Journal of ethnopharmacology最新文献

Ethnopharmacological relevance: Aesculus wilsonii Rehd.'s dried mature seeds are the source of escin, a significant triterpenoid saponin. Aesculus wilsonii Rehd was first mentioned in the Compendium of Materia Medica, according to the Chinese Pharmacopoeia. It possesses the effectiveness of anti-inflammatory as well as treating gastrointestinal disorders. Escin Ia is the primary active component of escin, exhibiting significant antioxidant and anti-inflammatory properties. An increasing number of studies have demonstrated that escin exhibits a broad spectrum of pharmacological activities beneficial for the protection against gastrointestinal diseases.

Aim of the study: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) that can be managed through pharmacological treatment; however, it features a high recurrence rate as well as propensity for complications. Therefore, reducing the rate of recurrence and improving the recurrence symptoms should be the primary focus of clinical prevention and treatment. Therefore, this research aims to study the effects of escin Ia on inflammation as well as oxidative stress in mice with chronic UC and to explain the molecular mechanisms underlying its potential to improve recurrent symptoms in UC mice.

Materials and methods: A mouse model of colitis produced via dextran sodium sulfate (DSS) was developed for in vivo studies. A model of inflammation was created in vitro using caco-2 cells that were generated by lipopolysaccharide (LPS). Through the observation of colitis symptoms and histological morphology in mice, the protective effect of escin Ia against colitis was ascertained. The enzyme-linked immunosorbent assay (ELISA) and biochemical kits were then harnessed to measure the levels of oxidative stress markers as well as inflammatory factors. Additionally, to identify the possible target and molecular mechanism of escin Ia, qRT-PCR and western blotting, immunofluorescence, molecular docking, and molecular dynamics modeling were employed.

Results: We demonstrated that escin Ia remarkably improved the colitis symptoms as well as histological features of DSS-treated mice, lowered the levels of proinflammatory cytokines as well as oxidative stress biomarkers, and subsequently restored the permeability of the intestinal mucosa. Additionally, high expression of LOXL2 significantly reduced the protective effects of escin Ia in both inflamed mice and Caco-2 cells. Furthermore, escin Ia exhibited a strong binding affinity and notable stability with LOXL2.

Conclusion: Escin Ia inhibits inflammation and oxidative stress through the LOXL2/MMP-9 pathway, thereby restoring intestinal mucosal barrier function. Improved recurrent symptoms in mice with enteritis.

Ethnopharmacological relevance: Prunella vulgaris L. (PV) is a widely distributed medicinal and edible plant used in traditional Chinese medicine for its anti-tumor, anti-inflammatory, anti-oxidant, hypoglycemic, and anti-hypertensive effects. Despite the numerous studies reporting on its cardiovascular protective effects, it is still not known whether PV could relieve myocardial ischemia-reperfusion (MI/R) injury.

Aim of the study: To investigate the effects of PV on MI/R injury and explore the underlying mechanism of action.

Materials and methods: Sprague-Dawley rats were orally administrated with the aqueous extract of P. vulgaris for 7 days before MI/R injury was induced. Echocardiography, infarct staining, and TUNEL assay were used to evaluate the protective effect of P. vulgaris. H₂O₂- and RSL3-stimulated H9C2 rat myocardial cells were used to explore the underlying mechanism. Ultra-high-performance liquid chromatography/mass spectrometer analysis was used to identify the chemical constituents of P. vulgaris. AutoDock was used to predict the binding affinity and the interactions between the main active compounds and Keap1. Nuclear factor erythroid 2-related factor 2 (Nrf2) knock-out mice were used to confirm whether the protective effect of P. vulgaris was mediated by Nrf2.

Results: P. vulgaris improved left ventricular systolic function and decreased the myocardial infarction area, which in turn helps alleviate MI/R injury. PV also increased the level of Nrf2 proteins and promoted the expression of HO-1, SOD, and GSH, thus upregulating the activity of the antioxidant system. The molecular docking simulations indicated that rosmarinic acid, salviaflaside, ursolic acid, and protocatechuic acid from P. vulgaris could strongly bind to Keap1 protein with good binding affinities. Additionally, ursolic acid was found to elevate NRF2 protein levels as well as promote NRF2 nuclear translocation. Moreover, the cardiac protective effect of PV or ursolic acid disappeared in NRF2-/- mice, indicating that this protective effect was mediated by NRF2. Besides, PV also increased the protein levels of GPX4 in MI/R rat or mice models, and this upregulation disappeared in NRF2-/- mice. Results from the RSL-3-induced ferroptosis H9C2 cell model showed that ursolic acid was the main active component of PV that protects cardiomyocytes against ferroptosis.

Conclusions: Collectively, the findings indicate that PV could alleviate MI/R injury by inhibiting oxidative stress and ferroptosis via the NRF2/GPX4 pathway, and ursolic acid is the main active component responsible for mediating both antioxidative and anti-ferroptosis effects, suggesting its potential use as a therapeutic agent against MI/R injury.

Ethnopharmacological relevance: Dendrobine, a bioactive compound isolated from the traditional Chinese medicinal herb, Dendrobium nobile Lindl, is recognized for its anti-inflammatory and antioxidant properties. However, its role and precise mechanisms in sepsis-associated acute lung injury (ALI) remain unexplored.

Aim of the study: To elucidate the anti-inflammatory and antioxidant effects of dendrobine in sepsis-associated ALI and explore its underlying mechanisms in a sepsis mouse model.

Materials and methods: A mouse model and THP-1 cells were established to assess protective effects of dendrobine against lipopolysaccharide (LPS)-triggered pathological damage to mouse lung tissue and inflammatory cytokine secretion. Network pharmacology, molecular docking, and Cellular Thermal Shift Assay experiments were employed to identify potential targets and signaling pathways associated with dendrobine. Furthermore, the application of LY294002, a selective inhibitor of PI3K, has allowed for a more precise elucidation of the molecular mechanisms underlying the protective effects of dendrobine.

Results: Dendrobine alleviated LPS-induced lung injury and inflammatory responses in a dose-dependent manner. We identified key targets of dendrobine and related pathways. Specifically, dendrobine activated the PI3K/AKT/GSK3β signaling cascade, which inhibited the production of inflammatory factors such as TNF-α and IL-6, and reduced reactive oxygen species (ROS) levels. This mechanism protected cells from LPS-induced damage. Furthermore, treatment with the PI3K inhibitor LY294002 counteracted the protective effects of dendrobine, thereby confirming the critical role of the PI3K/AKT/GSK3β axis in mediating its anti-inflammatory and cytoprotective functions.

Conclusions: This study, for the first time, demonstrates that dendrobine alleviates LPS-induced tissue damage in sepsis via the PI3K/AKT/GSK3β pathway. These findings highlight the potential of dendrobine as a therapeutic agent against sepsis-induced ALI.

Ethnopharmacological relevance: Quality control is a powerful method for ensuring the effectiveness and safety of herbal medicines. Phyllanthus emblica L. fruit (PE) has been extensively used in both Ayurvedic and traditional Chinese medicine. However, the current Indian and Chinese pharmacopeias set a minimum concentration threshold of gallic acid to identify qualified PE samples, without providing a clear framework to distinguish superior-quality PE samples.

Aim of the study: To establish an efficacy-oriented quality grading framework for herbal medicines, using PE, a medicinal plant known for its hepatoprotective activity, as an example.

Methods: First, a mouse model of alcohol-induced liver injury was developed to evaluate the hepatoprotective effects of PE. Second, a combined strategy of serum pharmacochemistry, network pharmacology, metabolomics and experimental validation was employed to identify key quality markers (Q-markers) linked to the hepatoprotective effects of PE. Finally, PE samples from different sources were collected to assess their hepatoprotective activities and Q-marker concentrations. A discriminant analysis model was then developed to classify PE samples into different quality grades by using Q-marker concentration as the predictive factor and hepatoprotective activity as the evaluation criterion.

Results: PE significantly alleviated liver damage, as evidenced by a reduction in pathological abnormalities and serum aminotransferase levels. Six hepatoprotective Q-markers in PE were identified and verified, including gallic acid, methyl gallate, corilagin, chebulagic acid, ellagic acid and quercitrin. Significant variability in Q-marker concentrations and hepatoprotective effects was observed among different sources of PF samples, and a discriminant analysis model accurately classified PE samples into distinct quality grades.

Conclusions: This study successfully established an efficacy-oriented quality grading framework for PE, providing a methodological approach for the quality classification of herbal medicines.

Ethnopharmacological relevance: Zuojin Pill (ZJP) is a traditional Chinese medicine (TCM) formula composed of Coptidis Rhizoma and Euodiae Fructus in a ratio of 6:1 (w/w), which has been widely used for treating gastrointestinal disorders, especially stomach heat syndrome (SHS). However, the active alkaloids in ZJP showed low plasma exposure in rats following oral administration, which failed to explain their potent pharmacological effects, thereby limiting further mechanism studies.

Aim of the study: This study aimed to investigate the in vivo exposure and tissue distribution propensities of the active alkaloids in normal and SHS rats following oral administration of ZJP.

Material and methods: A rat model of SHS was induced by oral administration of chili pepper decoction and anhydrous ethanol. Then, the plasma and tissue pharmacokinetics of active alkaloids, including four protoberberine alkaloids (PBAs) and three indole alkaloids (IDAs), were investigated following oral administration of ZJP. Furthermore, desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was employed to characterize the spatial distribution of active alkaloids in the stomach and liver. Western blot and immunofluorescence were employed to evaluate the gastric mucosal barrier integrity.

Results: Based on the tissue-to-plasma partition coefficient (Kp) values, the in vivo exposure levels of berberine (BBR), palmatine (PAL), coptisine (COP), and dehydroevodiamine (DHE) were found to be higher in tissues than in plasma, indicating a distinct tissue distribution propensity. Each alkaloid displayed the highest exposure in the gastrointestinal tissues, due to local penetration facilitated by its direct contact with the mucosal lining. Pathological states reduced the overall exposure of PBAs in the gastric mucosa. In non-gastrointestinal tissues, most alkaloids, especially BBR and COP, exhibited a potent liver distribution propensity with minimal impact from pathological states. According to DESI-MSI results, PBAs showed high exposure in the damaged regions of gastric mucosa, which was attributed to mucosal barrier damage and enhanced permeability. In the liver, PBAs were primarily localized in the parenchyma surrounding the central vein and portal area.

Conclusion: This study demonstrated the stomach and liver distribution propensity of the active alkaloids in ZJP, providing a scientific basis for these alkaloids as the pharmacodynamic material basis of ZJP against SHS from the perspective of drug exposure.