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

BackgroundRecurrent respiratory tract infections (RRTIs) have a negative impact on both children’s health and family wellbeing. Deficiency of ZhengQi used to be an instinct factor driving RRTI in Traditional Chinese Medicine (TCM). Our clinical observations suggest that children with gastrointestinal heat retention syndrome (GHRS) may have a greater risk of catching respiratory tract infections (RTIs). GHRS is a new predisposing factor for RRTI and it is dietary related. This study is aimed to explore association between GHRS and RRTI.MethodsA prospective cohort study has been conducted in Beijing, China; children aged 1–18 were enrolled. TCM symptoms, demographic and physiological characteristics were recorded by using semi-structured questionnaire. GHRS was considered as a predisposing factor. Children were followed up for next 12 months. We contacted with their parents using a face-to-face questionnaire survey, via email or phone every 3 months. Episodes of RTIs were recorded in detail.ResultsThree hundred thirty four children were enrolled and 307 (91.92 %) followed up for 12 months. The incidence of RTI was 4.32 episodes per child-year (95 % CI 4.03–4.61). 69 (43.13 %) children in the group with GHRS suffered from RRTI; there were 48 (32.65 %) children in group without GHRS. The risk ratio (RR) value of RRTI occurrence was 1.32 (95 % CI 0.91–1.91, P = 0.139), and the attributable risk percent (AR%) was 24.28 %. Dry stool and irritability were positively correlated with RTI episodes, age and BMI were negatively correlated with RTI episodes in a linear regression model. Dry stool (OR = 1.510) was positively correlated with RRTI occurrence, age (OR = 0.889) and BMI (OR = 0.858) were negatively correlated with RRTI occurrence in our logistic regression model.ConclusionsGHRS is associated with RRTI in this cohort. Dry stool was positively associated with RRTI, and BMI was negatively associated with RRTI. Studies with larger sample size and longer follow up are needed to further evaluate this association. Relieving GHRS should be considered when TCM practitioners treat RRTI children, and this may protect children from suffering RTIs.Trial registrationChinese Clinical Trial Registry Number: ChiCTR-CCH-13003756

Objective To explore changes in the gut microbiota (GM), urine metabolome and plasma proteome in individuals with allergies using multiomics analyses, and identify the key components and mechanism. Methods This was a cross-sectional study. All subjects were recruited to collect fecal, urine and blood samples. 16S rDNA sequencing was used to analyze the structure and function of the GM, liquid chromatography mass spectrometry was used to quantify metabolites in the urine, and data-independent acquisition quantitative proteome analysis was used to detect proteins in the plasma. Differences in GM, urine metabolites and plasma proteins between allergic and healthy individuals were displayed using principal component analysis (PCoA) and heatmap, and the co-occurrence network was visualized in Cytoscape using Spearman correlation among differential predominant genera, metabolites and proteins. The functional analysis was performed according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) dataset. The allergy-related cytokines, IL-4, IL-6 and IL-13, were measured to evaluate the effect of indole derivatives on LPS-induced macrophage activation. Results GM α indexes, β distances and the relative abundance of the core differential genera in the allergic group were different from those of healthy individuals, which resulted in a separate distribution in the PCoA and enterotypes. Similarly, the concentrations of 393 metabolites and 144 proteins were different between allergic and healthy individuals. Then, 634 significant correlations were identified among 6 predominant differential genera, 24 differential metabolites and 104 differential proteins, 301 of which were negative and 333 of which were positive. Notably, a core network centered on tryptophan metabolites, indole-3-butyric acid (IBA) and indole-3-lactic acid (ILA), displayed high consistency with the results of KEGG pathway analysis. In the LPS-stimulated macrophages, IBA reduced the expression of IL-4 and IL-6, and ILA inhibited the upregulation of IL-6. Conclusion The GM, urine metabolome and plasma proteome underwent systematic change in allergic individuals compared to healthy individuals, among which indole derivatives from tryptophan metabolism might play key roles in the progression of allergies and could serve as therapeutic targets of allergy.

Botanicals have attracted much attention in the field of anti-inflammatory due to their good pharmacological activity and efficacy. Andrographis paniculata is a natural plant ingredient that is widely used around the world. Andrographolide is the main active ingredient derived from Andrographis paniculata, which has a good effect on the treatment of inflammatory diseases. This article reviews the application, anti-inflammatory mechanism and molecular targets of andrographolide in different inflammatory diseases, including respiratory, digestive, immune, nervous, cardiovascular, skeletal, and tumor system diseases. And describe its toxicity and explain its safety. Studies have shown that andrographolide can be used to treat inflammatory lesions of various systemic diseases. In particular, it acts on many inflammation-related signalling pathways. The future direction of andrographolide research is also introduced, as is the recent research that indicates its potential clinical application as an anti-inflammatory agent.

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