Effects of Si-Miao-Yong-An decoction on myocardial I/R rats by regulating gut microbiota to inhibit LPS-induced TLR4/NF-κB signaling pathway.

BACKGROUND: Coronary Artery Disease (CAD) is primarily caused by inflammation which is closely linked to the gut microbiota. Si-Miao-Yong-An (SMYA) decoction is a traditional Chinese herbal formula with anti-inflammatory properties that found to be effective against CAD. However, it is still unclear whether SMYA can modulate gut microbiota and whether it contributes to the improvement of CAD by reducing inflammation and regulating the gut microbiota. METHODS: The identification of components in the SMYA extract was conducted using the HPLC method. A total of four groups of SD rats were orally administered with SMYA for 28 days. The levels of inflammatory biomarkers and myocardial damage biomarkers were measured through ELISA, while echocardiography was used to assess heart function. Histological alterations in the myocardial and colonic tissues were examined following H&E staining. Western blotting was performed to evaluate protein expression, whereas alterations in gut microbiota were determined by 16 s rDNA sequencing. RESULTS: SMYA was found to enhance cardiac function and decrease the expression of serum CK-MB and LDH. SMYA was also observed to inhibit the TLR4/NF-κB signaling pathway by downregulating the protein expression of myocardial TLR4, MyD88, and p-P65, leading to a reduction in serum pro-inflammatory factors. SMYA modified the composition of gut microbiota by decreasing the Firmicutes/Bacteroidetes ratio, modulating Prevotellaceae_Ga6A1 and Prevotellaceae_NK3B3 linked to the LPS/TLR4/NF-κB pathway, and increasing beneficial microbiota such as Bacteroidetes, Alloprevotella, and other bacterial species. Moreover, SMYA was found to safeguard the intestinal mucosal and villi structures, elevate the expression of tight junction protein (ZO-1, occludin), and reduce intestinal permeability and inflammation. CONCLUSIONS: The results indicate that SMYA has the potential to modulate the gut microbiota and protect the intestinal barrier, thereby reducing the translocation of LPS into circulation. SMYA was also found to inhibit the LPS-induced TLR4/NF-κB signaling pathway, leading to a decrease in the release of inflammatory factors, which ultimately mitigated myocardial injury. Hence, SMYA holds promise as a therapeutic agent for the management of CAD.

Network pharmacology-based approach to research the effect and mechanism of Si-Miao-Yong-An decoction against thromboangiitis obliterans.

BACKGROUND: Si-Miao-Yong-An decoction (SMYAD) is a conventional therapeutic formula for treat thromboangiitis obliterans (TAO), consisting of four Chinese herbs: Lonicerae japonicae Thunb. (Jinyinhua), Scrophularia ningpoensis Hemsl. (Xuanshen), Angelica sinensis (Oliv.) Diels (Danggui) and Glycyrrhiza uralensis Fisch. (Gancao). However, the mechanism of SMYAD in TAO treatment remains unclear. METHODS: Components, as well as potential targets of SMYAD in TAO therapy, were downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Subsequently, with the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signalling pathways of the targets enrichment were performed. Next, based on STRING online database, the protein interaction network of vital targets was built and analysed. Molecular docking and calculation of the binding affinity were performed using AutoDock. The PyMOL software was employed to observe docking outcomes of active compounds and protein targets. Based on the predicted outcomes of network pharmacology, in vivo and in vitro tests were performed for validation. In vivo experiment, the TAO rats model was established using sodium laurate injection into the femoral artery. The symptoms as well as pathological changes of the femoral artery were observed. Besides, the predicted targets were verified by the RT-qPCR, in vitro experiment. The cell viability in LPS-induced human umbilical vein endothelial cells (HUVECs) was detected using CCK-8 kit, and the predicted targets were also verified by the RT-qPCR. RESULTS: In the network pharmacology analysis, we obtained 105 chemical components in SMYAD and 24 therapeutic targets. We found that the mechanism SMYAD in TAO therapy was primarily associated with inflammation and angiogenesis by constructing multiple networks. Quercetin, vestitol and beta-sitosterol were important compounds, and interleukin-6 (IL6), MMP9, and VEGFA were key targets. According to molecular docking, active compounds (quercetin, vestitol and beta-sitosterol) and targets (IL6, MMP9 and VEGFA) showed good binding interactions. In in vivo experiment, SMYAD ameliorated the physical signs and pathological changes, inhibited the expression of IL6 and MMP9, and enhanced the expression of VEGFA. In an in vitro experiment, SMYAD increased the cell viability of LPS-induced HUVECs and the expression of VEGFA, and reduced the expression of IL6 and MMP9. CONCLUSIONS: This study showed that SMYAD improves TAO symptoms and inhibits the development of TAO. The mechanism could be associated with anti-inflammatory and therapeutic angiogenesis.

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis.

HJ11 is a novel traditional Chinese medicine developed from the appropriate addition and reduction of Si-Miao-Yong-An decoction, which has been commonly used to treat ischemia-reperfusion (I/R) injury in the clinical setting. However, the mechanism of action of HJ11 components remains unclear. Ferroptosis is a critical factor that promotes myocardial I/R injury, and the pathophysiological ferroptosis-mediated lipid peroxidation causes I/R injury. Therefore, this study explored whether HJ11 decoction ameliorates myocardial I/R injury by attenuating ACSL4-mediated ferroptosis. This study also explored the effect of ACSL4 expression on iron-dependent programmed cell death by preparing a rat model of myocardial I/R injury and oxygen glucose deprivation/reperfusion (OGD/R)-induced H9c2 cells. The results showed that HJ11 decoction improved cardiac function; attenuated I/R injury, apoptosis, oxidative stress, mitochondrial damage, and iron accumulation; and reduced infarct size in the myocardial I/R injury rat model. Additionally, HJ11 decoction suppressed the expression of ferroptosis-promoting proteins [Acyl-CoA synthetase long-chain family member 4 (ACSL4) and cyclooxygenase-2 (COX2)] but promoted the expression of ferroptosis-inhibiting proteins [ferritin heavy chain 1 (FTH1) and glutathione-dependent lipid hydroperoxidase glutathione peroxidase 4 (GPX4)] in the myocardial tissues of the I/R injury rat model. Similar results were found with the OGD/R-induced H9c2 cells. Interestingly, ACSL4 knockdown attenuated iron accumulation, oxidative stress, and ferroptosis in the OGD/R-treated H9c2 cells. However, ACSL4 overexpression counteracted the inhibitory effect of the HJ11 decoction on OGD/R-triggered oxidative stress and ferroptosis in H9c2 cells. These findings suggest that HJ11 decoction restrained the development of myocardial I/R injury by regulating ACSL4-mediated ferroptosis. Thus, HJ11 decoction may be an effective medication to treat myocardial I/R injury.

Study on syndrome differentiation strategy of phlegm and blood stasis syndromes of coronary heart disease based on expert consultation on medical cases.

BACKGROUND: It is becoming more and more important to judge whether patients with coronary heart disease (CHD) have phlegm and blood stasis syndromes in the process of traditional Chinese medicine (TCM) diagnosis and treatment of CHD. The syndrome differentiation strategy of phlegm and blood stasis syndromes of CHD is still not standardized, and it is particularly necessary to make syndrome differentiation simpler and more accurate. METHODS: Twenty-eight medical cases that met the criteria, comprising 10 ancient medical cases and 18 modern ones, were selected from the TCM literature, which were then analyzed by 57 experts via questionnaire. Statistical analysis of the data was mainly based on frequency analysis. RESULTS: (I) The average age of the 57 experts from 20 provinces was 48.9±8.5 years; 89.5% were associate professor or above, and 75.4% of them worked at a tertiary hospital. (II) Consistency of expert consultation over medical cases: for the ancient medical cases, the diagnostic consistency rate of phlegm syndrome was 27/34 (79.4%) and additional diagnosis rate of the blood stasis syndrome was 27/57 (47.4%); for the modern medical cases, the consistency rate compared with the original diagnosis of phlegm syndrome was 54/80 (67.5%) and that of blood stasis syndrome was 73/90 (81.1%). (III) The top five experts' diagnostic basics of phlegm syndrome were oppression in the chest, slippery pulse, greasy fur, coughing of phlegm, and chest pain; the top five diagnostic basics of blood stasis syndrome were chest pain, dark tongue, oppression in chest, red tongue, and ecchymosis on tongue. (IV) In the questionnaire consultation on CHD phlegm-blood stasis syndrome cases, the diagnostic basis of "symptom or (and) tongue manifestation" accounted for 12/27 (44.4%) of the diagnostic basics of phlegm syndrome and 28/38 (73.7%) of that of blood stasis syndrome basis. CONCLUSIONS: Modern Chinese medicine experts pay much attention to the diagnosis and treatment of CHD based on TCM pathology theories of phlegm and blood stasis. To collect and detect the patients' symptoms and tongue manifestation is an important strategy of the experts for CHD phlegm and blood stasis syndrome differentiation.

Screening of a potential leafhopper attractants and their applications in tea plantations.

Pheromones can be used as leafhopper attractants. However, commercial pheromone products, such as the Ingle lure, have certain limitations, including poor persistence in the field. In this study, (E)-2-hexenal, (Z)-3-hexen-1-ol, (Z)-3-hexenyl acetate, (E)-ocimene, linalool, and geraniol were selected and behaviorally tested as potential leafhopper attractants. Y-tube olfactometer tests showed that the C2 formulation was more effective than other formulations. In tea field trials, the number of leafhoppers caught by sticky board traps baited with C2 lures was greater than that caught by treatment. The number of leafhoppers attracted by the C2 lures was greater than that attracted by the commercial Ingle lures. Additionally, the total amount of active C2 components on lures was greater than that of the active components on the lure after 14 days. Thus, the results indicated that the C2 formulation may attract leafhoppers and have a greater persistence than other formulations in tea field.

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx.

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 µg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 µg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 µg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

[Clinical effect and mechanism of heat sensitive moxibustion for knee joint synovitis].

OBJECTIVE: To observe the effect of heat sensitive moxibustion based on the articular injection for knee joint synovitis. METHODS: Sixty-seven patients with knee joint synovitis were randomly assigned into an observation group (34 cases) and a control group (33 cases). Articular injection of triamcinolone was used in the control group for 2 courses, 2 times as a course, once 5 days. Based on the treatment in the control group, heat sensitive moxibustion was used in the observation group for 2 courses, 2 weeks as a course, 5 times a week. The acupoints were Yanglingquan (GB 34), Yinlingquan (SP 9), Liangqiu (ST 34), Xuehai (SP 10), Heding (EX-LE 2) or the pain point, subcutaneous nodules around the patella. American Knee Society (AKS) score was measured before and after treatment and one month after treatment. At the same time, the knee joint synovium thickness was measured by MRI; the knee joint effusion was observed by ultrasound; the serum interleukin-1 (IL-1) and matrix metalloproteinase-3 (MMP-3) were measured. RESULTS: After treatment, the AKS scores increased in the two groups (both P<0.05); after treatment and at follow-up, the AKS scores in the observation group were higher than those in the control group (both P<0.05); at follow-up, the AKS score in the control group was lower than that after treatment (P<0.05). After treatment, the synovium thickness, effusion, IL-1 and MMP-3 were lower than those before treatment in the two groups (all P<0.05); after treatment and at follow-up, the four indexes in the observation group were lower than those in the control group (all P<0.05); at follow-up, the four indexes in the control group increased than those after treatment (all P<0.05). CONCLUSION: Heat sensitive moxibustion combined with medicine articular injection can improve synovium inflammatory reaction and the absorption of effusion in the articular cavity,with long-time effect, which are better than simple medicine articular injection.

Multistage analysis method for detection of effective herb prescription from clinical data.

Determining effective traditional Chinese medicine (TCM) treatments for specific disease conditions or particular patient groups is a difficult issue that necessitates investigation because of the complicated personalized manifestations in real-world patients and the individualized combination therapies prescribed in clinical settings. In this study, a multistage analysis method that integrates propensity case matching, complex network analysis, and herb set enrichment analysis was proposed to identify effective herb prescriptions for particular diseases (e.g., insomnia). First, propensity case matching was applied to match clinical cases. Then, core network extraction and herb set enrichment were combined to detect core effective herb prescriptions. Effectiveness-based mutual information was used to detect strong herb-symptom relationships. This method was applied on a TCM clinical data set with 955 patients collected from well-designed observational studies. Results revealed that groups of herb prescriptions with higher effectiveness rates (76.9% vs. 42.8% for matched samples; 94.2% vs. 84.9% for all samples) compared with the original prescriptions were found. Particular patient groups with symptom manifestations were also identified to help investigate the indications of the effective herb prescriptions.

[Study on Macrocosmic Diagnostic Criteria for Coronary Heart Disease with Intermingled Phlegm- Blood Stasis Syndrome].

Macrocosmic diagnostic criteria for coronary heart disease (CHD) with phlegm-damp- ness syndrome (PDS) were established after screening based on macrocosmic indices of CHD with PDS after previous literature analyses and experts consultations. The weights of macrocosmic indices of PDS were compared using analytic hierarchy process (AHP). Macrocosmic diagnostic criteria for CHD with intermingled phlegmblood stasis syndrome were studied by combining with diagnostic criteria for CHD patients with blood stasis syndrome (BSS) set by Academician CHEN Ke-ji group.

Bu-Shen-Jian-Pi-Yi-Qi Therapy Prevents Alcohol-Induced Osteoporosis in Rats.

Bu-Shen-Jian-Pi-Yi-Qi therapy, which refers to reinforcing kidney, regulating qi, and invigorating spleen, is a traditional Chinese medicine, and we investigated its efficacy in treatment of alcohol-induced osteoporosis and its underlying mechanism. Forty adult male Sprague-Dawley rats were randomly assigned into alcohol-supplemented group, JIAN-GU-LING (JGL) group, calcium D3 + alfacalcidol group, and sham-treated group. Bone mineral density (BMD), bone mineral content (BMC), and bone biomechanical properties were assessed. Biochemical analyses of serum and urine specimens were detected. Reverse transcription-polymerase chain reaction was used to detect the mRNA level of vitamin D receptor (VDR). There were markedly lower bone metabolic markers and biomechanical properties in alcohol-supplemented group compared with sham-treated group (all P < 0.05). BMD, BMC, 25(OH)D3, and 1,25(OH)2D3 were elevated in JGL group relative to calcium D3 + alfacalcidol group (all P < 0.05). U-Ca/Cr and U-P/Cr in JGL group were higher than those in the calcium D3 + alfacalcidol group (all P < 0.05). VDR mRNA level in the JGL group was elevated markedly in comparison with alcohol + calcium D3 + alfacalcidol group (P < 0.05). Based on our results, Bu-Shen-Jian-Pi-Yi-Qi therapy inhibits bone loss, promotes bone formation, and effectively improves bone metabolism in rats with experimental alcoholic osteoporosis. The disease reversal is evidenced by increased BMD and BMC, improved biomechanical properties, elevated VDR mRNA level, enhanced response sensitivity of 1, 25(OH)2D3, and reduced S-Ca/P.

[Efficacy observation on infiltrative exophthalmos treated with acupuncture and acupoint massage].

OBJECTIVE: To observe the clinical efficacy of acupuncture combined with massage on infiltrative exophthalmos so as to provide a more effective treatment for infiltrative exophthalmos in hyperthyroidism. METHODS: Forty-five cases of infiltrative exophthalmos were randomly divided into an acupuncture massage group (25 cases) and a western medicine group (20 cases). In acupuncture massage group, acupuncture was applied mainly at Jingming (BL 1), Qiuhou (EX-HN 7), Chengqi (ST 1) and Shangming (Extra); and massage was applied in combination on the back of the neck and the local points around the orbit. In western medicine group, Dexamethasone and Methotrexate were used for intravenous infusion, and Prednisone was for oral administration. The exophthalmos extent and clinical efficacy were compared between two groups. RESULTS: Before and after the treatment, the exophthalmos extents were (20.27 +/- 1.22) mm and (18.11 +/- 0.87) mm in acupuncture massage group and were (20.34 +/- 1.20) mm and (19.47 +/- 1.11) mm in western medicine group separately, indicating remarkable improvement in two groups (both P < 0.01). The improvement in acupuncture massage group was superior remarkably to that in western medicine group (P < 0.01). The total effective rate (83.3%, 40/48) in acupuncture massage group was superior to that (53.8%, 21/39) in western medicine group, and with less adverse reaction. CONCLUSION: Acupuncture combined with acupoint massage is an advanced therapy and has definite efficacy on infiltrative exophthalmos, which is superior to the conventional treatment in western medicine.

Solid-phase synthesis of 1,2-diheterocyclic-substituted (E)-olefins from a supported selenium resin.

A library of 1,2,3-triazoles, isoxazoles, 1,2,4-oxadiazoles, and isoxazoline-containing 1,2-di-heterocyclic-substituted compounds with three points of diversity linked by an E double bond were prepared. Key steps include a 1,3-dipolar cycloaddition and Porco's two-step, one-pot condensation and alpha-alkylation reaction of selenium resins.

[Synthetical evaluation of promoting effect of some kinds of transdermal enhancers with grey relational cluster method].

OBJECTIVE: Synthetical evaluation of promoting effect of some kinds of transdermal enhancers was carried through. METHOD: Diclofenac sodium was used as model, and azone and l-menthol and synthetic borneol and olieic acid and essential oil from Cnidium monnieri were used as transdermal enhancers. Transdermal absorption experimentation of diclofenac sodium on the device of penetrating skins in vitro was done. Cumulation of permeation amount and penetrating rates and steady fluxes and lag times were observed, and grey relational cluster method was used to evaluate the promoting effect of some kinds of transdermal enhancers. RESULT: As for promoting effect on diclofenac sodium, azone and l-menthol were the best, and synthetic borneol and olieic acid ranked behind. CONCLUSION: Grey relational cluster method can evaluate promoting effect objectively and fairly.