Lycium barbarum glycopeptide alleviates neuroinflammation in spinal cord injury via modulating docosahexaenoic acid to inhibiting MAPKs/NF-kB and pyroptosis pathways.

BACKGROUND: Lycium barbarum polysaccharide (LBP) is an active ingredient extracted from Lycium barbarum that inhibits neuroinflammation, and Lycium barbarum glycopeptide (LbGp) is a glycoprotein with immunological activity that was purified and isolated from LBP. Previous studies have shown that LbGp can regulate the immune microenvironment, but its specific mechanism of action remains unclear. AIMS: In this study, we aimed to explore the mechanism of action of LbGp in the treatment of spinal cord injury through metabolomics and molecular experiments. METHODS: SD male rats were randomly assigned to three experimental groups, and after establishing the spinal cord hemisection model, LbGp was administered orally. Spinal cord tissue was sampled on the seventh day after surgery for molecular and metabolomic experiments. In vitro, LbGp was administered to mimic the inflammatory microenvironment by activating microglia, and its mechanism of action in suppressing neuroinflammation was further elaborated using metabolomics and molecular biology techniques such as western blotting and q-PCR. RESULTS: In vivo and in vitro experiments found that LbGp can improve the inflammatory microenvironment by inhibiting the NF-kB and pyroptosis pathways. Furthermore, LbGp induced the secretion of docosahexaenoic acid (DHA) by microglia, and DHA inhibited neuroinflammation through the MAPK/NF-κB and pyroptosis pathways. CONCLUSIONS: In summary, we hypothesize that LbGp improves the inflammatory microenvironment by regulating the secretion of DHA by microglia and thereby inhibiting the MAPK/NF-κB and pyroptosis pathways and promoting nerve repair and motor function recovery. This study provides a new direction for the treatment of spinal cord injury and elucidates the potential mechanism of action of LbGp.

Network pharmacology-based research on the effect of Scutellaria baicalensis on osteosarcoma and the underlying mechanism.

To explore the anti-tumor effects of Scutellaria baicalensis on osteosarcoma and its mechanism. Network pharmacology and molecular docking techniques were applied to investigate the effect and mechanism of Scutellaria baicalensis on osteosarcoma (OS). We analyzed the protein-protein interaction (PPI) network for potential targets of Scutellaria baicalensis for treating osteosarcoma and identified hub targets. We used KM curves to screen for hub targets that could effectively prolong the survival time of OS patients. We systematically performed gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of the Scutellaria baicalensis potential targets and predicted the Scutellaria baicalensis molecular mechanism and function in treating osteosarcoma. Through molecular docking, the binding process between the hub targets, which could prolong the survival time of sarcoma patients, and Scutellaria baicalensis was simulated. PPI network analysis of potential therapeutic targets discriminated 12 hub targets. The KM curves of the hub targets showed that upregulation of RXRA, RELA, ESR1, TNF, IL6, IL1B, and RB1 expression, and downregulation of MAPK1, VEGFA, MAPK14, CDK1, and PPARG expression were effective in improving the 5-year survival rate of OS patients. GO and KEGG enrichment demonstrated that Scutellaria baicalensis regulated multiple signaling pathways of OS. Molecular docking results indicated that Scutellaria baicalensis could bind freely to the above hub target, which could prolong the survival time of sarcoma patients. Scutellaria baicalensis acted on osteosarcoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways. Scutellaria baicalensis appears to have the potential to serve as a therapeutic drug for osteosarcoma and to prolong the survival of OS patients.

Tongqiao Huoxue Decoction ameliorates traumatic brain injury-induced gastrointestinal dysfunction by regulating CD36/15-LO/NR4A1 signaling, which fails when CD36 and CX3CR1 are deficient.

AIMS: Gastrointestinal (GI) dysfunction, as a common peripheral-organ complication after traumatic brain injury (TBI), is primarily characterized by gut inflammation and damage to the intestinal mucosal barrier (IMB). Previous studies have confirmed that TongQiao HuoXue Decoction (TQHXD) has strong anti-inflammatory properties and protects against gut injury. However, few have reported on the therapeutic effects of TQHXD in a TBI-induced GI dysfunction model. We aimed to explore the effects of TQHXD on TBI-induced GI dysfunction and the underlying mechanism thereof. METHODS: We assessed the protective effects and possible mechanism of TQHXD in treating TBI-induced GI dysfunction via gene engineering, histological staining, immunofluorescence (IF), 16S ribosomal ribonucleic acid (rRNA) sequencing, real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), Western blot (WB), and flow cytometry (FCM). RESULTS: TQHXD administration ameliorated TBI-induced GI dysfunction by modulating the abundance and structure of bacteria; reconstructing the destroyed epithelial and chemical barriers of the IMB; and improving M1/M2 macrophage, T-regulatory cell (Treg)/T helper 1 cell (Th1 ), as well as Th17 /Treg ratios to preserve homeostasis of the intestinal immune barrier. Notably, Cluster of Differentiation 36 (CD36)/15-lipoxygenase (15-LO)/nuclear receptor subfamily 4 group A member 1 (NR4A1) signaling was markedly stimulated in colonic tissue of TQHXD-treated mice. However, insufficiency of both CD36 and (C-X3-C motif) chemokine receptor 1 (CX3CR1) worsened GI dysfunction induced by TBI, which could not be rescued by TQHXD. CONCLUSION: TQHXD exerted therapeutic effects on TBI-induced GI dysfunction by regulating the intestinal biological, chemical, epithelial, and immune barriers of the IMB, and this effect resulted from the stimulation of CD36/NR4A1/15-LO signaling; however, it could not do so when CX3CR1 and CD36 were deficient. TQHXD might therefore be a potential drug candidate for treating TBI-induced GI dysfunction.

The Role of AMPK Signaling in Ulcerative Colitis.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease characterized by inflammation and ulcer formation of the intestinal mucosa. Due to its high recurrence rate, prolonged course, limited curative options, and significant impact on patients' quality of life, along with a notable potential for malignant transformation, UC is designated as a refractory global health challenge by the World Health Organization (WHO). The elucidation of the pathogenesis and therapeutic strategies for UC requires further in-depth investigation. AMP-activated protein kinase (AMPK) serves as a central regulator of cellular energy metabolic homeostasis. Emerging evidence indicates that interventions involving traditional Chinese medicine (TCM) components, as well as other pharmacological measures, exert beneficial effects on the intestinal mucosal inflammation and epithelial barrier dysfunction in UC by modulating AMPK signaling, thereby influencing biological processes such as cellular autophagy, apoptosis, inflammatory responses, macrophage polarization, and NLRP3 inflammasome-mediated pyroptosis. The role of AMPK in UC is of significant importance. This manuscript provides a comprehensive overview of the mechanisms through which AMPK is involved in UC, as well as a compilation of pharmacological agents capable of activating the AMPK signaling pathway within the context of UC. The primary objective is to facilitate a deeper comprehension of the pivotal role of AMPK in UC among researchers and clinical practitioners, thereby advancing the identification of novel therapeutic targets for interventions in UC.

Mechanism of HSP90 Inhibitor in the Treatment of DSS-induced Colitis in Mice by Inhibiting MAPK Pathway and Synergistic Effect of Compound Sophora Decoction.

BACKGROUND: The mechanism of Heat Shock Protein 90 (HSP90) in Ulcerative Colitis (UC) has been studied, and mitogenic-activated protein kinases (MAPK) also contribute to the pathogenesis of UC. However, the effect of the HSP90/MAPK pathway in UC is still unclear. Therefore, the mainstay of this research is to explore the mechanism of action of this pathway in UC. Compound sophorae decoction (CSD), as a Chinese herbal decoction, can synergistically affect the above process. OBJECTIVE: This study aimed to uncover the synergistic effects of HSP90 inhibitors regulating the MAPK pathway for treating DSS-induced colitis in mice and the synergistic effects of CSD. METHODS: This experiment used oral administration of standard diets containing 3% dextran sodium sulfate (DSS) to establish an experimental colitis model in mice. The model was treated with HSP90 inhibitor, CSD, or dexamethasone. Mouse feces, mobility, body weight, colon length, and colon histopathology scores were recorded daily to assess the degree of colitis inflammation. Expression levels of HSP90 and MAPK pathway-related genes and proteins were evaluated by Western blot and qPCR. The evaluation of intestinal mucosal permeability was measured by enzyme-linked immunosorbent assay (ELISA), which could detect the protein level of D-Amino Acid Oxidase (DAO) and D-lactic acid (D-LA). The same went for downstream molecules AFT-2, p53, and apoptosis-related proteins BAX, BCL-2, Caspase3, and survivin in the MAPK pathway. Immunohistochemical measured p-38, p-JNK, and p-ERK expressions. JAM-A and claudin-1 connexin were tested by immunofluorescence staining. The TUNEL method was for measuring the apoptosis rate of colonic epithelial cells. CBA kit determined the level of inflammatory factors of colons. RESULTS: HSP90 inhibitor can improve the degree of pathological damage in the colon of mice treated with DSS, increase the mice's weight and the length of the colon, and significantly reduce the disease activity index (DAI) score. Intraperitoneal injection of HSP90 inhibitor can reduce the expression of MAPK pathway markers P38, JNK, ERK, and their phosphorylation and decrease the content of AFT-2 and p53, which is downstream of the MAPK pathway. In addition, treatment of the HSP90 inhibitor up-regulated the expression of anti-apoptotic proteins BCL-2 and survivin, as well as down-regulated apoptotic protein caspase3, BAX in the colon of mice with colitis. Lower levels of inflammatory factors such as IL-6, MCP-1, IFN-γ, TNF, IL-12p70, and increased IL-10 were observed after HSP90 inhibitor therapy. Furthermore, the combination treatment of CSD can enhance the effect of the single HSP90 inhibitor treatment and play a synergistic effect. CONCLUSION: These data suggest that an HSP90 inhibitor is available to treat UC by inhibiting the MAPK signaling pathway. This axis can restore the intestinal mucosa barrier's function by reducing intestinal mucosa's permeability and inhibiting apoptosis of intestinal epithelial cells. The specific mechanism is that HSP90 inhibitor can reduce the pathological damage and inflammation levels of colitis mice, and reduce the apoptosis rate of colonic epithelial cells and the mucosal permeability, thereby restoring the mucosal barrier function. During this process, CSD works synergistically to improve the therapeutic effect of the HSP90 inhibitor.

COVID-19 infection with keratitis as the first clinical manifestation.

AIM: To report a case which keratitis is the first clinical manifestation of COVID-19 that occurred 3d earlier than the common COVID-19 symptoms. METHODS: Regular slit lamp examination, corneal scraping test, and chest computed tomography (CT) were performed for patients with COVID-19 infection. The ophthalmologic treatment included ganciclovir eye drop (50 mg/mL, 6 times/d). The treatment for diarrhea included Guifu Lizhong pills (TID). The antiviral therapy consisted of oseltamivir (75 mg capsule Q12H); therapy preventing bacterial infection consisted of azithromycin (250 mg tablet QD) and moxifloxacin (0.4 g tablet Q12H); and therapy for cough relief and fever prevention consisted of Chinese herbal decoction. RESULTS: A 35-year-old male suddenly suffered pain, photophobia, and tears in his right eye for one day without systemic COVID-19 symptoms. Patient was diagnosed with keratitis, which was seemingly different from common keratitis. Ganciclovir eye drop was initiated. The corneal scraping test for COVID-19 was positive. The chest CT images were abnormal confirming the diagnosis of COVID-19 infection. The antiviral and antibacterial therapies were initiated. Chinese herbal therapy was used for cough relief and fever prevention. After roughly two weeks, patient recovered from COVID-19. CONCLUSION: A new type of keratitis, atypical keratitis, is a clinical manifestation of COVID-19, and this clinical manifestation could appear 3d earlier than fever and cough. The earlier a COVID-19 clinical manifestation is identified, the earlier can a patient be directed to stay at home, and significantly fewer people would be infected.

Assessing the post-treatment therapeutic effect of tongxie in irritable bowel syndrome: A randomized controlled trial.

Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17-25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P < .001). Twenty-five weeks after the therapies were discontinued could be considered as IBS natural history. During this period, an average of 53.8-56.3% of patients (pool tongxie and placebo data together) had IBS symptoms (pain scale ≥ 3, stool consistency ≥ 5). In particular, at the end of this study (week 61), 145 (54.2%) patients had IBS symptoms. Our results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.

Effect of compound Sophorae decoction in the treatment of ulcerative colitis by tissue extract metabolomics approach.

OBJECTIVE: To investigate how compound Sophorae decoction (CSD) works on rats' models of ulcerative colitis (UC) induced by 2,4,6-trinitrobenzenesulfonic acid solution (TNBS) by metabolomics studies of colon, liver, and kidney tissue extracts. METHODS: Rats with UC induced by TNBS enema were used as models in this study. Metabolic profiles of the three tissues were analyzed and pathway analysis of biomarkers was performed after CSD administration and further integration of metabolic networks. RESULTS: Thirteen biomarkers were screened from colon, liver, and kidney tissue extracts, and the levels of these substances were up- or down-regulated in the model group, but their levels were reversed after CSD administration. These biomarkers were mainly related to Phenylalanine, tyrosine and tryptophan biosynthesis, Phenylalanine metabolism, Glutathione metabolism, Arachidonic acid metabolism, Nicotinate and nicotinamide metabolism, Alanine, aspartate and glutamate metabolism. CONCLUSION: CSD could significantly ameliorate the symptoms of UC by regulating multiple metabolic pathways.

8-hydroxypinoresinol-4-O-ß-D-glucoside from Valeriana officinalis L. Is a Novel Kv1.5 Channel Blocker.

ETHNOPHARMACOLOGY RELEVANCE: In folkloric medicine of many cultures, one of the medical uses of Valeriana officinalis Linn is to treat heart-related disease. Recently, it was shown that the ethanol extracts from V. officinalis could effectively prevent auricular fibrillation, and 8-hydroxypinoresinol-4-O-ß-D-glucoside (HPG) from the extracts is one of the two active compounds showing antiarrhythmia activities. AIM OF THE STUDY: The human Kv1.5 channel (hKv1.5) has potential antiarrhythmia activities, and this study arms at investigating the current blocking effects of HPG on hKv1.5 channel. MATERIAL AND METHODS: HPG was obtained from V. officinalis extracts, and hKv1.5 channels were expressed in HEK 293 cells. HPG was perfused while recording the current through hKv1.5 channels. Patch-clamp recording techniques were used to study the effects of HPG at various concentrations (10 µM, 30 µM, and 50 µM) on hKv1.5 channels. RESULTS: The present study demonstrated that HPG inhibited hKv1.5 channel current in a concentration-dependent manner; the higher the concentration, the greater is the inhibition at each depolarization potential. During washout, the channels did not full recover indicating that the un-coupling between HPG and hKv1.5 channels is a slow process. CONCLUSION: HPG may be an effective and safe active ingredient for AF having translational potential.

Compound Sophorae Decoction: treating ulcerative colitis by affecting multiple metabolic pathways.

Ulcerative colitis (UC) is a chronic refractory non-specific intestinal inflammatory disease that is difficult to be cured. The discovery of new ulcerative colitis-related metabolite biomarkers may help further understand UC and facilitate early diagnosis. It may also provide a basis for explaining the mechanism of drug action in the treatment of UC. Compound Sophorae Decoction (CSD) is an empirical formula used in the clinical treatment of UC. Although it is known to be efficacious, its mechanism of action in the treatment of UC is unclear. The purpose of this study was to investigate the changes in endogenous substances in UC rats and the effects of CSD on metabolic pathways using the metabonomics approach. Metabolomics studies in rats with UC and normal rats were performed using LC-MS/MS. Rats with UC induced using TNBS enema were used as the study models. Metabolic profiling and pathway analysis of biomarkers was performed using statistical and pathway enrichment analyses. 36 screened potential biomarkers were found to be significantly different between the UC and the normal groups; it was also found that CSD could modulate the levels of these potential biomarkers. CSD was found to be efficacious in UC by regulating multiple metabolic pathways.

Compound sophorae decoction enhances intestinal barrier function of dextran sodium sulfate induced colitis via regulating notch signaling pathway in mice.

BACKGROUND: Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive. METHODS: In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR. RESULTS: CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2. CONCLUSIONS: These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.

Differential Analysis of Serum Principal Components Treated with Compound Sophora Decoction and Related Compounds Based on High-Resolution Mass Spectrometry (HRMS).

OBJECTIVE: To compare the differences in the serum principal components in ulcerative colitis- (UC-) induced rats, treated with compound Sophora decoction, matrine, oxymatrine monomer mixture, and indirubin monomer, and to provide a modern scientific basis for elucidating the clinical efficacy of compound Sophora decoction for the treatment of UC. METHODS: The serum samples of rats from each group were obtained after drug administration, and the serum principal components of each group were analyzed by high-resolution mass spectrometry. Agilent Eclipse XDB C18 chromatographic column (100 mm × 2.1 mm, 3.5 m) was used for separation. The mobile phase was water (A) and methanol (B) (0.1% formic acid) gradient elution, 0-3 min (B: 20%-40%), 3-10 min (B: 40%-54%), 10-25 min (B: 54%), 25-35 min (B: 54%-70%), 35-45 min (B: 70%-80%), 45-50 min (B: 80%), 50-60 min (B: 80%-100%), 70-72 min (B: 100%-20%), and 72-77 min (B: 20%); flow rate, 300 µL/min; column temperature, 40°C; and injection volume, 10 µL. ESI source was selected and scanned in the positive and negative ion modes. The scanning range was 70-1500 m/z; ion-source gas 1 (GS1): 55 psi; ion-source gas 2 (GS2): 60 psi; CUR: 30 psi; ion-source temperature (TEM): 550°C; ion-source voltage (ISVF) : 5500 V/-4500 V; decluster voltage (DP): 100 V; collision energy (CE): 35 V/-35 V; collision energy gain (CES) : 15 V/-15 V; and data acquisition mode: IDA. After the data from each group were imported into MarkView 1.3, the molecular weights and retention times of different substances were obtained and qualitatively analyzed by ChemSpider and PeakView 2.0. RESULTS: In the negative ion mode, 26 differential compounds were identified in the compound Sophora decoction group (FFKST) compared to the model group (M), and 18 differential compounds were identified in the matrine and oxymatrine group (KST) compared to the model group (M). In the positive ion mode, 11 and 7 differential compounds were identified in the compound Sophora decoction group (FFKST) and the matrine and oxymatrine group (KST) compared to the model group (M), respectively. The responses of all compounds in each group were compared with each other. As the different principal component substances in the indirubin group (DYH) displayed little correlation with other groups, the different components in this group were not researched thoroughly. CONCLUSION: By comparing the differences in the serum principal components from each administration group, we found that the FFKST group exhibited enhanced synthesis of the serum principal components; however, the compound doses of matrine and oxymatrine monomers did not exhibit the same changes in the serum principal components of UC-induced rats. Finally, the traditional Chinese medicine compound is more advantageous than monomers.

The Chinese medicinal herb decoction QRZSLXF enhances anti-inflammatory effect in TNBS-induced colitis via balancing Th17/Tregs differentiation.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) is one of the most common chronic inflammatory illnesses of the gastrointestinal tract due to the imbalance of immune homeostasis of T helper cells and/or regulatory T cells (Tregs). The Traditional Chinese medicine herb has been clinically proven for use in the treatment of IBD but its possible mechanism remains unknown. The study aims to assess the effect of Chinese medicinal herb decoction QRZSLXF (Qing Re Zao Shi Liang Xue receipt) for the treatment of TNBS-induced experimental colitis in mice and explore its relevant mechanism involved in Th17 and Tregs. MATERIALS AND METHODS: Mice colitis was induced by 50% 2,4,6-Trinitrobenzenesulfonic Acid (TNBS) ethanol solution weekly manner. These established model mice were divided into model control (0.8% NaCl treatment), FICZ, naphthoflavone (NaFTV), dexamethasone (DXM), and QRZSLXF (QrLx) groups. The colonoscopy, H&E staining, and immune staining were used to analyze the disease severity, inflammatory condition and Th17 or Treg related factors expression. High-performance liquid chromatography-mass spectrometry (HPLC/MS) was used to assess the content of FICZ in the colon tissues. Western blot and ELISA were used to examine the expression of Th17 or Treg related factors protein levels. Flow cytometry analysis was performed to assess the number and ratio of Th17/Tregs in splenocytes, and mesenteric lymph node lymphocytes (MLNCs), and lamina propria mononuclear cells (LPMCs). RESULTS: NaFTV, DXM and QrLx groups intestinal inflammation scores were significantly lower than that in colitis model control and FICZ groups, while the IL-6, STAT3, and RORγt expression levels were significantly lower than those in the model control and FICZ groups. Mass spectrometry results showed FICZ that in both DXM and QrLx groups was lower than control model and FICZ groups. Flow cytometry results showed that DXM, NaFTV and QrLx could significantly reduce Th17 proportion and increase Treg proportion in splenocytes, MLNCs, and LPMCs. CONCLUSIONS: NaFTV and QrLx treatment could decrease symptoms and inflammatory colitis, by decreasing of FICZ concentration and AhR signaling in colon, resulting in reducing the expression of IL-6, STAT3, and RORγt, whereas increasing the expression of FOXP3, consequently reducing the proportion of Th17 cells and increasing the proportion of Treg cells, respectively.

A Review on Recent Advances in Aloperine Research: Pharmacological Activities and Underlying Biological Mechanisms.

Aloperine, a quinolizidine-type alkaloid, was first isolated from the seeds and leaves of herbal plant, Sophora alopecuroides L. Empirically, Sophora alopecuroides L. is appreciated for its anti-dysentry effect, a property that is commonly observed in other Sophora Genus phytomedicines. Following the rationale of reductionism, subsequent biochemical analyses attribute such anti-dysentry effect to the bactericidal activity of aloperine. From then on, the multiple roles of aloperine are gradually revealed. Accumulating evidence suggests that aloperine possesses multiple pharmacological activities and holds a promising potential in clinical conditions including skin hyper-sensitivity, tumor and inflammatory disorders etc.; however, the current knowledge on aloperine is interspersed and needs to be summarized. To facilitate further investigation, herein, we conclude the key pharmacological functions of aloperine, and most importantly, the underlying cellular and molecular mechanisms are clarified in detail to explain the functional mode of aloperine.

Critical thinking about three meta-analyses: can vitamin D alone or with calcium prevent fractures?

Critical thinking is crucially important in both research and practice. This article demonstrates that a lack of critical thinking in two meta-analyses resulted in a conclusion that contradicts another meta-analysis and popular opinions. Kahwati et al. and Zhao et al. drew a conclusion that "Vitamin D supplementation alone or with calcium was not associated with reduced fracture incidence among community-dwelling adults without known vitamin D deficiency, osteoporosis, or prior fracture", which apparently contradicted that of Tang et al. Kahwati et al. and Zhao et al. meta-analyzed vitamin D and/or calcium supplementation, which can decrease fracture risk factors, in a population with no known disorders of bone metabolism or vitamin D deficiency. They concluded that supplementation did not reduce fracture incidence. It is important to note that osteoporosis, which supplementation can prevent, and fractures are two distinct concepts. Zhao et al. presented their conclusion without including the conditions under which their conclusion was true. Subsequently, their conclusion was misleadingly interpreted by the public media as "Vitamin D and Calcium Don't Prevent Bone Fractures" and "Vitamin D Does Not Prevent Falls, Calcium Does Not Prevent Fractures-A $2 Billion Waste of Money". If study conclusions do not specify the applicable conditions, guidelines on medications, including supplements, are clinically unacceptable. Researchers must critically think about every step of their studies, including the way their conclusions are presented.

Uncovering the Anticancer Mechanism of Compound Sophorae Decoction against Ulcerative Colitis-Related Colorectal Cancer in Mice.

Compound sophorae decoction (CSD), a traditional Chinese medicine (TCM) formula, has been voluminously used in China to deal with ulcerative colitis and gained significant therapeutic effect. Tremendous explorations have unraveled a contributory role of inflammatory bowel disease (IBD) like ulcerative colitis (UC) and Crohn's disease (CD) at the onset of colorectal cancer, scilicet, and colitis-related cancer (CRC). In light of the anti-inflammatory properties of CSD in UC, we appraised its chemoprevention capacity and underlying mechanism in ulcerative colitis-related colorectal cancer (UCRCC), employing a model of azoxymethane (AOM) plus dextran sulfate sodium- (DSS-) induced colorectal cancer (CRC) in C57BL/6 mice. Rapturously, our results illuminated the ameliorative effect of CSD against UCRCC in mice portrayed by lesser polyps or adenomas, attenuated colonic xenograft tumor growth in company with the preferable well-being of mice in contrast to the Model Group. We examined significant downregulation of proinflammatory cytokines such as TNF-α, NF-κB, IL-6, STAT3, and IL-17 after exposure to CSD, with the concomitant repression of inflammation-associated proteins, including COX-2 and iNOS. Independent of this, treatment with CSD declined the proportion of T helper 17 cells (Th17) and protein level of matrix metallopeptidase 9 (MMP-9). Moreover, transmission electron microscopy (TEM) detected observably suppressed mitophagy in mice administered with CSD and that was paralleled by the pro-apoptotic effect as indicated by upregulating caspase-3 together with caspase-9 and deregulating B-cell lymphoma 2 (Bcl-2). In closing, these findings suggest CSD executes the UCRCC-inhibitory activity through counteracting inflammatory responses and rescuing detuning of apoptosis as well as neutralizing overactive mitophagy, concurring to build up an oncosuppressive microenvironment.

A Systematic Review Exploring the Anticancer Activity and Mechanisms of Glucomannan.

Glucomannan, long recognized as the active ingredient of the traditional Chinese medicinal herb Konjac glucomannan, is a naturally occurring polysaccharide existing in certain plant species and fungi. Due to its special property to also serve as a dietary supplement, glucomannan has been widely applied in clinic to lower body weight and circulation cholesterol level and to treat constipation, diabetes, and arterial sclerosis. Besides the regulatory role engaged with gastroenterological and metabolic syndrome, recently, its therapeutic effect and the underlying mechanisms in treating cancerous diseases have been appreciated by mounting researches. The present review aims to emphasize the multifaceted aspects of how glucomannan exerts its anti-tumor function.

Effect of compound sophorae decoction on dextran sodium sulfate (DSS)-induced colitis in mice by regulating Th17/Treg cell balance.

OBJECTIVE: Compound sophorae decoction, a Chinese medicinal formulae composed of six Chinese herbs, is effective for the clinical treatment of ulcerative colitis (UC). Some of its effective monomers had been proven to have suppressive effect on UC models. The aim of this study is to further explore the mechanism whether compound sophorae decoction ameliorates dextran sodium sulfate (DSS)-induced mice colitis by regulating the balance between T helper (Th) 17 and regulatory T (Treg) cells. METHODS: Experimental model of UC, established by drinking water with DSS, was treated with compound sophorae decoction and mesalazine. The stool, activity, body weight of the mice, colon length and colon histopathology were observed to evaluate severity of colitis. The concentration of cytokines in colonic tissues were detected by ELISA. The expression of phosphorylated nuclear factor-kappaB (NF-κB) p65, STAT3 and phosphorylated STAT3 in colonic tissues were determined by western blotting and immunohistochemistry. The percentage of Th17 and Treg cells in spleen and mesenteric lymph nodes (MLNs) were detected by flow cytometry. The levels of transcription factor ROR-γt and FOXP3 in colon tissues were detected by qRT-PCR and immunohistochemistry. RESULTS: The aqueous extract of compound sophorae decoction was able to improve the symptoms and pathological damage of mice. The body weight of mice were increased and DAI were significantly decreased; ulcers were slighter than DSS group. The administration of compound sophorae decoction reduced the level of inflammatory factors interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and phospho-NF-κB p65, and also decreased the proportions of Th17 cells in spleen and MLNs and the expression of ROR-γt, IL-17A, STAT3, IL-6 in colonic tissues; while the percentage of Treg cells in spleen and MLNs and the expression of FOXP3, transforming growth factor (TGF)-ß1, IL-10 in colonic tissues were upregulated. CONCLUSION: Overall, this study suggested that compound sophorae decoction significantly improves the symptoms and the pathological damage of mice with colitis and influences the immune function by regulating Th17/Treg cell balance in DSS-induced colitis in mice.

Are personalized tongxie formula based on diagnostic analyses more effective in reducing IBS symptoms?-A randomized controlled trial.

OBJECTIVES: To examine the efficacy and safety ofpersonalized tongxie formulas; to decrease type II errors to minimum. METHODS: Patients were randomized (1:1:1) into three groups given tongxie, placebo, or pinaverium 3 times daily for 4 weeks. Patients in the tongxie group were treated with personalized formulas based on TCM differential diagnosis, i.e., basic type of IBS, IBS due to liver depression and qi stagnation, excess heat in the liver, deficient spleen function, deficient kidney function, and others (groups 1-6). Primary endpoints were significantly greater reductions in abdominal pain and Bristol stool score. Secondary endpoints were reductions in pain and stool frequencies and abdominal discomfort and its frequency. RESULTS: There were significantly more patients whose stool consistencies were improved than pains were relieved in the entire population (p < 0.001), but there was no significantly difference in subpopulation group 3 (p > 0.05). There were significantly more patients whose stool frequencies were reduced than pain frequencies were reduced in the entire population (p < 0.001), but there were no significantly difference in the subpopulation Groups 1, 3, 4, and 6 (p > 0.05). Multiple active ingredients and their mechanisms of actions to relieve IBS symptoms were identified. CONCLUSION: The outcomes in subpopulations may be different from those of the entire population, indicating that personalized formulas are important to achieve optimal outcomes; the active ingredients and innovative mechanisms identified in this study can be the candidates for developing new IBS drugs, and used to manage IBS, respectively. TRIAL REGISTRATION: NCT01641224 (www.ClinicalTrials.gov).