Phytomedicine最新文献

Background: Melanoma, a highly malignant skin tumor, can develop systemic metastases during the early stage. Several studies of melanoma animal models indicate that curcumin, a natural plant extract, inhibits melanoma growth through various mechanisms. To evaluate the relationships among different experimental conditions, curcumin itself, its derivatives, and special formulations, it is necessary to conduct a systematic review and meta-analysis.

Purpose: This meta-analysis aims to evaluate the potential of Curcumin as a drug for inhibiting the growth of melanoma and to determine the optimal dosage range and treatment duration for Curcumin administration.

Methods: A systematic search of studies published from inception to December 2023 was conducted across six databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Wanfang Data, and VIP). Methodological quality was assessed using SYRCLE's RoB tool. Study heterogeneity was assessed using Cochran's Q test and I² statistics. Publication bias risk was evaluated using a funnel plot. All analyses were performed using R (version 4.3.3). Additionally, three-dimensional effect analysis and machine learning techniques were utilized to determine the optimal dosage range and treatment duration for Curcumin administration.

Results: Forty studies involving 989 animals were included. The results demonstrated that, relative to the control group, administration of Curcumin resulted in a significant reduction in tumor volume. [SMD=-3.44; 95 % CI (-4.25, -2.63); P<0.01; I² = 79 %] and tumor weight [SMD=-1.93; 95 % CI (-2.41, -1.45); P<0.01; I² = 75 %]. Additionally, Curcumin demonstrated a significant capacity to decrease the number of lung tumor nodules and microangiogenesis, as well as to extend survival time, in animal models. The results from three-dimensional effect analysis and machine learning emphasize that the optimal dosage range for Curcumin is 25-50 mg/kg, with an intervention duration of 10-20 days.

Conclusion: Curcumin can inhibit the growth of melanoma, and the dose-response relationship is not linear. However, further large-scale animal and clinical studies are required to confirm these conclusions.

Background: Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis and is currently lacking specific pharmacological treatments, highlighting the critical need for therapeutic development. Icariin (ICA), a prenylated flavonol glycoside, was previously found to exhibit several pharmacological effects, but its potential to combat CVB3 remains uninvestigated.

Purpose: This study aimed to elucidate the anti-CVB3 efficacy of ICA and elucidate its molecular mechanisms.

Methods: CVB3-infected HeLa cells, H9C2 cells and neonate rat ventricular cardiomyocytes (NRVCs) were selected as in vitro models, and were treated with ICA at 1 and 10 μM. Additionally, BALB/c mice that were infected with CVB3 via intraperitoneal injection were chosen as in vivo model and were treated with ICA or ribavirin over 3 days. The effect of ICA against CVB3 was determined by Cell Counting Kit-8 (CCK-8) assay, western blot, real-time fluorescence quantitative PCR (RT-qPCR), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and flow cytometry.

Results: In this study, it was found that ICA is capable of reducing CVB3 viral load both in vitro and in vivo. Mechanistic studies suggested that ICA prevents cardiomyocyte apoptosis by attenuating the S100 calcium binding protein A6 (S100A6)/β-catenin/c-Myc signaling pathway. Additionally, ICA inhibits the secretion of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and CXC motif chemokine ligand 2 (CXCL2) in heart tissue, thereby mitigating CVB3-induced myocarditis. Moreover, ICA also regulates the immune response of CD4⁺ T, CD8⁺ T and Treg cells by changing the cells numbers in spleen tissue. Lastly, ICA can reduce the load of other enteroviruses (such as CVA6, CVA16 and EV71) in rhabdomyosarcoma (RD) cells as well.

Conclusion: Our findings indicate that ICA provides significant protection against CVB3 infection by modulating the S100A6/β-catenin/c-Myc signaling pathway, suggesting its potential use as a novel drug against CVB3 infection in clinical application.

Introduction: Pidanjiangtang (PDJT) is a traditional Chinese medicine formula empirically used to treat impaired glucose tolerance (IGT) based on the "Pidan" theory from the classic ancient book Nei Jing. However, the mechanism of PDJT intervention for IGT remains to be studied.

Objective: This study aims to explore the mechanism of PDJT granules intervention in IGT by integrating gut microbiome and UHPLC-MS untargeted metabolomics.

Materials and methods: The IGT model was established in 6-week-old male Sprague-Dawley (SD) rats by feeding them a high-fat diet and using an STZ injection. The low, medium, and high doses of PDJT were used for six weeks. metformin (Glucophage) was used as the positive control drug. The efficacy of PDJT was evaluated using fasting blood glucose (FBG), blood glucose maximum (BGmax), blood lipid, and inflammatory factor levels. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PDJT intervention in IGT.

Results: PDJT could reverse the phenotype of IGT rats, reduce blood glucose levels, improve lipid metabolism disorder, and reduce inflammatory response. Gut microbiome analysis found that PDJT can improve gut microbiota composition and abundance of three phyla (Firmicutes, Bacteroidota, Desulfobacterota) and four genera (unclassified_f__Lachnospiraceae, Ruminococcus, Allobaculum, Desulfovibrio), which play an important role in the process of PDJT intervention on glucose metabolism and lipid metabolism in IGT rats. UHPLC-MS untargeted metabolomics showed that PDJT could regulate the levels of 258 metabolites in lipid metabolism pathways, inflammatory response pathways, fat and protein digestion, and absorption. The combined analysis of the two omics showed that improving the body's metabolism by gut microbes may be the possible mechanism of PDJT in treating IGT. Thus, this study provides a new method to integrate gut microbiome and UHPLC-MS untargeted metabolomics to evaluate the pharmacodynamics and mechanism of PDJT intervention in IGT, providing valuable ideas and insights for future research on the treatment of IGT with traditional Chinese medicine.

Background: Bone formation and resorption regulate bone homeostasis. Excessive osteoclastogenesis enhances bone resorption and causes osteoporosis. Although medicines targeting osteoclast have been developed, these drugs have several side effects. Natural compounds have advantages in safety and efficiency, making them potential candidates for osteoporosis treatment.

Purpose: This study aims to elucidate the role of damascenone (Dama) in osteoclastogenesis and osteoporosis.

Study design and methods: To demonstrate the effect of Dama on osteoclast differentiation and function, we performed multiple in vitro experiments including TRAP staining, F-actin staining, bone slice resorption assay, real-time PCR, and western bolt. Further, ROS detection, network pharmacology, microscale thermophoresis assay, and ChIP assay were conducted to elucidate the underlying molecular mechanism. Finally, the in vivo effects of Dama were verified using an ovariectomy induced osteoporosis mice model.

Results: Dama inhibited RANKL-induced osteoclast differentiation and bone resorptive function in vitro. The expression of osteoclast-related genes and activation of MAPKs and NF-κB signaling in osteoclast were also attenuated by Dama. Meanwhile, Dama reduced intracellular ROS level via up-regulating Nrf2 expression. Network pharmacology demonstrated that HDAC2 is the potential direct target of Dama. Dama inhibited HDAC2 function and increased H3K27ac level of Nrf2, which induced Nrf2 expression and activated ROS scavenging enzymes. Inhibiting NRF2 or activating HDAC2 attenuated the effect of Dama on osteoclastogenesis. Finally, Dama injection suppressed in vivo osteoclastogenesis and ameliorated bone loss induced by OVX.

Conclusion: Dama attenuates osteoclastogenesis by epigenetically modulating Nrf2 expression and ROS scavenge. This study provides evidence for Dama being a potential treatment for osteoporosis.