Ginseng–Astragalus–oxymatrine injection ameliorates cyclophosphamide-induced immunosuppression in mice and enhances the immune activity of RAW264.7 cells

Li, Yuangeng; Yu, Ping; Fu, Wenwen; Cai, Li-Dong; Yu, Ying; Feng, Zhiqiang; Wang, Yaozhen; Zhang, Fuyuan; Yu, Xiaofeng; Xu, Huali; Sui, Dayun

doi:10.1016/j.jep.2021.114387

Cited by 18 publications

(16 citation statements)

References 29 publications

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“…In addition, several studies reported that the injection of single doses of CTX (250–400 mg/kg) and smaller divided doses induce tolerance against ovine erythrocytes, bovine gamma globulin, and equine gamma globulin in mice [ 84 , 85 , 86 ]. To confirm the immunosuppressive properties of CTX, we assessed body weight and serum TNF-α and IL-6 levels instead of tolerance against the ovine erythrocyte test because many researchers determined the immunosuppression by measuring body weight and cytokines, such as TNF-α and IL-6 [ 26 , 28 , 29 , 30 ]. We showed that the body weight and serum TNF-α and IL-6 levels were reduced on the 7th day after CTX injection, indicating immunosuppression by CTX ( Supplementary Figure S3 ).…”

Section: Discussionmentioning

confidence: 99%

“…Cyclophosphamide (CTX) as an anti-cancer drug or an immunosuppressive agent has been used for the treatment of cancer or immune-mediated diseases [ 25 ]. Because CTX induces oxidative stress and has immunosuppressive properties, the CTX-induced immunosuppressive murine model has been extensively studied to establish the immunomodulatory effects of agents [ 26 , 27 , 28 , 29 , 30 ].…”

Section: Introductionmentioning

confidence: 99%

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SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Han

Kim

et al. 2022

Antioxidants

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Immune dysregulation is a risk factor for several diseases, including infectious diseases. Immunostimulatory agents have been used for the treatment of immune dysregulation, but deleterious adverse effects have been reported. The present study aims to establish the anti-oxidant and immunity-enhancing effects of Sambu-Tang (SBT), composed of Panax ginseng and Aconitum carmichaeli, and stigmasterol (Stig), an active compound of SBT. Immune-related factors were analyzed in RAW264.7 macrophage cells, mouse primary splenocytes, and the serum and spleen of cyclophosphamide-induced immunosuppressed mice. Results showed that the production levels of nitric oxide (NO) and expression levels of inducible NO synthase and heme oxygenase-1 were increased following SBT or Stig treatment in RAW264.7 cells. SBT or Stig increased the production levels of G-CSF, IFN-γ, IL-12, IL-2, IL-6, and TNF-α and induced the activation of NF-κB in RAW264.7 cells. SBT or Stig promoted splenic lymphocyte proliferation and increased splenic NK cell cytotoxic activity. In addition, SBT or Stig enhanced the levels of IFN-γ, IL-12, IL-2, IL-6, or TNF-α in the serum and spleen of the immunosuppressed mice. SBT or Stig increased the superoxide dismutase activity in the spleen. Collectively, SBT and Stig possess anti-oxidant and immunomodulatory activities, so they may be considered effective natural compounds for the treatment of various symptoms caused by immune dysregulation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Han

Kim

et al. 2022

Antioxidants

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“…Myocarditis can manifest with a variety of symptoms, such as palpitations, chest pain and arrhythmia (29). Based on the dialectical treatments described in TCM, Radix Sophorae flavescentis and Panax quinquefolium can be combined to treat myocarditis, thereby providing the superior synergistic effects of these Chinese herbs (30). In our unpublished studies, in vitro tissue culture and in vivo viral myocarditis animal models were used to perform antiviral pharmacodynamic experiments using different concentrations of KX.…”

Section: Discussionmentioning

confidence: 99%

Combination ofSophora flavescensalkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF‑κB and TGF‑β1 pathways

Liu

Lin

et al. 2022

Exp Ther Med

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Chronic cardiac inflammation and fibrosis can progress into severe forms of cardiomyopathy. Sophora flavescens alkaloids (KuShen) have been previously reported to exert anti-inflammatory effects, whereas Panax quinquefolium saponins (XiYangShen) has been shown to alleviate cardiac fibrosis. Therefore, the potential effects of their combination (KX) on different stages of autoimmune myocarditis were investigated in the present study. Mice were randomly divided into the following four groups: Control; experimental autoimmune myocarditis (EAM); KX-High (275 mg/kg); and KX-Low (138 mg/kg). A 21-day and a 60-day EAM model was established through multi-site subcutaneous injections of cardiac myosin mixed with complete Freund's adjuvant on days 0, 7, 21 and 42. Mice in the High and Low KX groups were treated by gavage (10 ml/kg) daily from day 0 (1 day before treatment) until sacrifice (day 21 or 60). Mice in the control and EAM groups received an equivalent volume of distilled water. The levels of lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTn-I), IL-1β, IL-6, TNF-α, TGF-β1, collagen type I (Col Ⅰ) and collagen type III (Col Ⅲ) were measured by ELISA in the mouse myocardial tissues or serum. Myocardial tissue structure and extent of fibrosis were visualized using H&E and Masson's staining. Western blotting and immunohistochemistry were used to measure the expression levels NF-κB and TGF-β1 pathway proteins in the myocardial tissues. The degree of inflammation in the 21-day EAM model was found to be significantly higher compared with that in the 60-day EAM model. KX significantly reduced the inflammatory response at 21 days by decreasing the expression levels of CK-MB, LDH, cTn-I, IL-1β, IL-6, TNF-α and TGF-β-activated kinase 1-binding protein 1/NF-κB pathway proteins. Myocardial fibrosis in the 60-day EAM model was also significantly worse compared with that in the 21-day EAM model. However, fibrosis was significantly delayed by treatment with KX. In addition, KX significantly decreased the expression levels of TGF-β1, Smad2, Smad4, Col I and Col III. Therefore, these data suggest that KX is beneficial for treating myocarditis by targeting multiple pathways.

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“…As one of the most important components of complementary and alternative medicines, traditional Chinese medicines (TCM) have been practiced in China and surrounding areas for thousands of years. With rich experiences in fighting diseases and the growing trend of acceptance of complementary and alternative medicines, studies have shown that polysaccharides from Lycium barbarum could regulate immune response depending on the modulation of gut microbiota (Ding et al, 2019 ); ginseng-astragalus-oxymatrine injection could ameliorate cyclophosphamide-induced immunosuppression in mice (Li et al, 2021 ). Whether it is used alone or in combination, traditional Chinese medicine can effectively play a therapeutic or healthcare effect.…”

Section: Introductionmentioning

confidence: 99%

Effects of compound small peptides of Chinese medicine on intestinal immunity and cecal intestinal flora in CTX immunosuppressed mice

Cui

Zhang

et al. 2022

Front. Microbiol.

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The study was designed to explore the improvement effect of CSPCM (compound small peptide of Chinese medicine) on intestinal immunity and microflora through the treatment of different doses of CSPCM. A total of 100 male Kunming mice were weighed and divided into five groups, namely, group A (control group), group B (model group), group C (0.1 g/kg·bw CSPCM), group D (0.2 g/kg·bw CSPCM), and group E (0.4 g/kg·bw CSPCM). The use of CTX (cyclophosphamide) caused a series of negative effects: the secretion of IL-2, IL-22, TNF-α, sIgA, length of the villi, and the area of Pey's node were significantly reduced (P < 0.05); the depth of crypt and the percent of CD3+ and CD4+ cells were significantly increased (P < 0.05); the cecal flora taxa decreased; the abundance of Firmicutes and Lactobacillus increased; and the abundance of Bacteroidetes, Deferribacteres, Proteobacteria, Mucispirillum, Bacteroides, and Flexisprra decreased. The addition of CSPCM improved the secretion of cytokines and the development of intestinal villi, crypts, and Pey's node. The number of CD3+ and CD4+ cells in groups C, D, and E was significantly higher than that in group B (P < 0.05). Compared with group B, the abundance of Firmicutes in groups C, D, and E was decreased, and the Bacteroidetes, Deferribacteres, and Proteobacteria increased. The abundance of Lactobacillus decreased, while that of Mucispirillum, Bacteroides, and Flexisprra increased. It is concluded that cyclophosphamide is extremely destructive to the intestinal area and has a great negative impact on the development of the small intestine, the intestinal immune system, and the intestinal flora. The CSPCM can improve the negative effects of CTX.

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Ginseng–Astragalus–oxymatrine injection ameliorates cyclophosphamide-induced immunosuppression in mice and enhances the immune activity of RAW264.7 cells

Cited by 18 publications

References 29 publications

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

SBT (Composed of Panax ginseng and Aconitum carmichaeli) and Stigmasterol Enhances Nitric Oxide Production and Exerts Curative Properties as a Potential Anti-Oxidant and Immunity-Enhancing Agent

Combination ofSophora flavescensalkaloids and Panax quinquefolium saponins modulates different stages of experimental autoimmune myocarditis via the NF‑κB and TGF‑β1 pathways

Effects of compound small peptides of Chinese medicine on intestinal immunity and cecal intestinal flora in CTX immunosuppressed mice

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