Journal of Natural Medicines最新文献

The miraculous golden tree of the century, neem or Azadirachta indica, has been used in ancient ayurvedic and traditional medicine since the inception of medicinal practices. The phytochemicals present in each part of this tree are known to possess the ability to cure a variety of diseases, from viral, bacterial, and fungal infections and associated pathogenesis to inflammatory diseases, different metabolic disorders, and cancers. Predominant phytochemicals from neem, azadirachtin, nimbin, nimbolide, quercetin, etc., are known to be potent anti-inflammatory, antiviral, and anti-cancer agents. These and many other bio-active compounds from neem restrict the viral spread and replication of β-coronaviruses, Human Immunodeficiency Virus, Herpes Simplex Virus, etc. Likewise, neem extracts and bio-active compounds from neem have been targeting cancer cells by restricting their proliferation, survival, and migration and inducing apoptosis, leading to the establishment of neem as a potent anti-cancer agent. Multiple studies have reported neem's efficiency in intervening with inflammatory pathways and oxidative stress pathways, which are known to be linked to viral infections and cancers. In this review, we discuss the role of methanolic neem bark extracts and their bio-active compounds in preventing β-coronavirus mouse hepatitis virus and SARS-CoV-2 replication and spread, and simultaneously the anti-cancer effects exerted by MNBE via activating pro-apoptotic markers, restricting the proliferation and migration of cervical cancer cells, inducing cell cycle arrest.

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Excessive glutamate in the central nervous system is a key pathogenic mechanism in neurodegenerative disorder. This study investigated the neuroprotective effect of acrovestone (AVT), an acetophenone dimer from Acronychia pedunculata, and its underlying mechanism in glutamate-induced neuroblastoma SH-SY5Y cells. The protective effect of AVT was evaluted through cell viability assay and analysis of apoptosis-related protein expression via Western blot analysis. Our finding revealed that AVT significantly improved cell viability under glutamate induced excitotoxicity conditions. Mechanistic investigations demonstrated that AVT attenuated the activation of pro-apoptotic proteins including ERK1/2, Bim, BAX, caspase-3, caspase-7, and caspase-9. Concurrently, AVT upregulated the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL. Furthermore, AVT modulated the Akt/FoxO3a signaling pathway, alleviating acute oxidative stress caused by glutamate exposure in SH-SY5Y cells. These results suggest that AVT inhibits glutamate-induced neurotoxicity by modulating apoptosis signaling pathway, highlighting its potential as a therapeutic candidate for preventing neurodegenerative diseases.

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Commiphora species, valued for their resinous cell saps rich in terpenoids and other compounds, are known for their therapeutic benefits. This study aimed to be the first NMR-based metabolome profiling of oleo-gum resin derived from endemic rare Commiphora species. Insights into taxonomic variation and tree sex differences were targeted for future correlation with bioactivities-related assays. Oleo-gum resins and cell sap were collected and extracted by methanol from four naturally growing Commiphora species, including C. gileadensis, C. quadricincta, C. kataf female, and C. kataf male. Afterward, NMR acquisition and spectra interpretation were carried out, including various 1D and 2D-techniques. A total of 36 metabolites were identified, including 3 cycloartane derivatives, 12 amino acids and their derivatives, 7 organic acids, 1 phenolic acid, 6 sugars and sugar alcohols, 6 terpenoids, and 1 nitrogenous compound. Multivariate analysis, employing both unsupervised and supervised modeling, facilitated classification of samples and provided a foundation for future authentication and quality control of these taxa. Notably, C. gileadensis cell sap and C. quadricincta oleo-gum resin were metabolically distinct, enriched in terpenoids such as cycloartane 24-en-1,2,3-triol (1) and 1-acetoxycycloartan-24-ene-2,3-diol (2), while trehalose (24) was more abundant in other species. Further, quantitative NMR (qNMR) quantified 9 metabolite markers detected at high levels in Commiphora accessions. In conclusion, terpenoids were found to be abundant and discriminant compounds in Commiphora products. The results shall aid in the future standardization of Commiphora oleo-gum resins to be included in nutraceuticals and for future correlation with bioactivities-related assays.

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D. huoshanense is a traditional Chinese medicine with antidiabetes effects, but the underlying metabolic regulatory mechanism remains unknown. Plasma metabolomic analysis was applied to assess the metabolic regulatory mechanism underlying the alleviation of streptozotocin-induced type 1 diabetes (STZ-T1D) by D. huoshanense. The successfully STZ-T1D model rats were assigned to the model group, the model + water extract of D. huoshanense (DHWE) group, and the model + metformin (MET) group. They were administered the corresponding medication by gavage. After 28 days, the plasma levels of glucose, malondialdehyde (MDA), C-reactive protein (CRP), and total antioxidant capacity (T-AOC) were determined. Morphological changes in the pancreatic islet tissue were analyzed via hematoxylin and eosin (H&E) staining. The expression of occludin-1, zonula occludens protein 1 (ZO-1) and protein kinase RNA-like endoplasmic reticulum kinase (PERK) in the ileum tissue was determined via western blotting. Nontargeted metabolome analysis of the plasma was performed via ultrahigh-performance liquid chromatography. The results revealed that DHWE reduced blood glucose, C-reactive protein, and MDA levels; increased plasma T-AOC; improved intestinal mucous integrity and pancreatic islet morphological structure; and alleviated intestinal endoplasmic reticulum stress. Plasma metabolomics revealed that DHWE significantly increased the levels of ascorbic acid 2-sulfate, L-thyroxine, phosphatidylcholine (PC) (14:0e/5:0), and PC (16:1e/4:0); decreased the levels of D-(-)-fructose and indole-3-lactic acid; and significantly affected ascorbate and aldarate metabolism and glyoxylate and dicarboxylate metabolism in STZ-T1D rats (p < 0.05), and the effects on the citric acid cycle and pyruvate metabolism tended to be significant (p < 0.1). This study confirmed that DHWE alleviated STZ-T1D by reducing oxidative stress and the inflammatory response, enhancing intestinal mucosa integrity and affecting mainly the energy metabolism and vitamin C metabolism of STZ-T1D rats.

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Atherosclerosis (AS) remains the main cause of vascular diseases. This study reveals the effects of safranal and underlying mechanisms in RAW264.7 macrophages under AS context, which is hoped to facilitate its clinical application. Safranal reduced AS progression in ApoE (−/−) mice, and it also increased the serum level of HDL-C and decreased the levels of TG, TC, and LDL-C as well as ALT and AST. Besides, safranal repressed the pathophysiological processes of OS (downregulated levels of ROS and MDA and upregulated biosynthesis of GSH), ERS (decreased protein levels of activating transcription factor 6, X-Box Binding Protein 1, and glucose-regulated protein, 78 kDa), and inflammation (downregulated serum levels of TNF-α, IL-1β, and IL-6) in vivo. Mechanistically, safranal repressed PI3K/Akt and NF-κB signaling pathways in vivo. On the cellular level, safranal treatment relieved the uptake of ox-LDL, and decreased contents of TG, TC, and LDL-C while increasing HDL-C level in ox-LDL-treated RAW264.7 macrophages. It also reduced the molecular indexes of pathophysiological processes (OS, ESR, and release of inflammatory mediators) in ox-LDL-exposed RAW264.7 macrophages. Notably, safranal treatment also impaired PI3K/Akt and NF-κB signaling pathways in ox-LDL-exposed RAW264.7 macrophages. Additionally, the PI3K agonist 740Y-P notably reversed the in vitro inhibitory effects of safranal on lipid deposition, productions of TC and TNF-α, and protein levels of molecules of PI3K/Akt and NF-κB signaling pathways. Safranal exerts anti-AS effects via repressing OS, ERS, and inflammation in ApoE (−/−) mice, and it also negatively modulates PI3K/Akt and NF-κB signaling pathways in RAW264.7 macrophages.

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Safranal reduces oxidative stress, endoplasmic reticulum stress, and release of inflammatory factors to relieve atherosclerosis progress partly via repressing PI3K/Akt and NF-κb pathways in RAW264.7 macrophages.

Ginsenoside Rh3, a bioactive component of ginsenosides, has gained attention for its potential therapeutic effects, especially in cancer treatment. However, its neurotoxic effects remain poorly characterized, raising concerns about its safety for clinical use. This study investigates the neurotoxic effects of ginsenoside Rh3 and explores the underlying mechanisms. We demonstrate that ginsenoside Rh3 induces significant cytotoxicity in Neuro-2a and C8-D1A cells, as confirmed by methyl thiazolyl tetrazolium (MTT) assays, live–dead staining, and lactate dehydrogenase (LDH) release assays. Neurotoxicity polymerase chain reaction (PCR) array analyses show that the cytotoxicity of ginsenoside Rh3 in Neuro-2a cells involves calcium ion transport, oxidative stress, inflammation, and programmed cell death (PCD). Specifically, ginsenoside Rh3 elevates intracellular Ca²⁺ levels by activating the inositol 1,4,5-triphosphate receptor (IP3R), which in turn increases oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 2. This cascade activates the phosphorylated nuclear factor-kappa B (NF-κB) signaling pathway, exacerbating apoptosis and leading to neuronal cell death. Molecular docking and dynamics simulations suggest direct interactions between ginsenoside Rh3 and both IP3R and NOX2. Notably, the neurotoxic effects of ginsenoside Rh3 were significantly attenuated by IP3R inhibitor 2-aminoethyl diphenylborinate (2-APB) and NOX2 inhibitor GSK2795039. These findings demonstrate that ginsenoside Rh3 induces neurotoxicity through IP3R-Ca²⁺/NOX2/NF-κB signaling pathways. This study provides critical insights into the safety concerns of ginsenoside Rh3, highlighting the need for caution in its clinical applications.

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