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Background: Psoriasis, a chronic skin condition characterized by systemic inflammation and altered gut microbiota, has been a target of Traditional Chinese Medicine (TCM) for centuries. Shenling Baizhu Powder (SLBZP), a TCM formulation, holds promise for treating inflammatory diseases, but its specific role in psoriasis and impact on gut microbiota is not fully understood.Objective: This study aims to elucidate the mechanism of SLBZP in treating psoriasis, integrating component analysis, network pharmacology, and experimental validation in mice models.Methods: We commenced with a detailed component analysis of SLBZP using liquid chromatograph and mass spectrometer (LC-MS). Network pharmacology analysis was used to predict the potential action targets and pathways of SLBZP in psoriasis. An in vivo experiment was conducted with psoriasis mice models, treated with SLBZP. Therapeutic effects were assessed via symptomatology, histopathology, and immunohistochemical analysis. Gut microbiota composition was analyzed using 16S rRNA gene sequencing.Results: A total of 42 main components and quality markers were identified, primarily from licorice and ginseng, including flavonoids, saponins and other markers. PPI topology analysis showed that TNF, IL-6, IL-1β, TP53 and JUN were the core DEPs. 168 signaling pathways including lipid and atherosclerosis, AGE-RAGE signaling pathway, IL-17 signaling pathway and Th17 cell differentiation were enriched by KEGG. SLBZP demonstrated significant therapeutic effects on psoriasis in mice, with alterations in skin pathology and biomarkers. Additionally, notable changes in gut microbiota composition were observed post-treatment, indicating a possible gut-skin axis involvement.Conclusion: This research has pinpointed lipid metabolism as a key pathway in the treatment of psoriasis with SLBZP. It explores how SLBZP’s modulation of gut microbiota and lipid metabolism can alleviate psoriasis, suggesting that balancing gut microbiota may reduce inflammation mediators and offer therapeutic benefits. This underscores lipid metabolism modulation as a potential new strategy in psoriasis treatment.

Hyperplasia of epidermal keratinocytes that depend on glycolysis is a new hallmark of psoriasis pathogenesis. Our previous studies demonstrated that PSORI-CM02 could halt the pathological progression of psoriasis by targeting inflammatory response and angiogenesis, but its effect(s) and mechanism(s) on proliferating keratinocytes remained unclear. In this study, we aim to identify components of PSORI-CM02 that are absorbed into the blood and to determine the effect(s) of PSORI-CM02 on keratinocyte proliferation and its molecular mechanism(s). We used the immortalized human epidermal keratinocyte cell line, HaCaT, as an in vitro model of proliferating keratinocytes and the imiquimod-induced psoriasis mouse (IMQ) as an in vivo model. Metabolite profiles of vehicle pharmaceutic serum (VPS), PSORI-CM02 pharmaceutic serum (PPS), and water extraction (PWE) were compared, and 23 components of PSORI-CM02 were identified that were absorbed into the blood of mice. Both PPS and PWE inhibited the proliferation of HaCaT cells and consequently reduced the expression of the proliferation marker ki67. Additionally, PPS and PWE reduced phosphorylation levels of mTOR pathway kinases. Seahorse experiments demonstrated that PPS significantly inhibited glycolysis, glycolytic capacity, and mitochondrial respiration, thus reducing ATP production in HaCaT cells. Upon treatments of PPS or PWE, hexokinase 2 (HK2) expression was significantly decreased, as observed from the set of glycolytic genes we screened. Finally, in the IMQ model, we observed that treatment with PSORI-CM02 or BPTES, an inhibitor of mTOR signaling, reduced hyperproliferation of epidermal keratinocytes, inhibited the expression of p-S6 and reduced the number of proliferating cell nuclear antigen (PCNA)-positive cells in lesioned skin. Taken together, we demonstrate that PSORI-CM02 has an anti-proliferative effect on psoriatic keratinocytes, at least in part, by inhibiting the mTOR/HK2/glycolysis axis.

Introduction: Psoriasis is an inflammatory autoimmune skin disease that is hard to cure and prone to relapse. Currently available global immunosuppressive agents for psoriasis may cause severe side effects, thus it is crucial to identify new therapeutic reagents and druggable signaling pathways for psoriasis.Methods: To check the effects of SOCE inhibitors on psoriasis, we used animal models, biochemical approaches, together with various imaging techniques, including calcium, confocal and FRET imaging.Results and discussion: Store operated calcium (Ca2+) entry (SOCE), mediated by STIM1 and Orai1, is crucial for the function of keratinocytes and immune cells, the two major players in psoriasis. Here we showed that a natural compound celastrol is a novel SOCE inhibitor, and it ameliorated the skin lesion and reduced PASI scores in imiquimod-induced psoriasis-like mice. Celastrol dose- and time-dependently inhibited SOCE in HEK cells and HaCaT cells, a keratinocyte cell line. Mechanistically, celastrol inhibited SOCE via its actions both on STIM1 and Orai1. It inhibited Ca2+ entry through constitutively-active Orai1 mutants independent of STIM1. Rather than blocking the conformational switch and oligomerization of STIM1 during SOCE activation, celastrol diminished the transition from oligomerized STIM1 into aggregates, thus locking STIM1 in a partially active state. As a result, it abolished the functional coupling between STIM1 and Orai1, diminishing SOCE signals. Overall, our findings identified a new SOCE inhibitor celastrol that suppresses psoriasis, suggesting that SOCE pathway may serve as a new druggable target for treating psoriasis.

Background: Probiotic and low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet are two commonly used management approaches for patients with irritable bowel syndrome (IBS). We aimed to evaluate the most effective combinations and components among different probiotics or low FODMAP diet through component network meta-analysis (NMA).Methods: We searched Embase, Ovid Medline, and Web of Science from inception to 21 January 2021. Randomized controlled trials (RCTs) examining the efficacy of probiotics and low FODMAP diet for IBS were included, with placebo, sham diet, or conventional treatments as controls. Binary outcomes were compared among treatments using the relative ratio (RR). A minimally contextualized framework recommended by the GRADE group was used to evaluate the certainty of evidence. The primary efficacy outcome was the relief of global IBS symptoms, and the secondary efficacy outcome was the reduction in IBS symptom scores or abdominal pain scores.Key Results: We included 76 RCTs (n = 8058) after screening 1940 articles. Eight RCTs were classified as low risk of bias. Standard network meta-analysis (NMA) showed that Lactobacillus (RR 1.74, 95% CI 1.22–2.48) and Bifidobacterium (RR 1.76, 95% CI 1.01–3.07) were the most effective for the primary efficacy outcome (high certainty evidence); component NMA showed that Bacillus (RR 5.67, 95% CI 1.88 to 17.08, p = 0.002) and Lactobacillus (RR 1.42, 95% CI 1.07 to 1.91, p = 0.017) were among the most effective components. The results of standard NMA and CNMA analysis of the improvement of overall IBS symptom scores or abdominal pain scores were consistent with this finding.Conclusion:Lactobacillus was the most effective component for the relief of IBS symptoms; Bifidobacterium and Bacillus were possibly effective and need further verification.Systematic Review Registration: website, identifier registration number.

Background: Emergence agitation (EA) is a common problem often observed in children after sevoflurane anesthesia, which can be prevented by dexmedetomidine and alfentanil. This study aims to compare the effectiveness of dexmedetomidine alone and with different doses of alfentanil in preventing EA in children under sevoflurane anesthesia.Materials and Methods: In a double-blind trial, 80 children (ASA I or II, 3–7 years old) undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia were randomly assigned into four groups: the control group, dexmedetomidine (DEX) group, dexmedetomidine plus 10 μg/kg alfentanil group (DEX + Alf1), and dexmedetomidine plus 20 μg/kg alfentanil group (DEX + ALf2). The incidence of EA was assessed with the Aono’s scale, and the severity of EA was evaluated with the Pediatric Anesthesia Emergence Delirium (PAED) scale. The time of tracheal extubation and time of wake were recorded. Postoperative pain and complications such as nausea and vomiting, cough, laryngospasm, and bradycardia were recorded.Results: The incidence of EA was 50% in the control group, 25% in the DEX group, and 5% in the DEX + Alf1 group, and it never happened in the DEX + Alf2 group. The Aono’s scale, the PAED scale, and the FLACC scale in the control group and the DEX group were significantly more than those in the DEX + Alf1 group and the DEX + Alf2 group after the tracheal extubation (p < 0.05). The time of tracheal extubation of the control group and the DEX group were significantly shorter than those in the DEX + Alf1 group and the DEX + Alf2 group (p < 0.05). The awakening time of the DEX + Alf2 group is significantly longer than those in other groups (p < 0.05). The case of postoperative nausea and vomiting in the DEX + Alf1 group was fewer than those in the other groups (p < 0.05). And, the cases of cough and laryngospasm and bronchospasm in the DEX + Alf1 group and the DEX + Alf2 group were significantly less than those in the control group and the DEX group after the tracheal extubation (p < 0.05).Conclusion: The combined administration of alfentanil and dexmedetomidine can reduce EA in children undergoing tonsillectomy alone and adenotonsillectomy with sevoflurane anesthesia. Dexmedetomidine plus 10 μg/kg alfentanil seems to be more appropriate than other dose combinations as it reduced EA and postoperative nausea and vomiting but did not prolong the time to awake.

Psoriasis is a chronic and refractory inflammatory and autoimmune-mediated cutaneous disease affecting approximately 2%–3% of the global population. Most of the current therapies could relieve symptoms rapidly, while the side effects cannot be negligible. Hence, it is urgent to explore much safer and more effective treatments. In the current work, we evaluated the potential beneficial effect of Punica granatum peel polysaccharides (PPPs) in an imiquimod-elicited psoriasis-like mouse model and unraveled their mechanism of action. Firstly, PPPs were isolated from P. granatum peels, and then the molecular weight was determined and monosaccharide analysis was performed. The results revealed that PPPs significantly ameliorated psoriasis-like skin lesions and reduced the Psoriasis Area and Severity Index (PASI) scores and transepidermal water loss (TEWL). PPPs also attenuated the expressions of CD3 and Ki67 in psoriasis-like mouse skin and suppressed the serum or skin levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-1β, IL-8, IL-17, and IL-23. Moreover, PPPs were able to upregulate the mRNA and protein expressions of aquaporin-3 (AQP3) and filaggrin (FLG) in the skin of mice. In addition, PPPs inhibited the NF-κB and STAT3 signaling pathways. Overall, these results indicated that PPPs ameliorated the symptoms of psoriasis through inhibition of the inflammatory cytokines by suppressing the NF-κB and STAT3 signaling pathways and improved skin barrier protection via enhancing AQP3 and FLG. These observations potentially contribute to providing theoretical and experimental evidence for the clinical application of PPPs for psoriasis.

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α–stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α–induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

Literary evidence depicts that aggregated β-amyloid (Aβ) leads to the pathogenesis of Alzheimer’s disease (AD). Although many traditional Chinese medicines (TCMs) are effective in treating neurodegenerative diseases, there is no effective way for identifying active compounds from their complicated chemical compositions. Instead of using a traditional herbal separation method with low efficiency, we herein apply UHPLC-DAD-TOF/MS for the accurate identification of the active compounds that inhibit the fibrillation of Aβ (1-42), via an evaluation of the peak area of individual chemical components in chromatogram, after incubation with an Aβ peptide. Using the neuroprotective herbal plant Scutellaria baicalensis (SB) as a study model, the inhibitory effect on Aβ by its individual compounds, were validated using the thioflavin-T (ThT) fluorescence assay, biolayer interferometry analysis, dot immunoblotting and native gel electrophoresis after UHPLC-DAD-TOF/MS analysis. The viability of cells after Aβ (1-42) incubation was further evaluated using both the tetrazolium dye (MTT) assay and flow cytometry analysis. Thirteen major chemical components in SB were identified by UHPLC-DAD-TOF/MS after incubation with Aβ (1–42). The peak areas of two components from SB, baicalein and baicalin, were significantly reduced after incubation with Aβ (1–42), compared to compounds alone, without incubation with Aβ (1–42). Consistently, both compounds inhibited the formation of Aβ (1–42) fibrils and increased the viability of cells after Aβ (1–42) incubation. Based on the hypothesis that active chemical components have to possess binding affinity to Aβ (1–42) to inhibit its fibrillation, a new application using UHPLC-DAD-TOF/MS for accurate identification of inhibitors from herbal plants on Aβ (1–42) fibrillation was developed.

Introduction: Cancer, particularly lung cancer, is a significant global healthcare challenge. Non-Small Cell Lung Cancer (NSCLC) constitutes 85% of cases. Patients often seek alternative therapies like Chinese medicine alongside Western treatments. This study investigates the survival outcomes and cost-effectiveness of adjunctive Chinese medicine therapy for NSCLC patients in Taiwan. Methods: We utilized the National Health Insurance Research Database in a retrospective cohort study from 2000 to 2018, focusing on NSCLC patients diagnosed between 2007 and 2013. After propensity score matching 1:5 ratio, then compared patients with and without adjunctive Chinese medicine therapy. Survival outcomes, cost-effectiveness, and sensitivity analyses were conducted. Results: The study involved 43,122 NSCLC patients with 5.76% receiving adjunctive Chinese medicine. There is no significant associated between the risk of death and adjuvant Chinese medicine therapy until 181-365 days of adjuvant treatment could reduce the risk of death (HR = 0.88, 95% CI: 0.80-0.98). Cost-effectiveness analysis showed an incremental cost-effectiveness ratio of 880,908 NT$/year. Conclusion: Adjunctive Chinese medicine therapy, particularly when administered for 181-365 days, significantly reduced the mortality risk among stage IV NSCLC patients. The cost-effectiveness aligns with willingness-to-pay thresholds, indicating economic benefit. [ABSTRACT FROM AUTHOR]

ShengFu oil is a compounded Chinese medicinal prescription, and provides antibacterial, anti-inflammatory, and analgesic effects, favoring burn wound repair. In this study, we aimed at investigating the effects of topical applications of ShengFu oil and its active ingredients in oral chemical burns and elucidating its regulatory effects on ß-catenin, COX-2, and MMP-9 expression caused by exposure to acid or alkaline agents. ShengFu oil contains 16 components, such as Frankincense, Radix Scutellariae and Radix Rehmanniae, and the main active ingredients from Frankincense are a-pinene, linalool, and n-octanol. Mouse models of oral chemical burns were induced by using glacial acetic acid or sodium hydroxide. Hematoxylin and eosin staining and immunohistochemical staining were used to detect the protein expressions of ß-catenin, COX-2, and MMP-9 in wound tissues. They were further quantified by multispectral imaging analysis to clarify the effective mechanism of ShengFu oil for intervening inflammatory factors and active components. Our results indicated that the application of ShengFu oil on oral chemical burns effectively stopped the oral burn bleeding and reduced the inflammatory reaction in the damaged tissues, demonstrating that ShengFu oil can promote wound tissue repair in burns caused by heat, acids, and alkalis. The immunohistochemical staining results illustrated that ShengFu oil and its active ingredients significantly reversed the abnormal changes in inflammation-related proteins in mouse tongue tissues that were caused by chemical burns. Regarding long-term toxic effects of ShengFu oil on the gastrointestinal tract, liver, and kidney system, the results of hematoxylin and eosin staining experiments depicted that ShengFu oil was safe and effective for liver, kidney, intestine, esophagus, and tongue. All of these demonstrated that ShengFu oil and its active ingredients are effective and safe in preventing and treating oral chemical burns by interfering with the inflammatory microenvironment. [ABSTRACT FROM AUTHOR]

We previously isolated an ethanol fraction of LSW (Liushenwan pill, a traditional Chinese medicine) which has been shown to prevent and treat liver cancer induced by nanodiethylnitrosamine (nanoDEN) in mice. In the present study, we utilized a high-pressure microfluidics technique to generate LSW lipid nanoparticles (nano-LSW) to reduce its toxicity, and enhance its inhibitory effect on tumor growth, and further evaluate its therapeutic effect using a nanoDEN-induced mouse model of liver cancer. Our in vitro results indicated that nano-LSW-low could induce apoptosis in HepG2 cells, but exhibited low toxicity in L02 cells. Furthermore, the in vivo results indicated that nano-LSW-low exerted minimal or no damage to normal hepatocytes, kidney, and small intestine tissues. In addition, our results showed that at the 20th week, the inflammatory infiltration in the mice in the model group increased severely, and partial pimelosis and fibrosis occurred. In contrast, the liver tissues in the mice treated with nano-LSW exhibited only slight inflammatory infiltration, without pimelosis and fibrosis. At the 30th week, 4 out of 5 liver tissues in the model group showed hyperplastic nodules by hematoxylin and eosin (H&E) staining. However, the liver tissues in the nano-LSW treatment group did not showed hyperplastic nodules. Immunohistochemical staining showed that, in contrast to the model group, the levels of COX-2, PCNA, β-catenin, and HMGB1 protein expressions were significantly lower in the nano-LSW-low group at the 20th and 30th week. Compared to model group, the COX-2, TNF-α, Smad-2, and TGF-β1 mRNA levels obviously decreased in the liver tissue after the nano-LSW-low treatment. Taken together, nano-LSW-low may serve as a potent therapeutic agent for preventing liver cancer by interfering with multiple critical factors for the tumor microenvironment during oncogenesis.

How β-catenin/COX-2 contribute to inflammation-induced fibroblasts migration remains poorly understood. Therefore, in this study, lipopolysaccharide (LPS) was used as a stimulus to accelerate the migration of NIH3T3 cells, which mimicked the tissue repair process. LPS treatment increased the cell migration in concentration-and time-dependent manner. And NS398, a COX-2 inhibitor, inhibited LPS-induced NIH3T3 cells migration. DKK-1, an antagonist of the Wnt/β-catenin signaling, also inhibited that migration. However, TWS119, an inducer of β-catenin via GSK-3β, increased the cell migration. LPS or TWS119 treatment increased COX-2, β-catenin, TGF-β1, and HMGB-1 expressions, and that could be attenuated by NS398 or DKK-1 addition. LPS induced the PGE2 production, and PGE2 increased the expression and nuclear translocation of β-catenin, while EP2 blocker, AH6809, alleviated those effects. TWS119 increased the luciferase activity in the COX-2 promoter. In conclusion, LPS stimulated the NIH3T3 fibroblasts migration through a positive feedback between β-catenin and COX-2, in which PGE2, EP2, TGF-β1, and HMGB-1 played as signal molecules.