A review of novel research technology to explore the mystery of traditional Chinese medicine: Terahertz.

During the 2022 Annual National Terahertz Biophysics Conference, the hypothesis was proposed that bio frequency electromagnetic fields sensitive points, akin to acupuncture points, exist in the human body. This development has prompted numerous researchers to apply terahertz technology to the field of traditional Chinese medicine (TCM). In recent years, terahertz technology has achieved notable progress in the field of TCM, particularly concerning the meridian-collateral system. This review systematically presents the advancements in terahertz technology and its implications on TCM theory from a biophysical perspective. Additionally, it summarizes the utilization of terahertz waves in elucidating aspects of TCM, particularly focusing on the scientific connotation of Qi, the theoretical foundation of the meridian-collateral system, and moxibustion in diagnosing and treating diseases. We aimed to explore the innovative applications and distinct advantages of terahertz technology in TCM and its feasibility as a pioneering technological tool for the modernization of TCM.

Therapeutic mechanisms of the medicine and food homology formula Xiao-Ke-Yin on glucolipid metabolic dysfunction revealed by transcriptomics, metabolomics and microbiomics in mice.

BACKGROUND: In recent decades, the prevalence of metabolic diseases, particularly diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), has increased dramatically, causing great public health and economic burdens worldwide. Traditional Chinese medicine (TCM) serves as an effective therapeutic choice. Xiao-Ke-Yin (XKY) is a medicine and food homology TCM formula consisting of nine "medicine and food homology" herbs and is used to ameliorate metabolic diseases, such as insulin resistance, diabetes, hyperlipidemia and NAFLD. However, despite its therapeutic potential in metabolic disorders, the underlying mechanisms of this TCM remain unclear. This study aimed to evaluate the therapeutic effectiveness of XKY on glucolipid metabolism dysfunction and explore the potential mechanisms in db/db mice. METHODS: To verify the effects of XKY, db/db mice were treated with different concentrations of XKY (5.2, 2.6 and 1.3 g/kg/d) and metformin (0.2 g/kg/d, a hypoglycemic positive control) for 6 weeks, respectively. During this study, we detected the body weight (BW) and fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), daily food intake and water intake. At the end of the animal experiment, blood samples, feces, liver and intestinal tissue of mice in all groups were collected. The potential mechanisms were investigated by using hepatic RNA sequencing, 16 S rRNA sequencing of the gut microbiota and metabolomics analysis. RESULTS: XKY efficiently mitigated hyperglycemia, IR, hyperlipidemia, inflammation and hepatic pathological injury in a dose dependent manner. Mechanistically, hepatic transcriptomic analysis showed that XKY treatment significantly reversed the upregulated cholesterol biosynthesis which was further confirmed by RT-qPCR. Additionally, XKY administration maintained intestinal epithelial homeostasis, modulated gut microbiota dysbiosis, and regulated its metabolites. In particular, XKY decreased secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) and lowered fecal secondary bile acid (lithocholic acid (LCA) and deoxycholic acid (DCA)) levels to promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signalling pathway. Furthermore, XKY regulated amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances. CONCLUSION: Taken together, our findings demonstrate that XKY is a promising "medicine food homology" formula for ameliorating glucolipid metabolism and reveal that the therapeutic effects of XKY may due to its downregulation of hepatic cholesterol biosynthesis and modulation of the dysbiosis of the gut microbiota and metabolites.

The bone-protective mechanisms of active components from TCM drugs in rheumatoid arthritis treatment.

Rheumatoid arthritis (RA) is an autoimmune disease whose hallmarks are synovial inflammation and irreversible bone destruction. Bone resorption resulting from osteoclasts involves the whole immune and bone systems. Breakdown of bone remodeling is attributed to overactive immune cells that produce large quantities of cytokines, upregulated differentiation of osteoclasts with enhanced resorptive activities, suppressed differentiation of osteoblasts, invading fibroblasts and microbiota dysbiosis. Despite the mitigation of inflammation, the existing treatment in Western medicine fails to prevent bone loss during disease progression. Traditional Chinese medicine (TCM) has been used for thousands of years in RA treatment, showing great efficacy in bone preservation. The complex components from the decoctions and prescriptions exhibit various pharmacological activities. This review summarizes the research progress that has been made in terms of the bone-protective effect of some representative compounds from TCM drugs and proposes the substantial mechanisms involved in bone metabolism to provide some clues for future studies. These active components systemically suppress bone destruction via inhibiting joint inflammation, osteoclast differentiation, and fibroblast proliferation. Neutrophil, gut microenvironment and microRNA has been proposed as future focus.

Tetrandrine Ameliorates Rheumatoid Arthritis in Mice by Alleviating Neutrophil Activities.

Rheumatoid arthritis (RA) is a common autoimmune disease worldwide. Neutrophils play critical roles in the onset and development of RA and are the promising target for RA treatment. Tetrandrine is a bis-benzyl isoquinoline alkaloid derived from the traditional Chinese herbal Stephania tetrandra S. Moore. Tetrandrine is effective in alleviating RA by inhibiting macrophage inflammatory response, fibroblast overproliferation, and pannus formation. However, whether tetrandrine regulates the activities of neutrophils in RA is largely unknown. In this study, we adopted adjuvant-induced arthritis (AA) murine model to explore the effect of tetrandrine on RA and neutrophils. Twenty-eight mice were divided into four groups. The control group was injected with PBS in the limbs and treated with PBS by intraperitoneal injection (i.p.) from Day 10 to Day 37. The arthritis murine model was induced by injecting FCA into the ankle joints of hind limbs. The AA group, the AA + TET group, and the AA + DEX group mice were treated with PBS, tetrandrine (6 mg/kg), or dexamethasone (1 mg/kg) i.p. daily, respectively. Arthritic scores were evaluated, and the joint diameter was measured every three days. A cytometric bead assay was performed to measure the concentrations of IFN-γ, TNF-α, and IL-6 in the serum. H&E staining and Safranin O-fast staining were adopted to monitor the tissue changes in the joint. Immunohistochemistry assays were applied to detect the MPO, NE, CitH3, and PAD4 expression levels. To assess the effect of tetrandrine on neutrophil activities in vitro, CCK8 tests were applied to determine cell viability. The qPCR and ELISA were performed to determine IL-1ß and IL-6 expression levels. Immunofluorescence assays were performed to measure the formation of NETs. The results indicated that tetrandrine significantly alleviated the symptoms of RA in terms of the ankle diameter (from 4.629 ± 2.729 to 3.957 ± 0.257; P < 0.01) and ankle score (from 4.000 ± 0.000 to 3.286 ± 0.756; P < 0.05). Tetrandrine treatment significantly increased the cartilage areas and decreased serum IL-6 significantly (from 5.954 ± 2.127 to 2.882 ± 2.013; P < 0.01). The immunohistochemistry assays also showed decreased expression levels of NE, MPO, PAD4, and CitH3 induced by tetrandrine in comparison with the AA group (P < 0.01). The qPCR assays and ELISAs showed that tetrandrine had an anti-inflammatory effect in vitro by significantly inhibiting IL-6 (P < 0.01). The immunofluorescence assays showed that NET formation induced by PMA could be reduced by tetrandrine (P < 0.01). In conclusion, tetrandrine has good efficacy in treating RA by regulating neutrophil-involved inflammation and NET formation.

Berberine-Based Heterogeneous Linear Supramolecules Neutralized the Acute Nephrotoxicity of Aristolochic Acid by the Self-Assembly Strategy.

Aristolochic acid (AA) has been reported to cause a series of health problems, including aristolochic acid nephropathy and liver cancer. However, AA-containing herbs are highly safe in combination with berberine (Ber)-containing herbs in traditional medicine, suggesting the possible neutralizing effect of Ber on the toxicity of AA. In the present study, in vivo systematic toxicological experiments performed in zebrafish and mice showed that the supramolecule self-assembly formed by Ber and AA significantly reduced the toxicity of AA and attenuated AA-induced acute kidney injury. Ber and AA can self-assemble into linear heterogenous supramolecules (A-B) via electrostatic attraction and π-π stacking, with the hydrophobic groups outside and the hydrophilic groups inside during the drug combination practice. This self-assembly strategy may block the toxic site of AA and hinder its metabolism. Meanwhile, A-B linear supramolecules did not disrupt the homeostasis of gut microflora as AA did. RNA-sequence analysis, immunostaining, and western blot of the mice kidney also showed that A-B supramolecules almost abolished the acute nephrotoxicity of AA in the activation of the immune system and tumorigenesis-related pathways.

Mechanisms exploration of Angelicae Sinensis Radix and Ligusticum Chuanxiong Rhizoma herb-pair for liver fibrosis prevention based on network pharmacology and experimental pharmacologylogy.

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl4)-induced fibrosis model. Measurement of liver functional enzyme activities and histopathological examination showed that DC dramatically reduced bile acid levels, inflammatory cell infiltration and collagen deposition caused by CCl4. The increased expression of liver fibrosis markers, such as collagen 1, fibronectin, α-smooth muscle actin (α-SMA) and transforming growth factor-ß (TGF-ß), and inflammatory factors, such as chemokine (C-C motif) ligand 2 (MCP-1), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and IL-6 in fibrotic mice were significantly downregulated by DC herb-pair through regulation of extracellular signal-regulated kinase 1/2 (ERK1/2)-protein kinase B (AKT) signaling pathways. Collectively, these results suggest that DC prevents the development of liver fibrosis by inhibiting collagen deposition, decreasing inflammatory reactions and bile acid accumulation, which provides insights into the mechanisms of herb-pair in improving liver fibrosis.

Integrated analyses of miRNA and mRNA profiles in leukocytes and serums in traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome and Pi-wei damp-heat syndrome resulting from chronic atrophic gastritis.

BACKGROUND: To investigate the microRNA (miRNA)-gene interactions underlying leukocyte functions and characteristics, especially the potential serum biomarkers, implicated in the traditional Chinese medicine (TCM)-defined Pi-qi-deficiency syndrome (PQDS) and Pi-wei damp-heat syndrome (PDHS) resulting from chronic atrophic gastritis (CAG). METHODS: Using RNA/miRNA-sequencing approach, compared with healthy control population, we identified the PDHS- or PQDS-specific miRNAs and genes in leukocytes or serums, especially the Zheng (syndrome)-specific miRNA-gene interactions, and further decoded their functions and pathways. RESULTS: Despite being the TCM-defined Zhengs resulting from the same disease of CAG, the Zheng-specific genes and miRNAs were not same. The PDHS-specific leukocyte genes were mainly involved in defense and immune responses, including NOD-like receptor signaling and several synapses-related pathways. The expression upregulation of PDHS-specific genes enriched in the neutrophil degranulation pathway, indicated the enhanced leukocyte degranulation activation. The PQDS-specific genes in leukocytes were implicated in inflammatory response, extracellular matrix (ECM) organization and collagen catabolism. They could be enriched in MAPK and IL17 signaling and helper T cell differentiation pathways, especially the pathways associated with cell-to-cell adhesion/junction and communication such as cell adhesion molecules, ECM organization and ECM-receptor interaction, probably contributing to the characteristics and functions of leukocytes. Also, the experimentally-supported miRNA-gene interactions, concerned with COL4A2, COL26A1, SPP1 and PROCR, were implicated in the regulation of pathways related to cell-to-cell adhesion/junction and communication, suggesting the potential roles of the PQDS-specific miRNA-gene interactions for the characteristic and functional changes of leukocytes. Interestingly, the PQDS-specific miRNAs in the serums and the corresponding leukocytes, seemed to have the common roles in contributing to the characteristics and functions of leukocytes. Importantly, the hsa-miR-122-5p could be a potential biomarker, capable of being contained and carried in plasma exosomes and much higher expression in both the leukocytes and corresponding serums in the CAG patients with PQDS rather than PDHS. CONCLUSIONS: These results may provide new insights into the characteristic and functional changes of leukocytes in the two Zhengs, PDHS and PQDS, especially the miRNA-mediated gene regulation underlying leukocyte characteristics and functions, with potential leukocyte and serum biomarkers for future application in integrative medicine. Trial registration ClinicalTrials.gov, NCT02915393. Registered on September 17, 2016.

The Mechanisms of Sijunzi Decoction in the Treatment of Chronic Gastritis Revealed by Network Pharmacology.

Chronic gastritis is characterized by inflammation in the gastric mucosa with a vicious circle in inflammatory cells and inflammatory mediators. Stomach adenocarcinoma would occur in the metaplastic gastric mucosa of chronic gastritis. Sijunzi decoction is a famous classical formula for the treatment of chronic gastritis. Although previous studies revealed some functions of Sijunzi decoction in treating chronic gastritis, the underlying mechanisms have not been illustrated clearly. In this study, we used network pharmacology to investigate the mechanism of Sijunzi decoction in treating chronic gastritis. Firstly, online datasets TCMSP, SWISS, and DisGeNET were used to investigate the functional mechanism of Sijunzi decoction against chronic gastritis and 18 genes were identified as targets of Sijunzi decoction in chronic gastritis. These 18 genes can be categorized into immunologically related genes and cancer-related genes. GO analysis showed that the 18 target genes were mainly enriched in angiogenesis, nitric oxide biosynthetic process, ERK1 and ERK2 cascade, cellular response to drug, and MAPK cascade. So, Sijunzi decoction alleviated chronic gastritis by inhibiting the local inflammatory response. Furthermore, we also investigated the impact of Sijunzi decoction on the peripheral blood leukocytes with our own RNA sequencing (RNA-seq) data of 11 chronic superficial gastritis patients. 102 differentially expressed genes (DEGs) were identified by comparing RNA-seq data of chronic superficial gastritis patients with healthy control groups. After performing a functional analysis on 102 DEGs and Sijunzi decoction potential targets and taking the intersection of these pathways, we found that platelet activation, angiogenesis, and pathways in cancer were candidate target pathways regulated by Sijunzi decoction. Thus, Sijunzi decoction also alleviates chronic gastritis by suppressing inflammatory response of peripheral blood leukocytes. Our results showed that Sijunzi decoction can ameliorate the local gastric inflammation and inflammations in peripheral blood leukocytes and might also reduce the incidence of stomach cancer in chronic gastritis.

Flavonoids from Aurantii Fructus Immaturus and Aurantii Fructus: promising phytomedicines for the treatment of liver diseases.

BACKGROUND: Liver diseases and related complications are major sources of morbidity and mortality, which places a huge financial burden on patients and lead to nonnegligible social problems. Therefore, the discovery of novel therapeutic drugs for the treatment of liver diseases is urgently required. Aurantii Fructus Immaturus (AFI) and Aurantii Fructus (AF) are frequently used herbal medicines in traditional Chinese medicine (TCM) formulas for the treatment of diverse ailments. A variety of bioactive ingredients have been isolated and identified from AFI and AF, including alkaloids, flavonoids, coumarins and volatile oils. MAIN BODY: Emerging evidence suggests that flavonoids, especially hesperidin (HD), naringenin (NIN), nobiletin (NOB), naringin (NRG), tangeretin (TN), hesperetin (HT) and eriodictyol (ED) are major representative bioactive ingredients that alleviate diseases through multi-targeting mechanisms, including anti-oxidative stress, anti-cytotoxicity, anti-inflammation, anti-fibrosis and anti-tumor mechanisms. In the current review, we summarize the recent progress in the research of hepatoprotective effects of HD, NIN, NOB, NRG, TN, HT and ED and highlight the potential underlying molecular mechanisms. We also point out the limitations of the current studies and shed light on further in-depth pharmacological and pharmacokinetic studies of these bioactive flavonoids. CONCLUSION: This review outlines the recent advances in the literature and highlights the potential of these flavonoids isolated from AFI and AF as therapeutic agents for the treatment of liver diseases. Further pharmacological studies will accelerate the development of natural products in AFI and AF and their derivatives as medicines with tantalizing prospects in the clinical application.

Long-Term Vegan Meditation Improved Human Gut Microbiota.

OBJECTIVE: Meditation has been widely used for the treatment of a variety of psychological, cardiovascular, and digestive diseases as well as chronic pain. Vegetarian diets can effectively prevent hypertension, metabolic diseases such as diabetes and obesity, and certain cancers. Meditation and vegetarian diets have been recognized as components of a healthy lifestyle and have therefore attracted more people around the world. Meditation can help regulate overall health through the neural-endocrine-immune network. Changes in dietary habits can affect the composition of the intestinal flora, which in turn affects human physiology, metabolism, nutrition, and immune function through the bacteria-intestine-brain axis. Here, we aimed to investigate the effect of long-term meditation and vegan diet on human intestinal flora. MATERIALS AND METHODS: The present study used 16S rDNA sequencing technology to detect the differences in intestinal flora between 12 healthy vegan subjects receiving long-term meditation training and 12 healthy omnivorous subjects who never received any meditation training. RESULTS: The results showed that, compared with the subjects in the omnivorous healthy control group who had never received any meditation training, the intestinal flora structure in the people who followed the long-term vegan meditation practices changed significantly. The intersection set between the results of the LEfSe analysis and the Wilcoxon rank sum test includes 14 bacterial genera. These 14 genera are defined as the dominant genera, and the AUC value was 0.92 in the ROC curve, which demonstrates that the 14 genera can be used as a biomarker to distinguish the two groups. Three beneficial bacteria genera (Bifidobacterium, Roseburia, and Subdoligranulum) were significantly enriched in the meditation group with a threshold of 4, according to the LDAs. The functional prediction of differentially enriched intestinal flora showed that the metabolism of tyrosine, propionate, niacin, and nicotinamide in the intestinal micro-organisms in the meditation group was significantly reduced compared with those in the control group, while the biosynthesis of flavones, flavone alcohols, butosin, and neomycin; flavonoid-mediated oocyte maturation; cytoskeleton protein pathways; and antigen processing and presentation were significantly enhanced. CONCLUSIONS: These results indicate that long-term vegan meditation plays a positive role in improving the body's immunity and adjusting endocrine and metabolic levels, enabling the body to be in a state of good health.

Integrated Analyses of lncRNA and mRNA Profiles Reveal Characteristic and Functional Changes of Leukocytes in Qi-Deficiency Constitution and Pi-Qi-Deficiency Syndrome of Chronic Superficial Gastritis.

METHODS: We adopted RNA-sequencing approach to identify differential lncRNAs and genes in leukocytes, clustered expression profiles, and analyzed biological functions and pathways of differential genes to decode their potential roles in contributing to characteristics and functions of leukocytes. In addition, interaction networks were created to detail the interactions between differential genes. In particular, we explored differential lncRNAs-mediated regulation of differential genes and predicted the subcellular location of lncRNAs to reveal their potential roles. RESULTS: Compared with TCM-defined balanced constitution (BC), 183 and 93 genes as well as 749 and 651 lncRNAs were differentially expressed (P < 0.05 and |log2 (fold change)| ≥1) in leukocytes of individuals from case populations 1 (QDC) and 2 (PQDS), respectively. Of them, 12 genes and 111 lncRNAs were common to each case population. Several networks were created to detail the interactions among case-specific genes, especially case-specific lncRNAs-mediated regulation of case-specific genes. Also, interaction networks were created for the common lncRNAs and genes. HCL analyses showed that differential genes and lncRNAs, especially the common genes and lncRNAs, kept similar expression patterns in both case populations. Furthermore, function enrichment analyses just indicated the common biological processes, namely, extracellular matrix organization and cell adhesion via plasma membrane adhesion molecules. In addition, most common genes underwent very tight and complex regulation of many trans- and cis-acting lncRNAs. In particular, of them, ADAMTSL5, COL26A1, COL27A1, MSH5, and LOC390937 could be regulated by multiple case-specific and common lncRNAs, including the means that directs binding of the common lncRNAs to their coded proteins. The common changes in the extracellular matrix and integral components of plasma membrane related to cell-cell adhesion/junction and communication may implicate the linkage between QDC and PQDS, contributing to alterations in characteristics and functions of leukocytes. CONCLUSIONS: These results may provide new insights into the characteristic and functional changes of leukocytes in QDC and PQDS, especially the mechanism underlying the linkage of QDC to PQDS, with potential leukocytes biomarkers for future application in integrative medicine.

Self-Assemblies Based on Traditional Medicine Berberine and Cinnamic Acid for Adhesion-Induced Inhibition Multidrug-Resistant Staphylococcus aureus.

S. aureus is resistant to various first-line antibiotics, and seeking multifarious strategies aimed at effective control of antibiotic-resistant behavior is urgently needed. Here, we report a two-component directed self-assembly mode: the phytochemicals berberine and cinnamic acid can directly self-assemble into nanoparticles (NPs) displaying good bacteriostastic activity. Compared with several first-line antibiotics, the obtained nanostructures have a better inhibitory effect on multidrug-resistant S. aureus (MRSA) and stronger ability for biofilm removal. These qualities are attributed to the fact that organic assemblies can first spontaneously adhere to the surface of the bacteria, infiltrate into the cell, and then lead to converging attack against MRSA; thereafter, multipath bactericidal mechanisms of NPs on MRSA are found by both transcriptomic analysis and quantitative Polymerase Chain Reaction analysis. Moreover, when combined with spectral data and single crystal X-ray diffraction, the NPs' self-assembly mechanism governed by hydrogen bonds and π-π stacking interactions is clearly elucidated. These non-covalent interactions induce the NPs' formation of butterfly-like one-dimensional self-assembled units and finally layered three-dimensional spatial configuration. In addition, biocompatibility tests show that the NPs are nonhemolytic with little toxicity in vitro and in vivo. This directed self-assembly mode can offer a new perspective toward the design of biocompatible antimicrobial nanomedicines for clinical translation.

Application and Mechanisms of Triptolide in the Treatment of Inflammatory Diseases-A Review.

Bioactive compounds from medicinal plants with anti-inflammatory and immunosuppressive effects have been emerging as important sources of drugs for the treatment of inflammatory disorders. Triptolide, a diterpene triepoxide, is a pharmacologically active compound isolated from Tripterygium wilfordii Hook F (TwHF) that is used as a remedy for inflammatory and autoimmune diseases. As the most promising bioactive compound obtained from TwHF, triptolide has attracted considerable interest recently, especially for its potent anti-inflammatory and immunosuppressive activities. Over the past few years, an increasing number of studies have been published emphasizing the value of triptolide in the treatment of diverse inflammatory disorders. Here, we systematically review the mechanism of action and the therapeutic properties of triptolide in various inflammatory diseases according to different systematic organs, including lupus nephritis, inflammatory bowel disease, asthma, and rheumatoid arthritis with pubmed and Embase. Based on this review, potential research strategies might contribute to the clinical application of triptolide in the future.

Emodin ameliorates rheumatoid arthritis by promoting neutrophil apoptosis and inhibiting neutrophil extracellular trap formation.

Rheumatoid arthritis (RA) is a chronic, systemic, synovitis-based inflammatory disease with unknown etiology. Neutrophils play important roles in the pathogenesis of RA. Apoptosis and NETosis of neutrophils are two major mechanisms of programmed cell death that differ in their morphological characteristics and effects on the immune system. In rheumatoid arthritis, delayed neutrophil apoptosis amplifies the inflammatory response; and massive release of NETs and their components may cause tissue damage and provide self-antigens. Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs. In this study, we evaluated the effect of emodin on a murine adjuvant-induced arthritis (AA) model of RA in vivo and on neutrophil apoptosis and NETosis in vitro. Our results show that emodin alleviated AA by reducing neutrophil infiltration and proinflammatory cytokine (interleukin-6, interferon-gamma and tumor necrosis factor-α) release. Emodin promoted apoptosis and inhibited autophagy and NETosis in neutrophils. These findings indicate that emodin represents a potential therapeutic agent for RA.

Long-term effects of acupuncture for chronic prostatitis/chronic pelvic pain syndrome: systematic review and single-arm meta-analyses.

BACKGROUND: Cumulative evidences indicate that acupuncture may ameliorate the symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). However, the long-lasting effects of acupuncture on CP/CPPS has not been fully evaluated. The objective of this study is to assess the sustained effects of acupuncture on CP/CPPS. METHODS: We searched PubMed, EMBASE, and CENTRAL databases for studies on the use of acupuncture in patients with CP/CPPS. Studies with long-term follow-up periods were included. Single-arm meta-analyses were performed using random-effects model. The primary outcome was the response rate at the end of follow-up period; the secondary outcomes were changes of the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores at the end of follow-up, including total score and 3 sub-scores (pain, urinary, and quality of life). RESULTS: Six studies with 310 patients were performed in data synthesis, among which four studies were randomized controlled trials (RCT) and two were case series studies. At the end of follow-up, the weighted "average" response rate was 68.4% (95% CI: 42.1% to 89.5%, n=226; I2=93.5%); the change of NIH-CPSI total score were -14.8 (95% CI: -17.0 to -12.6, n=310; I2=92.1%); the change of pain, urinary, and quality of life sub-scores were -6.0 (95% CI: -6.9 to -5.2, n=266; I2=83.6%), -2.6 (95% CI: -3.2 to -2.0, n=266; I2=87.9%), and -4.4 (95% CI: -6.2 to -2.6, n=266; I2=98.7%), respectively. The source of heterogeneity could not be identified owing to insufficient studies. CONCLUSIONS: Acupuncture may have clinically long-lasting benefits for CP/CPPS. However, current evidence is limited owing to insufficient data and significant heterogeneity. Further studies with larger sample size and long-term follow-up periods are warranted.

Triptolide inhibits the inflammatory activities of neutrophils to ameliorate chronic arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by cellular infiltration into the joints and cartilage destruction. Neutrophils play a crucial role in the pathogenesis of RA. Triptolide (TP) is a bioactive compound derived from Tripterygium wilfordii Hook F, which has been used in folk medicine as a treatment for a variety of inflammatory disorders, including RA, for many centuries. Previous studies have shown that TP possesses anti-arthritic activity. However, the anti-arthritic mechanism of TP remains to be fully defined. In the present study, we used the adjuvant-induced arthritis (AA) murine model of RA to investigate the impact of TP on RA and neutrophil function. TP alleviated AA by reducing neutrophil recruitment and suppressing the expression of interleukin-6 and tumour necrosis factor-α in vivo. TP also suppressed the expression of pro-inflammatory cytokines in neutrophils, promoted neutrophil apoptosis and inhibited the migration, NETosis and autophagy of neutrophils in vitro. Based on our findings, TP effectively ameliorates RA by down-regulating neutrophil inflammatory functions, indicating that TP represents a potential therapeutic agent for RA.

Geniposide attenuates inflammatory response by suppressing P2Y14 receptor and downstream ERK1/2 signaling pathway in oxygen and glucose deprivation-induced brain microvascular endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Fructus gardenia is widely used for treatment of stroke and infectious diseases in Chinese medicine. Geniposide is the key bioactive compound related to the pharmacodynamic actions of gardenia on ischemic stroke. The molecular mechanism by which geniposide improves the ischemic brain injury was observed in the study. AIM OF THE STUDY: Recent studies showed that geniposide had protective activities against the inflammatory response in ischemic stroke. However, the molecular mechanism of geniposide anti-inflammatory role has not yet been fully elucidated. In this study, we investigated the effect of geniposide on the expression of P2Y14 receptor and downstream signaling pathway in brain microvascular endothelial cells (BMECs). MATERIALS AND METHODS: An in vitro model of cerebral ischemia in BMECs was established by oxygen-glucose-deprivation (OGD). To further confirm the specific effect of geniposide on P2Y14 receptor and downstream signaling pathways, we set up a UDP-glucose (an agonist of the P2Y14 receptor) stimulated model. After administration of geniposide, the expression of P2Y14 receptor, phosphorylation of RAF-1, mitogen activated protein kinase kinase1/2 (MEK1/2), extracellular signal-regulated kinase 1/2 (ERK1/2), level of interleukin-8 (IL-8), interleukin-1ß (IL-1ß), monocyte chemotactic protein 1 (MCP-1) in BMECs were determined. RESULTS: The mRNA and protein expression of P2Y14 in the rat BMECs were up-regulated in OGD-induced injury. After administration of Geniposide, the expression of P2Y14 receptor was significantly down-regulated, the phosphorylation of RAF-1, MEK1/2, ERK1/2 were suppressed. Similar data were obtained in UDP-glc stimulated model. We also observed that geniposide markedly declined the production of IL-8, IL-1ß and MCP-1 in OGD-induced BMECs. CONCLUSION: Geniposide exerted anti-inflammatory effects by interfering with the expression of P2Y14 receptor, which subsequently inhibits the downstream ERK1/2 signaling pathways and the release of the pro-inflammatory cytokines IL-8, MCP-1, IL-1ß. Therefore, this study provides the evidence for gardenia's clinical application in cerebral ischemia.