Chebulinic acid attenuates glutamate-induced HT22 cell death by inhibiting oxidative stress,calcium influx and MAPKs phosphorylation

Glutamate-induced excitotoxicity and oxidative stress is a major causative factor in neuronal cell death in acute brain injuries and chronic neurodegenerative diseases. The prevention of oxidative stress is a potential therapeutic strategy. Therefore, in the present study, we aimed to examine a potential therapeutic agent and its protective mechanism against glutamate-mediated cell death. We first found that chebulinic acid isolated from extracts of the fruit of Terminalia chebula prevented glutamate-induced HT22 cell death. Chebulinic acid significantly reduced intracellular reactive oxygen species (ROS) production and Ca²⁺ influx induced by glutamate. We further demonstrated that chebulinic acid significantly decreased the phosphorylation of mitogen-activated protein kinases (MAPKs), including ERK1/2, JNK, and p38, as well as inhibiting pro-apoptotic Bax and increasing anti-apoptotic Bcl-2 protein expression. Moreover, we demonstrated that chebulinic acid significantly reduced the apoptosis induced by glutamate in HT22 cells. In conclusion, our results in this study suggest that chebulinic acid is a potent protectant against glutamate-induced neuronal cell death via inhibiting ROS production, Ca²⁺ influx, and phosphorylation of MAPKs, as well as reducing the ratio of Bax to Bcl-2, which contribute to oxidative stress-mediated neuronal cell death.     

Curcumin-induced inhibition of cellular reactive oxygen species generation: Novel therapeutic implications

There is evidence for increased levels of circulating reactive oxygen species (ROS) in diabetics, as indirectly inferred by the findings of increased lipid peroxidation and decreased antioxidant status. Direct measurements of intracellular generation of ROS using fluorescent dyes also demonstrate an association of oxidative stress with diabetes. Although phenolic compounds attenuate oxidative stress-related tissue damage, there are concerns over toxicity of synthetic phenolic antioxidants and this has considerably stimulated interest in investigating the role of natural phenolics in medicinal applications. Curcumin (the primary active principle in turmeric,Curcuma longa Linn.) has been claimed to represent a potential antioxidant and antiinflammatory agent with phytonutrient and bioprotective properties. However there are lack of molecular studies to demonstrate its cellular action and potential molecular targets. In this study the antioxidant effect of curcumin as a function of changes in cellular ROS generation was tested. Our results clearly demonstrate that curcumin abolished both phorbol-12 myristate-13 acetate (PMA) and thapsigargin-induced ROS generation in cells from control and diabetic subjects. The pattern of these ROS inhibitory effects as a function of dose-dependency suggests that curcumin mechanistically interferes with protein kinase C (PKC) and calcium regulation. Simultaneous measurements of ROS and Ca²⁺ influx suggest that a rise in cytosolic Ca²⁺ may be a trigger for increased ROS generation. We suggest that the antioxidant and antiangeogenic actions of curcumin, as a mechanism of inhibition of Ca²⁺ entry and PKC activity, should be further exploited to develop suitable and novel drugs for the treatment of diabetic retinopathy and other diabetic complications.     

Receptor for Activated C Kinase-1 protein from Penaeus monodon (Pm-RACK1) participates in the shrimp antioxidant response

Cellular oxidative stress responses are caused in many ways, but especially by disease and environmental stress. After the initial burst of reactive oxygen species (ROS), the effective elimination of ROS is crucial for the survival of organisms and is mediated by antioxidant defense mechanisms. In this paper, we investigate the possible antioxidant function of Penaeus monodon Receptor for Activated C Kinase-1 (Pm-RACK1). When Pm-RACK1 was over-expressed in Escherichia coli cells or Spodoptera frugiperda (Sf9) insect cells exposed to H₂O₂, it significantly protected the cells from oxidative damage induced by H₂O₂. When recombinant Pm-RACK1 protein was expressed as a histidine fusion protein in E. coli and purified with a Ni²⁺-column it possessed antioxidant functions that protected DNA from metal-catalyzed oxidation. Shrimp (Penaeus vannamei) held at an alkaline pH had a much higher hepatopancreatic expression of Pm-RACK1 than in those held at pH 7.4. The exposure of shrimp to alkaline pH is also known to increase ROS production. These results provide strong evidence that Pm-RACK1 can participate in the shrimp antioxidant response induced by the formation of ROS.     

Interactive effects of silicon and arbuscular mycorrhiza in modulating ascorbate-glutathione cycle and antioxidant scavenging capacity in differentially salt-tolerant <Emphasis Type="Italic">Cicer arietinum</Emphasis> L. genotypes subjected to long-term salinity

Salinity is the major environmental constraint that affects legume productivity by inducing oxidative stress. Individually, both silicon (Si) nutrition and mycorrhization have been reported to alleviate salt stress. However, the mechanisms adopted by both in mediating stress responses are poorly understood. Thus, pot trials were undertaken to evaluate comparative as well as interactive effects of Si and/or arbuscular mycorrhiza (AM) in alleviating NaCl toxicity in modulating oxidative stress and antioxidant defence mechanisms in two Cicer arietinum L. (chickpea) genotypes—HC 3 (salt-tolerant) and CSG 9505 (salt-sensitive). Plants subjected to different NaCl concentrations (0–100 mM) recorded a substantial increase in the rate of superoxide radical (O₂ ^·?), H₂O₂, lipoxygenase (LOX) activity and malondialdehyde (MDA) content, which induced leakage of ions and disturbed Ca²⁺/Na⁺ ratio in roots and leaves. Individually, Si and AM reduced oxidative burst by strengthening antioxidant enzymatic activities (superoxide dismutase (SOD), catalase (CAT) and guaiacol peroxidase (GPOX)). Si was relatively more efficient in reducing accumulation of stress metabolites, while mycorrhization significantly up-regulated antioxidant machinery and modulated ascorbate-glutathione (ASA-GSH) cycle. Combined applications of Si and AM complemented each other in reducing reactive oxygen species (ROS) build-up by further enhancing the antioxidant defence responses. Magnitude of ROS-mediated oxidative burden was lower in HC 3 which correlated strongly with more effective AM symbiosis, better capacity to accumulate Si and stronger defence response when compared with CSG 9505. Study indicated that Si and/or AM fungal amendments upgraded salt tolerance through a dynamic shift from oxidative destruction towards favourable antioxidant defence system in stressed chickpea plants.     

IDH2 deficiency exacerbates acetaminophen hepatotoxicity in mice via mitochondrial dysfunction-induced apoptosis

Acetaminophen (APAP)-induced hepatotoxicity is a major factor in liver failure and its toxicity is associated with the generation of reactive oxygen species (ROS), decreased levels of reduced glutathione (GSH) and overall oxidative stress. Mitochondrial NADP⁺-dependent isocitrate dehydrogenase (IDH2) was demonstrated as an essential enzyme for mitochondria to maintain their antioxidant system by generating NADPH, which is an essential reducing equivalent for GSH turnover in mitochondria. Here, we investigated the role of IDH2 in APAP-induced liver injury with IDH2 deficient (idh2^−/−) mice. Hepatotoxicity was promoted through apoptotic cell death following APAP administration in IDH2 deficient hepatocytes compared to that in wild-type hepatocytes. Apoptosis was found to result from the induction of ER stress and mitochondrial dysfunction as shown by the blocking the effect of phenylbutyrate and Mdivi1, respectively. In addition, mito-TEMPO, a scavenger of mitochondrial ROS, was seen to ameliorate APAP-induced hepatotoxicity in idh2^−/− mice. In conclusion, IDH2 deficiency leads to a fundamental shortage of GSH that increases susceptibility to ROS generation and oxidative stress. This leads to excessive mitochondrial dysfunction and ER stress induction in response to APAP administration. Our study provides further evidence that IDH2 has a protective role against APAP-induced liver injury and emphasizes the importance of the elaborate linkages and functions of the antioxidant system in liver health.     

Combined effects of hypoxia and excess Mn2+ on oxidative stress and antioxidant enzymes in tomato seedlings

Effects of high level of Mn²⁺ on the changes in ROS generation, root cell viability, antioxidant enzyme activities, and related gene expression in tomato (Solanum lycopersicum L., cv. Zhongza 9) seedlings were studied under normoxic and hypoxia conditions. Mn²⁺ concentrations, ranged between 10 and 200 ??M, led to significantly higher activities of superoxide dismutase (SOD), peroxidase (POD), ascorbate peroxidase (APOD), glutathione reductase (GR), and also ascorbic acid (AsA) content in leaves and roots, improved root cell viability, and decreased O ₂ ^·? accumulation compared with the higher Mn²⁺ level under hypoxia stress, which indicated that low Mn²⁺ could eliminate the active oxygen and protect the membrane lipid from the hypoxia hurt. When the concentration of Mn²⁺ reached 400?C600 ??M under hypoxia stress, the activities of SOD, POD, APOD, and GR and AsA content were decreased remarkably. In contrast, the MDA content was increased at the higher Mn²⁺ concentration. A number of antioxidant-related genes showed high expression at the lower level of Mn²⁺. The expression levels of SOD, POD, CAT, APOD, and GR genes were 7.95, 5.27, 3.18, 5.54, and 8.81 times compared to control, respectively. These results illustrated that the appropriate amount of Mn²⁺ could alleviate the detrimental effects of hypoxia stress, but reversely, the high level of Mn²⁺ just aggravated the existing damage to the tomato seedlings.     

Effect of phlorotannin-rich extracts of Ascophyllum nodosum and Himanthalia elongata (Phaeophyceae) on cellular oxidative markers in human HepG2 cells

Phlorotannins have received much attention due to their ecophysiological importance and potential applications in the biotechnology and food industries. Antioxidant activity studies in seaweeds have mainly focused on in vitro assays; however, there is a paucity of data regarding the effect of brown algal phlorotannins on living cultured cells. The aim of the present study was to investigate both direct and protective effects of phlorotannin-rich extracts on cell viability and the cellular oxidative status of cultured liver cells HepG2 against oxidative stress induced by tert-butyl hydroperoxide (t-BOOH). Extracts of the Phaeophyceae Ascophyllum nodosum (Fucaceae) and Himanthalia elongata (Himanthaliaceae) were submitted to gastrointestinal digestion prior to incubation for 20 h in a HepG2 culture at physiological concentrations (0.5–50 μg mL^?1). Various markers of cellular oxidative stress were then assessed, such as the generation of reactive oxygen species (ROS), antioxidant defences (concentration of reduced glutathione and activities of glutathione peroxidase, reductase and glutathione-S-transferase) and the levels of malondialdehyde as a marker for lipid peroxidation. The direct effect on cellular markers was assessed immediately after the incubation period, whereas for the protective effect, the incubation period was followed by a 3-h treatment with t-BOOH. The results indicated no effect on cell viability, and both extracts showed reduced levels of ROS and increased antioxidant defences in the direct treatment. Moreover, the extracts showed a significant protective effect against chemically induced oxidative stress in HepG2 cells by reducing ROS generation and enhancing antioxidant defences, hence supporting the utility of including brown algal extracts in functional food products.     

Protective Effects of Quercetin Against Cadmium Chloride-Induced Oxidative Injury in Goat Sperm and Zygotes

Quercetin, a plant-derived flavonoid, is frequently used as an antioxidant for efficient anti-oxidative capacity. However, whether quercetin has protective effects on goat sperm and preimplantation embryos against Cd²⁺-induced oxidative injury is still unclear. So, we researched the influence of quercetin on goat sperm and zygotes respectively under the oxidative stress induced by Cd²⁺. In our study, quercetin decreased the malonaldehyde (MDA) and reactive oxygen species (ROS) levels caused by Cd²⁺ in goat sperm (p?<?0.05), which facilitated sperm characteristics including motility, survival rates, membrane integrity, and mitochondria activity during storage in vitro and subsequent embryo development (p?<?0.05). Moreover, in goat zygotes, quercetin decreased peroxidation products including ROS, MDA, and carbonyl through preserving or maintaining mitochondrial function, gene expression, and anti-oxidative products such as glutathione peroxidase, superoxide dismutase, and catalase, which ameliorated subsequent embryo development and embryo quality (p?<?0.05). Taken together, these results suggest that quercetin protects both goat sperm and preimplantation embryos from Cd²⁺-induced oxidative stress.     

Thiol antioxidants protect human lens epithelial (HLE B-3) cells against tert-butyl hydroperoxide-induced oxidative damage and cytotoxicity

Oxidative damage to lens epithelial cells plays an important role in the development of age-related cataract, and the health of the lens has important implications for overall ocular health. As a result, there is a need for effective therapeutic agents that prevent oxidative damage to the lens. Thiol antioxidants such as tiopronin or N-(2-mercaptopropionyl)glycine (MPG), N-acetylcysteine amide (NACA), N-acetylcysteine (NAC), and exogenous glutathione (GSH) may be promising candidates for this purpose, but their ability to protect lens epithelial cells is not well understood. The effectiveness of these compounds was compared by exposing human lens epithelial cells (HLE B-3) to the chemical oxidant tert-butyl hydroperoxide (tBHP) and treating the cells with each of the antioxidant compounds. MTT cell viability, apoptosis, reactive oxygen species (ROS), and levels of intracellular GSH, the most important antioxidant in the lens, were measured after treatment. All four compounds provided some degree of protection against tBHP-induced oxidative stress and cytotoxicity. Cells treated with NACA exhibited the highest viability after exposure to tBHP, as well as decreased ROS and increased intracellular GSH. Exogenous GSH also preserved viability and increased intracellular GSH levels. MPG scavenged significant amounts of ROS, and NAC increased intracellular GSH levels. Our results suggest that both scavenging ROS and increasing GSH may be necessary for effective protection of lens epithelial cells. Further, the compounds tested may be useful for the development of therapeutic strategies that aim to prevent oxidative damage to the lens.     

Oxidative-induced membrane damage in diabetes lymphocytes: Effects on intracellular Ca2 + homeostasis

Oxidative stress is linked to several human diseases, including diabetes. However, the intracellular signal transduction pathways regulated by reactive oxygen species (ROS) remain to be established. Deleterious effects of ROS stem from interactions with various ion transport proteins such as ion channels and pumps, primarily altering Ca^{2 +} homeostasis and inducing cell dysfunction. This study characterized the Ca^{2 +} transport system in lymphocytes of patients with type-2 diabetes, evaluating the possible correlation between cell modifications and the existence of specific oxidative stress damage. Lymphocytes from type-2 diabetes patients displayed oxidative stress features (accumulation of some ROS species, membrane peroxidation, increase in protein carbonyls, increase in SOD and Catalase activity) and Ca^{2 +} dyshomeostasis (modified voltage-dependent and inositol 1,4,5-triphosphate-mediated Ca^{2 +} channel activities, decrease in Ca^{2 +} pumps activity). The data support a correlation between oxidative damage and alterations in intracellular Ca^{2 +} homeostasis, possibly due to modification of the ionic control in lymphocytes of type-2 diabetes patients.     

Neuroprotective Effects of Phenolic and Carboxylic Acids on Oxidative Stress-Induced Toxicity in Human Neuroblastoma SH-SY5Y Cells

An increase in oxidative stress is a key factor responsible for neurotoxicity induction and cell death leading to neurodegenerative diseases including Parkinson’s and Alzheimer’s diseases. Plant phenolics exert diverse bioactivities i.e., antioxidant, anti-inflammatory, and neuroprotective effects. Herein, phenolic compounds, namely protocatechuic aldehyde (PCA) constituents of Hydnophytum formicarum Jack. including vanillic acid (VA) and trans-ferulic acid (FA) found in Spilanthes acmella Murr., were explored for anti-neurodegenerative properties using an in vitro model of oxidative stress-induced neuroblastoma SH-SY5Y cells. Exposure of the neuronal cells with H₂O₂ resulted in the decrease of cell viability, but increasing in the level of reactive oxygen species (ROS) together with morphological changes and inducing cellular apoptosis. SH-SY5Y cells pretreated with 5 µM of PCA, VA, and FA were able to attenuate cell death caused by H₂O₂-induced toxicity, as well as decreased ROS level and apoptotic cells after 24 h of treatment. Pretreated SH-SY5Y cells with phenolic compounds also helped to upregulate H₂O₂-induced depletion of the expressions of sirtuin-1 (SIRT1) and forkhead box O (FoxO) 3a as well as induce the levels of antioxidant (superoxide dismutase (SOD) 2 and catalase) and antiapoptotic B-cell lymphoma 2 (Bcl-2) proteins. The findings suggest that these phenolics might be promising compounds against neurodegeneration.     

Effect of oxidative stress on telomere maintenance in aortic smooth muscle cells

Reactive oxygen species (ROS) and telomere dysfunction are both associated with aging and the development of age-related diseases. Although there is evidence for a direct relationship between ROS and telomere dysfunction as well as an independent association of oxidative stress and telomere attrition with age-related disorders, there has not been sufficient exploration of how the interaction between oxidative stress and telomere function may contribute to the pathophysiology of cardiovascular diseases (CVD). To better understand the complex relationships between oxidative stress, telomerase biology and pathophysiology, we examined the telomere biology of aortic smooth muscle cells (ASMCs) isolated from mutant mouse models of oxidative stress. We discovered that telomere lengths were significantly shorter in ASMCs isolated from superoxide dismutase 2 heterozygous (Sod2^+/?) mice, which exhibit increased arterial stiffness with aging, and the observed telomere attrition occurred over time. Furthermore, the telomere erosion occurred even though telomerase activity increased. In contrast, telomeres remained stable in wild-type and superoxide dismutase 1 heterozygous (Sod1^+/?) mice, which do not exhibit CVD phenotypes. The data indicate that mitochondrial oxidative stress, in particular elevated superoxide levels and decreased hydrogen peroxide levels, induces telomere erosion in the ASMCs of the Sod2^+/? mice. This reduction in telomere length occurs despite an increase in telomerase activity and correlates with the onset of disease phenotype. Our results suggest that the oxidative stress caused by imbalance in mitochondrial ROS, from deficient SOD2 activity as a model for mitochondrial dysfunction results in telomere dysfunction, which may contribute to pathogenesis of CVD.     

Iron-mediated degradation of ribosomes under oxidative stress is attenuated by manganese

Protein biosynthesis is fundamental to cellular life and requires the efficient functioning of the translational machinery. At the center of this machinery is the ribosome, a ribonucleoprotein complex that depends heavily on Mg²⁺ for structure. Recent work has indicated that other metal cations can substitute for Mg²⁺, raising questions about the role different metals may play in the maintenance of the ribosome under oxidative stress conditions. Here, we assess ribosomal integrity following oxidative stress both in vitro and in cells to elucidate details of the interactions between Fe²⁺ and the ribosome and identify Mn²⁺ as a factor capable of attenuating oxidant-induced Fe²⁺-mediated degradation of rRNA. We report that Fe²⁺ promotes degradation of all rRNA species of the yeast ribosome and that it is bound directly to RNA molecules. Furthermore, we demonstrate that Mn²⁺ competes with Fe²⁺ for rRNA-binding sites and that protection of ribosomes from Fe²⁺-mediated rRNA hydrolysis correlates with the restoration of cell viability. Our data, therefore, suggest a relationship between these two transition metals in controlling ribosome stability under oxidative stress.     

Oxidative stress in myelin sheath: The other face of the extramitochondrial oxidative phosphorylation ability

Abstract

Oxidative phosphorylation (OXPHOS) is not only the main source of ATP for the cell, but also a major source of reactive oxygen species (ROS), which lead to oxidative stress. At present, mitochondria are considered the organelles responsible for the OXPHOS, but in the last years we have demonstrated that it can also occur outside the mitochondrion. Myelin sheath is able to conduct an aerobic metabolism, producing ATP that we have hypothesized is transferred to the axon, to support its energetic demand.

In this work, spectrophotometric, cytofluorimetric, and luminometric analyses were employed to investigate the oxidative stress production in isolated myelin, as far as its respiratory activity is concerned. We have evaluated the levels of malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), markers of lipid peroxidation, as well as of hydrogen peroxide (H₂O₂), marker of ROS production. To assess the presence of endogenous antioxidant systems, superoxide dismutase, catalase, and glutathione peroxidase activities were assayed. The effect of certain uncoupling or antioxidant molecules on oxidative stress in myelin was also investigated.

We report that isolated myelin produces high levels of MDA, 4-HNE, and H₂O₂, likely through the pathway composed by Complex I–III–IV, but it also contains active superoxide dismutase, catalase, and glutathione peroxidase, as antioxidant defense. Uncoupling compounds or Complex I inhibitors increase oxidative stress, while antioxidant compounds limit ROS generation.

Data may shed new light on the role of myelin sheath in physiology and pathology. In particular, it can be presumed that the axonal degeneration associated with myelin loss in demyelinating diseases is related to oxidative stress caused by impaired OXPHOS.     

3,4-Dihydroxybenzaldehyde purified from the barley seeds (Hordeum vulgare) inhibits oxidative DNA damage and apoptosis via its antioxidant activity

Barley is a major crop worldwide. It has been reported that barley seeds have an effect on scavenging ROS. However, little has been known about the functional role of the barley on the inhibition of DNA damage and apoptosis by ROS. In this study, we purified 3,4-dihydroxybenzaldehyde from the barley with silica gel column chromatography and HPLC and then identified it by GC/MS. And we firstly investigated the inhibitory effects of 3,4-dihydroxybenzaldehyde purified from the barley on oxidative DNA damage and apoptosis induced by H₂O₂, the major mediator of oxidative stress and a potent mutagen. In antioxidant activity assay such as DPPH radical and hydroxyl radical scavenging assay, Fe²⁺ chelating assay, and intracellular ROS scavenging assay by DCF-DA, 3,4-dihydroxybenzaldehyde was found to scavenge DPPH radical, hydroxyl radical and intracellular ROS. Also it chelated Fe²⁺. In in vitro oxidative DNA damage assay and the expression level of phospho-H2A.X, it inhibited oxidative DNA damage and its treatment decreased the expression level of phospho-H2A.X. And in oxidative cell death and apoptosis assay via MTT assay and Hoechst 33342 staining, respectively, the treatment of 3,4-dihydroxybenzaldehyde attenuated H₂O₂-induced cell death and apoptosis. These results suggest that the barley may exert the inhibitory effect on H₂O₂-induced tumor development by blocking H₂O₂-induced oxidative DNA damage, cell death and apoptosis.     

扑草净对远志幼苗根系活力及氧化胁迫的影响

以远志(Polygala tenuifolia Willd.)为材料,应用组织化学和生物化学的方法研究不同浓度扑草净(0—400 mg/L)对远志幼苗生长、根系活力、膜脂过氧化、活性氧含量及抗氧化酶活性等的影响。10 mg/L扑草净对远志幼苗根系活力、细胞膜完整性及活性氧的积累几乎无显著影响,而25—400 mg/L扑草净处理则显著增加活性氧的积累,明显抑制根系活力且破坏细胞膜完整性;上述结果进一步被膜脂过氧化、质膜完整性、活性氧产生(O.2-和H2O2)的非损伤组织化学染色所证明。远志幼苗可通过多种抗氧化酶(SOD、POD、CAT、APX等)和非酶抗氧化剂(如脯氨酸)的相互协调作用,清除低浓度扑草净胁迫诱发产生的活性氧,减轻对细胞的伤害。研究结果表明,发芽期是远志对扑草净处理的敏感时期,较为安全的扑草净临界浓度为10 mg/L;25mg/L扑草净处理即引起远志幼苗氧化胁迫和膜脂过氧化,使细胞膜的完整性受到破坏,根系活力下降,抑制了远志幼苗的生长发育。该研究为远志抗除草剂胁迫机制及其栽培过程中除草剂的安全合理使用提供理论依据。     

The preventive and therapeutic effects of molecular hydrogen in ocular diseases and injuries where oxidative stress is involved

Oxidative stress initiates, accompanies and contributes to the development of several human diseases and injuries, including ocular diseases. Reactive oxygen species (ROS) can generate oxidative stress via excessive ROS production and/or decreased physiologically occurring antioxidants. To replace these weakened antioxidants, substances with effective antioxidant properties are needed in order to suppress oxidative stress and enable healing. Molecular hydrogen (H₂) is very suitable for this purpose due to its unique properties. H₂ is the only antioxidant that crosses the blood–brain and blood-ocular barriers. It quickly penetrates through tissue due to its small molecular size and effectively removes ROS, mainly hydroxyl radicals and peroxynitrite. Apart from its antioxidant effects, H₂ also displays anti-inflammatory, antiapoptotic, cytoprotective and mitohormetic properties. A significant advantage of H₂ is its nontoxicity, even when applied at high concentrations. In this review, we present the results of studies utilising H₂ in the treatment of ocular diseases involving oxidative stress. These results, obtained in experimental animals as well as in human clinical studies, show that the suppression of oxidative stress by H₂ treatment leads to the prevention or improvement of ocular diseases. In severe degenerative diseases, H₂ slows disease progression.     

Oxidative stress and production of bioactive monoterpene indole alkaloids: biotechnological implications

Monoterpene indole alkaloids (MIAs) encompass plant natural products with important pharmacological relevance. They include the anti-tumoral MIAs found in Catharanthus roseus and Camptotheca acuminata. The often low yields of bioactive alkaloids in plants has prompted research to identify the factors regulating MIA production. Oxidative stress is a general response associated with biotic and abiotic stresses leading to several secondary responses, including elicitation of MIA production. These changes in secondary metabolism may take place directly or via second messengers, such as Ca²⁺ and reactive oxygen species (ROS). H₂O₂ is the main ROS that participates in MIA biosynthesis. This review analyzes the links between oxidative stress, elicitation of bioactive MIA production and their potential roles in antioxidant defense, as well as exploring the implications to developing biotechnological strategies relevant for alkaloid supply.