PMID: 

Biotech Histochem. 2019 Nov 5:1-8. Epub 2019 Nov 5. PMID: 31687851

Abstract Title: 

The protective effects of thymoquinone on lung damage caused by cigarette smoke.

Abstract: 

Chronic obstructive pulmonary disease (COPD) is characterized by systemic inflammation that usually is caused by exposure to noxious particles or gases. Thymoquinone (TQ) prevents the production of inflammatory mediators, such as thromboxane B2 and leukotriene, by altering arachidonic acid metabolism. We investigated the preventive and curative effects of TQ on lung damage in rats caused by cigarette smoke (CS). We used 50 adult male rats, 30 of which were exposed to CS every day for 3 months. TQ in dimethylsulfoxide (DMSO) was administered intraperitoneally (i.p.) every day to ten animals to investigate the protective effects of TQ, and to ten other animals during the last 21 days to investigate the curative effect. Ten rats received saline for the last 21 days. Ten subjects were untreated controls. Ten controls that were not exposed to CS received TQ for the last ten days. Serum IL-8, IL-6, IL-1β and MMP-9 levels were measured using ELISA. IL-1β and IL-8 levels were elevated in the group exposed to CS compared to controls. IL-8 levels were decreased in the group that received only TQ compared to controls, which indicated the anti-inflammatory effect of TQ. The apoptotic index (AI) was increased in all groups that were exposed to CS compared to controls. The AI index was decreased in the group that received TQ for the last 21 days compared to the other CS groups. AI was increased in the group that received TQ daily compared to the other CS groups. Our findings indicate that TQ exerts curative effects for the inflammation caused by CS and may prevent apoptosis if administered in appropriate doses; however, long term TQ or DMSO exposure may produce cumulative toxic effects.

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PMID: 

Inflammation. 2019 Nov 9. Epub 2019 Nov 9. PMID: 31707574

Abstract Title: 

Thymoquinone Inhibits Neurogenic Inflammation Underlying Migraine Through Modulation of Calcitonin Gene-Related Peptide Release and Stabilization of Meningeal Mast Cells in Glyceryltrinitrate-Induced Migraine Model in Rats.

Abstract: 

Two main contributors of sterile neurogenic inflammation underlying migraine pain, calcitonin gene-related peptide (CGRP), and meningeal mast cells (MMCs) play a key role in the activation of the inflammatory cascade resulting in the sensitization of trigeminal nociceptors. It is well established that phytochemical agent thymoquinone exhibits multiple anti-inflammatory effects in different in vitro and in vivo models of neuroinflammation. But its effects on the CGRP release and meningeal mast cells are unknown. In the present study, we investigated the effects of thymoquinone on the CGRP release in migraine-related strategic structures which are crucial targets for anti-migraine drugs, and on the MMCs in glyceryl trinitrate (GTN)-induced in vivo migraine model as well as in the ex vivo meningeal preparations in rats. Anti-inflammatory thymoquinone ameliorated GTN-stimulated CGRP levels in plasma, and migraine-related structures including trigeminal ganglion and brainstem; moreover, thymoquinone inhibited degranulation of MMCs and prevented the increase in the number of MMCs in GTN-induced in vivo migraine model. However, in the ex vivo meningeal preparations, thymoquinone did not inhibit the GTN-induced CGRP release from trigeminal meningeal afferents. Our findings suggest that thymoquinone mediates modulation of CGRP release in trigeminal ganglion neurons and brainstem, and stabilization of MMCs. Thus, thymoquinone may be a promising candidate to prevent the meningeal neurogenic inflammation and consequently migraine.

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PMID: 

Biofactors. 2019 Nov 23. Epub 2019 Nov 23. PMID: 31758843

Abstract Title: 

Thymoquinone attenuates oxidative stress of kidney mitochondria and exerts nephroprotective effects in oxonic acid-induced hyperuricemia rats.

Abstract: 

BACKGROUND: Recent studies indicate hyperuricemia as an aggravating factor for kidney diseases progression. Basic research for novel agents to reduce hyperuricemia and kidney abnormalities will be highly rewarding. Herein, we report Thymoquinone (Tq) as an active constituent of Nigella sativa to have renal protective effective against oxonic acid (OA)-induced hyperuricemia, hypertension, and renal oxidative stress in rat models.METHODS: OA 750 mg/kg BW for 12 weeks was used to induce uricemia in Sprague dawley rats. Tq at 10 and 20 mg/kg BW were administered along with OA for treatment groups. Plasma uric acid concentration and systolic blood pressure were measured. Oxidative stress markers, total ATP content, and membrane bound ATPases were measured in renal mitochondria. Anti-oxidant enzymes were analyzed in the renal tissues. Apoptosis in renal tissue was detected. Key signaling proteins for apoptosis, oxidative stress, and lipid oxidation pathways were determined.RESULTS: OA induced both circulating uric acid levels and hypertension in the control group which was brought down on Tq treatments. Tq effectively prevented accumulation of uric acid and oxidative stress in the renal tissues. Tq also proved to increase the total ATP content of the renal mitochondria and prevented the apoptosis induced by OA. Tq increased the expressions of phosphorylated Akt, Nrf2, and HO-1 proteins while decreasing the levels of cleaved caspase-3 in renal cells.CONCLUSION: In summary, Tq exhibited protective effects on hyperuricemia-mediated renal oxidative stress and mitochondrial abnormalities which could be mediated by Nrf2/HO-1, Akt signaling pathways.

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PMID: 

BMC Complement Altern Med. 2019 Nov 27 ;19(1):334. Epub 2019 Nov 27. PMID: 31771651

Abstract Title: 

Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis.

Abstract: 

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model.METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis.RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation.CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

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PMID: 

J Complement Integr Med. 2019 Oct 26. Epub 2019 Oct 26. PMID: 31675349

Abstract Title: 

The impact of Crocus sativus stigma against methotrexate-induced liver toxicity in rats.

Abstract: 

Background The adverse effects of methotrexate (MTX) mainly hepatotoxicity restrict its clinical use. This study was designed to investigate the protective effects of saffron (Crocus sativus) (CS) extract on MTX-induced hepatotoxicity. Methods Twenty-eight male Wistar rats randomly divided into four equal groups. Except for control, all groups received a single intraperitoneal (i.p.) injection of MTX on the 3rd day of study. The CS extract was given (80 mg/kg i.p.) to rats 3 days before MTX and continued for the next 7 days (Pre&Post-CS group) or administrated after MTX injection and lasted for 7 days (Post-CS group). On the 11th day, all rats were sacrificed and their plasma levels of liver enzymes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were determined. Also, liver histopathology and hepatic levels of malondialdehyde (MDA), nitric oxide (NO) and super oxidase dismutase (SOD) were evaluated. Results The results showed that MTX significantly incremented plasma levels of AST, ALT, ALP and LDH (all p

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PMID: 

Clin Nutr ESPEN. 2019 Dec ;34:130-136. Epub 2019 Aug 16. PMID: 31677703

Abstract Title: 

Effect of saffron (Crocus sativus L.) on lipid profile, glycemic indices and antioxidant status among overweight/obese prediabetic individuals: A double-blinded, randomized controlled trial.

Abstract: 

OBJECTIVE: To investigate the effects of saffron (Crocus sativus L.) on lipid profile, glycemic and antioxidant status in overweight/obese individuals with prediabetes.METHODS: In this randomized, double-blind, placebo-controlled trial, the prediabetic patients were randomly assigned to receive saffron (15 mg/d) pills or placebo for eight weeks. Serum levels of lipid profile, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), blood urea nitrogen (BUN), creatinine, and diphenylpycrylhydrazyl (DPPH) radical scavenging activity were assessed biochemically at baseline and at 8 weeks after treatment. The adverse events, if any, were also recorded.RESULTS: Seventy-five of participants (36 in treatment and 39 in placebo groups) completed the study. Within-group comparisons revealed a significant effect of saffron supplementation on FBS (118.11 ± 3.55 vs. 109.14 ± 6.23), HbA1c (5.85 ± 0.12 vs. 5.70 ± 0.11), and DPPH (11.06 ± 3.24 vs. 13.46 ± 3.33) levels (P 

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PMID: 

Metab Brain Dis. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31728890

Abstract Title: 

Neuroprotective effect of Crocus sativus against cerebral ischemia in rats.

Abstract: 

The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral ischemia/reperfusion injury (I/R) in rats. Four groups of a total forty I/R rats with 60-min occlusion followed by 48 h reperfusion or sham surgery were used. The sham and left-brain I/R control groups where treated with normal saline. The rats of the other two groups received saffron extract (100 or 200 mg/kg, ip, respectively) for 3 successive weeks prior to left-brain I/R. Other four doses of saffron extractwere received by the rats of the last 2 groups 60 min prior to operation, during the surgery, and on days 1 and 2 following reperfusion. I/R group showed marked neurobehavioral, neurochemical and histopathological alterations. The results revealed a significant reduction in neurological deficit scores in the saffron-treated rats at both doses. Saffron significantly attenuated lipid peroxidation, decreased NO and brain natriuretic peptide (BNP) contents in I/R-brain tissue. On the other hand, saffron reversed the depletion of GSH in the injured brain. Moreover, saffron treatment evidently reduced apoptosis as revealed by a decrease in caspase-3 and Bax protein expression with a marked decrease in the apoptotic neuronal cells compared to I/R group. In addition, saffron administration effectively upregulated the expression of VEGF in I/R-brain tissue. In conclusion, saffron treatment offers significant neuroprotection against I/R damage possibly through diminishing oxidative stress and apoptosis and enhancement of VEGF.

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PMID: 

Avicenna J Phytomed. 2019 Nov-Dec;9(6):505-516. PMID: 31763210

Abstract Title: 

Evaluation of the effectiveness of crocin isolated from saffron in treatment of burning mouth syndrome: A randomized controlled trial.

Abstract: 

Objective: Burning mouth syndrome (BMS) is a debilitating disorder with few limited treatment modalities. Because of the proven association between BMS symptoms, and depression and anxiety, treatment modalities that alleviate the two latter etiologic factors can be clinically effective. Thus, owing to the antidepressant and potential analgesic effects of crocin (as an active constituent of saffron), the present study was performed to compare the effect of crocin and citalopram (as control) on BMS symptoms and depression/anxiety in patients with BMS.Materials and Methods: The present double-blind randomized clinical trial was carried out on BMS patients. Patients were randomly divided into citalopram (n=21) and crocin (n=26) groups and treated for 11 weeks. BMS symptoms (based on Visual Analysis Scale (VAS)), as well as anxiety and depression (based on Hamilton questionnaire) were evaluated at baseline and during the treatment period. Mann-Whitney, Chi-Square test, Independent t-test, Friedman, and Spearman correlation were employed for statistical analysis.Results: Our findings showed a significant effect for crocin on the severity of BMS symptoms, anxiety and depression in BMS patients.Conclusion: Crocin can be considered for treatment of BMS subjects with concurrent anxiety and/or depression.

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PMID: 

Phytother Res. 2019 Nov 25. Epub 2019 Nov 25. PMID: 31769107

Abstract Title: 

Crocin, an active constituent of Crocus sativus ameliorates cerulein induced pancreatic inflammation and oxidative stress.

Abstract: 

Acute pancreatitis (AP) is a disorder of the pancreas marked by profound inflammation and oxidative stress. Phytoconstituents presents an important toolbox of preventive strategies to combat inflammatory disorders. To this end, we selected the active constituent of Crocus sativus, crocin for evaluation against cerulein-induced AP, owing to its promising antiinflammatory activity in acute as well as chronic inflammatory conditions. The animals were randomly divided into five groups comprising of normal control, cerulein control, crocin low dose (30 mg/kg), crocin high dose (100 mg/kg), and crocin control (100 mg/kg). Various biochemical parameters and the levels of inflammatory cytokines and p65-NFκB were measured. The mechanism was investigated by histology and immunohistochemistry. We found that crocin significantly reduced the pancreatic edema, amylase, and lipase levels. It abrogated the oxidative stress incurred by cerulein challenge. We found that crocin modulated the pancreatic inflammatory cytokine levels. Crocin perturbed the nuclear translocation of p65-NFκB. Crocin reverted the pancreatic histology associated with AP. Furthermore, it upregulated the expression of Nrf-2 and downregulated the expression of IL-6, TNF-α, nitrotyrosine, and NFκB. Cumulatively, these results indicate that crocin has promising potential to prevent cerulein induced AP and regular intake of saffron can prove beneficial for the pancreatic health.

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PMID: 

Food Sci Nutr. 2019 Nov ;7(11):3403-3413. Epub 2019 Sep 18. PMID: 31762993

Abstract Title: 

Effects of Astragaloside IV on treatment of breast cancer cells execute possibly through regulation of Nrf2 via PI3K/AKT/mTOR signaling pathway.

Abstract: 

Traditional Chinese medicine (TCM) has from ancient times been applied in China for the treatment of breast cancer with its own unique theoretical system. Sanhuang decoction composed of astragalus membranaceus, prepared rhubarb, and rhizoma curcumae longae has traditionally been used for antioxidant stress, inflammatory reaction, and angiogenesis. However, the role and mechanism of Sanhuang decoction in breast cancer remains unknown. The present study demonstrated the antitumor activity of Sanhuang decoction against breast cancer xenografts in nude mice. Notably, Sanhuang decoction promoted severe necrosis and induced cell death. In addition, Sanhuang decoction obviously regulated the inflammation and oxidative stress. Despite these, Sanhuang decoction could increase the expression of Nrf2. Moreover, si-Nrf2 exhibited the opposite effects compared with the Sanhuang decoction treatment group and reversed the antibreast cancer role of Sanhuang decoction. Further, Sanhuang decoction remarkably suppressed the expression of PI3K/AKT/mTOR signaling pathway. Taken together, Sanhuang decoction was firstly evaluated to possess potent antibreast cancer effect in vivo through regulation of inflammation and oxidative stress accomplished by up-regulation of Nrf2 via PI3K/AKT/mTOR signaling pathway and Sanhuang decoction might be a powerful candidate formula for antibreast cancer.

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