Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.

Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities. Rationale: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism. Methods: Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry. Results: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1ß, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs production in PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism. Conclusions: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.

Hyperoside Suppresses Lipopolysaccharide-induced Inflammation and Apoptosis in Human Umbilical Vein Endothelial Cells.

Finding the novel drug from the effective components of traditional Chinese herbal medicine is a hotspot of the modern pharmacological research. Hyperoside (HYP) belongs to flavonoid glycosides, and it has various properties, such as anti-inflammation, anti-spasm, anti-diuretic, antitussive, lowering blood pressure, and lowering cholesterol effects as well as protective effects for the cardiac and cerebral blood vessels. The purpose of this study was to investigate the effects of HYP on inflammatory and apoptotic responses in vascular endothelial cells stimulated by lipopolysaccharide (LPS) and further to identify the possible mechanisms underlying these effects. In our study, human umbilical vein endothelial cells (HUVECs) were stimulated with 1 µg/mL LPS in the presence or absence of HYP (10, 20 and 50 µmol/L). Our results indicated that HYP alone exerted no cytotoxicity on HUVECs, while it had an up-regulatory effect on the viability of HUVECs induced by LPS in a dose-dependent manner; increased mRNA expression of IL-1ß, IL-6, TNFα and iNOS induced by LPS was attenuated after treatment with HYP both in a dose-and time-dependent manner; LPS-induced HUVECs apoptosis and cleaved-caspase 8, 9, 3 were all significantly reduced by HYP. Furthermore, the possible pathway involved in apoptosis and inflammation by HYP was detected, and the results showed that when treated with HYP, LPS-induced mitochondrial membrane instability was significantly inhibited through up-regulation of Bcl-2 and down-regulation of Bax. Furthermore, the expression of TLR4 and the phosphorylation of IκBα and p65 in LPS-treated cells were blocked by HYP. Our results suggested that HYP treatment prevented HUVECs from LPSinduced inflammation and apoptosis responses, which might be mediated by inhibiting TLR4/NFκB pathway.

Melatonin improves cardiac function in a mouse model of heart failure with preserved ejection fraction.

Melatonin has been shown to inhibit myocardial infarction-induced apoptosis, its function in heart failure with preserved ejection fraction (HFpEF) has not been investigated. This study aimed to investigate whether melatonin attenuates obesity-related HFpEF. Male mice were fed a high-fat diet (HFD) from weaning to 6 months of age to induce HFpEF. The mice were orally administered melatonin (50 mg/kg) by 3 weeks. Diastolic function was significantly improved by melatonin supplementation in mice fed an HFD. Melatonin attenuated obesity-induced myocardial oxidative stress and apoptosis and promoted the secretion of C1q/tumour necrosis factor-related protein 3 (CTRP3) by adipose tissue. And depletion of circulating CTRP3 largely abolished melatonin-mediated cardio-protection. Melatonin-mediated secretion of adipocyte-derived CTRP3 activated NF-E2-related factor 2 (Nrf2), which were largely abrogated by knocking down CTRP3 in adipocytes or Nrf2 in cardiomyocytes. Nrf2 activation was mediated by miR-200a, and a miR-200a antagomir offset the effects of melatonin-conditioned medium on Nrf2 expression. Our results indicate that melatonin can be used to treat and prevent obesity-related HFpEF.

Cardioprotective potential of Dendrobium officinale Kimura et Migo against myocardial ischemia in mice.

Dendrobium officinale Kimura et Migo has been used for thousands of years to promote body fluid production; however, little is currently known regarding its effects on the heart. The present study aimed to explore the cardioprotective potential of the water extract of Dendrobium officinale Kimura et Migo (DOE) on myocardial ischemia in mice. A mouse model of myocardial ischemia was induced following ligation of the left anterior descending coronary artery. Prior to the operation, mice were administered a vehicle or DOE for 2 weeks. Following the operation, ST elevation was measured. To estimate the extent of myocardial damage, infarct size analysis and histopathological examination were performed. The activities of cardiac marker enzymes [creatine kinase (CK)­MB and lactate dehydrogenase (LDH)] and antioxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] were also analyzed to explore the underlying mechanisms. Treatment with DOE decreased infarct size and the number of apoptotic cardiomyocytes; reduced serum CK­MB, LDH and MDA activities; and increased SOD levels. According to western blotting, DOE conferred protection against myocardial ischemic injury via the regulation of Meis1 expression. These results indicated that DOE may exert potential cardioprotective effects against myocardial ischemia; these effects may be associated with its antioxidant activity, and its ability to inhibit cardiac cell apoptosis and to regulate Meis1 expression.

[Treatment of cerebral palsy children by integrative medical sequential method: a clinical efficacy observation].

OBJECTIVE: To observe the efficacy of integrative medical sequential method in treating cerebral palsy (CP) children's intelligence development, muscular tension, serum interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-alpha). METHODS: Totally 111 CP children were randomly assigned to the control group (50 cases) and the treatment group (61 cases). All patients received comprehensive rehabilitation training and intravenous dripping of Monosialotetrahexosylganglioside Sodium Injection for 10 days. But those in the treatment group additionally received Chinese medical enema for brain resuscitation, relieving rigidity of muscles and activating collaterals for 14 days. Then they started another medication cycle and lasted for a total of 6 cycles. Serum IL-6 levels and TNF-alpha contents were determined before treatment. Scoring for muscular tension, Gesell score for intelligence development, contents of serum IL-6 and TNF-alpha were assessed before and after treatment in the two groups. RESULTS: Compared with before treatment in this group, muscular tension, Gesell scores for intelligence development all decreased in the two groups (P < 0.05). As for inter-group comparison, the decrement was more obvious in the treatment group than in the control group (P < 0.05). The total effective rate was 86.9% in the treatment group and 76.0% in the control group (P < 0.05). The contents of IL-6 and TNF-alpha were obviously reduced in the treatment group and the control group after treatment (P < 0.01). The decrement was more obvious in the treatment group (P < 0.05). CONCLUSION: The two treatment methods were effective for CP children, but the efficacy was superior in the treatment group than in the control group, indicating integrative medical methods could play a synergistic effect and optimize the treatment program for CP.

[Influence of different processed methods on 10 kinds of ginsensides in Panacis Quinquefolii Radix].

The influence on 10 kinds of ginsensides of different processed methods of Panacis Quinquefolii Radix was discussed. White Panacis Quinquefolii Radix (sliced and dried at -80 °C), red Panacis Quinquefolii Radix( steamed, sliced and dried at -80 °C) and commercial Radix Panacis Quinquefolii (dried by electric blast air) processed by different methods. HPLC-PDA-ESI- MS method was established before by our team. Ten kinds of ginsenosides of them were determined. The content of total ginsenosides were as follow: commercial Panacis Quinquefolii Radix > white Panacis Quinquefolii Radix > red Panacis Quinquefolii Radix. Compared with white Panacis Quinquefolii Radix, the content of Re, Rc, Rb3 and Rb2 of Red Radix Panacis Quinquefolii decreased but increased that of Rg,, Rb1. Both Rg2 and Rg, were not found in white Panacis Quinquefolii Radix and commercial Panacis Quinquefolii Radix by PDA detector, and low response in ESI-MS, while red Panacis Quinquefolii Radix was to the high content that of 0. 027% and 0.040 1%. The constituent of RA0 of red Panacis Quinquefolii Radix was higher than the other two. After Panacis Quinquefolii Radix processed, the kind and content of ginsensides were significantly changed. The constituent of some kinds of ginsensides was increased and some decreased. Rf was not found in all Panacis Quinquefolii Radix samples which were consistent with the former documents.

[Research on dynamic accumulation of nine ginsenosides and two pseudo-ginsenosides of Panax quinquefolium root of different growth years and harvest months in Canada].

OBJECTIVE: To research the dynamic accumulation of ginsenosides Rg1, Re, Rb1, Rg2, Rc, Rb2, Rb3, Rd, Rg3 and pseudo-ginsenosides F11,RT5, which was grown from one- to five-year-old and harvested from May to September of Panax quinquefolium root in Canada. METHODS: RP-HPLC-ELSD was adopted. The analysis was performed on a Dimaonsil C18 (250 mm x 4.6 mm, 5 µm) column, the mobile phase was acetonitrile (A)-deionized water (B) in gradient elution mode. The flow rate was 1.0 mL/min and column temperature was set at 30 °C. The carrier gas was nitrogen with flow rate of 2.8 L/min, the drift tube temperature was 100 °C, and the injection volume was 10 µL. The principle component analysis and cluster analysis of SPSS software (version 19.0) were conducted for the data analysis. RESULTS: The RP-HPLC-ELSD method for determining simultaneously nine ginsenosides and two pseudo-ginsenosides was established. The total content of ginsenosides of one- to two-year-old was low and increased from May to September in each year. That of three- to five-year-old declined from June to July and increased from August, and was the highest in September of three- to five-year-old samples. The total content from September of three-year-old samples was similar. The content of nine ginsenosides and two pseudo-ginsenosides was relatively high in all the samples except ginsenoside Rc, which wasn't determined in some samples. The ginsenosides Rd, Rb3 and pseudo-ginsenoside F11 were higher than others. The principle component analysis results showed that ginsenosides Rg1, Re, Rb1, Rc, Rb2, Rb3, Rg3 and pseudo-ginsenosides F11,RT5 could be the characteristic ginsenosides of Panax quinquefolium root in Canada. The cluster analysis indicated that the chemical constituent and dynamic accumulation of ginsenosides of one- to two-year-old was similar except the sample of July of four-year-old and there was no obvious difference of three- to five-year-old. CONCLUSION: With the consideration of the content of ginsenoside, cultivation cost of four- to five-year-old, and risk of waterlogging and plant diseases, it is suggested that Panax quinquefolium root from September of three-year-old can be regarded as the same quality.

Characterization of tibetan medicine zuota by multiple techniques.

Zuota is regarded as the king of Tibetan medicine. However, due to the confidentiality of this precious medicine, the scientific characterization of Zuota is very scarce, which limits the pharmacology and biosafety studies of Zuota. Herein, we collected four different Zuota samples from Tibet, Qinghai, Gansu, and Sichuan and characterized them by multiple techniques. Our results showed that Zuota was mainly an inorganic mixture of HgS, sulfur, and graphite. Morphologically, Zuota samples were composed of nanoparticles, which further aggregated into microsized particles. Chemically, the majorities of Zuota were S and Hg (in the forms of HgS and pure sulfur). All samples contained pure sulfur with orthorhombic crystalline. Zuota from Qinghai province had different HgS crystalline, namely, hexagonal crystalline. The others were all face-centered cubic crystalline. Carbon in Zuota NPs was in the form of graphite. The implication to future studies of Zuota was discussed.

[Impact of acupuncture on 24 h intraocular pressure of glaucoma].

OBJECTIVE: To explore the mechanism of acupuncture on the treatment of glaucoma so as to find out a kind of simple and effect approach to control and stabilize intraocular pressure (IOP) of patients with glaucoma. METHODS: Thirty-nine cases (75 eyes) of glaucoma (unstable control of IOP) were treated with acupuncture at Sibai (ST 2), Cuanzhu (BL 2), Jingming (BL 1), Qiuhou (EX-HN 7), etc. IOP before and after acupuncture, at 10 a.m, 2 p.m, 6 p.m, 10 p.m., at 5 a.m. and 7 a.m. on the second day as well as diurnal IOP variation in 24 h were observed separately. RESULTS: After acupuncture, IOP at each time point reduced as compared with that before acupuncture. IOP at 5 a.m., 7 a.m., 10 a.m., 6 p.m. and 10 p.m. after acupuncture was different significantly in statistics as compared with that before acupuncture correspondingly (all P<0.05). After acupuncture, 24 h diurnal IOP variation was (5.31 +/- 2.84) mmHg, which was lower significantly than (7.06 +/- 3.86) mmHg before acupuncture (P<0.05). CONCLUSION: For the patients with unstable control of IOP, acupuncture can not only reduce IOP, but also stabilize 24 h diurnal IOP variation and benefit the visual function of patients with glaucoma.

Songorine, a diterpenoid alkaloid of the genus Aconitum, is a novel GABA(A) receptor antagonist in rat brain.

Songorine, a diterpenoid alkaloid isolated from the genus Aconitum, was recently found to enhance the excitatory synaptic transmission in rat hippocampus. The mechanism underlying the effects was examined in the present study. The alkaloid at 0.1-300 microM inhibited the specific binding of [(3)H]muscimol to Triton-treated synaptic membranes of rat brain in a concentration-dependent manner (IC(50)=7.06 microM; 95% confidence limits: 3.28-10.84 microM). Scatchard analysis and Lineweaver-Burk double reciprocal plot of [(3)H]muscimol saturation binding data indicate a non-competitive inhibition of the alkaloid on the gamma-aminobutyric acid(A) (GABA(A)) receptor. In acutely dissociated rat hippocampal neurons the alkaloid did not elicit current response, but markedly inhibited the GABA-induced inward current (IC(50)=19.6 microM). The results suggest that songorine is a novel non-competitive antagonist at the GABA(A) receptor in rat brain.