[Effects of Geniposide on the Neuroinflammation in Chronic Cerebral Hypoperfusion Rat Model].

OBJECTIVE: To investigate the effects and the mechanism of geniposide on the neuroinflammation occured in the neurodegeneration course of a chronic cerebral hypoperfusion rat model. METHODS: Permanent bilateral common carotid arteries occlusions was performed to induce gradient cognitive deficit in rats. The sham group was used as control group. Then 18 rats that met the Screening Criteria were randomly selected 8 weeks post surgery, and were randomly divided into three groups, the 2-VO rats with saline solution group (2-VO+saline group), 2-VO rats with 50 mg/kg per day geniposide group (2-VO+G50) and 2-VO rats with 100 mg/kg per day geniposide group (2-VO+G100). All intervention groups were daily administered with geniposide or saline for 4 weeks. The sham-operated rats were administrated with saline. Then the rats were tested for Morris water maze to evaluate the memory and learning ability. Rats were sacrificed to obtain cortex and hippocampus tissues for HE staining and to detect expression level of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB), and the level of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. RESULTS: The 2-VO+saline group rats showed significant longer escape latency and less percent time in target quadrant, compared with sham-operation group ( P<0.05). The escape latency of 2-VO+G50 and 2-VO+G100 groups were shorter than the 2-VO+saline group ( P<0.05), but still longer than the sham group ( P<0.05), the percent time in target quadrant of which were more than the 2-VO+saline group and less than the sham group. However, there was no significant difference between these two groups. HE staining of sham group showed that neurons in the cortex and hippocampus lined up in order, cellar nucleus were big and globular. HE staining results showed that there were obviously neuoral cells loss, severe cytomorphosis, structural disappearance and nuclear fragmentation in the 2-VO+saline group. The 2-VO+G50 and 2-VO+G100 groups showed less neurodamage than the 2-VO+saline group with less neuoral cells loss, cytomorphosis and ambiguous nucleus. GFAP, iNOS, NF-κB were all highly expressed in the process of cognitive dysfunction in rats after chronic cerebral ischemia, however geniposide intervention (50 and 100 mg/kg per day) significantly decreased the expression of the above proteins. In addition, much more TNF-α and IL-6 were released in brain induced by chronic cerebral ischemia, and the levels were decreased after chronic geniposide oral treatment. No significant differences were detected between 2-VO+G50 and 2-VO+G100 groups. CONCLUSION: These findings demonstrated that geniposide significantly prevented cognition deterioration induced by chronic cerebral hypoperfusion in rats. Geniposide inhibited neuroinflammation occurred in the process of chronic cerebral ischemia probably via reducing iNOS and NF-κB expression and suppressing the release of inflammatory factor TNF-α and IL-6.

Traditional Chinese Medicine treatment as maintenance therapy in advanced non-small-cell lung cancer: A randomized controlled trial.

OBJECTIVES: Maintenance therapy for patients with advanced non-small-cell lung cancer (NSCLC) is an increasingly hot topic in the field of clinical NSCLC research. This study aimed to evaluate the effects of Traditional Chinese Medicine (TCM) treatment as maintenance therapy on time to progression (TTP), quality of life (QOL), overall survival (OS) and 1-year survival rate in patients with advanced NSCLC. METHODS: This study was conducted as a randomized, controlled, open-label trial. 64 non-progressive patients who responded to initial therapy were randomized 1:1 to the TCM arm (treated with herbal injection (Cinobufacini, 20ml/d, d1-d10), herbal decoction (d1-d21) and Chinese acupoint application (d1-d21), n=32) or to the chemotherapy arm (treated with pemetrexed (non-squamous NSCLC, 500mg/m(2), d1), docetaxel (75mg/m(2), d1) or gemcitabine (1250mg/m(2), d1 and d8), n=32). Each therapy cycle was 21 days. They were repeated until disease progression, unacceptable toxicity, or until the patients requested therapy discontinuation. The primary end point was TTP; the secondary end points were QOL, OS and 1-year survival rate. "Intention-to-treat" analysis included all randomized participants. RESULTS: TCM treatment prolonged median TTP for 0.7 months compared with chemotherapy, but it was not statistically significant (3.0 months vs. 2.3 months, P=0.114). Median OS time for TCM treatment did not offer a significant advantage over for chemotherapy (21.5 months vs. 18.8 months, P=0.601). 1-year survival rate of TCM treatment significantly improved than that of chemotherapy (78.1% vs. 53.1%, P=0.035). TCM treatment can significantly improve QOL when compared to chemotherapy as assessed by EORTC QLQ-C30 and EORTC QLQ-LC13 QOL instruments. CONCLUSIONS: TCM maintenance treatment had similar effects on TTP and OS compared with maintenance chemotherapy, but it improved patients' QOL and had higher 1-year survival rate. TCM Maintenance treatment is a promising option for advanced NSCLC patients without progression following first-line chemotherapy.

Zuo Jin Wan reverses P-gp-mediated drug-resistance by inhibiting activation of the PI3K/Akt/NF-κB pathway.

BACKGROUND: Zuo-Jin-Wan (ZJW), a traditional Chinese medicine formula, has been identified to be effective against drug resistance in cancer. In the present study, we investigated the effect of ZJW on acquired oxaliplatin-resistant and the PI3K/Akt/NF-κB pathway in vitro. METHODS: We tested the dose-response relationship of ZJW on reversing drug-resistance by CCK-8 assay and flow cytometry analysis in vitro. The protein expression of P-gp, MRP-2, LRP, and ABCB1 mRNA expression level were evaluated by Western blot and quantitative RT-PCR. The activities of PI3K/Akt/NF-κB pathway were also examined with or without ZJW, including Akt, IκB, p65 and their phosphorylation expression. RESULTS: We found that ZJW significantly enhanced the sensitivity of chemotherapeutic drugs and increased oxaliplatin (L-OHP)-induced cell apoptosis in a time- and dose-dependent manner. Moreover, both ZJW and a PI3K specific inhibitor (LY294002) suppressed phosphorylation of Akt (Ser473) and NF-κB, which is necessary in the activation of the PI3K/Akt/NF-κB pathway. The effect of ZJW in reversing drug-resistance and suppressing phosphorylation of Akt (Ser473) and NF-κB were weakened after treatment with a PI3K/Akt activator in HCT116/L-OHP cells. CONCLUSIONS: Our study has provided the first direct evidence that ZJW reverses drug-resistance in human colorectal cancer by blocking the PI3K/Akt/NF-κB signaling pathway, and could be considered as a useful drug for cancer therapy.

[Effect of integrated Chinese medical treatment (as maintenance therapy) on the survival time of patients with advanced non-small-cell lung cancer: a clinical study].

OBJECTIVE: To observe clinical effect of integrated Chinese medical (CM) treatment (as maintenance therapy) on the progression-free survival (PFS) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) after first-line chemotherapy. METHODS: The study was a prospective, randomized, controlled clinical trial. Totally 69 non-progressive advanced NSCLC patients treated with first-line chemotherapy were randomly assigned to the test group (34 cases) and the control group (35 cases). Patients in the control group were treated with one Western drug chemotherapy (Gemcitabine or Alimta or docetaxel). Those in the test group were treated with integrated CM treatment (CM decoction, CM Intravenous preparation, and point application). Each cycle consisted of 21 days. Treatment lasted till the disease progressed, or intolerable toxic/adverse reactions occurred, or patients refused to continue the treatment. Patients' life spans were regularly followed-up. RESULTS: (1) The median cycle of maintenance therapy was 2 cycles for two groups with no statistical difference (P =0.274). The median PFS was 12.43 weeks in the test group and 10.00 weeks in the control group, showing statistical difference (P =0.025). The middle survival time (MST) was 18.8 months in the test group and 16.73 months in the control group, showing no statistical difference (P =0.437). CONCLUSION: CM treatment (as maintenance therapy) showed quail effect to one Western drug chemotherapy in prolonging patients' life span.

Chemotherapy in conjunction with traditional Chinese medicine for survival of elderly patients with advanced non-small-cell lung cancer: protocol for a randomized double-blind controlled trial.

BACKGROUND: Traditional Chinese medicine (TCM) is considered an important complementary therapy with beneficial effects for cancer patients. Elderly patients with non-small-cell lung cancer (NSCLC) are a complex patient group with increasing co-morbidity and shrinking physiological reserve, and may derive substantial benefit from the supportive aspects of TCM. Researchers from Shanghai Longhua Hospital found that qi and yin deficiency is a common syndrome in patients with stage III or IV lung cancer. This project was designed to study the combination of single-agent chemotherapy with TCM methods of benefiting qi and yin in elderly patients with advanced NSCLC. METHODS AND DESIGN: This is a double-blind controlled, multi-center, and prospective study with randomly selected participants from elderly NSCLC patients in China. Seventy-six patients who meet the inclusion criteria will be allocated into two groups, which will receive treatments of 3-week single-agent chemotherapy with TCM or placebo for four cycles. Progression-free survival (PFS) is the primary end point, and the secondary end points are overall survival, objective response rate, time-to-progression, and quality of life (EORTC QLQ-LC43, and TCM syndrome score). Meanwhile, other end points such as toxicity, side effects and safety of the treatments will be assessed. DISCUSSION: Results from this study may provide evidence on the effectiveness, and parameters for the usage of single-agent chemotherapy combined with or without TCM on PFS of elderly patients with NSCLC. TRIAL REGISTRATION: ClinicalTrials.gov. (Identifier: NCT01780181).

Effects of Erlong Zuoci pill and its disassembled prescriptions on gentamicin-induced ototoxicity model in vitro.

OBJECTIVE: To study the effects of Erlong Zuoci Pill (, ELZCP) and its disassembled: prescriptions on gentamicin (GM)-induced ototoxicity model in vitro. METHODS: After the spiral organ of cochleae: of newborn mice (postnatal days: 2-3) cultured for 24 h, GM alone or combined with water extracting-alcohol precipitating solution of ELZCP or with its disassembled prescriptions was added. Hair cells were observed under a fluorescence microscope after TRITC-phalloidin staining, and the cochlear hair cell loss rate was calculated by counting the whole cochlear hair cells and analyzed by whole cochlear hair cells analyzing software. RESULTS: GM induced cochlear outer hair cells (OHCs) and inner hair cells (IHCs) injuries in a dose-dependent manner, and they were significantly different as compared with those in the normal control group (P<0.05, P<0.01). ELZCP at the concentration of 0.003-3 mg/mL could decrease the hair cells loss induced by the 0.3 mmol/L GM (P<0.05, P<0.01), the effects was in a dose-dependent manner, and the concentration of 0.3 mg/mL showed the optimal protective effect. For the ELZCP disassembled prescriptions, Liuwei-Dihuang could decrease OHC loss rate than that in the 0.3 mmol/L GM model group (P<0.05), but the OHC loss rate was still higher than that in the ELZCP group (P<0.01), which indicated that the protective effect of hair cells by Liuwei-Dihuang was not better than that of ELZCP. Poria decreased OHC loss rate from 72.1 % +/-3.7 % to 58.8 %+/- 8.2 % (P<0.05). CONCLUSIONS: ELZCP could play a role in antagonizing the injury of cochlear hair cells induced by GM ototoxicity,: and its disassembled prescriptions, Liuwei-Dihuang was the main component to protect the cochlear hair cells from GM-induced ototoxicity, and Magnetitum combined with Radix Bupleurui could strengthen the action of the whole prescription; Poria could reduce GM-induced OHC loss.