229
pharmacological action and work is going on for its clinical application and is under
phase trials. Colchicine, another well-studied compound from Colchicum autumnale, and FDA approved this as a drug for treatment of familial Mediterranean fever
as well as for the treatment and prevention of acute gout flares. Resveratrol, a stilbene derivative and phytoalexin are found in many plants and in grape fruits. Similar
to Curcumin, resveratrol also has high pharmacological activities and studies are
ongoing to manage its poor bioavailability. Quercetin is another herbal compound
which is also under phase II trial for chronic obstructive pulmonary disease (COPD)
and diabetes (Furst and Zundorf 2014).
Most of the ayurvedic formulations like asava and arishtas are developed from
these plants and are rich source of bioactive molecules. Combined effect of these
molecules leads to the cure of diseases. Ayurvedic formulations are prepared
through fermentation which also leads to the structural modifications in bioactive
molecules and can lead to better remedial power. Fermentation is a method in
Ayurveda for the preparation of medicines but an authentic reason for the preference
of this method is not yet explored. These fermentative steps are similar to the digestive transformation and metabolic transformation as described in classical texts of
the science of Ayurveda (Chandra et al. 2015). Traditional fermentation in ayurvedic
preparation takes place with the help of Woodfordia flowers rich in yeast. Our earlier reports suggest that the fermentation transforms the compounds present in the
materials used in different medicinal preparations (Chandra et al. 2015). Such transformed products have significantly increased pharmacological activity than normal
compounds. Berberine, an isoquinoline alkaloid found in various plants (Chandra
et al. 2015) and has so many biological properties, was found inhibiting PLA 2 and
its microbially transformed (Woodfordia as starter culture) product dihydroxyberberine has increased inhibition on PLA 2 (Naveen et al. 2013). Cuminaldehyde isolated from cumin seeds is a good 5- LOX inhibitor (Tomy et al. 2014a) and benzoic
acid, isolated from polyherbal preparations, also has higher inhibitory potential for
lipoxygenase enzymes. in vitro and in silico validations of these enzymes are a good
outcome for developing new drugs from polyherbals. Black pepper, used in many
ayurvedic formulations, and its constituent piperine have inhibitory activity against
COX 1 and LOX. Bio-transformed derivatives of piperine showed better inhibition
than piperine for lipoxygenase enzyme (Tomy et al. 2014b) and further related studies will explain their use as better anti-inflammatory agents.
9.3
Conclusions
Inflammation is the initial step in most of the diseases and also has an important role
in homeostasis. There are many mediators and their inhibitions are important in antiinflammatory mechanism. Mainly, studies are based on the specific enzymes that
come under the inflammatory pathways (PLA 2 , COX and LOX) and their inhibition
by molecules leading to the drug design process for inflammation. Rational drug
design, the new method in drug development, produces many synthetic lead molecules suitable for these drug targets. Traditional herbs also contain a large consortium
of bioactive molecules and they may also be explored to develop novel drug leads.
9 Anti-inflammatory Molecules: Enzyme Inhibitors
pharmacological action and work is going on for its clinical application and is under
phase trials. Colchicine, another well-studied compound from Colchicum autumnale, and FDA approved this as a drug for treatment of familial Mediterranean fever
as well as for the treatment and prevention of acute gout flares. Resveratrol, a stilbene derivative and phytoalexin are found in many plants and in grape fruits. Similar
to Curcumin, resveratrol also has high pharmacological activities and studies are
ongoing to manage its poor bioavailability. Quercetin is another herbal compound
which is also under phase II trial for chronic obstructive pulmonary disease (COPD)
and diabetes (Furst and Zundorf 2014).
Most of the ayurvedic formulations like asava and arishtas are developed from
these plants and are rich source of bioactive molecules. Combined effect of these
molecules leads to the cure of diseases. Ayurvedic formulations are prepared
through fermentation which also leads to the structural modifications in bioactive
molecules and can lead to better remedial power. Fermentation is a method in
Ayurveda for the preparation of medicines but an authentic reason for the preference
of this method is not yet explored. These fermentative steps are similar to the digestive transformation and metabolic transformation as described in classical texts of
the science of Ayurveda (Chandra et al. 2015). Traditional fermentation in ayurvedic
preparation takes place with the help of Woodfordia flowers rich in yeast. Our earlier reports suggest that the fermentation transforms the compounds present in the
materials used in different medicinal preparations (Chandra et al. 2015). Such transformed products have significantly increased pharmacological activity than normal
compounds. Berberine, an isoquinoline alkaloid found in various plants (Chandra
et al. 2015) and has so many biological properties, was found inhibiting PLA 2 and
its microbially transformed (Woodfordia as starter culture) product dihydroxyberberine has increased inhibition on PLA 2 (Naveen et al. 2013). Cuminaldehyde isolated from cumin seeds is a good 5- LOX inhibitor (Tomy et al. 2014a) and benzoic
acid, isolated from polyherbal preparations, also has higher inhibitory potential for
lipoxygenase enzymes. in vitro and in silico validations of these enzymes are a good
outcome for developing new drugs from polyherbals. Black pepper, used in many
ayurvedic formulations, and its constituent piperine have inhibitory activity against
COX 1 and LOX. Bio-transformed derivatives of piperine showed better inhibition
than piperine for lipoxygenase enzyme (Tomy et al. 2014b) and further related studies will explain their use as better anti-inflammatory agents.
9.3
Conclusions
Inflammation is the initial step in most of the diseases and also has an important role
in homeostasis. There are many mediators and their inhibitions are important in antiinflammatory mechanism. Mainly, studies are based on the specific enzymes that
come under the inflammatory pathways (PLA 2 , COX and LOX) and their inhibition
by molecules leading to the drug design process for inflammation. Rational drug
design, the new method in drug development, produces many synthetic lead molecules suitable for these drug targets. Traditional herbs also contain a large consortium
of bioactive molecules and they may also be explored to develop novel drug leads.
9 Anti-inflammatory Molecules: Enzyme Inhibitors