PMID: 

Psychopharmacology (Berl). 2020 Feb 22. Epub 2020 Feb 22. PMID: 32088834

Abstract Title: 

Chrysin attenuates traumatic brain injury-induced recognition memory decline, and anxiety/depression-like behaviors in rats: Insights into underlying mechanisms.

Abstract: 

RATIONALE: Cortical and hippocampal neuronal apoptosis and neuroinflammation are associated with behavioral deficits following traumatic brain injury (TBI).OBJECTIVES: The present study was designed to investigate the potential protective effects of flavonoid chrysin against TBI-induced vestibulomotor impairment, exploratory/locomotor dysfunctions, recognition memory decline, and anxiety/depression-like behaviors, as well as the verified possible involved mechanisms.METHODS: Chrysin (25, 50, or 100 mg/kg/day; P.O.) was administered to rats immediately after diffuse TBI induction, and it was continued for 3 or 14 days. Behavioral functions were assessed by employing standard behavioral paradigms at scheduled points in time. Three days post-TBI, inflammation status was assayed in both cerebral cortex and hippocampus using ELISA kits. Moreover, apoptosis and expression of Bcl-2 family proteins were examined by TUNEL staining and immunohistochemistry, respectively.RESULTS: The results indicated that treatment with chrysin improved vestibulomotor dysfunction, ameliorated recognition memory deficit, and attenuated anxiety/depression-like behaviors in the rats with TBI. Chrysin treatment also modulated inflammation status, reduced apoptotic index, and regulated Bcl-2 family proteins expression in the brains of rats with TBI.CONCLUSIONS: In conclusion, the results suggest that chrysin could be beneficial for protection against TBI-associated behavioral deficits, owing to its anti-apoptotic and anti-inflammatory properties.

read more

PMID: 

Ann Ital Chir. 2020 Jan 6 ;9. Epub 2020 Jan 6. PMID: 32129177

Abstract Title: 

The effects of chrysin in an experimental model of acute pancreatitis.

Abstract: 

PURPOSE: This experimental study was conducted to evaluate the possible effects of orally administered chrysin on acute pancreatitis.MATERIAL AND METHOD: Twenty four rats were procured. The animals were randomly divided into four groups. In Group I, only vehicle solution (5% dimethylsulfoksid) was administered, and in Group II, chrysin dissolved in the vehicle solution was administered for six days. In Group III and Group IV cerulein was administered to induce acute pancreatitis. In Group III, only vehicle solution was administered, and in Group IV, chrysin dissolved in the vehicle solution was administered orally for six days. Blood samples were analyzed and the pancreatic tissue specimens were evaluated for histopathological examination.RESULTS: Group III and Group IV, exhibited markedly higher levels of serum WBC, amylase, and lipase, compared with Groups I and II. In the pancreatitis induced groups, CRP and TOS values were found to be significantly higher. In Group II and Group IV, TAS values were significantly higher. The highest calculated OSI values were observed in Group III. Group IV OSI values were significantly lower than those in Group III and even in Group I. Noticeable histopathological changes were identified in the pancreatitis induced Groups III and IV. Compared with Group III, the extent and severity of pancreatic injuries were markedly lower in Group IV.CONCLUSION: Chrysin application reduced oxidative stress and histopathological parameters. The present study shows that chrysin can be used to treat pancreatic diseases.KEY WORDS: Acute pancreatitis, Cerulein, Chrysin.

read more

PMID: 

Eur J Pharmacol. 2020 Mar 15 ;871:172938. Epub 2020 Jan 17. PMID: 31958458

Abstract Title: 

α-Lipoic acid prevents the ionizing radiation-induced epithelial-mesenchymal transition and enhances the radiosensitivity in breast cancer cells.

Abstract: 

Radiotherapy is routinely used in the treatment of breast cancer. However, its efficiency is often limited by the development of radioresistance and metastasis. The cancer cells surviving irradiation show epithelial-mesenchymal transition (EMT) along with increased migration, invasion and metastasis. In this study, we have evaluated the role ofα-lipoic acid in preventing the radiation-induced EMT and in sensitizing the breast cancer cells to radiation. The breast cancer cell lines, MCF-7 and MDA-MB-231 were pretreated with lipoic acid, irradiated and the changes associated with cell growth, clonogenicity, migration, matrix metalloproteinases (MMPs), EMT and TGFβ signaling were measured. Our data showed that lipoic acid pretreatment sensitized the breast cancer cells to the ionizing radiation and inhibited the radiation-induced migration and the release of MMP2 and MMP9. Lipoic acid also prevented the TGFβ1 release and inhibited the radiation-induced EMT in breast cancer cells. The inhibition of TGFβ signaling by lipoic acid is associated with the inhibition of radiation-induced activation and translocation of NF-κB. These results suggest that α-lipoic acid inhibits the radiation-induced TGFβ signaling and nuclear translocation of NF-κB, thereby inhibiting the radiation-induced EMT and sensitizing the breast cancer cells to ionizing radiation.

read more

PMID: 

Microb Pathog. 2020 Feb 18 ;142:104077. Epub 2020 Feb 18. PMID: 32084579

Abstract Title: 

Alpha-linolenic acid protects against lipopolysaccharide-induced acute lung injury through anti-inflammatory and anti-oxidative pathways.

Abstract: 

Alpha-linolenic acid (ALA), an important component of polyunsaturated fatty acids (PUFAs), possesses potent anti-inflammatory properties. To date, the effects of ALA on acute lung injury (ALI) remains unknown. This study was designed to investigate the potential protective effects of ALA on LPS-induced ALI and the underpinning mechanisms. An animal model of ALI was established via intratracheally injection of lipopolysaccharide (LPS, 1 mg/kg). We found that lung wet/dry weight ratio and protein concentration in Bronchoalveolar lavage fluid (BALF) were dramatically decreased by ALA pretreatment. Treatment with ALA significantly alleviated the infiltration of total cells and neutrophils, while increased the number of the macrophages. ALA significantly inhibited the secretion of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) and increased anti-inflammatory cytokine. Moreover, we found that the levels of myeloperoxidase (MPO) and malondialdehyde (MDA) were highly increased in LPS-induced ALI, while the activities of glutathione (GSH) and superoxide dismutase (SOD) were decreased, which were reversed by ALA. ALA attenuated LPS-induced histopathological changes and apoptosis. Furthermore, ALA significantly inhibited the phosphorylation of IκBα andNF-κB (p65) activation in ALI. ALA showed anti-inflammatory effects in mice with LPS-induced ALI. NF-κB pathway may be involved in ALA mediated protective effects.

read more

PMID: 

Clin Exp Pharmacol Physiol. 2020 Feb 13. Epub 2020 Feb 13. PMID: 32052493

Abstract Title: 

Amelioration of cyclosporine-induced testicular toxicity by carvedilol and/or alpha-lipoic acid: Role of TGF-β1, the proinflammatory cytokines, Nrf2/HO-1 pathway and apoptosis.

Abstract: 

Cyclosporine is an immunosuppressive agent that is used to prevent organ rejection after organ transplantation. Due to the widespread use of this type of surgery, the effect of cyclosporine on reproduction and fertility should have a specific interest. Our aim was to assess the effect of carvedilol and/or alpha-lipoic acid on cyclosporine-inducedtesticular toxicity in rats. Sixty male Wistar rats were divided into 6 equal groups: Control; cyclosporine; cyclosporine + carvedilol; cyclosporine + alpha-lipoic acid; cyclosporine + carboxymethyl cellulose and cyclosporine + carvedilol + alpha-lipoic acid. Food intake, testis weight, testicular functions, serum testosterone, luteinizing hormone and follicle stimulating hormone were measured. Also, testicular tissue 3 β-hydroxysteroid dehydrogenase, 17 β- hydroxysteroid dehydrogenase, paroxonase-1, pro-inflammatory cytokines, transforming growth factor beta-1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Heme oxygenase-1 (HO-1) content and sperm characteristics were determined. Parts of the testes were subjected to histopathological and electron microscopic examination. Carvedilol/alpha-lipoic acid combination restored the food intake, testicular weight and functions, sperm characteristics, hormonal profile and the antioxidant defenses compared to the use of each of these drugs alone. Also, this combination significantly ameliorated inflammation (p

read more

PMID: 

Oncogene. 2020 Feb 14. Epub 2020 Feb 14. PMID: 32060422

Abstract Title: 

Lipoic acid-induced oxidative stress abrogates IGF-1R maturation by inhibiting the CREB/furin axis in breast cancer cell lines.

Abstract: 

The beneficial effects of lipoic acid (LA) in cancer treatment have been well documented in the last decade. Indeed, LA exerts crucial antiproliferative effects by reducing breast cancer cell viability, cell cycle progression and the epithelial-to-mesenchymal transition (EMT). However, the mechanisms of action (MOA) underlying these antiproliferative effects remain to be elucidated. Recently, we demonstrated that LA decreases breast cancer cell proliferation by inhibiting IGF-1R maturation via the downregulation of the proprotein convertase furin. The aim of the present study was to investigate the MOA by which LA inhibits furin expression in estrogen receptorα (ERα) (+) and (-) breast cancer cell lines. We unveil that LA exerts a pro-oxidant effect on these cell lines, the resulting reactive oxygen species (ROS) generated being responsible for the reduction in the expression of the major (CREB) protein. This transcription factor is overexpressed in many types of cancers and regulates the expression of furin in breast cancer cells independently of ERα, as evidenced herein by the inhibition of furin expression following CREB silencing. Consequently, our findings expose for the first time the complete MOA of LA via the CREB/furin axis leading to inhibition of breast cancer cell proliferation.

read more

PMID: 

FEBS Open Bio. 2020 Feb 23. Epub 2020 Feb 23. PMID: 32090494

Abstract Title: 

Alpha-lipoic acid inhibits lung cancer growth via mTOR-mediated autophagy inhibition.

Abstract: 

Lung cancer is the leading cause of cancer-related death, and there remains a need for novel therapies for this malignancy. Here, we examined the effects of alpha-lipoic acid (LA), a drug used for treating human diabetic complications, on lung cancer growth. We report that LA limited lung cancer growth in xenograft mice and reduced lung cancer A549 cell viability. We observed autophagy activation in human lung cancers, and report that LA inactivated autophagy in A549 cells. In addition, LA activated mTOR/p70S6K signaling. Inhibition of mTOR with rapamycin reversed LA-induced inactivation of autophagy and abolished LA-induced suppression of A549 cell viability. Altogether, the data suggest that LA exerts an anti-lung cancer effect through mTOR-mediated inhibition of autophagy, and thus LA may have therapeutic potential for lung cancer management.

read more

PMID: 

Int J Clin Pract. 2020 Feb 24:e13493. Epub 2020 Feb 24. PMID: 32091656

Abstract Title: 

Alpha-Lipoic acid supplementation significantly reduces the risk of obesity in an updated systematic review and dose response meta-analysis of randomized-placebo controlled clinical trials.

Abstract: 

BACKGROUND: There are numerous trials reported the effect of ALA on obesity measurements; while no summarized dose-response meta-analysis is available to address the effects of dose and duration of ALA supplementation on obesity measurements. We aimed to summarize the results of studies evaluating the effects of ALA supplementation on obesity measurements in a systematic review and dose-response meta-analysis.METHODS AND MATERIALS: In a systematic search from Scopus, PubMed, Embase, Proquest electronic databases up to January 2020 relevant studies were retrieved. Randomized, placebo-controlled trials investigating the effect of ALA supplementation on obesity measurements including weight, body mass index (BMI), waist circumference (WC), waist to hip ratio (WHR) and fat mass (FM) were included. Two class and dose-response meta-analysis were performed to data analysis.RESULTS: Totally, eighteen, twenty one and eight studies were included for the meta-analysis of ALA-weight, ALA-BMI, ALA-WC respectively. In the two-class meta-analysis, ALA treatment significantly reduced weight (WMD: -2.29 kg, 95% CI: -2.98, 1.60, P

read more

PMID: 

Int J Nanomedicine. 2020 ;15:729-734. Epub 2020 Jan 31. PMID: 32099361

Abstract Title: 

The Protective Roles of Vitamin E andα-Lipoic Acid Against Nephrotoxicity, Lipid Peroxidation, and Inflammatory Damage Induced by Gold Nanoparticles.

Abstract: 

Background: Recently, use of nanotechnology in biomedical applications such as drug delivery and diagnostic and therapeutic tools has increased greatly. This study evaluated gold nanoparticle (GNPs)-induced nephrotoxic effects in rats in vivo, and examined protective effects of alpha-lipoic acid (α-Lip) and Vitamin E (Vit E) against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs.Materials and Methods: Twenty-four male Wistar-Kyoto rats (220-240 g, 12 weeks old) were dosed with 50μL of 10 nm GNPs administered intraperitoneally with or without 200 mg/kg/day Vit E or 200 mg/kg/day α-Lip. Serum was prepared for biochemical analyses. Kidney function was evaluated through measurement of creatinine (CR), uric acid (URIC), and blood urea nitrogen (BUN). Oxidative stress and lipidperoxidation were evaluated by measurement of reduced glutathione (GSH) and malondialdehyde (MDA) in kidney tissue homogenates.Results and Conclusions: The results showed a significant rise in serum kidney function biomarkers including urea, URIC, CR, and BUN in GNP-treated rats compared to normal control rats. Furthermore, GNPs led to decreased GSH and elevated MDA levels. Vit E orα-Lip supplementation showed a beneficial effect against nephrotoxicity, lipid peroxidation, and inflammatory kidney damage induced by GNPs. This study suggests that use of natural antioxidants in combination with GNPs may be a useful tool in preventing GNPs toxicity.

read more

PMID: 

Mitochondrion. 2020 Feb 28. Epub 2020 Feb 28. PMID: 32119925

Abstract Title: 

Alpha lipoic acid and Vitamin E improve atorvastatin-induced mitochondrial dysfunctions in rats.

Abstract: 

To determine the effects of alpha lipoic acid (ALA) and vitamin E (Vit E) on mitochondrial dysfunction caused by statins. A total of 38 Wistar Albino rats were used in this study. The control group received dimethyl sulfoxide. The atorvastatin (A) group received atorvastatin (10 mg/kg). The A+ALA group received atorvastatin (10 mg/kg) and ALA (100 mg/kg). The A+Vit E group was administered atorvastatin (10 mg/kg) and Vit E (100 mg/kg). The A+ALA+Vit E group was administered atorvastatin (10 mg/kg), ALA (100 mg/kg) and Vit E (100 mg/kg). All applications were administered simultaneously by gavage for 20 days. ATP level and complex I activity were measured from liver, muscle, heart, kidney and brain. Atorvastatin significantly decreased the ATP levels in heart and kidney, while a slight decrease was seen in liver, muscle and brain. Atorvastatin caused an insignificant decrease in the complex I activity in all tissues examined. ALA administration significantly improved the ATP levels in the liver, heart and kidney, while Vit E improved the ATP levels in all tissues except the muscle compared to Atorvastatin group. Single administration of both ALA and vit E ameliorated complex I activity in the muscle, heart, kidney and brain. The combination of ALA and Vit E significantly improved the ATP levels in the liver, heart, kidney and brain and also provided significant improvements the complex I activity in all tissues. The undesirable effects of Atorvastatin on mitochondrial functions in this study ameliorated by using ALA and/or Vit E alone and in combination.

read more