Journal of ethnopharmacology最新文献

Ethnopharmacological relevance: Chronic kidney disease (CKD) poses an increasing challenge to the middle-aged and elderly population. Wenshenyang decoction (WSY), an herbal formula from China, has been shown to have a considerable effect on the recovery of the renal function in a real-world study. However, no randomized, double-blind, placebo-controlled, multicenter clinical trial to evaluate the efficacy and safety yet.

Aim of the study: This study aimed to investigate the efficacy, advantages, limitations, and safety, and provide insights into methods and strategies for utilizing WSY in CKD management.

Materials and methods: Participants were recruited from six tertiary hospitals in Beijing, China. Eligible participants were randomly assigned to receive either WSY and conventional Western medicine or placebo and conventional Western medicine in a 1:1 ratio. The treatment and follow-up cycles each lasted 90 days, with a total of six follow-up visits. The primary outcome measures were the change in 24-hour urine protein excretion (24h UPRO) and serum creatinine (SCR) from baseline at Visit 3 (90 days after the treatment) and Visit 5 (90 days after the follow-up). The secondary outcome measures were the improvement in symptoms and other renal function indicators. Additionally, we explored the correlation between the effect of WSY treatment and CKD type and stage through subgroup analysis. Finally, the safety of this decoction was assessed.

Results: In total, 257 participants were diagnosed with CKD characterized by kidney Yang deficiency. Of these patients, 240 underwent randomization, and 203 were included in the subsequent analysis. After 180 days of treatment and follow-up, there was a significant decrease in the primary outcome 24h UPRO (a 43.19% improvement at Visit 3, 95% CI: 27.68%, 58.71%; a 51.28% improvement at Visit 5, 95% CI: 31.40%, 71.16%), and SCR (a 16.34% improvement at Visit 3, 95% CI: 11.28%, 21.40%; a 20.52% improvement at Visit 5, 95% CI: 14.05%, 26.99%). Compared to the control group, the difference was statistically significant (p < 0.05). Additionally, the secondary outcome of symptom score showed that 79.21% of the patients felt "completely improved" and "greatly improved"; which was much higher than placebo (p < 0.05). Subgroup analysis showed that WSY was more effective for diabetic kidney disease (DKD) and stage 3 of CKD. No severe adverse events occurred during the period.

Conclusions: These results indicate that WSY could improve the renal function and alleviate the kidney Yang deficiency symptoms in patients with CKD without adverse effects. This study provided evidence-based medicine in the treatment of CKD with compound prescriptions of traditional Chinese medicine (TCM) and contributed to promoting the use of phytomedicine.

Ethnopharmacological relevance: Alzheimer's disease (AD) is a complex neurodegenerative disease affecting mental ability and neurocognitive functions. Crinum woodrowii Baker (C. woodrowii) is an endemic plant with significant ethnobotanical potential against neurological and inflammatory conditions with a characteristic improvement of cognitive functions.

Aim of the study: To assess the anti-AD potential of C. woodrowii extract through in-vitro assays and preclinical in-vivo screening and to validate its neuroprotective effect by biochemical and histopathological analysis.

Materials and methods: Herein, galantamine contents of the ethanolic extract of C. woodrowii were quantified using HPLC and LCMS. Further, the extract was examined for in-vitro cytotoxicity, anti-inflammatory, anti-cholinesterase activities, and in-vivo neuropharmacological studies.

Results: The extract exhibited low cytotoxicity on RAW 264.7 cells and the inhibition of LPS-induced nitric oxide production. The extract also showed anti-cholinesterase activities. The treatment with extract significantly rescued the rough eye phenotype in the Drosophila model of AD. In neuropharmacological screening, the extract showed no symptoms of acute oral toxicity in rats. The extract significantly reversed scopolamine-induced memory deficit in mice and improved their learning ability with memory retention in exteroceptive behavioral models. The pretreatment of mice with extract reinstated the elevated brain acetylcholinesterase, lipid peroxidation, and reduced glutathione levels due to scopolamine and aging. The extract also restored the altered superoxide dismutase and catalase levels. The extract alleviated neuronal tissue damage caused by the scopolamine, as indicated by the histological analyses of the brain.

Conclusion: Our findings suggested that the C. woodrowii extract has neuroprotective properties and ameliorates cognitive dysfunction and hence could be explored further as a potential neurotherapeutics for treating AD.

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.