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Potential Defensive Involvement of Methyl Jasmonate in Oxidative Stress and Its Related Molecular Mechanisms

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Gunjegaonkar Shivshankar M., Joshi Amol A., Wankhede Sagar B., Siraskar Balasaheb D., Merekar Abhijit N. and Shinde Sachin D.

Submitted: November 26th, 2021Reviewed: January 20th, 2022Published: March 24th, 2022

DOI: 10.5772/intechopen.102783

Plant Hormones - Recent Advances, New Perspectives and ApplicationsEdited by Christophe Hano

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Plant Hormones - Recent Advances, New Perspectives and Applications [Working Title]

Dr. Christophe F.E. Hano

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Jasmonic acid (JA), cytokinins (CK), gibberellins (GA), abscisic acid (ABA), ethylene (ET), and salicylic acid (SA) are potent plant stress hormones (phytohormones/PTH). Methyl jasmonate (MeJA), a volatile ester of JA, is derived from the petals of Jasminum grandiflorum (jasmine). The MeJA has been meticulously confirmed for its food, agricultural, and therapeutic uses in the treatment of a range of serious illnesses. Several scientific articles have studied and reported on the role of free radicals in the development of life-threatening clinical illnesses. The inflammatory signaling pathway is triggered by a weak or interfering endogenous antioxidant system, or the elaborated production of free radicals, which causes damage to key cellular components. The current chapter focused on and demonstrated MeJA’s multifunctional role in antioxidant and anti-inflammatory signaling mechanisms such as inhibition of NF-B (nuclear factor kappa-light-chain-enhancer of activated B cells), mitogen-activated protein kinase (MAPK or MAP kinase) pathway inhibition/down-regulation of pro-inflammatory mediators (IL, TNF-), cyclo-oxygenase (COX), and (LOX). The antioxidant effect of MeJA’s interaction with miRNA, transcription of nuclear factor erythroid 2-related 2 (Nfr2), activation of sirtuins (SIRTs), antioxidant and redox signaling pathway were also discussed in the chapter.


  • methyl jasmonate
  • anti-inflammatory
  • oxidative stress
  • free radicals
  • plant stress hormone

1. Introduction

Oxygen is continually used by the organism for a variety of important activities [1]. Reactive oxygen species (ROS) is a naturally occurring byproduct of oxygen metabolism that interacts with biological systems regularly [2, 3]. ROS has been involved in the breakdown of cell organelles such as DNA, proteins, and lipids, according to several studies. Radical scavenging molecules are important components of the antioxidative defense mechanism, protecting cells from free radical damage [4, 5]. Endogenous antioxidant systems (enzymatic/nonenzymatic) are important for balancing and fighting ROS such as H2O2, ROOR (organic hydroperoxide), NO (nitric oxide), O-(superoxide), and •OH (hydroxyl radicals), among others [6, 7]. Superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione reductase (GR) are enzymes in the human endogenous antioxidant system that play a role in the development of ROS-mediated oxidative stress [7, 8, 9, 10]. The extensive production of free radicals manifests in serious illnesses and disorders as diabetes [11], cardiovascular [12], inflammatory [13], and neurological diseases [14]. The production of ROS is triggered by many oxidizing enzymes (xanthine oxidases, NADPH oxidase) COX [15, 16] pro-inflammatory factors. A modest rise in ROS levels disturbs and interferes with cell proliferation and normal physiological processes, but a substantial increase in ROS levels causes catastrophic damage to cellular components [17, 18]. SOD, an important endogenous antioxidant metalloenzyme that scavenges H2O2 produced during oxygen metabolism [19], is an important endogenous antioxidant metalloenzyme. Because of the increased and unregulated synthesis of O-depletes in SOD storage, protecting the cell from hazardous chemicals created during aerobic respiration becomes challenging [20]. Through the conversion of GSH into selenium-containing GSH (GSSH) by GR (Glutathione reductase), the thiol-containing GSH is an essential reducing agent that eliminates reactive oxygen species [20, 21]. CATase is a kind of antioxidant that is responsible for the neutralization of H2O2. H2O2 causes lipid peroxidation, which is inhibited by CAT [22]. Many compounds are produced by lipid peroxidation, but one of the most significant is MDA (malondialdehyde) [9].


2. Multifunctional role of MeJA in several clinical ailments

2.1 Downregulation of NF-κB, MAPK pathway, and oxidative stress

The cytokines are important mediators and signaling molecules involved in several inflammatory pathological cascades. TNF- and the IL family (IL-1, IL-6, IL-15, IL-17, IL-18) are important cytokines [23]. The vital regulator in the synthesis of cytokine induction is the NF-κB signaling pathway. NF-κB is a family of proteins associated with DNA and activates cytokine synthesis genes [24]. The inhibitory protein (IkB) binds to NF-κB and blocks the translocation it from the cytoplasm to the nucleus. The number of stimuli affects IkB function by phosphorylation and degrading it. This allows NF-B to get activated, translocated to the nucleus from the cytoplasm, and triggers genes involved in the synthesis of inflammatory mediators. Agents that activate NF-κB include cytokines, mitogens, and ROS [25]. Another important signaling pathway in inflammation is the activation of MAP kinase under the influence of ROS. ROS induces phosphorylation of the MAP kinase family, including ERK, JNK, and p38 kinases [26]. Consequently, these kinases are responsible for the activation of transcription factors similar to NF-κB and regulate pro-inflammatory genes. Through enzymatic conversion from LOX and COX, ROS also significantly contributed to the synthesis of inflammatory mediators such as PG (prostaglandins), LT (leukotrienes), 5-HETE (5-Hydroxyeicosatetraenoic acid), and others [27, 28]. Studies have shown that antioxidant treatment effectively reduces pain and inflammation via downregulation of NF-B activation and cytokine synthesis [29, 30]. Nociceptive responses are detected by nociceptors found on c and fibers that innervate higher brain centers. Several studies have advocated that the activation of nociceptors and perception is mediated by inflammatory mediators [31]. The study revealed that MeJA significantly reduces the production of ROS-mediated oxidative stress and the generation of pro-inflammatory mediators and would be responsible for its anti-inflammatory and anti-nociceptive effects in-vivo and in-vitro [28, 32, 33, 34, 35]. Studies have demonstrated a significant reduction in pain and inflammation in MeJA-treated experimental animals intoxicated with LPS. The proposed underlying mechanism involved is downregulating the production of pro-inflammatory cytokines (IL, TNF-), expression of COX and LOX, PG, resolving disturbed redox status, inhibiting the generation of ROS/RNS, inactivation of inflammatory cells, and downregulation of transcription in the NF-B and MAPK signaling pathways [35].

2.2 Inhibition of neuronal peroxidation and oxidative stress

The progressive loss of memory is characterized by Alzheimer’s disease (AD). The common signs and symptoms include the inability to recall past events, calculate, plan and perform simple tasks, recognize people and relationships, etc. [36, 37]. The pathological lesion lies in central cholinergic pathways where the degeneration of cholinergic neuronal populations occurs [38]. Several studies have revealed that ROS and associated oxidative stress in the brain region is important in the development and progression of AD. Enhanced lipid peroxidation and diminished polyunsaturated fatty acids have been found in AD brains, which further support the role of ROS in the pathophysiology of the disease [39, 40]. Brain tissues are more susceptible to the deleterious effects of ROS because of their high rate of oxygen consumption, high iron content in many brain tissues, and generation of hydrogen peroxide in neuronal mitochondria cells [41, 42]. Postmortem studies have confirmed elevated levels of MDA, an index of lipid peroxidation in AD brains, which confirmed the role of oxidative stress in the pathogenesis of the disease [43]. Induction of AD in experimental animals can be done by the administration of chemical substances which interfere in a central cholinergic pathway. Scopolamine (SC)-induced memory dysfunction has been linked to its depletion of Ach (acetylcholine) stores, increased oxidative stress, and depletion of the endogenous antioxidant enzymes in brain tissues, which leads to neuronal damage. Tacrine, an AChE inhibitor like tacrine, was the first further donepezil and rivastigmine to be approved for the treatment of AD. It is reported that inflammation of brain cells appears to contribute to the development and progression of AD. Anti-inflammatory drugs such as NSAIDs, corticosteroids, and antioxidants may be effective strategies in Alzheimer’s disease [42, 43]. In a pharmacological screening of a new molecule, lipopolysaccharide (LPS) induced neuroinflammation is a highly validated and reported model [44, 45]. The underlying mechanism involves LPS-induced synthesis of inflammatory mediators and generation of ROS followed by damage to the neurons. MeJA has been screened for its memory performance-enhancing potential against LPS-induced neurotoxicity. The studies revealed that significant memory enhancement in MeJA treated animals was observed as compared to LPS treated. The underlying mechanism has been linked to MeJA antioxidant, anti-inflammatory potential using In-vivo as well as In-Vitro screening models [46, 47, 48].

2.3 Inhibition of mitochondrial dysfunctioning, inflammatory cytokines, and oxidative stress

Stress can influence the emotional factors and neurobehavioral characteristics of human beings and manifest anxiety [49]. The association of oxidative stress and neurodegenerative disorders, including anxiety, has been reported in several studies [50]. Anxiety is a stress response such as worry, fear, overwhelm, and distress to the environment that makes it difficult to continue to work or behave normally in day-to-day life [51]. The stress system components of the CNS are the limbic system, hypothalamus, pituitary, and endocrine hormones that play an integral part in the determination of mental health and behavioral responses [52]. These behavioral responses are regulated by the neurotransmitter/modulators and get interrupted by a variety of chemicals, xenobiotics, drugs, etc., and could change the normal neuronal function [53]. The brain tissues are rich in lipid substrates for oxidation, iron, and copper ions that catalyze free radical reactions which are abundant [54]. The sites of damage mediated by ROS are neuronal mitochondria dysfunction, which leads to psychiatric behavioral diseases like depression, anxiety, psychosis, and ataxia [55, 56]. Patients with anxiety, depression, and psychosis found enhanced levels of pro-inflammatory cytokines, specifically IL-6 and TNF-α, in their blood and brain. Pro-inflammatory cytokines degenerate neurons by activating signaling molecules such as phospholipase A2 (PLA2) and arachidonic acid (AA) [57, 58]. Activation of PLA2 and AA further increases ROS and additional inflammatory mediators like eicosanoids, which contribute to promoting inflammation and nerve degeneration [59]. AA has been found to have a direct role in apoptotic effects [63]. Anti-inflammatory, antioxidant dietary agents such as docosahexaenoic acid (DHA) have been shown in studies to prevent neuronal apoptosis and to be an important treatment option in neurodegenerative diseases [61]. NF-B expression has been found in neurodegenerative diseases, including anxiety [60]. Blocking of the NF-κB pathway remarkably reduces the levels of cytosolic and mitochondrial ROS generation and neuronal damage mediated by oxidative stress. MeJA has been studied for its antianxiety, adaptogenic, and anti-stress potential, and it has been shown to have a significant effect in animals [49, 61]. The underlying mechanism is that MeJA significantly reduces the levels of mitochondrial ROS by compensating with endogenous antioxidant enzymes like GSH, CAT, GPx, GR, SOD, and free radical scavenging activity. A significant reduction in IL and TNF-, as well as a significant inhibition of NO, which is responsible for the synthesis of pro-inflammatory mediators, has a direct effect on the inhibition of neurodegeneration. It was also reported that MeJA shows a switch-off effect on activation of the NF-B and MAPK transcription pathways, which have direct involvement in the generation of stress, anxiety, and other psychological disturbances [31, 34].

2.4 Inhibition of neuronal excitability and oxidative stress

Aggressive tendencies and behaviors in humans and animals have been demonstrated and linked to elevated inflammatory markers [62, 63]. As discussed earlier, brain tissues are more susceptible to the deleterious effects of ROS because of their high rate of oxygen consumption, high iron content in many brain tissues, and generation of hydrogen peroxide in neuronal mitochondria cells [40, 41]. ROS damages neuronal membranes, impairs the ability to deactivate receptors and ion channels, causes uncontrolled neurotransmitter release, and generally disrupts neuronal functioning [64, 65]. disturbed neuronal functioning contributes to neuronal excitotoxicity and is considered as a pathological cascade in neuronal diseases, particularly aggression. Excess excitatory neurotransmitter (glutamate) activity and weakened inhibitory (GABA) neurotransmitter signaling result in aggressive behavior changes. Over-activity of glutamate excitatory neurotransmitters progressively modulates the glutamate receptor and increases intracellular levels of Ca2+, which further disturbs the mitochondrial Ca2+ homeostasis, activates hydrolytic enzymes, and activates apoptotic signaling pathways. Several studies have established a link between increased nitric oxide synthase (NOS) activity and glutamate neurotoxicity, as well as associated behavioral aggressive tendencies [66, 67]. Evidence suggests that MeJA treatment can control disease progression by modulating oxidative stress-mediated by ROS/RNS and controlling inflammatory mediators via direct or indirect mechanisms [61, 68]. In conclusion, the antioxidant potential of MeJA controls the modulation of glutamate/GABAergic, increased Ca2+ influx through countering NO production, oxidative stress.

2.5 Inhibition of metalloproteinases and oxidative stress

The articular cartilage is avascular and does not receive any blood supply. Hence, the essential nutrients and oxygen are supplied to the cartilage through the synovial fluid [69]. Many metabolic reactions in chondrocytes are anaerobic and adapted to survive with a minimum oxygen tension [70]. In a pathological condition, oxygen tension fluctuates, leading to the generation of ROS by the chondrocytes. The main reactive species produced by chondrocytes are O2 radicals, NO, and their derivatives (ONOO-, H2O2) example, chondrocyte-derived free radical levels are important for the maintenance of ion homeostasis, but they also contribute to disease progression [71]. Enhanced levels of ROS lead to serious damage to both chondrocytes and extracellular matrix components of articular cartilage and disturb redox status [72]. The important component of the ECM like aggrecan is degraded by ONOO-and initiates the process of cartilage degradation [73]. Additionally, endogenously synthesized NO suppresses the synthesis of aggrecan. The tensile strength is primarily provided by a network of aggrecan hyaluronate collagen; free radicals disturb the collagen network and reduce the strength of the ECM. Free radicals inhibit collagen synthesis indirectly via interleukin-1 [74]. The proteoglycan synthesis is inhibited by H2O2 through the disturbing synthesis of triphosphate (ATP) [75]. The tissue inhibitors of metalloproteinases (TIMPs) are important inhibitors of MMP-mediated cartilage damage [76]. ONOO-and HOCl reduces the activity of TIMPs by inactivating them. The NO producing agent up regulated the synthesis of MMPs by enhancing collagenase mRNA expression [80]. Proteoglycan synthesis is down-regulated in the chondrocytes on exposure to H2O2 [77]. ROS participates in reducing the capacity of chondrogenic precursor cells to migrate and proliferate within the joint area. NO enhances the anti-proliferative effect of IL-1 as well as initiates chondrocyte apoptosis [78]. The fibroblast-like synoviocytes consume a large amount of oxygen as compared to chondrocytes. In oxidative stress, the accumulation of antioxidant enzymes like SOD, CAT, and GSH has been observed. These enzymes protect the chondrocytes and ECM degradation from free radicals [79]. An uncontrolled and abnormal increase in ROS levels causes apoptosis of chondrocytes. Several studies reveal that a minimum level of H2O2 in synoviocytes causes less damage to chondrocytes [80]. MeJA has shown a significant chondroprotective effect on LPS-induced cartilage damage. LPS induces the synthesis of pro-inflammatory mediators as well as creates severe oxidative stress. MeJA significantly reduces the inflammatory mediator’s activity as well as cartilage destructive MMP. Normalization of oxidative stress is accomplished by restoring antioxidant enzyme levels [27, 32].


3. Regulation of miRNA, SIRT, and HIF1α for an antioxidant mechanism

An oxidative stress state alters the expression level of different miRNAs (microRNAs) and causes significant changes in important cellular processes like cell differentiation, lipid metabolism, apoptosis, and organ development [81]. Severe clinical conditions like inflammation, cancer, cardiovascular diseases, diabetes mellitus, rheumatoid arthritis, neurological disorders have been correlated with altered miRNA expression [82]. Upregulation or downregulation of mRNA addresses pathophysiological modulation in retardation or development of diseases. Anticancer activity of MeJA against bladder, colorectal cancer cells has been shown via the downregulation of EZH2 (enhancer of zeste homolog 2) expression by induction of microRNA-101 [83, 84, 85]. MeJA antioxidant activity has been demonstrated via two pathways: first, inhibition or down-regulation of pro-inflammatory factors such as IL, TNF-mediated mitochondrial ROS production, and second, restoration of endogenous antioxidant enzymes [86, 87]. The latter mechanism involves an effect on the regulation of microRNA. Cellular redox status is regulated by redox-sensible transcription Nfr2 through the upregulation of antioxidant defense genes for SOD, CAT, GSH enzymes [88, 89, 90]. The activity of Nfr2 is regulated by miRNAs via downregulating the same [91, 92]. In conclusion, MeJA improves the antioxidant status and regulates oxidative stress by downregulating specific miR-155 and upregulating miR-101, which leads to the upregulation of Nfr2 activity. The indirect effect of MeJA on sirtuins (SIRTs) as an antioxidant and redox signaling pathway has been established through upregulation of Nfr2 activity by induction of miR-101. Researchers have extensively studied and reported that SIRTs are key signaling molecules that regulate the redox status of the cell and modulate cellular responses in a variety of pathological conditions over the last two decades [93]. SIRTs protect the cell from the deleterious effect of ROS and enhance the expression of genes responsible for the production of endogenous antioxidant enzymes. SIRTs are important for the fine balance between oxidant and antioxidant systems, regulating cellular biochemical reactions as well as maintaining an oxidative state. SIRTs, in association with antioxidant response elements (ARE), is involved in the regulation of gene expression when a cell is exposed to oxidative stress responses. ARE senses the altered cellular redox status and elicits transcriptional responses through activation of Nfr2. Nfr2 regulates the expression and production of several antioxidant enzymes and detoxification genes [94, 95]. Several studies have reported that MeJA significantly restores the levels of antioxidant enzymes and reduces oxidative stress and mediated damage [27, 50, 51, 96, 97]. The underlying mechanism may be Nfr2 mediated increased gene transcription for antioxidant enzymes through the upregulation of miRNA-101. MeJA down-regulates the expression of miRNA-155, leading to the stabilization of HIF-1 (hypoxia-inducible factor 1 alpha) [88]. The fall in oxygen tension in the cell below that needed for normal physiological demand causes a cellular hypoxic adaptive response. The hypoxic condition is crucial and important to target for a therapeutic approach, particularly in cardiovascular disease and cancer [98]. The key regulators of oxygen tension in cells are HIFs. HIF-1 regulates acute hypoxia, whereas HIF-2 and HIF-3 regulate chronic hypoxia. Recently, investigation suggests that miRNAs play an important role in the regulation of HIF [99]. Chronic hypoxic conditions lead to cellular apoptosis, which contributes to severe stroke or myocardial infarction. Alternatively, an intentional cellular hypoxia approach is practiced in the treatment of various types of cancer. Hypoxia induces oxidative stress via the overgeneration of reactive oxygen species (ROS). Targeting HIF through downregulation of miRNA-155 is a new dimension in the induction of cancer cell apoptosis [100]. MeJA anticancer activity has been largely correlated with the downregulation of miRNA-155, which inhibits expression of HIF, which insults cancerous cells and induces apoptosis. In summary, MeJA indicates unique and imperative aspects concerning the assimilated biological roles against oxidative stress, viz. reducing infiltration of inflammatory cells and their activation, inhibition of proinflammatory mediators (IL, TNF-), LOX and COX, downregulation of NF-B and MAPK transcription pathways, downregulation of miRNA-155, and upregulation of miRNA-101 and Nfr2 pathway (Figure 1).

Figure 1.

MeJA multifunctional role in oxidative stress and molecular interactions in antioxidant defense mechanism.

Reactive oxygen species (ROS)/reactive oxygen species (RNS) initiates signaling inflammatory pathways NF-κB (nuclear factor-kB)/MAPK (Mitogen-activated protein kinase) and induces synthesis of cytokines (IL and TNF-α), (MAPK) responsible to enhance activity of COX and increases the synthesis of pro-inflammatory mediators. Activity of COX (cyclooxygenase)/LOX (Lipoxygenase) is enhanced by ROS/RNS and induces synthesis of inflammatory mediators like (PGs, LTs, 5HTEL). The formed inflammatory mediators contribute to destructive effects on the different cells. Lipid peroxidation caused by ROS/RNS leads to damage to neuronal cells component and disturbs mitochondria functioning and induces neuronal cell degeneration and death and develops anxiety, psychosis, depression etc. The disturbed neuronal cell functioning cause’s uncontrolled release of neurotransmitter and causes imbalance between inhibitory (GABAergic) and excitatory (Glutmate) neuronal mechanism leads to aggressive tendencies & behaviors. On induction of inflammation PMN (polymorpho-nuclear neutrophil) activates and are important source for generation of ROS/RNS which further participate in inflammatory cascades. ROS/RNS increases activity of destructive MMP (matrix metalloproteinase) whereas protective tissue TIMPs (Inhibitor of metalloproteinase) is diminished. MMP selectively degrades the component of cartilage ECM (Extra cellular matrix) and causes cartilage damage, pain inflammation due to wear and tear of joints. MeJAregulates miR-155, miR-101 as well as sirtuins (SIRTs) antioxidant and redox signaling pathway leads to the upregulation of the Nfr2 (nuclear factor erythroid 2-related 2) activity. Up regulation of the Nfr2 increases gene transcription for antioxidant enzymes and reduces cellular oxidative stress.


4. Conclusion

PTH jasmonic acid and its derivatives like MeJA are important in the survival of plants in biotic and abiotic stressful conditions as well as have proved their effectiveness in the treatment of several clinical ailments. An important consideration has been pointed out to oxidative stress-mediated by ROS in the development of several pathological conditions like cardiovascular, metabolic, psychosis, and neurodegenerative disorders, cancer, etc. MeJA is not only effective in plants to relieve oxidative stress, but also effectively relieves the same in human beings. ROS activates several pathways like the NF-B and MAPK signaling pathway, increases the activity of inflammatory (PG, LT, 5HTEL) and pro-inflammatory mediators (IL, TNF-), triggers classes of degradative enzymes, disturbs cellular redox status and depletes antioxidant enzymes, induces lipid peroxidation of important cell components, and disturbs cellular normal physiology and construction. Targeting ROS/RNS by antioxidant molecules or disabling signaling pathways activated by ROS are important concerns for treatment options in severe diseases and disorders. MeJA has shown a prominent role in controlling and neutralizing signaling pathways like NF-κB and MAPK also effectively reduces the activity of inflammatory mediators, oxidative stress, and protects the cell and its components from ROS. On the other hand, methyl jasmonate has a positive interaction with miRNA-101 which activates Nfr2mediated upregulation of antioxidant defense genes for SOD, CAT, and GSH enzymes as well as indirectly boosts SIRT antioxidant and redox signaling pathways. Considering the potent role of MeJA and significant interference in oxidative stress and facilitated disease causative pathways, it could be an influential candidate in the treatment of numerous pathological conditions. Several molecules have been screened from natural and synthetic sources for their potential antioxidant benefits. Among them, MeJA has a multifaceted role against oxidative stress-mediated cellular damage. In conclusion, phytohormones like MeJA may be a protruding candidate for new drug discovery and a highly promising molecule for the pharmacotherapy of severe diseases or disorders.



We would like to acknowledge the Management and Principle of ASPM’s K. T. Patil College of, Osmanabad and JSPM’s Charak College of Pharmacy and Research, Pune for providing necessary facilities and infrastructure. The current chapter is not funded by any Government/Non-government organizations.


Conflict of interest

The authors declare no conflict of interest.


Acronyms and abbreviations


Jasmonic Acid






Abscisic Acid




Salicylic Acid




Methyl Jasmonate


Nuclear Factor Kappa-Light-chain-enhancer of Activated B cells


Mitogen-Activated Protein Kinase




Tumor Necrosis Factor alpha








Nuclear Factor Erythroid




Reactive Oxygen Species


Reactive Nitrogen Species


Hydrogen Peroxide


Organic Hydroperoxide


Nitric Oxide




Hydroxyl Radicals


Superoxide Dismutase






Glutathione Reductase




Inhibitory Protein B






5-Hydroxyeicosatetraenoic Acid


Alzheimer’s Disease




Acetylcholine Esterase


Non-Steroidal Anti-inflammatory drugs




Phospholipase A2


Arachidonic Acid


Docosahexaenoic Acid


Gamma-Aminobutyric Acid


Nitric Oxide Synthase


Extracellular Matrix


Tissue Inhibitors of Metalloproteinases


Matrix Metalloproteinases


Hypochlorous Acid


Enhancer of Zeste Homolog 2


Antioxidant Response Elements


Hypoxia Induced Factors


  1. 1.Apel K, Hirt H. Reactive oxygen species: Metabolism, oxidative stress, and signal transduction. Annual Review of Plant Biology. 2004;55:373-399
  2. 2.Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of aging. Nature. 2000;408(6809):239
  3. 3.Salvemini D, Cuzzocrea S. Oxidative stress in septic shock and disseminated intravascular coagulation. Free Radical Biology and Medicine. 2002;33(9):1173-1185
  4. 4.Farber JL. Mechanisms of cell injury by activated oxygen species. Environmental Health Perspectives. 1994;102(10):17-24
  5. 5.Mattill H. Antioxidants. Annual Review of Biochemistry. 1974;16(1):177-192
  6. 6.Brüne B, Zhou J, Von Knethen A. Nitric oxide, oxidative stress, and apoptosis. Kidney International. 2003;63:S22-S24
  7. 7.Noori S. An overview of oxidative stress and antioxidant defensive system. Open Access Scientific Reports. 2012;1(8):1-9
  8. 8.Rahman T, et al. Oxidative Stress and Human Health. Advances in Bioscience and Biotechnology. 2012;3:1-24
  9. 9.Sevanian A, Hochstein P. Mechanisms and consequences of lipid peroxidation in biological systems. Annual Review of Nutrition. 1985;5(1):365-390
  10. 10.Evans JL et al. Are oxidative stress—Activated signaling pathways mediators of insulin resistance and β-cell dysfunction? Diabetes. 2003;52(1):1-8
  11. 11.West IC. Radicals and oxidative stress in diabetes. Diabetic Medicine. 2000;17(3):171-180
  12. 12.Lefer DJ, Granger DN. Oxidative stress and cardiac disease. American Journal of Medicine. 2000;109(4):315-323
  13. 13.Singh U, Devaraj S, Jialal I. Vitamin E, oxidative stress, and inflammation. Annual Review of Nutrition. 2005;25:151-174
  14. 14.Ding Q , Dimayuga E, Keller JN. Proteasome regulation of oxidative stress in aging and age-related diseases of the CNS. Antioxidants & Redox Signaling. 2006;8(1-2):163-172
  15. 15.Hiran TS, Moulton PJ, Hancock JT. Detection of superoxide and NADPH oxidase in porcine articular chondrocytes. Free Radical Biology and Medicine. 1997;23(5):736-743
  16. 16.Fubini B, Hubbard A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radical Biology and Medicine. 2003;34(12):1507-1516
  17. 17.John Aitken R, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biology of Reproduction. 1989;41(1):183-197
  18. 18.Matés JM, Pérez-Gómez C, De Castro IN. Antioxidant enzymes and human diseases. Clinical Biochemistry. 1999;32(8):595-603
  19. 19.Oberley LW, Buettner GR. Role of superoxide dismutase in cancer: A review. Cancer Research. 1979;39(4):1141-1149
  20. 20.Vaziri ND et al. Oxidative stress and dysregulation of superoxide dismutase and NADPH oxidase in renal insufficiency. Kidney International. 2003;63(1):179-185
  21. 21.Chakravarthi S, Jessop CE, Bulleid NJ. The role of glutathione in disulphide bond formation and endoplasmic-reticulum-generated oxidative stress. EMBO Reports. 2006;7(3):271-275
  22. 22.Lieber CS. Role of oxidative stress and antioxidant therapy in alcoholic and nonalcoholic liver diseases. In: Advances in Pharmacology. Amsterdam, Netherlands: Elsevier; 1996. pp. 601-628
  23. 23.Gogos CA et al. Pro-versus anti-inflammatory cytokine profile in patients with severe sepsis: A marker for prognosis and future therapeutic options. The Journal of Infectious Diseases. 2000;181(1):176-180
  24. 24.Li Q , Verma IM. NF-κB regulation in the immune system. Nature Reviews Immunology. 2002;2(10):725-734
  25. 25.Adcock IM et al. Oxidative stress induces NFκB DNA binding and inducible NOS mRNA in human epithelial cells. Biochemical and Biophysical Research Communications. 1994;199(3):1518-1524
  26. 26.Ghosh J et al. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway. Toxicology and Applied Pharmacology. 2009;240(1):73-87
  27. 27.Johnstone M, Gearing AJ, Miller KM. A central role for astrocytes in the inflammatory response to β-amyloid; chemokines, cytokines and reactive oxygen species are produced. Journal of Neuroimmunology. 1999;93(1-2):182-193
  28. 28.Gunjegaonkar S, Shanmugarajan T. Methyl jasmonate a stress phytohormone attenuates LPS induced in vivo and in vitro arthritis. Molecular Biology Reports. 2019;46(1):647-656
  29. 29.Vaquero E et al. Localized pancreatic NF-κB activation and inflammatory response in taurocholate-induced pancreatitis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2001;280(6):G1197-G1208
  30. 30.Song P, Zhao Z-Q , Liu X-Y. Expression of IL-2 receptor in dorsal root ganglion neurons and peripheral antinociception. Neuroreport. 2000;11(7):1433-1436
  31. 31.Shanmugarajan T. Potential of plant stress hormone methyl Jasmonate against lipopolysaccharide attenuated oxidative stress and arthritis in experimental animals. International Journal of Green Pharmacy (IJGP). 2018;12(3):561-572
  32. 32.Umukoro S et al. Anti-inflammatory and membrane stabilizing properties of methyl jasmonate in rats. Chinese Journal of Natural Medicines. 2017;15(3):202-209
  33. 33.Umukoro S, Olugbemide AS. Antinociceptive effects of methyl jasmonate in experimental animals. Journal of Natural Medicines. 2011;65(3-4):466-470
  34. 34.Kim M et al. Methyl jasmonate inhibits lipopolysaccharide-induced inflammatory cytokine production via mitogen-activated protein kinase and nuclear factor-κB pathways in RAW 264.7 cells. Die Pharmazie-An International Journal of Pharmaceutical Sciences. 2016;71(9):540-543
  35. 35.Koedam EL et al. Early-versus late-onset Alzheimer’s disease: More than age alone. Journal of Alzheimer’s Disease. 2010;19(4):1401-1408
  36. 36.Schofield PW et al. The age at onset of Alzheimer’s disease and an intracranial area measurement: A relationship. Archives of Neurology. 1995;52(1):95-98
  37. 37.Spillantini MG, Goedert M. Tau protein pathology in neurodegenerative diseases. Trends in Neurosciences. 1998;21(10):428-433
  38. 38.Nunomura A et al. Involvement of oxidative stress in Alzheimer disease. Journal of Neuropathology & Experimental Neurology. 2006;65(7):631-641
  39. 39.Zhu X et al. Causes of oxidative stress in Alzheimer disease. Cellular and Molecular Life Sciences. 2007;64(17):2202-2210
  40. 40.Markesbery W, Lovell M. Four-hydroxynonenal, a product of lipid peroxidation, is increased in the brain in Alzheimer’s disease. Neurobiology of Aging. 1998;19(1):33-36
  41. 41.Williams TI et al. Increased levels of 4-hydroxynonenal and acrolein, neurotoxic markers of lipid peroxidation, in the brain in mild cognitive impairment and early Alzheimer’s disease. Neurobiology of Aging. 2006;27(8):1094-1099
  42. 42.Yamada K, Nabeshima T. Animal models of Alzheimer’s disease and evaluation of anti-dementia drugs. Pharmacology & Therapeutics. 2000;88(2):93-113
  43. 43.Zarifkar A et al.Agmatineprevents LPS-induced spatial memory impairment and hippocampal apoptosis. European Journal of Pharmacology. 2010;634(1-3):84-88
  44. 44.Kitazawa M et al. Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer’s disease. Journal of Neuroscience. 2005;25(39):8843-8853
  45. 45.Umukoro S, Eduviere A. Methyl jasmonate attenuated lipopolysaccharide-induced memory dysfunction through inhibition of neuroinflammatory markers and beta-amyloid generation in mice. European Neuropsychopharmacology. 2016;2(26):S647-S648
  46. 46.Eduviere AT et al. Methyl jasmonate enhances memory performance through inhibition of oxidative stress and acetylcholinesterase activity in mice. Life Sciences. 2015;132:20-26
  47. 47.Eduviere AT, Omorogbe O, Umukoro S. Methyl jasmonate ameliorates memory deficits in mice exposed to passive avoidance paradigm. Journal of Neuroscience Research. 2017;1:6
  48. 48.Annafi OS, Umukoro S, Eduviere AT. Evaluation of the anticonvulsant and anxiolytic potentials of methyl jasmonate in mice. Scientia Pharmaceutica. 2014;82(3):643-654
  49. 49.Chrousos GP, Gold PW. The concepts of stress and stress system disorders: Overview of physical and behavioral homeostasis. JAMA. 1992;267(9):1244-1252
  50. 50.Bouayed J, Rammal H, Soulimani R. Oxidative stress and anxiety: Relationship and cellular pathways. Oxidative Medicine and Cellular Longevity. 2009;2(2):63-67
  51. 51.Wilensky U. What is normal anyway? Therapy for epistemological anxiety. Educational Studies in Mathematics. 1997;33(2):171-202
  52. 52.Halliwell B. Oxidative stress and neurodegeneration: Where are we now? Journal of Neurochemistry. 2006;97(6):1634-1658
  53. 53.Bouayed J et al. Positive correlation between peripheral blood granulocyte oxidative status and level of anxiety in mice. European Journal of Pharmacology. 2007;564(1-3):146-149
  54. 54.Hakonen AH et al. Mitochondrial DNA polymerase W748S mutation: A common cause of autosomal recessive ataxia with ancient European origin. The American Journal of Human Genetics. 2005;77(3):430-441
  55. 55.Suomalainen A et al. Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. The Journal of Clinical Investigation. 1992;90(1):61-66
  56. 56.Crews FT et al. Alcohol-induced neurodegeneration: When, where and why? Alcoholism: Clinical and Experimental Research. 2004;28(2):350-364
  57. 57.Sun GY et al. Phospholipase A2 in the central nervous system implications for neurodegenerative diseases. Journal of Lipid Research. 2004;45(2):205-213
  58. 58.Caro AA, Cederbaum AI. Role of cytochrome P450 in phospholipase A2-and arachidonic acid-mediated cytotoxicity. Free Radical Biology and Medicine. 2006;40(3):364-375
  59. 59.Suganuma H et al. Maternal docosahexaenoic acid-enriched diet prevents neonatal brain injury. Neuropathology. 2010;30(6):597-605
  60. 60.Mattson MP, Camandola S. NF-κB in neuronal plasticity and neurodegenerative disorders. The Journal of Clinical Investigation. 2001;107(3):247-254
  61. 61.Terai K et al. Enhancement of immunoreactivity for NF-κB in human cerebral infarctions. Brain Research. 1996;739(1-2):343-349
  62. 62.Annafi OS et al. Probable mechanisms involved in the antipsychotic-like activity of methyl jasmonate in mice. Naunyn-Schmiedeberg’s Archives of Pharmacology. 2017;390(9):883-892
  63. 63.Zalcman SS, Siegel A. The neurobiology of aggression and rage: Role of cytokines. Brain, Behavior, and Immunity. 2006;20(6):507-514
  64. 64.Inagaki TK et al. Inflammation selectively enhances amygdala activity to socially threatening images. NeuroImage. 2012;59(4):3222-3226
  65. 65.Lebel CP, Bondy SC. Oxygen radicals: Common mediators of neurotoxicity. Neurotoxicology and Teratology. 1991;13(3):341-346
  66. 66.Gidron Y et al. The relation between psychological factors and DNA-damage: A critical review. Biological Psychology. 2006;72(3):291-304
  67. 67.Dawson TM, Dawson VL, Snyder SH. Molecular mechanisms of nitric oxide actions in the brain a. Annals of the New York Academy of Sciences. 1994;738(1):76-85
  68. 68.Hovatta I, Juhila J, Donner J. Oxidative stress in anxiety and comorbid disorders. Neuroscience Research. 2010;68(4):261-275
  69. 69.Umukoro S, Eduviere AT, Aladeokin AC. Anti-aggressive activity of methyl jasmonate and the probable mechanism of its action in mice. Pharmacology Biochemistry and Behavior. 2012;101(2):271-277
  70. 70.Díaz-Prado S et al. Potential use of the human amniotic membrane as a scaffold in human articular cartilage repair. Cell and Tissue Banking. 2010;11(2):183-195
  71. 71.Panseri S et al. Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surgery, Sports Traumatology, Arthroscopy. 2012;20(6):1182-1191
  72. 72.Gibson J et al. Oxygen and reactive oxygen species in articular cartilage: Modulators of ionic homeostasis. Pflügers Archiv-European Journal of Physiology. 2008;455(4):563-573
  73. 73.Martin JA et al. Effects of oxidative damage and telomerase activity on human articular cartilage chondrocyte senescence. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 2004;59(4):B324-B336
  74. 74.Billinghurst RC et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. The Journal of Clinical Investigation. 1997;99(7):1534-1545
  75. 75.Khan IM et al. Oxidative stress induces expression of osteoarthritis markers procollagen IIA and 3B3 (−) in adult bovine articular cartilage. Osteoarthritis and Cartilage. 2008;16(6):698-707
  76. 76.Murphy G. Tissue inhibitors of metalloproteinases. Genome Biology. 2011;12(11):233
  77. 77.Lotz M. The role of nitric oxide in articular cartilage damage. Rheumatic Disease Clinics of North America. 1999;25(2):269-282
  78. 78.Goldring MB. Osteoarthritis and cartilage: The role of cytokines. Current Rheumatology Reports. 2000;2(6):459-465
  79. 79.Schneider N et al. Synoviocytes, not chondrocytes, release free radicals after cycles of anoxia/re-oxygenation. Biochemical and Biophysical Research Communications. 2005;334(2):669-673
  80. 80.Jovanovic DV et al. Nitric oxide induced cell death in human osteoarthritic synoviocytes is mediated by tyrosine kinase activation and hydrogen peroxide and/or superoxide formation. The Journal of Rheumatology. 2002;29(10):2165-2175
  81. 81.Zhang L et al. MicroRNA-217 is involved in the progression of atherosclerosis through regulating inflammatory responses by targeting sirtuin 1. Molecular Medicine Reports. 2019;20(4):3182-3190
  82. 82.Engedal N et al. From oxidative stress damage to pathways, networks, and autophagy via microRNAs. Oxidative Medicine and Cellular Longevity. 2018;2018:1-16
  83. 83.Peng Z, Zhang Y. Methyl jasmonate induces the apoptosis of human colorectal cancer cells via downregulation of EZH2 expression by microRNA-101. Molecular Medicine Reports. 2017;15(2):957-962
  84. 84.Wang Y et al. Methyl jasmonate sensitizes human bladder cancer cells to gambogic acid-induced apoptosis through down-regulation of EZH 2 expression by miR-101. British Journal of Pharmacology. 2014;171(3):618-635
  85. 85.Cesari IM et al. Methyl jasmonate: Putative mechanisms of action on cancer cells cycle, metabolism, and apoptosis. International Journal of Cell Biology. 2014;2014:1-12
  86. 86.Kastl L et al. TNF-α mediates mitochondrial uncoupling and enhances ROS-dependent cell migration via NF-κB activation in liver cells. FEBS Letters. 2014;588(1):175-183
  87. 87.Dinkova-Kostova AT, Abramov AY. The emerging role of Nrf2 in mitochondrial function. Free Radical Biology and Medicine. 2015;88:179-188
  88. 88.Guo Y et al. Epigenetic regulation of Keap1-Nrf2 signaling. Free Radical Biology and Medicine. 2015;88:337-349
  89. 89.Yu D-S et al. Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway. Brain Research. 2017;1657:279-287
  90. 90.Sá-Nakanishi AB et al. Anti-inflammatory and antioxidant actions of methyl jasmonate are associated with metabolic modifications in the liver of arthritic rats. Oxidative Medicine and Cellular Longevity. 2018;2018:1-15
  91. 91.Yamakuchi M. MicroRNA regulation of SIRT1. Frontiers in Physiology. 2012;3:68
  92. 92.Choi S-E, Kemper JK. Regulation of SIRT1 by microRNAs. Molecules and Cells. 2013;36(5):385-392
  93. 93.Nguyen T, Sherratt PJ, Pickett CB. Regulatory mechanisms controlling gene expression mediated by the antioxidant response element. Annual Review of Pharmacology and Toxicology. 2003;43(1):233-260
  94. 94.Haigis MC, Sinclair DA. Mammalian sirtuins: Biological insights and disease relevance. Annual Review of Pathology: Mechanisms of Disease. 2010;5:253-295
  95. 95.Merksamer PI et al. The sirtuins, oxidative stress and aging: An emerging link. Aging (Albany NY). 2013;5(3):144
  96. 96.Gunjegaonkar S, Shanmugarajan T. Molecular mechanism of plant stress hormone methyl jasmonate for its anti-inflammatory activity. Plant Signaling & Behavior. 2019;14(10):e1642038
  97. 97.Umukoro S et al. Evaluation of adaptogenic-like property of methyl jasmonate in mice exposed to unpredictable chronic mild stress. Brain Research Bulletin. 2016;121:105-114
  98. 98.Pialoux V et al. Relationship between oxidative stress and HIF-1α mRNA during sustained hypoxia in humans. Free Radical Biology and Medicine. 2009;46(2):321-326
  99. 99.Nardinocchi L et al. Zinc downregulates HIF-1α and inhibits its activity in tumor cells in vitro and in vivo. PLoS One. 2010:5(12):1-8
  100. 100.Serocki M et al. miRNAs regulate the HIF switch during hypoxia: A novel therapeutic target. Angiogenesis. 2018;21(2):183-202

Written By

Gunjegaonkar Shivshankar M., Joshi Amol A., Wankhede Sagar B., Siraskar Balasaheb D., Merekar Abhijit N. and Shinde Sachin D.

Submitted: November 26th, 2021Reviewed: January 20th, 2022Published: March 24th, 2022