a similar study, deoxygedunin appeared to have anti-depression and learning
enhancement effects (Jang et al. 2010).
Huntington disease is a neurological disease characterized by abnormal movements, cognitive dysfunction, and psychiatric disease (Frank 2014). Till date, there
are no treatment to reverse the progression of this disease. A study by Yang and the
team showed that gedunin disaggregated mutant Huntingtin protein in Neuro-2a
cells, endogenous mutant Huntingtin progression and intranuclear inclusions in
Hungtinton disease patients derived cells (Yang et al. 2019).
16.2.3 Anti-inflammatory Effects of Gedunin
Inflammation is an adaptive immune response that underlies myriads of physiological and pathological conditions (Medzhitov 2008). Dysregulated inflammation
plays a crucial role in the development of many cellular and systemic disorders such
as cardiovascular diseases, cancer, neurodegenerative disorders, metabolic syndromes and autoimmune disease. For this reason, researchers have begun to
understand the underlying mechanism of inflammation in order to control or cure
the aforementioned diseases.
Ferraris et al. (2012) showed that pretreatment of gedunin reduced the level of
chemotactic mediators such as CCL2, CCL3, CCL5, CCL11, IL-5 and the lipid
mediator LTB 4 thus impairing the recruitment of eosinophil and T lymphocyte to the
site of inflammation of experimental mice. Subsequent study by Ferraris et al. (2012)
revealed that treatment with gedunin and derivatives in zymosan-induced inflammation experimental model has significantly improved knee edema progression,
reduced neutrophil accumulation and production of inflammation mediators such as
CXCL8/IL-8, IL-1b, IL-6, TNF-a, LBT4 and PGE2 (Conte et al. 2015).
Penido et al. (2005) studied on the anti-inflammatory and analgesic effects of
bioactive compounds from the seeds of Carapa guianensis Aublet, which consist of
gedunin and 6-acetoxygedunin, 7-deacetocy-7-oxogedunin. Orally given tetranortriterpenoids (TNTP) appeared to be able to reduce ovalbumin- and zymosan-induced
edema inflammation and protein extravasation to the site of inflammation in mice. It is
noteworthy that such efficacy of TNTP at 25–100 mg/kg was comparable to that of
commercially available anti-inflammatory drugs such as dexamethasone and
promethazine. Besides, the influx of leukocyte and the increase in inflammation
mediators such as TNF-a, IL-1b, CXCL8/IL-8 and prostaglandin E 2 induced by
various noxious stimuli were markedly observed after the treatment with TNTP
(Penido et al. 2006, 2005). Gedunin derivatives, 7-deacetylgedunin was reported to
reduce ear edema inflammation promoted by 12-O-tetradecanoylphorbol-13-acetate
(TPA) in experimental mice (Akihisa et al. 2009). A continuous investigation by
Akihisa et al. (2017) showed that Salannin and 7-deacetylgedunin reduced the
expression levels of the inducible nitric oxide synthase and cyclooxygenase proteins
in a dose dependent manner (Akihisa et al. 2017). Another study showed that gedunin
578
Y. S. Ong et al.
enhancement effects (Jang et al. 2010).
Huntington disease is a neurological disease characterized by abnormal movements, cognitive dysfunction, and psychiatric disease (Frank 2014). Till date, there
are no treatment to reverse the progression of this disease. A study by Yang and the
team showed that gedunin disaggregated mutant Huntingtin protein in Neuro-2a
cells, endogenous mutant Huntingtin progression and intranuclear inclusions in
Hungtinton disease patients derived cells (Yang et al. 2019).
16.2.3 Anti-inflammatory Effects of Gedunin
Inflammation is an adaptive immune response that underlies myriads of physiological and pathological conditions (Medzhitov 2008). Dysregulated inflammation
plays a crucial role in the development of many cellular and systemic disorders such
as cardiovascular diseases, cancer, neurodegenerative disorders, metabolic syndromes and autoimmune disease. For this reason, researchers have begun to
understand the underlying mechanism of inflammation in order to control or cure
the aforementioned diseases.
Ferraris et al. (2012) showed that pretreatment of gedunin reduced the level of
chemotactic mediators such as CCL2, CCL3, CCL5, CCL11, IL-5 and the lipid
mediator LTB 4 thus impairing the recruitment of eosinophil and T lymphocyte to the
site of inflammation of experimental mice. Subsequent study by Ferraris et al. (2012)
revealed that treatment with gedunin and derivatives in zymosan-induced inflammation experimental model has significantly improved knee edema progression,
reduced neutrophil accumulation and production of inflammation mediators such as
CXCL8/IL-8, IL-1b, IL-6, TNF-a, LBT4 and PGE2 (Conte et al. 2015).
Penido et al. (2005) studied on the anti-inflammatory and analgesic effects of
bioactive compounds from the seeds of Carapa guianensis Aublet, which consist of
gedunin and 6-acetoxygedunin, 7-deacetocy-7-oxogedunin. Orally given tetranortriterpenoids (TNTP) appeared to be able to reduce ovalbumin- and zymosan-induced
edema inflammation and protein extravasation to the site of inflammation in mice. It is
noteworthy that such efficacy of TNTP at 25–100 mg/kg was comparable to that of
commercially available anti-inflammatory drugs such as dexamethasone and
promethazine. Besides, the influx of leukocyte and the increase in inflammation
mediators such as TNF-a, IL-1b, CXCL8/IL-8 and prostaglandin E 2 induced by
various noxious stimuli were markedly observed after the treatment with TNTP
(Penido et al. 2006, 2005). Gedunin derivatives, 7-deacetylgedunin was reported to
reduce ear edema inflammation promoted by 12-O-tetradecanoylphorbol-13-acetate
(TPA) in experimental mice (Akihisa et al. 2009). A continuous investigation by
Akihisa et al. (2017) showed that Salannin and 7-deacetylgedunin reduced the
expression levels of the inducible nitric oxide synthase and cyclooxygenase proteins
in a dose dependent manner (Akihisa et al. 2017). Another study showed that gedunin
578
Y. S. Ong et al.