PMID: 

Clin Chim Acta. 2010 Nov 11 ;411(21-22):1580-6. Epub 2010 Jul 16. PMID: 20638374

Abstract Title: 

Making sense of epidemiological studies of young children exposed to thimerosal in vaccines.

Abstract: 

OBJECTIVE: To compare epidemiological studies dealing with neurological issues (compatible with Hg toxicity) linked to exposing newborns and infants to intramuscular doses of preservative-Hg resulting from vaccination with thimerosal-containing vaccines (TCV).METHODS: Major databases were searched for studies that addressed neurodevelopment outcomes other than autism. Eight studies were identified and compared.RESULTS: Information extracted from the studies done in the USA, the UK, and Italy is important in understanding the complex interplay of variables but insufficient to establish non-toxicity for infants and young children still receiving TCV: a) there is ambiguity in some studies reporting neurodevelopment outcomes that seem to depend on confounding variables; b) the risk of neurotoxicity due to low doses of thimerosal is plausible at least for susceptible infants; c) there is a need to address these issues in less developed countries still using TCV in pregnant mothers, newborns, and young children.CONCLUSIONS: Since the use of TCV is still inevitable in many countries, this increases the need to protect vulnerable infants and promote actions that strengthen neurodevelopment. Developing countries should intensify campaigns that include breastfeeding among efforts to help prime the central nervous system to tolerate exposure to neurotoxic substances, especially thimerosal-Hg.

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PMID: 

Anticancer Agents Med Chem. 2019 Jul 31. Epub 2019 Jul 31. PMID: 31364517

Abstract Title: 

Kaempferol improves TRAIL-Mediated apoptosis in leukemia MOLT-4 cells by inhibition of anti-apoptotic proteins and promotion of death receptors expression.

Abstract: 

INTRODUCTION: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) is a member of the tumor necrosis factor (TNF) superfamily, which stimulates apoptosis in a wide range of cancer cells via binding to death receptors 4 and 5 (DR4/5). Nevertheless, TRAIL has noticeable anti-cancer abilities; some cancer cells acquire resistance to TRAIL, and consequently its potential for inducing apoptosis in target cells is strongly diminished. Acute lymphoblastic leukemia MOLT-4 cell line is one of the most resistant cells to TRAIL that developed resistance to TRAIL via different pathways. We used TRAIL plus kaempferol to eliminate resistance of the MOLT-4 cells to TRAIL.MATERIAL AND METHODS: First, IC50 for kaempferol (95µM) was determined by using the MTT assay. Second, the viability of the MOLT-4 cells was assayed by FACS after Annexin V/PI staining, following treatment with TRAIL (50 and 100 nM) and kaempferol (95 µM) alone and together. Finally, the expression levels of the candidate genes involved in resistance to TRAIL were assayed by real-time PCR technique.RESULTS: Kaempferol plus TRAIL induced apoptosis robustly in MOLT-4 cells at 12, 24 and 48 hours after treatment. Additionally, we found that kaempferol could inhibit expression of the c-FLIP, X-IAP, cIAP1/2, FGF-8 and VEGF-beta, and conversely augment expression of the DR4/5 in MOLT-4 cells.CONCLUSION: We suggest that co-treatment of MOLT-4 cells with TRAIL plus kaempferol is a practical and attractive approach to eliminate cancers' resistance to TRAIL via inhibition of the intracellular anti-apoptotic proteins, upregulation of DR4/5 and also by suppression of the VEGF-beta (VEGFB) and FGF-8 expressions.

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PMID: 

J Expo Sci Environ Epidemiol. 2010 Nov ;20(7):598-601. Epub 2009 Dec 16. PMID: 20010978

Abstract Title: 

Infants' exposure to aluminum from vaccines and breast milk during the first 6 months.

Abstract: 

The success of vaccination programs in reducing and eliminating infectious diseases has contributed to an ever-increasing number of vaccines given at earlier ages (newborns and infants). Exposure to low levels of environmental toxic substances (including metals) at an early age raises plausible concerns over increasingly lower neuro-cognitive rates. Current immunization schedules with vaccines containing aluminum (as adjuvant) are given to infants, but thimerosal (as preservative) is found mostly in vaccines used in non-industrialized countries. Exclusively, breastfed infants (in Brazil) receiving a full recommended schedule of immunizations showed an exceedingly high exposure of Al (225 to 1750μg per dose) when compared with estimated levels absorbed from breast milk (2.0 μg). This study does not dispute the safety of vaccines but reinforces the need to study long-term effects of early exposure to neuro-toxic substances on the developing brain. Pragmatic vaccine safety needs to embraceconventional toxicology, addressing especial characteristics of unborn fetuses, neonates and infants exposed to low levels of aluminum, and ethylmercury traditionally considered innocuous to the central nervous system.

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PMID: 

Brain Res. 2019 Aug 1:146361. Epub 2019 Aug 1. PMID: 31377105

Abstract Title: 

Kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral ischemia/reperfusion rats.

Abstract: 

Kaempferol has been reported to act as an anti-inflammation agent in LPS-induced neuroinflammation in vitro and in vivo, but its role in the inflammation after cerebral ischemia/reperfusion (I/R) is unclear. The present study was to investigate the effect of kaempferol on inflammation in ischemic brain tissue and explore its mechanisms in cerebral I/R rats. Cerebral I/R rat model was established by middle cerebral artery occlusion for 60 min and following reperfusion. Kaempferol at doses of 25, 50 and 100 mg/kg was administered for 7 days after cerebral I/R. Kaempferol treatment significantly reduced cerebral infarct volume, attenuated inflammation and blood-brain barrier (BBB) disruption after cerebral I/R, thus improved neurological outcomes at the day 7 after cerebral I/R. Furthermore, the results also showed kaempferol treatment decreased the phosphorylation and nuclear transposition of transcription factor NF-κB p65, thus inhibited expression of various pro-inflammatory proteins. In conclusion, kaempferol attenuates neuroinflammation and blood brain barrier dysfunction to improve neurological deficits in cerebral ischemia/reperfusion rats, its mechanism is related to NF-κB pathway.

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PMID: 

Behav Brain Res. 2010 Nov 12 ;213(1):42-9. Epub 2010 Apr 28. PMID: 20433873

Abstract Title: 

Chronic metals ingestion by prairie voles produces sex-specific deficits in social behavior: an animal model of autism.

Abstract: 

We examined the effects of chronic metals ingestion on social behavior in the normally highly social prairie vole to test the hypothesis that metals may interact with central dopamine systems to produce the social withdrawal characteristic of autism. Relative to water-treated controls, 10 weeks of chronic ingestion of either Hg(++) or Cd(++) via drinking water significantly reduced social contact by male voles when they were given a choice between isolation or contact with an unfamiliar same-sex conspecific. The effects of metals ingestion were specific to males: no effects of metals exposure were seen in females. Metals ingestion did not alter behavior of males allowed to choose between isolation or their familiar cage-mates, rather than strangers. We also examined the possibility that metals ingestion affects central dopamine functioning by testing the voles' locomotor responses to peripheral administration of amphetamine. As with the social behavior, we found a sex-specific effect of metals on amphetamine responses. Males that consumed Hg(++) did not increase their locomotor activity in response to amphetamine, whereas similarly treated females and males that ingested only water significantly increased their locomotor activities. Thus, an ecologically relevant stimulus, metals ingestion, produced two of the hallmark characteristics of autism – social avoidance and a male-oriented bias. These results suggest that metals exposure may contribute to the development of autism, possibly by interacting with central dopamine function, and support the use of prairie voles as a model organism in which to study autism.

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PMID: 

Clin Exp Immunol. 2019 Aug 13. Epub 2019 Aug 13. PMID: 31407330

Abstract Title: 

Kaempferol attenuates imiquimod-induced psoriatic skin inflammation in a mouse model.

Abstract: 

Psoriasis is an immune-mediated inflammatory skin disease that mainly affects the skin barrier. Treatment for psoriasis mainly includes conventional immunosuppressive drugs. However, long-term treatment with global immunosuppressive agents may cause a variety of side effects, including nephrotoxicity and infections. Kaempferol, a natural flavonol present in various plants, is known to possess potent anti-inflammatory, antioxidant and anti-cancerous properties. However, it's unknown whether kaempferol is also anti-psoriatic. Here we established an imiquimod (IMQ)-induced psoriatic mouse model to explore the potential therapeutic effects of kaempferol on psoriatic skin lesion and inflammation. In this study, we demonstrated that treatment with kaempferol protected mice from developing psoriasis-like skin lesion induced by topical administration of IMQ. Kaempferol reduced CD3T cell infiltration and gene expression of major proinflammatory cytokines, including IL-6, IL-17A and TNFα, in the psoriatic skin lesion. It also down-regulated proinflammatory NFκB signaling in the skin. The therapeutic effects were associated with a significant increase in CD4FoxP3Treg frequency in the spleen and lymph nodes as well as FoxP3-positive staining in the skin lesion. On the other hand, depletion of CD4CD25Tregs reversed the therapeutic effects of kaempferol on the skin lesion. Kaempferol also lowered the percentage of IL17ACD4T cells in the spleen and lymph nodes of IMQ-induced psoriatic mice. Finally, kaempferol suppressed the proliferation of T cells in vitro and their mTOR signaling as well. Thus, our findings suggest that kaempferol may be a therapeutic drug for treating human psoriasis in the near future. This article is protected by copyright. All rights reserved.

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PMID: 

J BUON. 2019 May-Jun;24(3):975-981. PMID: 31424650

Abstract Title: 

Kaempferol exerts anti-proliferative effects on human ovarian cancer cells by inducing apoptosis, G0/G1 cell cycle arrest and modulation of MEK/ERK and STAT3 pathways.

Abstract: 

PURPOSE: Ovarian cancer causes significant mortality in women and is one of the most prevalent types of gynaecological cancer world over. Ovarian cancer is often diagnosed at advanced stages and the currently used anticancer drugs produce several adverse effects. Herein, we examined the anticancer effects of a natural flavonoid Kaempferol against a panel of ovarian cancer cells.METHODS: WST-1 and colony formations assays were used to examine the anti-proliferative effects of Kaempferol. AO/EB, DAPI and annexin V/PI staining assays were used to check apoptosis. Cell cycle analysis was performed by flow cytometry and western blotting was used to check the expression of the proteins.RESULTS: The results showed that Kaempferol could inhibit the growth of ovarian cancer cells with IC50 ranging between 25 to 50µM. However, the cytotoxic effects of Kaempferol were comparatively negligible against the normal SV40 cells with an IC50 of>120µM. Exploration of the mechanism of action revealed that Kaempferol exerts growth inhibitory effects on the OVACAR-3 ovarian cancer cells by apoptotic cell death. This was also accompanied with upregulation of apoptotic proteins such as caspase 3, 8 and 9 and Bax. Kaempferol also induced arrest ofthe OVACAR-3 cells at the G2/M check point of the cell cycle. In addition, Kaempferol could also inhibit the MEK/ERK and STAT3 signal transduction pathways.CONCLUSION: Taken together, these results suggest that Kaempferol exerts potent anticancer effects on ovarian cancer cells and may prove useful in the management of ovarian cancer.

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PMID: 

Acta Pharmacol Sin. 2019 Aug 19. Epub 2019 Aug 19. PMID: 31427695

Abstract Title: 

Rebalancing of the gut flora and microbial metabolism is responsible for the anti-arthritis effect of kaempferol.

Abstract: 

Kaempferol is a natural flavonol that possesses various pharmacological activities, including anti-arthritis effects, yet the underlying mechanisms remain controversial. To evaluate the anti-arthritis efficacy and the underlying mechanisms of kaempferol, collagen-induced arthritis (CIA) mice were treated with kaempferol intragastrically (200 mg · kg · d) and intraperitoneally (20 mg · kg · d). Pharmacodynamic and pharmacokinetic studies showed that the oral administration of kaempferol produced distinct anti-arthritis effects in model mice with arthritis in terms of the spleen index, arthritis index, paw thickness, and inflammatory factors; the bioavailability (1.5%, relative to that of the intraperitoneal injection) and circulatory exposure of kaempferol (C = 0.23 ± 0.06 ng/mL) and its primary metabolite kaempferol-3-O-glucuronide (C = 233.29 ± 89.64 ng/mL) were rather low. In contrast, the intraperitoneal injection of kaempferol caused marginal anti-arthritis effects, although it achieved a much higher in vivo exposure. The much higher kaempferol content in the gut implicated a potential mechanism involved in the gut. Analysis of 16S ribosomal RNA revealed that CIA caused imbalance of 14 types of bacteria at the family level, whereas kaempferol largely rebalanced the intestinal microbiota in CIA mice. A metabolomics study showed that kaempferol treatment significantly reversed the perturbation of metabolites involved in energy production and the tryptophan, fatty acid and secondary bile acid metabolisms in the gut contents of the CIA mice. In conclusion, we demonstrate for the first time that the high level of kaempferol in the gut regulates the intestinal flora and microbiotic metabolism, which are potentially responsible for the anti-arthritis activities of kaempferol.

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PMID: 

Molecules. 2018 Oct 10 ;23(10). Epub 2018 Oct 10. PMID: 30309003

Abstract Title: 

Kaempferol Attenuates ROS-Induced Hemolysis and the Molecular Mechanism of Its Induction of Apoptosis on Bladder Cancer.

Abstract: 

Bladder cancer has become the most common malignant urinary carcinoma. Studies have shown that significant antioxidant and bladder cancer-fighting properties of several plant-based diets like, ginger and amomum, are associated with their high kaempferol content. In this paper, we evaluated the antioxidant and anticancer activities of kaempferol and its mechanism of induction to apoptosis on bladder cancer cells. Our findings demonstrated that kaempferol showed an obvious radical scavenging activity in erythrocytes damaged by oxygen. Kaempferol promoted antioxidant enzymes, inhibited ROS generation and lipid peroxidation and finally prevented the occurrence of hemolysis. Additionally, kaempferol exhibited a strong inhibitory effect on bladder cancer cells and high safety on normal bladder cells. At the molecular level, kaempferol suppressed EJ bladder cancer cell proliferation by inhibiting the function of phosphorylated AKT (p-AKT), CyclinD1, CDK4, Bid, Mcl-1 and Bcl-xL, and promoting p-BRCA1, p-ATM, p53, p21, p38, Bax and Bid expression, and finally triggering apoptosis and S phase arrest. We found that Kaempferol exhibited strong anti-oxidant activity on erythrocyte and inhibitory effects on the growth of cancerous bladder cells through inducing apoptosis and S phase arrest. These findings suggested that kaempferol might be regarded as a bioactive food ingredient to prevent oxidative damage and treat bladder cancer.

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PMID: 

Iran J Med Sci. 2018 Nov ;43(6):623-632. PMID: 30510339

Abstract Title: 

Effects of the Hydroalcoholic Extract of theFruit on Osteoporosis Prevention in Ovariectomized Rats.

Abstract: 

Background: Several plants have been shown to possess antioxidant and estrogenic properties that can be useful in postmenopausal bone-loss prevention. The present study aimed to investigate the anti-osteoporotic effects of the hydroalcoholic extract of the(PG) fruit in ovariectomized (OVX) rats.Methods: Sixty female Sprague-Dawley rats were randomly divided into 6 groups: a control positive group, a sham-operated group, an OVX group given normal saline (OVX-only group), and 3 treatment groups comprising 2 OVX groups treated orally with 500 and 1000 mg/kg/d of the hydroalcoholic extract of the PG fruit respectively and an OVX group treated with an injection of 0.15 mg/kg of estradiol. The study was conducted over a 12-week period. Samples from the animals' blood, femoral bones, and uteri were collected for stereological and biochemical analyses. The data were analyzed using SPSS, version 19. A P value equal to or less than 0.05 was considered statistically significant.Results: The results revealed a significant decrease in the levels of calcium, total antioxidant capacity, and phosphorus as well as uterus weight, femoral ash density, femoral volume and weight, and numbers of osteocytes and osteoblasts. Moreover, there was an increase in the levels of alkaline phosphatase and urine deoxypyridinoline together with a rise in the number of osteoclasts in the OVX-only group compared to the control and treatment groups (P≤0.05). The hydroalcoholic extract of the PG fruit increased femoral weight and volume, femoral ash density, numbers of osteocytes and osteoblasts, and trabecular volume of the bones in comparison with the OVX-only group in a dose-dependent manner. No significant difference was observed between the groups in the levels of malondialdehyde and interleukin-6.Conclusion: The hydroalcoholic extract of thefruit prevented OVX-induced bone loss in the rats, with no proliferative effect on atrophic uteri; it should, therefore, be considered for treatment purposes.

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