Treatment of radiation-induced brain injury with bisdemethoxycurcumin.

Radiation therapy is considered the most effective non-surgical treatment for brain tumors. However, there are no available treatments for radiation-induced brain injury. Bisdemethoxycurcumin (BDMC) is a demethoxy derivative of curcumin that has anti-proliferative, anti-inflammatory, and anti-oxidant properties. To determine whether BDMC has the potential to treat radiation-induced brain injury, in this study, we established a rat model of radiation-induced brain injury by administering a single 30-Gy vertical dose of irradiation to the whole brain, followed by intraperitoneal injection of 500 µL of a 100 mg/kg BDMC solution every day for 5 successive weeks. Our results showed that BDMC increased the body weight of rats with radiation-induced brain injury, improved learning and memory, attenuated brain edema, inhibited astrocyte activation, and reduced oxidative stress. These findings suggest that BDMC protects against radiation-induced brain injury.

Community-Based Rehabilitation Promotes the Functional Recovery of Patients After Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH), a severe disorder with the high death rate, high recurrence rate and high disability rate, affected the quality of human life. Community-based rehabilitation (CBR) helps disabled people at both community and family levels. However, the effect of CBR on the recovery of people after ICH remains unclear. METHODS: Patients were treated with the CBR training program, subsequently, medication compliance test, clinical neural impairment measurements, functional comprehensive assessments, improved Barthel index score, and life qualities assessments were to performed at 3-month or 6-month intervention of CBR to evaluate the influence of CBR on the medication compliance, physical function and life quality of patients after ICH. RESULTS: After the treatment of CBR, we observed that, the rate of medication compliance, motor function, functional comprehensive rating scale score, modified Barthel index score, and generic quality of life inventory-74 in the CBR-treated group were significantly higher than that in the control group; the neural impairment measure score in the CBR-treated group was significantly decreased in comparison to the control group. CONCLUSION: CBR increased the medication compliance, promoted the recovery of the neurological function and improved the life qualities of ICH patients.

BDMC protects AD in vitro via AMPK and SIRT1.

BACKGROUND: Alzheimer's disease (AD) is a common neurodegenerative disorder without any satisfactory therapeutic approaches. AD is mainly characterized by the deposition of ß-amyloid protein (Aß) and extensive neuronal cell death. Curcumin, with anti-oxidative stress (OS) and cell apoptosis properties, plays essential roles in AD. However, whether bisdemethoxycurcumin (BDMC), a derivative of curcumin, can exert a neuroprotective effect in AD remains to be elucidated. METHODS: In this study, SK-N-SH cells were used to establish an in vitro model to investigate the effects of BDMC on the Aß1-42-induced neurotoxicity. SK-N-SH cells were pretreated with BDMC and with or without compound C and EX527 for 30 min after co-incubation with rotenone for 24 h. Subsequently, western blotting, cell viability assay and SOD and GSH activity measurement were performed. RESULTS: BDMC increased the cell survival, anti-OS ability, AMPK phosphorylation levels and SIRT1 in SK-N-SH cells treated with Aß1-42. However, after treatment with compound C, an AMPK inhibitor, and EX527, an SIRT1inhibitor, the neuroprotective roles of BDMC on SK-N-SH cells treated with Aß1-42 were inhibited. CONCLUSION: These results suggest that BDMC exerts a neuroprotective role on SK-N-SH cells in vitro via AMPK/SIRT1 signaling, laying the foundation for the application of BDMC in the treatment of neurodegenerative diseases related to AMPK/SIRT1 signaling.

Bisdemethoxycurcumin exerts a cell-protective effect via JAK2/STAT3 signaling in a rotenone-induced Parkinson's disease model in vitro.

INTRODUCTION: Oxidative stress and cell apoptosis have both been suggested to be closely associated with the pathogenesis of Parkinson's disease (PD). Previously, bisdemethoxycurcumin (BDMC) has been shown to exhibit several desirable characteristics as a candidate neuroprotective agent, including antioxidant and anti-inflammatory activities in the nervous system. However, whether BDMC can exert cell-protective roles in an in vitro model of PD remains unknown. MATERIAL AND METHODS: SH-SY5Y cells were pretreated with BDMC, with or without AG490 and SI-201, for 30 min, followed by a co-incubation with rotenone for 24 h. Subsequently, a cell viability assay and western blotting was performed, and SOD and GSH activities were analyzed. RESULTS: The results revealed that the pretreatment with BDMC enhanced the cell survival, antioxidative stress capacity and the phosphorylation levels of JAK/STAT3 in SH-SY5Y cells treated with rotenone. However, following the incubation with AG490 and SI-201, inhibitors of the JAK/STAT3 signaling pathway, BDMC was unable to exert cell-protective roles in SH-SY5Y cells treated with rotenone. CONCLUSIONS: In conclusion, the results suggested that BDMC may exert a cell-protective role in SH-SY5Y cells in vitro via JAK2/STAT3 signaling, thus suggesting the possible application of BDMC for the treatment of neurodegenerative diseases related to JAK2/STAT3 signaling.

Bisdemethoxycurcumin inhibits oxidative stress and antagonizes Alzheimer's disease by up-regulating SIRT1.

INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disease. It can lead to progressive cognitive impairment, memory loss, and behavioral alterations. So far, the exact cellular and molecular mechanisms underlying this disorder remain unclear. And there are no effective treatments to prevent, halt, or reverse AD. In recent years, Chinese traditional medicine has become a new force in the treatment of AD, and the typical representatives of natural herbal ingredients are curcumin and its derivatives. Bisdemethoxycurcumin (BDMC), which is a classical derivative of curcumin, was found to have neuroprotective effects against a cell model of Alzheimer's disease (AD) in our previous studies. This study investigated the intrinsic mechanism of BDMC against AD in animal models. METHODS: In this study, BDMC was injected into the lateral ventricles of normal C57BL/6 mice, APP/PS mice, and APP/PS mice treated with EX527 (the inhibitor of SIRT1). Y maze and Morris water maze were used to test the learning and memory ability of mice. Nissl staining was used to observe the morphological changes of neurons. Immunofluorescence staining was used to detect Aß deposition in mice. The activities of GSH and SOD were determined to observe the levels of oxidative stress in mice. And Western blot analyses were used to detect content of SIRT1 in mice. RESULTS: In the APP/PS mice, after BDMC intervention, their cognitive function improved, oxidative stress adjusted, the number of neurons increased, Aß deposition decreased, and the level of SIRT1 expression increased. However, when SIRT1 is inhibited, BDMC on the improvement in the learning and memory ability and the improvement on oxidative stress in APP/PS1 mice were reversed. CONCLUSION: Our findings demonstrated that in the AD mice, BDMC has antagonistic effect on AD. And an intermediate step in the antagonism effect is caused by SIRT1 upregulation, which leading to decreased oxidative stress. Based on these, we concluded that BDMC injection into the lateral ventricle can act against AD by upregulating SIRT1 to antioxidative stress.

Ionizing radiation modulates vascular endothelial growth factor expression through STAT3 signaling pathway in rat neonatal primary astrocyte cultures.

BACKGROUND AND PURPOSE: Radiation-induced brain injury (RBI) usually occurs six months to three years after irradiation, often shows cognitive dysfunction, epilepsy, and other neurological dysfunction. In severe cases, it can cause a wide range of cerebral edema, even herniation. It seriously threatens the survival of patients and their quality of life, and it becomes a key factor in limiting the radiation dose and lowering the therapeutic efficacy in recent years. Therefore, studying the pathogenesis of RBI and exploring new therapeutic targets are of great significance. METHODS: In our study, we observed the activation and secretory function in astrocytes as well as the intracellular signal transducer and activator of transcription 3 (STAT3) signal transduction pathway activation status after exposing different doses of X-ray irradiation by using MTT, Immunocytologic analysis, and Western blot analysis. Further, we used the same way to explore the role of vascular endothelial growth factor (VEGF) in signal transduction pathways playing in the activation of astrocytes after irradiating through the use of specificInhivascular endothelial growth factorbitors of STAT3. RESULTS: Ast can be directly activated, reactive hyperplasia and hypertrophy, the expression of the activation marker glial fibrillary acidic protein is increased, and the expression of vascular endothelial growth factor (VEGF) in the cells is increased, which may lead to RBI. After the addition of STAT3 pathway inhibitor, most of the Ast radiation activation was suppressed, and the expression of high-level expression of VEGF decreased after irradiation. CONCLUSION: Our findings demonstrated that X-ray irradiation directly induced the activation of astrocytes in a persistent manner and X-ray irradiation activated STAT3 signaling pathway. As the same time, we found that X-ray irradiation induced the activation of astrocytes and secretion cytokine. The STAT3 signaling pathway may participate in the pathogenesis of radiation-induced brain injury.

Effects of Diet Based on IgG Elimination Combined with Probiotics on Migraine Plus Irritable Bowel Syndrome.

Several research studies have revealed that migraine has a solid link with gastrointestinal diseases especially irritable bowel syndrome (IBS). This study was carried out to investigate therapeutic potential of diet based on IgG elimination combined with probiotics on migraine plus irritable bowel syndrome. A total of 60 patients diagnosed with migraine plus IBS were recruited for the study. IgG antibodies against 266 food varieties were detected by ELISA. Then, the subjects were randomized into three groups for treatment of IgG elimination diet or probiotics or diet combined with probiotics. Migraine symptom, gut function score, medication use, and serum serotonin level were measured at baseline, 7 weeks, and 14 weeks. Improvement of migraine and gut symptom was achieved at a certain time point. Reduced use of over-the-counter- (OTC-) analgesics was seen in all groups. However, use of triptans did not show significant difference. An increased serum serotonin level was seen in subjects treated with elimination diet and elimination diet combined with probiotics. IgG elimination diet combined with probiotics may be beneficial to migraine plus IBS. It may provide new insight by understanding the intricate relationship between migraine and gastrointestinal diseases.