Screening of Vietnamese medicinal plants for NF-κB signaling inhibitors: Assessing the activity of flavonoids from the stem bark of Oroxylum indicum

AbstractEthnopharmacological relevanceSeventeen plants used in Vietnamese traditional medicine for the treatment of inflammatory disorders were screened for NF-κB inhibitory activity. Oroxylum indicum, which exhibited activity, was investigated in detail.Materials and methodsForty plant extracts from 17 species were prepared by maceration using dichloromethane and methanol and were tested (10µg/mL) to evaluate their ability to inhibit NF-κB activation using TNF-α-stimulated HEK-293 cells stably transfected with a NF-κB-driven luciferase reporter. The active extract of Oroxylum indicum was subsequently fractionated by different chromatographic techniques. After isolation, all single compounds were identified by spectroscopic methods and assessed for NF-κB inhibitory effects.ResultsThe dichloromethane extracts obtained from Chromolaena odorata leaves and the stem bark of Oroxylum indicum showed distinct inhibitory effects on NF-κB activation at a concentration of 10µg/mL. The active extract of Oroxylum indicum was subjected to further phytochemical studies resulting in identification of four flavonoid aglyca and six flavonoid glycosides. Pharmacological evaluation of the obtained compounds identified oroxylin A as the most active substance (IC50=3.9µM, 95% CI: 3.5–4.4µM), while chrysin and hispidulin showed lower activity with IC50=7.2µM (95% CI: 6.0–8.8µM) and 9.0µM (95% CI: 7.9–10.2µM), respectively. Interestingly, in this study the activity of baicalein (IC50=28.1µM, 95% CI: 24.6–32.0µM) was weak. The isolated glycosides showed no inhibitory activity when tested at a concentration of 30µM. Quantification of the four active flavonoids in extracts and plant materials suggested that oroxylin A contributes to the NF-κB inhibitory activity of the stem barks of Oroxylum indicum to a greater extent than baicalein which was thought to be responsible for the anti-inflammatory activity of this plant.ConclusionsThe screening presented in this study identified the dichloromethane extracts of Chromolaena odorata and Oroxylum indicum as promising sources for NF-κB inhibitors. Hispidulin, baicalein, chrysin and oroxylin A, isolated from Oroxylum indicum, were identified as inhibitors of NF- κB activation

Identification and characterization of [6]-shogaol from ginger as inhibitor of vascular smooth muscle cell proliferation

Scope Vascular smooth muscle cell (VSMC) proliferation is involved in the pathogenesis of cardiovascular disease, making the identification of new counteracting agents and their mechanisms of action relevant. Ginger and its constituents have been reported to improve cardiovascular health, but no studies exist addressing a potential interference with VSMC proliferation. Methods and results The dichloromethane extract of ginger inhibited VSMC proliferation when monitored by resazurin metabolic conversion (IC50 = 2.5 μg/mL). The examination of major constituents from ginger yielded [6]-shogaol as the most active compound (IC50 = 2.7 μM). In the tested concentration range [6]-shogaol did not exhibit cytotoxicity toward VSMC and did not interfere with endothelial cell proliferation. [6]-shogaol inhibited DNA synthesis and induced accumulation of the VSMC in the G0/G1 cell-cycle phase accompanied with activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2)/HO-1 pathway. Since [6]-shogaol lost its antiproliferative activity in the presence of the heme oxygenase-1 (HO-1) inhibitor tin protoporphyrin IX, HO-1 induction appears to contribute to the antiproliferative effect. Conclusion This study demonstrates for the first time inhibitory potential of ginger constituents on VSMC proliferation. The presented data suggest that [6]-shogaol exerts its antiproliferative effect through accumulation of cells in the G0/G1 cell-cycle phase associated with activation of the Nrf2/HO-1 pathway

Xanthohumol attenuates tumour cell-mediated breaching of the lymphendothelial barrier and prevents intravasation and metastasis

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In vitro characterisation of the anti-intravasative properties of the marine product heteronemin

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Lignan Derivatives from Krameria lappacea Roots Inhibit Acute Inflammation in Vivo and Pro-inflammatory Mediators in Vitro

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (111) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID50 77 \u3bcg/cm2) as well compounds 111 (ID50 0.310.60 \u3bcmol/cm2) exhibited topical antiedematous properties comparable to those of indomethacin (ID50 0.29 \u3bcmol/cm2) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NFkB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E2 synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug

Polyyne Hybrid Compounds from Notopterygium incisum with Peroxisome Proliferator-Activated Receptor Gamma Agonistic Effects

[Image: see text] In the search for peroxisome proliferator-activated receptor gamma (PPARγ) active constituents from the roots and rhizomes of Notopterygium incisum, 11 new polyacetylene derivatives (1–11) were isolated. Their structures were elucidated by NMR and HRESIMS as new polyyne hybrid molecules of falcarindiol with sesquiterpenoid or phenylpropanoid moieties, named notoethers A–H (1–8) and notoincisols A–C (9–11), respectively. Notoincisol B (10) and notoincisol C (11) represent two new carbon skeletons. When tested for PPARγ activation in a luciferase reporter assay with HEK-293 cells, notoethers A–C (1–3), notoincisol A (9), and notoincisol B (10) showed promising agonistic activity (EC(50) values of 1.7 to 2.3 μM). In addition, notoincisol A (9) exhibited inhibitory activity on NO production of stimulated RAW 264.7 macrophages