Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC₅₀ of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of −8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

The effective components of Coptis chinensis were extracted by ultrasound-assisted technology, and the contents of palmatine and berberine were used as indexes by using Coptis chinensis as raw material and eutectic solvent as extractant. In addition, the effects of hydrogen bond donor type, molar ratio of hydrogen bond donor to acceptor, material-liquid ratio, water content of eutectic solvent system, sonication time, power, and ultrasonic temperature on the extraction rate of palmatine and berberine were studied. The optimum extraction technology of palmatine and berberine from Coptis chinensis was determined by single-factor experiment and response surface optimization test. As a result, it showed that the eutectic solvent system was constructed with choline chloride as hydrogen bond acceptor and phenol as hydrogen bond donor, with a molar ratio of 1:3. In addition, water content of the eutectic solvent system was 30, ratio of material to liquid was 30g/mL, ultrasonic time was 30min, ultrasonic power was 200W, and ultrasonic temperature was 60°C. At this time, the contents of palmatine and berberine in Coptis chinensis were 16.7145mg/g and 57.4013mg/g, respectively, which were predicted to be the same as the value, and the extraction effect was better than that of traditional extraction solvent method.

Inhibition of protein disulfide isomerase (PDI) has been attempted as a promising anti-cancer strategy. However, there is still no currently available PDI inhibitors approved for clinical use. Here, we isolated seven high yield alkaloids from Stephaniae tetrandrae Radix (STR), a medical herb frequently prescribed in anti-tumor condition, and identified two potent natural PDI inhibitors, dicentrine and dicentrinone. Among the seven alkaloids isolated, dicentrinone (1), dicentrine (2), tetrandrine (4), and fangchinoline (5) could significantly reduce cell viability in a dosage dependent manner detected by MTT assay in human hepatoma cells. To examine whether the candidate compounds are potent PDI inhibitors, we performed insulin turbidity assay and found dicentrine and dicentrinone, but not tetrandrine and fangchinoline, could effectively inhibit PDI activity, with IC50 of 56.70 μM and 43.95 μM respectively. Meanwhile, dicentrine and dicentrinone failed to further reduce the cell number index when co-treated with siRNA of PDI, suggesting the compounds behave as PDI inhibitors. Furthermore, dicentrinone and dicentrine have been successfully docked to the active pocket of PDI (PDB #3UEM) by molecular docking, suggesting the existence of physical interaction between compounds and PDI. Our results suggested that dicentrine and dicentrinone may be developed into safe PDI inhibitors.

Cancer-related fatigue (CRF) is a common symptom among patients with cancer, with a prevalence of >49%. CRF significantly affects the quality of life of patients and may also affect their overall survival. Pharmacological interventions serve as a last resort after carefully weighing the risks and benefits, with limited benefits for patients, many side effects, and adverse reactions. Compared to traditional medicine, nutritional approaches have fewer side effects, are highly accepted by patients, and do not affect the antitumor treatment of patients. Many studies have shown that nutritional approaches, as a form of complementary and alternative medicine, help improve the symptoms of CRF and the quality of life of patients. This study was designed to examine nutritional approaches to CRF and assess their effectiveness of nutritional approaches in improving CRF. We present an overview of clinical trials investigating nutritional approaches for CRF that have been published over the last 2 decades. A total of 33 records were obtained from 3 databases: Web of Science, MEDLINE, and PubMed. Some nutritional approaches, such as melatonin, PG2, and S-adenosyl-l-methionine, are potential options for CRF treatment. However, the trials included in the review varied widely in quality, most were weak in methodology, and there is currently insufficient evidence to conclude with certainty the effectiveness of nutritional approaches in reducing CRF. Therefore, the design and methods used in future complementary and alternative medicine trials should be more rigorous.