Phytotherapy Research最新文献

Alzheimer's disease (AD) is a complex neurodegenerative disease without any effective preventive or therapeutic drugs. Natural products with stable structures and pharmacological characteristics are valuable sources for the development of novel drugs for many complex diseases. This study aimed to discover potential natural compounds for the treatment of AD using new technologies and methods and explore the efficacy and mechanism of candidate compounds. AD-related large-scale genetic datasets were collated to construct disease-PPIs and natural products were collected from six databases to construct compound-protein interactions (CPIs). Potential relationships between natural compounds and AD were predicted via network proximity and gene enrichment analyses. Then, five AD-related cell models and d-galactose-induced aging rat model were established to evaluate the neuroprotective effects of candidate compounds in vitro and in vivo. We identified that 267 natural compounds were predicted to have close connections with AD and 19 compounds could exert protective effect in at least one cell model. Notably, purpurin exerted protective effect in three cell models and significantly improved the cognitive learning and memory functions, reduced the oxidative stress injuries and neuroinflammation, and enhanced the synaptic plasticity and neurotrophic effect in the brain of d-galactose-treated rats. In this study, AD-related natural compounds were identified via network proximity and gene enrichment analyses. In vivo and in vitro experiments revealed the therapeutic potential of purpurin for AD treatment, laying the foundation for further in-depth research and providing valuable information for the development of novel anti-AD drugs.

Female hormone-dependent cancers depend on estrogen for their growth. Numerous studies have explored the antitumor effect of dietary isoflavones on female hormone-dependent cancers. Still, few clinical evidence supports the use of isoflavones in female hormone-dependent cancer patients. This study was performed to examine the impact of dietary isoflavones on tumor growth of female hormone-dependent cancers and accelerate the transformation of research from bench to bedside. We searched PubMed Medline, Web of Science, and Google Scholar for relevant articles related to the effect of dietary isoflavone on tumor growth of experimental animal models of female hormone-dependent cancers from 1998 to 2024. The effects of dietary isoflavones on tumor growth were analyzed between the control and treatment groups using comprehensive meta-analysis software (CMA). We included 30 studies describing tumor growth focused on female hormone-dependent cancer types, including breast, ovarian, and uterine cancers. Overall, a pooled analysis revealed that dietary isoflavones reduced tumor volume (Hedge's g = -1.151, 95% CI = -1.717 to -0.585, p = 0.000) and tumor weight (Hedge's g = -2.584, 95% CI = -3.618 to -1.549, p = 0.000). On the other hand, dietary isoflavones increased tumor area (Hedge's g = 1.136, 95% CI = 0.752 to 1.520, p = 0.000). Dietary isoflavones have potential benefits and risks in female hormone-dependent cancers. Therefore, caution should be exercised when considering the intake of dietary isoflavones in female hormone-dependent cancer patients, particularly in the form of supplements.

The aim of this meta-analysis was to determine the effect of curcumin on a range of health outcomes. PubMed, EMBASE, Scopus, and Web of Science were searched from inception until September 2023. Randomized clinical trials (RCTs) that compared the effect of Curcuma longa L. with placebo were considered eligible. The risk of bias and overall certainty of evidence were assessed using the Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development, and Evaluation (GRADE), respectively. We meta-analyzed the effect sizes across eligible studies using the random-effects model. In total, 103 RCTs on 42 outcomes were included, incorporating a total population of 7216 participants. Overall, 23 out of 42 (55%) outcomes reported statistically significant effect sizes. The credibility of the evidence was rated as high for fasting blood sugar (FBS), C-reactive protein (CRP), high-density lipoprotein (HDL), and weight. The remaining outcomes presented moderate (waist circumference [WC], hip circumference [HC], body mass index [BMI], insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR], quantitative insulin-sensitivity check index [QUICKI], leptin, gamma-glutamyl transferase [GGT], glutathione [GSH], and superoxide dismutase [SOD]), low (14 outcomes), or very low (14 outcomes) evidence. In conclusion, curcumin supplementation can modify FBS and some glycemic indices, lipid parameters, as well as inflammatory and oxidative parameters. This updated summary of the accumulated evidence may help inform clinicians and future guidelines regarding medical and scientific interest in curcumin. However, due to limitations in the methodological quality of the included studies, well-designed and long-term RCTs with large sample sizes are needed. Trial registration: PROSPERO: CRD42021251969.

Ginseng is a kind of traditional Chinese medicine. It is widely believed that ginseng can improve cognitive function, but its clinical efficacy is still controversial. This study aimed to systematically evaluate the effects of ginseng on cognitive function improvement. This is a systematic review and meta-analysis of the randomized controlled trials (RCTs). Searching PubMed, Web of Science, the Cochrane Library, and Medline databases to collect RCTs of ginseng on the effects of human cognitive function. The time range is from the establishment of the database to December 2023. The main intervention in the trials was ginseng preparation. The Cochrane risk-of-bias tool 2.0 (RoB2.0) and Jadad scale were used to assess the risk of bias and evaluate the quality of the included articles. After data extraction, meta-analysis was performed using Stata 17.0 software. A total of 15 RCTs were included, and 671 patients were analyzed. The subjects included healthy people, patients of cognitive impairment, schizophrenia, hospitalized, and Alzheimer's disease. The intervention measures were mainly ginseng preparations. The meta-analysis results indicated that ginseng has a significant effect on memory improvement (SMD = 0.19, 95%CI: 0.02-0.36, p < 0.05), especially at high doses (SMD = 0.33, 95%CI: 0.04-0.61, p < 0.05). Ginseng did not have a positive effect on overall cognition, attention, and executive function (SMD = 0.06, 95%CI: -0.64-0.77, p = 0.86; SMD = 0.06, 95%CI: -0.12 to 0.23, p = 0.54; SMD = -0.03, 95%CI: -0.28 to 0.21, p = 0.79). Ginseng has some positive effects on cognitive improvement, especially on memory improvement. But in the future, more high-quality studies are needed to determine the effects of ginseng on cognitive function. Trial Registration: Prospero: CRD42024514231.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and diabesity (diabetes related to obesity) are interrelated since glucose and lipid alterations play a vital role in the development of both disorders. Due to their multi-variant metabolic features, more than one drug or natural product may be required to achieve proper therapeutic effects. This study aimed to evaluate the effectiveness of a formulation containing co-micronized palmitoylethanolamide and rutin (PEA-Rut) associated with hydroxytyrosol (HT), namely NORM3, against hepatic damage and metabolic alterations in high-fat diet (HFD)-induced diabesity in mice. NORM3 decreased the body weight and fat mass of obese mice. The formulation improved HFD-altered insulin sensitivity and hepatic glucose production and metabolism, as shown by glucose, insulin, pyruvate tolerance tests, Western blot, and real-time PCR. In the liver, NORM3 limited macro- and micro-vacuolar steatosis, as revealed by morphological analysis, and reduced the associated hepatic inflammation. NORM3 counteracted lipid dysfunctions of HFD animals, activating AMPK, a key cellular energy sensor, and normalizing the expression of carnitine palmitoyl-transferase (CPT)1, a rate-limiting enzyme of fatty acid β-oxidation, and other genes involved in lipid homeostasis. Relevantly, the hepatic antioxidant activity of NORM3 was proved (reduced ROS and increased detoxifying factors and enzymes). Finally, in vitro synergistic protective effects of the components (PEA-Rut and HT) on H₂O₂-induced oxidative challenge in HepG2 were determined (ROS production, inflammation, and antioxidant defense). Our results show the beneficial effect of NORM3 and its potential as an innovative phytotherapeutic combination in limiting hepatic damage progression and counteracting glucose and lipid dysmetabolism associated with diabesity.

Ferroptosis is a newly discovered type of cell death that exerts a crucial role in hepatic fibrosis. Formononetin (FMN), a natural isoflavone compound mainly isolated from Spatholobus suberectus Dunn, shows multiple biological activities, including antioxidant, anti-inflammatory, and hepatoprotection. This research aims to explore the regulatory mechanism of FMN in liver fibrosis and the relationship between NADPH oxidase 4 (NOX4) and ferroptosis. The effects of FMN on HSC ferroptosis were evaluated in rat model of CCl₄-induced hepatic fibrosis. In vitro, N-acetyl-L-cysteine (NAC) and deferoxamine (DFO) were used to block ferroptosis and then explored the anti-fibrotic effect of FMN. The target protein of FMN was identified by bio-orthogonal click chemistry reaction as well as drug affinity responsive target stability (DARTS), cellular thermal shift (CETSA), surface plasmon resonance (SPR) assays, and isothermal titration calorimetry (ITC) analysis. Here, we found that FMN exerted anti-fibrotic effects via inducing ferroptosis in activated HSCs. NAC and DFO prevented FMN-induced ferroptotic cell death and collagen reduction. Furthermore, FMN bound directly to NOX4 through possible active amino acid residues sites, and increased NOX4-based NADPH oxidase activity to enhance levels of NADP⁺/NADPH, thus promoting ferroptosis of activated HSCs and relieving liver fibrosis. These results demonstrate that the direct target and mechanism by which FMN improves liver fibrosis, suggesting that FMN may be a natural candidate for further development of liver fibrosis therapy.

MHO7 (6-epi-ophiobolin G), a novel component extracted from a mangrove fungus, exhibits significant anticancer effects against breast cancer. However, the precise mechanism underlying the anticancer effects of MHO7 in prostate cancer (PCa) is yet to be fully elucidated. Therefore, this study was undertaken to assess the effect of MHO7 on PCa cells and elucidate its underlying mechanism. A series of in vitro experiments were conducted, including Cell Counting Kit-8, and plate clone formation assays, flow cytometry analysis, electron microscopy, immunofluorescence staining, western blotting, and molecular dynamics simulation. Additionally, in vivo tumor xenograft models were employed. Our findings revealed that MHO7 could induce cellular autophagy at low concentration (2 μM) and apoptosis at relatively high concentration (4 and 8 μM), leading to significant PCa cell growth inhibition. Furthermore, MHO7 triggered endoplasmic reticulum (ER) stress, which subsequently stimulated autophagy and apoptosis via IRE1α/XBP-1s signaling pathway activation. Notably, IRE1α knockdown markedly reduced MHO7-induced autophagy and apoptosis. Moreover, MHO7 targeted the IRE1α protein, thereby enhancing its stability. MHO7 also exhibited substantial anticancer activity in tumor xenograft models. Our study revealed that MHO7 holds considerable potential as an anticancer agent against PCa, attributable to its activation of ER stress-induced autophagy and apoptosis at different concentrations, facilitated by the upregulation of IRE1α expression.

The high incidence and mortality rate of colorectal cancer have become a significant global health burden. Chemotherapy has been the traditional treatment for colorectal cancer and has demonstrated promising antitumor effects, leading to significant improvements in patient survival. However, the development of chemoresistance poses a major challenge during chemotherapy in colorectal cancer, significantly impeding treatment efficacy and affecting patient prognosis. Despite the development of a variety of novel anticolorectal cancer chemotherapy agents, their effectiveness and side effects vary, possibly due to the complex mechanisms of resistance in colorectal cancer. Abnormal drug metabolism or protein targets are the most direct causes of resistance. Further studies have revealed that these resistance mechanisms involve biochemical processes such as altered protein expression, autophagy, and epithelial-mesenchymal transitions. Herbal active ingredients offer an alternative treatment option and have shown promise in reversing colorectal cancer drug resistance. This paper aims to summarize the role of various biochemical processes and key protein targets in the occurrence and maintenance of resistance mechanisms in colorectal cancer. Additionally, it elaborates on the mechanisms of action of herbal active ingredients in reversing colorectal cancer drug resistance. The article also discusses the limitations and opportunities in developing novel anticolorectal cancer drugs based on herbal medicine.

Research indicates that bitter melon could be useful in the management of dyslipidemia. Still, there is disagreement concerning the findings. This systematic study was undertaken to clarify the impact of consuming bitter melon on lipid profile. The databases Web of Science, Cochrane Library, PubMed, and Scopus were queried from inception until February 9, 2023. The study assessed triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. The effect sizes were calculated using weighted mean differences (WMDs) and 95% confidence intervals (CIs). Eight randomized controlled trials (RCTs) with a total of 423 participants were included. Bitter melon consumption resulted in a significant decrease in plasma concentrations of TC (WMD; -9.71 mg/dL; CI: -17.69 to -1.74, p = 0.01) and TG (WMD; -10.24 mg/dL; CI: -19.92 to -0.56, p = 0.03), while bitter melon did not significantly lower blood LDL-C (WMD; -8.66 mg/dL; CI: -19.83 to 2.50, p = 0.12) and HDL-C concentrations (WMD; 0.54 mg/dL; CI: -2.38 to 3.45, p = 0.71). Subgroup analysis showed a significant decrease in TC and LDL-C and an increase in HDL-C at a dose of ≤ 2000 mg/day and an intervention period of ≤ 8 weeks. Also, the greatest impact of LDL-C and HDL-C was seen in diabetic and prediabetic people. Bitter melon supplementation positively impacts TC and TG levels. The limitations of this study were short-term trials (less than 3 months).