Rugosic acid A, derived from Rosa rugosa Thunb., is novel inhibitory agent for NF-κB and IL-6/STAT3 axis in acute lung injury model.

Rosa rugosa Thunb., is as a medicinal plant known for anti-diabetic, and anti-inflammatory activities. However, the specific active compounds responsible for the individual pharmacological effects of in R. rugosa extract (95% EtOH) remain unknown. Here, we hypothesized that terpenoid structure, the most abundant constituents in R. rugosa extract, are responsible for its anti-inflammatory activity. We investigated the phytochemical substituents (compounds 1-13) and newly purified 11-methoxy polisin A, and 13-methoxy bisaborosaol F using NMR and ESI-MS and to screened their effects on NO production in LPS-induced macrophages. Rugosic acid A (RA) induced to ameliorate NO production, iNOS, and pro-inflammatory cytokines associated with the NF-κB. And, RA suppressed IL-6 secretion and IL-6-mediated STAT3 activation in LPS-mediated inflammation. In addition, RA was evaluated in LPS-mediated acute lung injury (ALI) model similar to acute pneumonia. Our results suggested that RA was suppressed to translocate nuclear NF-κB and IL-6-mediated STAT3 activation. Finally, RA led to amelioration of ALI by decreasing myeloperoxidase (MPO) and inhibiting phosphorylation of NF-κB and STAT3. Our group originally found that R. rugosa extract had new methoxy compounds and RA may be alternative natural agent for acute pneumonia similar to severe acute respiratory syndrome by coronavirus.

High-throughput detection of antioxidants in mulberry fruit using correlations between high-resolution mass and activity profiles of chromatographic fractions.

BACKGROUND: Plant extracts contain a huge variety of pharmacologically active substances. Conventionally, various chromatographic methods must be applied several times to purify functional compounds to measure their functional activity. However, conventional purification methods are time-consuming and expensive due to the laborious purification process. Recently, a high-throughput discovery method that replaces such time-consuming purification processes was introduced; this method uses 15 T ultra-high-resolution Fourier transform ion cyclotron resonance mass spectrometry (15 T FT-ICR MS) and a high-throughput screening method. This 15 T FT-ICR MS provides unparalleled resolution and sub-ppm accuracy in mass measurements, while simultaneously detecting multiple compounds without separation. The high-throughput, simultaneous multi-component discovery method known as Scaling of Correlations between Activity and Mass Profiles (SCAMP) was used to detect functional compounds in a plant extract. We validated the performance of SCAMP using 33 fractions from antioxidant-rich mulberry ethyl acetate extract and known standard antioxidants. RESULTS: The mulberry fruit was first separated into 33 fractions by LC and analyzed using high-resolution mass spectrometry. The antioxidative strength of the 33 fractions and standard antioxidants was measured. To validate the efficiency of this antioxidant discovery method, correlations between the antioxidation activity profile and changes in mass intensity of components within the 33 fractions were calculated to provide relative scores for the antioxidant candidate list. Enrichment curves and area under the curve (AUC) values were then calculated to compare the performance of the methods. Using this improved scoring method, five strong antioxidants, chlorogenic acid (14.2 ng), dihydoxy quercetin (46.2 ng), rutin (154.0 ng), quercetin (71.7 ng) and luteolin (3.5 ng) in 2 kg mulberry fruit, were found within the top 20 candidates. CONCLUSIONS: We calculated AUCs in order to compare scoring methods quantitatively. Scoring systems were compared and calculated AUCs, where the AUCs for new scoring systems (0.98 and 0.99) were higher than the previously used correlation coefficient (AUC = 0.89). Using the new scoring algorithms, we successfully enriched thirteen unknown strong antioxidant candidates in addition to known antioxidants, methyl syringin and naringenin (3.5 ng) in mulberry extract. Targeted purification of these unknown candidates will significantly reduce purification time and labor.