fermentation of onions resulted in an intense meaty and liver sausage-like flavor under proper fermentation parameters. Using multisolvent and solvent-free aroma extractions coupled with gas chromatography-mass spectrometry-olfactometry, 5 odorants with high assigned flavor dilution (FD) factors (≥ 256) were identified in the fermented sample that have been reported in the literature as important aroma compounds of meat products: methyl palmitate, bis(2-methyl-furyl) disulfide, (E,E)-2,4-decadienal, γ-nonalactone, and eugenol. Using selected ion monitoring, the presence of bis(2-methyl-furyl) disulfide (meaty, savory, FD 256) after fermentation was confirmed. It was proposed that P. umbellatus enzymatically forms bis(2-methyl-furyl) disulfide from intermediates derived from the thermal degradation of thiamine.

A comparative study on flavor trapping techniques from the viewpoint of odorants of hot-pressed rapeseed oil.

Rapeseed oil, as one of the three major vegetable oils in the world, its matrix effect makes the decoding flavor a challenge. Solid-phase microextraction (SPME), SPME-Arrow, headspace stir bar sorptive extraction (HSSE), direct thermal desorption (DTD), and solvent-assisted flavor evaporation (SAFE) were compared based on the odorants in hot-pressed rapeseed oil. Besides, methodological validation for 31 aroma standards was conducted to compare reliability and robustness of these approaches. DTD showed the largest proportion of acids, while the other techniques extracted a majority of nitriles. The highest number of odorants was detected by SAFE (31), followed by HSSE (30), SPME-Arrow (30), SPME (24), and DTD (14). SPME-Arrow showed the best performance in linearity, recovery, and reproducibility followed by SPME, HSSE, DTD, and SAFE. Results reveal the advantages and limitations of diverse methodologies and provide valuable insights for the selection of extraction methods in an oil matrix and flavor decoding.

Retinol Saturase Mediates Retinoid Metabolism to Impair a Ferroptosis Defense System in Cancer Cells.

Ferroptosis is an iron-dependent form of regulated cell death induced by the lethal overload of lipid peroxides in cellular membranes. In recent years, modulating ferroptosis has gained attention as a potential therapeutic approach for tumor suppression. In the current study, retinol saturase (RETSAT) was identified as a significant ferroptosis mediator using a publicly accessible CRISPR/Cas9 screening dataset. RETSAT depletion protected tumor cells from lipid peroxidation and subsequent cell death triggered by various ferroptosis inducers. Furthermore, exogenous supplementation with retinoids, including retinol (the substrate of RETSAT) and its derivatives retinal and retinoic acid, also suppressed ferroptosis, whereas the product of RETSAT, 13, 14-dihydroretinol, failed to do so. As effective radical-trapping antioxidant, retinoids protected the lipid membrane from autoxidation and subsequent fragmentation, thus terminating the cascade of ferroptosis. Pseudotargeted lipidomic analysis identified an association between retinoid regulation of ferroptosis and lipid metabolism. Retinoic acid, but not 13, 14-dihydroretinoic acid, interacted with its nuclear receptor and activated transcription of stearoyl-CoA desaturase, which introduces the first double bond into saturated fatty acid and thus catalyzes the generation of monounsaturated fatty acid, a known ferroptosis suppressor. Therefore, RETSAT promotes ferroptosis by transforming retinol to 13, 14-dihydroretinol, thereby turning a strong anti-ferroptosis regulator into a relatively weak one. SIGNIFICANCE: Retinoids have ferroptosis-protective properties and can be metabolized by RETSAT to promote ferroptosis, suggesting the possibility of targeting retinoid metabolism in cancer as a treatment strategy to trigger ferroptosis.

Identification and analysis of a prognostic ferroptosis and iron-metabolism signature for esophageal squamous cell carcinoma.

Background: The role of ferroptosis in esophageal squamous cell carcinoma (ESCC) is still unclear. Methods: The association of iron metabolism and ferroptosis-related genes with the prognosis, copy number variation (CNV), TMB, and immune cell infiltration of ESCC was explored using data from the GEO and TCGA database and validated by immunofluorescence in 112 ESCC patients from our center. The potential anti-cancer drugs and compounds from the GDSC and the Connectivity Map database were also screened. Results: A total of 117 iron metabolism and ferroptosis-related genes were identified. We found the expressions of PRNP, SLC3A2, SLC39A8, and SLC39A14 negatively related to the prognosis of ESCC patients, while ATP6V0A1 and LCN2 were opposite, which was validated in 112 ESCC samples from our center. And a prognostic signature was constructed based on their expressions and Cox regression coefficient (ß). The low-score group exhibited a significantly worse OS. Besides, analysis of 179 ESCC samples from GSE53625 revealed that patients of poorly differentiation, more than 60 years, T4 stage, advanced N stage, advanced stage, and adjuvant therapy also exhibited a significantly shorter OS, based on which a nomogram to predict the OS was established. Moreover, the low-score group exhibited significantly higher CNV and TMB and more frequent mutations of TP53, MUC16, and NOTCH1. Higher proportion of Macrophages M2, and lower proportion of T cells follicular helper were observed in the low-score group. We discovered that AZD7762, Sunitinib, Cytarabine, Docetaxel, Vinblastine, and Elesclomol exhibited lower IC50 in the low-score group. And 20 potential compounds were identified from the CMap database. Conclusions: Six iron metabolism and ferroptosis-related genes were associated with the prognosis, CNV, TMB, and immune cell infiltration of ESCC. Some potential anti-cancer drugs and compounds may be helpful for OS.

Treating unstable angina with detoxifying and blood-activating formulae: A randomized controlled trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Detoxifying and blood-activating Chinese medicine granule formula, which includes 15 g of Polygonum cuspidatum Sieb. et Zucc. (Polygonum cuspidatum) and 10 g of Crataegus pinnatifida Bunge (Hawthorn), can relieve the symptoms and serve as supplementary treatment for unstable angina. AIM OF THE STUDY: This study aimed to explore the role of detoxifying and blood-activating formulae in the treatment of unstable angina and the potential mechanism involved. MATERIALS AND METHODS: A total of 144 participants with unstable angina were randomly divided into experimental and control groups. Both groups were treated with standardized Western medicine; the experimental group was additionally treated with detoxifying and blood-activating Chinese medicine granules, which included 15 g of P. cuspidatum and 10 g of C. pinnatifida for 4 weeks. The primary endpoint was the frequency of weekly angina pectoris attacks before and after treatment. The secondary endpoints, also observed before and after treatment, included blood glucose, blood lipids, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and adiponectin levels, as well as the ratio of pro/anti-inflammatory factors and evaluation scales of symptoms and syndromes in Chinese and Western medicine. RESULTS: In both experimental and control groups, the frequency of weekly angina pectoris attacks was lower after treatment (P < 0.01), but with no significant intergroup difference (P = 0.10). After intervention, the hs-CRP, TNF-α, and IL-6 levels decreased, while the IL-10 and adiponectin levels significantly increased in the experimental group (P < 0.05 or 0.01). The ratios of the inflammatory factors significantly decreased after treatment, particularly in the experimental group (P < 0.01). Symptoms and syndromes were also ameliorated in the experimental group (P < 0.01), showing a significant difference from the control group (P < 0.01). CONCLUSIONS: Detoxifying and blood-activating formulae can reduce the frequency and relieve symptoms of unstable angina, and this mechanism may be related to a regulation of the balance of pro- and anti-inflammatory factors.

A systematic review and meta-analysis on the efficacy and safety of traditional Chinese patent medicine Jinqi Jiangtang Tablet in the treatment of type 2 diabetes.

INTRODUCTION: At present, a large number of people in the world are suffering from type 2 diabetes (T2DM), so it is urgent to develop effective treatment measures of T2DM. In China, many clinical studies have shown that Jinqi Jiangtang Tablet (JQJTT), a traditional Chinese patent medicine (TCPM), has a good effect in the treatment of T2DM. This systematic review and meta-analysis is intended to assess the efficacy and safety of JQJTT plus conventional therapy in the treatment of T2DM. METHODS: Seven electronic databases were searched to include in eligible studies published from inception to May 24, 2018. Randomized controlled trials (RCTs) of JQJTT in combination with the conventional therapy versus conventional therapy alone or combined with placebo were included. The two reviewers independently conducted data extraction and quality assessment. For different variable types, the outcome measures were expressed as risk ratios (RRs) or mean differences (MDs). According to the value of I2, a fixed or random effect model was used for statistical analysis. RESULTS: Seventeen studies conducted in China were identified in this systematic review, which included 1,425 participants. The meta-analysis on the effective rate of the comparison groups showed a significant difference in favor of the JQJTT group (RR 1.34; 95%CI [1.02, 1.75]; p = 0.04). In addition, the results showed a statistically significant reduction in FBG (MD -0.85; 95%CI [-1.03, -0.68]; p < 0.00001), 2hPG (MD -1.95; 95%CI [-2.33, -1.56]; p < 0.00001), HbA1c (MD -0.76; 95%CI [-1.03, -0.49]; p < 0.00001), FINS (MD -3.05; 95%CI [-3.69, -2.42]; p < 0.00001), PINS (MD -10.22; 95%CI [-13.93, -6.50]; p < 0.00001), HOMA-IR (MD -1.11; 95%CI [-1.55, -0.68]; p < 0.00001), LDL-C (MD -0.37; 95%CI [-0.63, -0.11]; p = 0.006), TC (MD -0.46; 95%CI [-0.85, -0.08]; p = 0.02), TG (MD -0.34; 95%CI [-0.47, -0.20]; p < 0.00001) with JQJTT plus conventional therapy versus conventional therapy alone. There was no statistical difference between the two comparison groups in HDL-C, total incidence of adverse events and incidence of hypoglycemia. CONCLUSION: The available evidence indicates that JQJTT combined with conventional therapy for treating T2DM has a good performance in regulating glycolipid metabolism and improving insulin resistance. However, due to the limitations of this systematic review, the results should be interpreted with caution.

Songling Xuemaikang capsules for patients with low-to-medium risk hypertension: study protocol for a randomized controlled trial.

BACKGROUND: Hypertension is a major risk factor for cardio-cerebrovascular disease. Songling Xuemaikang capsules (SXC), a formulation of Chinese herbal patent medicine, has been used as a complementary medicine with conventional western medicine to treat patients with hypertension since 1994 in mainland China. However, the efficacy of treatment with SXC alone against hypertension remains unclear. METHODS/DESIGN: This is a multicenter, placebo-controlled, double-blinded, randomized controlled clinical trial. A total of 570 patients with low-to-medium risk hypertension are randomized in a 1:1 ratio to receive SXC or placebo three times daily for eight weeks. The primary outcomes are 24-h average systolic blood pressure and average diastolic blood pressure. The secondary outcomes are daytime average blood pressure, night-time average blood pressure, fluctuation of blood pressure, hypertension control rate, traditional Chinese medicine (TCM) syndrome scores, and quality-of-life scores. DISCUSSION: This is the first multicenter trial conducted to evaluate the efficacy and safety of TCM in patients with low-to-medium risk hypertension. Our study will provide evidence-based results of a complementary preventive measure for hypertension. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-IPR-17011383 . Registered on 12 May 2017.