Icariin promotes the repair of PC12 cells by inhibiting endoplasmic reticulum stress.

BACKGROUND: Endoplasmic reticulum stress (ERS) is one of the main mechanisms of spinal cord injury (SCI) pathology and can affect the physiological state of neurons. Icariin (ICA), the main pharmacological component of Epimedium, can relieve the symptoms of patients with SCI and has obvious protective effects on neurons through ERS. METHODS: PC12 cells were induced to differentiate into neurons by nerve growth factor and identified by flow cytometry. Cell proliferation was detected by CCK8 method, cell viability was detected by SRB assay, apoptosis was detected by flow cytometry and microstructure of ER was observed by transmission electron microscope. Western blot was used to detect the protein expression of CHOP and Grp78, and qPCR was used to detect the mRNA expression of CHOP and Grp78. RESULTS: The results of CCK8, SRB and flow cytometry showed that ICA could relieve ERS and reduce apoptosis of PC12 cells. The results of transmission microscope showed that ICA could reduce apoptosis of PC12 cells caused by ERS. The results of Western blot and q-PCR showed that ICA could inhibit ERS by down-regulating the expression of CHOP and Grp78. CONCLUSIONS: ICA can inhibit ERS and promote the repair of PC12 cells by down-regulating the expression of CHOP and Grp78. ICA has the potential to promote the recovery of spinal cord injury.

Jisuikang Promotes the Repair of Spinal Cord Injury in Rats by Regulating NgR/RhoA/ROCK Signal Pathway.

Jisuikang (JSK) is an herbal formula composed of many kinds of traditional Chinese medicine, which has been proved to be effective in promoting the rehabilitation of patients with spinal cord injury (SCI) after more than ten years of clinical application. However, the mechanisms of JSK promoting nerve regeneration are yet to be clarified. The aim of this study was to investigate the effects of JSK protecting neurons, specifically the regulation of NgR/RhoA/ROCK signal pathway. The motor function of rats was evaluated by the BBB score and inclined plate test, Golgi staining and transmission electron microscope were used to observe the microstructure of nerve tissue, and fluorescence double-labeling method was used to detect neuronal apoptosis. In this study, we found that JSK could improve the motor function of rats with SCI, protect the microstructure (mitochondria, endoplasmic reticulum, and dendritic spine) of neurons, and reduce the apoptosis rate of neurons in rats with SCI. In addition, JSK could inhibit the expression of Nogo receptor (NgR) in neurons and the NgR/RhoA/ROCK signal pathway in rats with SCI. These results indicated JSK could improve the motor function of rats with SCI by inhibiting the NgR/RhoA/ROCK signal pathway, which suggests the potential applicability of JSK as a nerve regeneration agent.

Acupuncture for Cancer Related Pain: Protocol for a Pragmatic Randomised Wait-List Controlled Trial.

BACKGROUND: Acupuncture has been proved effective for cancer related pain (CRP) in China, America and some other countries. However, there is relative lack of evidence to support the use of acupuncture for CRP in Australia. OBJECTIVES: To assess the effectiveness and safety of acupuncture for management of CRP in a real-world setting and to understand cancer patients' experience of undergoing acupuncture for CRP. METHODS: A pragmatic randomised controlled trial will be conducted in South Western Sydney Local Health District (SWSLHD) in NSW, Australia. Adults with cancer related pain (n = 106) will be randomised in a 1:1 ratio to receive the acupuncture intervention up front versus after a wait list period of 4 weeks. Pain level (by Numerical Rating Scale), analgesic use, auricular acupressure frequency and adverse events will be assessed at baseline, mid-treatment and post-treatment. Expectancy on trial outcome (by Credibility and Expectancy questionnaire) will be assessed at baseline. The perspective of the participants (by an interview) will be recorded after the last intervention. EXPECTED OUTCOMES: We hypothesise that acupuncture will relieve cancer related pain at mid-treatment and post-treatment. We also hypothesise that few adverse events will be provoked by acupuncture. TRIAL REGISTRATION: Australia New-Zealand Clinical Trial Registry (ACTRN12620000325909).

Osthole inhibits osteoclasts formation and bone resorption by regulating NF-κB signaling and NFATc1 activations stimulated by RANKL.

Chinese herbal medicine Fructus Cnidii has an outstanding effect on chronic lumbar pain and impotence, also has been used against osteoporosis with high frequency. Yet, the mechanisms of osthole, a derivative of Fructus Cnidii, on osteoclasts remains barely known. In this study, it was found out that osthole (10-6 mol/L, 10-5 mol/L) had the influence of inhibiting osteoclast formation and bone resorptive activities induced by receptor activator of nuclear factor κB ligand (RANKL), rather than affecting the viability of osteoclast-like cells. Furthermore, osthole could also inhibit the messenger RNA expressions of c-Src, tartrate-resistant acid phosphatase, ß3-Integrin, matrix metallopeptidase 9, and cathepsin K. The results of the mechanistic study indicated that osthole regulated the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) and nuclear factor-κB (NF-κB) activations following the RANKL stimulation. These findings suggested that the inhibitory effects of osthole were associated with restraining the activations of NFATc1 and NF-κB induced by RANKL. Thus osthole can be used as a potential treatment for abnormal bone-resorption related diseases.

Effects of Clematis chinensis Osbeck mediated by low-intensity pulsed ultrasound on transforming growth factor-ß/Smad signaling in rabbit articular chondrocytes.

PURPOSE: Clematis chinensis Osbeck (CCO) is an essential herb that has been shown to promote the biological functions of cartilage cells. In this study, we aimed to explore whether and how low-intensity pulsed ultrasound (LIPUS) enhanced CCO delivery into chondrocytes and stimulated biological activity in vitro. METHODS: Chondrocytes were isolated from knee articular cartilage of 2-week-old rabbits and treated with LIPUS plus CCO or recombinant transforming growth factor beta 1 (TGF-ß1; 0.5 ng/mL), with or without anti-TGF-ß1 antibodies (10 µg/mL), for 3 days. Cell proliferation was assessed by Cell-Counting Kit-8 assays. Immunocytochemistry, western blotting, and quantitative polymerase chain reaction were applied to detect the expression of type II collagen and some molecules in the TGF-ß1 signal pathway. RESULTS: LIPUS plus 0.1 mg/mL CCO solution promoted chondrocyte proliferation and type II collagen and TGF-ß1 expression synergistically in vitro (P < 0.05). In addition, treatment with anti-TGF-ß1 antibodies blocked this effect (P < 0.01), but not completely. CCO plus LIPUS also showed more enhanced effects on promoting TGF-ß receptor II and Smad2 signaling and reducing Smad7 signaling than either intervention separately (P < 0.05). CONCLUSIONS: CCO plus LIPUS promoted extracellular matrix deposition by accelerating the TGF-ß/Smad-signaling pathway in chondrocytes.

Efficacy and safety of Shaoyang Xibi decoction in patients with knee osteoarthritis: a multi-center, single-blind, randomized controlled trial.

PURPOSE: To observe the efficacy and safety of Shaoyang Xibi decoction (SYXBD) in patients with knee osteoarthritis (KOA), and to verify that the theory of ""Shaoyang dominating bone"" in Traditional Chinese Medicine (TCM) can be applied to KOA treatment. METHODS: Participants were randomly allocated to two groups: SYXBD (treatment group, n = 66) and Meloxicam (control group, n = 66). Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and 36-Item Short Form Health Survey (SF-36) were used to assess efficacy before the treatment and 8 weeks after the treatment. RESULTS: Baseline data before the treatment between the two groups were similar. The WOMAC scores significantly decreased and the SF-36 scores significantly increased after 8- week treatment in both groups compared with before the treatment (P < 0.05). SYXBD significantly decreased pain scores (P < 0.001), physical function scores (P < 0.001) and the total scores (P < 0.001) in WOMAC compared to Meloxicam. SYXBD significantly improved physical function (P = 0.021), bodily pain (P = 0.002) and general health (P = 0.014), with no significant difference in role emotional (P = 0.053), role physical (P = 0.517), vitality (P = 0.241), social function (P = 0.712) and mental health (P = 0.800) in SF-36 compared to Meloxicam. No adverse events were reported in the treatment group while 13 adverse events happened in the control group during the study. CONCLUSION: SYXBD, prepared based on the theory of ""Shaoyang dominating bone"", has a better curative efficay and safety in patients with KOA compared with Meloxicam. The TCM theory of ""Shaoyang dominating bone"" may be useful in KOA treatment.

Jisuikang, a Chinese herbal formula, increases neurotrophic factor expression and promotes the recovery of neurological function after spinal cord injury.

The Chinese medicine compound, Jisuikang, can promote recovery of neurological function by inhibiting lipid peroxidation, scavenging oxygen free radicals, and effectively improving the local microenvironment after spinal cord injury. However, the mechanism remains unclear. Thus, we established a rat model of acute spinal cord injury using a modified version of Allen's method. Jisuikang (50, 25, and 12.5 g/kg/d) and prednisolone were administered 30 minutes after anesthesia. Basso, Beattie, and Bresnahan locomotor scale scores and the oblique board test showed improved motor function recovery in the prednisone group and moderate-dose Jisuikang group compared with the other groups at 3-7 days post-injury. The rats in the moderate-dose Jisuikang group recovered best at 14 days post-injury. Hematoxylin-eosin staining and transmission electron microscopy showed that the survival rate of neurons in treatment groups increased after 3-7 days of administration. Further, the structure of neurons and glial cells was more distinct, especially in prednisolone and moderate-dose Jisuikang groups. Western blot assay and immunohistochemistry showed that expression of brain-derived neurotrophic factor (BDNF) in injured segments was maintained at a high level after 7-14 days of treatment. In contrast, expression of nerve growth factor (NGF) was down-regulated at 7 days after spinal cord injury. Real-time fluorescence quantitative polymerase chain reaction showed that expression of BDNF and NGF mRNA was induced in injured segments by prednisolone and Jisuikang. At 3-7 days after injury, the effect of prednisolone was greater, while 14 days after injury, the effect of moderate-dose Jisuikang was greater. These results confirm that Jisuikang can upregulate BDNF and NGF expression for a prolonged period after spinal cord injury and promote repair of acute spinal cord injury, with its effect being similar to prednisolone.