inhibited NLRP3 expression and inpaired production of TNF-a, IL-6 and nitric oxide
in-vivo (Borges et al. 2017).
16.2.4 Anti-parasitic Effects of Gedunin and Derivatives
Malaria is a vector-borne infectious disease caused by Plasmodium spp. parasitic
protozoan that belongs to the Apicomplexa phylum. Malaria is one of the major
public health problems that negatively impact on social and economy. In 2010, 1.2
million people worldwide were dead due to malaria (Murray et al. 2012). The
situation continues to deteriorate due to the fact that no preventive vaccination
against Plasmodium is available. The control of the disease thus relies heavily on
the treatment with antimalarial medications such as quinine, chloroquine,
sulfadoxine-pyrimethamine and amodiaquine over the decades (Sinha et al. 2014).
Due to massive spreads of antimalarial resistance, alternative therapeutic strategies
are urgently needed.
Gedunin was reported to possess antimalarial activities against Plasmodium falciparum, which accounted for most of the malaria cases worldwide (Khalid et al.
1986). The IC 50 of gedunin was about 1 lM upon 48 h of treatment, which was
comparable to the established antimalarial compound quinine. MacKinnon et al.
(1997) tested the antimalarial activities of gedunin and 9 derivatives isolated from
neem tree against P. falciparum. However, only gedunin exhibited the highest antimalarial activity with the IC 50 of 39 ng/mL against chloroquine-sensitive
P. falciparum clone, which was even higher than chloroquine and quinine
(MacKinnon et al. 1997). On top of that, synergistic study between gedunin and
chloroquine showed that gedunin extracted from the bark and the seed of Khaya
grandifoliola was able to exert synergistic effect when treated together with chloroquine (Bickii et al. 2000). Moreover, gedunin and derivative 7-methoxygedunin were
shown to have synergistic effect when acting together with dillapiol, which is a
commonly known antimalarial compound extracted from dill weed, in the mice
infected with Plasmodium berghei (Omar et al. 2003b). When acting alone,
7-methoxygedunin was able to inhibit the parasite level in infected mice by 67% at
50 mg/kg, while 80% of inhibition was achieved when 25 mg/kg dillapiole was
administered together with the same dose of 7-methoxygedunin (OMAR et al. 2003a).
On the other hand, gedunin and photogedunin have been reported for their
antifilarial activity against parasitic filarial nematodes Brugia malayi. In vitro study
showed that gedunin and photogedunin were active against adult worm (IC 50 of
0.24 and 0.21 lg/mL) comparable to the antiparasitic drug ivermectin (IC 50 of
1.61 lg/mL). In addition, in vivo study showed that gedunin and photogedunin
significantly suppressed the survival of the parasite in jird transplanted model
(Misra et al. 2011). Gedunin inhibited the growth of Babesia bovis, Babesia
bigemina, Babesia caballi and Theleria equi which are the causative agents of
bovine and equine piroplasmosis (Azirwan et al. 2019). Taken together, it is
plausible to mention that gedunin possesses strong antiparasitic activities that is
16 An Overview of the Bioactivities of Gedunin
579
in-vivo (Borges et al. 2017).
16.2.4 Anti-parasitic Effects of Gedunin and Derivatives
Malaria is a vector-borne infectious disease caused by Plasmodium spp. parasitic
protozoan that belongs to the Apicomplexa phylum. Malaria is one of the major
public health problems that negatively impact on social and economy. In 2010, 1.2
million people worldwide were dead due to malaria (Murray et al. 2012). The
situation continues to deteriorate due to the fact that no preventive vaccination
against Plasmodium is available. The control of the disease thus relies heavily on
the treatment with antimalarial medications such as quinine, chloroquine,
sulfadoxine-pyrimethamine and amodiaquine over the decades (Sinha et al. 2014).
Due to massive spreads of antimalarial resistance, alternative therapeutic strategies
are urgently needed.
Gedunin was reported to possess antimalarial activities against Plasmodium falciparum, which accounted for most of the malaria cases worldwide (Khalid et al.
1986). The IC 50 of gedunin was about 1 lM upon 48 h of treatment, which was
comparable to the established antimalarial compound quinine. MacKinnon et al.
(1997) tested the antimalarial activities of gedunin and 9 derivatives isolated from
neem tree against P. falciparum. However, only gedunin exhibited the highest antimalarial activity with the IC 50 of 39 ng/mL against chloroquine-sensitive
P. falciparum clone, which was even higher than chloroquine and quinine
(MacKinnon et al. 1997). On top of that, synergistic study between gedunin and
chloroquine showed that gedunin extracted from the bark and the seed of Khaya
grandifoliola was able to exert synergistic effect when treated together with chloroquine (Bickii et al. 2000). Moreover, gedunin and derivative 7-methoxygedunin were
shown to have synergistic effect when acting together with dillapiol, which is a
commonly known antimalarial compound extracted from dill weed, in the mice
infected with Plasmodium berghei (Omar et al. 2003b). When acting alone,
7-methoxygedunin was able to inhibit the parasite level in infected mice by 67% at
50 mg/kg, while 80% of inhibition was achieved when 25 mg/kg dillapiole was
administered together with the same dose of 7-methoxygedunin (OMAR et al. 2003a).
On the other hand, gedunin and photogedunin have been reported for their
antifilarial activity against parasitic filarial nematodes Brugia malayi. In vitro study
showed that gedunin and photogedunin were active against adult worm (IC 50 of
0.24 and 0.21 lg/mL) comparable to the antiparasitic drug ivermectin (IC 50 of
1.61 lg/mL). In addition, in vivo study showed that gedunin and photogedunin
significantly suppressed the survival of the parasite in jird transplanted model
(Misra et al. 2011). Gedunin inhibited the growth of Babesia bovis, Babesia
bigemina, Babesia caballi and Theleria equi which are the causative agents of
bovine and equine piroplasmosis (Azirwan et al. 2019). Taken together, it is
plausible to mention that gedunin possesses strong antiparasitic activities that is
16 An Overview of the Bioactivities of Gedunin
579