Phytotherapy Research最新文献

Depression, which affects millions of individuals worldwide, is associated with glucocorticoid (GC) impairment, with the FKBP51 protein playing a pivotal role. Ginsenosides, extracted from the root of Panax ginseng C.A. Mey, have demonstrated the potential to mitigate depression associated with GC dysregulation. This study evaluated the therapeutic efficacy of ethanol extract of P. ginseng (PG) in treating depression and its underlying FKBP51-linked mechanism. Using chronic unpredictable stress, a depression model was developed in Kunming mice to test the efficacy of PG by observing changes in behaviors and protein expression in depressed mice. The mechanism of action was investigated through transfection with HEK293T cells. Depressed mice treated with PG demonstrated notable improvements: the rate of weight loss was reduced, sucrose preference and open-field activity were enhanced, and the rate of apoptosis in hippocampal cells was decreased. Additionally, the HPA axis function appeared to be restored. These physiological adjustments coincided with an increase in GR levels and a decrease in FKBP51 levels. Altogether, these results suggested that PG treatment effectively alleviates depressive symptoms in mice. PG also moderated FKBP51-GR interaction, lessening FKBP51's restraint on GR nuclear entry. This modulation may enhance the sensitivity of the GR response, reinforcing the negative feedback regulation of the HPA axis and thereby reducing depressive symptoms in mice. These findings highlight the potential of PG as a promising curative treatment for depression, providing a basis for the development of innovative treatments targeting the FKBP51-GR pathway.

Obesity is a kind of chronic disease due to a long-term imbalance between energy intake and expenditure. In recent years, the number of obese people around the world has soared, and obesity problem should not be underestimated. Obesity is characterized by changes in the adipose microenvironment, mainly manifested as hypertrophy, chronic inflammatory status, hypoxia, and fibrosis, thus contributing to the pathological changes of other tissues. A plethora of phytochemicals have been found to improve adipose microenvironment, thus prevent and resist obesity, providing a new research direction for the treatment of obesity and related diseases. This paper discusses remodeling of the adipose tissue microenvironment as a therapeutic avenue and reviews the progress of phytochemicals in fighting obesity by improving the adipose microenvironment.

Cancer cells consume considerable glucose quantities and majorly employ glycolysis for ATP generation. This metabolic signature (the Warburg effect) allows cancer cells to channel glucose to biosynthesis to support and maintain their dramatic growth along with proliferation. Currently, our understanding of the metabolic and mechanistic implications of the Warburg effect along with its relationship with biosynthesis remains unclear. Herein, we illustrate that the tumor repressor p53 mediate Magnolol (MAG) triggers colon cancer cell apoptosis. And MAG regulates the glycolytic and oxidative phosphorylation steps through transcriptional modulation of its downstream genes TP53-induced glycolysis modulator and biosynthesis of cytochrome c oxidase, attenuating cell proliferation and tumor growth in vivo and in vitro. Meanwhile, we show that MAG cooperates with its own intestinal microflora characteristic metabolites to repress tumors, especially remarkably declined kynurenine (Kyn)/tryptophan (Trp) ratio. Besides, strong relationships of MAG influenced genes, microbiota, as well as metabolites, were explored. Therefore, we established that p53-microbiota-metabolites function as a mechanism, which enable therapy approaches against metabolism-implicated colorectal cancer, in particular MAG as a prospective candidate for treating colorectal cancer.

Drug-induced nephrotoxicity is a leading cause of acute kidney injury (AKI). A major obstacle in predicting AKI is the lack of a comprehensive experimental model that mimics stable and physiologically relevant kidney functions and accurately reflects the changes a drug induces. Organoids derived from human-induced pluripotent stem cells (iPSCs) are promising models because of their reproducibility and similarity to the in vivo conditions. In this study, Esculentoside A, the triterpene saponin with the highest concentration isolated from the root of Phytolacca acinose Roxb., was used to induce kidney injury models in vivo and kidney organoids. Esculentoside A induced AKI in mice, together with pathological changes and enhanced apoptosis. Moreover, Esculentoside A damaged podocytes and proximal tubular endothelial cells in kidney organoids in a similar way as in vivo. We also found that treatment with 60 μM Esculentoside A induced the known biomarkers of kidney damage and inflammatory cytokines (such as kidney injury molecule (KIM-1), β2-microglobulin (β2-M), and cystatin C (CysC)) in the organoids, in which activation of Cleaved Caspase-3 was involved, possibly due to lowered mitochondrial membrane potential. In summary, this study strongly suggests using kidney organoids as a reliable platform to assess Chinese medicine-induced nephrotoxicity.

Most human papillomavirus (HPV) types, including HPV16 and HPV18, are closely related to the occurrence of cervical cancer, predominantly through the action of viral oncoproteins E6 and E7. Curcumin, the active ingredient of the turmeric plant, has been gaining attention over the past two decades as an antioxidant, anti-inflammatory, and anticancer agent. In the present study, the HPV-positive cervical cancer cells HeLa and CaSki were treated with curcumin, and the results showed that curcumin has a dose-dependent and time-dependent inhibitory effect on cell viability. In addition, apoptosis induction was further quantitatively confirmed through flow cytometric analysis. Furthermore, the influence of different concentrations of curcumin on the mitochondrial membrane potential was evaluated through JC-1 staining and found to dramatically decrease the membrane potential in treated HeLa and CaSki cells, suggesting the critical role of the mitochondrial pathway in their apoptosis-inducing effect. This study also demonstrated the wound-healing potential of curcumin, and the results of transwell assays showed that curcumin treatment inhibited HeLa and CaSki cell invasion and migration in a dose-dependent manner compared with the control treatment. Curcumin also downregulated the expression of Bcl-2, N-cadherin, and Vimentin and upregulated the expression of Bax, C-caspase-3, and E-cadherin in both cell lines. Further research showed that curcumin also selectively inhibited the expression of the viral oncoproteins E6 and E7, as demonstrated by western blot analysis; moreover, the downregulation of E6 was more significant than that of E7. Our research also showed that coculture with cells infected with siE6 lentivirus (siE6 cells) can inhibit the proliferation, invasion, and metastasis of HPV-positive cells. While the siE6 cells were also treated with curcumin, the effect of curcumin monotherapy was offset. In summary, our research shows that curcumin regulates the apoptosis, migration, and invasion of cervical cancer cells, and the mechanism may be related to its ability to downregulate E6. This study provides a foundation for future research on the prevention and treatment of cervical cancer.

Euphorbia pekinensis (EP) is a commonly used Chinese medicine treating edema with potential hepatorenal toxicity. However, its toxic mechanism and prevention are remained to be explored. Oleanolic acid (OA) is a triterpene acid with potential hepatorenal protective activities. We investigated the protective effect and potential mechanism of OA on EP-induced hepatorenal toxicity. In this study, rats were given total diterpenes from EP (TDEP, 16 mg/kg) combined with OA (10, 20, 40 mg/kg) by gavage for 4 weeks. The results showed that TDEP administration could lead to a 3-4-fold increasement in hepatorenal biochemical parameters with histopathological injuries, while OA treatment could ameliorate them in a dose-dependent manner. At microbial and metabolic levels, intestinal flora and host metabolism were perturbed after TDEP administration. The disturbance of bile acid metabolism was the most significant metabolic pathway, with secondary bile acids increasing while conjugated bile acids decreased. OA treatment can improve the disorder of intestinal flora and metabolic bile acid spectrum. Further correlation analysis screened out that Escherichia-Shigella, Phascolarctobacterium, Acetatifactor, and Akkermansia were closely related to the bile acid metabolic disorder. In conclusion, oleanolic acid could prevent hepatorenal toxicity induced by EP by regulating bile acids metabolic disorder via intestinal flora improvement.

Osteoarthritis (OA), a joint disease associated with inflammatory processes, contributes to joint destruction. Esculin (ESC) extracted from the stem bark of Fraxinus rhynchophylla Hance has been shown to possess anti-inflammatory properties. In this study, we investigated the effect of ESC on chondrocytes treated with IL-1β and its molecular mechanism. The importance and potential mechanism of ESC in the progression of OA were evaluated. The viability of chondrocytes after exposure to ESC was examined through the CCK-8 assays. The cells were then subjected to quantitative polymerase chain reaction (qPCR), western blot, and enzyme-linked immunosorbent assay (ELISA) techniques to analyze the degradation of the extracellular matrix (ECM) and occurrence of inflammation. The NF-κB mechanism was evaluated by western blot analysis, immunofluorescence (IF), and luciferase reporter assay. Molecular docking was performed to allow for predictions on proteins that interact with ESC. Moreover, the significance of Sirt1 was explored through a knockdown experiment based on siRNA. Micro-computed tomography (CT), H&E, Safranin O-Fast Green (S-O), and immunohistochemical analyses were carried out to assess the treatment efficacy of ESC on OA in destabilization of medial meniscus (DMM) models. ESC treatment effectively inhibited ECM degradation, modulated the levels of pro-inflammatory factors, and regulated the NF-κB signaling in chondrocytes exposed to IL-1β. Mechanistically, we found that ESCs bound to Sirt1 to inhibit the activity of the NF-κB mechanism. Furthermore, ESC treatment suppressed OA progression in the DMM models. Our findings reveal that ESC ameliorates OA progression via modulating the Sirt1/NF-κB axis. This demonstrates that ESC has the potential to be applied in the treatment of OA.

Few studies have investigated the association between herbal medicine consumption and coronary artery disease severity. This cross-sectional study aimed to investigate the association between the frequency of medicinal herbs consumption and coronary artery stenosis (CAS), lipid profile, fasting blood sugar (FBS), and blood pressure level in participants undergoing coronary angiography. This study was conducted on 662 participants aged 35-75 years. Serum cardiometabolic markers were measured using standard kits. The extent and severity of CAS were evaluated using the Gensini score (GS) and syntax score (SS). Higher consumption of Thymus vulgaris and Sumac was associated with decreased odds of artery-clogging according to the GS. A higher intake of Thymus vulgaris and Mentha was associated with lower levels of serum cholesterol and triglyceride. Monthly intake of Thymus vulgaris, and weekly/daily intake of Mentha, Nigella Sativa, and Cuminum Cyminum were associated with lower low-density lipoprotein. Weekly/daily intake of Turmeric and Thymus vulgaris were associated with lower high-density lipoprotein levels and monthly intake of Mentha was related to lower serum FBS levels. Higher consumption of Mentha, Mentha pulegium L, Lavandula angustifolia, and Nigella Sativa was associated with lower levels of systolic blood pressure. According to the results of the present study, herbs consumption might be related to a reduction in CAS risk factors.

evidence from animal experiments indicates that anthocyanin supplements can contribute to intestinal health. Nevertheless, no evidence has linked dietary anthocyanins to the prevention potential against inflammatory bowel disease (IBD) in humans. We leveraged data from 188,044 IBD-free individuals (mean age 59 years; 55.2% females) from the prospective cohort UK Biobank. The anthocyanin intake was estimated using dietary information from validated 24 h dietary recalls. Incident IBD was ascertained via national health-related records. Genetic susceptibility to Crohn's disease (CD) and ulcerative colitis (UC) was estimated by polygenic risk scores and further categorized into low- and high-risk groups by median value. The Cox proportional regression model was applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During the mean follow-up of 9.7 years, we documented 255 CD and 606 UC. We found that compared with participants with the lowest quartiles of anthocyanin intake, those in the highest quartiles were associated with 24% (95% CI 6%-38%, p = 0.012; p-trend = 0.003) and 35% (95% CI 16%-49%, p = 0.001; p-trend < 0.001) reduced risk of IBD and UC, respectively. The inverse associations were stronger (p-interaction = 0.022) among individuals with a high genetic risk of UC. We did not observe a significant association between anthocyanin intake and CD (p-trend = 0.536). Higher dietary anthocyanin intake was associated with reduced risk of IBD and UC, but not CD. Genetic factors may modify the influence of dietary anthocyanin on UC susceptibility, and possible mechanisms need to be further elucidated in the future.

Dyslipidemia is a risk factor for cardiovascular diseases. Preclinical studies have shown that organosulfur compounds from the Alliaceae and Brassicaceae plants, such as garlic (Allium sativum L.) and broccoli (Brassica oleracea L.), have potential lipid-lowering effects. However, their clinical efficacy is controversial, especially in "drug-free" patients. The aim of this work was to summarize evidence on the lipid-lowering properties of extracts containing organosulfur compounds in patients with dyslipidemia. Studies were searched in four databases (Medline, Scopus, Embase, and CENTRAL), from inception to October 11, 2023.Controlled clinical studies on patients with dyslipidemia receiving Alliaceae or Brassicaceae were included. The outcome was the change in lipid parameters from baseline. Random-effect meta-analysis of the extracted data was performed using R software. The effect size was expressed as mean difference (MD) and 95% confidence interval (CI). The certainty of evidence was assessed with the GRADE approach. Out of 28 studies that were reviewed, 22 were included in the meta-analysis (publication period: 1981-2022). Results showed that Alliaceae extracts significantly reduce total cholesterol [MD: -15.2 mg/dL; 95% CI: -21.3; -9.1] and low-density lipoprotein cholesterol levels [MD: -12.0 mg/dL; 95% CI: -18.1; -5.7], although with low certainty of evidence. Conversely, the lipid-lowering properties of Brassicaceae extracts are still unexplored. Our results support the use of Alliaceae extracts in patients with hypercholesterolemia, but future high-quality studies are needed. Our work suggests further exploration of the efficacy of Brassicaceae extracts, which may have high nutraceutical/phytotherapeutic potential, opening new perspectives in the management of dyslipidemia.