Handelin
(Synonyms: 野菊花内酯) 目录号 : GC38025
Handelin 是来自Chrysanthemum boreale 的愈创木酚内酯二聚体，它通过下调 NF-κB 信号传导和促炎性细胞因子的产生而具有强大的抗炎活性。
Cas No.:62687-22-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Handelin is a guaianolide dimer from Chrysanthemum boreale that has potent anti-inflammatory activity by down-regulating NF-κB signaling and pro-inflammatory cytokine production[1].
Handelin (Compound 1; 10-40 μM; RAW 264.7 cells) treatment suppresses the LPS-induced (1 μg/mL) overexpression of iNOS and COX-2 protein levels in a concentration-dependent manner. Handelin also suppresseS the induction of pro-inflammatory cytokines TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells. Handelin also suppresses the activation of mitogen-activated protein kinases, including ERK and JNK signaling[1].Handelin (Compound 1; 10-40 μM; RAW 264.7 cells) treatment significantly reduces the iNOS and COX-2 mRNA levels in LPS- stimulated RAW 264.7 cells. The transcriptional activity of NF-κB stimulated with LPS is also suppressed by Handelin. In addition, the LPS-stimulated upregulation of miRNA-155 expression is suppressed by Handelin[1]. RT-PCR[1] Cell Line: RAW 264.7 cells
Handelin (Compound 1; 10-20 mg/kg; oral administration; for 30 mintues; male Sprague-Dawley rats) treatment inhibits acute inflammation in carrageenan-induced paw edema model. The serum level of IL-1β is also inhibited by Handelin in a carrageenan-induced paw edema model [1]. Animal Model: Male Sprague-Dawley (SD) rats (150-170 g, 5 weeks old) injected with carrageenan[1]
[1]. Y Pyee, et al. Suppression of inflammatory responses by handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production. J Nat Prod. 2014 Apr 25;77(4):917-24.
| Cas No. | 62687-22-3 | SDF | |
| 别名 | 野菊花内酯 | ||
| Canonical SMILES | C[C@]([C@]([C@@](OC1=O)([H])[C@@](C1=C)([H])CC[C@]2(O)C)([H])[C@@]32C4)(C=C3)[C@]54[C@@]([C@H]6OC(C)=O)([H])[C@]([C@](C(C)=CC7)([H])[C@]7([H])[C@](C)(O)C6)([H])OC5=O | ||
| 分子式 | C32H40O8 | 分子量 | 552.66 |
| 溶解度 | DMSO : 16.67 mg/mL (30.16 mM; Need ultrasonic) | 储存条件 | 4°C, protect from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.8094 mL | 9.0472 mL | 18.0943 mL |
| 5 mM | 0.3619 mL | 1.8094 mL | 3.6189 mL |
| 10 mM | 0.1809 mL | 0.9047 mL | 1.8094 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Handelin extends lifespan and healthspan of Caenorhabditis elegans by reducing ROS generation and improving motor function
Biogerontology 2022 Feb;23(1):115-128.PMID:35038074DOI:10.1007/s10522-022-09950-5.
Aging and aging-related disorders contribute to formidable socioeconomic and healthcare challenges. Several promising small molecules have been identified to target conserved genetic pathways delaying aging to extend lifespan and healthspan in many organisms. We previously found that extract from an edible and medicinal plant Chrysanthemum indicum L. (C. indicum L.) protect skin from UVB-induced photoaging, partially by reducing reactive oxygen species (ROS) generation. Thus, we hypothesized that C. indicum L. and its biological active compound may extend lifespan and health span in vivo. We find that both water and ethanol extracts from C. indicum L. extended lifespan of Caenorhabditis elegans, with better biological effect on life extending for ethanol extracts. As one of the major biological active compounds, Handelin extended lifespan of C. elegans too. RNA-seq analysis revealed overall gene expression change of C. elegans post stimulation of Handelin focus on several antioxidative proteins. Handelin significantly reduced ROS level and maintained the number and morphology of mitochondria. Moreover, Handelin improveed many C. elegans behaviors related to healthspan, including increased pharyngeal pumping and body movement. Muscle fiber imaging analyses revealed that Handelin maintains muscle architecture by stabilizing myofilaments. In conclusion, our present study finds a novel compound Handelin, from C. indicum L., which bring about biologically beneficial effects by mild stress response, termed as hormetin, that can extend both lifespan and healthspan in vivo on C. elegans. Further study on mammal animal model of natural aging or sarcopenia will verify the potential clinical value of Handelin.
Handelin Reduces Ultraviolet A-Induced Photoaging by Inhibiting Reactive Oxygen Species Generation and Enhancing Autophagy
Tohoku J Exp Med 2023 Feb 17;259(3):189-198.PMID:36476587DOI:10.1620/tjem.2022.J108.
Photoaging is mainly caused by the exposure of the skin to ultraviolet (UV) radiation. Among them, damage to human dermal fibroblast (HDF) cells caused by ultraviolet A (UVA) is the main cause of skin aging. Researchers have dedicated to identifying natural compounds from plants to fight against UV radiation-induced photoaging. We previously found that extracts from wild chrysanthemum could prevent acute damage and photoaging induced by UV irradiation. As one of the most abundant ingredients in wild chrysanthemum extract, Handelin was hypothesized to have the potential to prevent UVA-induced photoaging of skin fibroblast. In the present study, we report the great potential of Handelin in combating UVA-induced photoaging of fibroblasts. We firstly demonstrated that Handelin was safe for skin fibroblast as high as a concentration of 0.0125 μM, showing no toxicity on the cells and improved cell viability. Furthermore, Handelin can reduce UVA-induced cellular senescence, indicated by a reduced proportion of senescence-associated beta-galactose positive cells and the expression of P21. We then verified that Handelin pretreatment markedly attenuated the production of reactive oxygen species (ROS) generation after UVA irradiation. Meanwhile, we found that Handelin enhances autophagy after UVA irradiation, and autophagy is involved in the quality control of intracellular proteins after UV-induced damage (partially indirectly via ROS). Therefore, these results suggest that Handelin has a very high potential as an effective ingredient against UVA-induced skin aging. Moreover, this provides an important basis for further research on the photoprotective mechanism of Handelin.
The novel TAK1 inhibitor Handelin inhibits NF-κB and AP-1 activity to alleviate elastase-induced emphysema in mice
Life Sci 2023 Apr 15;319:121388.PMID:36640900DOI:10.1016/j.lfs.2023.121388.
Aims: Emphysema, one of the two major components of chronic obstructive pulmonary disease (COPD), is driven by aberrant inflammatory responses and associated with irreversible lung parenchymal destruction. As effective therapy for preventing or treating COPD/emphysema is yet unavailable, development of molecular targets and therapeutic agents for COPD/emphysema is required. Main methods and key findings: We identified handelin-a guaianolide dimer of sesquiterpene lactones- from a chemical library of 431 natural products as it exhibited potent inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) and reactive oxygen species (ROS) production, LPS-induced activation of nuclear factor κB (NF-κB), mitogen-activated protein kinase (MAPK)/AP-1, and expression of proinflammatory mediators in macrophage cells. In silico docking and biochemical studies enabled the identification of the ATP-binding pocket of transforming growth factor beta-activated kinase 1 (TAK1), a kinase upstream of NF-κB and MAPK/AP-1 pathways, as a molecular target for Handelin. Moreover, oral administration of Handelin (10 mg/kg) suppressed elastase-induced development of emphysematous phenotypes, including lung function disturbance, airspace enlargement, and increases in the level of neutrophils and CD8+ T cells in lung tissues, without overt toxicity. Consistent with in vitro results, analyses of lung tissues revealed that treatment with Handelin suppressed elastase-induced NF-κB and AP-1 activation in the lungs, followed by downregulation of their targets including interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase 9 (MMP9). Significance: These findings suggest that Handelin, as a TAK1 inhibitor, effectively prevents development of emphysema in an elastase-induced mouse model by inhibiting a proinflammatory mediators mediated by NF-κB and AP-1.
Suppression of inflammatory responses by Handelin, a guaianolide dimer from Chrysanthemum boreale, via downregulation of NF-κB signaling and pro-inflammatory cytokine production
J Nat Prod 2014 Apr 25;77(4):917-24.PMID:24689881DOI:10.1021/np4009877.
The anti-inflammatory activity of Handelin (1), a guaianolide dimer from Chrysanthemum boreale flowers, was evaluated in vivo, and the effects on mediators nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) and the nuclear factor-κB (NF-κB) and ERK/JNK signaling pathways were investigated in vitro. Compound 1 inhibited lipopolysaccharide (LPS)-induced production of NO and PGE2 in cultured mouse macrophage RAW 264.7 cells. The suppression of NO and PGE2 production by 1 was correlated with the downregulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compound 1 also suppressed the induction of pro-inflammatory cytokines TNF-α and IL-1β in LPS-stimulated RAW 264.7 cells. To further clarify the transcriptional regulatory pathway in the expression of iNOS and COX-2 by 1, the role of NF-κB was determined in RAW 264.7 cells. Compound 1 inhibits the binding activity of NF-κB into the nuclear proteins. The transcriptional activity of NF-κB stimulated with LPS was also suppressed by 1, which coincided with the inhibition of IκB degradation. Compound 1 also suppressed the activation of mitogen-activated protein kinases, including ERK and JNK signaling. In addition, the LPS-stimulated upregulation of miRNA-155 expression was suppressed by 1. The oral administration of 1 inhibited acute inflammation in carrageenan-induced paw and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema models. The serum level of IL-1β was also inhibited by 1 in a carrageenan-induced paw edema model. These findings suggest that the suppression of NF-κB activation and pro-inflammatory cytokine production may be a plausible mechanism of action for the anti-inflammatory activity of Handelin.
Autophagy and Hsp70 activation alleviate oral epithelial cell death induced by food-derived hypertonicity
Cell Stress Chaperones 2020 Mar;25(2):253-264.PMID:31975220DOI:10.1007/s12192-020-01068-2.
Stable intracellular and intercellular osmolarity is vital for all physiological processes. Although it is the first organ that receives food, the osmolarity around the mouth epithelium has never been systematically investigated. We found that oral epithelial cells are a population of ignored cells routinely exposed to hypertonic environments mainly composed of saline, glucose, etc. in vivo after chewing food. By using cultured oral epithelial cells as an in vitro model, we found that the hypotonic environments caused by both high NaCl and high glucose induced cell death in a dose- and time-dependent manner. Transcriptomics revealed similar expression profiles after high NaCl and high glucose stimulation. Most of the common differentially expressed genes were enriched in "mitophagy" and "autophagy" according to KEGG pathway enrichment analysis. Hypertonic stimulation for 1 to 6 h resulted in autophagosome formation. The activation of autophagy protected cells from high osmolarity-induced cell death. The activation of Hsp70 by the pharmacological activator Handelin significantly improved the cell survival rate after hypertonic stimulation. The protective role of Hsp70 activation was partially dependent on autophagy activation, indicating a crosstalk between Hsp70 and autophagy in hypertonic stress response. The extract of the handelin-containing herb Chrysanthemum indicum significantly protected oral epithelial cells from hypertonic-induced death, providing an inexpensive way to protect against hypertonic-induced oral epithelial damage. In conclusion, the present study emphasized the importance of changes in osmolarity in oral health for the first time. The identification of novel compounds or herbal plant extracts that can activate autophagy or HSPs may contribute to oral health and the food industry.