Search

Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear. Exploring the mechanism of BHP against EDRE. Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB). Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments. Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM. [Display omitted] • Presentation of "early diabetic retinal edema" as a crucial therapeutic point. • Dyslipidemia is believed to play a significant influence in the progression of EDRE. • The mechanism of BHP anti-EDRE was studied. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance G. rigescens Franch (Long Dan Cao in Chinese) is a well-known TCM herb. It is clinically used with other drugs for the treatment of brain diseases such as epilepsy, postherpetic neuralgia in China. Aim of study In our previous study, the 11 dihydroxybenzoates compounds with NGF mimicking activity from G. rigescens Franch were found. In the present study, the neurogenesis and neuroprotection of a mixture of benzoates ( n-GS) were investigated in animal level. Materials and methods The NGF mimicking activity of n-GS from G. rigescens Franch was examined in PC12 cells. The neurogenesis effects of n-GS were investigated in ICR mice with 5-bromo-2-deoxyuridine (BrdU) and neuronal neclei (NeuN) double immunostaining. Furthermore, the neuroprotection effects of n-GS on the memory in a scopolamine (SCO)-induced mouse model were evaluated with animal behavior tests. Results The NGF-mimicking function and neurogenesis of n-GS were observed in PC12 cells and in normal mice. Subsequently, we investigated the effects of n-GS on the memory in a SCO-induced mouse model. In Y-maze test, SCO significantly lowered the alternation. This finding was reversed by n-GS and donepezil (DONE). SCO significantly impaired the mice's performance in novel object recognition (NOR) and Morris water maze (MWM) tests. The time spent to explore the novel object was longer in the n-GS- and DONE-treated groups than in the SCO control group. In the MWM test, the escape latency of n-GS- and DONE-treated groups was shorter than that of the SCO control group. Mechanism study showed that SCO significantly reduced superoxide dismutase (SOD) but increased the activities of acetylcholinesterase (AChE) and the levels of malondialdehyde (MDA) in the hippocampus and cerebral cortex, which all can be improved by n-GS and DONE. Additionally, the phosphorylation of type 1 insulin-like growth factor (IGF-1) receptor, extracellular signal-regulated kinase (ERK), and cAMP responsive element-binding (CREB) protein in the hippocampus was significantly up-regulated in the treatment group compared with that in the SCO group. Conclusions n-GS could alleviate impaired memory of the SCO-induced mice model by inhibiting AChE activity and oxidative stress, and regulating the IGF-1R/ERK signaling pathway. [ABSTRACT FROM AUTHOR]

The association between PM 2.5 (particulate matter ≤ 2.5 µm) short-term exposure and its health effect is non-linear from the epidemiological studies. And this nonlinearity is suggested to be related with the PM 2.5 heterogeneity, however, the underlying biological mechanism is still unclear. Here, a total of 38 PM 2.5 filters were collected continuously for three weeks in winter Beijing, with the ambient PM 2.5 varying between 10 and 270 µg/m3. Human monocytes-derived macrophages (THP-1) were treated with PM 2.5 water-soluble elutes at 10 µg/mL to investigate the PM 2.5 short-term exposure effect from a proinflammatory perspective. The proinflammatory cytokine tumor necrosis factor (TNF) induced by the PM 2.5 elutes at equal concentrations were unequal, showing the heterogeneity of PM 2.5 proinflammatory potentials. Of the various chemical and biological components, lipopolysaccharide (LPS) showed a strong positive association with the TNF heterogeneity. However, some outliers were observed among the TNF-LPS association. Specifically, for PM 2.5 from relatively clean air episodes, the higher LPS amount corresponded to relatively low TNF levels. And this phenomenon was also observed in the promotion tests by treating macrophages with PM 2.5 elutes dosed with additional trace LPS. Gene expression analysis indicated the involvement of oxidative-stress related genes in the LPS signaling pathway. Therefore, a potential oxidative-stress-mediated suppression on the PM 2.5 -borne LPS proinflammatory effect was proposed to be accounted for the outliers. Overall, the results showed the differential role of LPS in the heterogeneity of PM 2.5 proinflammatory effects from a component-based perspective. Future experimental studies are needed to elucidate the signaling pathway of LPS attached on PM 2.5 from different air quality episodes. [Display omitted] [ABSTRACT FROM AUTHOR]

Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4)-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. The lavandulyl flavonoid (kurarinol A, 1) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What's more, we found that treatment with kurarinol A (1) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. These findings demonstrated that the novel compound (kurarinol A, 1) possessed notable hepatoprotective activity against CCl 4. It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury. [Display omitted] • Kurarinol A, a new lavandulyl flavonoid from S. flavescens , showed significant hepatoprotective activity against CCl 4 induced liver injury in vitro and in vivo for the first time. • Kurarinol A attenuate CCl 4 -induced oxidative damage by activating the mRNA levels of HO-1, SOD2 and Nrf2 in the hepatic. • Kurarinol A exerted hepatoprotective activities through possible mechanisms involved in modulating the TLR2/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

• IL-11 directly protects neuronal cells from oxidative damage caused by H 2 O 2 and reduces neuronal apoptosis. • Transcriptome analysis suggests that the JAK/STAT pathway may be involved in the antioxidant activity of IL-11. • Rescue experiments and animal models demonstrated that IL-11 prevented neuronal apoptosis caused by oxidative imbalance through activation of the JAK/STAT signaling pathway and promoted the recovery of motor function in SCI rats. Excess reactive oxygen species (ROS) generated by oxidative stress is a crucial factor affecting neuronal dysfunction after spinal cord injury (SCI). IL-11 has been reported to have antioxidative stress capacity. In the present study, we investigated the protective effect and mechanism of IL-11 against neuronal cell damage caused by oxidative imbalance. We established a H 2 O 2 -induced oxidative stress injury model in PC12 cells and observed the effects of IL-11 on cellular activity, morphology, oxidase and antioxidant enzymes, and ROS release. Furthermore, the effect of IL-11 on apoptosis of PC12 cells was assessed by flow cytometry, a TUNEL assay and Western blotting. Transcriptome analysis and rescue experiments revealed the mechanism by which IL-11 protects neurons from oxidative stress damage. For the in vivo investigation, an adenovirus-mediated IL-11 overexpression SCI rat model was constructed to validate the beneficial effect of IL-11 against SCI. IL-11 significantly improved the viability and enhanced the antioxidant activity of H 2 O 2 -treated PC12 cells while reducing ROS release. In addition, IL-11 reduced H 2 O 2 -induced PC12 cell apoptosis. Transcriptome analysis revealed that the JAK/STAT pathway may be related to the antioxidant activity of IL-11. Treatment with a JAK/STAT inhibitor (Stattic) exacerbated the oxidative damage induced by H 2 O 2 and attenuated the protective effects of IL-11. The results of in vivo studies showed that IL-11 prevented neuronal apoptosis due to oxidative imbalance and promoted the restoration of motor function in SCI rats by activating the JAK/STAT signaling pathway. IL-11 inhibited oxidative stress-induced neuronal apoptosis at least in part by activating the JAK/STAT signaling pathway and further promoted the recovery of motor function. These findings suggest that IL-11 may be an effective target for the treatment for SCI. [ABSTRACT FROM AUTHOR]

Phylloporia ribis (Schumach:Fr.)Ryvarden is a genus of needle Phellinus medicinal fungi, parasitic on the living rhizomes of hawthorn and pear trees. As a traditional Chinese medicine, Phylloporia ribis was used in folklore for long-term illness, weakness and memory loss in old age. Previous studies have shown that polysaccharides from Phylloporia ribis (PRG) significantly promoted synaptic growth in PC12 cells in a dose-dependent manner, exhibiting "NGF"-like neurotrophic activity. Aβ 25-35 damage to PC12 cells produced neurotoxicity and decreased cell survival, and PRG reduced the apoptosis rate, suggesting that PRG has neuroprotective effects. The studies confirmed that PRG had the potential to be a neuroprotective agent, but its neuroprotective mechanism remained unclear. We aimed to elucidate the neuroprotective effects of PRG in an Aβ 25-35 -induced Alzheimer's disease (AD) model. Highly-differentiated PC12 cells were treated with Aβ 25-35 (AD model) and PRG, and were assessed for cellular apoptosis, inflammatory factors, oxidative stress, and kinase phosphorylation. The results showed that the PRG groups effectively inhibited the neurotoxicity, mainly manifested by inhibiting mitochondrial oxidative stress, attenuating neuroinflammatory responses, and improving mitochondrial energy metabolism, eventually resulting in higher cell survival. The expression of p-ERK, p-CREB and BDNF proteins was increased in the PRG groups compared to the model group, which confirmed that PRG reversed the inhibition of the ERK pathway. We provide evidence for neuroprotection conferred by PRG and its mechanism by inhibiting ERK1/2 hyper-phosphorylation, prevention of mitochondrial stress, and subsequent prevention of apoptosis. The study highlights PRG as a promising candidate with neuroprotective effects, the potential of which can be harnessed for identifying novel therapeutic targets. [Display omitted] [ABSTRACT FROM AUTHOR]