Burning bush

The bioactives that are fairly unique to Euonymus Alatus include:

• Three glycosides of Cardenolide where the 3-carbon is attached by Rhamnose (To give Acovenosigenin A 3-O-α-L-rhamnopyranoside), Rhamnose attached to a Glucose (the diglycoside known as Euonymoside A), and then a triglycoside of Rhamnose with two glucose sugars in a chain (Euonymusoside A)^[3]
• 2-{1-(Hydroxy methyl)-4-hydroxy-3,5-dimethoxy-phenyl}-propan-1,3-diol (1.8% ethanol extract), 5R,6S-6,9,10-trihydroxy-megastigma-7-en-3-one (2.25% ethanolic extract) and 2-{4-(3-Hydroxy-propenyl)-3,5-dimethoxy-phenyl}-propane-1,3-diol;^[4]

With more common bioactives (found in many herbs) being:

• 5-caffeoylquinic acid (Chlorogenic Acid) from the stems^[5][5] at 4.5% of an 80% ethanolic extract;^[4] also the metabolite 3,4-dihydroxycinnamic acid (caffeic acid)^[6]
• Lignan compounds including (+)-syringaresinol and De-4′-methylyangabin^[7]
• Sesquilignans Hedyotol C and threo-buddlenol B^[7]
• Dilignans Hedyotisol C and Hedyotisol B^[7]
• Neolignans such as (−)- and (+)- simulanol, (-)- and (+)-dihydrodehyrodiconiferyl alcohol, and guaiacylglycerol-8-O-4′-(coniferyl alcohol) ether (both 7R,8S and 7S,8R configurations)^[7]
• Grasshopper ketone (2.55% methanolic extract)^[4]
• Syringin (2.65% methanolic extract)^[4]
• (+)-usnic acid and benzoic acids^[8]
• Quercetin at 0.011-0.016mg/g (50% ethanolic extract),^[9] Quercetin-3-O-D-galactopyronoside at 5.5% ethanolic extract,^[4] and Rutin at 0.265-0.275mg/g of the 50% ethanolic extract (seems to be best to concentrate Quercetin structures from E.Alatus).^[9] The related Quercetin structures Hyperoside and Quercitrin have also been isolated from this plant, as well as Quercetin 3,7-dirhamnoside^[10]
• Kaempferol^[11] and its 3,7-dirhamnoside Kaempferitrin^[10]
• Apigenin-3-O-L-rhamnopyranoside^[4]
• Catechin, dehydrodicatechin A, and catechin lactone A^[10]
• Daucosterol^[8]
• Symplocoside^[10]
• Taxifolin^[4]
• Naringenin^[4]
• Aromadendrin,^[4] which may fluctuate wildly^[12]

The total flavonoid content of Euonymus Alatus is 235.7mg/kg fresh weight.^[13]

Euonymus Alatus extract appears to be effective in inhibiting the aromatase enzyme in myometrial and leiomyomal cells (uterus related).^[14] Whether it affects other aromatase enzymes is not known, but if it does it may increase circulating testosterone levels.

Some flavonoid compounds from Euonymus Alatus appear to prevent triglyceride accumulation into differentiating 3T3-L1 adipocytes, with most potency at 25uM concentration coming from quercetin 3,7-dirhamnoside (79.1% of control; set at 100%), hyperoside (71.3%), kaempferitrin (62.3%), catechin lactone A (79.9%) and dehydrodicatechin A (70.2%);^[10] hyperoside has been reported with this inhibitory potency previously^[15] but may not be the consensus due to differing data elsewhere.^[16][17] The potency of these compounds is comparable to 25uM of resveratrol, with kaempferitrin trending to be more potent.^[10]

Both Kaempferol and Quercetin in Euonymus Alatus appear to be able to bind to the PPARγ receptor too weakly to induce adipocyte proliferation, and may block the pro-adipogenic effects of PPARγ agonists such as Rosiglitazone due to higher affinity (thus acting as receptor modulators).^[11] Despite these mechanisms, both appear to enhance glucose uptake into adipocytes.^[11]

Euonymus alatus methanolic extract has inhibitory potential on the α-glucosidase enzyme with an IC₅₀ value of 272µg/mL (in a yeast assay),^[18] and of 8 compounds purified from the plant for interactions with the α-glucosidase noted that 6 compounds had more efficacy than the active control Arcabose (IC₅₀ 679.7µM) including catechin (119.1µM), quercetin 3,7-dirhamnoside (39.6µM), hyperoside (31.6µM), kaempferitrin (23.0µM), catechin lactone A (71.8µM) and dehydrodicatechin A (102.5µM).^[10] Another compound (quercitrin) was found inactive on this assay^[10] but has been noted elsewhere to have an IC₅₀ of 38.4 µM.^[19]

Components have inhibitory potential on alpha-glucosidase, a carbohydrate digestive enzyme

When 500mg/kg of Euonymus Alatus (methanolic extract) is given to rats alongside a 1g/kg bolus of starch and having blood measured for the next 4 hours, supplementation was able to reduce the subsequent AUC of glucose by 25.5% relative to starch control;^[18] fecal analysis was not performed.

Inhibition of starch absorption has been noted to occur in rats following concomitant ingestion of Euonymus Alatus and starch

17.2mg/kg of an ethyl acetate fraction with a high flavonoid concentration (bioequivalent to 400mg/kg dry weight) is able to, over 7 days, reduce fasting blood glucose slightly in normal mice and more significantly in alloxan-induced diabetic mice; either of equal potency to or lesser than the active control of 140mg/kg Metformin (relatively low dose of Metformin).^[20] Over 4 weeks, this extraction was more effective than 140mg/kg Metformin in reducing fasting blood glucose in Alloxan-induced diabetic mice.^[20] One other study compared Euonymus Alatus (700mg/kg ethanolic extract) against Metformin (250mg/kg) and noted that while both were effective in reducing fasting blood glucose that Metformin was more potent.^[2]

Euonymus Alatus (80% methanolic extract) can inhibit NF-kB activation at 10-30ug/mL with an IC₅₀ of IC₅₀ value of 11.83μg/mL, via inhibiting the IKKβ pathway.^[21] Anti-inflammatory effects in this same in vitro model (RAW264.7 macrophage activation via LPS) have been noted to occur with all lignan compounds that were not dilignans^[7] (although flavonoids and isoprenoids may also be active^[4]) and the methanolic extract also appears to inhibit JNK1 (40.6%), JNK2 (28.7%), and JNK3 (32.9%) activation.^[21]

General anti-inflammatory properties in macrophage stimulation tests

At least one study has noted that, without incubation with LPS or another pro-inflammatory insult, that Euonymus Alatus was able to increase NF-kB activity and inflammatory biomarkers vicariously though recombinant IFNγ.^[22]

In cultured rat hepatocytes (liver cells) Euonymus Alatus appears to both exert direct anti-oxidant abilities and enhance anti-oxidant enzymes.^[23]