Electroacupuncture ameliorates AOM/DSS-induced mice colorectal cancer by inhibiting inflammation and promoting autophagy via the SIRT1/miR-215/Atg14 axis.

Colorectal cancer (CRC) is one of the most common tumors of the digestive tract, with the third-highest incidence and the second-highest mortality rate among all malignant tumors worldwide. However, treatment options for CRC remain limited. As a complementary therapy, acupuncture or electro-acupuncture (EA) has been widely applied in the treatment of various inflammation-related diseases, such as obesity, ulcerative colitis and tumors. Although numerous pre-clinical and clinical studies have investigated the beneficial effects of acupuncture on CRC, the mechanism underlying the therapeutic action of EA is largely unknown. Evidence from previous studies has revealed that SIRT1 participates in CRC progression by activating autophagy-related miRNAs. Using azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colorectal cancer model in mice, we explored whether EA treatment can inhibit inflammation and promote autophagy via the SIRT1/miR-215/Atg14 axis. Our results showed that EA notably alleviated the CRC in mice, by decreasing the tumor number and DAI scores, inflammation, and increasing body weight of mice. Besides, EA increased the expression of SIRT1 and autophagy. Further experiments showed that SIRT1 overexpression downregulated miR-215, and promoted the expression of Atg14, whereas SIRT1 knockdown induced opposite results. In conclusion, EA can ameliorate AOM/DSS-induced CRC through regulating the SIRT1-mediated miR-215/Atg14 axis by suppressing inflammation and promoting autophagy in mice. These findings reveal a potential molecular mechanism underlying the anti-CRC effect of EA indicating that EA is a promising therapeutic candidate for CRC.

Research progress on acupuncture treatment in central nervous system diseases based on NLRP3 inflammasome in animal models.

Central nervous system (CNS) disorders exhibit complex neurophysiological and pathological mechanisms, which seriously affect the quality of life in patients. Acupuncture, widely accepted as complementary and alternative medicine, has been proven to exert significant therapeutic effects on CNS diseases. As a part of the innate immune system, NLRP3 inflammasome contributes to the pathogenesis of CNS diseases via regulating neuroinflammation. To further explore the mechanisms of acupuncture regulating NLRP3 inflammasome in CNS diseases, our study focused on the effects of acupuncture on neuroinflammation and the NLRP3 inflammasome in vascular dementia, Alzheimer's disease, stroke, depression, and spinal cord injury. This study confirmed that the activation of NLRP3 inflammasome promotes the development of CNS diseases, and inhibiting the activation of NLRP3 inflammasome is a potential key target for the treatment of CNS diseases. In addition, it is concluded that acupuncture alleviates neuroinflammation by inhibiting the activation of the NLRP3 inflammasome pathway, thereby improving the progression of CNS diseases, which provides a theoretical basis for acupuncture to attenuate neuroinflammation and improve CNS diseases.

[Plasma components of Danzhi Xiaoyao Formula and its mechanism of action in treating perimenopausal depression based on UPLC-Q-TOF-MS~E integrated with network pharmacology].

In this study, ultra-performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS~E) was used to analyze the plasma components of Danzhi Xiaoyao Formula after oral administration. Forty-nine plasma components were found in the serum of rats by comparing the compound extract, drug-containing serum, and blank serum. Components, such as 6-hydroxycoumarin, poricoic acid F, deoxoglabrolide, 30-norhederagenin, kanzonol R, 3',6'-di-O-galloylpaeoniflorin, 16α-hydroxytrametenolic acid, 16-deoxyporicoic acid B, 3-O-acetyl-16α-hydroxytrametenolic acid, and 16α,25-dihydroxydehydroeburiconic acid, were first found in rat serum. Behavioral tests, including the tail suspension test, novel object recognition test, and novelty-suppressed feeding test, were conducted for behavioral analysis. It was confirmed that this formula had therapeutic effects on perimenopausal depression. Furthermore, in combination with the network pharmacology method, 53 core targets including MAPK1, HRAS, AKT1, EGFR, and ESR1 were screened, and these targets participated in 165 signaling pathways, including PI3K-AKT, AMPK, VEGFA, MAPK, and HIF-1. In summary, the potential effects of Danzhi Xiaoyao Formula in treating perimenopausal depression are associated with mechanisms in accelerating inflammation repair, improving neuroplasticity, affecting neurotransmitters, regulating estrogen levels, and promoting new blood vessel formation.

Relationship between acupuncture and transient receptor potential vanilloid: Current and future directions.

Acupuncture is a common complementary and alternative therapy around the world, but its mechanism remains still unclear. In the past decade, some studies indicated that transient receptor potential vanilloid (TRPV) channels play a great role in the response of acupuncture stimulation. In this article, we discussed the relationship between acupuncture and TRPV channels. Different from inhibitors and agonists, the regulation of acupuncture on TRPV channels is multi-targeted and biphasic control. Acupuncture stimulation shows significant modulation on TRPV1 and TRPV4 at the autonomic nervous system (ANS) including central and peripheral nervous systems. On the contrary, the abundant expression and functional participation of TRPV1 and TRPV4 were specific to acupuncture stimulation at acupoints. The enhancement or inhibition of TRPV channels at different anatomical levels will affect the therapeutic effect of acupuncture. In conclusion, TRPV channels help to understand the principle of acupuncture stimulation, and acupuncture also provides a potential approach to TRPV-related trials.

Electroacupuncture Pretreatment Exhibits Lung Protective and Anti-Inflammation Effects in Lipopolysaccharide-Induced Acute Lung Injury via SIRT1-Dependent Pathways.

To investigate the effect of electroacupuncture (EA) on acute lung injury (ALI), a lipopolysaccharide (LPS) induced ALI mouse model was used in this study. Before receiving intratracheal LPS instillation, mice were given EA at ST36 for 7 days as a long-term treatment or one time as a short-term treatment. Lung histopathological examination, lung injury scores, lung wet/dry (W/D) ratio, and inflammatory cytokines included proinflammation factors such as TNF-α, IL-1ß, and IL-6 and anti-inflammation factors such as IL-4 and IL-10 in serum and bronchoalveolar lavage fluid (BALF) were detected at the end of experiment. The results show that EA pretreatment ameliorated the lung damage and inflammatory response by LPS. In addition, we found that SIRT1 and its deacetylation of NF-κB were promoted after EA pretreatment in lung tissues. Meanwhile, the expression of angiotensin-converting enzyme 2 (ACE2) is also enhanced by EA pretreatment. Thus, the present findings suggest that EA could be a potential therapy of ALI.

Network Pharmacology and Molecular Docking-Based Investigation: Prunus mume Against Colorectal Cancer via Silencing RelA Expression.

Colorectal cancer (CRC) is one of the most pervasive cancers in the human disease spectrum worldwide, ranked the second most common cause of cancer death by the end of 2020. Prunus mume (PM) is an essential traditional Chinese medicine for the adjuvant treatment of solid tumors, including CRC. In the current study, we utilize means of network pharmacology, molecular docking, and multilayer experimental verification to research mechanism. The five bioactive compounds and a total of eight critical differentially expressed genes are screened out using the bioinformatics approaches of Cytoscape software, String database, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathways, and molecular docking. RelA has been proven to be highly expressed in CRC. Experiments in vitro have shown that kaempferol, the main active component of PM, dramatically inhibited the growth, migration, and invasion of CRC cells, and experiments in vivo have shown that PM effectively delays CRC formation and improves the survival cycle of mice. Further analysis shows that PM inhibits the CRC progression by down-regulating the expression level of RelA, Bax, caspase 3, caspase 9, and EGFR in CRC. PM and its extract are potentially effective therapeutics for the treatment of CRC via the RelA/nuclear factor κB signaling pathway.

[Electroacupuncture postpones growth of tumors by activating SIRT1 expression to reduce inflammatory reaction and facilitate cellular autophagy in mice with transformed colorectal carcinomas].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on tumor number, body conditions, inflammatory factors and expression levels of silent information regulator 1 (sirtuin 1, SIRT1) and autophagy-related proteins Beclin-1, P62, and LC3 in colorectal tissues in inflammatory-transformed colorectal cancer mice, so as to explore its underlying mechanisms in resisting tumor growth. METHODS: A total of 100 C57BL/6 male mice were randomly divided into normal control, model, EA, EA + SIRT1 inhibitor (EA+inhibitor) and agonist resveratrol (agonist) groups, with 20 mice in each group. EA (2 Hz, 1 mA) was applied to "Zusanli"(ST36)and "Fenglong"(ST40) for 20 min every time, 3 times a week for 11 weeks. Mice of the EA +inhibitor group received intraperitoneal injection of SIRT1 inhibitor EX527 (5 mg/kg) at the same time of EA treatment, and those of the agonist group received gavage of resveratrol (200 mg/kg, an agonist of SIRT1), 3 times a week for 11 weeks. The body mass was measured weekly. The disease activity index (DAI), colorectal length and tumor number in each group were recorded. The histopathological changes of colorectal tissues were observed by H.E. staining; the contents of interleukin 6 (IL-6), IL-10, IL-17, in the colorectal tissues were detected by enzyme-linked immunosorbent assay, and the expression levels of SITR1, Beclin-1, P62, and LC3 in colorectal tissues were detected by Western blot and real-time fluorescence quantitative PCR, respectively. RESULTS: Compared with the normal control group, the body weight, length of colorectum, the contents of IL-10, and the expression levels of SIRT1,Beclin-1 and LC3 mRNAs and proteins were significantly decreased (P<0.001), whereas the DAI score, the number of tumors, the contents of IL-6 and IL-17, and the expression levels of P62 mRNA and protein were significantly increased (P<0.000 1, P<0.001) in the model group. In comparison with the model group, the body weight, the length of colorectum, the contents of IL-10, and the expression levels of SIRT1,Beclin-1 and LC3 mRNAs and proteins were significantly increased (P<0.01,P<0.05,P<0.001), while the DAI scores, the numbers of tumors, the contents of IL-6 and IL-17, and the expression levels of P62 mRNA and protein were obviously decreased in the EA and agonist groups (P<0.01,P<0.05, P<0.001). No significant changes were found in all the above-mentioned indexes in the EA+inhibitor group in comparison with the model group (P>0.05). CONCLUSION: EA can reduce the number of tumors and inflammation reaction in colorectal tissue and improve the body condition in mice with colorectal cancer, which may be related to its functions in activating the expression of intestinal SIRT1, and then facilitating cellular autophagy.

Efficacy and safety of Brucea javanica oil emulsion for liver cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: Brucea javanica oil emulsion (BJOE), extracted from the Chinese herb Bruceae Fructus (Yadanzi), is a broad-spectrum anti-tumor drug and has been widely used for the treatment of liver cancer in China. The aim of this study is to systematically investigate the efficacy and safety of BJOE for the treatment of liver cancer. METHODS: Seven electronic databases including the Cochrane Library, PubMed, Excerpt Medica Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Scientific Journal Database, and Wanfang Database will be systematically retrieved for data extraction from their inceptions to September 2020. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal or presenting the findings at a relevant conference. CONCLUSION: The conclusion of this study will provide helpful evidence of the effect and safety of BJOE for the treatment of liver cancer in clinical practice. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/UC8XQ.

Crosstalk between Acupuncture and NF-κB in Inflammatory Diseases.

Acupuncture has been used in China for thousands of years and concerned as a typical alternative medicine in inflammatory diseases nowadays. The nuclear factor-κB (NF-κB) transcription factor is an important regulator of inflammation. In this article, we discuss the role of acupuncture in NF-κB pathways and also present the acupoints selection, acupuncture administration, and related inflammation diseases and models from previous studies to bring readers close to a more complete understanding of the mechanisms between acupuncture and NF-κB in inflammatory diseases.

[Functional prediction of Tanreqing Injection in brain diseases].

The study explores the application of Tanreqing Injection into brain components in brain diseases. The components of Tanreqing Injection and its existing components in rat cerebrospinal fluid were qualitatively analyzed by liquid chromatography-mass spectrometry(LC-MS). The possible mechanism of action of Tanreqing Injection into brain on brain diseases was predicted by network pharmacological theory. In this study, 17 brain-entry components of Tanreqing Injection were founded, and 222 core targets were obtained from network pharmacological results. The biological processes include 31 items such as negative regulation of apoptotic process, MAPK cascade, Ras protein signal transduction, and 22 items such as PI3 K-Akt signal transduction, MAPK signal transduction and neurotrophic factor signal transduction. Nine brain diseases including stroke, migraine and meningioma were screened out by predicting the effect of Tanreqing Injection on brain components, which provide ideas and directions for further study of a certain encephalopathy and lay a theoretical foundation for further revealing its molecular mechanism.

Synthesis and Biological Evaluation of (+)-Usnic Acid Derivatives as Potential Anti-Toxoplasma gondii Agents.

Six series of (+)-usnic acid derivatives were synthesized. The IC50 values of these compounds were determined in T. gondii infected HeLa cells (µM) and in HeLa cells (µM), and their selectivity indexes (SI) were calculated. In vitro, most of the derivatives tested in this study exhibited more anti activity than that of the parent compound (+)-usnic acid and the positive control drugs. Among these derivatives, methyl (E)-(1-(6-acetyl-7,9-dihydroxy-8,9b-dimethyl-1,3-dioxo-3,9b-dihydrodibenzo[b,d]furan-2(1H)-ylidene)ethyl)phenylalaninate (D3) showed the most effective anti-T. gondii activity (selectivity >2.77). In comparison with the clinically used positive control drugs sulfadiazine (selectivity 1.15), pyrimethamine (selectivity 0.89), spiramycin (selectivity 0.72), and the lead compound (+)-usnic acid (selectivity 0.96), D3 showed better results in vitro. Furthermore, D3 and (E)-6-acetyl-7,9-dihydroxy-8,9b-dimethyl-2-(1-(quinolin-6-ylamino)ethylidene)dibenzo[b,d]furan-1,3(2H,9bH)-dione (F3) had greater inhibitory effects on T. gondii (inhibition rates 76.0% and 64.6%) in vivo in comparison to spiramycin (inhibition rate 55.2%); in the peritoneal cavity of mice, the number of tachyzoites was significantly reduced (p < 0.001) in vivo. Additionally, some biochemical parameters were measured and spleen indexes were comprehensively evaluated, and the results indicated that mice treated with both compound D3 and compound F3 showed reduced hepatotoxicity and significantly enhanced antioxidative effects in comparison to the normal group. Granuloma and cyst formation were effected by the inhibition of compound D3 and compound F3 in liver sections. Overall, these results indicated that D3 and F3 for use as anti-T. gondii agents are promising lead compounds.

A combination of omega-3 and plant sterols regulate glucose and lipid metabolism in individuals with impaired glucose regulation: a randomized and controlled clinical trial.

BACKGROUND: Lipid metabolism imbalance has been recognized as one of the major drivers of impaired glucose metabolism in the context of type 2 diabetes mellitus (T2DM), the rates of which are steadily increasing worldwide. Impaired glucose regulation (IGR) plays a vital role in the prevention and treatment of T2DM. The goal of this study was to further clarify whether the combination of plant sterols (PS) and omega-3 fatty acids yields any synergistic effect that enhances the prevention and treatment of IGR. METHODS: A total of 200 participants were randomized to receive PS and omega-3 fatty acids (n = 50), PS alone (n = 50), omega-3 fatty acids alone (n = 50), or placebo soy bean powder plus placebo capsules (n = 50) for 12 weeks. Patient characteristics including body composition, blood pressure, glucose metabolism (Fasting plasma glucose (FPG), fasting insulin (FINS), glycosylated hemoglobin (HbA1c), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)), lipid metabolism (TG, TC, HDL-C, LDL-C) and inflammatory factors (Hs-CRP, IL-6) were all monitored in these IGR individuals. RESULTS: Compared to the placebo group, the group receiving the combined intervention exhibited significantly decreased TG, HDL-C, FBG, HOMA-IR and HbA1c. Omega-3 fatty acids alone were associated with significant reductions in waistline, TG, FBG, HOMA-IR and Hs-CRP. PS alone was only associated with decreased TG and Hs-CRP. No interventions produced significant changes in body weight, BMI, blood pressure, FINS, body fat percentage, visceral fat rating, TC, LDL-C or IL-6. CONCLUSIONS: In summary, this study has demonstrated for the first time that PS, omega-3 fatty acids or the combination thereof significantly improved inflammation, insulin resistance, as well as glucose and lipid metabolism in IGR individuals. These findings may provide a scientific basis for the development of nutritional products incorporating PS and omega-3 fatty acids, and also for the development of nutritional supplement strategies aimed at preventing the development of disease in the IGR population.

Baicalin attenuates non-alcoholic steatohepatitis by suppressing key regulators of lipid metabolism, inflammation and fibrosis in mice.

AIMS: Baicalin (BA), an active flavonoid compound originating from the herb of Scutellaria baicalensis Georgi, has been previously shown to exert anti-inflammation and anti-oxidant effects in liver diseases. However, the potential role of BA in the regulation of non-alcoholic steatohepatitis (NASH) remains elusive. In this study, we newly explored the hepatoprotective effects of BA in MCD diet-induced NASH by ameliorating hepatic steatosis, inflammation, fibrosis and apoptosis. MAIN METHODS: NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4weeks. The mice were simultaneously treated with or without BA for 4weeks. Serum liver functional markers and inflammatory indicators were assessed by biochemical and ELISA methods, respectively. The livers were histologically examined using H&E, Oil Red O and Masson's trichrome staining methods. The qRT-PCR, IHC and Western blotting assays were applied to analyze mechanisms underlying BA protection. KEY FINDINGS: BA treatment significantly attenuated MCD diet-induced hepatic lipid accumulation partly through regulating the expression of SREBP-1c, FASN, PPARα and CPT1a. BA treatment dramatically suppressed MCD diet-induced hepatic inflammation, which was associated with decrease in serum TNF-α, IL-1ß and MCP-1 production, macrophage influx and suppression of nuclear factor-κB activation. Additionally, BA was proved to prevent liver fibrosis, which appears to be mediated by inhibition of α-SMA, TGF-ß1 and Col1A1. Furthermore, BA markedly inhibited hepatocyte apoptosis and cleaved caspase-3 protein expression in MCD diet-induced mice. SIGNIFICANCE: These results provide a possible basis of the underlying mechanism for the application of BA in the treatment of NASH.

[Clinical value of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy in the treatment of advanced non-small cell lung cancer: a Meta-analysis].

OBJECTIVE: To investigate the clinical efficacy and safety of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy in the treatment of advanced non-small cell lung cancer (NCSLC) compared with chemotherapy alone. METHODS: Databases including Chinese National Knowledge Infrastructure, China Biology Medicine Disc, Wanfang, and MEDLINE were searched until April 1, 2014. Two assessors independently reviewed each trial. The primary outcome was the effective rate (ER) of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy. The secondary outcomes included quality of life improvement rate (QOLIR) and adverse reactions. Statistical calculations were performed by using Cochrane Collaboration Review Manager 5.2. RESULTS: A total of 888 patients from 15 studies, 13 randomized controlled trials (RCT) and two controlled clinical trials, were included. Compared with chemotherapy alone, Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract plus chemotherapy significantly improved ER [Risk ratio (RR) = 1.32, 95% CI, (1.14, 1.54)] (based on 15 studies) and QOLIR [RR = 2.04, 95% CI, (1.69, 2.47)] (based on 13 studies). Compared with chemotherapy alone, Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract plus chemotherapy significantly inhibited chemotherapy-induced white blood cell decline [RR = 0.79, 95% CI, (0.70, 0.90) (based on 10 studies), chemotherapy-induced platelet decline [RR = 0.77, 95% CI, (0.60, 0.98)] (based on 8 studies), and significantly alleviated nausea and vomiting (NV) [RR = 0.83, 95% CI, (0.71, 0.97)] (based on 7 studies). There was no significant difference in hemoglobin decline between the two therapies [RR = 0.88, 95% CI, (0.70, 1.09)] (based on 6 studies). CONCLUSION: This Meta-analysis suggests that Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract combined with chemotherapy may be more efficacious in the treatment of advanced NSCLC than chemotherapy alone. This effect includes enhancing ER and QOLIR, and weakening chemotherapy toxicity. However, large-scale RCTs are required to further investigate the short- and long-term effects of Tongguanteng (Radix seu Herba Marsdeniae Tenacissimae) extract.

Ancient records and modern research on the mechanisms of chinese herbal medicines in the treatment of diabetes mellitus.

Over the past decades, Chinese herbal medicines (CHM) have been extensively and intensively studied through from both clinical and experimental perspectives and CHM have been proved to be effective in the treatment of diabetes mellitus (DM). This study, by searching ancient records and modern research papers, reviewed CHM in terms of their clinical application and principal mechanism in the treatment of DM. We summarized the use of CHM mentioned in 54 famous ancient materia medica monographs and searched papers on the hypoglycemic effect of several representative CHM. Main mechanisms and limitations of CHM and further research direction for DM were discussed. On the basis of the study, we were led to conclude that TCM, as a main form of complementary and alternative medicine (CAM), was well recorded in ancient literatures and has less adverse effects as shown by modern studies. The mechanisms of CHM treatment of DM are complex, multilink, and multitarget, so we should find main hypoglycemic mechanism through doing research on CHM monomer active constituents. Many CHM monomer constituents possess noteworthy hypoglycemic effects. Therefore, developing a novel natural product for DM and its complications is of much significance. It is strongly significant to pay close attention to CHM for treatment of DM and its complications.

[Investigation of determining strontium in M. nitida Benth. var. hirsutissima. Z. Wei. by flame atomic absorption spectra].

The present paper is aimed to establish the method of determining the strontium in M. nitida Benth. var. hirsutissima. Z. Wei. by means of air-acetylene flame atomic absorption spectra, and also provide reference for the determination of the strontium in other traditional Chinese medicine. M. Nitida Benthvarhirsutissima Z. Wei. was taken as the object. The authors used nitric-perchloric acid as digestion solution to digest samples by microwave which was controlled by pressure, and used EDTA-2Na as the releasing agent to add in the samples for determining the strontium in M. nitida Benth. var. hirsutissima. Z. Wei. by FAAS. The results showed that the samples were entirely digested by microwave. The working curve was Y = 0.036 5x -0.001 1, r = 0.999 4, the range was 0-1.6 microg x mL(-1), the average recovery rate was 101.5% with RSD 2.04%, and the method detection limit was 0.008 2 microg x mL(-1) (n = 21). It is concluded that this method is simple and accurate. It has high sensitivity and can be effectively used for determining the strontium in this traditional Chinese medicine.