Current Progress and Outlook for Agrimonolide: A Promising Bioactive Compound from Agrimonia pilosa Ledeb.

Agrimonolide (AM), which is a derivative of isocoumarins, is found mainly in the herb Agrimonia pilosa Ledeb. This compound is highly lipophilic and readily crosses the blood-brain barrier. In recent years, interest has grown in the use of AM as a multitarget natural treatment for various diseases, such as cancer, inflammation, hepatic injury, myocardial damage, and diabetes mellitus. The potential mechanisms of these pharmacological effects have been clarified at cellular and molecular levels. AM shows no cytotoxicity over a range of concentrations in different types of cells, providing evidence for its good safety profile in vitro. These findings indicate that AM is a promising medicinal agent. However, most studies on AM's pharmacological activities, mechanisms of action, and safety lack substantial animal or human data. Additionally, the pharmacokinetics, metabolism, and disposition of this compound have received little attention. This review highlights the status of current information regarding the sources, properties, pharmacological effects, and safety of AM. Furthermore, potential strategies to resolve problematic issues identified in previous studies are fully discussed. This summary and analysis of the research progress of AM may inspire deeper investigations and more extensive applications of AM in the future.

Enhanced Oral Bioavailability of Chlormadinone Acetate through a Self-Microemulsifying Drug Delivery System for a Potential Dose Reduction.

Chlormadinone acetate (CMA) is a derivative of the naturally secreted hormone progesterone and exhibits reliable contraceptive and non-contraceptive benefits. Although the marketed product of CMA as oral tablets under the trade name Belara® has been highly successful, there is still room for further improvements in oral bioavailability and a reduction in the clinical dose to decrease related adverse effects. In the current study, a CMA-based self-microemulsifying drug delivery system (SMEDDS) was developed using 32% ethyl oleate as an oil phase, 40% Tween-80 as a surfactant, and 12% Transcutol P combined with 16% PEG400 as a cosurfactant, resulting in spherical droplets with a z-average particle size of 38.92 nm and an average zeta potential of - 3.18 mv. The in vitro release rate of CMA from CMA-SMEDDS in different media (distilled water, HCl solution at pH 1.2, phosphate buffers at pH 4.5 and pH 6.8) was significantly faster than that from Belara® in the first 15 min. A pharmacokinetic study in rats showed that the Cmax and AUC of CMA-SMEDDS were significantly higher (P < 0.01) than those of Belara®, with a 1.98-fold increase in oral bioavailability. In comparison with Belara®, the developed CMA-SMEDDS showed promising release profiles both in vitro and in vivo, which could potentially be useful in enhancing oral bioavailability and reducing the clinical dose of CMA.

(-)-Meptazinol-melatonin hybrids as novel dual inhibitors of cholinesterases and amyloid-ß aggregation with high antioxidant potency for Alzheimer's therapy.

The multifactorial pathogenesis of Alzheimer's disease (AD) implicates that multi-target-directed ligands (MTDLs) intervention may represent a promising therapy for AD. Amyloid-ß (Aß) aggregation and oxidative stress, two prominent neuropathological hallmarks in patients, play crucial roles in the neurotoxic cascade of this disease. In the present study, a series of novel (-)-meptazinol-melatonin hybrids were designed, synthesized and biologically characterized as potential MTDLs against AD. Among them, hybrids 7-7c displayed higher dual inhibitory potency toward cholinesterases (ChEs) and better oxygen radical absorbance capacity (ORAC) than the parental drugs. Furthermore, compound 7c could effectively inhibit Aß self-aggregation, showed favorable safety and the blood-brain barrier (BBB) permeability. Therefore, 7c may serve as a valuable candidate that is worthy of further investigations in the treatment of AD.

Sulfur inhibits the growth of androgen-independent prostate cancer in vivo.

Sulfur is a bright yellow crystalline solid at room temperature. The aim of the present study was to investigate the inhibitory effect of sulfur on prostate cancer (PCa) in vivo. Prostate tumors were developed by injecting 22Rv1 or DU-145 PCa cells into sulfur-treated or untreated nude mice. The weight and volume of the tumors were measured. The cancer cells were separated from the tumors, and analyzed for their growth rate and clonogenicity in culture. The expression of PCa-targeted genes was also assessed using real-time polymerase chain reaction. The rate of growth of 22Rv1 tumors in sulfur-treated nude mice gradually decreased, and was reduced by 41.99% (P<0.01) after 22 days when compared with that of the control group. In addition, the growth of DU-145 tumors was also suppressed by 75.16% (P<0.05) after 11 weeks. The clonogenicity of the sulfur-treated tumor cells decreased by 36.7% when compared with that of the control cells. However, no significant difference in cell growth was identified. mRNA levels of the androgen-receptor, prostate specific antigen and human Hox (NKX3.1) genes were significantly decreased by 32.8, 48.2 and 42.2% in sulfur-treated tumors, respectively. Additionally, it was found that the hydrogen sulfide concentration in the serum of sulfur-treated mice was increased by 4.73% (P<0.05). Sulfur significantly suppressed the growth of PCa in vivo. Since sulfur is a known ingredient used in traditional Chinese medicine, it may be used clinically for the treatment of PCa, independently or in combination with other medicine.