Phytotherapy Research最新文献

Mitophagy is a process by which cells selectively eliminate damaged or dysfunctional mitochondria through the autophagy-lysosome pathway, thereby maintaining mitochondrial quality and cellular homeostasis. This process is closely linked to the onset and progression of various heart diseases. Modern pharmacological research has demonstrated that phytochemicals can regulate mitochondrial homeostasis in cardiomyocytes through multiple mechanisms, influencing mitophagy and protecting cardiomyocytes, which in turn exerts anti-cardiovascular effects. However, the underlying mechanisms of these effects are not yet fully understood. This study summarizes the pharmacological effects and molecular mechanisms of mitophagy in heart diseases, aiming to provide reference for the research and treatment of phytochemicals targeting mitophagy against heart diseases. The results indicated that phytochemicals (such as Berberine, Ginsenoside Rg1, Quercetin, Resveratrol, Baicalein, and so on) can exert preventive and therapeutic effects on heart diseases (such as cardiac toxicity or damage, myocardial ischemia/reperfusion injury, heart failure, heart aging, cardiac hypertrophy, cardiomyopathy, and so on.) via regulating the PINK1/Parkin and FUNDC1-dependent mitophagy pathway. These compounds mainly exert their effects by regulating mitochondrial homeostasis, mitochondrial dynamics, mitochondrial oxidative stress, mitochondrial apoptosis, and mitochondrial energy metabolism. This study provides a reference that phytochemicals have effect on anti-cardiovascular effects by regulating mitophagy. However, further in-depth mechanistic and clinical research are needed in the future.

Myocardial ischemia-reperfusion injury (MI/RI) is a critical challenge for acute myocardial infarction therapy, as there is currently no ideal drug available. Glycogen synthase kinase 3 beta (GSK-3β) serves as an promising therapeutic target for treating MI/RI. Our previous studies have demonstrated that Ilex pubescens ameliorates MI/RI. The purpose of this study is to evaluate the therapeutic efficacy and potential mechanism of the screened GSK-3β inhibitor from Ilex pubescens against MI/RI. Three-dimensional-quantitative structure-activity relationship (3D-QSAR) modeling, molecular docking, the oxygen and glucose deprivation/reperfusion (OGD/R) and left anterior descending (LAD) artery ligation-induced MI/RI mice model, and western blotting analysis were used to screen and investigate the myocardial protective efficacy and mechanism. Here, we screened Pubescenoside D (PBD) as a GSK-3β inhibitor with an IC50 value of 0.3769 μM from Ilex pubescens, using 3D-QSAR modeling, molecular docking, and kinase assay verification. Ile217, Leu88, Phe93, and Phe67 are the key binding sites for PBD and GSK-3β. PBD protects cardiomyocytes against MI/RI in vitro and in vivo. Further mechanism studies show that PBD inhibits mitochondrial permeability transition pore (mPTP) opening by preventing GSK-3β-mediated the dissociation of hexokinase2 (HK2) from the outer membrane of the mitochondria and enhances mitophagy by suppressing GSK-3β activity, subsequently reducing cardiomyocyte apoptosis. Our findings shed light on the efficacy of PBD as a promising therapeutic agent in the treatment of MI/RI targeting GSK-3β.

Background: Diabetic nephropathy (DN) stands as one of the most severe complications of diabetes. Podocytes injury, particularly its attachment to the lateral glomerular basement membrane, serves as a crucial indicator of DN. Growing evidence suggests that berberine (BBR) can mitigate the onset and progression of DN. However, the molecular mechanisms through which BBR exerts its beneficial effects in the treatment of DN remain incompletely elucidated.

Purpose: To explore the underlying mechanisms by which BBR exerts its therapeutic effects in DN.

Methods: High-throughput lncRNA sequencing on the renal cortex of both the DN model group and the normal SD group was performed to dig for differentially expressed lncRNAs. The expression of LOC102549726 was evaluated using qPCR. The biological functions of LOC102549726 were analyzed in podocyets and DN rats. The bioinformatics techniques, qPCR and WB were used to explore the potential molecular mechanisms.

Results: We found that lncRNA LOC102549726 was highly expressed in renal cortex of DN rats and podocytes subjected to high glucose conditions. Silencing LOC102549726 inhibited migration and apoptosis of podocytes. Mechanistically, LOC102549726 was identified as a facilitator of the expression of EGF and forkhead box O1 (FOXO1). BBR, a known therapeutic agent for DN, exhibited the ability to diminish the level of LOC102549726, EGF and FOXO1 in both DN rats and podocytes.

Conclusion: Our findings suggested that BBR suppresses migration and apoptosis of podocytes in DN through targeting the LOC102549726/EGF/FOXO1 axis. This sheds light on a potential therapeutic avenue for mitigating the impact of DN on podocyte function.

The high prevalence of metabolic syndrome (MetS) is threatening the health of people around the world. The fruit of Cornus mas L. (CM) is rich in bioactive compounds that have the potential to promote health and improve chronic diseases associated with MetS. This systematic review aimed to compile data on the effects of CM supplementation on anthropometric and metabolic characteristics in patients with MetS. Scopus, Web of Sciences, PubMed, Embase, and the Cochrane library were employed to identify the eligible randomized controlled trials (RCTs) that assessed the effects of CM on anthropometric parameters, glycemia, and lipid profiles up to December 2024. The included articles were subjected to assessment using the Cochrane risk-of-bias tool and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. A heterogeneity test was conducted on the included trials using the I² statistic. A random-effects model was applied based on the results of the heterogeneity tests, and the pooled data were presented as the mean difference with a 95% confidence interval (CI). A total of five RCTs were included in the analysis, with a total sample size of 313 human subjects. The results indicated that CM had a significant effect on lowering body mass index (BMI) (MD: -0.31; 95% CI: -0.46 to -0.16, p < 0.0001, I² = 15%), hip circumference (HC) (MD: -0.84; 95% CI: -1.31 to -0.37, p = 0.0005, I² = 19%), fasting blood glucose (FBG) (MD: -4.85; 95% CI: -7.80 to -1.91, p = 0.001, I² = 24%), and total cholesterol (TC) levels (MD: -13.40; 95% CI: -18.93 to -7.87, p < 0.00001, I² = 30%). Furthermore, a notable elevation in high-density lipoprotein cholesterol (HDL-c) was observed in CM interventions (MD: 2.08; 95% CI: 0.03-4.13, p = 0.05, I² = 0%). Compared to the control group, the reduction in insulin (MD: -3.20; 95% CI: -5.25 to -1.15, p = 0.002, I² = 83%), glycosylated hemoglobin A1c (HbA1C) (MD: -0.36; 95% CI: -0.67 to -0.04, p = 0.03, I² = 89%), triglyceride (TG) (MD: -36.47, 95% CI: -62.03 to -10.91, p = 0.005, I² = 76%), and low-density lipoprotein cholesterol (LDL-c) (MD: -15.35; 95% CI: -25.63 to -5.06, p = 0.003, I² = 52%) were observed in CM interventions, although there was considerable heterogeneity in the results. In conclusion, the present findings suggest the beneficial effects of CM supplementation on MetS and related disorders. However, in order to establish a robust link between CM and MetS, further trials with adequate sample sizes are warranted.

Recent research has increasingly focused on phytochemicals as promising anticancer agents, with glucosinolates (GSLs) and their hydrolytic derivatives playing a central role. These sulfur-containing compounds, found in plants of the Brassicales order, are converted by myrosinase enzymes into biologically active products, primarily isothiocyanates (ITCs) and indoles, which exhibit significant anticancer properties. Indole-3-carbinol, diindolylmethane, sulforaphane (SFN), phenethyl isothiocyanate (PEITC), benzyl isothiocyanate, and allyl isothiocyanate have shown potent anticancer effects in animal models, particularly in breast, prostate, lung, melanoma, bladder, hepatoma, and gastrointestinal cancers. Clinical studies further support the chemopreventive effects of SFN and PEITC, particularly in detoxifying carcinogens and altering biochemical markers in cancer patients. These compounds have demonstrated good bioavailability, low toxicity, and minimal adverse effects, supporting their potential therapeutic application. Their anticancer mechanisms include the modulation of reactive oxygen species, suppression of cancer-related signaling pathways, and direct interaction with tumor cell proteins. Additionally, semi-synthetic derivatives of GSLs have been developed to enhance anticancer efficacy. In conclusion, GSLs and their derivatives offer significant potential as both chemopreventive and therapeutic agents, warranting further clinical investigation to optimize their application in cancer treatment.

Glioblastoma multiforme (GBM) is a highly aggressive brain malignancy with limited treatment options. Radiotherapy (RT) is often used for treating unresectable GBM; however, the outcomes are often limited due to the radioresistance of GBM. Therefore, the discovery of potential radiosensitizers to enhance GBM responses to RT is crucial. Beta-caryophyllene (BCP), a natural cannabinoid, promotes cancer apoptosis by upregulating the PPARγ signaling pathway and can cross the blood-brain barrier due to its lipophilic nature. This study aimed to evaluate the radiosensitizing potential of BCP in GBM cells. U87MG and GL261 cells and a GL261 tumor-bearing model were treated with RT, BCP, or both. Treatment efficacy was assessed using the MTT assay and tumor growth tracking, and the underlying mechanisms were investigated using western blotting, immunofluorescence staining, and other analyses. BCP synergistically enhanced the efficacy of RT in cell culture, as evidenced by the combination index determined through the MTT assay. This enhancement was mediated by the BCP-induced deceleration of DNA damage repair, as demonstrated by sustained γH2AX signal, upregulated PPARγ levels, and reduced expression of pAKT, pERK, and NF-κB, indicating apoptosis induction and inhibition of survival pathways. BCP significantly inhibited tumor growth in GL261 tumor-bearing mice with no discernible side effects. These findings indicate that BCP may serve as a potential radiosensitizer for improving RT outcomes in GBM by inhibiting DNA repair, inducing apoptosis, and suppressing anti-apoptotic and survival pathways.

Coptisine (COP), a naturally occurring alkaloid, is known for its diverse pharmacological effects and its supportive role in intestinal health. Despite this, the detailed mechanisms behind its therapeutic benefits are not yet fully understood. The objective of this study is to investigate the therapeutic potential of COP for the treatment of Ulcerative Colitis (UC) and to delineate the critical pathways by which it exerts its therapeutic effects. To assess COP's therapeutic effectiveness, mice were administered COP and monitored for clinical symptoms, activity, and disease activity index (DAI) changes. Intestinal histopathology, mucosal barrier function, and gut microbiota structure were evaluated, along with metabolic profiling, focusing on Prenol lipids in the colon to identify COP-induced metabolic shifts. Mice treated with COP exhibited significant relief from diarrhea and bleeding, along with increased activity and a marked reduction in DAI scores. Histopathological evaluation revealed a reduction in intestinal inflammation, and the intestinal mucosal barrier function was notably enhanced. The gut microbiota composition in COP-treated mice showed improvements. Additionally, the levels of Prenol lipids in the colon were elevated by COP treatment, which is crucial for the recovery of intestinal function. Our study demonstrates that COP effectively ameliorates colitis symptoms by modulating colon Prenol lipids metabolism, particularly under the influence of key bacterial species. The findings of this study provide novel insights into the therapeutic mechanisms of COP in the treatment of UC.

Obesity is a metabolic disorder that has become a global health concern. The existing pharmaceutical drugs for treating obesity have some side effects. Compounds from natural sources are prospective substitutes for treating chronic diseases such as obesity, with the added advantages of being safe and cost-effective. However, due to factors such as poor solubility, low bioavailability, and instability in the physiological environment, the therapeutic efficacy of phytoconstituents is limited. Nowadays, developing nanoscaled systems has emerged as a vital strategy for enhancing the delivery and therapeutic effect of phytoconstituents. The present study discusses and categorizes phytoconstituents with anti-obesity effects and concludes the main mechanisms underlying their effects. Importantly, strategies used to develop phytoconstituent-based nano-drug delivery systems (NDDS) for obesity treatment that show improved efficacy relative to traditional administration routes are reviewed. Finally, the progress of research on phytoconstituent-based NDDS for obesity treatment is summarized to provide a reference for the development of safe and effective treatment strategies for obesity.

Cervical cancer (CC) is a serious risk to women's health; it is necessary to explore less toxic and more effective therapies to cure CC. Triptolide (Tri) is the principal active constituent found in "Tripterygium Wilford," has been shown to have antitumor effects. This study set up to demonstrate whether Tri is capable of inducing ferroptosis in CC cells and its potential mechanism. In vitro, Tri was used to treat CC cells, and lipid peroxidation levels in CC cells were detected by flow cytometry, immunofluorescence, and other experiments; the molecular mechanism of Tri treatment of CC was explored by western blot; moreover, the regulatory effects of Tri on the NRF2/GPX4/xCT axis were verified by overexpressing NRF2 in reverse. In vivo, CC cells tumor-bearing mice were constructed to observe the effect of Tri treatment on tumor growth. In vitro, we have demonstrated that Tri prevents the growth and migration of CC cells. Further investigation revealed that Tri substantially enhances ferroptosis in CC cells by increasing lipid peroxidation accumulation. Mechanically, Tri significantly reduced the expression of NRF2, leading to a corresponding repression of the NRF2 downstream targets GPX4 and xCT. Moreover, overexpressing of NRF2 effectively reversed the impact of Tri on ferroptosis in CC cells. Additionally, animal experiments indicted that Tri markedly inhibited tumor size in nude mice by inhibiting the NRF2/GPX4/xCT axis. Tri exerts antitumor effects by triggering ferroptosis in CC cells through the NRF2/GPX4/xCT axis.

Monoamine oxidase B (MAO-B) has emerged as a therapeutic target for Alzheimer's disease (AD) due to its involvement in the synthesis of γ-aminobutyric acid (GABA) in reactive astrocytes, which inhibits neuronal activity. Suffruticosol B (Suf-B), isolated from Paeonia lactiflora, is one of the resveratrol oligomers. Although resveratrol oligomers have demonstrated neuroprotective effects, it remains unexplored whether Suf-B exerts therapeutic effects on AD by targeting MAO-B. In this study, we investigated whether Suf-B alleviates AD pathology by mitigating reactive astrogliosis and inhibiting the overproduction of astrocytic GABA. After confirming the MAO-B inhibitory effect of Suf-B through MAO-B enzyme assay, we administered Suf-B to APP/PS1 AD model mice. To test the potential therapeutic action of Suf-B in AD, a series of experiments were conducted, including behavioral tests such as the open field test, novel object recognition test, Barnes maze test, passive avoidance test, as well as immunohistochemistry and whole-cell patch-clamp recordings. We found that Suf-B markedly inhibited MAO-B activity without causing cytotoxicity. Immunohistochemistry and electrophysiology experiments demonstrated that Suf-B significantly reduced astrocyte reactivity, as well as an aberrant increase in GABA production and tonic GABA release from astrocytes in AD. Behavior test results indicated that Suf-B treatment restored cognitive function in APP/PS1 mice. In conclusion, Suf-B effectively reduces excessive GABA production in reactive astrocytes by inhibiting MAO-B, normalizing aberrant inhibition in hippocampal neurons in an AD mouse model. These results suggest that Suf-B has potential as a treatment for AD and may be applicable to other brain diseases associated with reactive astrogliosis.