Current Pharmaceutical Design - Volume 31, Issue 15, 2025

In vascular tissue, macrophages and inflammatory cells produce the enzyme lipoprotein-associated phospholipase A2 (Lp-PLA2). Treatment with fibrates decreases Lp-PLA2 levels in individuals with obesity and metabolic syndrome; however, these findings have not been fully clarified.

The goal of this study was to investigate the possible effects of fibrate therapy on Lp-PLA2 mass and activity through a meta-analysis of clinical trials.

Web of Science, PubMed, Scopus, Google Scholar, and ClinicalTrials.gov databases were searched using MeSH terms and keywords. Randomized controlled trials (RCT) evaluating the effect of statins on Lp- PLA2 mass and/or activity were included in the meta-analysis. Quantitative data were analyzed using a random-effects model and the generic inverse variance method.

The meta-analysis of 10 clinical trials indicated that fibrate treatment has no significant effect on Lp- PLA2 mass (fibrate vs. placebo/nothing = WMD: -3.29 ng/ml, 95% CI: -21.35, 14.78, p = 0.72; fibrate vs. active control = WMD: -1.08 ng/ml, 95% CI: -51.38, 49.22, p = 0.97); Lp-PLA2 activity (fibrate vs. active control = WMD: 0.84 nmol/ml/min, 95% CI: -0.17, 1.84, p = 0.10); HDL-LpPLA2 activity (fibrate vs. active control = WMD: 0.77 nmol/ml/min, 95% CI: -0.33, 1.88, p = 0.17); and secretory PLA2 (fibrate vs. active control = WMD: 0.37 ng/ml, 95% CI: -1.22, 1.97, p = 0.65). Also, the results of the sensitivity analysis were robust for all these parameters.

In conclusion, fibrate therapy did not reduce the mass and activity of Lp-PLA2.

Taohong Siwu decoction (THSWD), a traditional prescription for enhancing blood circulation and eliminating blood stasis, primarily comprises peach kernel, safflower, angelica, chuanxiong, and rehmannia. Modified Taohong Siwu decoction (MTHSWD), an advanced version of THSWD, incorporates additional ingredients such as epimedium, cinnamon, and Salvia miltiorrhiza. This addition serves to augment its efficacy in warming yang and promoting blood circulation. MTHSWD has excellent heart protection in cardiac damage, which indicates a promising application prospect. However, the mechanisms are yet unclear.

In this study, network pharmacology and molecular docking studies demonstrated that the effects of MTHSWD may be significantly influenced by the PI3K/Akt signaling pathway. In addition, to verify this mechanism, three groups were divided and randomly selected from among the 35 Sprague-Dawley rats: Myocardial infarction (MI) group, THSWD group, and MTHSWD group.

MTHSWD greatly improved fractional shortening as well as ejection fraction and reduced the infarct size. MTHSWD attenuated cell apoptosis by activating the Akt pathway in infarcted areas. In vitro, the cytoprotective effects of MTHSWD on H9C2 cells were significantly attenuated when PI3K/Akt was inhibited.

Therefore, the study found that MTHSWD had a positive effect on heart function after myocardial infarction by activating the Akt pathway.

Nitric oxide (NO) is a low-toxicity and high-efficiency anticancer treatment that can augment the cytotoxicity of doxorubicin (DOX) towards breast cancer cells, thereby exhibiting a favorable effect on chemotherapy sensitization.

The study aimed to establish a hydrogel that sensitizes chemotherapy by inducing local inflammatory stimulation to change the tumor microenvironment and promote NO production. The purpose of the study was to examine the anti-tumor effect in vivo and in vitro.

The functional properties of the composite hydrogels were tested by UV spectrophotometry and NO detection kit. CCK8, DCFH-DA fluorescent probe, Calcein-AM/PI detection kit, and confocal detection methods were used for the cytocompatibility and cytotoxicity of the composite hydrogels. The subcutaneous tumor volume, weight, and tumor inhibition rate of 4T1 breast cancer cells were evaluated for pharmacodynamic study in vivo.

Each component of hydrogel has good biocompatibility. The combination of gas therapy and chemotherapy can significantly enhance the effect of inhibiting tumor cell growth. The tumor growth of tumor-bearing mice in the hydrogel administration group was slow, and the tumor inhibition rate was 85.10%. The body weight grew steadily, and no significant pathological changes were observed in the H&E staining of major organs.

A composite hydrogel with alginate as the carrier was successfully established, which was based on improving the tumor microenvironment to trigger gas therapy combined with chemotherapy for tumor treatment.

This study aims to isolate and characterize potential cytotoxic compounds from the roots of Bauhinia variegata Linn. (Caesalpiniaceae) and evaluate their activity against human cancer cell lines. Five compounds, namely β-sitosterol (1), piperine (2), piperolein B (3), retrofractamide A (4), and dehydropipernonaline (5), were isolated from B. variegata roots using various chromatographic procedures.

The root extracts were prepared using aqueous and organic solvents, including n-hexane, ethyl acetate, and methanol. The isolated compounds were subjected to a sulforhodamine B cytotoxicity assay against DU-145 and PC-3 (prostate), HT-29 (colon), and MCF-7 (breast) human cancer cell lines. Among the isolates, compound 5 exhibited significant bioactivity against all tested cell lines. Compound 4 demonstrated in vitro activity, specifically against MCF-7 cancer cell lines.

Importantly, these compounds were identified for the first time from B. variegata roots. In conclusion, this study highlights the enhanced spectrum of cytotoxic activity exhibited by the isolated compounds. These findings encourage further investigation to elucidate the mechanism of action of these compounds against the respective cell lines.

The identification and characterization of these bioactive compounds contribute to the understanding of the potential therapeutic applications of B. variegata in cancer treatment.