Ginseng polysaccharides ameliorate ulcerative colitis via regulating gut microbiota and tryptophan metabolism.

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Ginsenoside Rh2 enhances immune surveillance of natural killer (NK) cells via inhibition of ERp5 in breast cancer.

BACKGROUND: One critical component of the immune system that prevents breast cancer cells from forming distant metastasis is natural killer (NK) cells participating in immune responses to tumors. Ginsenoside Rh2 (GRh2) as one of the major active ingredients of ginseng has been employed in treatment of cancers, but the function of GRh2 in modulating the development of breast cancer remains elusive. PURPOSE: This study was to dissect the effect of GRh2 against breast cancer and its potential mechanisms associated with NK cells, both in vitro and in vivo. METHODS: MDA-MB-231 and 4T1 cells were used to establish in situ and hematogenous mouse models. MDA-MB-231 and MCF-7 were respectively co-cultured with NK92MI cells or primary NK cells in vitro. Anti-tumor efficacy of GRh2 was verified by immunohistochemistry (IHC), Cell Counting Kit-8 (CCK8), high resolution micro-computed tomography (micro-CT) scanning of lungs and hematoxylin and eosin (H&E) staining. Lactate dehydrogenase (LDH) cytotoxicity assay, flow cytometry, in vivo depletion of NK cells, enzyme-linked immunosorbent assay (ELISA), western blot, quantitative reverse transcription polymerase chain reaction (qRT-PCR), immunofluorescence and cell transfection were performed for investigating the anti-tumor mechanisms of GRh2. Molecular docking, microscale thermophoresis (MST) and cellular thermal shift assay (CETSA) were employed to determine the binding between endoplasmic reticulum protein 5 (ERp5) and GRh2. RESULTS: We demonstrated that GRh2 exerted prominent impacts on retarding the growth and metastasis of breast cancer through boosting the cytotoxic function of NK cells, as validated by the elevated release of perforin, granzyme B and interferon-γ (IFN-γ). Mechanistical studies revealed that GRh2 was capable of diminishing the expression of ERp5 and GRh2 directly bound to ERp5 in MDA-MB-231 cells as well as on a recombinant protein level. GRh2 prevented the formation of soluble MICA (sMICA) and upregulated the expression level of MICA in vivo and in vitro. Importantly, the reduced lung metastasis of breast cancer by GRh2 was almost abolished upon the depletion of NK cells. Moreover, GRh2 was able to insert into the binding pocket of ERp5 directly. CONCLUSION: We firstly demonstrated that GRh2 played a pivotal role in augmenting NK cell activity by virtue of modulating the NKG2D-MICA signaling axis via directly binding to ERp5, and may be further optimized to a therapeutic agent for the treatment of breast cancer.

Chaga Medicinal Mushroom, Inonotus obliquus (Agaricomycetes), Polysaccharides Alleviate Photoaging by Regulating Nrf2 Pathway and Autophagy.

Inonotus obliquus is a medicinal mushroom that contains the valuable I. obliquus polysaccharides (IOP), which is known for its bioactive properties. Studies have shown that IOP could inhibit oxidative stress induced premature aging and DNA damage, and delay body aging. However, the molecular mechanism of IOP in improving skin photoaging remains unclear, which prevents the development and utilization of I. obliquus in the field of skin care. In this study, ultraviolet B (UVB) induced human immortalized keratinocyte (HaCaT) cell photoaging model was used to explore the mechanism of IOP in relieving skin photoaging. Results showed that IOP inhibited cell senescence and apoptosis by reducing the protein expressions of p16, p21, and p53. IOP increased HO-1, SOD, and CAT expressions to achieve Nrf2/HO-1 pathway, thus improving antioxidant effects and preventing ROS generation. Furthermore, IOP enhanced the expression levels of p-AMPK, LC3B, and Beclin-1 to alleviate the autophagy inhibition in UVB-induced HaCaT cells. Based on these findings, our data suggested that IOP may be used to develop effective natural anti-photoaging ingredients to promote skin health.

Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders.

Numerous pharmacological effects of quercetin have been illustrated, including antiinflammation, antioxidation, and anticancer properties. In recent years, the antioxidant activity of quercetin has been extensively reported, in particular, its impacts on glutathione, enzyme activity, signaling transduction pathways, and reactive oxygen species (ROS). Quercetin has also been demonstrated to exert a striking antiinflammatory effect mainly by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase, and preserving the integrity of mast cells. By regulating oxidative stress and inflammation, which are regarded as two critical processes involved in the defense and regular physiological operation of biological systems, quercetin has been validated to be effective in treating a variety of disorders. Symptoms of these reactions have been linked to degenerative processes and metabolic disorders, including metabolic syndrome, cardiovascular, neurodegeneration, cancer, and nonalcoholic fatty liver disease. Despite that evidence demonstrates that antioxidants are employed to prevent excessive oxidative and inflammatory processes, there are still concerns regarding the expense, accessibility, and side effects of agents. Notably, natural products, especially those derived from plants, are widely accessible, affordable, and generally safe. In this review, the antioxidant and antiinflammatory abilities of the active ingredient quercetin and its application in oxidative stress-related disorders have been outlined in detail.

Salvia mitiorrhiza Bunge aqueous extract attenuates infiltration of tumor-associated macrophages and potentiates anti-PD-L1 immunotherapy in colorectal cancer through modulating Cox2/PGE2 cascade.

ETHNOPHARMACOLOGICAL RELEVANCE: Based on the notion of traditional Chinese medicine, the theory of invigorating the circulation of blood is a prominent treatment for cancer in clinic. Therefore, Salvia miltiorrhiza Bunge, as a representative of Chinese medicine of invigorating the circulation of blood, has been proved to be an effective medicinal herb for treating cancer. AIM OF THE STUDY: To clarify the anti-cancer effect of Salvia miltiorrhiza Bunge aqueous extract (SMAE) on colorectal cancer (CRC) and investigate whether the therapeutic effect of SMAE was mediated by attenuating the infiltration of tumor-associated macrophages (TAMs) into the tumor microenvironment (TME). MATERIALS AND METHODS: High-performance liquid chromatography (HPLC) was used for determined the main compounds of SMAE. MC38 cells were subcutaneously injected into the mice to establish the mouse model of CRC. Tumor growth curve was detected by tumor volume measurement. The model group received distilled water irrigation once a day. SMAE-treated group received 5 g/kg or 10 g/kg SMAE once a day. Anti-PD-L1 treated group received 5 mg/kg anti-PD-L1 once every three days. Protein expression of Cox2 and PD-L1 was determined by Western blot assay. The secretion levels of PGE2, IL-1ß, IL-6, MCP-1, and GM-CSF were evaluated through ELISA. The mRNA expression of CSF1, CCL2, CXCL1, CXCL2, and CXCL3 was measured by using RT-qPCR. Staining of Ki67, TUNEL and Caspase3 was used to investigate cell proliferation and apoptosis. Immunohistochemical staining was used to determine CD8+ T cell distribution. H&E staining was used to confirm histopathological changes. The expressions of F4/80 and CD68 were measured by flow cytometry to identify macrophages in tumors and lymph nodes. The number of CD8+ T cells and the expression of PD-1, IFN-γ, and Granzyme B (GZMB) were determined by flow cytometry. RESULTS: SMAE significantly retarded the growth of MC38 mouse colorectal cancer. SMAE strikingly inhibited the expression of Cox2 and impaired the secretion of PGE2 in tumors, contributing to the attenuated intra-tumoral infiltration of TAMs via Cox2/PGE2 cascade. Meanwhile, SMAE augmented anti-tumor immunity by the elevated proportion of IFN-γ+ CD8+ T cells and GZMB+ CD8+ T cells, which decreased the tumor load. Furthermore, the combination of SMAE and anti-PD-L1 showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in MC38 xenograft model. CONCLUSIONS: SMAE attenuated the infiltration of TAMs into tumors and synergized with anti-PD-L1 to treat CRC via modulating Cox2/PGE2 cascade.

Centella asiatica alleviates psoriasis through JAK/STAT3-mediated inflammation: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Centella asiatica (L.) Urban (CA) is a dry herb of the Umbelliferae family, first mentioned in Shennong's Herbal Classic. It is known for its ability to clear heat and dampness, detoxify, and reduce swelling, making it a popular treatment for dermatitis, wound healing, and lupus erythematosus. Psoriasis is a chronic inflammatory skin disease that is characterized by clearly delineated erythema and squamous skin lesions. However, the effect of CA on regulating inflammation and its mechanism in the pathogenesis of psoriasis is still not fully understood. AIM OF THE STUDY: This study evaluated the effects of CA on inflammatory dermatosis by in vitro and in vivo studies. And clarified the important role of the JAK/STAT3 signaling pathway in the treatment of psoriasis with CA. METHODS AND MATERIALS: Different components of CA were extracted and analyzed for their total flavonoid and polyphenol contents. The antioxidant capacity of the CA extracts was determined using DPPH, ABTS, and FRAP methods. In vitro, HaCaT cells were induced by lipopolysaccharide (LPS, 20 µg·mL-1) to establish an inflammatory injury model, and the effects of CA extracts on oxidative stress, inflammation and skin barrier function were evaluated systematically. Annexin V-FITC/PI staining was utilized for detecting cell apoptosis, while the expression of NF-κB and JAK/STAT3 pathways were detected by RT-PCR and western blot. Combined with an in vivo mice model of Imiquimod (IMQ) induced psoriasis-like skin inflammation, the most effective CA extract for alleviating psoriasis was identified and its potential mechanism was investigated. RESULTS: CA extracts showed high antioxidant capacity and were able to increase the content of GSH and SOD while reducing intracellular ROS generation. Notably, CA ethyl acetate extract (CAE) was found to be the most effective. Furthermore, CA extracts effectively downregulate inflammatory factors (IFN-γ, CCL20, IL-6 and TNF-α) mRNA levels and improved the gene expressions of barrier protective factors AQP3 and FLG, among them CAE and n-hexane extract of CA (CAH) had better effects. Western blot analysis indicated that CAE and CAH had anti-inflammatory effects by inhibiting the activation of NF-κB and JAK/STAT3 pathways, and CAE exhibited the best regulatory effect at the dose of 25 µg·mL-1. In vivo experiment, the psoriasis-like skin inflammation mice model was established by 5% IMQ and treated CAE solution (10, 20, 40 mg·mL-1) for 7 days, the results showed that CAE intervention reduced the skin scale and blood scab, and significantly inhibited the secretion of inflammatory factors in both serum and skin lesions at the dose of 40 mg·mL-1. CONCLUSION: Centella asiatica extracts were effective in improving skin inflammation and skin barrier dysfunction, and also alleviated psoriasis through JAK/STAT3 pathway. The results provided experimental support for the potential use of Centella asiatica in functional food and skin care products.

Modeling and spectroscopic investigation of U(VI) removal on porous amidoxime-functionalized metal organic framework derived from macromolecular carbohydrate.

The investigation of interaction mechanism of U(VI) selective removal on amidoxime-functionalized metal organic framework (i.e., UiO-66(Zr)-AO) derived from macromolecular carbohydrate is conducive to apply metal organic frameworks in actual environmental remediation. The batch experiments showed that UiO-66(Zr)-AO displayed the fast removal rate (equilibrium time of 0.5 h), high adsorption capacity (384.6 mg/g), excellent regeneration performance (<10 % decrease after three cycles) towards U(VI) removal due to the unprecedented chemical stability, large surface area and simple fabrication. U(VI) removal at different pH can be satisfactorily fitted by diffuse layer modeling with cation exchange at low pH and an inner-sphere surface complexation at high pH. The inner-sphere surface complexation was further demonstrated by X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) analysis. These findings revealed that UiO-66(Zr)-AO can be an effective adsorbent to remove the radionuclides from aqueous solution, which is crucial for recycling of uranium resource and decreasing the uranium harm to the environment.

Characterization and antivibrio activity of chitosan-citral Schiff base calcium complex for a calcium citrate sustained release antibacterial agent.

Vibrio parahemolyticus is the "Number one killer" of seafood products. Anti-vibrio agents having low cost and high-safety are urgently needed to supplement the application needs. This work attempted to prepare CS-CT-CCa complex with citral (CT), chitosan (CS) and calcium citrate (CCa) as raw material by microwave-assisted high-pressure homogenization. Additionally the coordination structure and morphology of Bridge-CS-CT-Schiff base/OH-CCa were verified. The prepared CS-CT-CCa had a well-dispersed property (the size: 3.55~9.33 µm and the zeta potential: +38.7~+67.5 mV) and an excellent sustained released ability (sustained release up to 180 min). MIC, Glucose assay, MDA assay, biofilm formation inhibition assay, SEM, swimming and swarming motility assay demonstrated that CS-CT-CCa had strong (MIC of 128 µg/mL) and sustained (more than 12 h) inhibitory effects against V. parahaemolyticus. Meanwhile, CS-CT-CCa could increase the membrane permeability of V. parahaemolyticus and inhibit their biofilm-forming ability in a dose-dependent manner. It could be inferred that the antibacterial activities against V. parahaemolyticus caused inhibition of biofilm formation, swimming and swarming motilities. This study provided necessary data for the further design and development of chitosan antibacterial agents, food and feed additives.

Ginseng polysaccharides: Potential antitumor agents.

As a famous herbal medicine in China and Asia, ginseng (Panax ginseng C. A. Meyer) is also known as the "King of All Herbs" and has long been used in medicine and healthcare. In addition to the obvious biological activities of ginsenosides, ginseng polysaccharides (GPs) exhibit excellent antitumor, antioxidant stress, and immunomodulatory effects. In particular, GPs can exert an antitumor effect and is a potential immunomodulator. However, due to the complexity and diversity in the structures and components of GPs, their specific physicochemical properties, and underlying mechanisms remain unclear. In this article, we have summarized the factors influencing the antitumor activity of GPs and their mechanism of action, including the stimulation of the immune system, regulation of the gut microbiota, and direct action on tumor cells.

Systemic pharmacological verification of Salvia miltiorrhiza-Ginseng Chinese herb pair in inhibiting spontaneous breast cancer metastasis.

Breast cancer is the most commonly diagnosed cancer in the world, and metastasis is often the main cause of death in breast cancer patients. Salvia miltiorrhiza -Ginseng (SG) herb pair is clinically used for the treatment of cardiovascular diseases and cancers. However, the pharmacological action of this pair on breast cancer is yet unclear. In this study, a spontaneous metastasis model of breast cancer was constructed to assess the therapeutic value of SG. After administration of different doses of SG, the results showed that although it did not significantly inhibit tumor growth, high-dose SG administration could inhibit tumor metastasis. Then, based on systematic pharmacology combined with Gene Expression Omnibus (GEO) database, potential targets of drugs were identified such as vascular endothelial growth factor A (VEGFA), matrix metalloproteinase (MMP9), prostaglandin endoperoxide synthase2 (PTGS2), etc. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) analysis revealed that these targets were related to cytokine-mediated signaling pathway, cell migration and other biological processes and signaling pathways such as PI3K/Akt, etc. The systematic pharmacology analysis showed that SG effectively inhibited the VEGFA and MMP9-mediated biological events such as angiogenesis, epithelial-mesenchymal transition (EMT) and impaired tumor metastasis. Overall, our research aimed to provide new ideas for the treatment of breast cancer lung metastasis in traditional Chinese medicine.

Crosstalk between traditional Chinese medicine-derived polysaccharides and the gut microbiota: A new perspective to understand traditional Chinese medicine.

Polysaccharide is a kind of macromolecule polymer composed of monosaccharides connected by glycosidic bonds. Traditional Chinese medicine (TCM), composed of various bioactive ingredients, is usually rich in polysaccharides. In recent years, extensive research on TCM polysaccharides has demonstrated their pharmacological effects. Polysaccharides can hardly be catabolized by enzymes encoded by the human genome but can be degraded to absorbable metabolites by bacteria inhabiting the colon. Hence, the gut microbiota plays a vital role in degrading TCM polysaccharides into short-chain fatty acids (SCFAs) which exert physiological functions locally and systemically. Besides, TCM polysaccharides can also modulate the composition and activities of the gut microbiota by promoting the growth of beneficial bacteria and inhibiting the colonization of pathogenic bacteria, ultimately restoring gut homeostasis and improving human health. In this review, we discuss the extraction and pharmacological effects of TCM polysaccharides, various functions of the gut microbiota, and the interactions between TCM polysaccharides and the gut microbiota, illuminating the mechanisms of TCM polysaccharides modulating host physiology via the gut microbiota. To firmly establish the clinical efficacy of TCM polysaccharides, further high-quality studies especially clinical trials are needed. Generally, discussion on the interplay between TCM polysaccharides and the gut microbiota is expected to elucidate their application prospects and inspire new thoughts in the development of TCM.

Wumei pills attenuates 5-fluorouracil-induced intestinal mucositis through Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathway and microbiota regulation.

BACKGROUND: Radiotherapy and chemotherapy can kill tumor cells and improve the survival rate of cancer patients. However, they can also damage normal cells and cause serious intestinal toxicity, leading to gastrointestinal mucositis[1]. Traditional Chinese medicine is effective in improving the side effects of chemotherapy. Wumei pills (WMP) was originally documented in the Treatise on Exogenous Febrile Diseases. It has a significant effect on chronic diarrhea and other gastrointestinal diseases, but it is not clear whether it affects chemotherapy-induced intestinal mucositis (CIM). AIM: To explore the potential mechanism of WMP in the treatment of CIM through experimental research. METHODS: We used an intraperitoneal injection of 5-fluorouracil (5-Fu) to establish a CIM mouse model and an oral gavage of WMP decoction (11325 and 22650 mg/kg) to evaluate the efficacy of WMP in CIM. We evaluated the effect of WMP on CIM by observing the general conditions of the mice (body weight, food intake, spleen weight, diarrhea score, and hematoxylin and eosin stained tissues). The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and myeloperoxidase (MPO), as well as the Toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB (TLR4/MyD88/NF-κB) signaling pathway proteins and tight junction proteins (zonula occludens-1, claudin-1, E-cadherin, and mucin-2) was determined. Furthermore, intestinal permeability, intestinal flora, and the levels of short-chain fatty acids (SCFA) were also assessed. RESULTS: WMP effectively improved the body weight, spleen weight, food intake, diarrhea score, and inflammatory status of the mice with intestinal mucositis, which preliminarily confirmed the efficacy of WMP in CIM. Further experiments showed that in addition to reducing the levels of TNF-α, IL-1ß, IL-6, and MPO and inhibiting the expression of the TLR4/MyD88/NF-κB pathway proteins, WMP also repaired the integrity of the mucosal barrier of mice, regulated the intestinal flora, and increased the levels of SCFA (such as butyric acid). CONCLUSION: WMP can play a therapeutic role in CIM by alleviating inflammation, restoring the mucosal barrier, and regulating gut microbiota.

Kaempferol impairs aerobic glycolysis against melanoma metastasis via inhibiting the mitochondrial binding of HK2 and VDAC1.

Metastasis is the leading cause of death in melanoma patients. Aerobic glycolysis is a common metabolic feature in tumor and is closely related to cell growth and metastasis. Kaempferol (KAM) is one of the active ingredients in the total flavonoids of Chinese traditional medicine Sparganii Rhizoma. Studies have shown that it interferes with the cell cycle, apoptosis, angiogenesis and metastasis of tumor cells, but whether it can affect the aerobic glycolysis of melanoma is still unclear. Here, we explored the effects and mechanisms of KAM on melanoma metastasis and aerobic glycolysis. KAM inhibited the migration and invasion of A375 and B16F10 cells, and reduced the lung metastasis of melanoma cells. Extracellular acidification rates (ECAR) and glucose consumption were obviously suppressed by KAM, as well as the production of ATP, pyruvate and lactate. Mechanistically, the activity of hexokinase (HK), the first key kinase of aerobic glycolysis, was significantly inhibited by KAM. Although the total protein expression of HK2 was not significantly changed, the binding of HK2 and voltage-dependent anion channel 1 (VDAC1) on mitochondria was inhibited by KAM through AKT/GSK-3ß signal pathway. In conclusion, KAM inhibits melanoma metastasis via blocking aerobic glycolysis of melanoma cells, in which the binding of HK2 and VDAC1 on mitochondria was broken.

Effectiveness of redcore lotion in patients with vulvovaginal candidiasis: a systematic review and Meta-analysis.

OBJECTIVE: To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis (VVC) using a systematic review and Meta-analysis of randomized controlled trials. METHODS: A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019. Randomized controlled trials in the treatment for VVC were included; only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included. Relative risk (RR) and 95% confidence intervals (CI) were used in the Meta-analysis. RESULTS: Seven studies involving 768 patients suffering from VVC were identified; 468 of the patients were pregnant women (60.9%). Combination group (Redcore lotion plus miconazole) was more effective in reduCIng symptomatic episodes of VVC than miconazole alone, with respect to cure rate (RR, 1.31; 95% CI, 1.09-1.57; P = 0.01), fungal culture negative rate (RR, 1.21; 95% CI, 1.04-1.41; P = 0.01), and effective rate (RR, 1.18; 95% CI, 1.05-1.35; P = 0.01). Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate (RR, 1.48; 95% CI, 1.16-1.88, P < 0.01), fungal culture negative rate (RR, 1.26; 95% CI; 1.09-1.47; P < 0.01), and effective rate (RR, 1.25; 95% CI, 1.10-1.42; P < 0.01). Additionally, the observed risk of adverse events was lower in the combination medication group (RR, 0.30; 95% CI, 0.14-0.65; P < 0.01). CONCLUSIONS: Though overall quality of individual studies was low, Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx.

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Modulation of Gut Microbiota by Magnesium Isoglycyrrhizinate Mediates Enhancement of Intestinal Barrier Function and Amelioration of Methotrexate-Induced Liver Injury.

Background: The gut-liver axis plays a crucial role in various liver diseases. Therefore, targeting this crosstalk may provide a new treatment strategy for liver diseases. However, the exact mechanism underlying this crosstalk and its impact on drug-induced liver injury (DILI) requires clarification. Aim: This study aimed to investigate the potential mechanism and therapeutic effect of MgIG on MTX-induced liver injury, which is associated with the gut-liver axis and gut microbiota. Methods: An MTX-induced liver injury model was generated after 20-mg/kg/3d MTX application for 30 days. Meanwhile, the treatment group was treated with 40-mg/kg MgIG daily. Histological examination, aminotransferase, and aspartate aminotransferase enzyme levels were estimated to evaluate liver function. Immune cells infiltration and inflammatory cytokines were detected to indicate inflammation levels. Colon histological score, intestinal barrier leakage, and expression of tight junctions were employed to assess the intestinal injury. Bacterial translocation was observed using fluorescent in situ hybridisation, colony-forming unit counting, and lipopolysaccharide detection. Alterations in gut microbial composition were analysed using 16s rDNA sequencing and relative quantitative polymerase chain reaction. Short-chain-fatty-acids and lactic acid concentrations were then utilized to validate changes in metabolites of specific bacteria. Lactobacillus sp. supplement and fecal microbiota transplantation were used to evaluate gut microbiota contribution. Results: MTX-induced intestinal and liver injuries were significantly alleviated using MgIG treatment. Bacterial translocation resulting from the intestinal barrier disruption was considered a crucial cause of MTX-induced liver injury and the therapeutic target of MgIG. Moreover, MgIG was speculated to have changed the gut microbial composition by up-regulating probiotic Lactobacillus and down-regulating Muribaculaceae, thereby remodelling the intestinal barrier and inhibiting bacterial translocation. Conclusion: The MTX-induced intestinal barrier was protected owing to MgIG administration, which reshaped the gut microbial composition and inhibited bacterial translocation into the liver, thus attenuating MTX-related DILI.

Multi-material basis and multi-mechanisms of the Dahuang Zhechong pill for regulating Treg/Th1 balance in hepatocellular carcinoma.

BACKGROUND: Dahuang Zhechong pill (DHZCP) improves the inhibitory immune status of mice with hepatocellular carcinoma (HCC) by regulating Treg/Th1 balance. HYPOTHESIS/PURPOSE: To study the multi-material basis and multi-mechanisms of DHZCP against HCC by regulating Treg/Th1 balance in vitro and in vivo. METHODS: UPLC-MS/MS was used to detect the dynamic changes in 29 characteristic components of different polar parts of DHZCP. H&E and TUNEL were used to check pathological condition in HCC mice. The number of CD4+T, CD8+T, Treg, Th1, and Th1-like Treg cells was counted by flow cytometry. TGF-ß, IL-10, IFN-γ, and TNF-α content were detected by ELISA. α-Ketoglutarate and glutamine levels were detected by Trace1310/TSQ8000 GC-MS/MS. p-Smad2, and p-Smad3 protein levels were detected by WB, mRNA expression of Smad2, alanine-serine-cysteine transporter-2, glutaminase, and glutamate dehydrogenase were detected by RT-PCR. Simca-p multivariate data analysis software was used to evaluate the relationship between the different polar parts of DHZCP and the proportion of Treg cells. RESULTS: Water-soluble (PW) and ethyl acetate (PE) polar parts of DHZCP affected the HCC immune system by inhibiting the differentiation of Tregs, reversing the balance of Treg/Th1, and significantly reduced the tumor volume and weight. However, petroleum ether and n-butanol polar parts had no above actions. The changes in emodin, chrysophanol, aloe vera emodin, emodin-8-O-ß-D-glycoside, gallic acid, naringenin, baicalein, wogonin, norwogonin, apigenin, chrysin, glycyrrhizin, formononetin, and palmitic acid were closely related to the changes of Treg cells, which is the main material basis of DHZCP inhibition of Treg differentiation. Additionally, PW mainly inhibit the differentiation of Treg cells by affecting the metabolism of hepatoma cells, improving tumor microenvironment acidity, and glutamine depletion. However, PE inhibited the differentiation of Treg cells mainly by regulating the TGF-ß/Smad pathway. CONCLUSION: In this study, accurate analysis of multi-component was combined with pharmacodynamic evaluations to identify the pharmacodynamic substances of DHZCP in regulating Treg/Th1 balance, and clarified the multi-target mechanism of DHZCP to improve tumor immunity. The study style offers a novel approach for pharmacological research on TCM.

Dahuang Zhechong pills inhibit liver cancer growth in a mouse model by reversing Treg/Th1 balance / 中国天然药物

The infiltration of immune cells into the hepatocellular carcinoma microenvironment is the main reason why hepatocellular carcinoma patients are prone to carcinoma recurrence and the disease are incurable. Notably, the infiltration of Treg cells is the main trigger. Dahuang Zhechong pill (DHZCP) is a traditional Chinese herbal compound successful in the treatment of hepatitis and hepatocellular carcinoma. DHZCP can heal and nourish while slowing the onset of the disease, thereby strengthening the body's immune function. It can localize tumors and ultimately achieve the goal of eliminating tumors. In this study, an orthotopic liver cancer model of mice was used to explore the mechanism of DHZCP enhancing anti-tumor immunity, which showed more Th1 cells in the peripheral blood and spleen after DHZCP treatment, while more IFN-γ was secreted to activate CD8+ T cells and Treg cell production was inhibited, thereby suppressing the growth of HCC. Finally, we also analyzed the potential components of DHZCP from the perspective of modern targets using network pharmacology methods and experimental results.

Research progress in mechanism of Chinese herbal compounds and monomers in delaying lumbar intervertebral disc degeneration / 中国中药杂志

Traditional Chinese medicine has unique advantages in the treatment of degenerative bone and joint diseases, and its widely used in clinical practice. In recent years, many scholars have conducted a large number of basic studies on the delay of intervertebral disc degeneration by herbal compound and monomeric components from different perspectives. In order to further elucidate its mechanism of action, this paper summarizes the in vivo and in vitro experimental studies conducted at the level of both herbal compound and single components, respectively, in order to provide references for the basic research on the treatment of lumbar intervertebral disc degeneration by Chinese medicine. A summary shows that commonly used herbal compound prescriptions include both classical prescriptions such as Duhuo Jisheng Decoction, as well as clinical experience prescriptions such as Yiqi Huoxue Recipe. Angelicae Sinensis Radix, Chuanxiong Rhizoma, Rehmanniae Radix Praeparata, Achyranthis Bidentatae Radix, and Eucommiae Cortex were used most frequently. Tonic for deficiency and blood stasis activators were used most frequently. The most utilized monomeric components include icariin, ginsenoside Re, salvianolic acid B and aucubin. The main molecular mechanisms by which herbal compound and monomeric components delay of lumbar intervertebral disc degeneration include improving the intervertebral disc microenvironment, promoting the synthesis of aggregated proteoglycans and type Ⅱ collagen in the intervertebral disc, reducing the degradation of the extracellular matrix, and inhibiting apoptosis in the nucleus pulposus cells, etc. The main signaling pathways involved include Wnt/β-catenin signaling pathway, MAPK-related signaling pathway, mTOR signaling pathway, Fas/FasL signaling pathway, PI3 K/Akt signaling pathway, NF-κB signaling pathway, JAK/STAT signaling pathway, and hedgehog signaling pathway, etc.