Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

Identifying complementary and alternative medicine recommendations for anxiety treatment and care: a systematic review and critical assessment of comprehensive clinical practice guidelines.

Background: Clinical practice guidelines (CPGs) are used to guide decision-making, especially regarding complementary and alternative medicine (CAM) therapies that are unfamiliar to orthodox healthcare providers. This systematic review aimed to critically review and summarise CAM recommendations associated with anxiety management included in the existing CPGs. Methods: Seven databases, websites of six international guidelines developing institutions, and the National Centre for Complementary and Integrative Health website were systematically searched. Their reporting and methodological quality were evaluated using the Reporting Items for practice Guidelines in Healthcare checklist and the Appraisal of Guidelines for Research and Evaluation (2nd version) instrument, respectively. Results: Ten CPGs were included, with reporting rates between 51.4 and 88.6%. Seven of these were of moderate to high methodological quality. Seventeen CAM modalities were implicated, involving phytotherapeutics, mind-body practice, art therapy, and homeopathy. Applied relaxation was included in 70% CPGs, which varied in degree of support for its use in the treatment of generalised anxiety disorder. There were few recommendations for other therapies/products. Light therapy was not recommended for use in generalised anxiety disorder, and St John's wort and mindfulness were not recommended for use in social anxiety disorder in individual guidelines. Recommendations for the applicability of other therapies/products for treating a specific anxiety disorder were commonly graded as "unclear, unambiguous, or uncertain". No CAM recommendations were provided for separation anxiety disorder, specific phobia or selective mutism. Conclusion: Available guidelines are limited in providing logically explained graded CAM recommendations for anxiety treatment and care. A lack of high-quality evidence and multidisciplinary consultation during the guideline development are two major reasons. High quality and reliable clinical evidence and the engagement of a range of interdisciplinary stakeholders are needed for future CPG development and updating. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022373694, identifier CRD42022373694.

Managing depression with complementary and alternative medicine therapies: a scientometric analysis and visualization of research activities.

Background: Complementary and Alternative Medicine (CAM) interventions may prove to be an attractive option for the treatment of depression. The aim of this scientometric analysis is to determine the global scientific output of research regarding managing depression with CAM and identify the hotspots and frontiers within this theme. Methods: Publications regarding the utilization of CAM for treating depression were collected from the Web of Science Core Collection from 1993 to 2022, and analyzed and visualized by Bibliometrix R-package, VOSviewer, and CiteSpace. Results: A total of 1,710 publications were acquired. The number of annual publications showed an overall rapid upward trend, with the figure peaking at 179 in 2021. The USA was the leading research center. Totally 2,323 distinct institutions involving 7,638 scholars contributed to the research theme. However, most of the cooperation was limited to within the same country, institution or research team. The Journal of Alternative and Complementary Medicine was the most productive periodical. The CAM therapies of most interest to researchers were acupuncture and body-mind techniques, such as yoga, meditation and mindfulness. Systematic review and meta-analysis are commonly used methods. "Inflammation," "rating scale" and "psychological stress" were identified as the most studied trend topics recently. Conclusion: Managing depression with evidence-based CAM treatment is gaining attention globally. Body-mind techniques and acupuncture are growing research hotspots or emerging trending topics. Future studies are predicted to potentially investigate the possible mechanisms of action underlying CAM treatments in reducing depression in terms of modulation of psychological stress and inflammation levels. Cross-countries/institutes/team research collaborations should be encouraged and further enhanced.

Inhibitory effect of Portulaca oleracea L. aqueous extract and juice on NLRP3 inflammasome activation in an ulcerative colitis mouse model.

Portulaca oleracea L. (PO) is an edible and medicinal plant used for treating gastrointestinal diseases. However, the effects of PO on ulcerative colitis (UC) and underlying mechanisms remain unclear. This study investigated the effects of PO aqueous extract (POE) and PO juice (PJ) on dextran sulfate sodium (DSS)-induced UC in a mouse model and attempted to unravel their underlying mechanisms. The results revealed that PJ contains more bioactive compounds and has more overlapping targets with UC than POE. Both POE and PJ effectively reduced Disease Activity Index scores and inflammatory cell infiltration in the UC mouse model, but PJ had a better effect than POE. Furthermore, PJ inhibited pyroptosis by decreasing the expression of the NLRP3 inflammasome, while also repairing the dysfunction of the intestinal barrier by upregulating the expression of tight junction proteins. Therefore, based on the study findings, we concluded that PJ can improve DSS-induced UC and may suppress pyroptosis by interfering with the activation of the NLRP3 inflammasome.

Acupuncture for comorbid depression and insomnia in perimenopause: A feasibility patient-assessor-blinded, randomized, and sham-controlled clinical trial.

Background and objective: Whilst acupuncture is widely used for treating psychosomatic diseases, there is little high-quality evidence supporting its application in comorbid perimenopausal depression (PMD) and insomnia (PMI) which are common complaints during climacteric. This feasibility, patient-assessor-blinded, randomized, sham-controlled clinical trial addresses this gap by investigating the efficacy and safety of acupuncture on depressed mood and poor sleep in women with comorbid PMD and PMI. Methods: Seventy eligible participants were randomly assigned to either real-acupuncture (RA) or sham-acupuncture (SA) groups. Either RA or SA treatment were delivered in 17 sessions over 8 weeks. The primary outcomes for mood and sleep were changes on 17-items Hamilton Depression Rating Scale (HAM-D17) and Pittsburgh Sleep Quality Index (PSQI) scores, from baseline to 16-week follow-up. Secondary outcome measures involved anxiety symptoms, perimenopausal symptoms, quality of life, participants' experience of and satisfaction with the acupuncture treatment. Blood samples were taken to measure reproductive hormone levels. Intention-To-Treat and Per-Protocol analyses were conducted with linear mixed-effects models. The James' and Bang's blinding indices were used to assess the adequacy of blinding. Results: Sixty-five participants completed all treatment sessions, and 54 and 41 participants completed the eight- and 16-week follow-ups, respectively. At post-treatment and 8-week follow-up, the RA group showed a significantly greater reduction in PSQI scores than the SA group did; although the reduction of HAM-D17 scores in RA group was significant, the change was not statistically different from that of SA. There were no significant mean differences between baseline and 16-week follow-up in either HAM-D17 or PSQI in either group. There were no significant between-group differences in serum reproductive hormone levels. All treatments were tolerable and no serious adverse events were reported, and the blinding was successful. Conclusion: Acupuncture is safe and can contribute to clinically relevant improvements in comorbid PMD and PMI, with satisfactory short-and medium-term effects. Whether the anti-depressive benefit of acupuncture is specific or non-specific remains to be determined. No evidence was found for any longer-term benefit of acupuncture compared to sham at 16 weeks. Further research is required to elucidate mechanisms underlying the short to medium term effects of acupuncture.

Spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Systematically assessing the safety and effectiveness of spraying rhubarb powder solution under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding, and confirmation for further clinical research and application. METHODS: We searched the following databases up till November 2019: PubMed, the Cochrane Library, EMBASE, CNKI, WanFang Data, VIP and SinoMed. Randomized controlled trials (RCTs) were used to compare the curative effect of spraying rhubarb powder solution with other drugs under gastroscope for the treatment of acute non-varicose upper gastrointestinal bleeding. RESULTS: Out of 171 articles, 14 RCTs involving 1493 patients were included. All control groups included in the RCTs were treated with norepinephrine solution. The hemostatic effect of spraying rhubarb powder solution under gastroscope was examined for 24 h at high concentration (0.1 g/mL). The hemostatic effect at higher conc. (0.1 g/mL) found far more better than low conc.(RR = 1.48;95 %CI:1.25,1.75;P﹤0.00001) (0.03 g/mL)as homeostatic effect at low conc.is same that of norepinephrine solution (RR = 1.02;95 %CI:0.94,1.10;P = 0.62). Moreover within 48 h, rhubarb powder solution with 0.1 g/mL or 0.15 g/mL conc. have of significantly higher hemostatic effects than norepinephrine solution (RR = 1.18;95 % CI: 1.08, 1.30;P = 0.0003). Occurrence of rebleeding event within 48 h after successful hemostasis (RR = 0.42;95 %CI:0.24,0.74;P = 0.003) reduced exceptionally. After that the hemostatic effect of rhubarb powder solution with 0.1 g/mL conc.examined within 72 h again exhibited significant improvement than norepinephrine solution (RR = 1.19;95 %CI:1.12,1.26;P < 0.00001). On par with immediate hemostasis time, rhubarb powder solution took unprecedented less time than norepinephrine solution;(MD=-5.56S;95 %CI:-6.16, -4.95;P﹤0.00001). Additionally, the adverse reaction produced by rhubarb powder solution is much lower than norepinephrine solution (RR = 0.22;95 %CI:0.11,0.42;P < 0.00001). CONCLUSIONS: According to meta-analysis, Spraying rhubarb powder solution under gastroscope in the treatment of acute non-varicose upper gastrointestinal bleeding is superior to norepinephrine solution in improving hemostasis effect. Shortening immediate hemostasis time and reducing rebleeding,and is safe to use. Based on the results of this study, physicians can treat patients with acute non-varicose upper gastrointestinal bleeding by spraying rhubarb powder solution under gastroscope according to the patients' condition.However, the sample size included in this study is small and of substandard quality qu, and a large sample size clinical trial with strict design and normative report is needed to verify the safety and efficacy of rhubarb powder solution under gastroscope for acute non-varicose upper gastrointestinal bleeding.

Antimycin A shows selective antiproliferation to oral cancer cells by oxidative stress-mediated apoptosis and DNA damage.

The antibiotic antimycin A (AMA) is commonly used as an inhibitor for the electron transport chain but its application in anticancer studies is rare. Recently, the repurposing use of AMA in antiproliferation of several cancer cell types has been reported. However, it is rarely investigated in oral cancer cells. The purpose of this study is to investigate the selective antiproliferation ability of AMA treatment on oral cancer cells. Cell viability, flow cytometry, and western blotting were applied to explore its possible anticancer mechanism in terms of both concentration- and exposure time-effects. AMA shows the higher antiproliferation to two oral cancer CAL 27 and Ca9-22 cell lines than normal oral HGF-1 cell lines. Moreover, AMA induces the production of higher reactive oxygen species (ROS) levels and pan-caspase activation in oral cancer CAL 27 and Ca9-22 cells than in normal oral HGF-1 cells, providing the possible mechanism for its selective antiproliferation effect of AMA. In addition to ROS, AMA induces mitochondrial superoxide (MitoSOX) generation and depletes mitochondrial membrane potential (MitoMP). This further supports the AMA-induced oxidative stress changes in oral cancer CAL 27 and Ca9-22 cells. AMA also shows high expressions of annexin V in CAL 27 and Ca9-22 cells and cleaved forms of poly (ADP-ribose) polymerase (PARP), caspase 9, and caspase 3 in CAL 27 cells, supporting the apoptosis-inducing ability of AMA. Furthermore, AMA induces DNA damage (γH2AX and 8-oxo-2'-deoxyguanosine [8-oxodG]) in CAL 27 and Ca9-22 cells. Notably, the AMA-induced selective antiproliferation, oxidative stress, and DNA damage were partly prevented from N-acetylcysteine (NAC) pretreatments. Taken together, AMA selectively kills oral cancer cells in an oxidative stress-dependent mechanism involving apoptosis and DNA damage.

Ethyl Acetate Extract of Nepenthes ventricosa x maxima Exerts Preferential Killing to Oral Cancer Cells.

Nepenthes plants are a folk medicine in many Southeast Asia countries for curing diseases but its anticancer effect is rarely investigated. The objectives of this study were to investigate the antioral cancer ability of ethyl acetate extract of Nepenthes ventricosa x maxima (EANV). The preferential killing ability of EANV was determined by MTS-based cell viability assays. The bioactive effects were further screened by flow cytometry for apoptosis, oxidative stress, and DNA damage. At 24 h treatment, EANV dose dependently decreased six types of oral cancer cells, but the normal oral cells (HGF-1) kept a 90% viability. EANV also showed chronic antiproliferative effects and inhibited 3D sphere formation ability of oral cancer cells. Ca9-22 and CAL 27 oral cancer cells with high response to EANV increased subG1 populations and enhanced Annexin V- and pancaspase-detected apoptosis in these cells. EANV also induced the generation of reactive oxygen species (ROS) and mitochondrial superoxide and the dysfunction of mitochondrial membrane potential. Moreover, the oxidative DNA damage level such as 8-oxo-2'deoxyguanosine was increased in EANV-treated oral cancer cells. Taken together, EANV has a preferential killing effect against oral cancer cells associated with oxidative stress, apoptosis, and DNA damage, suggesting EANV as a potential antioral cancer agent.

A systematic review and meta-analysis of randomized controlled trials: Skin-patch of Chinese herbal medicine for patients with acute gouty arthritis.

AIMS: To evaluate the evidence of the effectiveness and safety of Chinese herbal medicine skin-patches for patients with acute gouty arthritis. BACKGROUND: Acute gouty arthritis is a problem that can limit the level of activity and impair the quality of life. In China, many clinical studies have demonstrated that skin-patches of Chinese herbal medicines benefit patients with acute gouty arthritis. However, the reported clinical effects vary. DESIGN: A systematic review and meta-analysis of randomized controlled trials. DATA SOURCES: Three English databases including CENTRAL (1993 to February 2017), PubMed (1966 to February 2017) and EMBASE (1974 to February 2017) and four Chinese databases including Chinese National Knowledge Infrastructure, Chinese VIP Information, SinoMed and Wanfang (all, 1949 - February 2017) were searched. Randomized controlled trials that compared skin-patches of Chinese herbal medicine with or without conventional treatments to conventional treatments, no treatment or a placebo treatment for patients with acute gouty arthritis were included. REVIEW METHODS: We conducted a systematic review and meta-analysis following the Cochrane process. Two authors selected the studies, extracted the data and evaluated the risk of bias of the included trials. RESULTS: Nineteen studies met our inclusion criteria. After synthesizing the data, the results showed that skin-patches of CHM combined with Western medicine seemed to be more effective than Western medicine alone for pain relief in patients with acute gouty arthritis and had fewer adverse events. CONCLUSION: Due to the quality of the data, larger and more rigorously designed clinical trials with proper outcome measures are necessary.

4ß-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

Reactive oxygen species (ROS) induction had been previously reported in 4ß-hydroxywithanolide (4ßHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4ßHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4ßHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4ßHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4ßHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4ßHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4ßHWE-treated oral cancer cells than in oral normal cells. All the 4ßHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4ßHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells.

Butanol-Partitioned Extraction from Aqueous Extract of Gracilaria tenuistipitata Inhibits Cell Proliferation of Oral Cancer Cells Involving Apoptosis and Oxidative Stress.

We have previously found that the aqueous extract of Gracilaria tenuistipitata (AEGT) and its partitioned fractions had antioxidant properties in biochemical assays. Although the butanol-partitioned fraction of AEGT (AEGT-pBuOH) had a stronger antioxidant performance than AEGT, its biological effects are still unknown. In this study, the cellular responses of oral cancer cells to AEGT-pBuOH were monitored in terms of cell viability, cell cycle progression, apoptosis, and oxidative stress responses. In an ATP content assay, the cell viability of oral cancer cells treated with AEGT-pBuOH was dose responsively inhibited (p < 0.005). For flow cytometry, AEGT-pBuOH was also found to dose responsively induce cell cycle disturbance by propidium iodide (PI) staining and to induce apoptosis by annexin V/PI and pan-caspase staining (p < 0.005). In AEGT-pBuOH-treated oral cancer cells, the reactive oxygen species (ROS) was increased and mitochondrial membrane potential was decreased in a dose-response manner (p < 0.005). These results suggest that AEGT-pBuOH inhibited the proliferation and induced apoptosis of oral cancer cells involving the ROS generation and mitochondrial depolarization.

Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage.

BACKGROUND: Cryptocarya-derived crude extracts and their compounds have been reported to have an antiproliferation effect on several types of cancers but their impact on oral cancer is less well understood. METHODS: We examined the cell proliferation effect and mechanism of C. concinna-derived cryptocaryone (CPC) on oral cancer cells in terms of cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial depolarization, and DNA damage. RESULTS: We found that CPC dose-responsively reduced cell viability of two types of oral cancer cells (Ca9-22 and CAL 27) in MTS assay. The CPC-induced dose-responsive apoptosis effects on Ca9-22 cells were confirmed by flow cytometry-based sub-G1 accumulation, annexin V staining, and pancaspase analyses. For oral cancer Ca9-22 cells, CPC also induced oxidative stress responses in terms of ROS generation and mitochondrial depolarization. Moreover, γH2AX flow cytometry showed DNA damage in CPC-treated Ca9-22 cells. CPC-induced cell responses in terms of cell viability, apoptosis, oxidative stress, and DNA damage were rescued by N-acetylcysteine pretreatment, suggesting that oxidative stress plays an important role in CPC-induced death of oral cancer cells. CONCLUSIONS: CPC is a potential ROS-mediated natural product for anti-oral cancer therapy.