Inhibitory effects of nobiletin and its major metabolites on lung tumorigenesis.

PMID: 

Food Funct. 2019 Oct 30. Epub 2019 Oct 30. PMID: 31664275

Abstract Title: 

Inhibitory effects of nobiletin and its major metabolites on lung tumorigenesis.

Abstract: 

Nobiletin (NBT), a citrus flavonoid, has been associated with various health benefits. Herein, we investigated the chemopreventive actions of NBT and its metabolites in a pulmonary carcinogenesis mouse model and human lung cancer cells. In 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-treated mice, the oral administration of NBT significantly suppressed lung tumorigenesis as evidenced by reduced tumor volume compared to the control mice. NBT also greatly attenuated cell proliferation in the lung of NNK-treated mice. Our previous study has identified three major metabolites of NBT, namely, 3'-demethylnobiletin (M1), 4'-demethylnobiletin (M2), and 3',4'-didemethylnobiletin (M3). In this study, we further determined the inhibitory effects of NBT and its metabolites on human non-small cell lung cancer (NSCLC) cells and the underlying mechanisms of action. Interestingly, we found that M2 and M3 exerted much stronger growth inhibition on both H460 and H1299 cells, compared to their parent compound NBT. Flow cytometry and western blotting analysis revealed that M2 and M3 caused significant cell cycle arrest and cellular apoptosis and profoundly modulated multiple proteins associated with cell proliferation and cell death, including p21, cyclin B1, CDK1, cyclin D1, CDK6, CDK4, Bax, cleaved caspase-1, and cleaved PARP. Overall, our results demonstrated that the oral administration of NBT significantly inhibited lung carcinogenesis in mice, and these chemopreventive effects could be attributed to its metabolites that showed potent anti-cancer effects.

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A combination of Citrus reticulata peel and black tea inhibits migration and invasion of liver cancer.

PMID: 

Mol Biol Rep. 2019 Oct 30. Epub 2019 Oct 30. PMID: 31673889

Abstract Title: 

A combination of Citrus reticulata peel and black tea inhibits migration and invasion of liver cancer via PI3K/AKT and MMPs signaling pathway.

Abstract: 

Liver cancer, one of the most common malignancies, is the second leading cause of cancer death in the world. The citrus reticulate peel and black tea have been studied for their beneficial health effects. In spite of the many studies have been reported, the underlying molecular mechanisms underlying its health benefits are still not fully understood. In present study, we developed a unique citrus reticulate peel black tea (CRPBT) by combined citrus reticulate peel and black tea and assessed its active ingredients, anti-oxidant and anti-liver cancer effects in vitro. The results suggested that CRPBT exhibited antioxidant capacity and effectively inhibited proliferation and migration of liver cancer cells in a dose- and time- dependent manner. Mechanistically, CRPBT significantly down-regulated phosphorylation of PI3K and AKT, and up-regulated the ratio of Bax/Bcl-2, and suppressed the expression of MMP2/9, N-cadherin and Vimetin proteins in liver cancer cells. Taken together, CRPBT has good effect on inhibiting migration, invasion, proliferation, and inducing apoptosis in liver cancer cells.

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Arctigenin induced apoptosis in hepatocellular carcinoma via ROS-mediated mitogen-activated protein kinases apoptosis pathway.

PMID: 

J Pharm Pharmacol. 2019 Oct 15. Epub 2019 Oct 15. PMID: 31617221

Abstract Title: 

Activation of reactive oxygen species-mediated mitogen-activated protein kinases pathway regulates both extrinsic and intrinsic apoptosis induced by arctigenin in Hep G2.

Abstract: 

OBJECTIVES: Arctigenin (ARG) has been proved to inhibit the viability of hepatocellular carcinoma (HCC) via inducing apoptosis. However, the precise mechanism remains unknown. The present study was aimed to further investigate the mechanism of ARG against HCC in vitro and in vivo.METHODS: Arctigenin was applied in vitro and in vivo. Western blotting, immunohistochemistry, etc., were used to investigate the mechanisms.KEY FINDINGS: The time-dependent enhancement of Bax/Bcl-2 ratio, cytochrome c release, Fas and FasL levels, caspase cascade activation and the loss in the mitochondrial out membrane potential indicated that both intrinsic and extrinsic apoptotic pathways were triggered by ARG. Moreover, Jun NH2-terminal kinase (JNK) and p38 phosphorylated time-dependently. And inhibition of the phosphorylation of either p38 or JNK led to a significant reduction in HepG2 apoptosis, owing to the crucial roles of p38 and JNK played in regulating the apoptosis pathways. In addition, ARG increased the generation of reactive oxygen species (ROS) in HepG2 cells, while the antioxidant N-acetyl cysteine almost reversed ARG-induced JNK and p38 activation, and dramatically decreased cell apoptosis. In vivo, ARG increased the cell apoptosis in tumour tissues, and p-p38, p-JNK and Bax were significantly upregulated.CONCLUSIONS: Our findings demonstrated that ARG induced apoptosis in HCC via ROS-mediated mitogen-activated protein kinases apoptosis pathway.

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Potential of Gentiana lutea for the treatment of obesity-associated diseases.

PMID: 

Curr Pharm Des. 2019 ;25(18):2071-2076. PMID: 31538881

Abstract Title: 

Potential of Gentiana lutea for the Treatment of Obesity-associated Diseases.

Abstract: 

BACKGROUND: Obesity, diabetes, and associated diseases are increasing all over the world, and pose a great burden on public health. According to the latest reports, 440 million people are suffering from diabetes. Diabetes is caused by impaired ability to produce or respond to the hormone insulin consequently resulting in hyperglycemia.METHODS: Data used for this review was obtained by using PUBMED/MEDLINE (1987-2018). The main data search terms were: Gentiana lutea, Gentiana lutea extract, Gentiana lutea constituents, obesity, diabetes mellitus, diabetic complications.RESULTS: In the present review, we describe the potential of root powder of yellow gentian (Gentiana lutea) for the prevention of obesity and diabetes including complications related to this disease.CONCLUSION: Reasonably effective, low-cost alternatives could fulfill an important role for a large part of the human population and could be of great value for the food market. Even a modest reduction of morbidity and mortality with respect to this disease translates into millions of lives saved.

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Matricaria chamomilla extract improves atopic dermatitis-like lesions in a murine model.

PMID: 

Rev Med Inst Mex Seguro Soc. 2017 Sep-Oct;55(5):587-593. PMID: 29193940

Abstract Title: 

[Matricaria chamomilla (aqueous extract) improves atopic dermatitis-like lesions in a murine model].

Abstract: 

BACKGROUND: Matricaria Chamomilla L. (Mch), popularly known as chamomile, has been used for centuries as an herbolary remedy due to its broad clinical spectrum. The aim of this study was to evaluate the effect of Mch associated to a vehicle with emollient function in induced atopic dermatitis (AD)-like lesions in a murine model.METHODS: AD was induced with dinitrochlorobenzene on 12 male seven-week old BALB/c mice. Animals were divided in three groups (control, GC; control negative, GCN; and experimental, GE). Liquid petrolatum was applied to the GCN and liquid petrolatum with aqueous extract of Mch at 7% to the GE. Induction and evolution of the lesions were verified by biopsy at 2nd and 6th week. Evaluation of peripheral blood cells to correlate inflammatory cells was made as well at the same weeks. Lesions were clinically evaluated at 2nd, 4th and 6th week. Scratching was monitored according to the observation methodology of Kobayashi et al.RESULTS: Mch aqueous extract associated to a vehicle with emollient function improves atopic dermatitis-like lesions after two weeks.

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Matricaria chamomilla extract is seen to reduce the adverse effects of formaldehyde on the reproductive system of male rats.

PMID: 

Andrologia. 2019 Oct ;51(9):e13362. Epub 2019 Jul 19. PMID: 31321807

Abstract Title: 

The effect of hydroethanolic extract of Matricaria chamomilla on the reproductive system of male rats exposed to formaldehyde.

Abstract: 

Formaldehyde is a common agent in our surrounding environment and can adversely affect the male reproductive system. In this study, the effectiveness of Matricaria chamomilla (MC) extract as an antioxidant was investigated in rats treated with formaldehyde. Thirty-two male Wistar rats were randomly divided into six groups: F (10 mg/kg formaldehyde), M200 (200 mg/kg MC extract), M500 (500 mg/kg MC extract), FM200 (10 mg/kg formaldehyde and 200 mg/kg MC extract), FM500 (10 mg/kg formaldehyde and 500 mg/kg MC extract) and control group (0.9% normal saline). Formaldehyde and MC extract were administered daily for 30 consecutive days via intraperitoneal injection. Hormonal status, sperm parameters, testis tissue histology, germinal cells apoptosis and stereological analyses of testis tissue were investigated. Testosterone and LH levels were significantly increased in FM200, FM500, F200 and F500 groups compared to Fgroup (p ≤ 0.05). Sperm count, motility and viability were significantly enhanced in FM200, FM500, F200 and F500 groups compared to F group (p ≤ 0.05). A decrease in the number of apoptotic germ cells in FM200, FM500, M200 and M500 groups (p ≤ 0.05) was evident. In particular, the MC extract in dose 500 mg/kg is seen to reduce the adverse effects of formaldehyde on the reproductive system of male rats.

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These findings suggest that Matricaria chamomilla extract could be a potent neuropharmacological agent against amnesia.

PMID: 

Phytomedicine. 2018 Aug 1 ;47:113-120. Epub 2018 May 7. PMID: 30166095

Abstract Title: 

Ameliorative effects of Matricaria chamomilla L. hydroalcoholic extract on scopolamine-induced memory impairment in rats: A behavioral and molecular study.

Abstract: 

BACKGROUND: Matricaria chamomilla L. is a medicinal herb traditionally used as the anti-inflammatory, antimicrobial, antiviral, anxiolytic and antidepressant agent. Nevertheless, supporting evidence demonstrated its memory enhancing activity and antioxidant properties.PURPOSE: To investigate the effects of the hydroalcoholic extract of M. chamomilla L. on memory processes in a scopolamine-induced a rat model of amnesia and to reveal its underlying mechanism of action.METHODS: The hydroalcoholic extract (25 and 75 mg/kg) was intraperitoneally administered to rats once daily for 7 days, and scopolamine (0.7 mg/kg) was injected 30 min before the behavioral testing to induce memory impairment. The phytochemical composition of the extract was quantified by HPLC/DAD analysis. Y-maze and radial arm-maze tests were employed for memory assessing. Acetylcholinesterase activity was measured in the rat hippocampus. Superoxide dismutase, glutathione peroxidase, and catalase specific activities along with the total content of reduced glutathione and protein carbonyl and malondialdehyde levels were also measured in the rat hippocampus. qRT-PCR was used to quantify BDNF mRNA and IL1β mRNA expression in the rat hippocampus.RESULTS: We first identified the chlorogenic acid, apigenin-7-glucoside, rutin, cynaroside, luteolin, apigenin and derivatives of apigenin-7-glucoside as the extract major components. Furthermore, we showed that the extract reversed the scopolamine-induced decreasing of the spontaneous alternation in the Y-maze test and the scopolamine-induced increasing of the working and reference memory errors in the radial arm maze test. Also, the scopolamine-induced alteration of the acetylcholinesterase activity and the oxidant-antioxidant balance in the rat hippocampus was recovered by the treatment with the extract. Finally, we demonstrated that the extract restored the scopolamine-decreased BDNF expression and increased IL1β expression in the rat hippocampus.CONCLUSION: These findings suggest that the extract could be a potent neuropharmacological agent against amnesia via modulating cholinergic activity, neuroinflammation and promoting antioxidant action in the rat hippocampus.

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Protective effect of Matricaria chamomilla ethanolic extract on hippocampal neuron damage in rats exposed to formaldehyde.

PMID: 

Oxid Med Cell Longev. 2018 ;2018:6414317. Epub 2018 Aug 14. PMID: 30186547

Abstract Title: 

Protective Effect ofEthanolic Extract on Hippocampal Neuron Damage in Rats Exposed to Formaldehyde.

Abstract: 

Formaldehyde, as a frequently used compound in many applications, crosses the blood-brain barrier and leads to hippocampal cell death and memory impairment. This study investigates the effects of ethanolic extract of(MC) on passive avoidance learning induced by damaged hippocampal cells and evaluates the antioxidant traits of MC. The male Wistar rats were divided into six (6 in each) groups: control (10 mg/kg normal saline), 200 (200 mg/kg MC extract), 500 (500 mg/kg MC extract), F (10 mg/kg formaldehyde), F200 (10 mg/kg formaldehyde and 200 mg/kg MC extract), and F500 (10 mg/kg formaldehyde and 500 mg/kg MC extract). Shuttle box assay was used for evaluation of passive avoidance learning. The apoptosis rate of hippocampal tissue, malondialdehyde (MDA) free radicals, and total antioxidant capacity was evaluated to determine the positive effect of the ethanolic extract of MC. We found that the ethanolic extract of MC reduced the cell death, time spent in a dark room, and MDA free radicals in the hippocampus, leading to increased total antioxidant capacity in this region. In conclusion, the ethanolic extract of MC could ameliorate formaldehyde-induced memory damage through decreasing cell death and MDA activity of the hippocampal region and increasing total antioxidant capacity.

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Arthur de Carvalho drops could be beneficial for the treatment of disorders of the gastrointestinal tract.

PMID: 

Pathophysiology. 2019 Sep 8. Epub 2019 Sep 8. PMID: 31668916

Abstract Title: 

Gastrointestinal effects of standardized Brazilian phytomedicine (Arthur de Carvalho Drops®) containing Matricaria recutita, Gentiana lutea and Foeniculum vulgare.

Abstract: 

Arthur de Carvalho Drops® (ACD) is a traditional Brazilian herbal medicine used to treat functional gastrointestinal disorders (FGIDs). ACD is a formulation of herbal extracts from Matricaria recutita (chamomile), Foeniculum vulgare (fennel) and Gentiana lutea L. (gentian). Considering the popular use for FGIDs, the aim of this work was to investigate the ACD effect on gastric and intestinal parameters with emphasis in a mechanistic approach using isolated duodenal preparations of rodents. Analytical method was developed and validated for quantify three actives principles/markers (Apigenin-7-glucoside, gentiopicroside and anethole) in ACD. The treatment with ACD significantly reduced the emetogenic stimuli induced by cisplatin in rats, showed a laxative effect, reduced the bethanechol-enhanced gastrointestinal transit and completely reversed the contraction induced by carbachol in rat duodenum. However, ACD did not alter the secretory gastric volume or total gastric acidity. The ACD affect the contractions of duodenal smooth muscle mediated by Cachannels and it is also able to inhibit the contractile response mediated by the release from its intracellular store. Furthermore, the relaxant effects of ACD appear independent of the nitric oxide pathway in rat duodenum. These results suggest that ACD could be beneficial for the treatment of disorders of the gastrointestinal tract.

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This review discusses how herbal teas may be beneficial in some areas of clinical and preventative health.

PMID: 

Plant Foods Hum Nutr. 2019 Sep ;74(3):266-276. PMID: 31243622

Abstract Title: 

Herbal Teas and their Health Benefits: A Scoping Review.

Abstract: 

Herbal teas are used as therapeutic vehicles in many forms of traditional medicine and are a popular global beverage. The purpose of this scoping review was to examine the evidence relating to the clinical efficacy and safety of herbal teas, and to identify the main research themes and gaps in knowledge to inform further work. A scoping review methodology was followed that set out the research question and described the sourcing, selection and analysis of studies. Overall, a total of 145 research publications were retrieved from global bibliographic databases, and after applying exclusion criteria, 21 remained. These studies looked at herbal tea use in female health, diabetes, heart disease and weight loss, with plant species including lavender, chamomile, fenugreek, stinging nettle, spearmint, hibiscus, yerba maté, echinacea and combinations of herbs. Observational studies explored associations between herbal tea consumption and cancer risk, liver health, and the risks linked to the consumption of environmental contaminants in the plant material. Despite plant materials being the basis for drug discovery,and the popularity of herbal teas, the number of articles exploring clinical efficacy and safety is small. In this review we discuss how herbal teas may be beneficial in some areas of clinical and preventative health, and what further research is required to understand whether regular consumption can contribute to healthy living more generally.

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