Baohuoside I suppresses the NLRP3 inflammasome activation via targeting GPER to fight against Parkinson's disease.

BACKGROUND: Accumulating evidence indicates the crucial role of microglia-mediated inflammation and the NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis in the pathogenesis of Parkinson's disease (PD). Baohuoside I, a natural flavonoid extracted from Herba Epimedii, has been shown to possess anti-inflammatory effects, but its potential neuroprotective effects and mechanism against PD have not been documented. STUDY DESIGN AND METHODS: The anti-inflammatory effects of Baohuoside I were evaluated by LPS-induced BV2 cells or primary microglia isolated from wide type or G protein-coupled estrogen receptor (GPER) gene knockout mice. The underlying mechanism related to GPER-mediated NLRP3 inflammasome inhibition was further explored using LPS-induced GPER+/+ or GPER-/- mouse models of PD. The neuroprotective effects of Baohuoside I were detected through western blot analysis, real-time PCR, molecular docking, mouse behavioral tests, immunofluorescence, and immunohistochemistry. RESULTS: Baohuoside I significantly alleviated LPS-induced neuroinflammation by inhibiting the activation of NF-κB signal and the increase of pyroptosis levels as evidenced by the downregulated expression of pyroptosis-related proteins (NLRP3, ASC, pro-Caspase-1, IL-1ß) in microglia cells. Intragastric administration of Baohuoside I protected against LPS-induced motor dysfunction and loss of dopaminergic neurons, reduced pro-inflammatory cytokines expressions, and inhibited microglial (Iba-1) and astrocyte (GFAP) activation in the nigrostriatal pathway in LPS-induced mouse model of PD. Pretreatment with GPER antagonist G15 in microglia cells or GPER gene deletion in mice significantly blocked the inhibitory effects of Baohuoside I on LPS-induced neuroinflammation and activation of the NLRP3/ASC/Caspase-1 pathway. Molecular docking further indicated that Baohuoside I might bind to GPER directly with a binding energy of -10.4 kcal/mol. CONCLUSION: Baohuoside I provides neuroprotective effects against PD by inhibiting the activation of the NF-κB signal and NLRP3/ASC/Caspase-1 pathway. The molecular target for its anti-inflammatory effects is proved to be GPER in the PD mouse model. Baohuoside I may be a valuable anti-neuroinflammatory agent and a drug with well-defined target for the treatment of PD.

[Analysis and prospects of common problems in clinical data mining of traditional Chinese medicine prescriptions].

Mining data from traditional Chinese medicine(TCM) prescriptions is one of the important methods for inheriting the experience of famous doctors and developing new drugs. However, current research work has problems such as to be optimized research plans and non-standard statistics. The main problems and corresponding solutions summarized by the research mainly include four aspects.(1)The research plan design needs to consider the efficacy and quality of individual cases.(2)The significance of the difference in confidence order of association rules needs to be further considered, and the lift should not be ignored.(3)The clustering analysis steps are complex. The selection of clustering variables should comprehensively consider factors such as the frequency of TCM, network topology parameters, and practical application significance. The selection of distance calculation and clustering methods should be improved based on the characteristics of TCM clinical data. Jaccard distance and its improvement plan should be given attention in the future. A single, unexplained clustering result should not be presented, but the final clustering plan should be selected based on a comprehensive consideration of TCM clinical characteristics and objective evaluation indicators for clustering.(4)When calculating correlation coefficients, algorithms that are only suitable for continuous variables should not be applied to binary variables. This article explained the connotations of the above problems based on the characteristics of TCM clinical research and statistical principles and proposed corresponding suggestions to provide important references for future data mining research work.

Astragalus mongholicus Bunge and Panax Notoginseng Formula (A&P) Combined With Bifidobacterium Contribute a Renoprotective Effect in Chronic Kidney Disease Through Inhibiting Macrophage Inflammatory Response in Kidney and Intestine.

There is increasing evidence that Chronic Kidney Disease (CKD) can cause intestinal dysfunction, which in turn aggravates the progression of kidney disease. Studies have shown that the immune response of macrophage plays an important role in promoting inflammation in kidney and intestine of CKD. Astragalus mongholicus Bunge and Panax notoginseng formula (A&P) is a widely used traditional medicine for the treatment of CKD in China, however, the underlying mechanism is largely unclear. In this study, we aimed to explore the role of A&P and Bifidobacterium combination treatment in regulation of inflammatory response of macrophage in kidney and intestine of CKD mouse, as well as the potential molecular mechanism. We established a CKD mouse model with 5/6 nephrectomy and a macrophage inflammatory cellular model with LPS and urotoxin in vivo and in vitro. The results showed that A&P combined with Bifidobacterium significantly reduced the expression and secretion of IL-1ß, IL-6, TNFα, and MCP-1 in kidney and blood, as well as in inflammatory macrophage. Interestingly, A&P combined with Bifidobacterium strongly improved the intestinal flora and protected the intestinal barrier. Notably, the maintainer of macrophage polarization, Mincle, was activated in kidney and intestine of CKD mouse as well as in urotoxin stimulated macrophage, that was effectively inhibited by the treatment of A&P and Bifidobacterium combination. Overexpression of Mincle by genetic modification can abolish the inhibitory effects of A&P combined with Bifidobacterium on inflammation in urotoxin stimulated RAW264.7 cells. In summary, these findings demonstrated that A&P combined with Bifidobacterium can protect kidney against CKD by down-regulating macrophage inflammatory response in kidney and intestine via suppressing Mincle signaling, which provides a new insight in the treatment of CKD with traditional medicine.

Case of professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" in promoting the absorption of COVID-19.

A case of the absorption of corona virus disease 2019 (COVID-19) promoted by professor Xu ZOU's acupuncture technique for "benefiting kidney and strengthening anti-pathogenic qi" is introduced. A female patient suffered from COVID-19, 64 years old, had been treated with acupuncture and Chinese herb granules for 10 days on the base of the oral administration of moxifloxacin. In the re-examination, the chest CT image indicated that the absorption of COVID-19 was obvious as compared with before, the nucleic acid test of novel corona virus was negative and the patient narrated no obvious discomfort. Acupuncture therapy plays its active adjuvant effect in the whole process of the treatment of COVID-19.

Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound relieved cisplatin-induced acute kidney injury through inhibiting the mincle maintained macrophage inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute kidney injury (AKI) is a common disease in hospitalized patients, especially in critically ill patients. It is characterised with high morbidity and mortality, and is also an important cause of chronic kidney disease and chronic renal failure. Astragalus propinquus Schischkin and Panax notoginseng (A&P) compound, a famous traditional Chinese medicine, consists of Astragalus propinquus Schischkin, Panax notoginseng, Angelica sinensis, Achyranthes bidentata, and Ecklonia kurome, has been widely used for the treatment of various kidney diseases in the southwest of China. However, the effects of A&P on treatment of AKI and its underlying mechanism are needed to be uncovered. AIM OF THE STUDY: Recent researches reported that Mincle (Macrophage-inducible C-type lectin) plays a key role in renal injury of AKI by regulating the expression and secretion of inflammatory cytokines on macrophage through modulating NF-κB signaling pathway. Here, we aimed to investigate the renoprotective effect of A&P on AKI and whether by inhibiting Mincle. MATERIALS AND METHODS: We established a lipopolysaccharide (LPS)-induced Bone Marrow-Derived Macrophage (BMDM) inflammatory cell model and a cisplatin-induced mouse AKI model in vitro and in vivo. Renal histopathology staining was performed to observe kidney morphology. The expression and secretion of inflammatory cytokines were detected by real-time PCR and Enzyme-linked immunosorbent assay. Western blotting was used to detect the protein levels and Flow cytometry performed to detect polarization of macrophage. RESULTS: The results showed that A&P significantly reduced the mRNA expression of IL-1ß, IL-6, TNFα and MCP-1 in LPS-stimulated BMDM cells, and secretion of IL-1ß and IL-6 in supernatant. The same results were found in Cisplatin-induced AKI kidney and serum after treatment with A&P. The data also showed that A&P strongly reduced the mRNA and protein levels of Mincle in vitro and vivo, and also inhibited the activation of Syk and NF-κB. Notably, A&P down-regulated the M1 macrophage marker iNOS, which may relate to the inhibition of Mincle. Interestingly, both overexpression of Mincle by transfection of pcDNA3.1-Mincle plasmid and administration of TDB (a ligand of Mincle) can significantly abolished the A&P-inhibited inflammation in BMDM, suggesting Mincle pathway play a key role in macrophage inflammation in AKI. CONCLUSION: Our findings indicated that A&P protected kidney from inhibiting inflammation through down-regulating of Mincle pathway in macrophage in AKI. It provides a potential medicine compound for the treatment of AKI.

Effects of Electroacupuncture at Baihui,Dazhui and Shenshu Acupoints on Ability of Learning and Memory and Synapses of Neurons in Hippocampal CA1 in SAMP8 Mice / 中国康复理论与实践

Objective To observe the effect of electroacupuncture (EA) at Baihui (GV20), Dazhui (GV14) and Shenshu (BL23) acu-points on cognitive function and the synapse of neurons in hippocampal CA1 in SAMP8 mice,to explore the mechanism of EA in the treat-ment of Alzheimer's disease(AD).Methods A total of 24 seven-month-old SAMP8 mice were randomly divided into model group(n=12) and EA group (n=12), and the same age SAMR1 mice were as control group (n=12).The EA group accepted EA at Baihui, Dazhui and Shenshu for 30 days.They were assessed with Morris maze test.The expression of synaptophysin(SYN)and postsynaptic density protein 95(PSD95)in hippocampal CA1 region were detected with immunohistochemistry.The morphology and density of synapse in hippocampal CA1 region was observed with transmission electron microscopy.Results Compared with the model group,the latency of Morris maze de-creased in EA group(P<0.05),the time staying in the quadrant of the platform increased(P<0.05),as well as the number passing the origi-nal platform(P<0.05),with the more expression of SYN and PSD95 in hippocampal CA1 region(P<0.001),and more and completed syn-apse.Conclusion EA can improve the learning and memory ability of SAMP8 mice by increasing the expression of SYN and PSD95 to pro-tect the ultrastructure of synapses in hippocampal CA1 region.

A study on effects of Sheshang capsule on blood coagulation function of patients bitten by Trimeresurus stejnegeri snake / 中国中西医结合急救杂志

Objective To investigate the mechanism of traditional Chinese medicine (TCM) Sheshang capsule for treatment of blood coagulation dysfunction in patients bitten by Trimeresurus stejnegeri snake. Methods A prospective study was conducted. Seventy Trimeresurus stejnegeri snake envenoming patients whose manifestations conformed to the diagnostic criteria of the fire toxin syndrome in TCM were assigned into therapy group and control group by random number table (each, 35 cases). The basic treatments (including wound disinfection, intramuscular injection of 1 500 U tetanus antitoxin, conventional dose of antibiotics, 10 mg dexamethasone, 40 mg omeprazole) and 10 Jidesheng Sheyao tablets three times a day were applied in the control group. In the therapy group, the basic treatments the same as those of the control group were given, and in the mean time 5 Sheshang capsules (the drug was prepared in our hospital including ingredients:rhubarb, coptidis rhizoma, pleione bulbocodioides, elecampane inula root, bayberry bark, borneol and so on) were administered three times a day. The therapeutic course in the two groups was 1 week. The levels of platelet α-granule membrane protein (CD62p), thromboxane B2 (TXB2), platelet factor 3 (PF3) and von Willebrand factor (vWF) in serum were measured by enzyme linked immunosorbent assay (ELISA) before and after treatment. Results Before treatment, there were no significant differences in CD62p, TXB2, PF3 and vWF between therapy group and control group [CD62p (μg/L):3.81±1.64 vs. 3.52±1.43, TXB2 (μg/L):13.04±1.67 vs. 13.31±1.14, PF3 (μg/L): 2.84±1.08 vs. 2.88±1.23, vWF (μg/L):12.36±2.42 vs. 11.89±2.08, all P>0.05]. After treatment, the levels of CD62p, TXB2 and PF3 were increased, while vWF decreased compared with those before treatment in both groups, the level changes in therapy group being more remarkable [CD62p (μg/L): 6.73±1.77 vs. 5.81±1.62, TXB2 (μg/L):18.65±1.77 vs. 17.90±1.68, PF3 (μg/L):5.61±1.48 vs. 4.77±1.24, vWF (μg/L):3.87±1.01 vs. 4.58±1.09, P < 0.05 or P < 0.01]. Conclusion The Sheshang capsule is capable of treating patients with blood coagulative disorder after Trimeresurus stejnegeri snake bite, and its mechanism is possibly related to the improvement of platelet activation function and amelioration of the damage of vascular endothelial cells.

Effects of Yishen Jiangzhuo Granule on the bone metabolism of patients with stage 3-4 chronic kidney disease and its correlation with the immune indices / 中国中西医结合杂志

<p><b>UNLABELLED</b>OBJECTIVE To explore the changes of bone gla protein (BGP) and tartrate resistant acid phosphatase (TRACP) in patients with stage 3 -4 chronic kidney disease (CKD) before and after treatment, to study their correlation with interleukin-17 (IL-17) and regulatory T cells (Treg), and the effects of Yishen Jiangzhuo Granule (YJG) on the bone metabolism.</p><p><b>METHODS</b>Fifty-three patients with stage 3-4 CKD were randomly assigned to the treatment group and the control group using random digit table. The following parameters in blood were detected: Treg (CD4+ CD25+ CD127lo) using tri-chrism fluorescent labeling by flow cytometry; levels of TRACP, BGP, and IL-17 by double antibody sandwich ELISA. The hemoglobin (HGB) content was detected using Beckman-Coulter heme/analysis. The urinary contents of creatinine (UCr) were determined using reversed HPLC. The blood contents of calcium (Ca), phosphate (P), blood urea nitrogen (BUN), serum creatinine (SCr), and plasma albumin (ALB) were determined using automatic biochemical analyzer. Then the calcium-phosphate (Ca x P) product was calculated on the basis of blood contents of Ca and P. The clearance rate of endogenous creatinine (CCr) was calculated on the basis of blood BUN and SCr contents.</p><p><b>RESULTS</b>(1) There was no obvious change in CD4+ CD25+ CD127lo in the two groups before and after treatment (P > 0.05). Compared with before treatment in the same group, there were statistical difference in the levels of CD4+ and TRACP in the two groups, as well as the IL-17 level in the control group (P < 0.01, P < 0.05). But compared with the healthy group, statistical difference was shown in each index (except CD4+) (P < 0.01). Compared with the control group after treatment, there was no statistical difference in each index of the treatment group after treatment (P > 0.05). Compared with before treatment in the same group, the levels of Hb, ALB, and CCr increased (P < 0.05, P < 0.01), and the SCr level decreased in the two groups after treatment (P < 0.05). Compared with the control group after treatment, the SCr level decreased and the CCr level increased more obviously in the treatment group (P < 0.05). There was no correlation among the levels of IL-17, TRACP, BGP, and Treg between before and after treatment in the two groups.</p><p><b>CONCLUSIONS</b>YJG could improve the kidney function and delay the progression of micro-inflammation of stage 3 -4 CKD patients. It could not improve the level of CD4+ CD25+ CD127lo. It also showed no effects on bone metabolism. The CD4+ T cells were differentiated to Th17 cells in stage 3-4 CKD patients. Their immunity was in a state of anergy but continually activated. The inflammatory factors in patients with stage 3-4 CKD play important roles in inducing the activation of osteoclasts.</p>