Jiawei guomin decoction regulates the degranulation of mast cells in atopic dermatitis mice via the HIS/PAR-2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Guomin decoction (GMD) is a traditional Chinese medicine commonly used in clinical practice. It has traditionally been used to treat all allergic diseases. Currently, Jiawei Guomin Decoction (JWGMD) is used to treat sensitive skin after initial therapy. Although it has a significant clinical therapeutic effect, the exact role of mast cell degranulation in treating atopic dermatitis (AD) is still unclear. AIM OF THE STUDY: GMD and JWGMD can both treat allergic diseases, while JWGMD focuses on skin allergies. This study aims to explore the potential effect of JWGMD on the degranulation of mast cells in an AD mouse model induced by 2,4-dinitrofluorobenzene (DNFB) and investigate the effectiveness of JWGMD in alleviating disease progression to further provide specific therapeutic targets for treating AD. MATERIALS AND METHODS: The scratching times and skin lesions of model mice induced by DNFB were observed, and skin tissues were collected for subsequent measurement. Histopathological changes in the back skin of mice were observed by haematoxylin eosin (H&E) staining, Toluidine blue staining was used to detect the degranulation of mouse skin mast cells, and the relationship between the expression of histamine (HIS), mast cell tryptase (MCT) and mast cell degranulation was analysed by enzyme-linked immunosorbent assay (ELISA). The expression of protease-activated receptor-2 (PAR-2), histamine 1 receptor (H1R), H2R, H4R and MCT proteins in AD mice was detected by Western blot (WB). Immunofluorescence assay (IFA) further confirmed the localization of PAR-2, H1R, H2R, H4R, and MCT proteins in the skin. Quantitative real-time PCR (qPCR) was used to determine PAR-2, H1R, H2R and H4R mRNA levels in skin lesions to further clarify the mechanism by which JWGMD amplifies mast cell degranulation in AD. In addition, a reliable ultrahigh-performance liquid chromatography-quadrupole electrostatic field orbitrap mass spectrometry (UPLC-QE-MS) nontargeted metabolomics analysis was performed to analyse the differences in metabolite abundance between GMD and JWGMD, and these results were used to identify the active components in JWGMD that may have antipruritic and anti-inflammatory properties and inhibit mast cell degranulation. RESULTS: After intermittent stimulation with DNFB, the skin lesions showed extensive desquamation, dryness, scabbing, skin thickening, and slight bleeding. Both treatments alleviated this phenomenon and reduced the number of scratches, with JWGMD being the most effective. JWGMD can significantly reduce inflammatory cell infiltration, oedema, and some capillary neogenesis in mice and reduce the degranulation of mast cells. The ELISA results showed that JWGMD can increase the levels of MCT and HIS proteins. The WB and IFA results demonstrated that JWGMD reduced the expression levels of PAR-2, H1R, H4R, and MCT proteins in skin lesions, with protein localization mainly in the epidermal layer, while H2R protein levels were increased and mainly localized in the dermis. In addition, JWGMD downregulates the mRNA expression of PAR-2, H1R, H2R, and H4R. Interestingly, through UPLC-QE-MS nontargeted metabolomic analysis, we detected the anti-inflammatory and antiallergy active substances in JWGMD, such as methyl eugenol, dictamnine and sinapine. CONCLUSIONS: JWGMD may alleviate itching through methyl syringol, dictamnine, sinapine and other substances, and its mechanism may be related to inhibiting the HIS/PAR-2 pathway in AD model mice and further regulating the self-amplification of mast cell degranulation. JWGMD is a potential drug for treating AD. Therefore, it deserves continuous attention and research.

Effect of summer acupoint application treatment (SAAT) on gut microbiota in healthy Asian adults: A randomized controlled trial.

Acupoint application has served as an important complementary and adjunctive therapy in China. The purpose of this study is to explore the impact of summer acupoint application treatment (SAAT) on the abundance and biological structure of gut microbiota in healthy Asian adults. Based on the CONSORT guidelines, 72 healthy adults were included in this study, randomly divided into 2 groups, receiving either traditional (acupoint application within known relevant meridians, Group A) or sham (treated with placebo prepared by mixing the equal amount of starch and water, Group B) SAAT. SAAT stickers include extracts from Rhizoma Corydalis, Sinapis alba, Euphorbia kansui, Asari Herba, and the treatment group received 3 sessions of SAAT for 24 months, administered to BL13 (Feishu), BL17 (Geshu), BL20 (Pishu), and BL23 (Shenshu) acupoints. Fecal microbial analyses via ribosomal ribonucleic acid (rRNA) sequencing were performed on donor stool samples before and after 2 years of SAAT or placebo treatment to analyze the abundances, diversity, and structure of gut microbiota. No significant baseline differences were present between groups. At the phylum level, the baseline relative abundance of Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria was identified in fecal samples collected from each group. After treatment, the relative abundance of Firmicutes was significantly increased in both groups (P < .05). Notably, a significant decrease in the relative abundance of Fusobacteria was observed in the SAAT treatment group (P < .001), while the abundance of Bacteroidetes was decreased significantly in the placebo group (P < .05). At the genus level, the relative abundance of Faecalibacterium and Subdoligranulum species in the 2 groups were all significantly increased (P < .05). In addition, a significant reduction in the relative abundance of Blautia, Bacteroides, and Dorea in Group A (P < .05) and Eubacterium hallii group and Anaerostipes (P < .05) in Group B was observed after treatment. Our findings indicated SAAT substantially influenced the bacterial community structure in the gut microbiota of healthy Asian adults, which might serve as potential therapeutic targets for related diseases, and provided a foundation for future studies aimed at elucidating the microbial mechanisms underlying SAAT for the treatment of various conditions such as obesity, insulin resistance, irritable bowel syndrome.

Efficacy and safety of Chinese herbal medicine in the treatment of chronic pruritus: A systematic review and meta-analysis of randomized controlled trials.

Background: Chronic pruritus (CP) is a common and aggravating symptom associated with skin and systemic diseases. Although clinical reports suggest that Chinese herbal medicine (CHM) is safe and effective in Chronic pruritus treatment, evidence to prove it is lacking. Therefore, in this review, we evaluated the therapeutic effects and safety of Chinese herbal medicine for the treatment of Chronic pruritus. Methods: Nine databases were searched for relevant randomized controlled trials (RCTs) from the inception of the database to 20 April 2022. The randomized controlled trials that compared the treatment of Chinese herbal medicine or a combination of Chinese herbal medicine and conventional western medicine treatment (WM) with western medicine treatment intervention for patients with Chronic pruritus were selected. We evaluated the effects of treatment with Chinese herbal medicine on the degree of pruritus, the Dermatology Life Quality Index (DLQI) score, response rate, recurrence rate, and incidence of adverse events in patients with Chronic pruritus. The risk of bias in each trial was evaluated using the Cochrane Collaboration tool. The RevMan software (version 5.3) was used for performing meta-analyses to determine the comparative effects. Results: Twenty-four randomized controlled trials were included, compared with placebo, moderate-quality evidence from one study showed that Chinese herbal medicine was associated with reduced visual analogue scale (VAS) (MD: -2.08; 95% CI = -2.34 to -1.82). Compared with western medicine treatment, low-to moderate-quality evidence from 8 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = -1.80, 95% CI = -2.98 to -.62), and 7 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.26; 95% CI = 1.19-1.34). Compared with combination of Chinese herbal medicine and western medicine treatment, 16 studies indicated that Chinese herbal medicine was associated with reduced visual analogue scale, 4 studies indicated that Chinese herbal medicine was associated with reduced Dermatology Life Quality Index (MD = -2.37, 95% CI = -2.61 to -2.13), and 13 studies indicated that Chinese herbal medicine was associated with improved Effective rate (RR: 1.28; 95% CI = 1.21-1.36). No significant difference in the occurrence of adverse events in using Chinese herbal medicine or western medicine treatment was reported. Conclusion: The efficacy of Chinese herbal medicine used with or without western medicine treatment was better than western medicine treatment in treating chronic pruritus. However, only a few good studies are available regarding Chronic pruritus, and thus, high-quality studies are necessary to validate the conclusions of this study.

Multi-Pharmaceutical Activities of Chinese Herbal Polysaccharides in the Treatment of Pulmonary Fibrosis: Concept and Future Prospects.

Pulmonary fibrosis is a fatal chronic progressive respiratory disease, characterized by continuous scarring of the lung parenchyma, leading to respiratory failure and death. The incidence of PF has increased over time. There are drugs, yet, there are some limitations. Hence, it is of importance to find new therapies and new drugs to replace the treatment of pulmonary fibrosis. In recent years, there have been a great number of research reports on the treatment of traditional Chinese medicine polysaccharides in various system fields. Among them, the treatment of PF has also gained extensive attention. This review summarized the source of polysaccharides, the drug activity of traditional Chinese medicine, and the protective effects on targets of Pulmonary fibrosis. We hope it can inspire researchers to design and develop polysaccharides, serving as a reference for potential clinical therapeutic drugs.

Associations of regular glucosamine use with all-cause and cause-specific mortality: a large prospective cohort study.

OBJECTIVES: To evaluate the associations of regular glucosamine use with all-cause and cause-specific mortality in a large prospective cohort. METHODS: This population-based prospective cohort study included 495 077 women and men (mean (SD) age, 56.6 (8.1) years) from the UK Biobank study. Participants were recruited from 2006 to 2010 and were followed up through 2018. We evaluated all-cause mortality and mortality due to cardiovascular disease (CVD), cancer, respiratory and digestive disease. HRs and 95% CIs for all-cause and cause-specific mortality were calculated using Cox proportional hazards models with adjustment for potential confounding variables. RESULTS: At baseline, 19.1% of the participants reported regular use of glucosamine supplements. During a median follow-up of 8.9 years (IQR 8.3-9.7 years), 19 882 all-cause deaths were recorded, including 3802 CVD deaths, 8090 cancer deaths, 3380 respiratory disease deaths and 1061 digestive disease deaths. In multivariable adjusted analyses, the HRs associated with glucosamine use were 0.85 (95% CI 0.82 to 0.89) for all-cause mortality, 0.82 (95% CI 0.74 to 0.90) for CVD mortality, 0.94 (95% CI 0.88 to 0.99) for cancer mortality, 0.73 (95% CI 0.66 to 0.81) for respiratory mortality and 0.74 (95% CI 0.62 to 0.90) for digestive mortality. The inverse associations of glucosamine use with all-cause mortality seemed to be somewhat stronger among current than non-current smokers (p for interaction=0.00080). CONCLUSIONS: Regular glucosamine supplementation was associated with lower mortality due to all causes, cancer, CVD, respiratory and digestive diseases.

Associations of habitual fish oil supplementation with cardiovascular outcomes and all cause mortality: evidence from a large population based cohort study.

OBJECTIVES: To evaluate the associations of habitual fish oil supplementation with cardiovascular disease (CVD) and mortality in a large prospective cohort. DESIGN: Population based, prospective cohort study. SETTING: UK Biobank. PARTICIPANTS: A total of 427 678 men and women aged between 40 and 69 who had no CVD or cancer at baseline were enrolled between 2006 and 2010 and followed up to the end of 2018. MAIN EXPOSURE: All participants answered questions on the habitual use of supplements, including fish oil. MAIN OUTCOME MEASURES: All cause mortality, CVD mortality, and CVD events. RESULTS: At baseline, 133 438 (31.2%) of the 427 678 participants reported habitual use of fish oil supplements. The multivariable adjusted hazard ratios for habitual users of fish oil versus non-users were 0.87 (95% confidence interval 0.83 to 0.90) for all cause mortality, 0.84 (0.78 to 0.91) for CVD mortality, and 0.93 (0.90 to 0.96) for incident CVD events. For CVD events, the association seemed to be stronger among those with prevalent hypertension (P for interaction=0.005). CONCLUSIONS: Habitual use of fish oil seems to be associated with a lower risk of all cause and CVD mortality and to provide a marginal benefit against CVD events among the general population.

Plasma 25-Hydroxyvitamin D Concentrations Are Inversely Associated with All-Cause Mortality among a Prospective Cohort of Chinese Adults Aged ≥80 Years.

BACKGROUND: High concentrations of plasma 25-hydroxyvitamin D [25(OH)D], a marker of circulating vitamin D, have been associated with a lower risk of mortality in epidemiologic studies of multiple populations, but the association for Chinese adults aged ≥80 y (oldest old) remains unclear. OBJECTIVE: We investigated the association between plasma [25(OH)D] concentration and all-cause mortality among Chinese adults aged ≥80 y. DESIGN: The present study is a prospective cohort study of 2185 Chinese older adults (median age: 93 y). Prospective all-cause mortality data were analyzed for survival in relation to plasma 25(OH)D using Cox proportional hazards regression models, with adjustments for potential sociodemographic and lifestyle confounders and biomarkers. The associations were measured with HR and 95% CIs. RESULTS: The median plasma 25(OH)D concentration was 34.4 nmol/L at baseline. Over the 5466 person-year follow-up period, 1100 deaths were identified. Men and women were analyzed together as no effect modification by sex was found. After adjusting for multiple potential confounders, the risk of all-cause mortality decreased as the plasma 25(OH)D concentration increased (P-trend <0.01). Compared with the lowest age-specific quartile of plasma 25(OH)D, the adjusted HRs for mortality for the second, third, and fourth age-specific quartiles were 0.72 (95% CI: 0.57, 0.90), 0.73 (95% CI: 0.58, 0.93), and 0.61 (95% CI: 0.47, 0.81), respectively. The observed associations were broadly consistent across age and other subgroups. Sensitivity analyses generated similar results after excluding participants who died within 2 y of follow-up or after further adjustment for ethnicity and chronic diseases. CONCLUSIONS: A higher plasma 25-hydroxyvitamin D concentration was associated with a reduced risk of all-cause mortality among Chinese adults aged ≥80 y. This observed inverse association warrants further investigation in randomized controlled trials testing vitamin D supplementation in this age group.

DietaryFish and Long-Chain n-3 Polyunsaturated Fatty Acids Intake and Risk of Atrial Fibrillation: A Meta-Analysis.

Findings on the association between long-term intake of fish or long-chain n-3 polyunsaturated fatty acids (PUFAs) and risk of atrial fibrillation (AF) are inconsistent in observational studies. We conducted a meta-analysis of prospective studies to separately examine the associations between fish consumption and dietary intake of n-3 PUFAs with the risk of AF. A systematic search was conducted in PubMed and Embase to identify relevant studies. Risk estimates were combined using a random-effect model. Seven prospective cohort studies covering 206,811 participants and 12,913 AF cases were eligible. The summary relative risk of AF for the highest vs. lowest category of fish consumption and dietary intake of n-3 PUFAs was 1.01(95% confidence interval: 0.94-1.09) and 1.03 (95% confidence interval: 0.97-1.09), respectively. These null associations persisted in subgroup and dose-response analyses. There was little evidence of publication bias. This meta-analysis suggests that neither long-term intake of fish, nor of n-3 PUFAs were significantly associated with lower risk of AF.

Curcumin treatment alters ERK-1/2 signaling in vitro and inhibits nasopharyngeal carcinoma proliferation in mouse xenografts.

Curcumin, a plant phenol, has been used for centuries in traditional medicines for its anti-inflammatory and anti-neoplastic properties. The compound is believed to act on a range of proteins involved in cell cycle regulation. In this study, the effect of curcumin on ERK-1/2 pathway protein expression and on proliferation of nasopharyngeal carcinoma cells was investigated. CNE-2Z nasopharyngeal carcinoma cells were cultured with 10, 20, 40, or 80 µM curcumin for 24 h before proliferation was assessed by MTT colorimetry. Cell proliferation was increasingly inhibited as the concentration of curcumin increased (P<0.005). Additionally, Western blotting revealed that expression of p-ERK-1/2, MMP-9, and TIMP-1 was altered following curcumin treatment, also in a dose-dependent manner. Expression of p-ERK-1/2 and MMP-9 decreased, while expression of TIMP-1 increased (P<0.05). Finally, CNE-2Z cells were xenografted under the skin of 18 nude mice. Mice were treated with vehicle only (control), 24 mg/kg curcumin (low-dose group), or 50 mg/kg curcumin (high-dose group) every other day for 40 days beginning 24 h after xenografting. Compared to tumors from the control group, the volume and weight of xenograft tumors was significantly lower in both curcumin groups, with a higher magnitude of difference in the high-dose curcumin group (P<0.05). These results indicate that curcumin treatment can inhibit proliferation of nasopharyngeal carcinoma cells and alter expression of proteins in the ERK-1/2 signaling pathway. Therefore, curcumin warrants further investigation as a potential treatment for nasopharyngeal cancer.

[Application of quantitative evaluation on multicomponent drug interaction in anti-HIV research].

OBJECTIVE: To quantitatively evaluate mutual relations of 4 component drugs in anti-HIV action. METHODS: The effect of TCM four components on cell growth was detected using MTT assay. The antiviral effects of 4 components were observed at the maximal nonvenomous dose. The combination index (CI) value of combined two or four components were calculated using median-effect principle. The mutual relations of two or four components for antiviral actions were assessed using CI. RESULTS: Synergism was dominant in combination of A and B, and the effect was dose-dependent. Antagonism was dominant in combination of C and D, and the effect was dose-dependent. But the combination of A, B, C, and D was synergistic when the inhibition rate was over 10%. CONCLUSION: Median-effect principle can be used to quantitatively assess the anti-HIV effect of four components.