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Objectives: High reactive oxygen species (ROS) levels lead to cell death, and the testes are among the most vulnerable organs to oxidative damage. Rg1, an active ingredient extracted from the natural medicine ginseng, has potential anti-inflammatory, antioxidant and antiapoptotic properties. Our previous studies showed that Rg1 can effectively improve spermatogenic function in mice, but the specific mechanism remains unclear. The purpose of this study was to investigate the effect of Rg1 on oxidative stress and spermatogonium apoptosis in D-gal-induced testicular toxicity and elucidate the associated mechanism. Methods: Male C57BL/6 mice at 6–8 weeks of age were intraperitoneally injected with D-gal (200 mg/kg) for 42 days to establish a testicular injury model, and on day 16, 40 mg/kg Rg1-rich saline was injected intraperitoneally. Concurrently, we established an in vitro model of D-gal-damaged spermatogonia, which was treated with Rg1. Results: We found that treatment with the ginsenoside Rg1 reduced D-gal-induced oxidative stress and spermatogonium apoptosis in vivo and in vitro. Mechanistically, we found that Rg1 activated Akt/bad signaling and reduced D-gal-induced spermatogonium apoptosis. Discussion: We provide evidence showing that the antioxidant effect of Rg1 is mediated by the Akt/GSK-3β/NRF2 axis. Based on these findings, we consider Rg1 a potential treatment for testicular oxidative damage. [ABSTRACT FROM AUTHOR]

5-Fluorouracil (5-FU)-injured stromal cells may cause chronic bone marrow suppression; however, the underlying mechanism remains unclear. Angelica sinensis polysaccharide (ASP), the main biologically active ingredient of the Chinese herb, Angelica sinensis (Oliv.) Diels (Apiaceae), may enrich the blood and promote antioxidation. This study investigated the protective antioxidative effects of ASP on perivascular mesenchymal progenitors (PMPs) and their interactions with hematopoietic cells. PMPs were dissociated from C57BL/6 mouse femur and tibia and were subsequently divided into the control, ASP (0.1 g/L), 5-FU (0.025 g/L), and 5-FU + ASP (pre-treatment with 0.1 g/L ASP for 6 h, together with 0.025 g/L 5-FU) then cultured for 48 h. Hematopoietic cells were co-cultured on these feeder layers for 24 h. Cell proliferation, senescence, apoptosis, and oxidative indices were detected, along with stromal osteogenic and adipogenic differentiation potentials. Intercellular and intracellular signaling was analyzed by real-time quantitative reverse transcription polymerase chain reaction and Western blotting. ASP ameliorated the reactive oxygen species production/scavenge balance in PMPs; improved osteogenic differentiation; increased SCF, CXCL12, VLA-4/VCAM-1, ICAM-1/LFA1, and TPO/MPL, Ang-1/Tie-2 gene expression. Further, the ASP-treated feeder layer alleviated hematopoietic cells senescence (from 21.9 ± 1.47 to 12.1 ± 1.13); decreased P53, P21, p-GSK-3β, β-catenin and cyclin-D1 protein expression, and increased glycogen synthase kinase (GSK)-3β protein expression in co-cultured hematopoietic cells. ASP delayed oxidative stress-induced premature senescence of 5-FU-treated feeder co-cultured hematopoietic cells via down-regulation of overactivated Wnt/β-catenin signaling. These findings provide a new strategy for alleviating myelosuppressive stress. [ABSTRACT FROM AUTHOR]

Angelica Sinensis polysaccharide (ASP), the main active component of Angelica sinensis, possesses antioxidative and anti-apoptotic properties. In this study, we have investigated the antagonistic effect of ASP on 5-FU-induced injury of mouse spleen in vivo and splenocytes in vitro, and its possible mechanism. Our results showed that ASP inhibited 5-FU-induced decreases in spleen weight and organ index in mice, restored the number of peripheral blood leukocytes and lymphocytes, repaired spleen structure disorder and functional impairment, rescued serum IL-2, IL-6, and IFN-γ levels, and relieved 5-FU-induced mitochondrial swelling， reduced the oxidant accumulation including MDA and ROS, whereas increasing the activities of GSH, SOD and CAT. The mechanism may be related to ASP downregulation of Keap1 protein expression thus motivating the nuclear translocation of Nrf2. Furthermore, ASP alleviated the apoptosis of spleens in vivo and splenocytes in vitro, and reactivated PI3K / AKT signalling. In conclusion, the protective effect of ASP on spleens and splenocytes may be related to the reduction of oxidative stress and apoptosis via reactivation of Nrf2 and PI3K/AKT pathways. This study has provided a new protective agent for minimizing the spleen injury caused by 5-FU and a new idea for improving the prognosis of chemotherapy patients. [Display omitted] • ASP restores spleen immune function by alleviating 5-FU-induced apoptosis and oxidative stress. • ASP ameliorates 5-FU-induced oxidative stress through activation of Nrf2. • ASP reactivates PI3K/AKT pathways inhibited by 5-FU to reduce apoptosis. [ABSTRACT FROM AUTHOR]

B-lymphocytopenia among myelosuppression is the most intractable side effect of chemotherapy. Here, we investigated ways to alleviate 5-fluorouracil-caused stress hematopoietic impairment. We found that intraperitoneally injected ASP (Angelica sinensis polysaccharides) (100 mg/kg per day), one main active ingredient of Angelica sinensis, for consecutive 7 days, significantly recovered mouse bone marrow pro-B and pre-B cells, reversed the capacity of CFU-PreB colony forming, thus alleviating B cell reduction in the spleen and peripheral blood, as well as ameliorating immunoglobin from spleen and serum. The mechanism is related to the protective effects of ASP on IL-7 producing cells, including perivascular Leptin+ and CXCL12+ mesenchymal stem and progenitor cells (MSPCs), thus promoting IL-7 production, and activating IL-7R-mediated STAT5, PI3K-AKT signaling, including survival signals and EBF1, PAX5 transcription factor expression. Additionally, ASP's IL-7 promoting effect was demonstrated to be associated with maintaining osteogenesis/adipogenesis balance of MSPCs via the NRF2 antioxidant pathway. Collectively, our findings indicate that ASP reverse stress B-lymphocytopenia via improving Nrf2 signaling, promoting IL-7 production in MSPCs, and subsequently maintaining survival, proliferation, and differentiation of B cell progenitors, which may represent a promising therapeutic strategy. [Display omitted] • Angelica Sinensis Polysaccharides restore 5-Fluorouracil-induced B-lymphocytopenia. • Angelica Sinensis Polysaccharides antagonize 5-Fluorouracil-caused mesenchymal progenitor oxidative stress via Nrf2 signaling, keeping osteogenic differentiation potential, protecting IL-7 producing cells. • Angelica Sinensis Polysaccharides reverse 5-Fluorouracil-induced decreased IL-7-IL-7R signaling, rescuing the proliferation, survival and differentiation of B cell progenitors. [ABSTRACT FROM AUTHOR]