Stress and reward in the maternal brain of mothers with borderline personality disorder: a script-based fMRI study.

Borderline personality disorder (BPD) is associated with altered neural activity in regions of salience and emotion regulation. An exaggerated sensitization to emotionally salient situations, increased experience of emotions, and dysfunctional regulative abilities could be reasons for increased distress also during parenting. Mothers with BPD tend to have less reciprocal mother-child interactions (MCI) and reveal altered cortisol and oxytocin reactivity in the interaction with their child, which could indicate altered processing of stress and reward. Here, we studied underlying neural mechanisms of disrupted MCI in BPD. Twenty-five mothers with BPD and 28 healthy mothers participated in a script-driven imagery functional magnetic resonance imaging (fMRI)-paradigm. Scripts described stressful or rewarding MCI with the own child, or situations in which the mother was alone. Mothers with BPD showed larger activities in the bilateral insula and anterior cingulate cortex (ACC) compared to healthy mothers during the imagination of MCI and non-MCI. Already in the precursory phase while listening to the scripts, a similar pattern emerged with stronger activity in the left anterior insula (AINS), but not in the ACC. This AINS activity correlated negatively with the quality of real-life MCI for mothers with BPD. Mothers with BPD reported lower affect and higher arousal. An exaggerated sensitization to different, emotionally salient situations together with dysfunctional emotion regulation abilities, as reflected by increased insula and ACC activity, might hinder sensitive maternal behavior in mothers with BPD. These results underline the importance for psychotherapeutic interventions to improve emotional hyperarousal and emotion regulation in patients with BPD, especially in affected mothers caring for young children.

Microsocial analysis of dyadic interactions with toddlers and mothers with borderline personality disorder.

Borderline personality disorder (BPD) is known for disruptions in mother-child interaction, but possible underlying patterns of micro-behavior are barely understood. This is the first study examining behavioral dyadic synchrony-the coordinated and reciprocal adaptation of behavior-and regulation on a micro-level and relating it to macro-behavior in mothers with BPD and their toddlers. Twenty-five mothers with BPD and 29 healthy mothers participated with their 18- to 36-month-old toddlers in a frustration-inducing paradigm. Mother and toddler behavior was continuously micro-coded for gaze, affect, and vocalization. Synchrony, operationalized as the simultaneous engagement in social gaze and positive affect, and (co-)regulative behaviors and their contingencies were analyzed and associated with borderline symptom severity, the overall quality of interaction, and child internalizing and externalizing behavioral problems. Dyads with mothers with BPD showed significantly less synchrony compared to dyads with healthy mothers. Low synchrony was associated with high BPD symptom severity and low overall interaction quality. Dyads with BPD used the same amount of regulative behaviors as dyads with healthy mothers. Though both groups equally responded to children's negative emotionality, mothers with BPD were less effective in drawing the dyad back into synchrony. For dyads with BPD, regulative behaviors were negatively associated with child externalizing behaviors. BPD symptomology may reduce the effectiveness of mothers' attempts to attune to their child's needs. An emphasis on synchrony and regulative behaviors may be an important therapeutic target for parenting programs in mothers with BPD.

[The parent-child relationship in the context of parental mental illness-Possibilities for intervention]. / Die Eltern-Kind-Beziehung im Kontext elterlicher psychischer Erkrankung ­ Möglichkeiten zur Intervention.

The parent-child relationship is the earliest and one of the most important close social relationships in a person's life. It begins even during pregnancy, is expressed in interactions and is accompanied by many neurobiological processes. A sensitive interaction with the parent who is well-adapted to the needs of the child, is necessary for a healthy child development; however, parents with mental disorders often face more difficulties in parenting than healthy parents. They tend to exhibit more intrusive or withdrawn behavior and report experiencing increased stress in parenting, which in turn can be a risk factor for the mental disorder. At the same time, parenting can be a great resource. Early recognition of stress in parenting is central to healthy child development and also to the parent's mental health. In addition to disorder-specific treatment for parents, parent-child focused interventions can be used in relationship or interaction disorders. This article presents and discusses different prevention and intervention approaches.

Altered hormonal patterns in borderline personality disorder mother-child interactions.

BACKGROUND: Oxytocin, cortisol, and testosterone are involved in the processing of reward and stress and greatly influence mother-child interactions. Altered hormonal systems have been associated with borderline personality disorder (BPD), a disorder characterized by interpersonal deficits. Mothers with BPD tend to perceive interactions with the child as less rewarding and more stressful and interactions are often less reciprocal and have more negative states (i.e. constricted, tense, uncoordinated behaviors). Their children are at elevated risk for psychopathologies. Here, we studied underlying hormonal mechanisms of disrupted mother-child interaction in BPD. METHODS: Twenty-five mothers with BPD and 29 healthy mothers with their 18- to 36-month-old toddlers participated in a free-play mother-child interaction, which was evaluated with the Coding Interactive Behavior (CIB) Manual. Maternal blood samples were analyzed at baseline for oxytocin, cortisol, and testosterone, and after interaction for oxytocin and cortisol. RESULTS: Oxytocin decreased and cortisol remained unchanged in mothers with BPD while healthy mothers showed stable oxytocin and decreased cortisol after interaction. Testosterone basal levels were significantly higher in mothers with BPD. Cortisol reactivity and testosterone levels mediated the association between maternal BPD and dyadic negative states during interaction. CONCLUSIONS: These findings suggest that alterations in oxytocin, cortisol, and testosterone contribute to disruptions in mother-child interaction in BPD. Interacting with their child might not result in reward and relief of stress in mothers with BPD in the same way as in healthy mothers. Further research is needed to understand more about dyadic bio-behavioral processes in order to provide targeted parenting support. This could break the cycle of transgenerational transmission and improve maternal and child well-being.

The relationships between subclinical OCD symptoms, beta/gamma-band power, and the rate of evidence integration during perceptual decision making.

Previous studies have demonstrated that the rate of evidence integration during perceptual decision making, a specific computationally defined parameter, is negatively correlated with both subclinical symptoms of OCD measured on a continuum and categorically diagnosed patient status. However, the neural mechanisms underlying this deficit are unknown. Separate work has shown that both gamma and beta-band power are related to evidence integration, and differences in beta-band power in particular have been hypothesized to hinder flexible behavioral control. We sought to unify these two disparate literatures, one on OCD-related information processing differences constrained by behavioral data alone, and the other on the neural correlates of evidence integration. Using computational modeling and scalp EEG, we tested (N = 67) the relationships between subclinical symptom scores, drift rate, and gamma/beta-band activity during perceptual decision making. We replicated both prior work showing deficits in evidence integration as a function of OCD symptoms, and work showing a relationship between evidence integration and gamma and beta-band power. As predicted, the slope of beta-band power was correlated with OCD symptoms. However, the relationships between OCD symptoms and drift rate and the slopes of gamma and beta-band power and drift rate remained unchanged when simultaneously accounting for all variables, speaking against the hypothesis that differences in band-band power explain drift rate deficits.

Patients With Personality Disorders in Everyday Clinical Practice­Implications of the ICD-11.

BACKGROUND: Patients with difficult personalities or personality disorders are a special challenge for primary care physicians. Their style of interpersonal interaction is often difficult. As the ICD-11 classification comes into use, a new systematic approach to diagnosis is being introduced that focuses on the patient's functional impairments in everyday life. We describe the implications for the diagnosis and treatment of patients of this type. METHODS: This review is based on pertinent publications retrieved by a selective search, with particular attention to primary care and to somatic morbidity and mortality. RESULTS: 10-12% of the population suffers from personality disorders. A high degree of psychiatric comorbidity is typical; somatic diseases are also more than twice as common as in the general population. In emergency medicine, persons with personality disorders are more likely than others to present with a suicide attempt. Their lifetime risk of suicide is between 1.4% and 4.5% (the latter for persons with borderline personality disorder). CONCLUSION: Primary care physicians have an important role in the initial diagnosis of patients with personality disorders and in the planning of their treatment. Such patients require special care and attention from their physicians in view of their elevated somatic morbidity and mortality. In everyday clinical practice, physicians who encounter patients with complex and persistent mental problems, or just with a difficult style of interpersonal interaction, should consider the possibility of a personality disorder and motivate such patients to undergo psychotherapy, if indicated.

Early life maltreatment affects intrinsic neural function in mothers.

Early life maltreatment (ELM) has an impact on brain functions involved in parenting and is associated with impaired maternal sensitivity. Here, we investigated the influence of ELM on intrinsic neural function and its associations with maternal sensitivity in mothers without a current episode of a mental disorder. Twenty-seven mothers with ELM and 29 mothers without ELM were examined using resting-state functional magnetic resonance imaging, followed by Amplitude of Low Frequency Fluctuations, regional homogeneity and seed-based functional connectivity analyses. Videotaped interactions between mothers and their school-aged children were conducted to assess maternal sensitivity based on the Emotional Availability Scales. Regional and functional connectivity measures were used to investigate associations between intrinsic activity and emotional availability. Mothers with ELM showed reduced maternal sensitivity and lower intrinsic neural activity in the right superior frontal gyrus, the left precuneus, the left middle occipital gyrus, and the parietal cortex (left angular and right supramarginal gyrus) compared to mothers without ELM (p < .001, whole-brain). Amplitude of Low Frequency Fluctuations in the superior frontal gyrus was positively associated with maternal sensitivity across all participants (p = .002). The data suggest a behavioral and neural signature of ELM even in currently mentally healthy mothers. In particular, effects of ELM were found in distinct brain regions involved in social cognition and executive control. These ELM-related alterations may be associated with maternal behavior.

[Disease burden of borderline personality disorder: cost of illness, somatic comorbidity and mortality]. / Krankheitslast der Borderline-Persönlichkeitsstörung: Krankheitskosten, somatische Komorbidität und Mortalität.

BACKGROUND: Severe mental illnesses (SMI) are characterized by high psychosocial impairment as well as by increased somatic morbidity and mortality. The term SMI commonly includes psychotic, bipolar and severe unipolar depressive disorders but borderline personality disorder (BPD) also shows severe sequelae of the disease. MATERIAL AND METHODS: Published reviews and studies since 2010 examining disease burden of BPD, in terms of direct and indirect costs of illness, somatic comorbidity, and mortality were included. Furthermore, administrative data (clinically recorded billing data in Germany), comorbidity and mortality from a comprehensive analysis (n > 59 million, age ≥ 18 years) are reported. RESULTS: International studies reveal an increased disease burden, comorbidity, and mortality for BPD. In Germany BPD (administrative 1­year prevalence 0.34%) is associated with increased rates of somatic sequelae of trauma, hepatitis, HIV, COPD, asthma, and obesity. The estimated reduced life expectancy is 5.0-9.3 years of life lost (depending on age and sex). DISCUSSION: The burden of disease in BPD is clearly increased (cost of illness, somatic comorbidity and mortality). The increased mortality can mainly be explained by deaths as a consequence of poor physical health and associated BPD-related health behavior and only to a lesser degree by suicide. These results highlight the importance of classifying BPD as an SMI and the necessity to provide not only psychotherapeutic and psychiatric but also adequate somatic prevention and treatment. Individual improvement of everyday care as well as establishing new interdisciplinary and multiprofessional services could enhance health equality for people with BPD.

Proteomic analysis of human iPSC-derived sensory neurons implicates cell stress and microtubule dynamics dysfunction in bortezomib-induced peripheral neurotoxicity.

The neurotoxic effects of the chemotherapeutic agent bortezomib on dorsal root ganglia sensory neurons are well documented, yet the mechanistic underpinnings that govern these cellular processes remain incompletely understood. In this study, system-wide proteomic changes were identified in human induced pluripotent stem cell-derived sensory neurons (iSNs) exposed to a clinically relevant dose of bortezomib. Label-free mass spectrometry facilitated the identification of approximately 2800 iSN proteins that exhibited differential levels in the setting of bortezomib. A significant proportion of these proteins affect the cellular processes of microtubule dynamics, cytoskeletal and cytoplasmic organization, and molecular transport, and pathway analysis revealed an enrichment of proteins in signaling pathways attributable to the unfolded protein response and the integrated stress response. Alterations in microtubule-associated proteins suggest a multifaceted relationship exists between bortezomib-induced proteotoxicity and microtubule cytoskeletal architecture, and MAP2 was prioritized as a topmost influential candidate. We observed a significant reduction in the overall levels of MAP2c in somata without discernable changes in neurites. As MAP2 is known to affect cellular processes including axonogenesis, neurite extension and branching, and neurite morphology, its altered levels are suggestive of a prominent role in bortezomib-induced neurotoxicity.

Oxytocin Normalizes Approach-Avoidance Behavior in Women With Borderline Personality Disorder.

Background: Interpersonal deficits are a core symptom of borderline personality disorder (BPD), which could be related to increased social threat sensitivity and a tendency to approach rather than avoid interpersonal threats. The neuropeptide oxytocin has been shown to reduce threat sensitivity in patients with BPD and to modify approach-avoidance behavior in healthy volunteers. Methods: In a randomized, double-blind placebo-controlled between-subject design, 53 unmedicated women with BPD and 61 healthy women participated in an approach-avoidance task 75 min after intranasal substance administration (24 IU of oxytocin or placebo). The task assesses automatic approach-avoidance tendencies in reaction to facial expressions of happiness and anger. Results: While healthy participants responded faster to happy than angry faces, the opposite response pattern, that is, faster reactions to angry than happy faces, was found in patients with BPD. In the oxytocin condition, the "congruency effect" (i.e., faster avoidance of facial anger and approach of facial happiness vice versa) was increased in both groups. Notably, patients with BPD exhibited a congruency effect toward angry faces in the oxytocin but not in the placebo condition. Conclusions: This is the second report of deficient fast, automatic avoidance responses in terms of approach behavior toward interpersonal threat cues in patients with BPD. Intranasally administered oxytocin was found to strengthen avoidance behavior to social threat cues and, thus, to normalize fast action tendencies in BPD. Together with the previously reported oxytocinergic reduction of social threat hypersensitivity, these results suggest beneficial effects of oxytocin on interpersonal dysfunctioning in BPD.

Oxytocin modulates intrinsic neural activity in patients with chronic low back pain.

BACKGROUND: Modulation of pain perception by oxytocin (OXT) has attracted increased scientific and clinical interest. Neural mechanisms underlying these effects are poorly understood. In this study, we aimed to investigate the effects of intranasally applied OXT on intrinsic neural activity in patients with chronic low back pain (cLBP). METHODS: Twenty-four male patients with cLBP and 23 healthy males were examined using resting-state functional magnetic resonance imaging. Participants were scanned twice and received either intranasally applied OXT (24 international units) or placebo 40 min before scanning. The fractional amplitude of low-frequency fluctuations (fALFF) was computed to investigate regionally specific effects of OXT on intrinsic neural activity. In addition a multivariate statistical data analysis strategy was employed to explore OXT-effects on functional network strength. RESULTS: Differential effects of OXT were observed in cLBP and healthy controls. FALFF decreased in left nucleus accumbens and right thalamus in cLBP and increased in right thalamus in healthy controls after OXT application compared to placebo. OXT also induced activity changes in bilateral thalamus, left caudate nucleus and right amygdala in cLBP. OXT was associated with increased medial frontal, parietal and occipital functional network strength, though this effect was not group-specific. Regression analyses revealed significant associations between left nucleus accumbens, left caudate nucleus and right amygdala with pain-specific psychometric scores in cLBP. CONCLUSIONS: These data suggest OXT-related modulation of regional activity and neural network strength in patients with cLBP and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by OXT. SIGNIFICANCE: Our data suggest significant oxytocin-related modulation of intrinsic regional activity and neural network strength in patients with chronic low back pain and healthy controls. In patients, distinct regions of the pain matrix may be responsive to modulation by oxytocin. Therapeutic effects of oxytocin for improved pain treatment need to be further investigated.

Cognitive remediation therapy modulates intrinsic neural activity in patients with major depression.

BACKGROUND: Cognitive impairment is a core feature of major depressive disorder (MDD). Cognitive remediation may improve cognition in MDD, yet so far, the underlying neural mechanisms are unclear. This study investigated changes in intrinsic neural activity in MDD after a cognitive remediation trial. METHODS: In a longitudinal design, 20 patients with MDD and pronounced cognitive deficits and 18 healthy controls (HC) were examined using resting-state functional magnetic resonance imaging. MDD patients received structured cognitive remediation therapy (CRT) over 5 weeks. The whole-brain fractional amplitude of low-frequency fluctuations was computed before the first and after the last training session. Univariate methods were used to address regionally-specific effects, and a multivariate data analysis strategy was employed to investigate functional network strength (FNS). RESULTS: MDD patients significantly improved in cognitive function after CRT. Baseline comparisons revealed increased right caudate activity and reduced activity in the left frontal cortex, parietal lobule, insula, and precuneus in MDD compared to HC. In patients, reduced FNS was found in a bilateral prefrontal system at baseline (p < 0.05, uncorrected). In MDD, intrinsic neural activity increased in right inferior frontal gyrus after CRT (p < 0.05, small volume corrected). Left inferior parietal lobule, left insula, left precuneus, and right caudate activity showed associations with cognitive improvement (p < 0.05, uncorrected). Prefrontal network strength increased in patients after CRT, but this increase was not associated with improved cognitive performance. CONCLUSIONS: Our findings support the role of intrinsic neural activity of the prefrontal cortex as a possible mediator of cognitive improvement following CRT in MDD.

Autism and Reactions to Provocation in a Social and Non-social Context.

Externalizing behaviors in individuals with autism spectrum disorder (ASD) are often either reduced or elevated compared to healthy controls (HCs). This study investigated the moderating role of context in ASD by comparing 32 individuals with ASD to 40 HCs during a social and a non-social provocation task. Compared to HCs, individuals with ASD showed similar externalizing behavior in the social context. In the non-social context reactions after provocation were enhanced relative to non-provoking situations. The findings implicate that the context is an important influencing variable when comparing individuals with ASD to HCs after being provoked. Impulsivity, trait aggression and empathy did not predict behavior in the ASD group but were partly related to observed behavior in HCs.

The Sound and Face of Others: Vocal Priming Effects on Facial Emotion Processing in Posttraumatic Stress Disorder.

INTRODUCTION: Facial expressions and vocal intonation are key signals in the communication of emotions. Individuals with posttraumatic stress disorder (PTSD) are known to show an impaired perception of facial emotions. So far, research on multimodal emotional stimuli or the priming effects on emotion processing has been absent in PTSD. Therefore, we conducted a study to investigate the influence of vocal priming on facial emotion processing and classification in PTSD using electroencephalography. METHODS: Twenty-one women with PTSD compared to 28 healthy women were asked to classify emotion-morphed faces with predominantly angry, ambiguous, or predominantly happy expressions primed by either an angry or a happy voice. Responses and reaction times as well as the N170, a component reflecting configural face processing, were analyzed. RESULTS: Patients with PTSD were slower in classifying emotional faces that were primed by either an angry or happy voice compared to the healthy controls (HCs; η2 = 0.14). Additionally, patients with PTSD were faster in classifying facial expressions after angry compared to happy vocal primes (η2 = 0.14). HCs did not show this effect. Correlation analyses revealed positive associations between emotion (dys-)regulation and reaction times in patients with PTSD but not in HCs (r = 0.64-0.76). Furthermore, patients with PTSD showed greater N170 amplitudes for predominantly angry and ambiguous faces than HCs (η2 = 0.07). CONCLUSION: Data suggest that patients with PTSD experience more difficulties when processing complex social stimuli than HCs. The altered processing of complex social-emotional signals could amplify PTSD symptoms, thus qualifying as an explicit therapy target.

Neurobiological Mechanisms Mediating Emotion Dysregulation as Targets of Change in Borderline Personality Disorder.

Emotion dysregulation is a hallmark of borderline personality disorder (BPD). Most interventions for patients with BPD, therefore, aim at the improvement of emotion regulation. In the current paper, we provide an overview of studies investigating the effects of psychotherapeutic or pharmacological interventions on neurobiological correlates of various aspects of emotion regulation. In fact, studies suggest that the prefrontal-limbic circuit may play a major role in mediating effects of clinically efficacious psychotherapeutic treatments, i.e., they lead to clinical improvement via modulating the function and structure of the amygdala, the insula, and the dorsal anterior cingulate cortex, as well as prefrontal areas involved in the cognitive regulation of emotions, and enhancing the coupling of limbic and prefrontal areas. Oxytocin as a promising pharmacological approach to emotion dysregulation in BPD was shown to dampen amygdala activity in response to emotional stimuli. Understanding the brain mechanisms that mediate treatment effects will harness further development of targeted mechanism-based interventions for patients with BPD.

Remnants and changes in facial emotion processing in women with remitted borderline personality disorder: an EEG study.

According to longitudinal studies, most individuals with borderline personality disorder (BPD) achieve remission. Since BPD is characterized by disturbed emotion recognition, this study investigated behavioral and electrophysiological correlates of facial emotion classification and processing in remitted BPD. 32 women with remitted BPD (rBPD), 32 women with current BPD (cBPD), and 28 healthy women (HC) participated in an emotion classification paradigm comprising blends of angry and happy faces while behavioral and electroencephalographic (event-related potentials) data were recorded. rBPD demonstrated a convergence in behavior towards HC in terms of responses and reaction times. They evaluated maximally ambiguous faces more positively and exhibited faster reaction times when classifying predominantly happy faces compared to cBPD. Group × facial emotion interaction effects were found in early electrophysiological processes with post hoc tests indicating differences between rBPD and cBPD but not between rBPD and HC. However, BPD-like impairments were still found in rBPD in later processing (P300). Our results suggest a reduction in negativity bias in rBPD on the behavioral level and a normalization of earlier stages of facial processing on the neural level, while alterations in later, more cognitive processing do not remit. Early processing may be more state-like, while later impairments may be more trait-like. Further research may need to focus on these stable components.

Exogenous testosterone in a non-social provocation paradigm potentiates anger but not behavioral aggression.

Animal studies suggest a causal link between testosterone and aggression. However, in human research the exact role of this hormone is still unclear, having been linked to dominance and approach behavior rather than to aggression per se. In a social context, the induction of aggression might be confounded with dominance or status changes, which potentially influence the association between aggression and testosterone. The objective of the current study was to investigate the influence of testosterone on non-social aggression in a double-blind, placebo-controlled experiment including 90 healthy male participants. To this end, we developed an innovative paradigm in which participants were provoked by a malfunctioning joystick restraining them from a promised reward. As measures for aggression throughout the task the joystick amplitude was recorded and anger was assessed via emotional self-ratings. Participants reacted to the provocation with a significant shift to more negative emotions and increased implicit aggressive behavior, reflected in the force exerted to pull the joystick following provocation. Importantly, the study demonstrated first evidence for a modulating influence of testosterone on non-social aggression in males: Self-rated anger was significantly elevated in the testosterone group compared to the placebo group as a function of provocation. Testosterone administration did not significantly influence the implicit aggressive response. These findings demonstrate a potentiating effect of testosterone on provocation-related anger in a non-social context. Furthermore, the results highlight the importance of disentangling different components of aggression and characterizing different influencing factors when inferring on hormonal effects.

Reduced Responsiveness to Social Provocation in Autism Spectrum Disorder.

Deficits in emotion processing and social interaction are prominent symptoms of autism spectrum disorder (ASD). ASD has also been associated with aggressive tendencies towards self and others. The prevalence of aggressive behavior in this disorder, its etiology and its impact on social life are still unclear. This study investigated behavioral and physiological effects of social provocation in patients with ASD and healthy controls. We used a modified Taylor Aggression Paradigm in 24 high-functioning patients with ASD and 24 healthy controls. Participants were instructed to play against a fictitious human opponent. Money withdrawals toward the participant represented provocation and money deduction by the participant denoted aggressive behavior. Throughout the measurement, electrodermal activity (EDA) was recorded. Healthy controls showed higher aggressive responses to high provocation compared to low provocation, which demonstrated the effectiveness of the used procedure in eliciting aggression. Patients' responses were not influenced by the level of social provocation, although in both groups aggression was higher after lost compared to won trials. Physiologically, controls showed fewer but higher EDA amplitudes when responding aggressively, whereas patients displayed the opposite pattern of more but lower EDA amplitudes. The modified Taylor Aggression Paradigm successfully elicited aggression and revealed different behavioral and neurophysiological responses in patients and healthy controls. Patients' aggressive behavior as well as their physiological responses were less modulated by level of provocation compared to controls. Therapeutic attempts for patients might concentrate on improving empathic abilities and the understanding of social situations, including provocation and aggressive behavior.

Lipoxygenase inhibitors from natural plant sources. Part 2: medicinal plants with inhibitory activity on arachidonate 12-lipoxygenase, 15-lipoxygenase and leukotriene receptor antagonists.

The metabolism of arachidonic acid can be catalysed by either one of two enzyme families: the cyclooxygenases or the lipoxygenases. The lipoxygenase enzymes are classed into several subcategories including 5-, 12- and 15-lipoxygenases. The 5-lipoxygenase pathway has been the major focus of study due to the pronounced pro-inflammatory role of leukotrienes and the approval of 5-lipoxygenase inhibitors and leukotriene receptor antagonists for the clinical treatment of asthma. Although less well characterized, the 12-lipoxygenase as well as the 15-lipoxygenase pathway may also play an important role in the progression of human diseases such as cancer, psoriasis and atherosclerosis. The present review article summarizes the findings from an extensive literature search on plants that have been assessed for 12- and 15-lipoxygenase inhibitory activity as well as for leukotriene receptor antagonistic properties. The results are presented in a tabular format, and a discussion about promising plant species and natural compounds as well as relevant in vitro assays are included in this article.

Lipoxygenase inhibitors from natural plant sources. Part 1: Medicinal plants with inhibitory activity on arachidonate 5-lipoxygenase and 5-lipoxygenase[sol ]cyclooxygenase.

Arachidonate 5-lipoxygenase is the key enzyme in leukotriene biosynthesis and catalyses the initial steps in the conversion of arachidonic acid to biologically active leukotrienes. Leukotrienes are considered as potent mediators of inflammatory and allergic reactions and regarding their pro-inflammatory properties the inhibition of 5-lipoxygenase pathway is considered to be interesting in the treatment of a variety of inflammatory diseases. Besides 5-lipoxygenase inhibitors, drugs able to block the 5-lipoxygenase as well as the cyclooxygenase metabolic pathway are also of therapeutic value. A potential source for new 5-lipoxygenase inhibitors is undoubtedly provided by the abundance of medicinal plants used in traditional medicine. The present review article reports the results from a comprehensive literature search of plants that have been tested for 5-lipoxygenase inhibitory activity over the past 15 years. The obtained information is summarized in a tabular format and promising plant species and chemical classes of compounds are presented. Relevant in vitro tests are also described in this article.