Integrated Network Pharmacology and Metabolomics Analysis to Reveal the Potential Mechanism of Siwu Paste on Aplastic Anemia Induced by Chemotherapy Drugs.

Purpose: This study aimed to reveal the multicomponent synergy mechanisms of SWP based on network pharmacology and metabolomics for exploring the relationships of active ingredients, biological targets, and crucial metabolic pathways. Materials: Network pharmacology, including TRRUST, GO, and KEGG, enrichment was used to discover the active ingredients and potential regulation mechanisms of SWP. LC-MS and multivariate data analysis method were further applied to analyze serum metabolomics profiling for discovering the potential metabolic mechanisms of SWP on AA induced by Cyclophosphamide (CTX) and 1-Acetyl-2-phenylhydrazine (APH). Results: A total of 27 important bioactive ingredients meeting the ADME (absorption, distribution, metabolism, and excretion) screening criteria from SWP were selected. Interaction networks were constructed and validated based on the 10 associated ingredients with the relevant targets. A total of 125 biomarkers were found by Metabolomics approach, which associated with the development of AA, mainly involved in amino acid metabolism and lipid metabolism. While SWP can reverse the above 12 metabolites changed by AA. Network analysis revealed the synergistic effects of SWP through the 43 crucial pathways, including Sphingolipid signaling pathway, Sphingolipid metabolism, Arginine and proline metabolism, VEGF signaling pathway, Estrogen signaling pathway. Conclusion: The study suggested that SWP is a useful alternative for the treatment of AA induced by CTX + APH. Its potential mechanisms are to improve hematopoietic microenvironment and promote bone marrow hematopoiesis therapies.

Siwu Paste protects bone marrow hematopoietic function in rats with blood deficiency syndrome by regulating TLR4/NF-κB/NLRP3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Siwu Paste (SWP) was recorded in the first national Pharmacopoeia of China, "Tai Ping Hui Min He Ji Ju Fang", it showed excellent effects in regulating all syndromes relevant to blood. AIM OF THE STUDY: This study aimed to investigate the protective effects of Siwu Paste (SWP) on bone marrow hematopoietic by using rats' model with blood deficiency syndrome induced by chemotherapy. MATERIALS AND METHODS: Animal model with blood deficiency syndrome was successfully established by evaluating their peripheral blood cell level and erythrocyte membrane energy metabolism enzyme activity. Serum hematopoietic cytokine levels were detected by using Enzyme-linked immunosorbent assay (ELISA). Hematoxylin-Eosin (HE) staining method was used to observe the pathological morphology of femur bone marrow, and the viability of BMSC was detected by Cell Counting Kit (CCK-8). Furthermore, the expression of toll-like receptor 4 (TLR4), nuclear transcription factor kB (NF-κB), and NOD-like receptor protein 3 (NLRP3) protein in femur bone marrow were detected by using Western-blotting and High-content cell imaging analysis system (HCA). RESULTS: Obtained results showed that SWP could significantly improve the status of anemia, regulate the expressions of serum hematopoietic cytokines, and protect bone marrow hematopoietic cells. Furthermore, the expressions of TLR4, NF-κB, and NLRP3 protein were inhibited in bone marrow hematopoietic cells. CONCLUSIONS: Siwu Paste (SWP) could recover the bone marrow hematopoietic functions in rats with blood deficiency syndrome. The therapeutic mechanism may be related to the regulation of serum hematopoietic cytokines, and inhibition of TLR4/NF-κB/NLRP3 signaling pathway.

Influence of polluted SY River on child growth and sex hormones.

OBJECTIVE: To investigate the influence of the polluted SY River on children's growth and sex hormones, and provide scientific data for assessment of the polluted status of the SY River. METHODS: The study areas were selected randomly from the SY River Basin. Lead (Pb), mercury (Hg), arsenic (As), phthalates (DEP, DBP, DMP, DEHP), and bisphenol A (BPA) were measured both in the river water and in the drinking water. School children were selected by cluster sampling (n=154). Physical development indexes (height, weight, bust-circumference, and skinfold thickness) and sex hormones [testosterone (T) and estradiol (E2)] were measured for all the children. RESULTS: The contents of Pb and Hg exceeded Class V standards of surface water quality in each section of the river and other indicators exceeded Class III. Compared to the control area, the concentrations of Pb, Hg, As, BPA, DEP, and DBP in the drinking water were significantly higher than in the polluted area (P<0.05). Children from the control area had significantly lower E2 and T than children from the polluted area (P<0.05). Among anthropometric results, only skinfold thickness had statistically significant difference between the two groups (P<0.05), while the other indexes showed no significant differences between the two groups (P>0.05). CONCLUSION: The drinking water has been polluted by the SY River and affected serum sex hormone levels of children living in the polluted area.