Sustained silencing peanut allergy by xanthopurpurin is associated with suppression of peripheral and bone marrow IgE-producing B cell.

Introduction: Peanut allergy is an immunoglobulin E (IgE) mediated food allergy. Rubia cordifolia L. (R. cordifolia), a Chinese herbal medicine, protects against peanut-induced anaphylaxis by suppressing IgE production in vivo. This study aims to identify IgE-inhibitory compounds from the water extract of R. cordifolia and investigate the underlying mechanisms using in vitro and in vivo models. Methods: Compounds were isolated from R. cordifolia water extract and their bioactivity on IgE production was assessed using a human myeloma U266 cell line. The purified active compound, xanthopurpurin (XPP), was identified by LC-MS and NMR. Peanut-allergic C3H/HeJ mice were orally administered with or without XPP at 200µg or 400µg per mouse per day for 4 weeks. Serum peanut-specific IgE levels, symptom scores, body temperatures, and plasma histamine levels were measured at challenge. Cytokines in splenocyte cultures were determined by ELISA, and IgE + B cells were analyzed by flow cytometry. Acute and sub-chronic toxicity were evaluated. IL-4 promoter DNA methylation, RNA-Seq, and qPCR analysis were performed to determine the regulatory mechanisms of XPP. Results: XPP significantly and dose-dependently suppressed the IgE production in U266 cells. XPP significantly reduced peanut-specific IgE (>80%, p <0.01), and plasma histamine levels and protected the mice against peanut-allergic reactions in both early and late treatment experiments (p < 0.05, n=9). XPP showed a strong protective effect even 5 weeks after discontinuing the treatment. XPP significantly reduced the IL-4 level without affecting IgG or IgA and IFN-γ production. Flow cytometry data showed that XPP reduced peripheral and bone marrow IgE + B cells compared to the untreated group. XPP increased IL-4 promoter methylation. RNA-Seq and RT-PCR experiments revealed that XPP regulated the gene expression of CCND1, DUSP4, SDC1, ETS1, PTPRC, and IL6R, which are related to plasma cell IgE production. All safety testing results were in the normal range. Conclusions: XPP successfully protected peanut-allergic mice against peanut anaphylaxis by suppressing IgE production. XPP suppresses murine IgE-producing B cell numbers and inhibits IgE production and associated genes in human plasma cells. XPP may be a potential therapy for IgE-mediated food allergy.

Reduction of Th2 inflammation and fibrosis in eosinophilic esophagitis in a murine model by citri reticulatae pericarpium.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammation and subepithelial fibrosis play major roles in the early pathology of eosinophilic esophagitis (EoE). However, there are currently no pharmacotherapeutic interventions that directly target eosinophilic esophagitis. Citri Reticulatae Pericarpium (CRP, known as Chen-Pi) is one of most frequently used qi-regulating drugs in Chinese medicine and nutrition. CRP is rich with flavonones and polymethoxy flavones, both of which exhibit superior anti-inflammatory, anti-allergic and anti-fibrosis effects. This study is to investigate intervention effect of CRP on EoE, to identify its active compounds and to explore its underlying mechanisms. METHODS: The CRP extract was obtained by liquid-liquid extraction with 70% ethanol, and its main components were identified by HPLC and TLC chromatography as hesperidin, nobiletin, tangeretin, and narirutin in turn. Furthermore, we evaluated its effect and underlying mechanisms in an PN (Peanut protein extract)-sensitized murine model of food allergy induced EoE. RESULTS: CRP treatment attenuated EoE model mice symptomatology, blocked hypothermia, reduced the production of PN-specific IgE and IgG1 and TH2 cytokines (interleukin (IL)-4 and IL-5), and increased the level of anti-inflammatory cytokines IL-10 and interferon (IFN)-γ. CRP treatment also significantly alleviated the pathological damage and reduced fibrosis in inflamed tissues like esophagus, lung, and intestine. These results were strongly associated with reducing the expression of p-p38 mitogen-activated protein kinase (MAPK), transforming growth factor beta1 (TGF-ß1) and p-Smad 3 proteins. CONCLUSION: CRP extract markedly inhibited TH2 immune response and attenuated subepithelial fibrosis with a dose-dependent manner through down-regulating MAPK/TGF-ß signaling pathway. It is suggested that CRP extract might serve as a potential therapy for food allergy-induced EoE like disease.

Double-Blind, Placebo-Controlled Study of E-B-FAHF-2 in Combination With Omalizumab-Facilitated Multiallergen Oral Immunotherapy.

BACKGROUND: Oral immunotherapy (OIT) is limited by adverse events, and most patients require continued treatment to maintain their increased threshold. Adjunctive treatments have been explored to increase the safety and efficacy of OIT. OBJECTIVE: This study aimed to determine the safety and efficacy of enhanced, butanol purified Food Allergy Herbal Formula-2 (E-B-FAHF-2) for inducing remission in subjects undergoing omalizumab-facilitated multiallergen OIT (multi-OIT). METHODS: In this double-blind, placebo-controlled clinical trial, subjects were randomized 1:1 to receive either E-B-FAHF-2 or placebo, starting 2 months before OIT and continuing throughout OIT. All subjects received a 4-month course of omalizumab, starting 2 months before OIT through the 2-month OIT build-up phase. After 24 months of multi-OIT (maintenance dose of 1000 mg of each allergen), desensitization and remission were assessed. The primary objective was to determine if subjects in the E-B-FAHF-2 group (EOIT) were more likely than the placebo group (OIT) to develop remission to all 3 allergens treated with multi-OIT, as defined by the absence of dose-limiting symptoms to a cumulative dose of 4444 mg of protein after discontinuing treatment for 3 months. RESULTS: Thirty-three subjects were randomized. A total of 63.6% were desensitized to 4444 mg of protein for each allergen at 26 months, and 24.2% met the primary outcome of remission at 29 months, with no difference between the treatment groups. There was good adherence (>85%) with study medications, with no difference between the treatment groups. There was no difference in reported overall adverse events between the treatment groups. CONCLUSION: Omalizumab-facilitated multifood OIT was safe and effective, and remission was achieved in about a quarter of subjects. However, outcomes were not improved by the addition of E-B-FAHF-2.

Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.

Goals: To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. Methods: Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. Results: 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. Conclusion: W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.

Successful management of chronic urticaria and food allergies in a pediatric population using integrative traditional Chinese medicine therapy: a case series.

BACKGROUND: Food allergy is becoming increasingly common among the pediatric population. Despite strict avoidance of food allergens, a subgroup of sensitive individuals still develops frequent, persistent, and difficult to treat hives (FPDTH) for which there is no curative therapy. Although these cases are rare, these patients are in most need of therapy. CASE PRESENTATIONS: This is a retrospective review of 3 pediatric patients with highly sensitive food allergies who initially presented with hives daily or every other day, or multiple times a day, but achieved marked remission after traditional Chinese medicine (TCM) therapies. Patient 1 (P1) is a 5-year-old who has experienced 140 reactions in his lifetime. Reactions were mostly hives with 4 episodes of anaphylaxis. P1 had used Prednisone 20 times, had an Epinephrine injection 4 times, and had 3 emergency room (ER) visits. Patient 2 (P2) is a 12-year-old who had experienced hives since age 3. Despite daily antihistamine use, P2 had > 730 reactions in his lifetime at the time of presentation including 2 episodes of anaphylaxis. He had been prescribed prednisone 4 times, an Epinephrine injection 2 times, and had 1 ER visit. Patient 3 (P3) is a 20-month-old girl who had experienced > 120 reactions including 1 episode of anaphylaxis. She was on daily desonide and frequently used an antihistamine, yet still had required a course of prednisone once, an Epinephrine injection once, and had 1 ER visit to manage her reaction. After presenting to our clinic, patients received internal and external TCM treatments, including herbal baths and creams (Remedy A-D) as basic remedies to reduce food reactions, including but not limited to frequent hives. Within 7-9 months of TCM treatment, remarkably all patients had complete remission of atopic symptoms. All three patients also experienced an improvement in other conditions including food intolerance, diarrhea, anxiety, eczema, and environmental allergies. After 1 year of treatment, all three patients had reductions in food-specific IgE levels that had been previously elevated, and additionally, P1 and P3, who initially had high total IgE levels, experienced a marked decrease in total IgE levels as well. All three patients continued to introduce foods into their diet that they previously had reactions to, and all 3 patients remain symptom-free. CONCLUSIONS: Three pediatric patients with a known history of multiple food sensitivities and physician-diagnosed food allergies that presented with FPDTH underwent a TCM regimen and experienced dramatic improvement in symptoms and reduction in their IgE levels. This regimen appears to be effective in FPDTH population although a further study in a controlled clinical setting is required.

Using a System Pharmacology Method to Search for the Potential Targets and Pathways of Yinqiaosan against COVID-19.

The first reported case of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei, China. Thereafter, it spread through China and worldwide in only a few months, reaching a pandemic level. It can cause severe respiratory illnesses such as pneumonia and lung failure. Since the onset of the disease, the rapid response and intervention of traditional Chinese medicine (TCM) have played a significant role in the effective control of the epidemic. Yinqiaosan (YQS) was used to treat COVID-19 pneumonia, with good curative effects. However, a systematic overview of its active compounds and the therapeutic mechanisms underlying its action has yet to be performed. The purpose of the current study is to explore the compounds and mechanism of YQS in treating COVID-19 pneumonia using system pharmacology. A system pharmacology method involving drug-likeness assessment, oral bioavailability forecasting, virtual docking, and network analysis was applied to estimate the active compounds, hub targets, and key pathways of YQS in the treatment of COVID-19 pneumonia. With this method, 117 active compounds were successfully identified in YQS, and 77 potential targets were obtained from the targets of 95 compounds and COVID-19 pneumonia. The results show that YQS may act in treating COVID-19 pneumonia and its complications (atherosclerosis and nephropathy) through Kaposi sarcoma-related herpesvirus infection and the AGE-RAGE signaling pathway in diabetic complications and pathways in cancer. We distinguished the hub molecular targets within pathways such as TNF, GAPDH, MAPK3, MAPK1, EGFR, CASP3, MAPK8, mTOR, IL-2, and MAPK14. Five of the more highly active compounds (acacetin, kaempferol, luteolin, naringenin, and quercetin) have anti-inflammatory and antioxidative properties. In summary, by introducing a systematic network pharmacology method, our research perfectly forecasts the active compounds, potential targets, and key pathways of YQS applied to COVID-19 and helps to comprehensively clarify its mechanism of action.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance. We previously demonstrated that Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI) suppressed Th2 and increased IFN-γ in patients with asthma and in animal models, but its bioactive compound is unknown. Ganoderic acid beta (GAB) was isolated from Ganoderma lucidum (one herb in ASHMI). Human peripheral blood mononuclear cells (PBMCs) from adult patients with asthma were cultured with GAB or dexamethasone (Dex) in the presence of environmental allergens. The cytokine levels of IL-10, IFN-γ, IL-5, transcription factors T-bet, Foxp-3, and GATA3 were measured. Following 3-day culture, GAB, but not Dex, significantly increased IL-10 and IFN-γ levels by allergic patients' PBMCs. Following 6-day treatment, GAB inhibited IL-5 production, but IL-10 and IFN-γ remained high. Dex suppressed production of all three cytokines. GAB suppressed GATA3 and maintained Foxp-3 and T-bet gene expression, while Dex significantly suppressed GATA3 and T-bet expression. GAB simultaneously increased IL-10, IFN-γ associated with induction of T-bet and Foxp3, while suppressing IL-5, which was associated with suppression of GATA3, demonstrating unique beneficial cytokine modulatory effect, which distinguishes from Dex's overall suppression.

Computational analysis to define efficacy & molecular mechanisms of 7, 4'- Dihydroxyflavone on eosinophilic esophagitis: Ex-vivo validation in human esophagus biopsies.

Introduction: Eosinophilic Esophagitis (EoE) is a chronic condition characterized by eosinophilic inflammation of the esophagus which leads to esophageal dysfunction with common symptoms including vomiting, feeding difficulty, dysphagia, abdominal pain. Current main treatment options of EoE include dietary elimination and swallowed steroids. Diet elimination approach could lead to identifying the trigger food(s), but it often requires repeated upper endoscopy with general anesthesia and potentially could negatively affect nutrition intake and growth of the child and individuals' quality of life. Although the swallowed steroid treatment of effective, the EoE will universally recur after discontinuation of the treatment. Digestive Tea formula (DTF) has been used by the Traditional Chinese Medicine (TCM) practice to improve GI symptoms in EoE patients, including abdominal pain, GE reflux, and abnormal bowel movement. Previously, a flavonoid small molecule compound 7, 4 dihydroxy flavone (DHF) from Glycyrrhiza uralensis in DTF inhibited eotaxin, Th2 cytokine and IgE production in vitro and in vivo. Method: This study comprehensively evaluates the potential therapeutic and immunological mechanisms underlying DHF improvement of symptoms related to EoE using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analyses, in silico molecular docking and dynamic simulation followed by ex-vivo target validation by qRT-PCR using cultured human esophagus biopsy specimen with or without DHF from patients with EoE. Results: Computational analyses defined 29 common targets of DHF on EoE, among which TNF-α, IL-6, IL1ß, MAPK1, MAPK3 and AKT1 were most important. Docking analysis and dynamic simulation revealed that DHF directly binds TNF-α with a free binding energy of -7.7 kcal/mol with greater stability and flexibility. Subsequently, in the human esophagus biopsy culture system, significant reduction in levels of TNF-α, IL-6, IL-8 and IL1-ß was found in the supernatant of biopsy sample cultured with DHF. Furthermore, the gene expression profile showed significant reduction in levels of TNF-α, IL1-ß, IL-6, CCND and MAPK1 in the esophagus biopsy sample cultured with DHF. Discussion: Taken together, the current study provides us an insight into the molecular mechanisms underlying multi-targeted benefits of DHF in the treatment of EoE and paves the way for facilitating more effective EoE therapies.

Anti-IgE effect of small-molecule-compound arctigenin on food allergy in association with a distinct transcriptome profile.

BACKGROUND: Excessive production of IgE plays a major role in the pathology of food allergy. In an attempt to identify anti-IgE natural products, Arctium Lappa was one of the most effective herbs among approximately 300 screened medicinal herbs. However, little is known about its anti-IgE compounds. OBJECTIVE: To identify compounds from Arctium Lappa for targeted therapy on IgE production and explore their underlying mechanisms. METHODS: Liquid-liquid extraction and column chromatographic methods were used to purify the compounds. IgE inhibitory effects were determined on IgE-producing human myeloma U266 cells, peanut-allergic murine model and PBMCs from food-allergic patients. Genes involved in IgE inhibition in PBMCs were studied by RNA sequencing. RESULTS: The main compounds isolated were identified as arctiin and arctigenin. Both compounds significantly inhibited IgE production in U266 cells, with arctigenin the most potent (IC50=5.09µg/mL). Arctigenin (at a dose of 13 mg/kg) markedly reduced peanut-specific IgE levels, blocked hypothermia and histamine release in a peanut-allergic mouse model. Arctigenin also significantly reduced IgE production and Th2 cytokines (IL-5, IL-13) by PBMCs. We found 479 differentially expressed genes in PBMCs with arctigenin treatment (p < .001 and fold-change ≥1.5), involving 24 gene ontology terms (p < .001, FDR <0.05); cell division was the most significant. Eleven genes including UBE2C and BCL6 were validated by qPCR. CONCLUSION: Arctigenin markedly inhibited IgE production in U266 cells, peanut-allergic murine model and PBMCs from allergic patients by down-regulating cell division, cell cycle-related genes and up-regulating anti-inflammatory factors.

Formononetin isolated from Sophorae flavescentis inhibits B cell-IgE production by regulating ER-stress transcription factor XBP-1.

Rationale: IgE plays an important pathologic role in most, if not all, allergic conditions. We previously showed that ASHMI (anti-asthma herbal medicine intervention) suppressed IgE production in murine models of asthma and in asthma subjects. However, the active compounds in ASHMI responsible for the IgE suppression are still unknown. Objective: We sought to identify the compound(s) in ASHMI that are responsible for IgE inhibition as well as investigate the mechanisms by which the identified compound(s) decreases IgE production. Methods: The compounds in Sophorae Flavescentis were separated using Column chromatography and preparative-HPLC. The separated compounds were identified using LC-MS and 1H-NMR. U266 cells, an IgE-producing plasma cell line, were cultured with various concentrations of identified compounds. The levels of IgE production by the U266 cell were measured by ELISA. Trypan blue exclusion was used to determine the cell viability. The gene expression of XBP-1 and IgE-heavy chain was determined by RT-PCR. Results: A single compound identified as formononetin was isolated from Sophorae Flavescentis. Formononetin significantly and dose dependently decreased the IgE production in U266 cells across a concentration range of 2-20 µg/ml (p < 0.05-0.001 vs. untreated cells) with an IC50 value of 3.43 µg/ml. There was no cytotoxicity at any tested concentration. Formononetin significantly decreased XBP-1, and IgE-heavy chain gene expression compared with untreated cells (p < 0.001). Conclusion: Formononetin decreased IgE production in human B cell line U266 cells in a dose-dependent fashion through the regulation of XBP-1 ER transcription. Formononetin may be a potential therapy for allergic asthma and other IgE-mediated diseases.

Butanol Purified Food Allergy Herbal Formula-2 Has an Immunomodulating Effect ex-vivo in Pediatric Crohn's Disease Subjects.

Background: TNF-α has a major role in the pathogenesis of Crohn's disease (CD). In contrast, GM-CSF may be beneficial for its anti-inflammatory role in a subset of patients with CD with antibodies against GM-CSF as seen in prior trials of GM-CSF which resulted in clinical improvement in CD. We developed butanol purified Food Allergy Herbal Formula-2 (B-FAHF-2) by refining FAHF-2. FAHF-2 suppressed TNF-α production by human peripheral blood mononuclear cells (PBMCs) and colonic mucosa, and abrogated colitis in a murine model. We sought to examine the effect of B-FAHF-2 and the herbs that comprise it on TNF-α and GM-CSF production as a potential herbal therapy for the treatment of CD. Methods: B-FAHF-2 was examined using high pressure liquid chromatography (HPLC) and compared to the original formulation, FAHF-2. PBMCs from pediatric patients with CD were cultured with lipopolysaccharide and B-FAHF-2, individual herbs or medium alone. Colonic biopsy specimens were cultured with or without B-FAHF-2. TNF-α and GM-CSF were measured by enzyme-linked immunosorbent assay (ELISA). B-FAHF-2 efficacy was tested in vivo in the CD45Rbhi transfer model. Results: B-FAHF-2 had a similar HPLC fingerprint as FAHF-2 but decreased TNF-α production by PBMCs and colonic mucosa from pediatric CD subjects at 20% of the FAHF-2 dose. B-FAHF-2 increased GM-CSF production by PBMCs and colonic mucosa from pediatric CD subjects including those with antibodies to GM-CSF. Of B-FAHF-2's herbal constituents, only Huang Bai suppressed TNF-α and increased GM-CSF production. In the murine model, B-FAHF-2 treatment alleviated colitis. Conclusions: B-FAHF-2 decreased TNF-α production by PBMCs and colonic mucosa from pediatric subjects at a lower dose than FAHF-2. B-FAHF-2 also increased GM-CSF production by PBMCs independent of antibodies. B-FAHF-2 may have a benefit in CD patients.

[Effect of fresh Phragmitis Rhizoma on airway inflammation in chronic bronchitis based on TGF-ß signaling pathway].

This study aims to explore the mechanism of fresh Phragmitis Rhizoma against chronic bronchitis airway inflammation. The SD rats of SPF grade were divided into control group, model group, Guilongkechuanning group(GLKCN, 1.125 g·kg~(-1)), high-dose fresh Phragmitis Rhizoma group(LG-HD, 15 g·kg~(-1)), and low-dose fresh Phragmitis Rhizoma group(LG-LD, 7.5 g·kg~(-1)). The chronic bronchitis models of rats in other groups except the control group were induced by the modified smoking method. From the 15 th day of modeling, the rats were given corresponding agents by gavage for 20 consecutive days. After the last administration, the rats were sacrificed for sample collection. Enzyme-linked immunosorbent assay(ELISA) was employed to detect serum transforming growth factor-ß(TGF-ß) and interleukin-6(IL-6) levels. The protein expression of TGF-ß, IL-1ß and IL-6 in lung tissue was detected by immunohistochemical method. Masson staining was performed to detect collagen fibers and muscle fibers in lung tissue, and HE staining to detect the pathological changes of lung tissue. Human bronchial epithelial(16 HBE) cells were cultured in vitro, and CCK-8(cell counting kit-8) method was used to detect the cytotoxicity of cigarette smoke extract(CSE) and fresh Phragmitis Rhizoma. After the exposure of 16 HBE cells to 3.5% CSE and appropriate concentration(800, 400 µg·mL~(-1)) of fresh Phragmitis Rhizoma for 24 h, quantitative real-time PCR was conducted to determine the mRNA levels of TGF-ß and IL-1ß, and Western blot was employed to determine the protein levels of TGF-ß and IL-6 in the cells. The rat model of chronic bronchitis induced by smoking was successfully established. Fresh Phragmitis Rhizoma reduced serum TGF-ß and IL-6 levels, down-regulated the protein levels of TGF-ß, IL-1ß, and IL-6 in lung tissue, and alleviated pathological changes and fibrotic lesions in lung tissue. Moreover, it down-regulated the CSE-induced protein expression of TGF-ß and IL-6 as well as the mRNA level of TGF-ß in 16 HBE cells. These results indicated that fresh Phragmitis Rhizoma could prevent airway inflammation from chronic bronchitis and promote cell repair by inhibiting the TGF-ß signaling pathway.

Improvement of skin lesions in corticosteroid withdrawal-associated severe eczema by multicomponent traditional Chinese medicine therapy.

RATIONALE: We recently showed that multicomponent traditional Chinese medicine (TCM) therapy had steroid-sparing effects in moderate-to-severe eczema. We sought to evaluate TCM effects in severe eczema in a 7-year-old male with refractory disease and corticosteroid withdrawal syndrome. METHODS: Prior to referral, the patient had been treated since infancy with increasingly intensive standard of care, including high-dose topical and systemic corticosteroid and antibiotic therapy and was unable to tolerate further steroid treatment. The patient was administered a combination of oral and topical TCM for 17 months following discontinuation of his steroid regimen. His overall medical condition was assessed by SCORAD criteria and laboratory evaluations of serum IgE, absolute eosinophil count, and liver and kidney function tests. RESULTS: The patient showed rapid improvement of clinical measures of disease after starting TCM therapy, with marked improvement of sleep quality within the first week, complete resolution of itching, oozing, and erythema at 2 weeks, and a 79% and 99% decrease in his SCORAD values after one month and 3-6 months of TCM, respectively. Serum total IgE decreased by 75% (from 19,000 to 4630 (kIU/L), and absolute eosinophil counts decreased by 60% (from 1000 to 427 cells/µL) after 12 months of treatment. The patient did not require oral or topical steroids during the 17-month trial of TCM. TCM was tapered without complications. His dermatologic manifestations continued to be well-controlled 3 months after discontinuation. CONCLUSION: This case study suggests TCM should be further evaluated in controlled clinical studies of patients with severe, refractory eczema and steroid withdrawal syndrome.

Systems Pharmacology and In Silico Docking Analysis Uncover Association of CA2, PPARG, RXRA, and VDR with the Mechanisms Underlying the Shi Zhen Tea Formula Effect on Eczema.

Eczema is a complex chronic inflammatory skin disease impacted by environmental factors, infections, immune disorders, and deficiencies in skin barrier function. Shi Zhen Tea (SZT), derived from traditional Chinese medicine Xiao-Feng-San, has shown to be an effective integrative therapy for treating skin lesions, itching, and sleeping loss, and it facilitates reduction of topical steroid and antihistamine use in pediatric and adult patients with severe eczema. Yet, its active compounds and therapeutic mechanisms have not been elucidated. In this study, we sought to investigate the active compounds and molecular mechanisms of SZT in treating eczema using systems pharmacology and in silico docking analysis. SZT is composed of 4 medicinal herbs, Baizhu (Atractylodis macrocephalae rhizome), Jingjie (Schizonepetae herba), Kushen (Sophorae flavescentis radix), and Niubangzi (Arctii fructus). We first identified 51 active compounds from SZT and their 81 potential molecular targets by high-throughput computational analysis, from which we identified 4 major pathways including Th17 cell differentiation, metabolic pathways, pathways in cancer, and the PI3K-Akt signaling pathway. Through network analysis of the compound-target pathway, we identified hub molecular targets within these pathways including carbonic anhydrase II (CA2), peroxisome proliferator activated receptor γ (PPAR γ), retinoid X receptor α (RXRA), and vitamin D receptor (VDR). We further identified top 5 compounds including cynarine, stigmasterin, kushenol, ß-sitosterol, and (24S)-24-propylcholesta-5-ene-3ß-ol as putative key active compounds on the basis of their molecular docking scores with identified hub target proteins. Our study provides an insight into the therapeutic mechanism underlying multiscale benefits of SZT for eczema and paves the way for developing new and potentially more effective eczema therapies.

[Data mining of drug use rules based on traditional Chinese medicine treatment of ulcerative colitis].

To explore the drug use rules of traditional Chinese medicine(TCM) in the treatment of ulcerative colitis, and to provide some references for clinical treatment. The full-text search of "ulcerative colitis+TCM" was conducted based on CNKI. The literatures published from 2000 to 2020 were selected, and the clinical prescriptions for ulcerative colitis were selected according to the inclusion and exclusion criteria. The statistical processing and association rule analysis were carried out with use of Excel 2013, Clementine 12.0 and IBM SPSS Statistics 25.0 statistical software. A total of 177 prescriptions were obtained after retrieval of 3 432 relevant literatures, including 93 oral prescriptions and 84 enema prescriptions. Among them, Glycyrrhizae Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, Coptidis Rhizoma, Aucklandiae Radix and Paeoniae Radix Alba were the most frequently used drugs in oral administration, with the functions of tonifying, heat clearing and Qi regulating. The drugs with high frequency in enema included Bletillae Rhizoma, Coptidis Rhizoma, Sanguisorbae Radix, Phellodendri Chinensis Cortex and Sophorae Flavescentis Radix, with the functions of heat clearing, blood stopping and tonifying. Both oral and enema means of drugs were mainly of warm, cold and slightly cold properties, and bitter and sweet flavors, involving spleen, stomach, lung and large intestine. In cluster analysis, oral and enema drugs were divi-ded into 5 groups. Accordingly, in the treatment of ulcerative colitis, tonifying medicine, heat clearing medicine and Qi regulating medicine are often used for oral administration and heat clearing medicine, hemostatic medicine and tonifying medicine are often used for enema administration. On this basis, they are combined with diuretic drugs and astringent drugs respectively.

PEGylated Phthalocyanine-Functionalized Graphene Oxide with Ultrahigh-Efficient Photothermal Performance for Triple-Mode Antibacterial Therapy.

This study proposes a novel multifunctional synergistic antibacterial phototherapy technique for the rapid healing of bacteria-infected wounds. By binding PEGylated phthalocyanines to the surface of graphene oxide via noncovalent functionalization, the photothermal conversion efficiency of the obtained nanocomposites can be significantly increased, which shows that the sample temperature can achieve nearly 100 °C after only 10 min of 450 nm light illumination at a concentration ≥25 µg/mL. Moreover, the nanocomposites can rapidly generate singlet oxygen under 680 nm light irradiation and physically cut bacterial cell membranes. The triple effects are expected to obtain a synergistic antibacterial efficiency and reduce the emergence of bacterial resistance. After dual-light irradiation for 10 min, the generation of hyperthermia and singlet oxygen can cause the death of Gram-positive and Gram-negative bacteria. The results of an in vivo experiment revealed that the as-prepared nanocomposites combined with dual-light-triggered antibacterial therapy can effectively restrain the inflammatory reaction and accelerate the healing of bacteria-infected wounds. These were confirmed by the examination of pathological tissue sections and inflammatory factors in rats with bacteria-infected wounds. This nanotherapeutic platform is a potential photoactivated antimicrobial strategy for the prevention and treatment of bacterial infection.

A small molecule compound berberine as an orally active therapeutic candidate against COVID-19 and SARS: A computational and mechanistic study.

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.

[Analysis of animal models of ulcerative colitis based on characteristics of clinical symptoms of traditional Chinese and Wes-tern medicine].

This article aims to provide a good experimental method for the study of drug treatment of ulcerative colitis. According to the characteristics of ulcerative colitis's clinical symptoms, common ulcerative colitis animal models were analyzed. Based on the characteristics of clinical symptoms of traditional Chinese medicine and Western medicine for ulcerative colitis disease, the existing commonly used animal models of ulcerative colitis were analyzed to summarize the current matching degree, advantages and disadvantages of the exi-sting animal models of ulcerative colitis and clinical symptoms. At present, studies on ulcerative colitis mainly adopt four types of induction modeling methods, such as immunization, chemical stimulation, compound method and gene model. There are many reported methods of colitis modeling, but no model can reflect the characteristics of clinical symptoms of ulcerative colitis treated with Western or Chinese medicine. This article summarizes the characteristics, clinically relevant symptoms and applicable scope of immunization, chemical stimulation, compound method, and gene model, so as to provide a reliable animal model for subsequent studies of prevention and treatment of colitis.

[Analysis of animal models of chronic skin ulcers based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

Based on the characteristics of clinical symptoms of chronic skin ulcers in traditional Chinese and Western medicine, the current animal models of skin ulcers are summarized. This article analyzes the advantages and disadvantages of animal models according to the etiology and pathogenesis of chronic skin ulcers, traditional Chinese and Western medicine diagnostic criteria and observation indicators, and eva-luates the agreement between the existing animal models and the characteristics of clinical syndromes of traditional Chinese and Western medicine for chronic skin ulcers. Through analysis and comparison, it is found that most of the existing modeling methods are single-factor animal models, and there are certain gaps in the physiological and pathological characteristics of chronic skin ulcers caused by clinical multi-factors and interactions. Most of the modeling methods are guided by Western medicine. The lack of pathogenic factors of traditional Chinese medicine(TCM) in the process of modeling. Therefore, this article proposes to establish a reasonable quantification standard for chronic skin ulcer animal models, and to establish a combination model of chronic skin ulcer disease with traditional Chinese and Western medicine as the focus of future animal model research.

[Analysis of animal models of heart failure based on characteristics of clinical symptoms of traditional Chinese and Western medicine].

The incidence of heart failure has increased year by year, with a negative impact on quality of life and life expectancy of patients. Reproduction of animal models that meet the characteristics of clinical symptoms is a prerequisite for conducting experimental studies relating to heart failure. Based on the characteristics of clinical symptoms of heart failure in traditional Chinese medicine(TCM) and Western medicine, the existing common animal models of heart failure were explored, and the clinical anastomosis of the existing animal models was analyzed based on the clinical diagnostic criteria of heart failure in TCM and Western medicine. After analysis and comparison, it can be seen that the existing modeling methods are mostly single-factor animal models, with certain gaps between the characteristics of clinical multi-factors and interactions that jointly lead to heart failure, and the modeling methods were mostly guided by Western medicine, with a lack of TCM pathogenic factors in the model process, which is different from the clinical diagnostic criteria of Chinese and Western medicine for heart failure. In terms of syndrome differentiation, heart failure is classified into heart and lung Qi deficiency syndrome, Qi and Yin deficiency syndrome, heart and kidney Yang deficiency syndrome, Qi deficiency and blood stasis syndrome, Yang deficiency and water flooding syndrome, phlegm-drinking obstructive lung syndrome, Yin and yang exhausted syndrome. The existing animal models mostly confused them, with no effective and recognized method for modeling at present. There are major limitations in studies of Chinese medicine. Therefore, based on clinical characteristics of heart failure in Chinese and Western medicine, this article analyzed the existing animal models, defined their advantages and disadvantages and application prospects, and then suggested further improving the corresponding animal models of heart failure and standardizing the model evaluation, so as to improve the clinical coincidence between animal models and Chinese and Western medicine, make heart failure animal models better serve scientific studies, and promote relevant mechanism studies, pathological change studies and drug screening.