PMID: 

Phytother Res. 2019 Nov 19. Epub 2019 Nov 19. PMID: 31742775

Abstract Title: 

A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction.

Abstract: 

Many developed countries are experiencing a rapidly"greying"population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo-controlled, double-blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects.

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PMID: 

Biomolecules. 2020 Jan 25 ;10(2). Epub 2020 Jan 25. PMID: 31991752

Abstract Title: 

Super Critical Fluid Extracted Fatty Acids fromSeeds Repair Psoriasis-Like Skin Lesions and Attenuate Pro-Inflammatory Cytokines (TNF-α and IL-6) Release.

Abstract: 

(1) Background:Dunal (Ashwagandha) is a widely used medicinal herb in traditional medicinal systems with extensive research on various plant parts. Surprisingly, seeds ofhave never been investigated for their therapeutic potential. (2) Methods:seeds were extracted for fatty acids (WSSO) using super critical fluid extraction, and was analyzed by gas chromatography. Its therapeutic potential in psoriasis-like skin etiologies was investigated using a 12-O tetradecanoyl phorbol 13-acetate (TPA)-induced psoriatic mouse model. Psoriatic inflammation along with psoriatic lesions and histopathological scores were recorded. WSSO was also tested on murine macrophage (RAW264.7), human epidermoid (A431), and monocytic (THP-1) cells, stimulated with TPA or lipo poly-saccharide (LPS) to induce pro-inflammatory cytokine (IL-6 and TNF-α) release. NFκB promoter activity was also measured by luciferase reporter assay. (3) Results: Topical application of WSSO with concurrent oral doses significantly reduced inflammation-induced edema, and repaired psoriatic lesions and associated histopathological scores. Inhibition of pro-inflammatory cytokines release was observed in WSSO-treated A431 and THP-1 cells, along with reduced NFκB expression. WSSO also inhibited reactive nitrogen species (RNS) in LPS-stimulated RAW264.7 cells. (4) Conclusion: Here we show that the fatty acids fromseeds have strong anti-inflammatory properties, along with remarkable therapeutic potential on psoriasis-like skin etiologies.

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PMID: 

Microorganisms. 2020 Jan 25 ;8(2). Epub 2020 Jan 25. PMID: 31991820

Abstract Title: 

Biostimulating Gut Microbiome with Bilberry Anthocyanin Combo to Enhance Anti-PD-L1 Efficiency against Murine Colon Cancer.

Abstract: 

Recent advances have revealed the essential role of gut microbiomes in the therapeutic efficiency of immune checkpoint inhibitors (ICIs). Inspired by biostimulation, a method using nutrients to accelerate the growth of soil microorganisms and the recovery of soil microbial consortia, here we propose a bilberry anthocyanin combo containing chitosan and low molecular citrus pectin (LCP), in which LCP-chitosan is used to encapsulate anthocyanins so to enhance its digestive stability and, moreover, modulate the microbiome more favorable for the PD-L1 blockade treatment. Using murine MC38 colon cancer as a model system, we examined the effects of the combo on modulating the gut microbiome and therapeutic efficiency of PD-L1 blockade treatment. It was shown that bilberry anthocyanins enriched the subdominant species, increased both the concentration and the proportion of butyrate in feces and enhanced intratumoral CD8T cell infiltrations. The application of the bilberry anthocyanin combo restored the species diversity of gut microbiome decreased by LCP-chitosan and achieved the best control of tumor growth. These preliminary results indicated unprecedented opportunities of probiotics combo in improving the therapeutic efficiency of immune checkpoint inhibitor through manipulating gut microbiome.

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PMID: 

Can J Gastroenterol Hepatol. 2019 ;2019:5236149. Epub 2019 Nov 22. PMID: 31886154

Abstract Title: 

Blueberry Attenuates Liver Fibrosis, Protects Intestinal Epithelial Barrier, and Maintains Gut Microbiota Homeostasis.

Abstract: 

Objective: Recently, blueberry has been identified as a candidate for the treatment of liver fibrosis. Given the role of gut-liver axis in liver fibrosis and the importance of the gut microbiota homeostasis to the maintenance of the intestinal epithelial barrier, this study aimed to investigate whether blueberry could attenuate liver fibrosis and protect the intestinal epithelial barrier by maintaining the homeostasis of the gut microbiota.Method: A CCl-induced rat liver fibrosis model was used to detect the roles of blueberry in liver fibrosis and intestinal epithelial barrier. The liver weight and body weight were measured, the liver function was monitored by ALT and AST activity, protein and mRNA were determined by western blot and RT-qPCR, and the gut microbiome was detected by Miseq.Results: The results showed that blueberry could reduce the rate of liver weight/body weight gain (

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PMID: 

Nutr Res. 2019 Nov 7 ;73:83-96. Epub 2019 Nov 7. PMID: 31923607

Abstract Title: 

Phenolic-enriched blueberry-leaf extract attenuates glucose homeostasis, pancreaticβ-cell function, and insulin sensitivity in high-fat diet-induced diabetic mice.

Abstract: 

Blueberry fruit exhibits strong antioxidant activity owing to the presence of anthocyanin. As blueberry-leaf extract (BLE) contains chlorogenic acid and flavonol glycosides, we hypothesized that phenolic-enriched BLE would improve glucose homeostasis and insulin sensitivity. In this study, we examined whether BLE administration decreases the glucose levels and enhances the pancreatic function in mice with high-fat diet (HFD)-induced obesity and diabetes. C57BL/6J mice were divided into the following four groups: control diet (CD), HFD (60 kcal% fat diet), BLE (HFD with 1% BLE wt/wt diet), and yerba mate extract (YME; HFD with 0.5% YME wt/wt diet). Dietary BLE and YME reduced glucose tolerance, body weight, and plasma glucose, glycated hemoglobin, insulin, homeostasis model assessment of insulin resistance, triglyceride (TG), and non-esterified fatty acid levels. Compared with those of the HFD group, BLE was found to significantly reduce the pancreatic islet size and insulin content. Moreover, it increased the mRNA levels of pancreaticβ-cell proliferation-related genes, Ngn3, MafA, Pax4, Ins1, and Ins2, and pancreatic insulin signaling-related genes, IRS-1, IRS-2, PIK3ca, PDK1, PKCε, and GLUT-2, and decreased the transcriptional expression of the β-cell apoptosis-related gene, FoxO1. Both BLE and YME improved insulin sensitivity by inhibiting TG synthesis and enhancing lipid utilization in the liver and white adipose tissue (WAT). In pancreatic MIN6 β-cells, BLE and its main component (chlorogenic acid) increased β-cell proliferation and promoted insulin signaling. Overall, BLE enriched with phenolic compounds has thecapacity to prevent HFD-induced glucose tolerance and hyperglycemia by improving the pancreatic β-cell function.

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PMID: 

Nutrients. 2018 Oct 4 ;10(10). Epub 2018 Oct 4. PMID: 30287740

Abstract Title: 

Welsh Onion Root () Restores Ovarian Functions from Letrozole Induced-Polycystic Ovary Syndrome.

Abstract: 

Polycystic ovarian syndrome (PCOS) is an endocrine, metabolic, and systemic disease. It is mainly characterized by hyperandrogenism, oligomenorrhea, and high levels of luteinizing hormone (LH). There is no obvious therapy for PCOS, so patients have received symptomatic therapy. Welsh onion () is well-known in Asian countries for its usage in food ingredients and traditional medicines. It is also studied for its many effects. These include activation of immune responses, antihypertensive effects, and antioxidant effects. Using letrozole-induced PCOS rats, we focused on herbal therapy using extract of(AF;) roots to improve ovarian functions. As a nonsteroidal aromatase inhibitor, letrozole blocks conversion of testosterone to estrogen and subsequently induces PCOS phenomenon. We divided six-week-old female rats into four groups, including control, letrozole, letrozole + AF extract, and temporary letrozole groups. In our study, treatment with AF extract shows a low plasma LH/FSH ratio, and reveals high estrogen levels, ovarian morphology, folliculogenesis-related genes, and aromatase expression under PCOS mimic conditions. We concluded that AF extract administration influenced aromatase production, enhanced the estrogen steroid synthesis, and consequently restored the estrogenic feedback mechanism on the pituitary-ovary system.

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PMID: 

Folia Morphol (Warsz). 2019 ;78(3):554-563. Epub 2018 Dec 21. PMID: 30575005

Abstract Title: 

Evaluation of antioxidant and anti-lipid peroxidation potentials of Nigella sativa and onion extract on nicotine-induced lung damage.

Abstract: 

BACKGROUND: The present work aimed to compare the protective effect of Nigella sativa (NS) and onion extract on the nicotine-induced lung damage in rats. The antioxidant and anti-lipid peroxidation potentials of both agents on nicotine-induced lung damage were studied.MATERIALS AND METHODS: Thirty-six Sprague-Dawley albino rats, treated for 18 weeks, were divided into six groups: one negative control group, two positive control groups (oral onion and oral NS), nicotine-treated group, onion extract-treated group (concomitant nicotine and onion extract) and NS-treated group (concomitant nicotine and NS oil). The assessment of lung structure was based on haematoxylin and eosin and transmission electron microscopy. Lung malondialdehyde (MDA), superoxide dismutase activity (SOD), catalase (CAT), lung glutathione (GSH), and epithelial lining fluid GSH (ELF GSH) were used for assessment of the antioxidant and anti-lipid peroxidation potentials of NS and onion extract.RESULTS: The lung of the nicotine-treated group exhibited emphysematous air spaces, collapsed corrugated alveoli with ruptured interalveolar septa in some specimen and thickened septa in the others, massive congestion, extravasation of red blood cells, inflammatory cellular infiltration and fluid exudate. Much improvement was observed in the onion-treated group despite the presence of residual pathological affection. The lung in the NS-treated group showed the nearly normal architecture with slight congestion. Administration of nicotine promoted lipid peroxidation (elevation of MDA) and decreased the level of the antioxidant markers (SOD, CAT, lung GSH and ELF GSH). With the use of onion extract and NS, the level of MDA decreased by 17.85% and 35.71% while the levels of SOD, CAT, GSH, and ELF GSH increased. The increase was more prominent in the NS-treated group. The levels in the NS-treated group reached nearly the level markers of the control group.CONCLUSIONS: Nigella sativa and onion extract attenuate the pathological effect of nicotine in the lung rats through antioxidative and anti-lipid peroxidative mechanisms with higher protection to NS.

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PMID: 

Biomed Pharmacother. 2019 Jan ;109:2482-2491. Epub 2018 Dec 1. PMID: 30551509

Abstract Title: 

Wild edible onions – Allium flavum and Allium carinatum – successfully prevent adverse effects of chemotherapeutic drug doxorubicin.

Abstract: 

The objective of this study was to evaluate potential of two chemically characterized edible wild onion species, Allium flavum and Allium carinatum, to reduce side effects of cytostatic doxorubicin (Dox). Since Dox application is mainly limited due to its high cardiotoxicity, while there are no approved cardioprotective agents for the prevention of Dox adverse effects, new co-treatments are urgently needed. Here, we showed that methanol extracts expressed high antioxidant activity and synergistically increased Dox anticancer activity against human hepatoma (HepG2) and lung carcinoma (A549) cells, while protected normal human fibroblasts (MRC-5) from Dox cytotoxicity. Analysis of the antioxidative enzymes level (catalase and superoxide dismutases) showed that the catalase level was differently altered in cancer cells compared to normal cells upon applied treatments. In vivo toxicity evaluation in the zebrafish model revealed significantly lower toxicity of extracts compared to Dox, and no teratogenic effects at applied doses. We found that extracts successfully rescued the Dox-treated embryos of life-threating cardiomyopathy, while at the same time reduced developmental toxicity and neutropenia. Further analysis demonstrated that extracts had higher anti-angiogenic activity than sunitinib or auranofin, clinically used antiangiogenic drugs. In addition, angiogenesis was markedly more suppressed in Dox-extract cotreatments than upon single treatments.

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PMID: 

Biomolecules. 2019 06 11 ;9(6). Epub 2019 Jun 11. PMID: 31212721

Abstract Title: 

Marjoram Relaxes Rat Thoracic Aorta Via a PI3-K/eNOS/cGMP Pathway.

Abstract: 

Despite pharmacotherapeutic advances, cardiovascular disease (CVD) remains the primary cause of global mortality. Alternative approaches, such as herbal medicine, continue to be sought to reduce this burden.is recognized for many medicinal values, yet its vasculoprotective effects remain poorly investigated. Here, we subjected rat thoracic aortae to increasing doses of an ethanolic extract of(OME). OME induced relaxation in a dose-dependent manner in endothelium-intact rings. This relaxation was significantly blunted in denuded rings. N(ω)-nitro-l-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) significantly reduced the OME-induced vasorelaxation. Cyclic guanosine monophosphate (cGMP) levels were also increased by OME. Moreover, wortmannin or LY294002 significantly reduced OME-induced vasorelaxation. Blockers of ATP-sensitive or Ca2+-activated potassium channels such as glibenclamide or tetraethylamonium (TEA), respectively, did not significantly affect OME-induced relaxation. Similarly, verapamil, a Cachannel blocker, indomethacin, a non-selective cyclooxygenase inhibitor, and pyrilamine, a H1 histamine receptor blocker, did not significantly modulate the observed relaxation. Taken together, our results show that OME induces vasorelaxation via an endothelium-dependent mechanism involving the phosphoinositide 3-kinase (PI3-K)/ endothelial nitric oxide (NO) synthase (eNOS)/cGMP pathway. Our findings further support the medicinal value of marjoram and provide a basis for its beneficial intake. Although consuming marjoram may have an antihypertensive effect, further studies are needed to better determine its effects in different vascular beds.

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PMID: 

J Ethnopharmacol. 2019 Jul 15 ;239:111503. Epub 2018 Sep 11. PMID: 30217790

Abstract Title: 

Origanum majorana L. extract exhibit positive cooperative effects on the main mechanisms involved in acute infectious diarrhea.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Origanum majorana L. (Lamiaceae) is commonly used in Moroccan folk medicine to treat infantile colic, abdominal discomfort and diarrhea. Liquid stools and abdominal discomfort observed in acute infectious diarrhea are the consequences of imbalance between intestinal water secretion and absorption in the lumen, and relaxation of smooth muscle surrounding the intestinal mucosa.AIM OF THE STUDY: The objective of our study was to see if aqueous extract of Origanum majorana L. (AEOM) may exhibit an effect on those deleterious mechanisms.MATERIALS AND METHODS: The effect of AEOM on electrogenic Clsecretion and Naabsorption, the two main mechanisms underlying water movement in the intestine, was assessed on intestinal pieces of mice intestine mounted, in vitro, in Ussing chambers. AEOM effect on muscle relaxation was measured on rat intestinal smooth muscle mounted in an isotonic transducer.RESULTS: 1) AEOM placed on the serosal (i.e. blood) side of the piece of jejunum entirely inhibited in a concentration-dependent manner the Forskolin-induced electrogenic chloride secretion, with an IC= 654 ± 8 µg/mL. 2) AEOM placed on the mucosal (i.e. luminal) side stimulated in a concentration-dependent manner an electrogenic Naabsorption, with an IC= 476.9 ± 1 µg/mL. 3) AEOM (1 mg/mL) inhibition of Forskolin-induced electrogenic secretion was almost entirely prevented by prior exposure to Cachannels or neurotransmitters inhibitors. 4) AEOM (1 mg/mL) proabsorptive effect was greater in the ileum and progressively declined in the jejunum, distal colon and proximal colon (minimal). 5) AEOM inhibited in a concentration-dependent manner smooth muscle Carbachol or KCl induced contraction, with an IC= 1.64 ± 0.2 mg/mL or 1.92 ± 0.8 mg/mL, respectively.CONCLUSION: the present results indicate that aqueous extract of Origanum majorana L. exhibit positive cooperative effects on the main mechanisms that are involved in acute infectious diarrhea.

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