PMID: 

Chem Biol Interact. 2019 Dec 21:108926. Epub 2019 Dec 21. PMID: 31874164

Abstract Title: 

GSPE alleviates renal fibrosis by inhibiting the activation of C3/ HMGB1/ TGF-β1 pathway.

Abstract: 

Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a variety of protective effects, such as antioxidant, anti-atherosclerosis and other pharmacological effects. As a member of the complement system, complement component 3 (C3) deposition in the glomerulus is recognized as an important causative mediator of various kidney diseases. In this study, we aimed to identify the effect of GSPE on C3 in the chronic kidney fibrosis and evaluate the possible mechanism. We observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO. GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation. In vitro, we found that C3 stimulated HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro-inflammatory cytokines including TGF-β1 in primary renal tubular epithelial cells (PTEC), which could be inhibited by GSPE. Meanwhile, GSPE could also decreased HMGB1-induced EMT of PTEC through suppresses the HMGB1/TLR4/p65/TGF-β pathway. In addition, the myofibroblast activation was inhibited by GSPE via TGF-β1/Smad2/3 signaling pathways in normal rat kidney fibroblast (NRK-49F) cells. Overall, these observations provide that GSPE alleviates renal fibrosis by inhibiting the C3/HMGB1/TGF-β1 pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis.

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PMID: 

J Clin Neurosci. 2019 Dec 14. Epub 2019 Dec 14. PMID: 31848037

Abstract Title: 

Potential role of cannabidiol for seizure control in a patient with recurrent glioma.

Abstract: 

Glioma-related epilepsy significantly impact on patients' quality of life, and can often be difficult to treat. Seizures cause significant morbidity for example neurocognitive deterioration, which may result from seizures themselves or due to adverse effects from antiepileptic drugs. Management of tumour with surgery, radiotherapy and chemotherapy may contribute to seizure control, but tumour related epilepsy is often refractory despite adequate treatment with standard anti-epileptic medications. Given the increasing interest in medicinal cannabis (or cannabidiol or CBD) as an anti-epileptic drug, CBD may help with seizure control in glioma patients with treatment-refractory seizures. Here we present a case of a young lady with recurrent glioma who had refractory seizures despite multiple anti-epileptic agents, who had significant benefit with CBD.

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PMID: 

J Am Pharm Assoc (2003). 2019 Dec 19. Epub 2019 Dec 19. PMID: 31866386

Abstract Title: 

Use of cannabidiol in anxiety and anxiety-related disorders.

Abstract: 

OBJECTIVE: Cannabidiol (CBD) has a proposed novel role in the management of anxiety owing to its actions on the endocannabinoid system. The purpose of this systematic review was to evaluate the current evidence on the safety and efficacy of CBD in anxiety and anxiety-related disorders.DATA SOURCES: A literature search was conducted on PubMed, Google Scholar, and International Pharmaceutical Abstracts from database inception through June 2019. A bibliographic search of relevant articles was also conducted.STUDY SELECTION: Articles published from case reports, case series, or randomized controlled trials on human subjects were included in the review if they examined the safety and efficacy of CBD therapy in anxiety and anxiety-related disorders.DATA EXTRACTION: Two reviewers independently extracted the following data from the articles: year of publication; study design; patient characteristics (sex; type of anxiety disorder; use of concomitant anxiolytic therapy); dosing strategy and route of CBD administration; and safety and efficacy outcomes.RESULTS: Eight articles were included in the review: 6 small, randomized controlled trials; 1 case series; and 1 case report. These studies examined the role of CBD in the anxiety response of healthy volunteers; in generalized anxiety disorder; in social anxiety disorder; and in the anxiety component of posttraumatic stress syndrome. No articles that evaluated CBD in panic disorder, specific phobia, separation anxiety, and obsessive-compulsive disorder were identified. In the studies, CBD was administered orally as a capsule or as a sublingual spray and as either monotherapy or adjunctive therapy. Doses varied widely, with studies employing fixed CBD doses ranging from 6 mg to 400 mg per dose. Various anxiety assessment scales were used in the studies to assess efficacy, with CBD demonstrating improved clinical outcomes among the instruments. In general, CBD was well-tolerated and associated with minimal adverse effects, with the most commonly noted adverse effects being fatigue and sedation.CONCLUSION: CBD has a promising role as alternative therapy in the management of anxiety disorders. However, more studies with standardized approaches to dosing and clinical outcome measurements are needed to determine the appropriate dosing strategy for CBD and its place in therapy.

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PMID: 

Food Funct. 2019 Sep 1 ;10(9):5732-5738. Epub 2019 Aug 27. PMID: 31453617

Abstract Title: 

Metabolic effects ofα-lipoic acid supplementation in pre-diabetics: a randomized, placebo-controlled pilot study.

Abstract: 

Supplementation of health promoting nutraceuticals may be an effective adjunct strategy with other lifestyle and drug approaches to impede disease progression in prediabetic subjects.α-Lipoic acid, a naturally occurring short-chain fatty acid, has been extensively evaluated for its antioxidant and glycemic control properties but has rarely been investigated as a lipid-lowering strategy. We conducted a pilot study to examine the effects of α-lipoic acid supplementation on glycemic control and lipid profile in pre-diabetic, overweight/obese adults. The study was designed as a free-living, randomized, two-phase, placebo-controlled cross-over study with 12 pre-diabetic, dyslipidemic subjects. Eligible subjects completed two thirty-day phases (in random order) consisting of aplacebo (600 mg cellulose per day) and α-lipoic acid treatment (600 mg day). Although no change (p0.05) in serum lipids (including total cholesterol, LDL-C, HDL-C, triglycerides, LDL-C/HDL-C, and TC/HDL-C) were observed. Study results suggest thatα-lipoic acid supplementation may be a useful strategy to improve insulin sensitivity in pre-diabetic subjects but is not effective in modulating serum lipids.

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PMID: 

Biol Pharm Bull. 2019 ;42(9):1456-1463. PMID: 31474707

Abstract Title: 

Chronic Treatment withα-Lipoic Acid Improves Endothelium-Dependent Vasorelaxation of Aortas in High-Fat Diet-Fed Mice.

Abstract: 

α-Lipoic acid (ALA) is used as a dietary supplement and known as an anti-oxidant. The present study aimed to examine whether ALA improves endothelial dysfunction in high-fat diet-fed obese mice. After feeding a high-fat diet to Institute of Cancer Research (ICR) mice for 4 weeks, the mice were maintained with a high-fat diet (group HF) or a high-fat diet containing ALA (25 mg/d, group HF + ALA) for an additional 20 weeks. Age-matched normal diet-fed mice were also used (group Normal). Chronic oral treatment with ALA did not affect various plasma parameters or body weights. As compared with the aortas of Normal mice, those from HF mice showed impaired endothelium-dependent relaxation in response to clonidine. However, such an impairment was not observed in the aortas from HF + ALA mice. The plasma levels of thiobarbituric acid reactive substances, an indicator of oxidative stress, were significantly decreased in HF + ALA mice compared with HF mice, confirming the anti-oxidative effects of ALA. In addition, when the impaired clonidine-induced vasorelaxation of aortas from normal mice under high glucose conditions was used as a model of acute oxidative stress, the vasorelaxation responses were improved in the presence of ALA at 100 µM. Our results suggested that the chronic oral administration of ALA improves endothelial dysfunction in high-fat diet-fed obese mice possibly through the reduction in oxidative stress in vivo.

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PMID: 

Biotech Histochem. 2019 Nov 5:1-6. Epub 2019 Nov 5. PMID: 31687838

Abstract Title: 

Protective effect of alpha lipoic acid on cisplatin induced hepatotoxicity in rats.

Abstract: 

We investigated the protective effect of alpha lipoic acid (ALA) against cisplatin (CIS) induced hepatotoxicity in rats. ALA is an antioxidant and anti-inflammatory agent that exhibits free radical scavenger properties and direct antioxidant effects on recycling of other cellular antioxidants. We used four equal groups of rats. The control group: saline solution (0.9%) was administered intraperitoneally (i.p.); ALA group: administered a single dose 100 mg/kg ALA i.p. for 10 days; CIS group was administered a single dose 5 mg/kg CIS i.p. on the first day of the study; CIS + ALA group was administered a single dose 5 mg/kg CIS i.p. on the first day of study, then 100 mg/kg ALA i.p. for 10 days. In the CIS group, Bax, caspase3, malondialdehyde (MDA), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were increased, whereas Bcl-2, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were decreased compared to the control group. In the CIS + ALA group, Bax, caspase 3, MDA, AST and ALT levels were decreased, whereas Bcl-2, SOD, CAT and GPx levels were increased compared to the CIS group. In the CIS group we found intense perivenule sinusoid dilation, karyomegaly, pyknotic and karyolytic cells, central vein congestion, parenchymal inflammation, mild bile duct proliferation and periportal sinusoid dilation. Histological liver damage was reduced in the CIS + ALA group. ALA may useful for treating CIS induced hepatotoxicity owing to its antioxidant and anti-inflammatory effects.

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PMID: 

Hum Exp Toxicol. 2019 Dec 4:960327119891212. Epub 2019 Dec 4. PMID: 31797693

Abstract Title: 

α-Lipoic acid modulates liver fibrosis: A cross talk between TGF-β1, autophagy, and apoptosis.

Abstract: 

Autophagy and apoptosis are important players in the progression of hepatic fibrosis via activation of hepatic stellate cells (HSCs). Despite the recently depicted antifibrotic effects of alpha-lipoic acid (ALA), however, its modulatory effects on HSCs autophagy remain unverified. Our study aimed to elucidate the underlying antifibrotic mechanisms through which ALA mediates HSC autophagy and apoptosis. Liver fibrosis was induced via thioacetamide (TAA) intoxication in rats; TAA-intoxicated rats were treated with either silymarin or ALA. Effect of ALA on biochemical parameters and immunohistopathological examinations was measured and compared to silymarin. ALA restored normal hepatic architecture (S1 vs. S4), liver functions, hepatic glutathione, and transforming growth factor-β1 levels. ALA ameliorated hepatic levels of malondialdehyde, platelet-derived growth factor, tissue inhibitor metalloproteinases-1, hydroxyproline, and expression of alpha-smooth muscle actin. Moreover, ALA significantly reduced messenger RNA expression of LC3-II genes and triggered caspase-3 expression. Interestingly, ALA exhibited superior activities over silymarin regarding suppression of proliferation, activation and autophagy of HSCs, collagen deposition, and induction of HSCs apoptosis. In conclusion, treatment of TAA-intoxicated rats with ALA inhibited autophagy and induced apoptoticclearance of activated HSCs. Accordingly, this study provides mechanistic insights into the possible applicability of ALA in the treatment of hepatic fibrosis.

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PMID: 

Curr Med Sci. 2019 Dec ;39(6):920-928. Epub 2019 Dec 16. PMID: 31845223

Abstract Title: 

Protective Effects ofα-Lipoic Acid on Vascular Oxidative Stress in Rats with Hyperuricemia.

Abstract: 

The aim of the present study was to observe the protective effects ofα-lipoic acid (ALA) on vascular injury in rats with hyperuricemia (HUA). The ALA treatment groups (10, 30 and 90 mg/kg, respectively) were administered with ALA via gavage for 2 weeks. Subsequently, the levels of blood urea nitrogen (BUN), creatinine (CREA), uric acid (UA), total cholesterol (TC),high density lipoprotein-C (HDL-C) and low density lipoprotein-C (LDL-C) were measured; the activities of glutathione peroxidase (GSH-Px), catalase (CAT), malonaldehyde (MDA), superoxide dismutase (SOD) and xanthine oxidase (XOD) were also determined. The thoracic aorta of rats in each experimentalgroup was observed under a light microscope; ultrastructural analysis was performed. SOD and CAT protein contents were investigated by Western blotting. The results revealed that: i) Compared with the model group, the levels of UA were decreased in the ALA groups and the levels of BUN, CREA, TC, andLDL-C decreased in the 30 and 90 mg/kg ALA groups (P

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PMID: 

PLoS One. 2019 ;14(12):e0226769. Epub 2019 Dec 26. PMID: 31877176

Abstract Title: 

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway.

Abstract: 

The production of reactive oxygen species (ROS) by cisplatin is one of the major mechanisms of cisplatin-induced cytotoxicity. We examined the preventive effect ofα-lipoic acid (LA) on cisplatin-induced toxicity via its antioxidant effects on in vitro and ex vivo culture systems. To elucidate the mechanism of the antioxidant activity of LA, NRF2 was inhibited using NRF2 siRNA, and the change in antioxidant activity of LA was characterized. MTT assays showedthat LA was safe at concentrations up to 0.5 mM in HEI-OC1 cells and had a protective effect against cisplatin-induced cytotoxicity. Intracellular ROS production in HEI-OC1 cells was rapidly increased by cisplatin for up to 48 h. However, treatment with LA significantly reduced the production of ROSand increased the expression of the antioxidant proteins HO-1 and SOD1. Ex vivo, the organs of Corti of the group pretreated with LA exhibited better preservation than the group that received cisplatin alone. We also confirmed the nuclear translocation of NRF2 after LA administration, and that NRF2inhibition decreased the antioxidant activity of LA. Together, these results indicate that the antioxidant activity of LA was through the activation of the NRF2/HO-1 antioxidant pathway.

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PMID: 

J Ethnopharmacol. 2019 Dec 19 ;250:112482. Epub 2019 Dec 19. PMID: 31866512

Abstract Title: 

Effects of passion fruit peel flour (Passiflora edulis f. flavicarpa O. Deg.) in cafeteria diet-induced metabolic disorders.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Passiflora edulis f. flavicarpa O. Deg. is a native Brazilian fruit known as sour or yellow passion fruit. From its peel, mainly in the northeast of Brazil, is produced a flour that is largely used as folk medicine to treat diabetes and other metabolic conditions.AIM OF THE STUDY: The aim of the study was to show the effects of P. edulis peel flour (PEPF) in metabolic disorders caused by cafeteria diet in mice.MATERIAL AND METHODS: The antioxidant activity in vitro of PEPF extract was determined by ferric reducing/antioxidant power,β-carotene/linoleic acid system and nitric oxide scavenging activity assay. C57BL/6 mice divided in 3 groups: Control group, fed on a standard diet (AIN); Cafeteria diet (CAF) group, fed on a cafeteria diet, and PEPF group, fed on a cafeteria diet containing 15% of PEPF, during 16 weeks. The glucose tolerance and insulin sensitivity were evaluated through the glucose tolerance test (GTT) and the insulin tolerance test (ITT). After the intervention period, blood, hepatic, pancreatic and adipose tissues were collected for biochemical and histological analysis. Cholesterol, triglyceride, interleukins and antioxidant enzymes were measured in the liver tissue.RESULTS: PEPF extract presented antioxidant activity in the higher concentrations in the performed assays. The PEPF intake decreased the body weight gain, fat deposition, predominantly in the liver, improved the glucose tolerance and insulin sensitivity in metabolic changes caused by cafeteria diet.CONCLUSION: Together, the data herein obtained points out that P. edulis peel flour supplementation in metabolic syndrome condition induced by CAF-diet, prevents insulin and glucose resistance, hepatic steatosis and adiposity.

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