Search

Background: Datura stramonium L. is widely used across the world for its therapeutic potential to treat inflammatory disorders. The current work was designed to isolate and identify steroidal lactones from D. stramonium leaves and evaluate their anti-inflammatory and analgesic properties., Methods: Several compounds were isolated from D. stramonium leaves and characterized by nuclear magnetic resonance and high-resonance electron spray ionization mass spectrometry techniques. Further, anti-inflammatory properties of these compounds were evaluated by in vitro assays, such as release of NO and pro-inflammatory cytokines by lipopolysaccharide (LPS)-activated J774A.1 macrophages. Using in vivo models, anti-inflammatory and analgesic effects were examined by mouse tail-flick, carrageenan-induced inflammation in rat paw model, vascular permeability in rats, and acetic acid-induced writhing in mice. The docking studies were performed for assessing the binding efficiency of the test compounds with cyclooxygenase-1 (COX-1) and COX-2, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), inducible nitric oxide synthases (iNOS) and nuclear factor-κB (NF-κB)., Results: Three lactones were isolated and confirmed as daturalactone (D1), 12-deoxywithastramonolide (D23), and daturilin (D27). Further, the isolated compounds showed nitric oxide inhibition and pro-inflammatory cytokines released by LPS-activated J774A.1 macrophages. The in vivo results suggest that D1, D23 and D27 (20 mg/kg) were able to reduce the pain and inflammation in various animal models. The docking analysis showed that these three compounds actively bind with COX-1, COX-2, LOX-1, NF-κB, and iNOS, validating the anti-inflammatory effects of the lactones., Conclusion: These findings demonstrate substantial anti-inflammatory and analgesic properties of D. stramonium-derived lactones and their potential as anti-inflammatory agents to treat chronic inflammatory ailments., (Copyright © 2021. Published by Elsevier GmbH.)

Datura stramonium L. is an important Ayurvedic herb of the nightshade family (Solanaceae) used in the treatment of innumerable diseases for centuries. Previously, we reported the isolation of three steroidal lactones (Daturalactone (D1), 12-Deoxywithastramonalide (D23), and Daturilin (D27) from D. stramonium L. The present study was designed to evaluate in vitro immunomodulatory potential of these lactones on human peripheral blood mononuclear cells (PBMC). The data revealed that the lactones from D. stramonium significantly enhanced the proliferation of the human PBMC and increased the IL-2, IFN-γ, and TNF-α secretion. Flow cytometry data showed a significant up-regulation of CD3, CD8, and CD56 expression on PBMC. Enhanced intracellular granulysin expression was also observed in Datura lactones treated PBMC. Granulysin is an immunomarker and enhanced expression of granulysin depict activation of Cytotoxic T Lymphocytes and Natural Killer cells. Further, the micro-cytotoxicity assay was performed by co-culturing lactone-activated lymphocytes and target cells (colon cancer cells; HCT-116 and SW620, and pancreatic cancer cells; Panc-1 cells). The human PBMC activated with the lactones exhibited enhanced cancer cell death as compared to the untreated PBMC. It was found that the D27-treated lymphocytes showed higher cancer-killing potential as compared to D1- or D23-activated immune cells. Additionally, mechanistic studies showed that the stimulated lymphocytes enhanced ROS production and loss of mitochondrial membrane potential in the target cancer cells. The current study showed immuno-potentiating effects of D. stramonium lactones on human PBMC. [ABSTRACT FROM AUTHOR]

The current study deals with the investigation of the antioxidant, anti-inflammatory and immunomodulatory properties of the essential oil from Datura stramonium leaves (D. oil). The GC-MS analysis showed that the dominant compounds present in the D. oil were neophytadiene (Phytol acetate) (10.76%), β-damascenone (9.67%), and β- eudesmol (7.2%). D. oil exhibited in vitro scavenging potential of free radicals by DPPH and ABTS assays (IC50 values 71.35 ±1.06 μg/ml and 61.01 ± 1.07 μg/ml, respectively). We found that D. oil decreased the nitric oxide production in LPS-stimulated J774A.1 cells by 52.43% without affecting their cell viability. D. oil was found to stimulate the proliferation of human peripheral blood mononuclear cells (PBMC) and, also enhanced the secretion of IL-2, IFN-γ and TNF-α. Furthermore, D. oil treatment of PBMC induced the expression of CD3, CD8, and CD56 and intracellular granulysin levels in the immune cells. The treatment of human lymphocytes by D. oil enhanced their ability to kill colon cancer cells HCT-116 (51.09 ± 7.5%) and SW620 (48.57 ± 8.08%) at 20:1 (effector: target ratio). Moreover, these activated lymphocytes cause target cell death by reactive oxygen species and by damaging mitochondrial membrane potential of these cells. Taken together, the current findings showed D. oil as immunotherapeutic agent which can be used for colon cancer treatment. [ABSTRACT FROM AUTHOR]