Gastrodin regulates the TLR4/TRAF6/NF-κB pathway to reduce neuroinflammation and microglial activation in an AD model.

BACKGROUND: Gastrodia elata (Orchidaceae) is a medicinal plant used in traditional Chinese medicine. The rhizomes contain numerous active components, of which Gastrodin (p-hydroxymethylphenyl-B-D-glucopyranoside) forms the basis of the traditional medicine Gastrodiae Rhizoma. Gastrodin is also found in other medicinal plants and has neuroprotective, antioxidant, and anti-inflammatory effects. Neuroinflammation plays a crucial role in neurodegeneration. Research indicates that consuming meals and drinks containing Gastrodiaelata can enhance cognitive functioning and memory in elderly patients. The mechanisms relevant to the problem have not been completely understood. PURPOSE: The aim was to examine the in vivo and in vitro anti-neuroinflammatory effects of Gastrodin. STUDY DESIGN: The neuroprotective effects of Gastrodin on the TLR4/TRAF6/NF-κB pathway and Stat3 phosphorylation in LPS-treated C57BL/6 mice and BV-2 cells were investigated. METHODS: 1. C57BL/6 mice were assigned to model, gastrodin, donepezil, and control groups (n = 10 per group). The Gastrodin group received 100 mg/kg/d for five days, and the Dopenezil group 1.3 mg/kg/d. A neuroinflammation model was established by administering intraperitoneal injections of 2 mg/kg LPS to all groups, excluding the control. To induce microglial activation in Gastrodin-treated mouse microglial BV-2 cells, 1 µg/ml LPS was introduced for 24 h Morris water mazes were utilized to evaluate learning and spatial memory. Expression and subcellular localization of TLR4/TRAF6/NF-κB axis-related proteins and p-Stat3, Iba-1, GFAP, iNOS, and CD206 were assessed by immunofluorescence, western blots, and ELISA. qRT-PCR was performed to determine and measure IL-1ß, TNF-α, cell migration, and phagocytosis. Overexpression of TRAF6 was induced by transfection, and the effect of Gastrodin on IL-1ß and p-NF-κB p65 levels was assessed. RESULTS: 1. In mice, gastrodin treatment mitigated LPS-induced deficits in learning and spatial memory, as well as reducing neuroinflammation in the hippocampus, expression of TLR4/TRAF6/NF-κB pathway proteins, activation of microglia and astrocytes, and phosphorylation of Stat3. 2. Gastrodin pretreatment improved LPS-induced inflammation in vitro, reducing expression of TLR4/TRAF6/NF-κB-associated proteins and p-Stat3, inducing microglial transformation from M1 to M2, and inhibiting migration and phagocytosis. Overexpression of TRAF6 inhibited the Gastrodin-induced effects. CONCLUSION: Gastrodin suppresses neuroinflammation and microglial activation by modifying the TLR4/TRAF6/NF-κB pathway and Stat3 phosphorylation.

Anlotinib followed by transarterial chemoembolization and radiofrequency ablation is a safe and effective initial treatment for hepatocellular carcinoma patients with portal vein tumor thrombus: A retrospective case series study.

BACKGROUND: Portal vein tumor thrombus (PVTT) remains a poor prognostic factor occurring in about 10%-40% of patients with hepatocellular carcinoma (HCC) for the optimal treatment is controversial. Anlotinib is an novel small molecule inhibitor that has a broad spectrum of inhibitory activities on tumor angiogenesis and growth. However, so far, no studies have reported the use of anlotinib in the treatment of HCC patients with PVTT. Here, we evaluated the safety and efficacy of anlotinib, followed by transarterial chemoembolization (TACE) and radiofrequency ablation (RFA) for the treatment of patients with HCC and PVTT. MATERIALS AND METHODS: A total of 145 consecutive HCC patients who underwent TACE in combination with RFA were enrolled in the retrospective study. Twenty-eight patients were diagnosed with PVTT and received anlotinib as basic treatment. The adverse events (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for AEs Version 4.0. Time to tumor progression (TTP) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: The most common toxicities related to anlotinib were pharyngalgia (53.6%), fatigue (42.9%), and hand-foot skin reaction (39.3%). The median OS was 13 months (range: 3-18 months) with 1-year OS rate of 64.3%. The median TTP was 7 months (range: 1-12 months) with 6-month rate of 46.4%. CONCLUSION: Anlotinib followed by TACE and RFA is a safe and effective initial treatment modality for HCC patients with PVTT. Anlotinib may be a promising therapeutic option for relieving and/or stabilizing HCC with PVTT.

[Effects of dihydromyricetin on the migration and invasion of human gastric cancer MKN45 cells and its mechanism].

OBJECTIVE: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human gastric cancer MKN45 cells and its mechanism and provide experimental basis for the prevention and treatment of gastric cancer with Traditional Chinese Medicine (TCM). METHODS: MKN45 cells were pre-treated with DHM (0,10,20,30,40,50 µmol/L) for 24 and 48 hours respectively. Cell viability treated with different concentrations of DHM was detected by Cell Counting kit (CCK-8) assay, cell migration was measured by wound healing assay, and cell invasion was tested by Transwell assay. Cells were pre-treated with DHM or co-treated with c-Jun N-terminal kinase (JNK) pathway inhibitor SP600125, then, the levels of migration- and invasion-related proteins were tested by Western blot. RESULTS: DHM concentration-dependently inhibited cell migration and invasion and downregulated matrix metalloprotein -2 (MMP-2) and phosphorylated JNK (pJNK) expression in MKN45 cells, followed by upregulation of E-cadherin and downregulation of Vimentin. Co-treatment with DHM and JNK inhibitor SP600125 further suppressed MMP-2 expression and cell invasion in MKN45 cells, suggesting that DHM inhibited MKN45 cells metastasis through JNK/MMP-2 pathway. CONCLUSION: DHM can inhibit cell migration and invasion in human gastric cancer MKN45 cells through downregulating MMP-2 expression via JNK signaling pathway and reverse epithelial-mesenchymal transition (EMT), implying that DHM could have the potential to serve as an anti-metastatic agent for treating gastric cancer.

Trillium tschonoskii maxim saponin mitigates D-galactose-induced brain aging of rats through rescuing dysfunctional autophagy mediated by Rheb-mTOR signal pathway.

During the expansion of aging population, the study correlated with brain aging is one of the important research topics. Developing novel and effective strategies for delaying brain aging is highly desired. Brain aging is characteristics of impaired cognitive capacity due to dysfunctional autophagy regulated by Rheb-mTOR signal pathway in hippocampal tissues. In the present study, we have established a rat model with brain aging through subcutaneous injection of D-galactose (D-gal). Upon the intervention of Trillium tschonoskii Maxim (TTM) saponin, one of bioactive components from local natural herbs in China, the learning and memory capacity of D-gal-induced aging rats was evaluated through Morris water maze test, and the regulation of Rheb-mTOR signal pathway and functional status of autophagy in hippocampal tissues of D-gal-induced aging rats was explored by Western blot. TTM saponin revealed an obvious function to improve learning and memory capacity of D-gal-induced aging rats through up-regulating Rheb and down-regulating mTOR, thereby rescuing dysfunctional autophagy to execute anti-aging role. Meanwhile, this study confirmed the function of TTM saponin for preventing and treating brain aging, and provided a reference for the development and utilization of natural products in health promotion and aging-associated disease treatment.

[Intervention effect of trillium tschonoskii maxim extract solution on myocardial injury in diabetic rats].

OBJECTIVE: To study the protective effect and the underlying mechanism of trillium tschonoskii maxim (TTM, Traditional Chinese Medicine) on myocardial injury of diabetic rats induced by high-fat diet and streptozotocin (STZ), which will lay a theoretical foundation for further exploring its pharmacological effect. METHODS: SD male rats received high fat diet and STZ (35 mg/kg) via tail vein injection were modeled into diabetic rats, the levels of brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) in serum, the contents of superoxide (SOD), glutathione peroxidase (GPX),malondialdehyde (MDA) in cardiac tissues, and cardiac myocyte apoptosis index were tested in all groups after the last administration. RESULTS: Compared with that in the model group, SOD and GPX activities were significantly increased and levels of BNP、cTnI、cardiac weight index (CWI)、apoptosis index (AI) were decreased in TTM and metformin (Met) group. The effects of TTM were better than traditional medicine metformin in enhancing GPX activity and decreasing collagen level. CONCLUSIONS: TTM can inhibit myocardial apoptosis by reducing oxidative stress responses in diabetic rats, which can slow down collagen fiber production to protect the myocardial cell injury.

[Effects of Se-riched soybean peptide on antioxidant function in rats of fatty liver caused by high-fat diet].

OBJECTIVE: To explore the effect of Se-riched soybean peptide (SSP) on antioxidant function in rats of fatty liver caused by high-fat diet. METHODS: Forty Wistar rats were divided into 4 groups randomly and fed with standard diet and water (NC), high-fat diet and water (HC), high-fat diet and SSP (0.1 g/d) (SeH), standard diet and SSP (0.1 g/d) (SeN) respectively. After 10 weeks, the rats were killed to investigate the pimelosis level in liver tissues by Sudan III staining and the expression of hepatic GRP78 by immunohistochemical analysis. We also analyzed the changes of liver function, blood lipid, the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in livers and serum. RESULTS: The pimelosis level, total cholesterol (TC), triglyceride (TG), MDA contents and the expression of GRP78 in HC group were significantly higher than those in NC, SeN, SeH groups. The activities of GSH-Px and SOD in liver and serum were markedly up-regulated in SeH (P < 0.01). There was no significant difference between NC and SeN groups. CONCLUSION: SSP can improve liver cell injury and the antioxidant functions in rats with fatty liver effectively and decrease the expression of GRP78 in liver.