Total paeony glycoside relieves neuroinflammation to exert antidepressant effect via the interplay between NLRP3 inflammasome, pyroptosis and autophagy.

BACKGROUND: Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied. PURPOSE: To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy. STUDY DESIGN: A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG. METHODS: The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated. RESULTS: TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1ß, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG. CONCLUSION: These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

Ginseng Stem-and-Leaf Saponins Mitigate Chlorpyrifos-Evoked Intestinal Toxicity In Vivo and In Vitro: Oxidative Stress, Inflammatory Response and Apoptosis.

In recent years, the phenomenon of acute poisoning and organ damage caused by organophosphorus pesticides (OPs) has been a frequent occurrence. Chlorpyrifos (CPF) is one of the most widely used organophosphorus pesticides. The main active components of ginseng stems and leaves are total ginseng stem-and-leaf saponins (GSLSs), which have various biological effects, including anti-inflammatory, antioxidant and anti-tumor activities. We speculate that these could have great potential in the treatment of severe diseases and the relief of organophosphorus-pesticide-induced side effects; however, their mechanism of action is still unknown. At present, our work aims to evaluate the effects of GSLSs on the antioxidation of CPF in vivo and in vitro and their potential pharmacological mechanisms. Mice treated with CPF (5 mg/kg) showed severe intestinal mucosal injury, an elevated diamine oxidase (DAO) index, the decreased expression of occlusive protein-1 (ZO-1) and occlusive protein, an impaired intestinal mucosal oxidation system and intestinal villi relaxation. In addition, chlorpyrifos exposure significantly increased the contents of the inflammatory factor TNF-α and the oxidative-stress-related indicators superoxide dismutase (SOD), catalase (CAT), glutathione SH (GSH), glutathione peroxidase (GSH-PX), reactive oxygen species (ROS) and total antioxidant capacity (T-AOC); elevated the level of lipid peroxide malondialdehyde (MDA); reversed the expression of Bax and caspase; and activated NF-κB-related proteins. Interestingly, GSLS supplementation at doses of 100 and 200 mg/kg significantly reversed these changes after treatment. Similar results were observed in cultured RAW264.7 cells. Using flow cytometry, Hoechst staining showed that GSLSs (30 µg/mL, 60 µg/mL) could improve the cell injury and apoptosis caused by CPF and reduce the accumulation of ROS in cells. In conclusion, GSLSs play a protective role against CPF-induced enterotoxicity by inhibiting NF-κB-mediated apoptosis and alleviating oxidative stress and inflammation.

Chitosan/gallnut tannins composite fiber with improved tensile, antibacterial and fluorescence properties.

Natural extracts gallnut tannins (GTs) were used as functional components to prepare chitosan/gallnut tannins (CS/GTs) composite fiber by blended solution spinning. Chitosan fiber has great potential to be used as absorbent suture and dressing due to its good biocompatibility. However, the weak mechanical properties limited its application. Chitosan and GTs were blended in aqueous solution of acetic acid to spin the composite fiber. The results indicated that CS/GTs fiber can be easily prepared due to the appropriate rheology characteristics for blended solution. Compared with pure chitosan fiber, CS/GTs fiber with 10% GTs showed lower hydrophilicity and higher dry, wet breaking strength by more than 40% due to ionic cross-linking between chitosan and GTs. The bacterial reduction to Staphylococcus aureus increased from 49.0 to 99.7% and about double green and red fluorescent intensity were observed for CS/GTs fiber. GTs have great potentiality in improving the properties of chitosan fiber.

Cordycepin mitigates MPTP-induced Parkinson's disease through inhibiting TLR/NF-κB signaling pathway.

Parkinson's disease (PD) is a neurodegenerative disease with movement disorder. PD is characterized by the loss of dopaminergic (DA) neurons in the substantia nigra. Cordycepin, a small molecule extracted from cordyceps sinensis, has neuroprotective, anti-inflammatory, antioxidant and anti-tumor properties. In this study, we explored its possible beneficial effects on PD. PD rat models and cell models were established via 1­methyl­4­phenyl­1,2,3,6­tetrahydropyridine (MPTP) injection and LPS treatment respectively, and cordycepin was administered. The motor functions of rats were examined, and the tyrosine hydroxylase (TH)-positive DA neurons and Iba1-positive microglia were detected by immunohistochemical and immunofluorescence staining. The expression levels of inflammatory and oxidative stress-related factors were also measured in vivo and in vitro. In addition, the TLR/NF-κB pathway was investigated to explore the mechanism. We found that in vivo, MPTP injection introduced motor disorders, the loss of DA neurons and the activation of TLR/NF-κB signaling pathway. Cordycepin treatment alleviated these MPTP-induced changes. In vitro, the results were confirmed in Lipopolysaccharide (LPS)-induced cells. Moreover, cordycepin mitigated the cytotoxic effects on PC12 cells produced by microglia. In conclusion, cordycepin alleviated PD symptoms by inhibiting TLR/NF-κB signaling pathway in vivo and in vitro.

[Non-alcoholic fatty liver disease of liver stagnation and spleen deficiency pattern treated with acupoint embedding therapy: a randomized controlled trial].

OBJECTIVE: To compare the difference between the acupoint embedding therapy and polyene phosphatidylcholine capsules in the clinical efficacy on non-alcoholic fatty liver disease (NAFLD) of liver stagnation and spleen deficiency pattern. METHODS: The multi-center clinical trial was adopted and 180 cases of NAFLD of liver stagnation and spleen deficiency pattern were randomized into an embedding therapy group and a western medication group, 90 cases in each one. On the basis of general treatment such as diet control and proper physical exercise, in the embedding therapy group, the acupoint embedding therapy was applied to Ganshu (BL 18), Tai-chong (LR 3), Fenglong (ST 40), Zusanli (ST 36) and Sanyinjiao (SP 6), once every 7 days; in the western medication group, polyene phosphatidylcholine capsules (essentiale) were prescribed, 228 mg/capsule, 2 capsules each time, three times a day. In 6 months of treatment, TCM syndrome score, liver enzymology, blood lipid and abdomen B-ultrasound examination were observed and compared before and after treatment between the two groups. RESULTS: (1) For TCM syndrome score, the total score in the embedding therapy group was lower significantly than that in the western medication group (P<0. 05); (2) For liver enzymology and blood lipid, the levels of serum alanine transarninase (ALT), serum glutamic oxalacetic transaminase (AST), total cholesterol (TC) and triacylglycerol (TG) in the embedding therapy group were reduced significantly as compared with those in the western medication group (all P<0. 05); (3) For abdomen B-ultrasound examination, the fatty liver degree in the embedding therapy group was relieved significantly as compared with that in the western medication group (P< 0. 05); (4) For clinical efficacy, the total effective rate was 89. 8%o (79/88) in the embedding therapy group, higher significantly than 76. 7% (69/90) in the western medication group(P<0. 05). CONCLUSION: The acupoint embedding therapy achieves the definite efficacy on NAFLD of liver stagnation and spleen deficiency pattern, better than polyene phosphatidylcholine capsules.

[Electroacupuncture Intervention Inhibits the Decline of Learning-memory Ability and Overex- pression of Cleaved Caspase-3 and Bax in Hippocampus Induced by Isoflurane in APPswe/PS 1].

OBJECTIVE: To investigate the protection mechanism of electroacupuncture (EA) therapy against Alzheimer's disease (AD)-like neurotoxicity induced by Isoflurane. METHODS: Twenty-four APPswe/PS 1 dE9 double transgenic mice (one of the most extensively used transgenic mouse model of AD) and 24 littermate wild-type mice were randomly assigned into control (Con) group, isoflurane (Iso) group and EA group, respectively (n = 8 in each group). EA (2 Hz/100 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Yongquan" (KI 1) for 15 min, once a day for 3 days. The transgenic mice were exposed to a closed box filled with 1.2% isoflurane + 30% O2 +70% N2 for 4 h. The animals' learning-memory ability was detected by Morris water maze test. The expression of cleaved Caspase-3 in the CA 1 area of hippocampus was detected by immunohistochemistry, and that of hippocampal Bcl-2 and Bax proteins detected by Western blot. RESULTS: Compared with the wilde-type mice, the average escape latency of place navigation test was significantly longer, while the percentage of target-quadrant stay time and the target- platform crossing times of spacial probe test were marked decreased in AD + lso mice (P < 0.05). After acupuncture intervention, the abovementioned changes were reversed (P < 0.05). Correspondingly, compared with the AD-Con group, the number of hippocampal activated Caspase-3-positive cells and the expression of Bax protein were significantly increased in the AD-Iso group (P < 0.05). After EA intervention, the increased Caspase-3-positive cell number and Bax protein expression were remarkably down-regulated in the AD-EA group, and the decreased ratio of Bcl-2/Bax in AD-Iso mice was obviously up-regulated in AD-EA mice (P < 0.05). No significant changes were found in the average escape latency, the percentage of target-quadrant stay time and the target-platofrm corssing times, and inthe number of hippocampal activated Caspase-3-positive cells, the expression levels of hippocampal Bcl-2 and Sax and the ratio of Bcl-2/Bax in the three groups of wilde-type mice (P > 0.05). CONCLUSION: EA intervention can improve the learning-memory ability in AD + Isoflurane mice, suggesting a reduction of AD-like neurotoxicity, which may be associated with its actions in inhibiting the overexpression of activated Caspase-3 and Bax proteins in the hippocampus.

[Effects of needle pricking therapy of Zhuang minority medicine on expression of pulmonary T-bet, GATA-binding protein 3 genes and thymic stromal lymphopoietin protein in the lung of asthma mice].

OBJECTIVE: To observe the effect of needle pricking therapy on the expression of thymic stromal lymphopoietin (TSLP) protein, T-box expressed in T cells(T-bet)mRNA and GATA-binding protein-3 (GATA 3) mRNA in the lung tissue of mice with asthma, so as to explore its mechanism underlying improvement of asthma. METHODS: Thirty female BALB/c mice were randomly divided into control, model and needle pricking groups (10 mice/group). The asthma model was established by i. p. of Ovalbumin (OVA) suspension fluid (containing Aluminium Hydroxide 400 microg and OVA 100 microg, 50 microg/L) and forced inhalation of atomized OVA. A sharp needle was held to prick "Dazhui" (GV 14),"Feishu" (BL 13), "Dingchuan" (EX-B 1),"Fengmen" (BL 12),"Shenshu" (BL 23) and "Pishu" (BL 20) acupoint regions to let a little bit of white fibrous tissue out, then to insert into the acupoints to about 1 mm in depth, once a day for seven times. The lung tissue was taken for detecting the expression of T-bet mRNA and GATA-3 mRNA by RT-PCR and for determining the immunoactivity of TSLP by immunofluorescence method. In addition, HE staining was used to examine the pathologic changes of the lung tissue. RESULTS: Compared with the control group, the expression levels of GATA-3 mRNA and TSLP protein of the lung tissue in the model group were significantly increased (P < 0.01), whereas that of T-bet mRNA was remarkably decreased (P < 0.05). Following needle prick stimulation treatment, the expression levels of GATA-3 mRNA and TSLP protein were markedly down-regulated (P < 0.01) and that of T-bet mRNA was obviously upregulated (P < 0.05). After the treatment, pathological changes including hyperemia of the pulmonary alveoli, epithelial thickening, narrowing of the lumina, and infiltration of many inflammatory cells around the tracheal blood vessels were improved. CONCLUSION: Needle pricking therapy can regulate the expression of pulmonary TSLP protein and GATA 3 and T-bet genes in mice with asthma, which may contribute to its effect in improving pulmonary pathological changes of asthma mice.

Honokiol suppresses TNF-α-induced migration and matrix metalloproteinase expression by blocking NF-κB activation via the ERK signaling pathway in rat aortic smooth muscle cells.

Honokiol, a small-molecule polyphenol derived and isolated from the Chinese medicinal herb Magnolia officinalis, has been shown to possess a wide range of pharmacological activities. In the present study, we aimed to investigate the effects of honokiol on tumor necrosis factor-α (TNF-α)-induced migration in rat aortic smooth muscle cells (RASMCs). We found that honokiol inhibited TNF-α-induced RASMC proliferation and migration in a dose-dependent manner. At the molecular level, pretreatment with honokiol blocked TNF-α-induced protein expression of matrix metalloproteinase (MMP)-2 and MMP-9, nuclear factor (NF)-κB activation, and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation. Moreover, NF-κB inhibitor (BAY 11-7028) and ERK inhibitor (U0126) also mimicked the inhibitory effects of honokiol in TNF-α-treated RASMCs. In conclusion, these results indicate that honokiol suppresses TNF-α-induced migration and MMP expression by blocking NF-κB activation via the ERK signaling pathway in RASMCs. Our findings support honokiol as a promising novel agent for the prevention and treatment of atherosclerosis.

[The influence of Solanum lyratum Thunb extract on apoptosis and the expression of fas/fasL genes in Hela cells].

OBJECTIVE: To explore the effects of Solanum lyratum Thunb (SL) extract on the apoptosis and the expression of fas and fasL genes in Hela cells. METHODS: The proliferation inhibitory rate was evaluated by MTF assay. Induction of cell apoptosis rate was determined by flow cytometry. The expression of Fas protein was detected by two-step immunhistochemical staining. The expression of fas and fasL mRNA was detected by semi-quantitive RT-PCR. RESULTS: SL extract displayed strong proliferation inhibitory effect in a dose-and-time-dependent manner against Hela cell. The rate of apoptosis was increased obviously. The expression of fas mRNA and protein was increased significantly, and fasL mRNA was decreased markedly. CONCLUSION: SL can induce apoptosis by up-regulating expression of fas and fasL genes, and inhibit the development of Hela cells.