Aloe-emodin (AE), known as 1,8-dihydroxy-3-hydroxymethyl-anthraquinone, is a naturally occurring anthraquinone that has attracted attention for its diverse pharmacological applications. AE is mainly found in plant species, such as Aloe vera, Rheum palmatum, and Polygonum multiflorum. Accumulating preclinical studies suggest that AE exerts anticancer, antimicrobial, antiviral, antiparasitic, hepatoprotective, neuroprotective, cardioprotective, and anti-inflammatory properties. In particular, its anticancer effects, involving apoptosis induction, oxidative stress inhibition, mitochondrial dysfunction, and inhibition of proliferative and metastatic pathways across multiple cancer cell lines, are especially well-characterized. AE demonstrates promising preclinical results, with a range of effective in vitro doses of 0.05 to 100 µM and in vivo doses of 25-100 mg/kg in animals; however, higher micromolar concentrations have been reported to have cytotoxic and hepatotoxic effects, highlighting AE's translational potential while necessitating further safety evaluation. Simultaneously, proliferative signaling pathways, such as PI3K/Akt/mTOR and MAPK, are widely investigated; some potential signaling pathways, like PIP2 stimulation, which also activates the AKT/mTOR pathway, are still unexplored. AE combats various infectious diseases targeting gram-positive and gram-negative bacteria, influenza A, herpes simplex virus, Japanese encephalitis virus, enterovirus 71, and parasites such as Leishmania. Despite the promising pharmacological effects of AE, its clinical application is limited by poor pharmacokinetics, such as low bioavailability, rapid clearance, and inadequate intestinal absorption, along with safety risks like liver, kidney, and light-induced toxicity. Overcoming these challenges require improved delivery systems, structural modifications, and detailed toxicity profiling. Our review consolidates current pharmacological evidence, identifies research gaps, and suggests modifications and future directions for AE as a potential therapeutic agent.

2024-02-01·Biochemical pharmacology

1,8-Dihydroxy-3-methoxy-anthraquinone inhibits tumor angiogenesis through HIF-1α downregulation

Article

作者: Hye Jung Bang ; Joo-Hyun Hong ; Ki Hyun Kim ; Seung Hye Cho ; Hyo-Jong Lee ; Su Jung Hwang

Photorhabdus luminescens is a gram-negative bioluminescent bacterium known as an intestinal bacterium that coexists in the digestive tract of insect-pathogenic nematodes. As part of our ongoing exploration to identify bioactive compounds from diverse natural resources, the chemical analysis of the cultures of P. luminescens KACC 12254 via LC/MS and TLC-based analyses enabled the isolation and identification of a major fluorescent compound. Its chemical structure was elucidated as 1,8-dihydroxy-3-methoxyanthraquinone (DMA) using HR-ESI-MS and NMR analysis. In this study, we conducted comprehensive investigations utilizing human colorectal cancer HCT116 cells, human umbilical cord vascular endothelial cells (HUVECs), and zebrafish embryos to assess the potential benefits of DMA in suppressing tumor angiogenesis. Our results convincingly demonstrate that DMA effectively suppresses the stability of hypoxia-inducible factor-1α (HIF-1α) protein and its target genes without inducing any cytotoxic effects. Furthermore, DMA demonstrates the ability to inhibit HIF-1α transcriptional activation and mitigate the production of reactive oxygen species (ROS). In our in vitro experiments, DMA exhibits notable inhibitory effects on VEGF-mediated tube formation, migration, and invasion in HUVECs. Additionally, in vivo investigations using zebrafish embryos confirm the antiangiogenic properties of DMA. Notably, DMA does not exhibit any adverse developmental or cardiotoxic effects in the in vivo setting. Moreover, we observe DMA's capability to restrain tumor growth through the downregulation of PI3K/AKT and c-RAF/ERK pathway. Collectively, these compelling findings underscore DMA's potential as a promising therapeutic candidate for targeted intervention against HIF-1α and angiogenesis in cancer treatment.

2018-01-28·Journal of microbiology and biotechnology4区 · 工程技术

Neuroprotective and Anti-Neuroinflammatory Activities of Anthraquinones Isolated from Photorhabdus temperata Culture Broth

4区 · 工程技术

Article

作者: Lee, Kyeong-Yeoll ; Song, Kyung-Sik ; Yang, Eun-Ju ; Kim, Seo-Hyun

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, 75 µM 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, Ca²⁺ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-γ-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-α. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

100 项与 DMA(Sungkyunkwan University) 相关的药物交易

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