This product is isolated and purified from the herb of Galium aparine L.
[5-(Hexopyranosyloxy)-1-oxo-2a,4a,5,7b-tetrahydro-1H-2,6-dioxacyclopenta[cd]inden-4-yl]methyl acetate/Asperulosid/RUBICHLORIC ACID/ASPERULOSIDE/1H-2,6-Dioxacyclopent[cd]inden-1-one, 4-[(acetyloxy)methyl]-5-(hexopyranosyloxy)-2a,4a,5,7b-tetrahydro-
Nat Prod Res. 2014;28(8):586-8. Monoterpenoids glycosides content from two Mediterranean populations of Crucianella maritima L.[Pubmed: 24499293]METHODS AND RESULTS:In this study, the iridoidic content of two accessions of Crucianella maritima L., one from Sardinia and the second from Latium, was examined and compared. From a qualitative point of view, the iridoidic pattern of the two samples was similar, since the same compounds (Asperuloside, asperulosidic acid and deacetyl asperulosidic acid) were isolated. Asperuloside was the main compound in both accessions. Asperulosidic acid was the second compound in the accession from Sardinia, while the accession from Latium exhibited a similar amount of asperulosidic acid and deacetyl asperulosidic acid.CONCLUSIONS: These iridoids can be considered as chemotaxonomic markers for parts of the Rubiaceae family, in particular for the Rubioideae subfamily to which C. maritima belongs.
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Acute myeloid leukemia (AML) is a complicated disease of hematopoietic stem cell disorders. However, its pathogenesis mechanisms and therapeutic treatments still remain vague. Asperuloside (ASP) is an iridoid glycoside found in Herba Paederiae, and is a component from traditional Chinese herbal medicine. ASP has been suggested to have various pharmacological activities, such as anti-tumor and anti-inflammation. In this study, we explored the effects of ASP on apoptosis and endoplasmic reticulum (ER) stress in human leukemia cells and in human primary leukemia blasts. ASP treatments selectively reduced the cell viability of human leukemia cells and primary leukemia blasts in a dose-dependent manner. We also found that ASP induced cell death via promoting the cleavage of Caspase-9, -3 and poly (ADP-ribose) polymerase (PARP), which was along with the loss of mitochondrial membrane potential and Cyto-c release from the mitochondria. In addition, we found that ASP significantly induced ER stress in leukemia cells by improving the protein expression levels of glucose-regulated protein of 78 kDa (GRP78), phosphorylated protein kinase RNA-like ER kinase (PERK), phosphorylated eukaryotic translation initiation factor 2 alpha (eIF2α), C/EBP homologous protein (CHOP), phosphorylated inositol-requiring enzyme 1 (p-IRE1), X-box binding protein 1 (XBP1), activating transcription factor-6 (ATF6) and cleaved Caspase-12. Moreover, ER stress suppression markedly abrogated ASP-induced apoptosis. In addition, GRP78 knockdown significantly diminished ER stress and apoptosis triggered by ASP. Importantly, co-immunoprecipitation (IP) analysis further indicated that ASP regulated the interaction between GRP78 and PERK, subsequently meditating the apoptotic cell death. In vivo leukemia xenografts finally validated ER stress and apoptosis were related to the tumor growth reduction induced by ASP. The overall survival of mice was also improved by ASP treatments, accompanied with the significantly reduced number of white blood cells and elevated red blood cells. Together, our present results showed that ASP exerted anti-leukemic effects at least partially via inducing apoptosis regulated by ER stress, and suggested that ASP might be a novel and effective therapeutic strategy for treating human leukemia.
Acute myeloid leukemia (AML); Apoptosis; Asperuloside (ASP); ER stress; GRP78 and PERK.
Asperuloside Exhibits a Novel Anti-Leukemic Activity by Triggering ER Stress-Regulated Apoptosis via Targeting GRP78
Chao Rong 1 , Wu Wei 2 , Tian Yu-Hong 3
Eucommia leaves (Eucommia ulmoides Oliver) contain chlorogenic acid (a caffeic acid derivative) and geniposidic acid and asperuloside (ASP), iridoid glucosides used in beverages. We used a metabolic syndrome rat model, produced by feeding a 35 % high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of ASP. These effects were compared with Eucommia leaf extract (ELE), the positive control, which exhibits anti-obesity effects. A total of six rats were studied for 3 months in five groups. ASP suppressed body weight, visceral fat weight, food intake and circulating levels of glucose, insulin and lipids, and increased the plasma adiponectin level in rats on a HFD. These effects are similar to those of ELE, except for the influence on the plasma glucose level. RT-PCR studies showed that ASP (like ELE with known anti-obesity effects) diminished isocitrate dehydrogenase 3α, NADH dehydrogenase flavoprotein 1 (Comp I) mRNA and fatty acid synthase levels (white adipose tissue), increased carnitine palmitoyltransferase 1α and acyl-CoA dehydrogenase, very-long-chain mRNA levels (liver), and increased Glut4, citrate synthase, isocitrate dehydrogenase 3α, succinyl CoA synthase, peroxisomal 3-ketoacyl-CoA thiolase, dihydrolipoamide succinyl transferase and succinate dehydrogenase mRNA levels (skeletal muscle) under HFD conditions. Interestingly, ASP administration resulted in significantly increased mRNA levels of uncoupling protein 1 (UCP1) in the brown adipose tissue of HFD-fed rats; ELE did not affect the expression of UCP1. The increased expression of UCP1 may be negated by many ingredients other than ASP in the ELE. These findings suggest that chronic administration of ASP stimulates anti-obesity and anti-metabolic syndrome activity in HFD-fed rats across several organs, similar to ELE administration; thus, ASP may be an important ingredient of ELE.
ASP, asperuloside; BAT, brown adipose tissue; Acadvl, acyl-CoA dehydrogenase, very long chain; Anti-obesity effects; Asperuloside; CHA, chlorogenic acid; Comp I, NADH dehydrogenase flavoprotein 1; Comp IV, cytochrome c oxidase, subunit 4a; Cpt1α, carnitine palmitoyltransferase 1α; Cs, citrate synthase; ELE, Eucommia leaf extract; Eucommia ulmoides Oliver; FA, fatty acid; Fas, fatty acid synthase; GEA, geniposidic acid; HFD, high-fat diet; Idh3α, isocitrate dehydrogenase 3α; Metabolic function; Ogdh, dihydrolipoamide succinyl transferase; Sol. M., soleus muscle; UCP, uncoupling protein; WAT, white adipose tissue.
Asperuloside Stimulates Metabolic Function in Rats Across Several Organs Under High-Fat Diet Conditions, Acting Like the Major Ingredient of Eucommia Leaves With Anti-Obesity Activity
Takahiko Fujikawa 1 , Tetsuya Hirata 2 , Shingo Hosoo 2 , Kenji Nakajima 2 , Atsunori Wada 2 , Yutaka Yurugi 3 , Hideaki Soya 4 , Takashi Matsui 4 , Akihiko Yamaguchi 5 , Masato Ogata 6 , Sansei Nishibe 7
2012 Sep 5
Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine. In this study, we aimed to investigate the protective effects and potential mechanisms of asperuloside action on inflammatory responses in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells and an LPS-induced lung injury model. The pro-inflammatory cytokines and signaling pathways were measured by enzyme-linked immunosorbent assays (ELISA) and Western blotting to determine the effects of asperuloside. We found that asperuloside can significantly downregulate tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 levels in vitro and in vivo, and treatment with asperuloside significantly reduced the lung wet-to-dry weight, histological alterations and myeloperoxidase activity in a murine model of LPS-induced acute lung injury (ALI). In addition, Western blot analysis that pretreatment with asperuloside remarkably blunted the phosphorylation of inhibitor of nuclear factor kappa-B (IκBα), extracellular signal-related kinases 1 and 2 (ERK1/2), c-Jun. N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) in LPS-stimulated inflammation. These results indicate that asperuloside exerts its anti-inflammatory effect in correlation with inhibition of a pro-inflammatory mediator through suppressing nuclear factor kappa-B (NF-κB) nuclear translocation and MAPK phosphorylation in a dose-dependent manner.
Acute lung injury; Asperuloside; Cytokines; Lipopolysaccharide; MAPKs; NF-κB.
Pretreatment With the Compound Asperuloside Decreases Acute Lung Injury via Inhibiting MAPK and NF-κB Signaling in a Murine Model
Jiaming Qiu 1 , Gefu Chi 2 , Qianchao Wu 1 , Yanlei Ren 3 , Chengzhen Chen 4 , Haihua Feng 5