Neuroprotective Effects of Shenqi Fuzheng Injection in a Transgenic SOD1-G93A Mouse Model of Amyotrophic Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, in the pathogenesis of which oxidative stress (OS) was believed to play a key role. Shenqi Fuzheng Injection (SFI) concocted from two kinds of Chinese medicinal herbs, Radix Codonopsis and Radix Astragali, was proven to be eligible to reduce the OS injury and increase the activity of the nuclear factor-erythroid-2–related factor 2 (Nrf2) pathway, an antioxidant enzymes inducer.Objective: We aim to investigate the effects and potential mechanisms underlying the action of SFI on a well-established transgenic mouse model of ALS.Methods: Transgenic SOD1-G93A mice were intraperitoneally injected with SFI (40 ml/kg) three times a week from 87 days of age. Motor function, survival, pathological manifestations in the brain, and Nrf2 pathway-related assessments of the mice were performed.Results: SFI treatment efficiently postponed the disease onset (p = 0.022) and extended the overall survival (p = 0.038) of the SOD1-G93A mice. Moreover, SFI significantly reduced motor neuron loss (p < 0.001) and astrocytic activation (p < 0.05) in the motor cortex of the brain of SOD1-G93A mice at 130 days of age. The protective effects of SFI in the SOD1-G93A mice were associated with decreasing the level of malondialdehyde (p < 0.05) and increasing the levels of superoxide dismutase (p < 0.05), Nrf2 (p < 0.05), heme oxygenase-1 (p < 0.05), and glutathione S-transferase (p < 0.05) in the SOD1-G93A mice.Conclusion: The SFI treatment efficiently extended the overall survival and improved the pathological manifestations of the brain via alleviating the OS injury and activating the Nrf2 pathway in the animal model of ALS, which made SFI a potentially promising candidate for ALS treatment.

Shenqi Fuzheng Injection (SFI) Enhances IFN-α Inhibitory Effect on Hepatocellular Carcinoma Cells by Reducing VEGF Expression: Validation by Gene Silencing Technique

Shenqi Fuzheng Injection (SFI) is a traditional Chinese medicine injection with anticancer properties and is mainly composed of ginseng and astragalus. Its efficacy has been confirmed in clinical trials, but the mechanism remains unclear. We investigated the effect of SFI on vascular endothelial growth factor (VEGF) gene expression in hepatocellular carcinoma (HCC) cells and identified its possible mechanism of synergistic effects when combined with the chemotherapeutic drug interferon (IFN-) α. An MTT assay was used to measure the inhibition effects of low-dose IFN-α (6000 IU) with or without SFI (0.5 g/L) on the HCC cell line MHCC97. VEGF-silenced MHCC97L-mir200 cell lines were prepared using lentiviral vectors and evaluated by real-time PCR to determine the inhibition effect. We examined MHCC97L-mir200 and MHCC97L cells by MTT assay, using IFN-α alone or in combination with SFI. The inhibition ratio of IFN-α (6000 IU) was -29.5%, while that for IFN-α (6000 IU) + SFI (0.5 g/L) was 17.0%, which was significantly higher than that for the IFN-α group (P < 0.01). The VEGF gene was silenced successfully in MHCC97-L cells. After interference of VEGF, the inhibition by SFI and IFN-α in MHCC97L-mir200 did not differ from that in MHCC97-L cells (P > 0.05). SFI can reduce the expression of VEGF in HCC, which can increase the efficacy of IFN-α, providing a theoretical basis for clinical application.

Shenqi Fuzheng Injection impairs bile duct ligation-induced cholestatic liver injury in vivo

Background and aim: The aim of the present study sought to determine the protective function of Shenqi Fuzheng Injection (SFI) in cholestatic liver injury. Methods: Cholestatic liver injury was induced in a 7-day bile duct-ligated (BDL) rat model. Rats were divided into three groups that were comprised of: (1) Sham; (2) BDL model; and (3) SFI treatment. The sham and BDL groups were treated with an appropriate volume of 0.9% sodium chloride as the vehicle, and the SFI group was administered SFI at a dose of 20 ml/kg/day, via tail vein injection. Results: SFI significantly (all at P<0.01) decreased the levels of serum aspartate aminotransferase and alanine aminotransferase as compared with the BDL group, which was associated with reduced severity of inflammatory cell infiltration and hepatic damage. Moreover, SFI significantly decreased the levels of hepatic interleukin-6 (P<0.01), tumor necrosis factor-α (P=0.041), and malondialdehyde (P=0.026), and significantly increased the levels of total superoxide dismutase (P<0.01), and the GSH/GSSG ratio (P=0.041) in the liver. Western blot analysis showed that SFI increased PPAR-γ expression; however, SFI treatment decreased cyclooxygenase-2 (COX-2) expression and the phosphorylation of NF-κBp65. Conclusions: These data demonstrated that SFI attenuated both inflammation and oxidative stress, and disrupted cholestatic liver injury. The involved mechanism was dependent, at least in part, on regulating PPAR-γ, COX-2, and NF-κBp65 expression.