ABSTRACT The aging process involves chronic inflammation and oxidative stress in the brain, which increase susceptibility to neurodegeneration, age‐related pathologies, and anxiety‐like behavior. Dysbiosis of the gut microbiota and increased anxiety‐like behavior are related to one another and are both characteristic of aging. This study investigated the effects of an infusion prepared from the plant Pulicaria incisa ( Pi ) on locomotor activity, exploratory behavior, and the composition of the microbiomes of aging mice, with a focus on its mechanism of action. An open‐field test was used to evaluate locomotor activity and exploratory behavior in old mice that had been fed Pi infusion daily. Changes in the gut microbiota were examined using 16S rRNA gene sequencing and subsequent bioinformatic analysis. The antagonistic activity of the probiotic Bacilli against pathogenic bacteria was evaluated in vitro and in vivo using a C. elegans model. We observed a significant improvement in locomotor activity and exploratory behavior of aging mice treated with Pi infusion, accompanied by a reduced number of pyknotic neurons in the hippocampus, as compared to age‐matched controls. Analysis of gut microbiota revealed that Pi consumption restored levels of commensal Bacilli and significantly reduced Clostridia levels in Pi ‐treated aging mice, as compared to untreated aging mice. These changes might be associated with the Pi ‐induced antagonistic activity of probiotic Bacilli against pathogenic bacteria. Our findings suggest that consuming Pi infusion can alleviate aging‐induced reduction in locomotor activity and exploratory behavior, and gut–microbiota dysbiosis. They support the use of this prebiotic infusion as a nutritional intervention.

Traumatic brain injury (TBI) is a significant global health issue, causing cognitive, motor, and psychological impairments while increasing neurodegenerative disease risk. Essential oil extracted from Pelargonium graveolens (Pg), also known as geranium oil, is Food and Drug Administration (FDA)-approved and classified as generally recognized as safe for use in the food industry. Pg oil contains low molecular weight lipophilic compounds, which potentially traverse the blood-brain barrier and modulate brain functions. We have previously demonstrated that Pg oil exhibits anti-inflammatory and neuroprotective effects. Given the significant role of these processes in TBI pathophysiology and the absence of FDA-approved treatments, our goal in this study was to investigate the therapeutic potential of Pg oil in the closed-head injury (CHI) model for TBI. For this purpose, male C57BL/6JOlaHsd mice (8-9 weeks old, 20-25 g) underwent CHI using a modified weight-drop device and were treated orally with Pg oil for 2 weeks; 56 mice served as controls. Treatment group assignment was randomized based on neurological severity score (NSS) evaluation at 1-hour postinjury. Mice were monitored for 1 month following injury using a comprehensive behavioral battery administered in a blinded manner, then sacrificed for histopathological assessment. Pg was obtained from the Newe Ya'ar Research Center MAP Germplasm collection and prepared via steam distillation. The essential oil composition was characterized using gas chromatography-mass spectrometry (GC-MS). The therapeutic efficacy of Pg oil was demonstrated through multiple behavioral assessments, including the Barnes Maze, Y-maze, and novel object recognition test. Pg oil significantly enhanced cognitive performance in the injured mice, with effects persisting for at least 1-month post-injury. Histopathological evaluation revealed that Pg oil reduced axonal damage and increased neuronal survival in cortical and hippocampal regions. Additionally, Pg oil treatment significantly improved brain tissue preservation, as evidenced by reduced cortical and corpus callosum atrophy and decreased ventricle enlargement. The therapeutic benefits stemmed from anti-inflammatory and antioxidant activities, evidenced by reduced tumor necrosis factor-α, interleukin-1β, and lipid peroxidation levels, along with M2 phenotype immunomodulation, and elevated phosphorylated cyclic-AMP response element binding protein levels. The exclusive use of male mice in this study necessitates future investigation of Pg effects in female subjects. Our findings support the potential applications of Pg oil as a novel nutraceutical and a therapeutic candidate for TBI treatment and improvement of cognitive outcomes, warranting further translational research in TBI patients.

Garlic (Allium sativum L.) has been consumed globally as a functional food and traditional medicine for various ailments. Its active organosulfur compounds (OSCs) have demonstrated significant anticancer properties, particularly against gastric cancer. However, a comprehensive review of these effects and the underlying molecular mechanisms, including their role in overcoming drug resistance, is currently lacking. This review systematically examines both preclinical and clinical studies on the anticancer effects of garlic and its organosulfur compounds against gastric cancer, with a focus on patents. Emphasis is placed on explaining the mechanisms of action, exploring how these compounds can overcome drug resistance, and highlighting relevant patents that have been granted in this field. The literature search included databases, like PubMed, Web of Science, Google Scholar, ScienceDirect, and patent databases, including articles and patents published up to October 2024. Preclinical studies demonstrate that garlic-derived organosulfur compounds possess anticancer activities against gastric cancer. They work through multiple mechanisms, including inducing apoptosis, causing cell cycle arrest, inhibiting cancer stem cell properties, suppressing epithelial-mesenchymal transition, and modulating key signaling pathways, like PI3K/Akt and NF-κB. These compounds also show potential in overcoming drug resistance by downregulating multidrug resistance proteins and enhancing the effectiveness of standard chemotherapy drugs. Clinical studies suggest that regular garlic consumption may reduce the risk of gastric cancer and improve outcomes in patients undergoing chemotherapy. This review highlights the significant potential of garlic's organosulfur compounds as complementary agents in gastric cancer prevention and treatment and emphasizes the relevance of existing patents and the need for further clinical trials to confirm these effects and develop effective therapeutic strategies.

In recent decades, there has been growing evidence of the significant potential of plant-derived functional foods and beverages for improving human health. Pulicaria incisa is a desert plant that has been used for many years as a tea substitute, and its extracts are used in traditional medicine in Asia and Africa. This review aims to provide an up-to-date summary of the food applications, traditional uses, biological and pharmacological properties, and chemical constituents of various P. incisa extracts. A variety of biological effects of the plant have been demonstrated in vitro and in vivo, including beneficial effects on brain cells and anti-cancerous, anti-inflammatory, anti-oxidant, cytotoxic, hypoglycemic, hypocholesterolemic, anti-microbial and anti-fungal activities. This broad spectrum of beneficial activities suggests the potential uses of P. incisa as an additive to dry food products or functional beverages.

Parkinson's disease (PD) is an incurable neurodegenerative disease characterized by motor and non-motor disabilities resulting from neuronal cell death in the substantia nigra and striatum. Microglial activation and oxidative stress are two of the primary mechanisms driving that neuronal death. Here, we evaluated the effects of geranium oil on 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) mouse model for PD, on microglial activation, and oxidative stress. We demonstrate that oral treatment with geranium oil improved motor performance in this model. The therapeutic effects of geranium oil were observed as a significant increase in rotarod latency and distance among the mice treated with geranium oil, as compared to vehicle-treated MPTP mice. Geranium oil also prevented dopaminergic neuron death in the substantia nigra of the treated mice. These therapeutic effects can be partially attributed to the antioxidant and anti-inflammatory properties of geranium oil, which were observed as attenuated accumulation of reactive oxygen species and inhibition of the secretion of proinflammatory cytokines from geranium oil-treated activated microglial cells. A repeated-dose oral toxicity study showed that geranium oil is not toxic to mice. In light of that finding and since geranium oil is defined by the FDA as generally recognized as safe (GRAS), we do not foresee any toxicity problems in the future and suggest that geranium oil may be a safe and effective oral treatment for PD. Since the MPTP model is only one of the preclinical models for PD, further studies are needed to confirm that geranium oil can be used to prevent or treat PD.

Reactive oxygen species (ROS) and oxidative stress increase susceptibility to neurodegeneration and other age-related pathologies. We have previously demonstrated that an infusion prepared from Pulicaria incisa (Pi) has protective, anti-inflammatory, and antioxidative effects in glial cells. However, the neuroprotective activities of Pi infusion in cultured neurons and aging mice have never been studied. In the following study, the effects of Pi infusion were explored in a hydrogen peroxide (H2O2)-induced oxidative stress model in SH-SY5Y human neuroblastoma cells. Profiling of the infusion by gas chromatography-mass spectrometry identified chlorogenic acid, quercetin, and aucubin as some of its main constituents. H2O2-induced ROS accumulation and caspase 3 activity decreased SH-SY5Y viability and were prevented upon the pretreatment of cells with Pi infusion. Additionally, the Pi infusion upregulated cellular levels and the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) as well as the phosphorylation of cyclic AMP response element-binding protein (CREB). Aging mice treated daily for 18 months with Pi infusion exhibited reduced neuronal cell death in the hippocampus as compared to age-matched controls. We, therefore, propose Pi infusion as a candidate regulator of oxidative stress in the brain.

Plant-derived substances have been shown to affect potential targets in inflammatory diseases. We have previously purified from the desert plant Achillea fragrantissima , a sesquiterpene lactone named achillolide A, and demonstrated its anti-inflammatory activities in cultured brain macrophages named microglial cells. In the present study, we further investigated achillolide A in alleviating atopic dermatitis, a chronic and recurring inflammatory skin disease. We investigated achillolide A for its in vivo anti-inflammatory activity using the oxazolone model of atopic dermatitis in mice, in which oxazolone induces ear swelling. Our results show that mice treated with achillolide A showed a significant decrease in the oxazolone-induced ear swelling. Since macrophages are inflammatory cells that play a pivotal role in the pathogenesis of atopic dermatitis, the anti-inflammatory effects of achillolide A were also studied in spleen cells. We demonstrated that achillolide A reduced the levels of LPS-induced inflammatory cytokines IL-2, IL-6, TNFα, IFNγ and IL-12 that were secreted from cultured splenocytes. These data suggest that achillolide A should be considered for further research in treating atopic dermatitis.

Traditionally, horticultural research has concentrated on plant biochemistry and physiology, agricultural aspects, crop resistance to diseases, and so on. However, all plants contain many and various phytochemicals, with diverse biological activities. Throughout most of human history, before the development of the conventional pharmaceutical industry, herbal extracts containing these bioactive molecules were used to treat various diseases and symptoms. Herbal substances have also inspired the development of conventional medicines, with some of these medicines requiring a doctor’s prescription. The process of discovering plant substances with medical activities is long and multistaged, and is based on both ethnobotanical knowledge and experimental evidence. Due to the development of new areas of science, scientists have gained better understanding regarding the potential of plants beyond these classical research areas. This is why horticultural research expanded to new areas that bridge between human health and horticulture, the horticulture-health interphase.

SummaryPeppers are rich in health‐promoting phytochemicals, which are involved in the defence mechanisms against cancer. To select a lead variety of pepper with anti‐proliferative activity against colon cancer cells and liver cancer cells, high antioxidant activity, and high concentrations of capsaicin, flavonoids and phenolics, we compared these attributes in nine different pepper accessions belonging to Capsicum annuum and C. chinense. Quality parameters such as weight loss and total soluble solids content were tested as well. The different parameters were determined immediately after harvest and after prolonged storage and marketing simulation. A significant variation of these traits was detected among the accessions. C. chinense line 1745 had the highest antioxidant activity, the highest levels of capsaicin and flavonoids, a high and specific anti‐cancer activity, and the lowest weight loss level during postharvest storage. It is proposed that line 1745 has potential for use as a source for health‐promoting traits and should be further evaluated for use as a nutraceutical for the prevention and treatment of colon and liver cancers.

Alzheimer’s disease (AD) is the most prevalent cause of dementia in adults. Current available drugs for AD transiently alleviate some of the symptoms, but do not modify the disease mechanism or cure it. Therefore, new drugs are desperately needed. Key contributors to AD are amyloid beta (Aβ)- and reactive oxygen species (ROS)-induced cytotoxicities. Plant-derived substances have been shown to affect various potential targets in various diseases including AD. Therefore, phytochemicals which can protect neuronal cells against these insults might help in preventing and treating this disease. In the following research, we have isolated the sesquiterpene lactone achillolide A from the plant Achillea fragrantissima and, for the first time, characterized its effects on Aβ-treated neuroblastoma cells. Aβ is a peptide derived from the sequential cleavage of amyloid precursor protein, and is part of the pathogenesis of AD. Our current study aimed to determine whether achillolide A can interfere with Aβ-induced processes in Neuro2a cells, and protect them from its toxicity. Our results show that achillolide A decreased Aβ-induced death and enhanced the viability of Neuro2a cells. In addition, achillolide A reduced the accumulation of Aβ-induced ROS and inhibited the phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase and p44/42 mitogen-activated protein kinase in these cells. We therefore suggest that achillolide A may have therapeutic potential for the treatment of AD.

Plant derivatives offer a novel and natural source of therapeutics. The desert plant Achillea fragrantissima (Forssk) Sch. Bip (Af) is characterized by protective antioxidative and anti-inflammatory properties. Here, we examined the effect of two Af-derived phytochemicals on learning and memory, amyloid-β protein precursor (AβPP) metabolism, and tau phosphorylation in the familial Alzheimer's disease-linked APPswe/PS1ΔE9 mouse model. We observed that mice that were injected with the phytochemicals showed a trend of improvement, albeit statistically insignificant, in the Novel Object Recognition task. However, we did not observe improvement in contextual fear conditioning, suggesting that the benefits of treatment may be either indirect or task-specific. In addition, we observed an increase in the full-length form of AβPP in the brains of mice treated with Af-derived phytochemicals. Interestingly, both in vivo and in vitro, there was no change in levels of soluble Aβ, oligomeric Aβ, or the carboxyl terminus fragments of AβPP (APP-CTFs), suggesting that the increase in full length AβPP does not exacerbate AβPP pathology, but may stabilize the full-length form of the molecule. Together, our data suggest that phytochemicals present in Af may have a modest positive impact on the progression of Alzheimer's disease.

Alzheimer’s disease is a neurodegenerative disease, characterized by progressive decline in memory and cognitive functions, that results from loss of neurons in the brain. Amyloid beta (Aβ) protein and oxidative stress are major contributors to Alzheimer’s disease, therefore, protecting neuronal cells against Aβ-induced toxicity and oxidative stress might form an effective approach for treatment of this disease. 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF) is a flavonoid we have purified from the plant Achillea fragrantissima; and the present study examined, for the first time, the effects of this compound on Aβ-toxicity to neuronal cells.

Glutamate toxicity is a major contributor to the pathophysiology of numerous neurodegenerative diseases including amyotrophic lateral sclerosis and Alzheimer’s disease. Therefore, protecting neuronal cells against glutamate-induced cytotoxicity might be an effective approach for the treatment of these diseases. We have previously purified from the medicinal plant Achillea fragrantissima two bioactive compounds which were not studied before: the sesquiterpene lactone achillolide A and the flavonoid 3,5,4′-trihydroxy-6,7,3′-trimethoxyflavone (TTF). We have shown that these compounds protect astrocytes from oxidative stress-induced cell death and inhibit microglial activation. The current study examined for the first time their effects on differentiated mouse neuroblastoma N2a cells and on glutamate toxicity. We have found that, although these compounds belong to different chemical families, they protect neuronal cells from glutamate toxicity. We further demonstrate that this protective effect might be, at least partially, due to inhibitory effects of these compounds on the levels of reactive oxygen species produced following treatment with glutamate.

Activated microglial cells release various mediators, which cause neuronal cell death and have been implicated in different neurological disorders. The present study demonstrates that an infusion prepared from the plant Pulicaria incisa (Pi) inhibits microglial activation and down-regulates levels of the inflammatory cytokines interleukin (IL)-1β, IL-6, and of the toxic mediators nitric oxide and glutamate. The infusion was also shown to have antioxidant properties in cell-free assays (e.g., differential pulse voltammetry) and in a cellular assay, in which the infusion attenuated the induced accumulation of intracellular reactive oxygen species (ROS). We found that Pi infusion is rich in polyphenols, especially chlorogenic acids and ferulic acids, which might be responsible for the observed activities. It is proposed that Pi infusion be further evaluated for use as a functional beverage for the prevention and/or treatment of chronic diseases, especially neurodegenerative disorders in which microglial activation and oxidative stress play important roles.

Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain astrocytes (primary cultures) was determined by lactate dehydrogenase (LDH) activity, intracellular ROS levels were detected using 2′,7′-dichlorofluorescein diacetate, in vitro antioxidant activity was measured by differential pulse voltammetry, and protein phosphorylation was determined using specific ELISA kits. We have found that achillolide A prevented the H2O2-induced death of astrocytes, and attenuated the induced intracellular accumulation of reactive oxygen species (ROS). These activities could be attributed to the inhibition of the H2O2-induced phosphorylation of MAP/ERK kinase 1 (MEK1) and p44/42 mitogen-activated protein kinases (MAPK), and to the antioxidant activity of achillolide A, but not to H2O2 scavenging. This is the first study that demonstrates its protective effects on brain astrocytes, and its ability to interfere with MAPK activation. We propose that achillolide A deserves further evaluation for its potential to be developed as a drug for the prevention/treatment of neurodegenerative diseases and brain injuries where oxidative stress is part of the pathophysiology.

The demand for organic food products has increased over the last decades; however, the health effects of organically grown products are controversial and knowledge about how different fertilization regimes affect nutritionally and health relevant components is still limited. The aim of the present study was to determine the effect of organic and conventional mineral-based fertilizers on the quality of sweet red peppers. The parameters tested were anti-proliferative activity against cancer cells and the concentrations of antioxidants, flavonoids, phenolics, and vitamin C. The decay incidence, percentage of weight loss, and total soluble solids (TSS) content were also evaluated. The different parameters were tested in fresh peppers immediately after harvest and after cold storage. Our results show that the anti-proliferative activity of pepper extracts against colon cancer cells is similar in fresh organically and conventionally fertilized sweet red peppers. While in conventionally fertilized peppers the extent of the anti-proliferative activity was not affected by long storage, stored organic peppers lost 50% of their inhibitory activity. We also found that the levels of antioxidants, polyphenols, flavonoids, and vitamin C, as well as the general quality of the peppers were not significantly affected by the different fertilization practices nor by long storage.