Methanol Extract of <i>Xanthium strumarium</i> L. Possesses Anti-inflammatory and Anti-nociceptive Activities

Abstract

Nitric oxides (NOs) and prostaglandins (PGs) are wellknown proinflammatory mediators in the pathogenesis of inflammation.1) NO plays a major role in the regulation of vascular tone, neurotransmission, platelet aggregation, and other homeostatic mechanisms.2) NO is synthesized by the three isoforms of nitric oxide synthase (NOS); neuronal NOS (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS). Although nNOS and eNOS are constitutively expressed, iNOS is expressed in response to interferon-g, lipopolysccharide (LPS), and a variety of proinflammatory cytokines. [3][4][5] The proinflammatory properties of NO are attributed to the excessive production of NO by iNOS and are influenced by factors such as interactions between NO and other oxidants (e.g., peroxynitrite formation with the superoxide anion), the duration of NO production, and substrate availability. A number of studies have shown that the chronic phase of inflammation in particular, is correlated with an increase in iNOS activity. 6) Moreover, elevated levels of NO have been detected in a variety of pathophysiological processes, including circulatory shock, inflammation, and cancer. 5,7,8) Cyclooxygenase (COX) is involved in the inflammatory process and catalyzes the rate-limiting step in the synthesis of prostaglandins from arachidonic acid. COX exists in two isoforms; COX-1 and COX-2. 9) Like nNOS and eNOS, COX-1 is expressed constitutively in most tissues and appears to be responsible for maintaining normal physiological functions. On the other hand, COX-2 is detected in only certain types of tissues and is induced transiently by growth factors, proinflammatory cytokines, tumor promoters, and bacterial toxins. 10,11) LPS is a major inflammatory molecule that triggers the production of proinflammatory cytokines such as TNF-a in various cell types.12,13) TNF-a plays a key role in the induction and perpetuation of inflammation in autoimmune reactions by activating T cells and macrophages, and by up-regulating other proinflammatory cytokines and endothelial adhesion molecules, such as intercellular adhesion molecule 1 and vascular cell adhesion molecule 1, which enhance the recruitment of leukocytes to sites of inflammation. 14)Like a TNF-a, LPS is known to activate transcription factors such as nuclear factor-kappa B (NF-kB)/Rel, activator protein (AP)-1, NF-IL6 and CREB/ATF. These nuclear factors are important for the expressions of numerous genes, which include IL-1b in macrophages. 15,16) Transcription factors belonging to the NF-kB family regulate a range of genes that mediate inflammation and cell survival.17) NF-kB exists in most cells as homodimeric or heterodimeric complexes containing p50 and p65 subunits, and remains inactive in the cytoplasm in association with the NF-kB inhibitory protein Ik B. Moreover, the activation of NF-kB is tightly controlled by a series of inhibitory proteins (IkB-a, IkB-b, and IkB-e) that sequester the NF-kB complex in the cytoplasm and prevent it from binding to nuclear DNA. The pathway of NF-kB induction in res...

In vitro immunomodulating properties of selected Sudanese medicinal plants

“…Furthermore, Singh (1999) reported that fixed oil of Ocimum basilicum possess significant anti-inflammatory activity against carrageenan and different other mediator-induced paw oedema in rats. Recently, Kim et al (2005) reported that the methanolic extract of Xanthium brasilicum semen inhibit nitric oxide, prostaglandin E2, and tumor necrosis factor alpha (TNF-␣) production in RAW 264.7. These anti-inflammatory and/or antioxidant activities, reported for the above mentioned plant species, further support our findings.…”

Inflammation: the foundation of diseases and disorders. A review of phytomedicines of South African origin used to treat pain and inflammatory conditions.

“…In another dimension, NF B plays a critical role in the regulation of genes involved in the expression of proinflammatory enzymes (iNOS, COX-1 and 2, TNF-), suppression of NF B in its binding capacity to DNA by constituents of phytomedicine are likely to reduced the expression of nitric oxide and prostaglandin enzymes (Kim et al, 2005). As mentioned in Table 2, several herbal extracts of South African origin contain complicated mixtures of organic chemicals, including fatty acids, sterols, alkaloids, flavonoids, glycosides, saponins, tannins, and terpenes.…”

PDK1 in NF-κB signaling is a target of Xanthium strumarium methanolic extract-mediated anti-inflammatory activities

“…Thus, it was reported that methanol extract of this plant is able to suppress the expression of inflammatory genes via blockade of NF-κB (Kim et al, 2005). Xanthatin, one of Xanthium strumarium ingredients, was also known to inhibit the synthesis of PGE 2 (Nibret et al, 2011).…”