PMID: 

J Exp Clin Cancer Res. 2019 Aug 16 ;38(1):360. Epub 2019 Aug 16. PMID: 31419989

Abstract Title: 

Curcumin C3 complex®/Bioperine® has antineoplastic activity in mesothelioma: an in vitro and in vivo analysis.

Abstract: 

BACKGROUND: A major limitation in the treatment for malignant mesothelioma is related to serious side effects caused by chemotherapeutics and to the development of cancer-resistance. Advances in cancer therapies have been reached thanks to the introduction of alternative approaches, such as the use of phytochemicals. Curcumin-C3complex®/Bioperine® is a commercially standardized extract containing a ratio-defined mixture of three curcuminoids and piperine that greatly increase its bioavailability. Interestingly, the anticancer effect of this formulation has been described in different studies and several clinical trials have been started, but to our knowledge none refers to human mesothelioma.METHODS: Curcumin-C3complex®/Bioperine® anticancer effect was evaluated in vitro in different human mesothelioma cell lines analysing cell proliferation, colony-forming assay, wound healing assays, invasion assay and FACS analysis. In vivo anticancer properties were analysed in a mesothelioma xenograft mouse model in CD1 Nude mice.RESULTS: Curcumin-C3complex®/Bioperine® in vitro induced growth inhibition in all mesothelioma cell lines analysed in a dose- and time-depended manner and reduced self-renewal cell migration and cell invasive ability. Cell death was due to apoptosis. The analysis of the molecular signalling pathway suggested that intrinsicapoptotic pathway is activated by this treatment. This treatment in vivo delayed the growth of the ectopic tumours in a mesothelioma xenograft mouse model.CONCLUSIONS: Curcumin-C3complex®/Bioperine® treatment strongly reduces in vitro tumorigenic properties of mesothelioma cells by impairing cellular self-renewal ability, proliferative cell rate and cell migration and delays tumor growth in xenograft mouse model by reducing angiogenesis and increasing apoptosis. Considering thatcurcumin in vivo synergizes drug effects, its administration to treatment regimen may help to enhance drug therapeutic efficacy in mesothelioma. Our results suggest that implementation of standard pharmacological therapies with novel compounds may pave the way to develop alternative approaches to mesothelioma.

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PMID: 

Gen Dent. 2019 Jan-Feb;67(1):22-26. PMID: 30644826

Abstract Title: 

Antimicrobial activity of noncytotoxic concentrations of Salvia officinalis extract against bacterial and fungal species from the oral cavity.

Abstract: 

The use of medicinal plants can be an alternative method for the control of microorganisms responsible for human infections. This study evaluated the antimicrobial activity of Salvia officinalis Linnaeus (sage) extract on clinical samples isolated from the oral cavity and reference strains of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Candida albicans, Candida tropicalis, and Candida glabrata. In addition, testing assessed the cytotoxic effect of S officinalis on murine macrophages (RAW 264.7). Minimum inhibitory, minimum bactericidal, and minimum fungicidal concentrations of S officinalis extract were determined by broth microdilution method in 60 microbial samples. The cytotoxicity was checked by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The quantities of the proinflammatory cytokines interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) produced by RAW 264.7 were analyzed by an enzyme-linked immunosorbent assay. An S officinalis concentration of 50.0 mg/mL was effective against all microorganisms. Regarding cytotoxicity, the groups treated with 50.0-, 25.0-, and 12.5-mg/mL concentrations of S officinalis presented cell viability statistically similar to that of the control group, which was 100% viable. The production of IL-1β and TNF-α was inhibited at a 50.0-mg/mL concentration of S officinalis. Thus, S officinalis extract presented antimicrobial activity on all isolates ofStaphylococcus spp, S mutans, and Candida spp. No cytotoxic effect was observed, as demonstrated by the survival of RAW 264.7 and inhibition of IL-1β and of TNF-α.

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PMID: 

J Obstet Gynaecol Res. 2019 Apr ;45(4):897-907. Epub 2019 Jan 20. PMID: 30663184

Abstract Title: 

Comparing the effectiveness of Salvia officinalis, clotrimazole and their combination on vulvovaginal candidiasis: A randomized, controlled clinical trial.

Abstract: 

AIM: To determine the effect of vaginal tablet of Salvia officinalis, alone and in combination with Clotrimazole, on the recovery of Vulvovaginal candidiasis.METHODS: In this triple-blind randomized controlled trial, 111 participants were randomly assigned into three groups of 37 patients using block randomization with block sizes of 6 and 9, and allocation ratio of 1:1:1: 100 mg vaginal tablet of Clotrimazole and Placebo (CP), 400 mg vaginal tablet of S. officinalis and Placebo (SP), and vaginal tablet of S. officinalis and Clotrimazole (SC), once daily for 7 days. On the seventh day after the treatment was ended up, Vulvovaginal candidiasis were examined by vaginal symptoms and wet test, and if positive, they were examined by culture in chrome agar Candida medium.RESULTS: Socio-demographic characteristics was similar (P > 0.05). Thirty-six, 36 and 35 patients, respectively in CP, SC and SP groups recruited in the study. The frequency of a positive wet test confirmed by Sabrodextrose agar medium 7 days after treatment was significantly lower in SC group than the reference group of CP (adjusted odds ratio = 0.09, 95% confidence interval: 0.93-0.932, P = 0.043). There was no significant difference between SP and CP group (P = 0.071, 95% confidence interval: 0.032-1.151, adjusted odds ratio = 0.192). Also, there was no significant difference between the three groups in terms of vaginal symptomsat the baseline (P > 0.05), however the statistical differences were indicated after the intervention in cheesy discharge, pruritus and Vulvovaginal edema (P 

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PMID: 

Oxid Med Cell Longev. 2019 ;2019:9658267. Epub 2019 Nov 11. PMID: 31827714

Abstract Title: 

Cerebroprotective Effect against Cerebral Ischemia of the Combined Extract ofandin Metabolic Syndrome Rats.

Abstract: 

The novel strategy against ischemic stroke in metabolic syndrome (MetS) targeting at oxidative stress and inflammation has gained attention due to the limitation of the current therapy. Due to the antioxidant and anti-inflammation of the combined extract ofand, the cerebroprotective effect against cerebral ischemia in MetS condition has been focused. Since no data were available, this study was set up to determine the effects of the combined extract ofL. andLinn. against ischemic stroke in the animal model of metabolic syndrome. The possible underlying mechanism was also further investigated. Male Wistar rats (180-220 g) were fed with high-carbohydrate high-fat diet (HCHF diet) to induce metabolic syndrome-like condition. Then, MetS rats were subjected to reperfusion injury at the right middle cerebral artery. The combined extract ofand(OA extract) at doses of 0.5, 5, and 50 mg/kg BW was fed once daily for 21 days. Neurological assessment was performed every 7 days throughout the experimental period. At the end of study, brain infarction volume, neuron and glial fibrillary acidic protein- (GFAP-) positive cell density, the oxidative stress status, the expressions ofproinflammatory cytokines (NF-B, IL-6), and eNOS in the cortical area together with the expression of VCAM-1 and the histological changes of common carotid artery were determined. It was found that OA extract decreased brain infarction, neurological score, oxidative stress status, and inflammatory mediators but increased eNOS expression in the cortical area; the increased VCAM-1 and intima-media thickness together with the reduction of lumen diameter of common carotid artery of MetS eats with MCAO were also mitigated by OA extract. These data suggest the cerebroprotective effect of OA, and the underlying mechanism may occur partly via the improvement of oxidative stress status, inflammation, and brain blood supply.

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PMID: 

Saudi J Biol Sci. 2019 Nov ;26(7):1473-1477. Epub 2018 Sep 1. PMID: 31762612

Abstract Title: 

Therapeutic potential of the methanolic extract ofseeds on mice infected with.

Abstract: 

The present study aimed to investigate the therapeutic potential of the methanolic extract ofseeds in mice experimentally infected withA total of thirty-two male Swiss albino mice were randomly divided into four groups: the first group was the normal control, while the second, third and fourth groups were infected intraperitoneally with 1 × 10trypanosomes. The third and fourth groups were treated with 100 μl ofseed extract (LSSE) at a dose of 200 mg/kg body weight intraperitoneally (infected + LSSEI) and orally (infected + LSSEO) respectively, once a day, for a period of four days. Parasitaemia was found to be significantly raised in the untreated infected group, reaching 2 × 10at day 4 post-infection, but was significantly reduced by 65.5% and 88% in the mice treated orally and intraperitoneally with LSSE, respectively. The erythrocyte count, HCT, haemoglobin content, leucocyte count and the percentage of lymphocytes was significantly reduced in the untreated infected group, while the treatment with LSSE returned these parameters to their pre-infection values. In addition, our study proved that LSSE provided protection against liver tissue damage and decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The present study also established that intraperitoneal injection of LSSE is more effective than oral administration in the treatment of trypanosome infection in mice. In conclusion, the infection caused haematological, biochemical and histological changes that were ameliorated following treatment with LSSE.

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PMID: 

J Biochem Mol Toxicol. 2019 Oct ;33(10):e22386. Epub 2019 Aug 27. PMID: 31454128

Abstract Title: 

Curcumin synergistically potentiates the protective effect of sitagliptin against chronic deltamethrin nephrotoxicity in rats: Impact on pro-inflammatory cytokines and Nrf2/Ho-1 pathway.

Abstract: 

Deltamethrin (DLM) is a synthesized organophosphorus acaricide and bug spray, broadly utilized for veterinary and farming purposes. Although its exposure to humans and animals causes toxicity in the kidney and other primary organs, our objective was to assess the defensive effects of sitagliptin (Sita) and additionally curcumin (Cur) in the DLM-intoxicated rats' kidney. DLM-intoxicated rats revealed a huge increase of various biochemical parameters in serum identified with kidney damage: uric acid, urea, and creatinine. DLM intoxication altogether increased renal lipid peroxidation, and critically restrained antioxidative biomarkers including superoxide dismutase, glutathione, and glutathione peroxidase. Likewise, it increased the tumor necrosis factor-α, interleukin 6 (IL-6) and IL-1β level in serum. Additionally, DLM intoxication diminished the outflow of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway in rats. Both Sita and Cur act against DLM-prompted serum along with renal tissue biochemical parameterswhen utilized alone or in a mix alongside DLM intoxication. Besides this, both Sita and Cur delivered synergetic nephroprotective, antioxidative, and anti-inflammatory impacts. Consequently, it could be presumed that Sita as well as Cur administration can limit the poisonous impacts of DLM by theirfree radical-scavenging, strong antioxidant, and Nrf2/HO-1 pathway upregulation activity.

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PMID: 

J Biochem Mol Toxicol. 2019 Oct ;33(10):e22384. Epub 2019 Aug 30. PMID: 31468665

Abstract Title: 

Palliative effect of curcumin on doxorubicin-induced testicular damage in male rats.

Abstract: 

This study aimed to investigate the effect of curcumin (CUR) on doxorubicin (DOX)-induced testicular damage in male rats. Thirty-five adult male Wistar rats were used. Control group was received saline for 7 days. CUR group received CUR for 7 days. DOX group received single dose DOX on the 5th day. DOX+ CUR-100 group received 100 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX + CUR-200 group received 200 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX treatment decreased in sperm motility rate, live sperm percentages, cellular antioxidants, and increased malondialdehyde (MDA) levels, necrosis, degenerations, and slimming in seminiferous tubules, and DNA damages in testes by inducing oxidative stress. CUR treatment mitigated significantly these side effects when compared with DOX group in a dose-dependent manner. In conclusion, CUR treatment can be used in the mitigation of DOX-induced testicular toxicity.

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PMID: 

Nan Fang Yi Ke Da Xue Xue Bao. 2019 Aug 30 ;39(8):911-916. PMID: 31511210

Abstract Title: 

[Curcumin suppresses invasiveness and migration of human glioma cells in vitro by inhibiting HDGF/β-catenin complex].

Abstract: 

OBJECTIVE: To investigate the effect of curcumin on the invasion and migration of human glioma cellsand explore the molecular mechanisms.METHODS: MTT assay was used for screening the optimal curcumin concentrations. The effects of curcumin on the invasion and metastasis of human glioma cell lines U251 and LN229 were tested using Transwell assay, Boyden assay and wound-healing assays. The expression of the related proteins and their interactions were determined using Western blotting and coimmunoprecipitation assay.RESULTS: Curcumin at the concentration of 20μmol/L for 48 h was used as the optimal condition for subsequent cell treatment. In the two glioma cell lines, curcumin significantly suppressed the invasion and migration of the cells (< 0.05) and lowered the expressions of hepatoma-derived growth factor (HDGF), Ncadherin, vimentin, Snail and Slug, but increased the expression of E-cadherin. Interference of HDGF in curcumin-treated glioma cells synergistically inhibited the epithelial-mesenchymal transition (EMT) signals, while overexpression of HDGF significantly reversed the inhibitory effect of curcumin on EMT; curcumin treatment could significantly reduce the binding of HDGF toβ-catenin.CONCLUSIONS: Curcumin suppresses EMT signal by reducing HDGF/β-catenin complex and thereby lowers the migration and invasion abilities of human glioma cells.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2019 Jul ;44(14):3107-3115. PMID: 31602860

Abstract Title: 

[Curcumin inhibits proliferation,migration and invasion of gastric cancer cells via Wnt3a/β-catenin/EMT signaling pathway].

Abstract: 

The aim of this paper was to investigate the effects of curcumin on the proliferation,migration,invasion and apoptosis of human gastric cancer cells and to explore the potential mechanisms. SGC7901,MKN45 and NCI N87 cells lines were cultured under different concentrations of curcumin( 2. 5,5,10,20,40,80 and 160μmol·L~(-1)) at different time points( 12,24,48 and 72 h),and the effect of curcumin on cell proliferation was detected by CCK-8 assay. The migration and invasiveness of cells were determined by wound healing and Transwell assays,the apoptosis rate was assessed by flow cytometry,the expression ofN-cadherin,E-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6,Bcl-2 and Bax were detected by Western blot,and the enzymatic activity of caspase-3,caspase-8 and caspase-9 was evaluated via caspase kit. RESULTS:: indicated that the proliferation of MKN45 cells was significantly inhibited by curcumin in a dose-and time-dependent manner( IC50= 21. 93 μmol·L~(-1)). Moreover,curcumin could inhibit the migration and invasion of MKN45 cells,downregulate the expression of N-cadherin,snail1,Wnt3 a,p-β-catenin,p-LRP6 and Bcl-2,and upregulate the expression of E-cadherin and Bax,it could increase the activity of caspase-3,caspase-8,caspase-9 and induce apoptosis as well. The potential mechanism is through inhibiting the Wnt3 a/β-catenin/EMT pathway,regulating Bcl-2 signaling and caspase pathway,which might provide new potential strategies for gastric cancer treatment.

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PMID: 

Molecules. 2019 Oct 29 ;24(21). Epub 2019 Oct 29. PMID: 31671767

Abstract Title: 

Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin.

Abstract: 

In this study, we investigated whether the curcuminoids, CLEFMA and EF24, improved cisplatin efficacy and reduced cisplatin ototoxicity. We used the lung cancer cell line, A549, to determine the effects of the curcuminoids and cisplatin on cell viability and several apoptotic signaling mechanisms. Cellular viability was measured using the MTT assay. A scratch assay was used to measure cell migration and fluorescent spectrophotometry to measure reactive oxygen species (ROS) production. Western blots and luminescence assays were used to measure the expression and activity of apoptosis-inducing factor (AIF), caspases-3/7, -8, -9, and -12, c-Jun N-terminal kinases (JNK), mitogen-activated protein kinase (MAPK), and proto-oncogene tyrosine-protein kinase (Src). A zebrafish model was used to evaluate auditory effects. Cisplatin, the curcuminoids, and their combinations had similar effects on cell viability (ICvalues: 2-16μM) and AIF, caspase-12, JNK, MAPK, and Src expression, while caspase-3/7, -8, and -9 activity was unchanged or decreased. Cisplatin increased ROS yield (1.2-fold), and curcuminoid and combination treatments reduced ROS (0.75-0.85-fold). Combination treatments reduced A549 migration (0.51-0.53-fold). Both curcuminoids reduced auditory threshold shifts induced by cisplatin. In summary, cisplatin and the curcuminoids might cause cell death through AIF and caspase-12. The curcuminoids may potentiate cisplatin's effect against A549 migration, but may counteract cisplatin's effect to increase ROSproduction. The curcuminoids might also prevent cisplatin ototoxicity.

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