Abscisic Acid: A Phytohormone and Mammalian Cytokine as Novel Pharmacon with Potential for Future Development into Clinical Applications

Abstract

The isoprenoid stress-associated phytohormone abscisic acid (ABA) has recently been recognized to possess multifaceted biological functions in mammals and to exert potent curative effects in a number of clinically relevant human diseases. Studies with human specimens have unequivocally shown that ABA retains its stress-related functional attributes, previously identified in plants, which contribute to enhanced inflammatory defense mechanisms in mammals. Besides, studies performed in animal models revealed prominent anti-inflammatory properties of ABA as indicated by a marked reduction of immune cell infiltrates at the sites of inflammation. Thus, ABA treatment ultimately leads to the profound improvement of both non-communicable and communicable diseases which are associated with an overall alleviated course of inflammation. In addition to its action on the mammalian immune system, ABA was also shown to exert diverse physiological functions on non-immune components. One of the most remarkable features of ABA is to stimulate and expand mesenchymal stem cells, which may open a new avenue for its potential use in the field of regenerative medicine. Furthermore, ABA has been reported to play an important role in the maintenance of glycemic control. In this review, we summarize current understanding of the significance of ABA in the mammalian system, its prophylactic and therapeutic effects in various disease settings and the future directions for the development of ABA as novel drug candidate for the improved treatment of inflammatory and infectious human diseases.

Abscisic acid induces a transient shift in signaling that enhances NF-κB-mediated parasite killing in the midgut of Anopheles stephensi without reducing lifespan or fecundity

“…Interestingly, in plants ABA can activate or inhibit AMPK signaling in a tissue dependent manner [69], suggesting that the effects of ABA in the mosquito could vary across tissues. Further, pro- and anti-inflammatory effects of ABA have been reported for acute infection and chronic diseases, respectively, in mammals [70] suggesting that the effects of ABA in mosquitoes could vary depending on the nature of the infecting pathogen or in response to changes in associated microbiota.…”

Abscisic Acid as Pathogen Effector and Immune Regulator

“…Furthermore, endogenous induction of serum ABA in response to glucose challenge has been shown to stimulate insulin release and is impaired in patients suffering from type 2 diabetes (Bruzzone et al, 2008, 2012a; Ameri et al, 2015). ABA has recently attracted the attention of several research groups as a potential drug lead (Bassaganya-Riera et al, 2010; Sakthivel et al, 2016) because of these promising biological activities. One study has already shown that fruits and vegetables with high ABA contents (such as figs and apricots) are beneficial against hyperglycemia in both rats and humans (Magnone et al, 2015), which makes ABA a potential pharmacognostic drug or nutraceutical.…”

“…If that is the case, the role of ABA in host-pathogen and mutualistic interactions would be ancient and a universal theme among different organisms and organism interactions. The physiological effects of ABA in animals, especially related to immunity, inflammation and metabolic control, have sparked an interest in utilizing this pathway as a pharmacological target (Sakthivel et al, 2016), which has led to several recent papers on ABA functions in animals. However, the most famous plant hormone with pharmacological effects in humans is salicylic acid (SA).…”

Comparative transcriptome analysis between an evolved abscisic acid-overproducing mutant Botrytis cinerea TBC-A and its ancestral strain Botrytis cinerea TBC-6

“…Besides, ABA activity has also been reported in sponges5, and most recently in mammals with the function of immune modulation and glucose homeostasis regulation67. Thus ABA is also recognized as a candidate for medical applications89.…”