Pharmacokinetics Study of Rabdosia Rubescens Drop Pills Based on UPLC-MS/MS

Background: Rabdosia rubescens drop pills have the effects of clearing away heat and toxin, detumescence, relieving pain. Objective: A simple and sensitive method for simultaneous determination of oridonin, ponicidin, and rosmarinic acid in rat plasma was developed based on ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Methods: Chromatographic separation was performed on a Waters ACQUITY UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with a mobile phase consisting of water containing 0.2% formic acid (mobile phase A) and methanol (mobile phase B) at a flow rate of 0.3 mL/min over a total run time of 3.8 min. All analytes were measured with optimized multiple reaction monitoring (MRM) in positive and negative ion ESI mode. Results: The transitions of oridonin, ponicidin, rosmarinic acid, diphenhydramine, and chloramphenicol were 365.3→347.3, 363.3→345.2, 359.0→160.9, 256.0→167.2, and 321.1→151.9, respectively. The linear ranges were 1-256 ng/mL for ponicidin and rosmarinic acid and 2-512 ng/mL for oridonin. The validated method wasstable and reliable. There was no significant difference in the half-life (t1/2) of the three analytes at three doses. The area under the curve (AUC0-t) and peak concentration (Cmax) of the three analytes decreased linearly in each dose range, and the linear correlation R2 of each analyte under the three doses was greater than 0.95. Conclusion: This method was successfully applied to pharmacokinetic studies of oridonin, ponicidin, and rosmarinic acid in rat plasma after intragastric administration of Rabdosia rubescens drop pills.

Oridonin Attenuates Diabetes‑Induced Renal Fibrosis via Inhibition of the TXNIP/NLRP3 and NF‑κB Pathway in Rats

Background: Oxidative stress and its induced inflammation are important pathological processes of diabetic nephropathy (DN). Oridonin, a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory properties, it is also a newly reported NLRP3 inhibitor. However, the renoprotective effects of Oridonin and the underlying molecular mechanisms have not been explored in DN. We hypothesized that Oridonin could reduce NLRP3 pathway and ameliorate diabetes‑induced renal fibrosis.Methods: We used STZ-induced diabetic rats combined high-fat diet to establish a T2DM animal model, and then treated with Oridonin (10, 20 mg/kg/day) for two weeks. Kidney function and renal fibrosis were assessed. In addition, the expression of inflammatory factors and fibrotic markers were analyzed by western blot.Results: Oridonin treatment preserved kidney function and markedly limited the renal fibrosis size in diabetic rats. The renal fibrotic markers were inhibited in the 10 mg/kg/day group and 20 mg/kg/day group compared to the T2DM group. Moreover, the expression levels of TXNIP/NLRP3 and NF‑κB pathway were decreased in the Oridonin treatment group compared to non-treated group. Conclusions: The NLRP3-inflammasome inhibitor Oridonin reduces renal fibrosis and preserves kidney function in T2DM rat model, which indicates potential therapeutic effect of Oridonin on DN.

Preparation of microcrystalline cellulose from Rabdosia rubescens residue and study on its membrane properties

Microcrystalline cellulose (MCC) was prepared easily from Rabdosia rubescens residue to realize the efficient utilization of waste resources. The yield was about 95.03% under the optimal conditions. Then, MCC membrane was prepared by phase transformation method and its structure and mechanical properties were studied systemically. The results showed the cellulose crystal structure changed from type I to type II in the process of forming membrane, and the thermal stability decreased simultaneously. The content of MCC in casting solution has great influence on the mechanical properties of membranes. The higher the content of MCC, the better the comprehensive mechanical properties of the membranes is. When MCC content is 9%, the tensile strength and elongation at break can reach 8.38 MPa and 26.72%, which is better than traditional cellulose membranes. Finally, the separation properties were studied by separation BSA from water. The results showed that the rejection rate and water flux changed positively and negatively with the change of MCC content. When the content was 5%, the membrane demonstrated the best comprehensive performance, its rejection for BSA was 37.23 g/(m2 h), the corresponding rejection rate and water flux were 88.87% and 41.89 L/(m2 h) respectively.

Preparation of microcrystalline cellulose from Rabdosia rubescens and study on its membrane properties

Microcrystalline cellulose (MCC) from Rabdosia rubescens was prepared by acid hydrolysis, and the corresponding yield of MCC was about 94% when the hydrochloric acid concentration was 10%, the acid hydrolysis time was 70min and the acid hydrolysis temperature was 70℃. The MCC was dissolved in N-methylmorpholine-N-oxide(NMMO)by phase transformation method to prepare MCC membrane. The structure and mechanical properties of MCC membrane were studied systemically. The results showed that the cellulose structure changed from type I to type II in the process of membrane formation, and the thermal stability also decreased. The content of MCC in the casting solution has a great influence on the mechanical properties of the membranes. The higher the content of MCC, the better the comprehensive mechanical properties of the membranes. When the MCC content is 9%, the tensile strength is 8.38 MPa and the elongation at break is 26.72%. Finally, the separation properties of membrane studed by separation bovine serum albumin (BSA) from water. The results showed that the rejection rate and water flux changed positively and negatively with the change of MCC content. When the content was 5%, MCC membrane showed the best comprehensive performance, its rejection of BSA was 37.23 g/(m2·h), and the corresponding rejection rate and water flux were 88.87% and 41.89 L/(m2·h) respectively.

Quorum Sensing Inhibitory Activities of Oridonin in Pseudomonas Aeruginosa

Pseudomonas aeruginosa is an opportunistic pathogen, and it can produce cell-associated and extracellular virulence factors. Several of these virulence factors have been demonstrated to be regulated by quorum sensing (QS). Disabling QS system with anti-infective agent is considered as a potential strategy to prevent bacterial infection. Rabdosia rubescens has been used as antibacterial agents for many centuries in China. In this study, Oridonin, the major active components of Rabdosia rubescens, was tested for QS inhibition in Pseudomonas aeruginosa. QS inhibitory activity is demonstrated by reduction in pyocyanin (58.4%), rhamnolipids (64.3%), elastase (58.6%), and protease (49.1%) in Pseudomonas aeruginosa PAO1 at 125 µg/ml (MIC) concentration. Biofilm formation by Pseudomonas aeruginosa PAO1 was reduced considerably (40.3-57.7%) over control. These findings suggest that Oridonin might be a potent Quorum Sensing Inhibitor (QSI) and anti-biofilm agent in the treatment of Pseudomonas aeruginosa infections.