What we need to know about the germ-free animal models.

The gut microbiota (GM), as a forgotten organ, refers to the microbial community that resides in the gastrointestinal tract and plays a critical role in a variety of physiological activities in different body organs. The GM affects its targets through neurological, metabolic, immune, and endocrine pathways. The GM is a dynamic system for which exogenous and endogenous factors have negative or positive effects on its density and composition. Since the mid-twentieth century, laboratory animals are known as the major tools for preclinical research; however, each model has its own limitations. So far, two main models have been used to explore the effects of the GM under normal and abnormal conditions: the isolated germ-free and antibiotic-treated models. Both methods have strengths and weaknesses. In many fields of host-microbe interactions, research on these animal models are known as appropriate experimental subjects that enable investigators to directly assess the role of the microbiota on all features of physiology. These animal models present biological model systems to either study outcomes of the absence of microbes, or to verify the effects of colonization with specific and known microbial species. This paper reviews these current approaches and gives advantages and disadvantages of both models.

The influence of propolis plus Hyoscyamus niger L. against COVID-19: A phase II, multicenter, placebo-controlled, randomized trial.

The incubation period of COVID-19 symptoms, along with the proliferation and high transmission rate of the SARS-CoV-2 virus, is the cause of an uncontrolled epidemic worldwide. Vaccination is the front line of prevention, and antiinflammatory and antiviral drugs are the treatment of this disease. In addition, some herbal therapy approaches can be a good way to deal with this disease. The aim of this study was to evaluate the effect of propolis syrup with Hyoscyamus niger L. extract in hospitalized patients with COVID-19 with acute disease conditions in a double-blinded approach. The study was performed on 140 patients with COVID-19 in a double-blind, randomized, and multicentral approach. The main inclusion criterion was the presence of a severe type of COVID-19 disease. The duration of treatment with syrup was 6 days and 30 CC per day in the form of three meals. On Days 0, 2, 4, and 6, arterial blood oxygen levels, C-reactive protein (CRP), erythrocyte sedimentation rate, and white blood cell, as well as the patient's clinical symptoms such as fever and chills, cough and shortness of breath, chest pain, and other symptoms, were recorded and analyzed. Propolis syrup with H. niger L. significantly reduces cough from the second day, relieving shortness of breath on the fourth day, and significantly reduces CRP, weakness, and lethargy, as well as significantly increased arterial blood oxygen pressure on the sixth day compared to the placebo group (p < 0.05). The results in patients are such that in the most severe conditions of the disease 80% < SpO2 (oxygen saturation), the healing process of the syrup on reducing CRP and increasing arterial blood oxygen pressure from the fourth day is significantly different compared with the placebo group (p < 0.05). The use of syrup is associated with a reduction of 3.6 days in the hospitalization period compared with the placebo group. Propolis syrup with H. niger L. has effectiveness in the viral and inflammatory phases on clinical symptoms and blood parameters and arterial blood oxygen levels of patients with COVID-19. Also, it reduces referrals to the intensive care unit and mortality in hospitalized patients with COVID-19. So, this syrup promises to be an effective treatment in the great challenge of COVID-19.

Effect of postnatal environmental enrichment on LTP induction in the CA1 area of hippocampus of prenatally traffic noise-stressed female rats.

Early-life stress negatively alters mammalian brain programming. Environmental enrichment (EE) has beneficial effects on brain structure and function. This study aimed to evaluate the effects of postnatal environmental enrichment on long-term potentiation (LTP) induction in the hippocampal CA1 area of prenatally stressed female rats. The pregnant Wistar rats were housed in a standard animal room and exposed to traffic noise stress 2 hours/day during the third week of pregnancy. Their offspring either remained intact (ST) or received enrichment (SE) for a month starting from postnatal day 21. The control groups either remained intact (CO) or received enrichment (CE). Basic field excitatory post-synaptic potentials (fEPSPs) were recorded in the CA1 area; then, LTP was induced by high-frequency stimulation. Finally, the serum levels of corticosterone were measured. Our results showed that while the prenatal noise stress decreased the baseline responses of the ST rats when compared to the control rats (P < 0.001), the postnatal EE increased the fEPSPs of both the CE and SE animals when compared to the respective controls. Additionally, high-frequency stimulation (HFS) induced LTP in the fEPSPs of the CO rats (P < 0.001) and failed to induce LTP in the fEPSPs of the ST animals. The enriched condition caused increased potentiation of post-HFS responses in the controls (P < 0.001) and restored the disrupted synaptic plasticity of the CA1 area in the prenatally stressed rats. Likewise, the postnatal EE decreased the elevated serum corticosterone of prenatally stressed offspring (P < 0.001). In conclusion, the postnatal EE restored the stress induced impairment of synaptic plasticity in rats' female offspring.

Protective effects of nanocurcumin against stress-induced deterioration in the intestine.

The therapeutic activities of curcumin have long been investigated in some chronic and inflammatory diseases. This study was designed to investigate the protective effects of nanocurcumin on intestinal barrier function, apoptosis, and oxidative stress in rats exposed to traffic noise. Forty rats were divided into four groups: two traffic noise-exposed groups of animals that received either vehicle (NOISE) or nanocurcumin (NCUR + NOISE) and two control groups that either remained intact (CON) or received nanocurcumin (NCUR). Nanocurcumin injection (15 mg/Kg/ip) and traffic noise exposure were administered daily for two weeks. The relative protein expression of intestinal tight junctions, occludin, and ZO-1 and Bax/Bcl-2 ratio was measured to evaluate barrier integrity and apoptosis in intestinal samples, respectively. Plasma D-lactate concentration was examined as a criterion of intestinal permeability. Corticosterone, superoxide dismutase (SOD) activity, glutathione (GSH), total antioxidant capacity (TAC), and nitrite were measured in serum. The noise exposure increased Bax/Bcl-2 ratio, corticosterone, and oxidative stress in the NOISE animals. Nanocurcumin treatment improved the Bax/Bcl-2 ratio and reduced corticosterone and oxidative stress in the NCUR + NOISE animals. The expression of tight junction proteins was decreased while the concentration of D-lactate was increased in the NOISE animals. Nanocurcumin did not efficiently impact the expression of tight junction proteins and the D-lactate level in the NCUR + NOISE group. Nanocurcumin administration displayed antioxidant and anti-apoptotic roles in the noise-exposed rats, however, it did not affect the intestinal barrier integrity. We concluded that reduced apoptosis in the intestine might be related to the antioxidant activity of nanocurcumin and its modulatory effects on the HPA axis in the nanocurcumin-treated animals.

Nanocurcumin substantially alleviates noise stress-induced anxiety-like behavior: The roles of tight junctions and NMDA receptors in the hippocampus.

Environmental noise stress affects non-auditory brain regions such as the hippocampus; an area of the brain implicated in cognition and emotion. Recent experimental data indicate that dysfunction of the blood-brain barrier (BBB) and overexpression of NMDA receptors may cause anxiety. In this experiment, we evaluated the effect of nanocurcumin on anxiety-like behavior and the expression of tight junctions and NMDA receptor subunits in the hippocampus of rats exposed to traffic noise. Forty rats were assigned to control (CON), stress (ST), nanocurcumin (NC), and nanocurcumin+stress (NC+ST) groups. Anxiety-like behavior was evaluated through an elevated zero maze apparatus. The gene expression of tight junctions and NMDA receptor subunits was examined by real-time PCR in the hippocampus. Statistical analysis showed that noise exposure developed anxiety-like behavior and elevated the corticosterone level in the ST group compared to the CON group. The nanocurcumin administration decreased the stress and anxiety in the NC+ST group compared to the ST animals. While the noise stress reduced the gene expression of tight junctions occludin, claudin-5, and ZO-1, the nanocurcumin administration increased them in the NC+ST animals. Furthermore, the noise stress elevated the gene expression of the NMDA receptor subunits GRIN1 and GRIN2B. The NC+ST animals showed a modification of these subunits compared to the ST animals. Our findings showed that noise exposure promotes stress and anxiety and impairs the NMDA receptor structure and BBB integrity. The nanocurcumin treatment partly restores the destructive effects of noise exposure.

Good bacteria, oxidative stress and neurological disorders: Possible therapeutical considerations.

Although oxidative agents such as free radicals can fight pathogens, an imbalance of oxidant/anti-oxidant activity can lead to harmful effects in our body known as oxidative stress. Various cellular organelles produce oxidative agents as well as anti-oxidants. The main oxidative stressors are classified under the free radical species; reactive oxygen species and reactive nitrogen species. On the other hand, superoxide dismutase, glutathione peroxidase, catalase and Glutathione are the main enzymatic mechanisms against oxidations. Gut microbiota with trillions of beneficial bacteria plays a considerable role in the production of anti-oxidants. Emerging evidence indicates an association between damaged intestinal flora and oxidative stress. Probiotics as beneficial bacteria are shown to restore damaged intestinal microbiota. Extensive evidence indicates the helpful effects of probiotics on the balance of anti-oxidant/oxidant agents. Since oxidative stressors play an important role in the development of some neurological disorders, intestinal microbiota modification and probiotic supplements are considered as suggested treatments to prevent or even relieve symptoms in the brain diseases. This review considers the beneficial effect of the gut and probiotic bacteria in either fighting the oxidative factors or producing the anti-oxidative biomarkers.

Effects of nano-curcumin on noise stress-induced hippocampus-dependent memory impairment: behavioral and electrophysiological aspects.

BACKGROUND: Noise pollution is one of the fundamental factors in the etiology of many disorders. Noise stress adversely affects cognitive behaviors and long-term potentiation (LTP), the candidate mechanism of learning and memory. In the present study, we examined the neuroprotective effects of nano-curcumin on behavioral and electrophysiological aspects of hippocampus-dependent memory in noise-exposed animals. METHODS: The stressed animals received either vehicle (ST) or nano-curcumin (NANO + ST) for 2 weeks. The control groups remained either intact (CON) or received nano-curcumin (NANO + CON). The ST and NANO + ST groups were exposed to daily noise for 2 weeks. The spatial memory was assessed in the Morris water maze. The LTP was investigated through field potential recording in the CA3-CA1 pathway of the hippocampus. Serum corticosterone level was measured at the end of the experiments. RESULTS: The ST group showed a lower cognitive function and suppressed LTP compared to the CON group. The nano-curcumin treatment improved the maze navigation and LTP induction compared to the ST group. While the stress exposure elevated the serum level of corticosterone in the ST animals, nano-curcumin treatment reduced it. CONCLUSIONS: The nano-curcumin treatment restores impaired behavioral and electrophysiological aspects of learning and memory in the noise-exposed animals. The plasma corticosterone levels may be associated with changes in cognitive behavior and synaptic plasticity.

The microbiota-gut- hippocampus axis.

Introduction: It is well known that the intestinal bacteria substantially affect physiological processes in many body organs. Especially, through a bidirectional communication called as gut-microbiota-brain axis, the gut microbiota deeply influences development and function of the nervous system. Hippocampus, as a part of medial temporal lobe, is known to be involved in cognition, emotion, and anxiety. Growing evidence indicates that the hippocampus is a target of the gut microbiota. We used a broad search linking the hippocampus with the gut microbiota and probiotics. Methods: All experimental studies and clinical trials published until end of 2021 were reviewed. Influence of the gut microbiota on the behavioral, electrophysiological, biochemical and histological aspects of the hippocampus were evaluated in this review. Results: The effect of disrupted gut microbiota and probiotic supplements on the microbiota-hippocampus link is also considered. Studies show that a healthy gut microbiota is necessary for normal hippocampus dependent learning and memory and synaptic plasticity. The known current mechanisms are production and modulation of neurotrophins, neurotransmitters and receptors, regulation of intracellular molecular processes, normalizing the inflammatory/anti-inflammatory and oxidative/antioxidant factors, and histological stability of the hippocampus. Activity of the hippocampal neuronal circuits as well as behavioral functions of the hippocampus positively respond to different mixtures of probiotic bacteria. Discussion: Growing evidence from animal researches indicate a close association between the hippocampus with the gut microbiota and probiotic bacteria as well. However, human studies and clinical trials verifying such a link are scant. Since the most of papers on this topic have been published over the past 3 years, intensive future research awaits.

Alzheimer's disease treatment: The share of herbal medicines.

One of the most frequent forms of dementia in neurological disorders is Alzheimer's disease (AD). It is a chronic neurodegenerative disease characterized by impaired learning and memory. Pathological symptoms as extracellular amyloid-beta (Aß) plaques and intracellular accumulation of neurofibrillary tangles occur in AD. Due to the aging of the population and increased prevalence of AD, discovery of new therapeutic agents with the highest effectiveness and fewer side effect seems to be necessary. Numerous synthetic medicines such as tacrine, donepezil, galantamine, rivastigmine, memantine, glutathione, ascorbic acid, ubiquinone, ibuprofen, and ladostigil are routinely used for reduction of the symptoms and prevention of disease progression. Nowadays, herbal medicines have attracted popular attention for numerous beneficial effects with little side effects. Lavandula angustifolia, Ginkgo biloba, Melissa officinalis, Crocus sativus, Ginseng, Salvia miltiorrhiza, and Magnolia officinalis have been widely used for relief of symptoms of some neurological disorders. This paper reviews the therapeutic effects of phytomedicines with prominent effects against various factors implicated in the emergence and progression of AD.

Interplay of Good Bacteria and Central Nervous System: Cognitive Aspects and Mechanistic Considerations.

The human gastrointestinal tract hosts trillions of microorganisms that is called "gut microbiota." The gut microbiota is involved in a wide variety of physiological features and functions of the body. Thus, it is not surprising that any damage to the gut microbiota is associated with disorders in different body systems. Probiotics, defined as living microorganisms with health benefits for the host, can support or restore the composition of the gut microbiota. Numerous investigations have proved a relationship between the gut microbiota with normal brain function as well as many brain diseases, in which cognitive dysfunction is a common clinical problem. On the other hand, increasing evidence suggests that the existence of a healthy gut microbiota is crucial for normal cognitive processing. In this regard, interplay of the gut microbiota and cognition has been under focus of recent researches. In the present paper, I review findings of the studies considering beneficial effects of either gut microbiota or probiotic bacteria on the brain cognitive function in the healthy and disease statuses.

Probiotic treatment differentially affects the behavioral and electrophysiological aspects in ethanol exposed animals.

OBJECTIVES: Harmful effects of alcohol on brain function including cognitive phenomena are well known. Damage to gut microbiota is linked to neurological disorders. Evidence indicates that intestinal flora can be strengthened by probiotic bacteria. In this study, we evaluated the effect of probiotics administration on LTP induction in rats receiving ethanol. MATERIALS AND METHODS: To assess if probiotic treatment influences toxic effect of ethanol, vehicle (CON) and probiotic treated (CON+PRO) control rats, and chronic ethanol (CE) exposed and CE probiotic treated (CE+PRO) animals were entered into the experiments. Shuttle box test and in vivo electrophysiological recordings were accomplished to evaluate memory and hippocampal baseline filed excitatory postsynaptic potentials (fEPSPs) and long term potentiation (LTP), respectively. RESULTS: Ethanol impaired memory in the CE rats. It also diminished the slope size of fEPSPs and prevented LTP induction. While the probiotic supplementation improved memory in the CE+PRO rats, it did not influence synaptic transmission in these animals. CONCLUSION: Conclusively, behavioral but not electrophysiological aspect of cognition is sensitive to probiotic treatment in the ethanol exposed animals.

Environmental enrichment restores impaired spatial memory and synaptic plasticity in prenatally stress exposed rats: The role of GABAergic neurotransmission.

Evidence shows that prenatal stress negatively affects cognitive functions and activity of neuronal circuits in postnatal age. Environmental enrichment counteracts deficits induced by early life stress. We examined if behavioural function and synaptic plasticity are sensitive to prenatal stress and, how much environmental enrichment and GABAergic system impact these phenomena. Animals were exposed to noise stress during the third trimester of foetal life. Groups of the stressed animals remained intact (S-SH) or received enrichment (S-EE) from postnatal day 22 for one month. Also, two groups received either saline (S-SH-S) or bicuculline (S-SH-B). One enriched group received muscimol (S-EE-M). The control groups were intact (C-SH), enriched (C-EE), or received bicuculline (C-SH-B) or saline (C-SH-S). We assessed learning and memory and, hippocampal long-term potentiation (LTP). Serum corticosterone levels were detected as a measure of stress condition. We found that stress reduced spatial performance and suppressed LTP in the S-SH animals. Postnatal enrichment restored both spatial learning and memory and synaptic plasticity in the S-EE rats. GABAergic antagonism strengthens maze performance and LTP induction in the S-SH-B group. However, muscimol prevented the positive effects of enrichment in the S-EE-M animals. Environmental enrichment and GABAergic modulation may improve disrupted spatial performance and synaptic plasticity.

Behavioral and electrophysiological aspects of cognition in neonate rats lactated by morphine addicted mothers.

OBJECTIVES: In addition to genetic factors, environmental phenomena during postnatal age highly affect development and, in turn, function of the brain. The present work evaluates if morphine consumption during lactation period influences the spatial performances and synaptic plasticity in rats at neonatal period of age. MATERIALS AND METHODS: Three groups of mothers were subcutaneously administered by 5 (M5), 10 (M10) or 20 (M20) mg/kg morphine every 12 hours during the lactation period. At 45 days old, their offspring were introduced to Morris water maze for assessment of spatial learning and memory. Basic field excitatory post-synaptic potentials (fEPSPs) were recorded in the CA1 area of hippocampus and, then, long term potentiation (LTP) was induced by tetanic stimulation. RESULTS: We found that the M10 and M20 rats spent more time and traveled longer distance to find the hidden platform of maze when compared to the control animals (P<0.05 for all comparisons). Similarly, these two morphine-exposed groups were inferior in the memory consolidation compared to their control counterparts. Comparing control and M20 rats revealed that morphine exposure decreases the mean amplitude and slope 10-90% of fEPSPs about 30 percent (P<0.001 for both comparisons) and inhibits the LTP induction in the CA1 area circuits. CONCLUSION: The present study provides behavioral and electrophysiological proofs for negative effect of morphine on the hippocampal-related function in the neonatally morphine-exposed rats.

The Effects of Probiotic Lactobacillus and Bifidobacterium Strains on Memory and Learning Behavior, Long-Term Potentiation (LTP), and Some Biochemical Parameters in ß-Amyloid-Induced Rat's Model of Alzheimer's Disease.

This study assessed the effects of probiotic supplementation on spatial learning and memory, long-term potentiation (LTP), paired-pulse facilitation (PPF) ratios, nitric oxide (NO) concentrations, and lipid profiles in a rat model of amyloid beta (Aß)(1-42)-induced Alzheimer's disease (AD). Forty rats were randomly divided into 4 groups. The sham (control and prevention) group received intracerebroventricular (ICV) injections of artificial cerebrospinal fluid, the Alzheimer group received ICV injection of Aß(1-42), and the probiotic+Alzheimer group received 500 mg probiotics daily (15×109 colony-forming unit) by gavage for 4 weeks before and 2 weeks after injection of Aß(1-42). The Morris water maze test was performed for evaluation of spatial learning and memory. LTP and PPF ratios were measured to evaluate longterm synaptic plasticity and pre-synaptic mechanisms, respectively. The results showed that probiotic supplementation significantly improved learning, but not memory impairment, and increased PPF ratios compared to those in the Alzheimer group. Both Aß(1-42) injection and probiotic supplementation alone did not significantly effect plasma level of NO. Probiotic supplementation of rats in the probiotic (6 weeks)+Alzheimer group decreased serum levels of total cholesterol, triglyceride, and very low-density lipoprotein-cholesterol significantly compared to the Alzheimer group. The results of this study suggest that probiotic supplementation may positively impact learning capacity and LTP in rats with AD, most likely via the release of neurotransmitters via presynaptic mechanisms or via a protective effect on serum lipid profiles.

Probiotic treatment improves the impaired spatial cognitive performance and restores synaptic plasticity in an animal model of Alzheimer's disease.

Studies demonstrate that damage to gut microbiota is associated with some brain disorders including neurodegenerative diseases such as Alzheimer's disease (AD). Accordingly, supporting gut microbiota has been considered as a possible strategy for AD treatment. We evaluated behavioral and electrophysiological aspects of the brain function in an animal model of AD made by intracerebroventricular injection of ß-amyloid. Two groups of control rats recieved either water as vehicle (Con) or probitics (Pro + Con). Also two groups of Alzheimeric animals were treated by either vehicle (Alz) or probiotics (Pro + Alz). Sham group was only subjected to surgical procedure and received the vehicle. Spatial learning and memory was assessed in Morris water maze. Also, basic synaptic transmission and long-term potentiation (LTP) were assessed by recording field excitatory postsynaptic potentials (fEPSPs) in hippocampus. Change in anti-oxidant/oxidant factors was assessed via measuring plasma level of total anti-oxidant capacity (TAC) and malondealdehyde (MDA). Brain staining was done to confirm ß-amyloid accumulation. Fecal bacteria quantification was accomplished to find how probiotic supplement affected gut microbiota. We found that while the Alz animals displayed a weak spatial performance, probiotic treatment improved the maze navigation in the Pro + Alz rats. Whereas basic synaptic transmission remained unchanged in the Alz rats, LTP was suppressed in this group. Probiotic treatment significantly restored LTP in the Pro + Alz group and further enhanced it in the Pro + Con rats. The intervention also showed a favorable effect on balance of the anti-oxidant/oxidant biomarkers in the Pro + Alz rats. This study provides the first proof on positive effect of probiotics on synaptic plasticity in an animal model of AD.

Probiotic supplementation improves the cognitive function and the anxiety-like behaviors in the stressed rats.

OBJECTIVES: Prenatal stresses increase incidence of neurodevelopmental disorders and influence cognitive abilities. Glucocorticoids are released in stress condition as endpoint activation of hypothalamus-pituitary-adrenal (HPA) axis. Evidence indicates a cross-talk between gut microbiota and brain function. This study assesses the effect of probiotic supplementation on behavioral functionand HPA axis action in stressed rats. MATERIALS AND METHODS: The young rats born from dams exposed to noise stress (ST) during third trimester of pregnancy were used. Two groups of stressed animals were received a two-week probiotic supplementation before (pre-ST) and after (post-ST) birth. The time and distance to find hidden platform in Morris water maze were evaluated as spatial memory. Also entry to open arms in elevated plus-maze was considered as anxiety-like behaviors. The serum level of corticosterone was measured as the HPA axis function. RESULTS: While the stressed rats decreased entries to open arms to one third compared to the controls (CON) the probiotic treatment increased the entries by two times. The ST rats required more time and distance to find the platform than did the CON animals. The pre- and post-ST rats significantly restored the impaired behavior almost near the CON ones. While the serum corticosterone concentration increased by 50% in the ST rats it was reduced to almost normal level in the pre- and post-ST rats. CONCLUSION: Our findings confirmed a link between the gut microbiome and probiotics with the behavioral functions and HPA axis. The probiotic treatment favorably affected the stress-dependent behavioral disorders and the interaction between HPA and gut-brain-microbiota axes.

Effect of probiotic supplementation on seizure activity and cognitive performance in PTZ-induced chemical kindling.

Epilepsy is one of the most common neurological disorders that severely affect life quality of many people worldwide. Ion transport in the neuronal membrane, inhibitory-excitatory mechanisms, and regulatory modulator systems have been implicated in the pathogenesis of epilepsy. A bidirectional communication is proposed between brain and gut where the brain modulates the gastrointestinal tract, and the gut can affect brain function and behavior. The gut microbiome takes an important role in health and disease where dysbiosis is involved in several neurological disorders. Probiotics as living microorganisms are beneficial to humans and animals when adequately administered. In the present work, we evaluated the effect of a probiotic bacteria mixture on seizure activity, cognitive function, and gamma-aminobutyric acid (GABA), nitric oxide (NO), malondealdehyde (MDA), and total antioxidant capacity (TAC) level of the brain tissue in the pentylenetetrazole (PTZ)-induced kindled rats. The Racine score and performance in water maze were considered as indices of the epileptic severity and the spatial learning and memory, respectively. We found that the probiotic supplementation substantially reduces seizure severity so that almost no probiotic-treated animals showed full kindling. The oral bacteriotherapy partially improved the spatial learning and memory in the kindled rats. The intervention decreased NO and MDA and increased TAC concentration of the brain. The probiotic treatment also increased the inhibitory neurotransmitter GABA. Our findings are the first preclinical report to show positive effect of probiotic bacteria on seizure-induced neurological disorders. Further investigation is required to answer the questions raised about the probable mechanisms involved.

Corrigendum: Does Severity of Alzheimer's Disease Contribute to Its Responsiveness to Modifying Gut Microbiota? A Double Blind Clinical Trial.

[This corrects the article DOI: 10.3389/fneur.2018.00662.].

Lavandula angustifolia biological characteristics: An in vitro study.

OBJECTIVE: Lavender is an aromatic shrub belonging to the Lamiaceae family. The flowers and leaves in different forms of extracts are used as herbal medicine. The accumulation of amyloid beta (Aß) plaques, reduction of acetylcholine due to hyperactivity of acetylcholinesterase, and glutamate neurotoxicity are known to be involved in decreased level of cognitive function. In our previous study, we proved that the aqueous extract of lavender improves learning and memory. This in vitro study was designed to evaluate antiaggregative, antioxidant, and antiacetylcholinesterase activities of the herbal medicine. METHODS: Thin layer chromatography, high-performance liquid chromatography, thioflavin, atomic force microscope (AFM), Elleman,and 2,2-diphenyl-1-picryl hydrazyl techniques were used for qualitative analysis, quantitative analysis, antiaggregative characteristics, anti-acetylcholinestrase activity and antioxidant activity of the lavender extract, respectively. RESULTS: We found chromatographic peaks of caffeic acid and luteolin-7-glycosid in the lavender extract. Our results indicated that aqueous extract of lavender dose-dependently inhibits the formation of Aß aggregate. The AFM technique showed that lavender largely diminished the Aß fibril formation. We also observed a considerable radical scavenging activity of the extract. CONCLUSIONS: Prevention of Aß plaque formation and antioxidant activity along with nontoxic features of the lavender extract promise possible effectiveness of this plant on improving some neurological disorders including Alzheimer's disease.