In another study, Sharma et al. (2014) proved the synergistic effect sub-lethal
dose of ethanolic neem leaf extract and cisplatin in reducing the viability of breast
(MCF-7) and cervical (HeLa) cancer cells compared to individual compound alone.
It was reported that 1 µM of cisplatin used in combination with 50–100 µg/mL
neem leaf extract resulted in a significant (71–82%) reduction of MCF-7 cells as
compared to the compounds alone (85–93.1%). The calculated Combinational
indices (CI) in the studies were reported to be <1, indicating a synergistic interaction
between the two drugs at their respective treatment dosage (Sharma et al. 2014).
16.2.2 Anti-neurological Disorders and Cryoprotective
Effects of Gedunin
Neurodegeneration is a progressive deterioration of neuronal structures and functions resulting to cognitive disability and dementia primarily affecting aging population (Ramanan and Saykin 2013). Alzheimer’s disease, Parkinson's disease,
Amyotrophic lateral sclerosis and Hungtington disease are the few commonly
known neurodegenerative disorders. These diseases remain uncured despite
extensive basic research and drug discovery to ameliorate the conditions. Some
research showed that gedunin and its derivatives were able to protect the neurons
against b-amyloid (Ab) and other stressors.
It is widely known that the accumulation of Ab oligomers or fibrils contributes
to neurodegenerative pathology in Alzheimer’s disease (Murphy and LeVine 2010).
Gedunin significantly suppressed the cell death in neuronal cells subjected to Ab
cytotoxicity (Lu et al. 2009). Gedunin derivatives, deacetylgedunin,
deacetoxy-7-oxogedunin and deoxygedunin are the HSF1/Hsp70 activators and
thus protecting neuronal cells from cell death induced by MG-132 cytotoxicity
(Zhang et al. 2009). Recent study by Tom and his colleagues demonstrated that
gedunin inhibited Ab 1-42 -induced NF-jB activation, the expression of nitric oxide
and IL-1b level (Tom et al. 2019).
Brain-derived neurotrophic factors (BDNF) are a family of neurotrophins that
plays an essential role in the maintenance of central nervous system (Thoenen
1991). BDNF binds to transmembrane TrkB receptor and activates downstream
signaling cascades that are responsible for a variety of neuronal protections against
ischemic injury, glutamate toxicity, and programmed cell death (Leeds et al. 2005;
Lindholm et al. 1993; Schabitz et al. 2000). Smirnova et al. (2011) reported that
gedunin was able to rescue neuronal cells from the cell death caused by glutamate
and its analog by acting as a direct activator of NF-E2-related factor 2 (Nrf2), a
transcriptional regulator of cellular detoxification and antioxidant defense.
Deoxygedunin has been reported as an agonist of BDNF by eliciting the strongest
stimulatory effect on TrkB signaling cascades and executing neuronal protection
against cell death induced by oxygen–glucose deprivation (OGD) and glutamate. In
16 An Overview of the Bioactivities of Gedunin
577
dose of ethanolic neem leaf extract and cisplatin in reducing the viability of breast
(MCF-7) and cervical (HeLa) cancer cells compared to individual compound alone.
It was reported that 1 µM of cisplatin used in combination with 50–100 µg/mL
neem leaf extract resulted in a significant (71–82%) reduction of MCF-7 cells as
compared to the compounds alone (85–93.1%). The calculated Combinational
indices (CI) in the studies were reported to be <1, indicating a synergistic interaction
between the two drugs at their respective treatment dosage (Sharma et al. 2014).
16.2.2 Anti-neurological Disorders and Cryoprotective
Effects of Gedunin
Neurodegeneration is a progressive deterioration of neuronal structures and functions resulting to cognitive disability and dementia primarily affecting aging population (Ramanan and Saykin 2013). Alzheimer’s disease, Parkinson's disease,
Amyotrophic lateral sclerosis and Hungtington disease are the few commonly
known neurodegenerative disorders. These diseases remain uncured despite
extensive basic research and drug discovery to ameliorate the conditions. Some
research showed that gedunin and its derivatives were able to protect the neurons
against b-amyloid (Ab) and other stressors.
It is widely known that the accumulation of Ab oligomers or fibrils contributes
to neurodegenerative pathology in Alzheimer’s disease (Murphy and LeVine 2010).
Gedunin significantly suppressed the cell death in neuronal cells subjected to Ab
cytotoxicity (Lu et al. 2009). Gedunin derivatives, deacetylgedunin,
deacetoxy-7-oxogedunin and deoxygedunin are the HSF1/Hsp70 activators and
thus protecting neuronal cells from cell death induced by MG-132 cytotoxicity
(Zhang et al. 2009). Recent study by Tom and his colleagues demonstrated that
gedunin inhibited Ab 1-42 -induced NF-jB activation, the expression of nitric oxide
and IL-1b level (Tom et al. 2019).
Brain-derived neurotrophic factors (BDNF) are a family of neurotrophins that
plays an essential role in the maintenance of central nervous system (Thoenen
1991). BDNF binds to transmembrane TrkB receptor and activates downstream
signaling cascades that are responsible for a variety of neuronal protections against
ischemic injury, glutamate toxicity, and programmed cell death (Leeds et al. 2005;
Lindholm et al. 1993; Schabitz et al. 2000). Smirnova et al. (2011) reported that
gedunin was able to rescue neuronal cells from the cell death caused by glutamate
and its analog by acting as a direct activator of NF-E2-related factor 2 (Nrf2), a
transcriptional regulator of cellular detoxification and antioxidant defense.
Deoxygedunin has been reported as an agonist of BDNF by eliciting the strongest
stimulatory effect on TrkB signaling cascades and executing neuronal protection
against cell death induced by oxygen–glucose deprivation (OGD) and glutamate. In
16 An Overview of the Bioactivities of Gedunin
577