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.

Anti-Planktonic and Anti-Biofilm Properties of Pentacyclic Triterpenes—Asiatic Acid and Ursolic Acid as Promising Antibacterial Future Pharmaceuticals

Due to the ever-increasing number of multidrug-resistant bacteria, research concerning plant-derived compounds with antimicrobial mechanisms of action has been conducted. Pentacyclic triterpenes, which have a broad spectrum of medicinal properties, are one of such groups. Asiatic acid (AA) and ursolic acid (UA), which belong to this group, exhibit diverse biological activities that include antioxidant, anti-inflammatory, diuretic, and immunostimulatory. Some of these articles usually contain only a short section describing the antibacterial effects of AA or UA. Therefore, our review article aims to provide the reader with a broader understanding of the activity of these acids against pathogenic bacteria. The bacteria in the human body can live in the planktonic form and create a biofilm structure. Therefore, we found it valuable to present the action of AA and UA on both planktonic and biofilm cultures. The article also presents mechanisms of the biological activity of these substances against microorganisms.

Design, synthesis, anticancer activity and mechanism studies of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid

A series of novel 2-amino-4-aryl-pyrimidine derivatives of ursolic acid were designed, synthesized, and evaluated for their anticancer activities against four cancer cell lines (MCF-7, HeLa, HepG2, and A549) and a...

Nanoparticles use for Delivering Ursolic Acid in Cancer Therapy: A Scoping Review

Ursolic acid is a natural pentacyclic triterpenoid that exerts a potent anticancer effect. Furthermore, it is classified as a BCS class IV compound possessing low permeability and water solubility, consequently demonstrating limited bioavailability in addition to low therapeutic effectiveness. Nanoparticles are developed to modify the physical characteristics of drug and can often be produced in the range of 30–200 nm, providing highly effective cancer therapy due to the Enhanced Permeation and Retention (EPR) Effect. This study aims to provide a review of the efficacy and safety of various types of Ursolic Acid-loading nanoparticles within the setting of preclinical and clinical anticancer studies. This literature study used scoping review method, where the extracted data must comply with the journal inclusion criteria of within years of 2010–2020. The identification stage produced 237 suitable articles. Duplicate screening was then conducted followed by the initial selection of 18 articles that had been reviewed and extracted for data analysis. Based on this review, the use of nanoparticles can be seen to increase the anticancer efficacy of Ursolic Acid in terms of several parameters including pharmacokinetic data, survival rates and inhibition rates, as well as the absence of serious toxicity in preclinical and clinical trials in terms of several parameters including body weight, blood clinical chemistry, and organ histipathology. Based on this review, the use of nanoparticles has been able to increase the anticancer efficacy of Ursolic Acid, as well as show the absence of serious toxicity in preclinical and clinical trials. Evenmore, the liposome carrier provides development data that has reached the clinical trial phase I. The use of nanoparticle provides high potential for Ursolic Acid delivery in cancer therapy.