Integration of gut microbiota and metabolomics for the hematopoiesis of Siwu paste on anemia rats.

Background: To investigate the regulation mechanism of hematopoiesis of Siwu paste (SWP) in anemia rats, which is a classic Chinese prescription used for nourishing blood or blood deficiency over 1000 years. Methods: Blood cell and biochemical analysis were used to evaluate the hematopoietic function of SWP in anemia rats. The intestinal microbial composition was analyzed with 16S rRNA gene sequencing, and the metabolites were profiled using UPLC-TripleTOF system nontargeting metabolomics. Results: SWP can improve the levels of red blood cells, hemoglobin, platelet, hematocrit value, white blood cells, lymphocyte, EPO, TPO, and GM-CSF in anemia rats, and significantly change the microbial community and its metabolites. The correlation analysis of intestinal microbiota-hematopoietic efficacy shows that 13 kinds of different intestinal flora were related to hematopoietic efficacy, in which Prevotella_1, Prevotella_9, Lactobacillus, and norank_f__Muribaculaceae were significantly positively correlated with hematopoiesis, nine kinds of intestinal flora are negatively correlated with hematopoietic effect. Compared with anemia rats, 218 potential metabolic biomarkers and 36 metabolites with significant differences were identified in the SWP treatment group, and the key metabolites were mainly amino acids and lipids. An in-depth analysis of metabolic pathways showed that SWP mainly affected 7 metabolic pathways, including aminobenzoic acid degradation and tryptophan metabolism. Conclusion: The study provides novel insights into the regulation of hematopoiesis of SWP in anemia rats that were correlated with gut microbiota and the metabolites, which through the restoration of the firmicutes/bacteroidetes ratio.

Polygonatum cyrtonema Hua Polysaccharides Protect BV2 Microglia Relief Oxidative Stress and Ferroptosis by Regulating NRF2/HO-1 Pathway.

Neuronal-regulated cell death (RCD) due to the accumulation of ROS within the central nervous system (CNS) is one of the crucial causes of central system diseases. Caspase-dependent apoptosis is the only form of RCD. As research progressed, several nonapoptotic cell death pathway RCDs were identified. Ferroptosis is a nonapoptotic RCD characterized by lipid peroxidation and plasma membrane damage. Polygonatum cyrtonema Hua. Polysaccharides (PCP) are an effective antioxidant. Based on this, the protective effect and mechanism of PCP against H2O2-induced microglial injury were investigated. Furthermore, the protective mechanism of PCP against ferroptosis in microglia was explored. Our results indicated that PCP could reduce oxidative stress-induced ROS accumulation by activating the NRF2/HO-1 signaling pathway, thus attenuating RCD in microglia. Subsequent studies have revealed that PCP alleviates ferroptosis in microglia due to protein levels of ERASTIN/RSL3 inhibitor SLC7A11/GPX4 by activating the NRF2/HO-1 signaling pathway. Therefore, we hypothesized that PCP exerts antioxidative and anti-ferroptosis effects by activating the expression of the NRF2/HO-1 pathway. This facilitates new ideas for clinically effective prevention and treatment of diseases due to accumulated reactive oxygen species in the CNS. Simultaneously, PCP has the development potential as a new drug candidate for treating CNS diseases.

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.