PMID: 

Int J Mol Sci. 2020 Mar 7 ;21(5). Epub 2020 Mar 7. PMID: 32155978

Abstract Title: 

Curcumin as an Anticancer Agent in Malignant Mesothelioma: A Review.

Abstract: 

Malignant mesothelioma is an infrequent tumor that initiates from the mesothelial cells lining of body cavities. The great majority of mesotheliomas originate in the pleural cavity, while the remaining cases initiate in the peritoneal cavity, in the pericardial cavity or on the tunica vaginalis. Usually, mesotheliomas grow in a diffuse pattern and tend to enclose and compress the organs in the various body cavities. Mesothelioma incidence is increasing worldwide and still today, the prognosis is very poor, with a reported median survival of approximately one year from presentation. Thus, the development of alternative and more effective therapies is currently an urgent requirement. The aim of this review article was to describe recent findings about the anti-cancer activity of curcumin and some of its derivatives on mesotheliomas. The potential clinical implications of these findings are discussed.

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PMID: 

Chem Biol Interact. 2020 Apr 1 ;320:109022. Epub 2020 Feb 27. PMID: 32112862

Abstract Title: 

Thymoquinone suppresses invasion and metastasis in bladder cancer cells by reversing EMT through the Wnt/β-catenin signaling pathway.

Abstract: 

Epithelial mesenchymal transformation plays a crucial role in the metastasis of bladder cancer, which makes bladder cancer difficult to cure. Bladder cancer is the most common malignancy of the urinary system, and distant metastasis is the leading cause of death. Therefore, finding a bioactive drug that can specifically inhibit epithelial mesenchymal transformation may be a new direction for bladder cancer treatment in the future. Thymoquinone (TQ), the major active compound isolated from black seed oil (Nigella sativa), has been reported to exhibit anti-inflammatory and anticancer abilities. TQ can exhibit its antitumor effect by inhibiting the proliferation and metastasis of cancer cells. However, the underlying mechanism of TQ as a tumor inhibitor in bladder cancer remains poorly understood. First, in this research, we demonstrate that TQ can reverse EMT by upregulating epithelial markers, such as E-cadherin, and downregulating mesenchymal markers, such as N-cadherin and vimentin. Furthermore, we demonstrate that TQ can suppress the activation of the Wnt/β-catenin signaling pathway and inhibit the expression of β-catenin target genes, such as MYC, Axin-2, MMP7, CyclinD1 and MET, which play crucial roles in EMT and cancer progression. Additionally, we demonstrate that TQ can inhibit the growth of xenografts and restrict the formation of tumor metastatic foci in the lung. Taken together, our findings confirm the antimetastatic effect of TQ in bladder cancer cells for the first time and also provide new evidence for the development of TQ as a novel treatment for metastatic bladder cancer.

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PMID: 

Iran J Basic Med Sci. 2019 Dec ;22(12):1432-1439. PMID: 32133061

Abstract Title: 

Effects of thymoquinone in prevention of experimental contrast-induced nephropathy in rats.

Abstract: 

Objectives: This study aimed to show the effects of thymoquinone, which is known for its antioxidant, anti-inflammatory, and renal protective effects in contrast-induced nephropathy.Materials and Methods: This is an experimental study in rats. 7 groups were included within the scope of our study: sham-vehicle (n=3), premedication-control (n=6), model (n=6), isolated thymoquinone (n=3+3), low-dose thymoquinone (n=6), and high-dose thymoquinone (n=7). In addition to 48 hr of water deprivation, we pre-medicated the rats with intra-peritoneal indomethacin and L-NAME administration. After premedication, 12.5 ml/kg dose of a high osmolar contrast agent-diatrizoat (Urografin %76) was administrated. Thymoquinone was administrated in two different doses of 1 mg/kg and 1.75 mg/kg for four days intraperitoneally. Renal functions, histopathological differences, oxidative stress parameters, and inflammatory indicators of rats were evaluated at the end of the study.Results: Significant decreases were observed in levels of serum creatinine and serum BUN with low-dose thymoquinone (1 mg/kg) administration. In light microscopy, significantly less histopathological damage was observed in the low-dose thymoquinone group compared to the contrast agent group. While high-dose thymoquinone is accepted as ineffective biochemically, toxic evidence was identified histopathologically. There were no significant differences between M and TA groups for serum MDA and SOD levels, which were compared to evaluate oxidative stress (0.99,0.98; respectively). TNF-α, iNOS, and NF-кB gene expressions were not significantly different between all groups (0.748,0.531,0.910; respectively).Conclusion: This experimental study has demonstrated for the first time the protective effect of the TQ substance for CIN in 1 mg/kg dose, in the accompaniment of biochemical and histopathological data in rats.

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PMID: 

Food Chem Toxicol. 2020 Mar 9:111253. Epub 2020 Mar 9. PMID: 32165235

Abstract Title: 

Thymoquinone induces apoptosis of human renal carcinoma Caki-1 cells by inhibiting JAK2/STAT3 through pro-oxidant effect.

Abstract: 

Currently, there are limited effective treatment options for renal cell carcinoma (RCC), due to its poor responses to conventional therapies. Instead of using extrinsic anti-cancer drugs, cancer cell-intrinsic reactive oxygen species (ROS) can be a weapon of RCC treatment. In the present study, we found that the phytochemical thymoquinone (TQ), a bioactive natural product obtained from the black cumin seeds of Nigella sativa, generates intracellular ROS in human renal cancer Caki-1 cells. Treatment of Caki-1 cells with high concentration of TQ up-regulated pro-apoptotic p53 and Bax expression, while downregulated anti-apoptotic Bcl-2 and Bcl-xl expression. Simultaneously, TQ suppressed the pro-oncogenic JAK2/STAT3 pathway, resulting in decreased expression of Bcl-2, Bcl-xl, cyclin D1, cyclin D2, and survivin. Thus, TQ can integrate between apoptosis and the pro-survival JAK2/STAT3 pathway through the Bcl family members, collectively magnifying Caki-1 cell apoptosis. However, treatment with the ROS scavenger N-acetyl cysteine significantly blocked TQ-induced apoptosis as well as incorporated signaling pathways, supporting that its pro-oxidant property is crucial for Caki-1 cell apoptosis. Moreover, TQ reduced the tumor xenograft growth of Caki-1 cells in nude mice. Taken together, these data suggest that TQ is a prominent anti-cancer drug to treat human RCC by enhancing apoptosis through its pro-oxidant nature.

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PMID: 

Ann Ital Chir. 2020 ;91:131-136. PMID: 32180584

Abstract Title: 

Comparison of the effects of thymoquinone and silymarin on the brain of rats having ischemia-reperfusion in the lower extremities.

Abstract: 

AIM: We aimed to show whether ischemia reperfusion (I/R) injury causes damage on brain or not, and whether thymoquinone and silymarin, as antioxidant and anti-inflammatory herbs, have beneficial effects on this damage or not.METHODS: Forty Wistar albino rats were carried out and were randomized to 4 groups with equal numbers (n=10): sham group, implemented of only anesthesia; control group, implemented of anesthesia and I/R injury; silymarin group, implemented of anesthesia and I/R injury and treated with a dose of 200 milligram/kg silymarin ip and thymoquinone group, implemented of anesthesia and I/R injury and treated with a dose of 20 mg/kg thymoquinone. Serum lipid hydroperoxide (LOOH) and total free sulfhydryl (Sh) levels were determined. Light microscopy was used to evaluate histological changes in brain tissue.RESULTS: Serum LOOH levels (0.21± 0.04 for control group, 0.29 ± 0.01 for sham group, 0.23 ± 0.09 for silymarin group, 0.29 ± 0.09 for thymoquinone group) were significantly higher and Sh levels (10.74 ± 1.71 for control group, 6.82 ± 0.24 for sham group, 9.12 ± 1.04 for silymarin group, 8.41 ± 1.12 for thymoquinone group)were significantly lower in control, silymarin and thymoquinone groups compared to control group (p

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PMID: 

Cureus. 2020 Feb 13 ;12(2):e6979. Epub 2020 Feb 13. PMID: 32089976

Abstract Title: 

The Carotenoid Compound of Saffron Crocetin Alleviates Effects of Ischemia Reperfusion Injury via a Mechanism Possibly Involving MiR-127.

Abstract: 

Renal impairment is associated with high mortality rates in severely ill patients. The need to prevent and treat renal damage underlines the importance of understanding the pathophysiological mechanisms that characterize it. This could also enable early diagnosis and the design of alternative therapeutic approaches. The aim of this study is to investigate the effect of crocetin, a known antioxidant, on the prevention of renal damage due to ischemia-reperfusion injury and the investigation of the mechanisms involved. The present study was performed on C57BL/6 mice aged 10-12 weeks. The animals had access to water and food ad libitum. The experiment, as described in materials and methods, was completed at 24 h, in which case the kidneys were removed for further study, both at tissue morphology (with immunohistochemistry) and changes in the level of miRs' expression by qRT-PCR. Accordingly, using the automatic precision analyzer, the serum levels of the basic parameters currently used clinically for the monitoring of renal function were determined. The administration of crocetin, despite the short presence of the substance in the body, affects all the biochemical parameters analyzed (urea, creatinine, uric acid, and ions of Na, K, Cl, P, Mg and Ca),​​causing significant decrease of their measured values. Crocetin also resulted in a significant limitation of the inflammation elements and the degree of epithelial damage. Furthermore, the administration of crocetin appears to restore levels of expression of miR21, miR127 and miR132.

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PMID: 

Sci Rep. 2020 Feb 27 ;10(1):3654. Epub 2020 Feb 27. PMID: 32107408

Abstract Title: 

Delivering Crocetin across the Blood-Brain Barrier by Usingγ-Cyclodextrin to Treat Alzheimer's Disease.

Abstract: 

Crocetin (CRT) has shown various neuroprotective effects such as antioxidant activities and the inhibition of amyloidβ fibril formation, and thus is a potential therapeutic candidate for Alzheimer's disease (AD). However, poor water solubility and bioavailability are the major obstacles in formulation development and pharmaceutical applications of CRT. In this study, a novel water-soluble CRT-γ-cyclodextrin inclusion complex suitable for intravenous injection was developed. The inclusion complex was nontoxic to normal neuroblastoma cells (N2a cells and SH-SY5Y cells) and AD model cells (7PA2 cells). Furthermore, it showed stronger ability to downregulate the expression of C-terminus fragments and level ofamyloid β in 7PA2 cell line as compared to the CRT free drug. Both inclusion complex and CRT were able to prevent SH-SY5Y cell death from HO-induced toxicity. The pharmacokinetics and biodistribution studies showed that CRT-γ-cyclodextrin inclusion complex significantly increased the bioavailability of CRT and facilitated CRT crossing the blood-brain barrier to enter the brain. This data shows a water-soluble γ-cyclodextrin inclusion complex helped to deliver CRT across the blood-brain barrier. This success should fuel further pharmaceutical research on CRT in the treatment for AD, and it should engender research on γ-cyclodextrin with other drugs that have so far not been explored.

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PMID: 

Front Med. 2020 Mar 13. Epub 2020 Mar 13. PMID: 32170559

Abstract Title: 

Combination of western medicine and Chinese traditional patent medicine in treating a family case of COVID-19 in Wuhan.

Abstract: 

In December 2019, an outbreak of novel Coronavirus (2019-nCoV) occurred in Wuhan, Hubei Province, China. By February 14, 2020, it has led to 66 492 confirmed patients in China and high mortality up to∼2.96% (1123/37 914) in Wuhan. Here we report the first family case of coronavirus disease 2019 (COVID-19) confirmed in Wuhan and treated using the combination of western medicine and Chinese traditional patent medicine Shuanghuanglian oral liquid (SHL). This report describes the identification, diagnosis, clinical course, and management of three cases from a family, suggests the expected therapeutic effects of SHL on COVID-19, and warrants further clinical trials.

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PMID: 

Chin J Integr Med. 2020 Feb 17. Epub 2020 Feb 17. PMID: 32065348

Abstract Title: 

Can Chinese Medicine Be Used for Prevention of Corona Virus Disease 2019 (COVID-19)? A Review of Historical Classics, Research Evidence and Current Prevention Programs.

Abstract: 

OBJECTIVE: Since December 2019, an outbreak of corona virus disease 2019 (COVID-19) occurred in Wuhan, and rapidly spread to almost all parts of China. This was followed by prevention programs recommending Chinese medicine (CM) for the prevention. In order to provide evidence for CM recommendations, we reviewed ancient classics and human studies.METHODS: Historical records on prevention and treatment of infections in CM classics, clinical evidence of CM on the prevention of severe acute respiratory syndrome (SARS) and H1N1 influenza, and CM prevention programs issued by health authorities in China since the COVID-19 outbreak were retrieved from different databases and websites till 12 February, 2020. Research evidence included data from clinical trials, cohort or other population studies using CM for preventing contagious respiratory virus diseases.RESULTS: The use of CM to prevent epidemics of infectious diseases was traced back to ancient Chinese practice cited in Huangdi's Internal Classic (Huang Di Nei Jing) where preventive effects were recorded. There were 3 studies using CM for prevention of SARS and 4 studies for H1N1 influenza. None of the participants who took CM contracted SARS in the 3 studies. The infection rate of H1N1 influenza in the CM group was significantly lower than the non-CM group (relative risk 0.36, 95% confidence interval 0.24-0.52; n=4). For prevention of COVID-19, 23 provinces in China issued CM programs. The main principles of CM use were to tonify qi to protect from external pathogens, disperse wind and discharge heat, and resolve dampness. The most frequently used herbs included Radix astragali (Huangqi), Radix glycyrrhizae (Gancao), Radix saposhnikoviae (Fangfeng), Rhizoma Atractylodis Macrocephalae (Baizhu), Lonicerae Japonicae Flos (Jinyinhua), and Fructus forsythia (Lianqiao).CONCLUSIONS: Based on historical records and human evidence of SARS and H1N1 influenza prevention, Chinese herbal formula could be an alternative approach for prevention of COVID-19 in high-risk population. Prospective, rigorous population studies are warranted to confirm the potential preventive effect of CM.

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PMID: 

J Integr Med. 2020 03 ;18(2):87-88. Epub 2020 Feb 19. PMID: 32122812

Abstract Title: 

Traditional Chinese medicine is a resource for drug discovery against 2019 novel coronavirus (SARS-CoV-2).

Abstract: 

[n/a]

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