Therapeutic Potential of Jasmonic Acid: Comparison
Please note this is a comparison between Version 1 by Iwona Jarocka-Karpowicz and Version 2 by Lindsay Dong.

The main representatives of jasmonate compounds include jasmonic acid and its derivatives, mainly methyl jasmonate. Extracts from plants rich in jasmonic compounds show a broad spectrum of activity, i.e., anti-cancer, anti-inflammatory and cosmetic. Studies of the biological activity of jasmonic acid and its derivatives in mammals are based on their structural similarity to prostaglandins and the compounds can be used as natural therapeutics for inflammation. Jasmonates also constitute a potential group of anti-cancer drugs that can be used alone or in combination with other known chemotherapeutic agents.

  • jasmonic acid
  • methyl jasmonate
  • anti-inflammation
  • anti-cancer
  • anti-aging

 

1. Jasmonate Compounds in Plants

Jasmonates are lipid derivatives (cyclic derivatives of unsaturated fatty acids) that belong to the group of plant growth regulators, which do not have a complex chemical structure [1]. The best known compounds belonging to the group are jasmonic acid (JA) and its methyl ester–methyl jasmonate (MJ) [2]. Jasmonic acid was first isolated from filtrates of the fungus Lasiodiplodia theobromae [3]. Its methyl derivative, however, was the first compound from the large group of jasmonates isolated from the essential oils of Jasminum grandiflorurm [4] and Rosmarinum officinalis [5].

The presence of jasmon compounds has been confirmed in almost all types of tissues of higher plants, i.e., flowering plants, bryophytes, and ferns. They are present, among others, in stems (combinations with amino acids), roots, tubers, leaves (combinations with amino acids; isoleucine or valine), flowers (conjugates with phenylalanine, tryptophan, and tyrosine), fruits (conjugates with isoleucine), and flower pollen [6]. Jasmonates are also components of essential oils and give fragrance to many flowers (e.g., jasmine) and fruits (e.g., apples).

Depending on the type, species, and age of the plant, the content of jasmonate compounds varies widely, ranging from 3 to 10 µg per 1 g of fresh weight [7][8][8,9]. More jasmonate compounds are present in the generative parts of the plant, i.e., the pericarp, fruit, and seeds, than in the vegetative parts, i.e., stems and leaves [7][8]. Biological and physicochemical factors as well as mechanical damage have a large influence on the increase in the amount of jasmonates [8][9][9,10]. Moreover, the amount of jasmonate compounds in the plant decreases with age (Figure 1) [7][8].
Figure 1.
Factors influencing the changes in the levels of jasmonate compounds in the plant.

2. Chemical Structure of Jasmonate

In plants, jasmonic acid exists in the following forms: (-)-JA and (+)-epi-JA. Due to the fact that cis stereoisomers are thermodynamically less stable, they epimerize at the C-7 atom to the stable trans form, which at the same time shows higher biological activity (Figure 2).

Figure 2. Structure-activity relationship of jasmonate compounds in relation to jasmonic acid. [↓, decreased activity; ↑, increased activity.; −, inactive; +, active].

37. Biological Activity of Jasmonates and Their Derivatives

3.1. Anti-Inflammatory

7.1. Anti-Inflammatory

The first studies on the potential anti-inflammatory activity of jasmonate compounds concerned MJ derived from Gracilaria verrucosa and showed that the effectiveness of MJ was comparable with or more effective than that of prostaglandin compounds [10][65]. The study demonstrated the inhibitory effect of MJ on the production of pro-inflammatory mediators (NO, IL-6 and TNF-α) in lipopolysaccharide activated RAW 264.7 mouse macrophages. However, the growing interest in jasmonic acid as a potential therapeutic agent led to the synthesis of new derivatives in order to obtain more active compounds. The basic structural modification changing the activity of jasmonates was the introduction of a double bond in the cyclopentyl ring. Chemically, α,β-unsaturated carbonyl compounds are electrophilic centers that are highly susceptible to addition reactions with nucleophiles such as free sulfhydryl groups of reduced glutathione or cysteine residues in proteins. Thus, prostaglandins are compounds in which cyclopentenone is the pharmacophore responsible for the biological activity of these compounds [11][66]. Therefore, the introduction of unsaturated bonds into the structure of methyl jasmonate with the formation of methyl 4,5-didehydrojasmonate (DHJM) resulted in the formation of compounds showing higher anti-inflammatory activity than similar prostaglandins [12][62].
In 2012, Dang et al. synthesized a series of derivatives with various fragments of jasmonate esters, evaluated their resistance to hydrolysis and converted them into derivatives with a chlorine atom in the position of α-cyclopentenone [13][67]. The most active analogs in this series were t-butyl and hydroxyethyl esters, which was confirmed by the fact that the chain branching and the increased hydrophilicity in relation to the methyl moiety in MJ affect the anti-inflammatory activity (Table 12 and Figure 36).