Network pharmacology and in vivo studies reveal the neuroprotective effects of paeoniflorin on Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that has still not been effectively treated. Paeoniflorin is a traditional Chinese medicine with potential neuroprotective effects against brain injury; however, the beneficial effects and mechanisms of action in AD have not been clarified. We aimed to explore the mechanisms of action of paeoniflorin in AD using network pharmacology and experimental validation. Network pharmacology analysis revealed 30 candidate targets through the intersection of the targets of paeoniflorin and related genes in AD, which were mainly enriched in oxidative stress and inflammation. Moreover, key targets of paeoniflorin against AD, namely Nrf2 (encoded by NFE2L2) and TLR4, were screened and found to be closely related to oxidative stress and inflammation. Subsequent in vivo experiments revealed that paeoniflorin treatment improved the cognition of APP/PS1 mice by ameliorating oxidative stress and neuroinflammation, which were associated with the upregulation of Nrf2 and HO1, and the downregulation of TLR4. Collectively, the present study demonstrates that paeoniflorin alleviates cognitive impairment in AD by regulating oxidative stress and neuroinflammation, and that Nrf2, HO1, and TLR4 could be key targets.

Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

BACKGROUND: Garlic (Allium sativum), the underground bulb of the Allium genus, has been consumed on Earth for thousands of years. Many clinical trials of garlic supplementation on components of metabolic syndrome (MetS) have emerged in recent years, but there is no consensus on the effect. This meta-analysis aimed at systematically evaluating the effect of garlic supplementation on components of MetS. METHODS: In this meta-analysis, we searched Pubmed, Embase, Cochrane, Medline, Web of Science databases, and clinical trials online sites from inception to November 1, 2022, with language restrictions to English. We engaged participants > 18 years and eligible for the clinical diagnosis of MetS or those with metabolic disorders and garlic was the only intervention. Outcomes included waist circumference, and body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure, and fasting blood glucose. Meta-regression and subgroup analyses were conducted based on six covariates (total sample size, the mean age, the mean dose, the duration of intervention, the oral form of garlic, and the dietary intervention). RESULTS: Results from 19 RCTs were included engaging 999 participants. Compared to placebo, garlic significantly reduced TG [SMD (95%CI) = -0.66 (-1.23, -0.09)], TC [SMD (95%CI) = -0.43 (-0.86, -0.01)], LDL [SMD (95%CI) = -0.44(-0.88, -0.01)], DBP [SMD (95%CI) = -1.33 (-2.14, -0.53)], BMI [SMD (95%CI) = -1.10(-1.90, -0.20)], and WC [SMD (95%CI) = -0.78(-1.09, -0.47)]. Meta-regression showed age and sample size are potential effect modifiers. CONCLUSION: According to the results of meta-analysis, the modulatory effect of garlic on some MetS components is evident. More high-quality, large-scale RCTs are needed to confirm iat based on the high heterogeneity and potential publication bias of the current data. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=373228 , ID: CRD42022373228.

Role of puerarin in pathological cardiac remodeling: A review.

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Integrated pharmacokinetics of ginsenosides after intravenous administration of YiQiFuMai powder injection in rats with chronic heart failure by UFLC-MS/MS.

YiQiFuMai powder injection (YQFM), derived from the classical traditional Chinese medicine (TCM) formula Shengmai San, is a modern preparation widely used to combat cardiovascular diseases, chronic heart failure (CHF) for example, in clinical practice in China. Ginsenosides are the major components of YQFM, which are responsible for its therapeutic effect. In this research, we developed a rapid, sensitive and simple method for simultaneous determination of ten ginsenosides from YQFM in CHF rat plasma with ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS). After solid phase extraction (SPE), chromatography was done on an Acquity UPLC HSS T3 column (1.8µm, 100mm×2.1mm, i.d.) through an 8.0min gradient elution with acetonitrile and 0.1% formic acid in water, while mass spectrometry was performed in the positive ion electrospray ionization (ESI) mode. A good linearity was achieved for each analyte with correlation coefficient (r) >0.9920. The lower limits of quantification (LLOQ) were 1.25ng/mL for ginsenoside Rg1, Rd, Re and Rh1, 2.5ng/mL for ginsenoside Rf, Rg3, Rb2 and Rb3 and 5.0ng/mL for ginsenoside Rb1 and Rc, respectively. All the precision (RSD) data ranged from 1.7-14.5% and the accuracy (RE) data was within ±13.73%. Moreover, the validated method has been applied to investigate the integrated pharmacokinetic profiles of ginsenosides in CHF rats following intravenous administration of YQFM successfully.

GC-MS/MS method for the determination and pharmacokinetic analysis of borneol and muscone in rat after the intravenous administration of Xingnaojing injection.

A simple and sensitive gas chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of borneol and muscone in rat plasma. The analytes and internal standard, naphthalene, were extracted using a convenient one-step liquid-liquid extraction method with ethyl acetate. The chromatographic separation was realized on a HP-5MS capillary column and detected in multiple reaction monitoring mode. Excellent linearity (R2  ≥ 0.996) was shown over 10.0-5000 ng/mL for borneol and 2.5-250 ng/mL for muscone. The lower limit of quantitation was 10 and 2.5 ng/mL for borneol and muscone, respectively. The intra- and interday precisions were less than 7.52%, and the accuracy values were between  -8.03 and 14.52%. The extraction recovery, matrix effect, and stability were sufficient to meet the Food and Drug Administration criteria. Meanwhile, the assay was successfully applied to the preclinical pharmacokinetic study of borneol and muscone following intravenous administration of Xingnaojing injection, a modern Chinese herbal medicine preparation.