PMID: 

PLoS One. 2019 ;14(10):e0224495. Epub 2019 Oct 25. PMID: 31652284

Abstract Title: 

Antibacterial activity of varying UMF-graded Manuka honeys.

Abstract: 

Honey has been used as a traditional remedy for skin and soft tissue infections due to its ability to promote wound healing. Manuka honey is recognized for its unusually abundant content of the antibacterial compound, methylglyoxal (MGO). The Unique Manuka Factor (UMF) grading system reflects the MGO concentration in Manuka honey sold commercially. Our objective was to observe if UMF values correlated with the antibacterial activity of Manuka honey against a variety of pathogens purchased over the counter. The antibacterial effect of Manuka honey with UMF values of 5+, 10+, and 15+ from the same manufacturer was assessed by the broth microdilution method. Minimum inhibitory concentration (MIC) values were determined against 128 isolates from wound cultures representing gram-positive, gram-negative, drug-susceptible, and multi-drug resistant (MDR) organisms. Lower MICs were observed with UMF 5+ honey for staphylococci (n = 73, including 25 methicillin-resistant S. aureus) and Pseudomonas aeruginosa (n = 22, including 10 MDR) compared to UMF 10+ honey (p

read more

PMID: 

J Pharmacol Exp Ther. 2019 Nov ;371(2):360-374. Epub 2019 Aug 16. PMID: 31420528

Abstract Title: 

Withaferin A Improves Nonalcoholic Steatohepatitis in Mice.

Abstract: 

Nonalcoholic steatohepatitis (NASH) is the progressive stage of nonalcoholic fatty liver disease that highly increases the risk of cirrhosis and liver cancer, and there are few therapeutic options available in the clinic. Withaferin A (WA), extracted from the ayurvedic medicine, has a wide range of pharmacological activities; however, little is known about its effects on NASH. To explore the role of WA in treating NASH, two well defined NASH models were used, the methionine-choline-deficient diet and the 40 kcal% high-fat diet (HFD). In both NASH models, WA treatment or control vehicle was administered to evaluate its hepatoprotective effects. As assessed by biochemical and histologic analyses, WA prevented and therapeutically improved liver injury in both models, as revealed by lower serum aminotransaminases, hepatic steatosis, liver inflammation, and fibrosis. In the HFD-induced NASH model, both elevated serum ceramides and increased hepatic oxidative stress were decreased in the WA-treated group compared with the control vehicle-treated group. To further explore whether WA has an anti-NASH effect independent of its known action in leptin signaling associated with obesity, leptin signaling-deficient ob/ob mice maintained on an HFD were used to induce NASH. WA therapeutically reduced NASH in HFD-treated leptin-deficient ob/ob mice, thus demonstrating a leptin-independent hepatoprotective effect. This study revealed that WA treatment could be an option for NASH treatment.

read more

PMID: 

BMC Complement Altern Med. 2019 Aug 15 ;19(1):217. Epub 2019 Aug 15. PMID: 31416451

Abstract Title: 

Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation.

Abstract: 

BACKGROUND: Systemic inflammation driven neuroinflammation is an event which correlates with pathogenesis of several neurodegenerative diseases. Therefore, targeting peripheral and central inflammation simultaneously could be a promising approach for the management of these diseases. Nowadays, herbal medicines are emerging as potent therapeutics against various brain pathologies. Therefore, in this contemporary study, the neuroprotective activity of Ashwagandha (Withania somnifera) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system.METHODS: To achieve this aim, young adult wistar strain male albino rats were randomized into four groups: (i) Control, (ii) LPS alone, (iii) LPS + ASH-WEX, (iv) ASH-WEX alone. Post regimen, the animals were subjected to Rotarod, Narrow Beam Walking and Novel Object Recognition test to analyze their neuromuscular coordination, working memory and learning functions. The rats were then sacrificed to isolate the brain regions and expressionof proteins associated with synaptic plasticity and cell survival was studied using Western blotting and Quantitative real time PCR. Further, neuroprotective potential of ASH-WEX and its active fraction (FIV) against inflammatory neurodegeneration was studied and validated using in vitro model system of microglial conditioned medium-treated neuronal cultures and microglial-neuronal co-cultures.RESULTS: Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. Since microglial-neuronal crosstalk is crucial for maintaining CNS homeostasis, the current study was further extended to ascertain whether LPS-mediated microglial activation caused damage to neurons via direct cell to cell contact or through secretion of inflammatory mediators. ASH-WEX and FIV pretreatment was found to restore neurite outgrowth and protect neurons from apoptotic cell death caused by LPS-induced neuroinflammation in both activated microglial conditioned medium-treated neuronal cultures as well as microglial-neuronal co-cultures.CONCLUSION: This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.

read more

PMID: 

J Pak Med Assoc. 2019 Oct ;69(10):1479-1485. PMID: 31622301

Abstract Title: 

Anti-oxidative and anti-proliferative activities of extracted phytochemical compound thymoquinone.

Abstract: 

OBJECTIVE: To evaluate the anti-oxidant and anti-proliferative potential of Thymoquinone extracted from the essential oil of indigenous herbs of Nigella sativa and Thymus vulgaris.METHODS: Extraction and quantification of Thymoquinone was carried out in July, 2017 in Department of Environmental Science, Lahore College for Women University (LCWU), Lahore. Thymoquinone was extracted from seeds of Nigella Sativa and aerial parts of Thymus vulgaris by employing soxhlet extraction with 1:4 ratios of nhexane and methanol. High Performance Liquid Chromatography was used to quantify Thymoquinone from the methanolic extracted oil of sample by applying calibration curve method. Extracted Thymoquinone was identified by sample peaks obtained at retention time were compared with peak of standard Thymoquinone at respective time. The Thymoquinone obtained from both samples was then subjected to Fourier-transform infrared spectroscopy for confirmation by identifying its functional groups. Anti-oxidant activities of both samples were measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assay in Department of Environmental Science, LCWU. In-vitro anti-proliferative activities of extracted Thymoquinone were evaluated in HeLa cell cancer lines by cell proliferations Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay in Department of Microbiology, University of Veterinary and Animal Sciences (UVAS), Lahore. SPSS 18 and Graph pad prism 18 was used for data analysis.RESULTS: Soxhlet extraction with solvents ratios yielded 48.92% oil from Nigella sativa and 23.2 % from Thymus vulgaris. High Performance Liquid Chromatography peak of standard Thymoquinone was measured at retention time of 5.5 min which was then compared with the peak obtained from both samples at the similar retention time. The extracted Thymoquinone from both samples were quantified by calibration curve method showing 614.25 mg/L from Nigella sativa and 548.86 mg/L from Thymus vulgaris. The two anti-oxidant assays of both samples compared with standard Thymoquinone showed significant scavenging activities in dose amount manner. Cell proliferation of HeLa cancer significantly decreased with dose response manner (p

read more

PMID: 

Int J Radiat Biol. 2019 Oct 22:1-28. Epub 2019 Oct 22. PMID: 31638880

Abstract Title: 

Nigella sativa oil and Thymoquinone reduce oxidative stress in the brain tissue of rats exposed to full head irradiation.

Abstract: 

To evaluate the antioxidant and radio-protective effects of Nigella sativa oil (NSO) and thymoquinone (TQ) on radiation-induced oxidative stress in brain tissue.Fifty-four Sprague-Dawley rats were divided into six groups to test the radio-protective effectiveness of Nigella sativa oil and thymoquine administered by either orogastric tube or intraperitoneal injection. Appropriate control groups were also studied.: Brain antioxidant capacity, as measured by the levels of total superoxide scavenger activity (TSSA), non-enzymatic superoxide scavenger activity (NSSA), superoxide dismutase, paraoxonase (PON) activities, total antioxidant status and total sulfhydryl (-SH) group, were lower in the irradiation (IR) only group while xanthine oxidase (XO) activity, total oxidant status (TOS), oxidative stress index (OSI) and lipid hydroperoxide (LOOH) levels were higher in the group compared with all other groups. Brain glutathione-S-transferase (GST) activity significantly decreased in the IR only group when compared with the control groups. Glutathione peroxidase (GSH-Px) activity was lower in the IR only, NSO plus IR, TQ plus IR groups when compared with the control group of TQ. Arylesterase (ARYL) activity was not statistically significant in the IR only group compared with all other groups.: The results suggest that Nigella sativa oil (NSO) and its active component, TQ, clearly protect brain tissue from radiation-induced oxidative stress.

read more

PMID: 

J Pharmacopuncture. 2019 Sep ;22(3):176-183. Epub 2019 Sep 30. PMID: 31673449

Abstract Title: 

Induction of Apoptosis and Growth-Inhibition by Thymoquinone in ACHN and GP-293 Cell Lines in Comparable with Cis-Platinum.

Abstract: 

Objective: In the current work, we investigated the cytotoxic and apoptotic effects of Thymoquinone (TQ), an active compound of Nigella sativa (N. sativa) and Cis-platinum, on normal renal epithelial (GP-293) and human renal adenocarcinoma cell lines (ACHN).Methods: GP-293 and ACHN cell lines were cultured in Dulbecco's modified Eagle's medium (DMEM) with 10% Fetal bovine serum (FBS) and 1% penicillin plus streptomycin antibiotic. The MTT assay was used for cellular viability assessment. Viability of cells was observed using inverted light microscope 24, 48 and 72 h after exposure of the cells to various concentrations of TQ (1, 2.5, 5, 10, 50 and 100μg/ml) and Cis-platinum (0.5, 1, 1.5, 2, 3, 6 and 12.5 μg/ml). Moreover, apoptosis was analyzed with a flow-cytometry method. The untreated cells were considered as control group.Results: Morphological changes such as reduced cell number and increased intercellular distance and reduced cell viability in ACHN and GP-293cell lines were observed in both TQ and Cis-platinum groups; however, Cis-platinum had greater effect on ACHN cell line than GP-293 cell line. In addition, GP-293 cell line was more sensitive to TQ compared to ACHN cell line. Furthermore, TQ and Cis-platinum had apoptotic effects on both ACHN and GP-293 cell lines.Conclusion: Our findings demonstrated that TQ and Cis-platinum had cytotoxic and apoptotic effects on both cell lines, However, GP-293 cell line was more sensitive to TQ. Additionally, Cis-platinum was more effective on ACHN cell line than on GP-293 cell line.

read more

PMID: 

J Environ Pathol Toxicol Oncol. 2019 ;38(2):185-194. PMID: 31679281

Abstract Title: 

AgNPs from Nigella sativa Control Breast Cancer: An In Vitro Study.

Abstract: 

In our current study, we synthesized silver nanoparticles (AgNPs) from an aqueous seed extract of Nigella sativa. The seed extract contains phytochemical compounds including phenols, terpenoids, and flavonoids that may act as reducing agents and are able to convert metal ions to metal nanoparticles. The formation of synthesized AgNPs was characterized using UV-visible spectroscopy, Fourier transform infra-red spectroscopy (FT-IR), scanning electron microscopy (SEM) and energy dispersive analysis of X-rays (EDX). The efficacy of N-AgNPs against human breast cancer (MCF-7) cells was tested. The synthesized AgNPs displayed dose-dependent cytotoxicity (1-200µg/mL) against MCF-7 cells. Morphological alterations of the cells also appeared as bright field images. Treatment of synthesized AgNPs altered the expression of Bax and Bcl-2 (apoptotic proteins) and COX-2 (inflammatory marker) in MCF-7 cells. To our knowledge, this is the first report demonstrating that N-AgNPs from Nigella sativa can induce apoptosis in MCF-7 cells.

read more

PMID: 

J Nucl Med. 2019 Nov 1. Epub 2019 Nov 1. PMID: 31676729

Abstract Title: 

Rapid Brain Nicotine Uptake from Electronic Cigarettes.

Abstract: 

This study sought to determine brain nicotine kinetics from the use of increasingly popular electronic cigarettes (E-cigs).Brain uptake of nicotine following inhalation from E-cigs was directly assessed in 17 E-cig users (8 females), usingC-nicotine and positron emission tomography. The brain nicotine kinetics parameters from E-cigs were compared with those from smoking combustible cigarettes (C-cigs).After inhalation of a single puff of E-cig vapor, brain nicotine concentration rose quickly (mean T1/2 27 sec) with a peak amplitude 25% higher in females than males, resembling previous observations with C-cigs. Nonetheless, brain nicotine accumulation from E-cigs was smaller than that from C-cigs in both males and females (24% and 32%, respectively).E-cigs can deliver nicotine rapidly to the brain. Therefore, to the extent that rapid brain uptake promotes smoking reward, e-cigarettes might maintain a degree of nicotine dependence and also serve as non-combustible substitutes for cigarettes.

read more

PMID: 

Phytomedicine. 2019 Sep 16 ;65:153091. Epub 2019 Sep 16. PMID: 31654988

Abstract Title: 

Total Glucosides of Paeony protects against collagen-induced mouse arthritis via inhibiting follicular helper T cell differentiation.

Abstract: 

BACKGROUND: The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response.PURPOSE: The aim of this study was to investigate the effects and mechanisms of TGP on RA.STUDY DESIGN: Type II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated.METHODS: DBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry.RESULTS: Our study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen.CONCLUSION: TGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.

read more

PMID: 

J Ethnopharmacol. 2019 Jun 12 ;237:74-80. Epub 2019 Mar 21. PMID: 30904702

Abstract Title: 

Preclinical investigation of the cardiovascular actions induced by aqueous extract of Pimpinella anisum L. seeds in rats.

Abstract: 

ETHNOPHARMACOLOGY RELEVANCE: Pimpinella anisum is used in traditional medicine because of its pharmacological properties which include cardiovascular action. However, no scientific information supports this use.AIM OF THE STUDY: This study investigated the effects of Pimpinella on arterial blood pressure (BP) and its pharmacological mechanism of action.MATERIAL AND METHODS: Pimpinella seeds were extracted with water, concentrated and freeze-dried yielding the aqueous extract (AE). A non-invasive BP assessment method was used (via the caudal artery) on Wistar, Wistar Kyoto, SHRs and rats that were submitted to high intake of dietary salt. Direct BP and heart rate were evaluated in Wistar rats in the absence or presence of atropine, L-NAME and angiotensin II. Spontaneous diuresis and the effect of AE on depolarized portal vein of Wistar rats was also examined.RESULTS: The data revealed that AE reduced BP in all groups evaluated and its effects were not due to diuretic, sympatholytic or parasympathomimetic actions. Additionally, it was shown that AE does not act as an angiotensin receptor blocker and does not induce hypotension by reducing vascular resistance induced by oxide nitric. In the depolarized portal vein, AE inhibited calcium influx, which indicates that AE acts as calcium channel blocker.CONCLUSION: This study validates the cardiovascular actions of Pimpinella and characterizes the hypotensive effects of Pimpinella that are related to the blockade of calcium channels.

read more