3β,23-Dihydroxy-12-ene-28-ursolic Acid Isolated from Cyclocarya paliurus Alleviates NLRP3 Inflammasome-Mediated Gout via PI3K-AKT-mTOR-Dependent Autophagy

Gout is regarded as a painful inflammatory arthritis induced by the deposition of monosodium urate crystals in joints and soft tissues. Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated IL-1β production plays a crucial role in the pathological process of gout. Cyclocarya paliurus (CP) tea was found to have an effect on reducing the blood uric acid level of people with hyperuricemia and gout. However, its medicinal ingredients and mechanism for the treatment of gout are still unclear. Thus, this study was designed to investigate the effects of the active triterpenoids isolated from C. paliurus on gout and explore the underlying mechanism. The results showed that compound 2 (3β,23-dihydroxy-12-ene-28-ursolic acid) from C. paliurus significantly decreased the protein expression of IL-1β, caspase-1, pro-IL-1β, pro-caspase-1, and NLRP3. Furthermore, the production of ROS in the intracellular was reduced after compound 2 treatment. However, ROS agonist rotenone remarkably reversed the inhibitory effect of compound 2 on the protein expression of NLRP3 inflammasome. Additionally, the expression level of LC3 and the ratio of LC3II/LC3I were increased, but the expression level of p62 was suppressed by compound 2 whereas an autophagy inhibitor 3-methyladenine (3-MA) significantly abolished the inhibitory effects of compound 2 on the generation of ROS and the protein expression of NLRP3 inflammasome. Moreover, compound 2 could ameliorate the expression ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Interestingly, mTOR activator MHY-1485 could block the promotion effect of compound 2 on autophagy regulation and inhibitory effect of compound 2 on induction of ROS and IL-1β. In conclusion, these findings suggested that compound 2 may effectively improve NLRP3 inflammasome-mediated gout via PI3K-AKT-mTOR-dependent autophagy and could be further investigated as a potential agent against gout.

Potential Role of Natural Plant Medicine Cyclocarya paliurus in the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a common chronic metabolic disease that has become increasingly prevalent worldwide. It poses a serious threat to human health and places a considerable burden on global social medical work. To meet the increasing demand for T2DM treatment, research on hypoglycemic drugs is rapidly developing. Cyclocarya paliurus (Batal.) Iljinskaja is a medicinal plant that grows in China. The leaves of C. paliurus contain polysaccharides, triterpenoids, and other chemical components, which have numerous health benefits. Therefore, the use of this plant has attracted extensive attention in the medical community. Over the past few decades, contemporary pharmacological studies on C. paliurus extracts have revealed that it has abundant biological activities. Multiple in vitro and in vivo experiments have shown that C. paliurus extracts are safe and can play a therapeutic role in T2DM through anti-inflammatory and antioxidation activities, and intestinal flora regulation. Its efficacy is closely related to many factors, such as extraction, separation, purification, and modification. Based on summarizing the existing extraction methods, this article further reviews the potential mechanism of C. paliurus extracts in T2DM treatment, and we aimed to provide a reference for future research on natural plant medicine for the prevention and treatment of T2DM and its related complications.

Microencapsulation of Cyclocarya paliurus (Batal.) Iljinskaja Extracts: A Promising Technique to Protect Phenolic Compounds and Antioxidant Capacities

This study aimed to protect phenolic compounds of Cyclocarya paliurus (Batal.) Iljinskaja (C. paliurus) using a microencapsulation technique. Ethanol and aqueous extracts were prepared from C. paliurus leaves and microencapsulated via microfluidic-jet spray drying using three types of wall material: (1) maltodextrin (MD; 10–13, DE) alone; (2) MD:gum acacia (GA) of 1:1 ratio; (3) MD:GA of 1:3 ratio. The powders’ physicochemical properties, microstructure, and phenolic profiles were investigated, emphasizing the retentions of the total and individual phenolic compounds and their antioxidant capacities (AOC) after spray drying. Results showed that all powders had good physical properties, including high solubilities (88.81 to 99.12%), low moisture contents (4.09 to 6.64%) and low water activities (0.11 to 0.19). The extract type used for encapsulation was significantly (p < 0.05) influenced the powder color, and more importantly the retention of total phenolic compounds (TPC) and AOC. Overall, the ethanol extract powders showed higher TPC and AOC values (50.93–63.94 mg gallic acid equivalents/g and 444.63–513.49 µM TE/g, respectively), while powders derived from the aqueous extract exhibited superior solubility, attractive color, and good retention of individual phenolic compounds after spray drying. The high-quality powders obtained in the current study will bring opportunities for use in functional food products with potential health benefits.

Anti-Hyperglycemic Effects of Refined Fractions from Cyclocarya Paliurus Leaves on Streptozotocin-Induced Diabetic Mice

To identify the chemical components responsible for the anti-hyperglycemic effect of Cyclocarya paliurus (Batal.) Iljinsk (Juglandaceae) leaves, an ethanol extract (CPE) and a water extract (CPW) of C. paliurus leaves, as well as their total flavonoids (CPF), triterpenoids (CPT) and crude polysaccharides (CPP), were prepared and assessed on streptozotocin (STZ)-induced diabetic mice. After being orally administrated once a day for 24 days, CPF (300 mg/kg), CPP (180 mg/kg), or CPF+CPP (300 mg/kg CPF + 180 mg/kg CPP) treatment reversed STZ-induced body weight and muscle mass losses. The glucose tolerance tests and insulin tolerance tests suggested that CPF, CPP, and CPF+CPP showed anti-hyperglycemic effect in STZ-induced diabetic mice. Furthermore, CPF enhances glucose-stimulated insulin secretion in MIN6 cells and insulin-stimulated glucose uptake in C2C12 myotubes. CPF and CPP suppressed inflammatory cytokine levels in STZ-induced diabetic mice. Additionally, CPF and CPP improved STZ-induced diabetic nephropathy assessed by H&E staining, blood urea nitrogen content, and urine creatinine level. The molecular networking and Emperor analysis results indicated that CPF showed potential anti-hyperglycemic effects, and HPLC–MS/MS analysis indicated that CPF contains 3 phenolic acids and 9 flavonoids. In contrast, CPT (650 mg/kg) and CPC (300 mg/kg CPF + 180 mg/kg CPP + 650 mg/kg CPT) did not show anti-hyperglycemic effect. Taken together, polysaccharides and flavonoids are responsible for the anti-hyperglycemic effect of C. paliurus leaves, and the clinical application of C. paliurus need to be refined.