Total cucurbitacins from Herpetospermum pedunculosum pericarp do better than Hu-lu-su-pian (HLSP) in its safety and hepatoprotective efficacy.

The pericarp of Herpetospermum pedunculosum (HPP) has traditionally been used for treating jaundice and hepatitis. However, the specific hepatoprotective components and their safety/efficacy profiles remain unclear. This study aimed to characterize the total cucurbitacins (TCs) extracted from HPP and evaluate their hepatoprotective potential. As a reference, Hu-lu-su-pian (HLSP), a known hepatoprotective drug containing cucurbitacins, was used for comparison of chemical composition, effects, and safety. Molecular networking based on UHPLC-MS/MS identified cucurbitacin B, isocucurbitacin B, and cucurbitacin E as the major components in TCs, comprising 70.3%, 26.1%, and 3.6% as determined by RP-HPLC, respectively. TCs treatment significantly reversed CCl4-induced metabolic changes associated with liver damage in a dose-dependent manner, impacting pathways including energy metabolism, oxidative stress and phenylalanine metabolism, and showed superior efficacy to HLSP. Safety evaluation also showed that TCs were safe, with higher LD50 and no observable adverse effect level (NOAEL) values than HLSP. The median lethal dose (LD50) and NOAEL values of TCs were 36.21 and 15 mg/kg body weight (BW), respectively, while the LD50 of HLSP was 14 mg/kg BW. In summary, TCs extracted from HPP demonstrated promising potential as a natural hepatoprotective agent, warranting further investigation into synergistic effects of individual cucurbitacin components.

Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph-Mass Spectrometry Based Metabolomic Approach.

Radix Polygoni Multiflori (PM) is a well-known nootropic used in traditional Chinese medicine (TCM). Considering the efficacy and application discrepancy between raw (RPM) and processed PM (PPM), the similarities and differences between them in the treatment of vascular dementia (VaD) is intriguing. In this study, a VaD rat model was constructed by 2-vessel occlusion (2-VO). During 28 days of treatment, plasma was collected on days 7, 14, 21, and 28 after the start of dosing and the metabolic profile was analyzed by HPLC-MS/MS-based metabolomics. The Morris Water Maze Test, hematoxylin-eosin and Nissl staining, and biochemical analysis were used to assess cognitive function, pathogenic alterations and oxidative stress, respectively. RPM and PPM effectivelyreducedthe 2VO-induced cognitive impairment and mitigated histological alterations in hippocampus tissue. The 2-VO model significantly elevated MDA level and decreased SOD activity and GSH level, indicating severe oxidative stress, which could also be attenuated by RPM and PPM treatment. RPM outperformed PPM in decreasing MDA levels while PPM outperformed RPM in increasing GSH levels. Differential metabolites were subjected to Metabolite Set Enrichment Analysis (MSEA) and genes corresponding to proteins having interactions with metabolites were further annotated with Gene Ontology (GO). Both RPM and PPM ameliorated VaD-relevant vitamin B6 metabolism, pentose phosphate pathways, and taurine and hypotaurine metabolism. In addition, the metabolism of cysteine and methionine was regulated only by RPM, and riboflavin metabolism was modulated only by PPM. The results suggested that raw and processed PM had comparable efficacy in the treatment of VaD but also with some mechanistic differenece.

A novel open-source raspberry Pi-based behavioral testing in zebrafish.

The zebrafish (Danio rerio) is widely used as a promising high-throughput model organism in neurobehavioral research. The mobility of zebrafish can be dissected into multiple behavior endpoints to assess its neurobehavioral performance. However, such facilities on the market are expensive and clumsy to be used in laboratories. Here, we designed a low-cost, automatic zebrafish behavior assay apparatus, barely without unintentional human operational errors. The data acquisition part, composed of Raspberry Pi and HQ Camera, automatically performs video recording and data storage. Then, the data processing process is also on the Raspberry Pi. Water droplets and inner wall reflection of multi-well cell culture plates (used for placing zebrafish) will affect the accuracy of object recognition. And during the rapid movement of zebrafish, the probability of zebrafish tracking loss increased significantly. Thus, ROI region and related thresholds were set, and the Kalman filter algorithm was performed to estimate the best position of zebrafish in each frame. In addition, all functions of this device are realized by the custom-written behavior analysis algorithm, which makes the optimization of the setup more efficient. Furthermore, this setup was also used to analyze the behavioral changes of zebrafish under different concentrations of alcohol exposure to verify the reliability and accuracy. The alcohol exposure induced an inverted U-shape dose-dependent behavior change in zebrafish, which was consistent with previous studies, showcasing that the data obtained from the setup proposed in this study are accurate and reliable. Finally, the setup was comprehensively assessed by evaluating the accuracy of zebrafish detection (precision, recall, F-score), and predicting alcohol concentration by XGBoost. In conclusion, this study provides a simple, and low-cost package for the determination of multiple behavioral parameters of zebrafish with high accuracy, which could be easily adapted for various other fields.

Development of galangal essential oil-based microemulsion gel for transdermal delivery of flurbiprofen: simultaneous permeability evaluation of flurbiprofen and 1,8-cineole.

Flurbiprofen (FP) is one of the most potent nonsteroidal anti-inflammatory drugs with very low bioavailability of approximately 12% following transdermal administration, compared to that after oral administration. This study aimed to deliver FP as a microemulsion (ME) gel by transdermal administration. Galangal essential oil (GEO) was extracted from Rhizoma Alpiniae Officinarum and identified by GC-MS. The most abundant constituent was determined to be 1,8-cineole (52.06%). Compared to azone, GEO was proved to exert significantly higher (p < .01) penetration enhancement effect and significantly (p < .001) lower skin cell toxicity. The formulation (FP-GEO-ME gel) was prepared using GEO as an oil phase and a penetration enhancer. Compared to that of FP solution, the enhancement ratio (ER) of FP-GEO-ME gel was 4.06. In addition, more than 25% 1,8-cineole permeated through the rat skin. In vivo pharmacokinetic studies revealed that the AUC0-t of FP after transdermal administration of FP-GEO-ME gel was higher by approximately 4.56-fold than that of marketed FP cataplasms. The relative bioavailability of FP and 1,8-cineole after transdermal administration compared to oral administration of FP-GEO-ME were determined to be 96.58% and 85.49%, respectively. FP-GEO-ME gel significantly inhibited carrageenan-induced hind-paw edema and decreased PGE2 levels in rat serum. GEO-ME gel also exhibited significant anti-inflammatory effects at 2 h after the therapy (p < .05). The synergistic effects of FP and GEO were expected for the application of FP-GEO-ME gel. In conclusion, GEO-ME gel may be a promising formulation for transdermal administration of anti-inflammatory hydrophobic drugs, such as FP.