Asperuloside

Int. Immunopharmacol., 2016 Feb;31:109-15.

Pretreatment with the compound asperuloside decreases acute lung injury via inhibiting MAPK and NF-κB signaling in a murine model.[Pubmed: 26710167 ]

Asperuloside, an iridoid glycoside found in Herba Paederiae, is a component from traditional Chinese herbal medicine.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

Int J Mol Sci . 2018 Jul 12;19(7):2027.

Asperuloside and Asperulosidic Acid Exert an Anti-Inflammatory Effect via Suppression of the NF-κB and MAPK Signaling Pathways in LPS-Induced RAW 264.7 Macrophages[Pubmed: 30002289 ]

Abstract Hedyotis diffusa is a folk herb that is used for treating inflammation-related diseases in Asia. Previous studies have found that iridoids in H. diffusa play an important role in its anti-inflammatory activity. This study aimed to investigate the anti-inflammatory effect and potential mechanism of five iridoids (Asperuloside (ASP), asperulosidic acid (ASPA), desacetyl asperulosidic acid (DAA), scandoside methyl ester (SME), and E-6-O-p-coumaroyl scandoside methyl ester (CSME)) that are presented in H. diffusa using lipopolysaccharide (LPS)-induced RAW 264.7 cells. ASP and ASPA significantly decreased the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in parallel with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), TNF-α, and IL-6 mRNA expression in LPS-induced RAW 264.7 cells. ASP treatment suppressed the phosphorylation of the inhibitors of nuclear factor-kappaB alpha (IκB-α), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). The inhibitory effect of ASPA was similar to that of ASP, except for p38 phosphorylation. In summary, the anti-inflammatory effects of ASP and ASPA are related to the inhibition of inflammatory cytokines and mediators via suppression of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways, which provides scientific evidence for the potential application of H. diffusa. Keywords: anti-inflammation; iridoids; mitogen-activated protein kinase; nuclear factor-kappaB.

J Nutr Sci. 2012 Sep 5;1:e10.

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.[Pubmed: 25191539]

Eucommia leaves (Eucommia ulmoides Oliver) contain chlorogenic acid (a caffeic acid derivative) and geniposidic acid and Asperuloside (ASP), iridoid glucosides used in beverages.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.

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.