Direct Stimulation of Adult Neural Stem/Progenitor Cells In Vitro and Neurogenesis In Vivo by Salvianolic Acid B

Background: Small molecules have been shown to modulate the neurogenesis processes. In search for new therapeutic drugs, the herbs used in traditional medicines for neurogenesis are promising candidates. Methodology and Principal Findings: We selected a total of 45 natural compounds from Traditional Chinese herbal medicines which are extensively used in China to treat stroke clinically, and tested their proliferation-inducing activities on neural stem/progenitor cells (NSPCs). The screening results showed that salvianolic acid B (Sal B) displayed marked effects on the induction of proliferation of NSPCs. We further demonstrated that Sal B promoted NSPCs proliferation in dose- and time-dependent manners. To explore the molecular mechanism, PI3K/Akt, MEK/ERK and Notch signaling pathways were investigated. Cell proliferation assay demonstrated that Ly294002 (PI3K/Akt inhibitor), but neither U0126 (ERK inhibitor) nor DAPT (Notch inhibitor) inhibited the Sal B-induced proliferation of cells. Western Blotting results showed that stimulation of NSPCs with Sal B enhanced the phosphorylation of Akt, and Ly294002 abolished this effect, confirming the role of Akt in Sal B mediated proliferation of NSPCs. Rats exposed to transient cerebral ischemia were treated for 4 weeks with Sal B from the 7th day after stroke. BrdU incorporation assay results showed that exposure Sal B could maintain the proliferation of NSPCs after cerebral ischemia. Morris water maze test showed that delayed post-ischemic treatment with Sal B improved cognitive impairment after stroke in rats

The Efficacy of Jing Wan Hong Ointment for Nerve Injury Diabetic Foot Ulcer and Its Mechanisms

Jing Wan Hong ointment contains 30 kinds of Chinese herbs, with functions of activating blood circulation to disperse blood stasis, clearing heat, eliminating dampness, and reducing swelling by detoxification. Therefore, Jing Wan Hong ointment may facilitate the healing of ulcers. The aim of this study was to evaluate the efficacy and mechanisms of Jing Wan Hong ointment for healing diabetic foot ulceration in Wistar rats induced by streptozotocin and sciatic nerve damage. The results showed that Jing Wan Hong ointment had a marked effect on foot ulcers in diabetic rats induced by initial nerve injury. These effects were manifested by reducing the foot ulcer size and Wagner grade after seven days of treatment. The diabetic rats with foot ulcers were almost healed after 21 days of treatment. Moreover, the mechanisms of this effect seem to be dependent on increased expression of PDGF mRNA, but there was no influence on the expression of TGF-β, VEGF, and FLT-1 mRNA

Optimization of High-yield ACE Inhibitory Peptide Fermented Milk by Response Surface Methodology and Its Texture and Flavor Characteristics

For the sake of producing fermented milk enriched in Angiotensin-I converting enzyme (ACE) inhibitory peptides, the fermented milk was fortified with sodium caseinate and a high ACE inhibitory peptide producing strain Lb. plantarum M11. The factors of sodium caseinate addition amount, inoculation amount, and fermentation temperature were selected for investigation. Aside from that, a three-factor, three-level response surface experiment was conducted on the basis of single-factor experiments to obtain the optimal process conditions for producing ACE inhibitory peptide-enriched fermented milk, as well as to probe deep into the effects of sodium caseinate and Lb. plantarum M11 on the texture and flavor characteristics of the fermented milk. As demonstrated by the results, the highest ACE inhibitory activity of the fermented milk was 83.15% when the condition was set as a sodium caseinate addition amount of 2%, inoculation amount of 1.5×107 CFU/mL, and fermentation temperature of 40 ℃. The addition of Lb. plantarum M11 and sodium caseinate strikingly heightened the hardness, consistency, cohesiveness, and viscosity index of the fermented milk (P<0.05), resulting in better texture characteristics. As illustrated by the electronic tongue analysis results, the addition of Lb. plantarum M11 enhanced the acidity and richness of the fermented milk, and neither Lb. plantarum M11 nor sodium caseinate had a significant impact on saltiness, bitterness, astringency, astringent aftertaste, bitter aftertaste, or umami. This study provides a theoretical basis for the development of functional fermented milk with antihypertensive activity

The efficacy of betulinic acid in triple-negative breast cancer

Purpose: The treatment of triple-negative breast cancer remains a daunting challenge with the standard-of-care treatments eventually failing due to acquired drug resistance, toxic side effects and the presence of a deregulated immune response. New treatments for overcoming these drawbacks include the use of plant extracts. Study design: In this study, the efficacy of betulinic acid, a naturally abundant phytochemical exhibiting anti-inflammatory and anti-proliferative activity, has been evaluated for the treatment of triple-negative breast cancer MDA-MB-231 and MDA-MB-468 cell lines. Furthermore, the ability of betulinic acid to inhibit angiogenesis was also determined. Results: Here, we report that betulinic acid was able to inhibit the inflammatory response, inhibit angiogenesis and cause cell cycle arrest ultimately causing apoptosis in triple-negative breast cancer cells. Our findings support that the identification of naturally occurring anti-tumour compounds may provide a chemotherapeutic approach for the treatment of triple-negative breast cancer. Conclusion: Overall, our results provide a molecular basis for the ability of betulinic acid to mediate apoptosis, suppress inflammation and inhibit angiogenesis in triple-negative breast cancer cell lines

Regulated deficit irrigation improved fruit quality and water use efficiency of pear-jujube trees

Regulated deficit irrigation (RDI) was applied on field-grown pear-jujube trees in 2005 and 2006 and its effects on crop water-consumption, yield and fruit quality were investigated. Treatments included severe, moderate and low water deficit treatments at bud burst to leafing, flowering to fruit set, fruit growth and fruit maturation stages. Different deficit irrigation levels at different growth stages had significant effects on the fruit yield and quality. Moderate and severe water deficits at bud burst to leafing and fruit maturation stages increased fruit yield by 13.2-31.9% and 9.7-17.5%, respectively. Fruit yield under low water deficit at fruit growth and fruit maturation stages was similar to that of full irrigation (FI) treatment. All water deficit treatments reduced water consumption by 5-18% and saved irrigation water by 13-25% when compared to the FI treatment. During the bud burst to leafing stage, moderate and severe water deficits did not have effect on the fruit quality, but significantly saved irrigation water and increased fruit yield. Low water deficit during the fruit growth stage and low, moderate and severe water deficits during the fruit maturation stage had no significant effect on the fruit weight and fruit volume but reduced fruit water content slightly, which led to much reduced rotten fruit percentage during the post-harvest storage period. Such water deficit treatments also shortened the fruit maturation period by 10-15 d and raised the market price of the fruit. Fruit quality shown as fruit firmness, soluble solid content, sugar/acid ratio and vitamin C (VC) content were all enhanced as a result of deficit irrigation. Our results suggest that RDI should be adopted as a beneficial agricultural practice in the production of pear-jujube fruit.

Reversal of Muscle Atrophy by Zhimu-Huangbai Herb-Pair via Akt/mTOR/FoxO3 Signal Pathway in Streptozotocin-Induced Diabetic Mice

<div><p>Skeletal muscle atrophy is one of the serious complications of diabetes. Zhimu-Huangbai herb-pair (ZB) is widely used in Chinese traditional medicine formulas for treating Xiaoke (known as diabetes) and its complications. However, the effect of ZB on reversal of muscle atrophy and the underlying mechanisms remain unknown. In this research, we investigated the effect and possible mechanisms of ZB on skeletal muscle atrophy in diabetic mice. Animal model of diabetic muscle atrophy was developed by high fat diet (HFD) feeding plus streptozotocin (STZ) injection. After oral adminstration of ZB for 6 weeks, the effects of ZB on reversal of muscle atrophy and the underlying mechanisms were evaluated by biochemical, histological and western blot methods. The skeletal muscle weight, strength, and cross-sectional area of diabetic mice were significantly increased by ZB treatment. Biochemical results showed that ZB treatment reduced the serum glucose level, and elevated the serum insulin-like growth factor 1 (IGF-1) and insulin levels significantly compared with untreated diabetic group. The western blot results showed that ZB activated the mTOR signal pathway, shown as increased phosphorylations (p-) of Akt, mTOR, Raptor, S6K1 and reduced Foxo3 expression compared with the model group. ZB could reverse muscle atrophy in diabetic mice. This may be through activation of mTOR signaling pathway that promotes protein synthesis, and inactivation foxo3 protein that inhibits protein degradation. These findings suggested that ZB may be considered as a potential candidate drug in treatment of diabetic muscle atrophy.</p></div

Salvianolic acid B promoted NSPCs proliferation in a PI3K/Akt -independent pathway.

<p>NSPCs were cultured in the proliferation medium containing Sal B (20 µM) in the presence and absence of the PI3K inhibitor Ly294002 (20 µM), MEK inhibitor U0126 (10 µM) or Notch inhibitor DAPT (10 µM) for 2 days. Cell survival was assessed by MTS assay. Data represent the mean ± S.D. from three independent experiments. **<i>P</i><0.01 as compared with control,##<i>P</i><0.01 as compared with Sal B-treated cells.</p

ZB increased muscle weight and protein content of diabetic mice.

<p>A: gastrocnemius weight of the mice during treatment in each group. B: quadriceps weight of the mice during treatment in each group. C: total gastrocnemius protein of the mice during treatment in each group. D: total quadriceps protein of the mice during treatment in each group. Data are expressed as the means±SD. Data are expressed as the means±SD. * <i>P</i><0.01, ** <i>P</i><0.01 vs. nondiabetic control. ^# P<0.05 vs. Model group.</p