Therapeutic effect of notoginseng saponins before and after fermentation on blood deficiency rats.

Notoginseng saponins (NS) are the active ingredients in Panax notoginseng (Burk.) F.H. Chen (PN). NS can be transformed depending on how the extract is processed. Fermentation has been shown to produce secondary ginsenosides with increased bioavailability. However, the therapeutic effect of fermented NS (FNS) requires further study. The present study compared the compositions and activities of FNS and NS in blood deficiency rats, which resembles the symptoms of anemia in modern medicine, induced by acetylphenylhydrazine and cyclophosphamide. A total of 32 rats were randomly divided into control, model, FNS and NS groups. A blood deficiency model was established and then treatment was orally administered for 21 days. The results of component analysis indicated that some saponins transformed during the fermentation process resulting in a decrease of notoginsenoside R1, and ginsenosides Rg1, Rb1 and Re, and an increase in ginsenosides Rd, Rh2, compound K, protopanaxadiol and protopanaxatriol. The animal results showed that both FNS and NS increased the number of white blood cells (WBCs), red blood cells, hemoglobin, platelets and reticulocytes, and the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO) and thrombopoietin (TPO), decreased the G0/G1 phase and increased G2/M phase, and decreased the apoptosis rate of bone marrow (BM) cells, which suggested a contribution to the recovery of hematopoietic function of the BM cells. FNS and NS increased the protein expression levels of the cytokines IL-4, IL-10, IL-12, IL-13, TGF-ß, IL-6, IFN-γ and TNF-α, and the mRNA expression levels of transcription factors GATA binding protein 3 and T-box expressed in T cell (T-bet). FNS and NS treatment also increased the number of CD4+ T cells, and decreased the enlargement of the rat spleen and thymus atrophy, which indicated a protective effect on the organs of the immune system. The results of the present study demonstrated that compared with NS, FNS showed an improved ability to increase the levels of WBCs, lymphocytes, GM-CSF, EPO, TPO, aspartate aminotransferase, IL-10, IL-12, IL-13 and TNF-α, and the mRNA expression levels of T-bet, and decrease alanine aminotransferase levels. The differences seen for FNS treatment could arise from their improved bioavailability compared with NS, due to the larger proportion of hydrophobic ginsenosides produced during fermentation.

Prevention effect of total ginsenosides and ginseng extract from Panax ginseng on cyclophosphamide-induced immunosuppression in mice.

Oral decoction is widely applied in traditional Chinese medicines. The polysaccharides of decoction promote the exposure of small molecules and increase their bioavailability. This study mainly compared the component and activities of total ginsenosides (TGS) and ginseng extract (GE) on immunosuppressed mice induced by cyclophosphamide. Thirty-two mice were randomly divided into control, model, TGS, and GE groups. The mice were orally administered for 28 days and then injected with cyclophosphamide on the last four days. The results of component analysis showed the total content of 12 ginsenosides in TGS (67.21%) was higher than GE (2.04%); the total content of 17 amino acids in TGS (1.41%) was lower than GE (5.36%); the total content of 10 monosaccharides was similar in TGS (74.12%) and GE (76.36%). The animal results showed that both TGS and GE protected the hematopoietic function of bone marrow by inhibiting cell apoptosis, and recovering the normal cell cycle of BM; maintained the dynamic balance between the Th1 and Th2 cells; also protected the spleen, thymus, and liver. Meanwhile, TGS and GE protected the intestinal bacteria of immunosuppressed mice by increasing the abundance of lactobacillus and decreasing the abundance of the odoribacter and clostridia_UCG-014. The prevention effect of GE was superior to TGS in some parameters. In conclusion, TGS and GE protected the immune function of immunosuppressed mice induced by cyclophosphamide. Meanwhile, GE showed higher bioavailability and bioactivity compared with TGS, because the synergistic effect of polysaccharides and ginsenosides plays an important role in protecting the immune function.

Prevention Effect of Protopanaxadiol-Type Saponins Saponins and Protopanaxatriol-Type Saponins on Myelosuppression Mice Induced by Cyclophosphamide.

Ginsenosides from ginseng are used as a therapeutic agent for various diseases. They enhance the immunomodulatory effect in cyclophosphamide (CP)-treated tumor disease. The structural characteristics of steroidal saponins are mainly divided into protopanaxadiol-type saponin (PDS) and protopanaxatriol-type saponin (PTS). At present, few researchers have studied which kind of saponin plays a more important role, thus, we compared the prevention effect of PDS and PTS on myelosuppression mice induced by CP. The components and contents of saponin and monosaccharide were analyzed by using ultra high performance liquid chromatography-charged aerosol detector (UPLC-CAD) and reversed phase-high performance liquid chromatography (RP-HPLC), respectively. Thirty-two mice were randomly divided into four groups, including control, model (CP), CP+PDS, and CP+PTS. The mice were orally administered with PDS or PTS for 28 days and then injected with CP saline solution on 25, 26, 27, and 28 days at a dose of 50 mg × kg-1. After the end of modeling, the whole blood of mice from the ophthalmic venous plexus was collected to detect routine blood tests, inflammatory cytokines, and hematopoiesis-related cytokines. Cell cycle and the apoptosis of bone marrow in the right femur were detected. The spleen and thymus were used to calculate the organ index and histological examination, and splenocytes were used to detect the percentage of CD4+ and CD25+ T cells. In the saponins analysis, PDS mainly included the Rb1, Rc, Rb2, and Rd of protopanaxadiol-type ginsenosides (accounted for 91.64%), and PTS mainly included the Re, Rg1, and Rf of protopanaxatriol-type ginsenosides (accounted for 75.46%). The animal results showed that both PDS and PTS improved the most indicators of myelosuppression mice induced by CP, including increased weight, blood cell numbers, hematopoiesis-related cytokines, and inflammatory cytokines; promoted the cell cycle of bone marrow and inhibited the apoptosis of bone marrow; elevated the spleen and thymus indexes and CD4+ count of splenocytes. The prevention effect of PDS was better than PTS in some indicators, such as red blood cells, hemoglobin, interleukin (IL)-1ß, IL-4, IL-10, tumor necrosis factor-α, CD4+, and thymus index. These results suggest both PDS and PTS can prevent myelosuppression of mice induced by CP. Meanwhile, PDS and its metabolite showed higher bioavailability and bioactivity compared with PTS.