the larval growth inhibitory effects of gedunin derivative, 6b-hydroxygedunin,
against the gram pod borer, Helicoverpa armigera (Hubner) and the Asian armyworm, Spodoptera litura (Fabricius). The 6b-hydroxygedunin inhibited the growth
of the larvae by 50% at a concentration 21.5 lg/mL. Interestingly, the efficacy of
6b-hydroxygedunin was two-fold greater than gedunin. In addition, gedunin and
deacetylgedunin were tested against Anopheles stephensi which is the major vector
of malaria. Nathan et al. (2005) reported that deacetylgedunin possessed high
inhibitory activity against the growth of larvae, pupae and adult as well as the
production of egg of A. stephensi. However, the mechanisms of the insecticidal,
repellent and growth inhibitory of these compounds are not well understood.
16.3 Commercial Potential of Gedunin
Considering the multiple therapeutic effects of gedunin that have been reported in
the literature, it is not surprised that patents have been registered for gedunin and its
derivatives. Thus far, Vinson-Hieronymus et al. (2011) has patented gedunin and its
derivatives (publication number: US 2011/0,263,693 A1), together with celastrol to
inhibit Hsp90. As mentioned earlier, Hsp90 is a multitasking molecule that governs
the maturation of an array of diverse cellular functions. It is also a specific client
protein that acts as signal transducers implicated in the molecular mechanisms of
normal cellular biology, disease and evolutionary processes (Kaplan and Li 2012).
Thus, by inhibiting Hsp90, pathological processes like cancer and inflammation can
thus be suppressed (Kaplan and Li 2012; Chatterjee et al. 2007). On the other hand,
gedunin has been patented as a substrate of polymeric wound care material (publication number: US 2013/0,209,534 A1) for its antimicrobial properties and the
ability to aid in wound healing. The neuroprotective effects of gedunin and a
number of limonoids have also granted the inventor Steiner and colleagues a patent
(publication number: US 2010/0,056,617 A1) disclosing the method of preparation
and the utilization of these compounds.
16.4 Conclusion and Gaps of Knowledge
The tremendous robust evidences to date have shown that gedunin and its
derivative possess multiple therapeutic effects including anti-cancer,
anti-inflammatory, anti-parasitic, antimicrobial and insect growth inhibition.
However, most of the studies are limited to in vitro phase with or without the
comparison to commercialized drugs. We thus look forward to have extensive
animal model-based evidences in order to understand how gedunin and its
derivatives work in in vivo systems. This will then fill the gaps of the pharmacological understandings of gedunin and its derivative such as bioavailability, pharmacokinetics and pharmacodynamics. Nonetheless, toxicology screening is yet to
16 An Overview of the Bioactivities of Gedunin
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against the gram pod borer, Helicoverpa armigera (Hubner) and the Asian armyworm, Spodoptera litura (Fabricius). The 6b-hydroxygedunin inhibited the growth
of the larvae by 50% at a concentration 21.5 lg/mL. Interestingly, the efficacy of
6b-hydroxygedunin was two-fold greater than gedunin. In addition, gedunin and
deacetylgedunin were tested against Anopheles stephensi which is the major vector
of malaria. Nathan et al. (2005) reported that deacetylgedunin possessed high
inhibitory activity against the growth of larvae, pupae and adult as well as the
production of egg of A. stephensi. However, the mechanisms of the insecticidal,
repellent and growth inhibitory of these compounds are not well understood.
16.3 Commercial Potential of Gedunin
Considering the multiple therapeutic effects of gedunin that have been reported in
the literature, it is not surprised that patents have been registered for gedunin and its
derivatives. Thus far, Vinson-Hieronymus et al. (2011) has patented gedunin and its
derivatives (publication number: US 2011/0,263,693 A1), together with celastrol to
inhibit Hsp90. As mentioned earlier, Hsp90 is a multitasking molecule that governs
the maturation of an array of diverse cellular functions. It is also a specific client
protein that acts as signal transducers implicated in the molecular mechanisms of
normal cellular biology, disease and evolutionary processes (Kaplan and Li 2012).
Thus, by inhibiting Hsp90, pathological processes like cancer and inflammation can
thus be suppressed (Kaplan and Li 2012; Chatterjee et al. 2007). On the other hand,
gedunin has been patented as a substrate of polymeric wound care material (publication number: US 2013/0,209,534 A1) for its antimicrobial properties and the
ability to aid in wound healing. The neuroprotective effects of gedunin and a
number of limonoids have also granted the inventor Steiner and colleagues a patent
(publication number: US 2010/0,056,617 A1) disclosing the method of preparation
and the utilization of these compounds.
16.4 Conclusion and Gaps of Knowledge
The tremendous robust evidences to date have shown that gedunin and its
derivative possess multiple therapeutic effects including anti-cancer,
anti-inflammatory, anti-parasitic, antimicrobial and insect growth inhibition.
However, most of the studies are limited to in vitro phase with or without the
comparison to commercialized drugs. We thus look forward to have extensive
animal model-based evidences in order to understand how gedunin and its
derivatives work in in vivo systems. This will then fill the gaps of the pharmacological understandings of gedunin and its derivative such as bioavailability, pharmacokinetics and pharmacodynamics. Nonetheless, toxicology screening is yet to
16 An Overview of the Bioactivities of Gedunin
581