Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway.

BACKGROUND AND AIMS: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. METHODS: ApoE-/- mice were fed a high-cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An invitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. RESULTS: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 µg/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL-6, IL-1ß, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-κB signaling pathway. CONCLUSIONS: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-κB signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

PPI-amoxicillin dual therapy for Helicobacter pylori infection: An update based on a systematic review and meta-analysis.

BACKGROUND AND AIMS: The efficacy of PPI-amoxicillin dual therapy (high-dose dual therapy) in the eradication of Helicobacter pylori is controversial. We aimed to investigate whether PPI-amoxicillin dual therapy is effective. METHODS: We searched several publication databases for randomized controlled trials (RCTs) that compared PPI-amoxicillin dual therapy with controls up to March 2019. Meta-analyses of eradication rates were performed using random-effects models. RESULTS: Data from twelve RCTs including 2249 patients suggested that PPI-amoxicillin dual therapy and the current mainstream guidelines-recommended therapies achieved similar efficacy (83.2% vs 85.3%, risk ratio [RR]: 1.00, 95% CI 0.97-1.03, intention-to-treat analysis), (87.5% vs 90.1%, RR: 0.98, 95% CI 0.95-1.02, per-protocol analysis), and compliance (94.3% vs 93.5%, RR: 1.11, 95% CI 0.78-1.59), but side effects were less likely in the dual therapy (12.9% vs 28.0%, RR: 0.53, 95% CI 0.37-0.76). Further subgroup analyses showed that the seven RCTs (1302 patients) that reported antimicrobial susceptibility test results also showed that PPI-amoxicillin dual therapy and the current guidelines-recommended therapies achieved similar efficacy, and PPI-amoxicillin dual therapy was as effective for rescue therapy (RR: 0.97, 95% CI 0.89-1.05) as for first-line treatment (RR: 0.97, 95% CI 0.93-1.02). CONCLUSIONS: Compared with the current mainstream guidelines-recommended therapies, PPI-amoxicillin dual therapy has the same efficacy and compliance, and generally PPI-amoxicillin dual therapy causes fewer side effects.

Withaminimas A-F, six withanolides with potential anti-inflammatory activity from Physalis minima.

Withaminimas A-F (1-6), six new withaphysalin-type withanolides were isolated from the aerial parts of Physalis minima L.. The structures of these compounds were elucidated through a variety of spectroscopic techniques including HR-MS, NMR, and ECD. Compound 1 belongs to rare 18-norwithanolides, and 2-3 were 13/14-secowithanolides. According to the traditional usage of P. minima, inhibitory effects on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated, and compounds 1-4 exhibited significant inhibitory effects with IC50 values among 3.91-18.46 µmol·L-1.

The Anti-inflammatory Activities of Two Major Withanolides from Physalis minima Via Acting on NF-κB, STAT3, and HO-1 in LPS-Stimulated RAW264.7 Cells.

Physalis minima has been traditionally used as a folk herbal medicine in China for the treatment of many inflammatory diseases. However, little is known about its anti-inflammatory constituents and associated molecular mechanisms. In our study, withaphysalin A (WA) and 2, 3-dihydro-withaphysalin C (WC), two major withanolide-type compounds, were obtained from the anti-inflammatory fraction of P. minima. Both WA and WC significantly inhibited the production of nitrite oxide (NO), prostaglandin E2 (PGE2), and several pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-activated RAW264.7 macrophages. Further research indicated that they downregulated the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, they also suppressed nuclear translocation of NF-κB p65, phosphorylation of STAT3, and upregulated HO-1 expression. Intriguingly, the activation of MAPKs was suppressed by WA but was not altered by WC. Taken together, these data provide scientific evidence for elucidating the major bioactive constituents and related molecular mechanisms for the traditional use of P. minima and suggest that WA and WC can be attractive therapeutic candidates for various inflammatory diseases.

Efficacy and safety of high-dose dual therapy for Helicobacter pylori rescue therapy: A systematic review and meta-analysis.

OBJECTIVE: Although some studies have reported >90% success with high-dose dual proton pump inhibitor (PPI)-amoxicillin dual therapy for Helicobacter pylori (H. pylori) eradication, the efficacy of this therapy remains controversial. We aimed to re-evaluate the efficacy and safety of high-dose dual therapy on H. pylori eradication. METHODS: We searched PubMed, the Cochrane Library, and EMBASE for randomized clinical trials (RCTs) evaluating the efficacy of high-dose PPI-amoxicillin dual therapy as the rescue therapy on H. pylori eradication. Treatment effect was determined with a fixed-effect model using the inverse variance method and was expressed as risk ratio (RR) with 95% confidence interval (CI). RESULTS: Because of significant statistical heterogeneity (χ2  15.98, I2  = 69%) among the six studies that qualified, four RCTs that included 473 patients with H. pylori infection after eradication failure were assessed. The meta-analysis showed that high-dose dual therapy and guideline-recommended rescue therapies achieved similar efficacy (81.3% vs 81.5%, RR 1.00 [95% CI 0.93-1.08], intention-to-treat analysis), compliance (95.3% vs 95.4%, RR 1.00 [95% CI 0.97-1.03]), and side effects (17.9% vs 19.7%, RR 0.88 [95% CI 0.62-1.25]). CONCLUSIONS: High-dose PPI-amoxicillin dual therapy is comparable to recommended rescue therapies for H. pylori infection. More researches are needed to determine the efficacy of high-dose dual therapy as a first-line therapy.

Three New Cytotoxic Withanolides from the Chinese Folk Medicine Physalis angulata.

Physagulides M-O, three new withanolides (1-3), were isolated from the aerial parts of Physalis angulata L. Their structures were elucidated through extensive spectroscopic techniques, including 1D and 2D NMR, and HRESIMS. The absolute configurations (22-R) of these new compounds were determined by CD analysis. Compounds 1 and 3 showed significant selective cytotoxic activities on the MG-63 cell line, with IC50 values of 4.28 and 5.44 µM, respectively.

[Observation on therapeutic effect of auricular point sticking combined with Tongshiji treatment on child ametropic amblyopia].

OBJECTIVE: To compare therapeutic effects of auricular point sticking combined with Tongshiji treatment and simple Tongshiji treatment on child ametropic amblyopia. METHODS: Three hundred children of ametropic amblyopia were classified as mild, moderate and severe groups, 100 cases in each group. The each group was again randomly divided into a simple Tongshiji treatment (control group) and a auricular point sticking combined with Tongshiji treatment group (observation group). Their therapeutic effects were compared. RESULTS: The total effective rate in the observation group were 100.0%, 79.8% and 71.0%, and in the control group were 100.0%, 54.3% and 48.2% respectivety for mild, moderate and severe groups. For the mild amblyopia children, there was no significant difference between the two groups in the therapeutic effect; for the moderate and severe ametropic amblyopia children, the therapeutic effect in the observation group was better than that in the control group (P<0.05). CONCLUSION: Auricular point sticking combined with Tongshiji treatment for child ametropic amblyopia is of characteristics of convenient manipulation, obvious and rapid therapeutic effect.