bims-supasi 2023-12-31 papers

Food Chem. 2023 Dec 23. pii: S0308-8146(23)02891-1. [Epub ahead of print]440 138273

Quantitative determination of chondroitin sulfate with various molecular weights in raw materials by pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate.

Zhiqing Tian, Fan Jiang, Shuifang Zhu.

A simple and reliable HPLC method was developed for quantification of chondroitin sulfate (CS). The procedure is based on precolumn hydrolysis of CS to liberate galactosamine and subsequent derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Hydrolysis and derivatization conditions were optimized. A linear correlation coefficient of 0.9999 was calculated within the range of 10-1500 μg/mL from the standard curve. The method produces good precision and good accuracy (100.75 % recovery). An advantage over other common methods is its ability to quantify CS of all molecular weights and structures, as evidenced by the determination of CS fractions with narrow molecular weight distributions obtained through depolymerization by different methods, while enzymatic HPLC was proven to be infeasible. Extraction recoveries of CS from monosaccharide mixed samples were > 93 %. The reliability was also validated by a small difference (-1.95 % to 4.12 %) relative to enzymatic HPLC results in analysing representative CS samples of different animal origins and suppliers.

Keywords: 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC); Chondroitin sulfate; Galactosamine; Glycosaminoglycan; Hexosamine derivatization; Low molecular weight

DOI: https://doi.org/10.1016/j.foodchem.2023.138273

Brain. 2023 Dec 26. pii: awad430. [Epub ahead of print]

Increased expression of chondroitin sulfate proteoglycans in dentate gyrus and amygdala causes postinfectious seizures.

Dipan C Patel, Nathaniel Swift, Bhanu P Tewari, Jack L Browning, Courtney Prim, Lata Chaunsali, Ian F Kimbrough, Michelle L Olsen, Harald Sontheimer.

Alterations in the extracellular matrix (ECM) are common in patients with epilepsy and in animal models of epilepsy, yet whether they are cause or consequence of seizures and epilepsy development is unknown. Using Theiler's murine encephalomyelitis virus (TMEV) infection-induced model of acquired epilepsy, we find de novo expression of chondroitin sulfate proteoglycans (CSPGs), a major ECM component, in dentate gyrus (DG) and amygdala exclusively in mice with acute seizures. Preventing synthesis of CSPGs specifically in DG and amygdala by deletion of the major CSPG aggrecan reduced seizure burden. Patch-clamp recordings from dentate granule cells (DGCs) revealed enhanced intrinsic and synaptic excitability in seizing mice that was significantly ameliorated by aggrecan deletion. In situ experiments suggest that DGCs hyperexcitability results from negatively charged CSPGs increasing stationary cations on the membrane thereby depolarizing neurons, increasing their intrinsic and synaptic excitability. These results show increased expression of CSPGs in the DG and amygdala as one of the causal factors for TMEV-induced acute seizures. We also show identical changes in CSPGs in pilocarpine-induced epilepsy suggesting that enhanced CSPGs in the DG and amygdala may be a common ictogenic factor and potential therapeutic target.

Keywords: hippocampus; matrix metalloproteinases; minocycline; potassium; resting membrane potential

DOI: https://doi.org/10.1093/brain/awad430

Eur J Pharm Sci. 2023 Dec 26. pii: S0928-0987(23)00313-5. [Epub ahead of print] 106685

Construction of chrysophanol loaded nanoparticles with N-octyl-O-sulfate chitosan for enhanced nephroprotective effect.

Qingxue Wei, Fuping Gao, Leiping Gao, Hong Gao, Jian Zhang, Rui Bao, Hang Zhang, Jiapeng Wang, Qiusheng Shen, Mingjia Gu.

Natural occurring anthraquinone like chrysophanol has been studied because of its anti-diabetic, anti-tumor, anti-inflammatory, hepatoprotective and neuroprotective properties. Nonetheless, its poor water solubility and unstable nature are big concerns in achieving efficient delivery and associated pharmacokinetic and pharmacodynamic effects. Herein, this study sought to solve the above-mentioned problem through development of chrysophanol-loaded nanoparticles to enhance the bioavailability of chrysophanol and to evaluate its anti-renal fibrosis effect in rats. After synthesis of a safe N-octyl-O-sulfate chitosan, we used it to prepare chrysophanol-loaded nanoparticles through dialysis technique before we performed and physical characterization. Also, we tested the stability of the nanoparticles for 21 days at 4°C and room temperature (25°C) and evaluated their pharmacokinetics and anti-renal fibrosis effect in rat model of chronic kidney disease (CKD). In terms of results, the nano-preparation demonstrated an acceptable narrow size distribution, wherein the encapsulation rate, size, polydispersed index (PDI) and electrokinetic potential at room temperature were respectively 83.41±0.89%, 364.88±13.62 nm, 0.192±0.015 and 23.78±1.39 mV. During 21 days of storage, we observed that size of particles and electrokinetic potential altered slightly but the difference was statistically insignificant (p > 0.05). Also, in vitro release studies showed that the formulation reached 84.74% at 24 h. Chrysophanol nanoparticles showed a 2.57-fold increase in bioavailability compared to unformulated chrysophanol. More importantly, chrysophanol nanoparticles demonstrated certain renal internalization properties and anti-renal fibrosis effects, which could ultimately result in reduced blood-urea nitrogen (BUN), kidney-injury molecule-1 (KIM-1) and serum creatinine (SCr) levels in model rats. In conclusion, the prepared chrysophanol-loaded nanoparticles potentially increased bioavailability and enhanced nephroprotective effects of chrysophanol.

Keywords: Chrysophanol; N-Octyl-O-sulfate chitosan; bioavailability; chronic kidney disease; nanoparticles

DOI: https://doi.org/10.1016/j.ejps.2023.106685