Catalpol rescues cognitive deficits by attenuating amyloid ß plaques and neuroinflammation.

This study sought to investigate the anti-amyloid ß (Aß) and anti-neuroinflammatory effects of catalpol in an Alzheimer's disease (AD) mouse model. METHODS: The effects of catalpol on Aß formation were investigated by thioflavin T assay. The effect of catalpol on generating inflammatory cytokines from microglial cells and the cytotoxicity of microglial cells on HT22 hippocampal cells were assessed by real-time quantitative PCR, ELISA, redox reactions, and cell viability. APPswe/PS1ΔE9 mice were treated with catalpol, and their cognitive ability was investigated using the water maze and novel object recognition tests. Immunohistochemistry and immunofluorescence were used to probe for protein markers of microglia and astrocyte, Aß deposits, and NF-κB pathway activity. Aß peptides, neuroinflammation, and nitric oxide production were examined using ELISA and redox reactions. RESULTS: Catalpol potently inhibited Aß fibril and oligomer formation. In microglial cells stimulated by Aß, catalpol alleviated the expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and inducible nitric oxide synthase (iNOS) but promoted the expression of the anti-inflammatory cytokine IL-10. Catalpol alleviated the cytotoxic effects of Aß-exposed microglia on HT22 cells. Treatment with catalpol in APPswe/PS1ΔE9 mice downregulated neuroinflammation production, decreased Aß deposits in the brains and alleviated cognitive impairment. Catalpol treatment decreased the number of IBA-positive microglia and GFAP-positive astrocytes and their activities of the NF-κB pathway in the hippocampus of APPswe/PS1ΔE9 mice. CONCLUSION: The administration of catalpol protected neurons by preventing neuroinflammation and Aß deposits in an AD mouse model. Therefore, catalpol may be a promising strategy for treating AD.

Modified Renshen Yangrong decoction enhances angiogenesis in ischemic stroke through promotion of MicroRNA-210 expression by regulating the HIF/VEGF/Notch signaling pathway.

OBJECTIVE: This study aims to investigate the efficacy of modified Ginseng Yangrong decoction (GSYRD) promoting angiogenesis after ischemic stroke. METHODS: In an in vivo study, rats that survived surgery were allocated into four groups: the control group and model group were treated with normal saline, the GSYRD group was treated with 18.9 mg/kg of GSYRD daily, and the positive control group was treated with Tongxinluo (TXL) (1 g/kg/d). At the end of the seven-day treatment, the area of cerebral infarction, the expression changes of miRNA-210 and ephrin A3 were determined. In an in vitro study, HUVECs were divided into a normal control serum group (NC group), normal control serum OGD group (Oxygen Glucose Deprivation group) (OGD group), OGD + drug-containing serum group (OGD+GSYRD group), and OGD + drug-containing serum + ES group (Endostatin group) (OGD+GSYRD+ES group). The cells in all groups except the NC group were cultured in a sugar-free DMEM medium under hypoxia for 48 h. Cell proliferation, angiogenic structure formation ability, the expression changes of miRNA-210, ephrin A3, and the HIF/VEGF/Notch signaling pathway-related molecules were determined. RESULTS: In vivo, GSYRD significantly reduced infarct size (p < .01), the expression of miRNA-210 and ephrin A3 were decreased in the GSYRD group (p < .05). In vitro, the cell proliferation and tube formation ability were significantly increased in the GSYRD group (p < .05), and the expression of miRNA-210 and ephrin A3 was decreased (p < .05). In addition, in the GSYRD group, the expression of the HIF/VEGF/Notch signaling pathway-related molecules was significantly increased (p < .01 or p < .05). CONCLUSION: GSYRD promotes cerebral protection following angiogenesis and ischemic brain injury. The specific mechanism was activating the HIF/VEGF/Notch signaling pathway via miRNA-210.

Hirudo Lyophilized Powder Ameliorates Renal Injury in Diabetic Rats by Suppressing Oxidative Stress and Inflammation.

As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.

Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway.

INTRODUCTION: The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. MATERIALS AND METHODS: The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1ß, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. RESULTS: After treatment with Shentong Zhuyu Decoction medicated serum, the OD570 value, migrative and invasive abilities, and the secretion of IL-1ß, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). CONCLUSIONS: Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.

[Effect of Acupoint Application Therapy of Summer Treatment for Winter Diseases on Nerve-Endocrine-Immune Network System in Patient with Non-Acute Attack Asthma].

Objective To observe the effect of acupoint application therapy in summer to treat winter diseases (abbreviated as AATSTWD) on nerve-endocrine-immune network system in patients with non-acute attack asthma, and to study possible mechanisms. Methods Fifty healthy volunteers were re- cruited as the normal control group and 50 patients with non-acute attack asthma were recruited as the asthma group. Patients in the normal control group received no intervention. Those in the control group were treated with acupoint application therapy on hot days (applied on the first day of three dog days, 3 times in total). Blood samples were tested before treatment and after 3 times of application. The contents of serum immunoglobulin E (IgE) , interleukin-4 (IL-4) , plasma substance P (SP) , and vasoactive intes- tinal peptide (VIP) were detected using radioimmunoassay. Contents of immunoglobulin A and G (IgA, IgG) were tested by immunoturbidimetry. Content of interferon-y (INF-y) were tested by enzyme linked immunosorbent assay. Results Compared with the normal control group, serum contents of IgA, igG, IFN-y, and plasma VIP decreased, contents of IgE, IL-4, and SP significantly increased in the asthma group before treatment (P <0. 05). Compared with before treatment in the same group, serum contents of IgA, IgG, VIP, and IFN-y increased, and contents of IgE, IL-4, and SP decreased in the asthma group after treatment (P <0. 05). Conclusion Acupoint application therapy in summer to treat winter diseases method could prevent and treat bronchial asthma possibly through improving immune function, control- ling the release of cytokines , and regulating neurotransmitters.