Abstract
Cyclophosphamide is a commonly used anticancer drug, and immunosuppression is one of the most common side effects. How to recover the immunological function is important for cyclophosphamide-treated patients. In the present study, Phellodendri Cortex polysaccharides (CPP) could enhance the proliferation of mouse spleen lymphocytes in vitro. The immunoregulatory function of CPP was then investigated in cyclophosphamide-induced immunosuppressed mice. In CPP-treated groups, mice were orally treated with CPP at doses of 1, 0.5, and 0.25 g/kg bodyweight from 1 to 11 d, respectively. The cyclophosphamide was administrated in CPP and cyclophosphamide groups from 12 to 14 d. In the cyclophosphamide and normal control groups, the mice received equal volume of saline from 1 to 14 d. The results showed that CPP (1 g/kg) could significantly increase the bodyweight of mice, even during cyclophosphamide treatment. The organ coefficients of the spleen and thymus were recovered by CPP treatment. CPP upregulated the contents of cytokines (IL-2, IL-6, IFN-γ, and TNF-α) in serum, which were downregulated by cyclophosphamide. The mRNA levels of these cytokines were also elevated by CPP treatment in the spleen. Cyclophosphamide upregulated the expressions of NF-κB p65, TLR4, and MyD88, suggesting that the NF-κB signaling pathway was activated by cyclophosphamide. After CPP treatment, it was recovered to normal level. These results indicated that CPP alleviated the cyclophosphamide-induced immunosuppression.
Highlights
Phellodendri Cortex (“Huangbo” in Chinese), a traditional Chinese herbal, is derived from Phellodendron chinense Schneid. or Phellodendron amurense Rupr. and known as Phellodendri Cortex Chinensis (CPC) and Phellodendri Cortex Amurensis (CPA), respectively [1]
Cyclophosphamide can induce immunosuppression which is one of the most common side effects; it is used widely in organ transplantation and autoimmune disease [14]. e immunosuppression induced by cyclophosphamide or its metabolite could affect both cellmediated and humoral immunity [15]. e immune system is closely relevant to host’s somatic functions, such as aging [16], mental state [17], inflammation [18], and various infections [19,20,21], which consists of different cell populations [16]
Extraction and Purification of Polysaccharides. e Phellodendri Cortex was purchased from Sichuan Zhongyong Pharmaceutical Co., Ltd. (Chengdu, China). e dried Phellodendri Cortex powder (200 g) was defatted by ethanol at 75°C for 6 h, and the defatted powder was decocted in distilled water for 3 times (1 : 10, g/v). e decoction was collected and concentrated, and ethanol was added (v/v, 1 : 3). e supernatant was removed by centrifugation, and the sediment was collected. e crude polysaccharides were dissolved in hot water and deproteinized with Sevag’s reagent, followed by dialysis against distilled water for 3 d to remove other impurities
Summary
Phellodendri Cortex (“Huangbo” in Chinese), a traditional Chinese herbal, is derived from Phellodendron chinense Schneid. or Phellodendron amurense Rupr. (family Rutaceae) and known as Phellodendri Cortex Chinensis (CPC) and Phellodendri Cortex Amurensis (CPA), respectively [1]. Cyclophosphamide can induce immunosuppression which is one of the most common side effects; it is used widely in organ transplantation and autoimmune disease [14]. E immunosuppression induced by cyclophosphamide or its metabolite could affect both cellmediated and humoral immunity [15]. Phellodendri Cortex polysaccharides (CPP) exhibited potent antitumor activity against sarcoma [24]. Few studies were conducted to evaluate immunoenhancement activity of CPP under immunosuppression. The immune-stimulation activity of CPP was investigated in immunosuppressive mice induced by cyclophosphamide for developing a new herbalderived immunostimulant
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