Prostate carcinoma is the most frequently diagnosed malignancy and the second leading cause of death of men in the United States. To date, no effective therapeutic treatment allows abrogation of the progression of prostate cancer to more invasive forms. In this study, we identified Saussurea involucrata Kar. et Kir., a rare traditional Chinese medicinal herb, as a potential agent for androgen-independent prostate cancer patients and investigated its biological mechanism as an antineoplastic agent. S. involucrata caused a concentration- and time-dependent inhibition of cell proliferation in human hormone-resistant prostate cancer PC-3 cells. Moreover, in vitro studies in a panel of several types of human cancer cell lines revealed that S. involucrata inhibited cell proliferation with high potency. To evaluate the bioactive compounds, we successively extracted the S. involucrata with fractions of methanol (SI-1), ethyl acetate (SI-2), n-butanol (SI-3), and water (SI-4). Among these extracts, SI-2 contains the most effective bioactivity. SI-2 treatment resulted in significant time-dependent growth inhibition together with G1 phase cell cycle arrest and apoptosis in PC3 cells. In addition, SI-2 treatment strongly induced p21WAF1/CIP and p27KIP1 expression, independent of the p53 pathway, and downregulated expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4). SI-2 treatment increased levels of Bax, cytochrome c, activated caspase-3, and active caspase-9 and decreased Bcl-2 expression level. One of the major targets for the therapy in prostate cancer can be epidermal growth factor receptor (EGFR). SI-2 markedly reduced phosphorylation of EGFR and inhibited activation of AKT and STAT3. Moreover, p.o. administration of SI-2 induced a dose-dependent inhibition of PC-3 tumor growth in vivo. In summary, our study identifies S. involucrata as an effective inhibitor of EGFR signaling in human hormone-resistant prostate cancer PC-3 cells. We suggest that S. involucrata could be developed as an agent for the management of EGFR-positive human cancers.

Taxol, a type of antimitotic agent, could modulate local inflammatory conditions in peripheral nerves, which may impair their regeneration and recovery when injured. This study provided in vivo trials of silicone rubber chambers to bridge a long 10 mm sciatic nerve defect in taxol-treated rats. It was aimed to determine the effects of electrical stimulation at various frequencies on regeneration of the sciatic nerves in the bridging conduits. Taxol-treated rats were divided into four groups (n = 10/group): sham control (no current delivered from the stimulator); and electrical stimulation (3 times/week for 3 weeks at 2, 20, and 200 Hz with 1 mA current intensity). Neuronal electrophysiology, animal behavior, neuronal connectivity, macrophage infiltration, calcitonin gene-related peptide (CGRP) expression levels, and morphological observations were evaluated. At the end of 4 weeks, animals in the low- (2 Hz) and medium-frequency (20 Hz) groups had dramatic higher rates of successful regeneration (90% and 80%) across the wide gap as compared to the groups of sham and high-frequency (200 Hz) (60% and 50%). In addition, the 2 Hz group had significantly larger amplitudes and evoked muscle action potentials compared to the sham and the 200 Hz group, respectively (P < 0.05). Heat, cold plate licking latencies, motor coordination, and neuronal connectivity were unaffected by the electrical stimulation. Macrophage density, CGRP expression level, and axon number were all significantly increased in the 20 Hz group compared to the sham group (P < 0.05). This study suggested that low- (2 Hz) to medium-frequency (20 Hz) electrical stimulation could ameliorate local inflammatory conditions to augment recovery of regenerating nerves by accelerating their regrowth and improving electrophysiological function in taxol-treated peripheral nerve injury repaired with the silicone rubber conduit.

Background: Swimming is commonly considered to be an efficient rehabilitation exercise to treat peripheral nerve injury. However, the most effective resistance level and exercise duration is still unclear. We investigated the effects and mechanisms of swimming at various exertion levels in a rat sciatic nerve transection model.Methods: Sciatic nerve transection rats were randomized into the following four groups based on swimming duration (from the 7th day to the 28th day post-surgery): sedentary control group (SC), S10 group (10 min/3 times/week), S20 group (20 min/3 times/week), and S30 group (30 min/3 times/week) (n = 10 each). Axon regeneration, electrophysiological properties, muscular weights, macrophage infiltration, and nerve repair associated maker, calcitonin gene-related peptide (CGRP), were measured.Results: Dramatic higher successful percentages of nerve regeneration across the 10-mm gaps in swimming groups compared to the SC group. Total area of nerve regeneration significantly improved in the S10 group; however, electrophysiological properties, muscular weights, and macrophage infiltration in the regenerated nerves of rats did not differ significantly between the various exercise groups. CGRP expression was significantly increased in the spinal cord of rats in the S20 group.Conclusions: Our data indicated that CGRP-related axonal regeneration improved significantly with moderate swimming. These results should inspire new studies in physiotherapeutic practice for related human treatment.

BackgroundLarge gap healing is a difficult issue in the recovery of peripheral nerve injury. The present study provides in vivo trials of silicone rubber chambers filled with collagen containing IFN-γ or IL-4 to bridge a 15 mm sciatic nerve defect in rats. Fillings of NGF and normal saline were used as the positive and negative controls. Neuronal electrophysiology, neuronal connectivity, macrophage infiltration, location and expression levels of calcitonin gene-related peptide and histology of the regenerated nerves were evaluated.ResultsAt the end of 6 weeks, animals from the groups of NGF and IL-4 had dramatic higher rates of successful regeneration (100 and 80%) across the wide gap as compared to the groups of IFN-γ and saline controls (30 and 40%). In addition, the NGF group had significantly higher NCV and shorter latency compared to IFN-γ group (P < 0.05). The IL-4 group recruited significantly more macrophages in the nerves as compared to the saline controls and the NGF-treated animals (P < 0.05).ConclusionsThe current study demonstrated that NGF and IL-4 show potential growth-promoting capability for peripheral nerve regeneration. These fillings in the bridging conduits may modulate local inflammatory conditions affecting recovery of the nerves.

Fatigue is a noticeable and highly prevalent symptom in tense, industriously, and economically affluent modern society. Therefore, new antifatigue agents to smooth the fatigue feature are an energetic topic. The total ethanol extract (ESI) of Saussurea involucrata Kar et Kir., known as Tian-Shan snow lotus, was evaluated for antifatigue activity in ICR mice with mice forced swimming test and the determination of the contents of blood lactic acid and serum urea nitrogen. ESI (0.05, 0.15, 0.25 g/kg) was administered orally to mice for 4 weeks. The average swimming times to exhaustion of the ESI-treated ICR mice (0.15, 0.25 g/kg) were prolonged by 132% and 180% (p<0.001) with a lessening of fatigue compared with that of the control group. Analysis of biochemical parameters showed that levels of serum urea nitrogen and blood lactic acid of experimental groups were also decreased significantly (p<0.001) compared with that of the control group. The antioxidant activity of ESI was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical-scavenging assay and the hydrogen peroxide-induced luminol chemiluminescence assay and the results indicated that ESI exerts DPPH scavenging ability and reducing power. These results provide scientific evidence that S. involucrata may have been potential as an antifatigue agent.