Daphnetin: A bioactive natural coumarin with diverse therapeutic potentials

Abstract

Daphnetin (DAP), a coumarin derivative extracted from Daphne species, is biologically active phytochemical with copious bioactivities including anti-inflammatory, anti-oxidant, neuroprotective, analgesic, anti-pyretic, anti-malarial, anti-bacterial, anti-arthritic, neuroprotective, hepatoprotective, nephroprotective, and anti-cancer activities. A wide range of studies have been conducted exploring the significance and therapeutic potential of DAP. This study reviewed various databases such as NCBI, PubMed, Web of Science, Scopus and Google Scholar for published research articles regarding the sources, synthesis, and various bioactivities of DAP using different key words, including but not limited to “pharmacological activities,” “sources,” “neuroprotective effect,” “synthesis,” “cancer,” “anti-inflammatory effect” of “daphnetin.” Furthermore, this review encompasses both in-vivo and in-vitro studies on DAP for treating various diseases. A comprehensive review of the literature revealed that the DAP had a promising pharmacological and safety profile, and could be employed as a pharmaceutical moiety to treat a variety of illnesses including microbial infections, cancer, arthritis, hepatic damage, inflammation and neurological anomalies. The current review intends to provide an in-depth focus on all pharmacological activities and therapeutic approaches for the pharmaceutical and biomedical researchers.

Daphnetin Improves Neuropathic Pain by Inhibiting the Expression of Chemokines and Inflammatory Factors in the Spinal Cord and Interfering with Glial Cell Polarization

“…We observed a significant downregulation in both TWT and MWT in rats after the intrathecal injection of daphnetin for 1 h. This effect lasted for 24 h. We reasonably speculated that the intrathecal injection of daphnetin was able to effectively improve NP in rats. The typical inflammatory pathway NF-κB and the release of inflammatory factors mediated by inhibiting the apoptosis proteins (IAPS) and cyclooxygenase-2 (COX-2) were also inhibited by daphnetin [ 16 ]. Some scholars pointed out that daphnetin was able to effectively inhibit the activation of glial cells in the spinal cord in inflammatory pain, which is related to its inhibition of the NF-κB pathway in the spinal cord [ 43 ].…”

“…Daphnetin (Dap), structured as 7,8-dihydroxycoumarin, as detailed in Figure 1 A, is the main active ingredient extracted from Daphne giraldii Nitsche, a plant of the family daphne, with a wealth of biological activities, including anti-inflammatory, antioxidant, neuroprotective, analgesic, and anticancer activities [ 16 ]. Daphnetin significantly inhibits the development of adjuvant arthritis by inhibiting the production of pro-inflammatory cytokines [ 17 ].…”

New Chromones from Bouvardia ternifolia (Cav.) Schltdl with Anti-Inflammatory and Immunomodulatory Activity

“…Scopoletin has been described in various anti-inflammatory and antioxidant activities [ 23 , 24 ], especially in identifying the modulation of NF-κB expression, mediated by Nrf2 [ 25 ], which allows us to suppose that both the extracts and fractions of B. ternifolia have a fully justified anti-inflammatory effect. In the joints, it is observed that the pathophysiological process of RA that developed secondary to the administration of CFA caused a significant increase in the production of TNF-α, IL-6, and IL-1β [ 3 ].…”

“…In the joints, it is observed that the pathophysiological process of RA that developed secondary to the administration of CFA caused a significant increase in the production of TNF-α, IL-6, and IL-1β [ 3 ]. Allthe tested treatments derived from B. ternifolia , M4 could prevent the production of these proinflammatory cytokines, which may be related to ternifolial, which, as already mentioned, has an anti-inflammatory [ 23 , 24 ] and immunomodulatory effect [ 25 ]. Similarly, RA generates a significant increase in IL-17, which is associated with CD4+ T cells that promote inflammation, bone erosion, and cartilage degradation by the stimulating expression of NF-κB-specific activator receptor ligand (RANKL) and produce IL-17, which stimulates synovial macrophages and FLS [ 26 , 27 ] and to plasma cells that also promote inflammation through the production of cytokines and autoantibodies [ 14 , 28 ]; treatments based on extracts and fractions of B. ternifolia decreased the level of IL-17, particularly M3.…”

“…Similarly, RA generates a significant increase in IL-17, which is associated with CD4+ T cells that promote inflammation, bone erosion, and cartilage degradation by the stimulating expression of NF-κB-specific activator receptor ligand (RANKL) and produce IL-17, which stimulates synovial macrophages and FLS [ 26 , 27 ] and to plasma cells that also promote inflammation through the production of cytokines and autoantibodies [ 14 , 28 ]; treatments based on extracts and fractions of B. ternifolia decreased the level of IL-17, particularly M3. The presence of ternifolial, ternifoliol, and scopoletin could be responsible for this anti-IL-17 effect [ 23 , 24 , 25 ]. Regarding the response mediated by IL-10, it should be considered that RAresults from subverted immunological tolerance [ 29 ].…”