Diterpenoid Lactones with Anti-Inflammatory Effects from the Aerial Parts of Andrographis paniculata

Abstract

Andrographis paniculata (AP) has been widely used in China for centuries to treat various diseases, and especially to treat inflammation. Diterpenoid lactones are the main anti-inflammatory components of AP. However, systematic chemical composition and biological activities, as well as key pharmacophores, of these diterpenoid lactones from AP have not yet been clearly understood. In this study, 17 diterpenoid lactones, including 2 new compounds, were identified by spectroscopic methods, and most of them attenuated the generation of TNF-α and IL-6 in LPS-induced RAW 274.7 cells examined by ELISA. Pharmacophores of diterpenoid lactones responsible for the anti-inflammatory activities were revealed based on the quantitative structure-activity relationship (QSAR) models. Moreover, new compounds (AP-1 and AP-4) exerted anti-inflammatory activity in LPS microinjection-induced zebrafish, which might be correlated with the inhibition of the translocation of NF-κB p65 from cytoplasm to nucleus. Our study provides guidelines for future structure modification and rational drug design of diterpenoid lactones with anti-inflammatory properties in medical chemistry.

Chemical constituents and their biological activities from Taunggyi (Shan state) medicinal plants

“…The mechanism of cell death induced by compound 51 in PANC-1 and PSN-1 cell using microscopical observation, EB/AO double staining, and flow cytometry were also studied in the same report. Compounds 108 and 109 displayed potential anti-inflammatory activities in vitro and in vivo [47]. Furthermore, Hanh et al, 2020 [48], documented that compound 63 (IC 50 31.8, 43.5, 37.9, 45.9, and 42.…”

Screening of Bufadienolides from Toad Venom Identifies Gammabufotalin as a Potential Anti-inflammatory Agent

“…LPS is a typical proinflammatory agent that can trigger an inflammatory response and consequently activate a series of signaling cascades. Our research group initiatively established a zebrafish inflammatory model by microinjecting LPS into the yolk [19], which has been widely used in the rapid screening of anti-inflammatory drugs in vivo [20][21][22]. In this study, the anti-inflammatory effects of 14 bufadienolides at nontoxic doses (1, 4, and 12: 50 µM; 2, 13, and 14: 10 µM; 3 and 6: 5 µM; 5 and 8: 1 µM; 7, 9, and 11: 0.5 µM; 10: 4 µM) were evaluated for the first time using an LPS-stimulated zebrafish inflammatory model.…”

“…Our research group has successfully used these models in studying traditional Chinese medicines on inflammatory diseases [20,34]. Toad venom has been traditionally used for treating infectious and inflammatory diseases in China for thousands of years.…”

“…Larvae at 3 dpf were anesthetized with 0.02 % tricaine and immobilized in a clear petri dish coated with 2 % agarose (Sigma-Aldrich). Subsequently 2 nL of LPS (0.5 mg/mL) were microinjected into the yolks to construct the inflammatory model [19,20] by a cell microinjector (PM1000; MicroData Instrument, Inc.). Next, these larvae were divided randomly into a 24-well plate (n = 20/well) and treated with various bufadienolides.…”

“…Twelve hours after LPS microinjection with or without drug administration, the zebrafish (n = 30) were fixed in 4 % (w/v) paraformaldehyde, dehydrated in graded ethanol, embedded with paraffin (Leica), and cut into 4-µm sections. The specimens were subsequently stained with H&E (Yuanye Biotech) and observed under an IX 53 light microscope (Olympus) [20].…”