PMID: 

Neuroreport. 2019 Nov 6 ;30(16):1129-1134. PMID: 31568207

Abstract Title: 

Concentration- and time-dependent effects of myo-inositol on evoked epileptic afterdischarge in the hippocampus in vivo.

Abstract: 

Epilepsy is one of the most widespread neurological diseases characterized by spontaneous recurrent seizures. There is no cure for epilepsy, and available pharmacological treatments with anti-seizure drugs are only symptomatic. Moreover, about third of epilepsy patients are resistant to the anti-seizure drugs. Thus, it is essential to discover new anti-epilepsy drugs. Recently, myo-inositol has been identified as a promising antiepileptic compound. In the present study, using electrophysiological method, we examined for the first time, the effect of myo-inositol on the generation of epileptic afterdischarges in the hippocampus evoked by a local electrical stimulation. This was achieved by implanting two electrodes with a cannula into the same dorsal hippocampus, which allowed for simultaneous local injection of myo-inositol or saline and afterdischarges induction and recording from the same hippocampus. We found that myo-inositol has time- and concentration-dependent effects on the evoked afterdischarges. Specifically, 5 minutes after 1 M myo-inositol infusion, the afterdischarges duration was significantly decreased as compared to preinjection durations in the same animals and also as compared to preinjection level durations in saline injected or contralateral hippocampus myo-inositol infused animals. Further, 0.055 M myo-inositol significantly decreased afterdischarges duration at 5 minutes as compared to 40 minutes post-injection. At both concentrations, the afterdischarges duration recovered to the pre-injection value at 40 minutes after the myo-inositol injection. The present data, taken together with our previous results, strongly suggest that myo-inositol has significant local seizure-suppressant effect.

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PMID: 

Andrology. 2019 Oct 21. Epub 2019 Oct 21. PMID: 31637826

Abstract Title: 

Myo-inositol in health and disease. Its impact upon semen parameters and male fertility.

Abstract: 

BACKGROUND: Myo-inositol (cis-1,2,3,5-trans-4,6-cyclohexanehexol; MI) is the most prominent of nine Inositol stereoisomers. MI, its phosphate derivatives and associated lipids, are widely found in vegetables and animal tissues and are known to participate in numerous biological processes.OBJECTIVES: To perform a review analysis on MI presence, functions, and impact in male fertility.MATERIALS AND METHODS: A thorough search of listed publications in PubMed on MI and its derivatives was done.RESULTS: Published information was found and compiled on MI identification, natural dietary sources and absorption, biosynthesis, concentrations, as well as MI as its derivatives (PI, PIP, GPI, IPG) roles in several human tissues and body fluids in health and disease. A section was focused on MI presence, biosynthesis and functions in the mammalian male genital tract and in spermatozoa, and summarized reports describing the impact of in vivo and in vitro MI supplementation upon human semen quality and fertility. Studies reported a discrete improvement in sperm motility in fresh and frozen-thawed semen, and a better sperm performance in natural and assisted fertility.DISCUSSION AND CONCLUSION: MI was reported as an effective supplement for sperm quality. In any case, several study designs lack appropriate controls or data analysis to confirm the relevance of the findings. While promising, larger prospective randomized controlled studies will be required to confirm the positive effect of MI supplementation in male infertility management. Moreover, further investigations are encouraged to unravel MI roles in sperm physiology and the underlying molecular mechanisms.

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PMID: 

Reprod Biomed Online. 2016 Dec ;33(6):770-780. Epub 2016 Sep 16. PMID: 27717596

Abstract Title: 

Inositol as putative integrative treatment for PCOS.

Abstract: 

Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols. Such compounds are mainly represented in humans by two inositol stereoisomers: myo-inositol (MYO) and d-chiro-inositol (DCI). MYO is the precursor of inositol triphosphate, a second messenger that regulates thyroid-stimulating hormone (TSH) and FSH as well as insulin. DCI derives from the conversion of myo-inositol via an insulin-dependent pathway. Several preliminary studies have indicated possible benefits of inositol therapy in PCOS patients, but to date no meta-analysis has been performed. This review aims to give clinical insights for the clinical use of inositol in PCOS.

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PMID: 

Cureus. 2019 Sep 16 ;11(9):e5671. Epub 2019 Sep 16. PMID: 31720147

Abstract Title: 

Inositol Supplementation in the Prevention of Gestational Diabetes Mellitus.

Abstract: 

Inositol, an emerging novel therapy for the treatment of gestational diabetes mellitus (GDM), is a cyclic polyol that has insulin-like effects and plays an important role in glucose homeostasis. The conventional treatment of GDM with insulin and oral antihyperglycemic drugs usually comes with side effects, paving the way for and shedding spotlight on clinical trials involving inositol. This review analyzed a host of recent trials that involved inositol supplementation for preventing GDM and their positive outcomes in reducing the rate of GDM among obese and overweight pregnant women, as well as women with polycystic ovarian syndrome (PCOS) or a family history of type 2 diabetes mellitus.

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PMID: 

Cell Death Differ. 2019 Jun 17. Epub 2019 Jun 17. PMID: 31209359

Abstract Title: 

Magnesium protects against sepsis by blocking gasdermin D N-terminal-induced pyroptosis.

Abstract: 

Hypomagnesemia is a significant risk factor for critically ill patients to develop sepsis, a life-threatening disease with a mortality rate over 25%. Our clinic data analysis showed that hypomagnesemia is associated with a decreased monocyte count in septic patients. At the cellular level, we found that Mginhibits pyroptosis. Specifically, Mglimits the oligomerization and membrane localization of gasdermin D N-terminal (GSDMD-NT) upon the activation of either the canonical or noncanonical pyroptotic pathway. Mechanistically, we demonstrated that Cainflux is a prerequisite for the function of GSDMD-NT. Mgblocks Cainflux by inhibiting the ATP-gated Cachannel P2X7, thereby impeding the function of GSDMD-NT and inhibiting lipopolysaccharide (LPS)-induced noncanonical pyroptosis. Furthermore, Mgadministration protects mice from LPS-induced lethal septic shock. Together, our data reveal the underlying mechanism of how Mginhibits pyroptosis and suggest potential clinic applications of magnesium supplementation for sepsis prevention and treatment.

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PMID: 

Front Oncol. 2019 ;9:752. Epub 2019 Oct 1. PMID: 31632899

Abstract Title: 

Magnolol Suppresses TGF-β-Induced Epithelial-to-Mesenchymal Transition in Human Colorectal Cancer Cells.

Abstract: 

Tumor metastasis is the end state of a multistep process that includes dissemination of tumor cells to distant organs and requires tumor cells to adapt to different tissue microenvironments. During metastasis, tumor cells undergo a morphological change known as transdifferentiation or the epithelial-to-mesenchymal transition (EMT). In normal embryonic development, the EMT occurs in the context of morphogenesis in a variety of tissues. Over the course of this process, epithelial cells lose their cell-cell adhesion and polarity properties. In this study, we investigated whether magnolol could suppress the EMT in human colorectal cancer cells. To this end, we examined the epithelial markers E-cadherin, ZO-1, and claudin and the mesenchymal markers N-cadherin, TWIST1, Slug, and Snail. Magnolol effectively inhibited EMT in human colon cancer cell lines by upregulating epithelial markers and downregulating mesenchymal markers. The EMT is induced by the TGF-β signaling pathway. To determine whether magnolol disrupts TGF-β signaling, we examined several mediators of this pathway, and found that magnolol decreased the levels of phosphorylated (i.e., active) ERK, GSK3β, and Smad. We conclude that magnolol blocks migration in HCT116 cells by suppressingTGF-β signaling.

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PMID: 

Environ Toxicol. 2019 Nov 12. Epub 2019 Nov 12. PMID: 31714653

Abstract Title: 

Apoptosis induction and ERK/NF-κB inactivation are associated with magnolol-inhibited tumor progression in hepatocellular carcinoma in vivo.

Abstract: 

Although hepatitis B and/or hepatitis C virus were recognized as major risk factor for the development of hepatocellular carcinoma (HCC), certain occupational, environmental, and lifestyle factors also play key roles in HCC tumorigenesis. Moreover, in molecular signaling route, extracellular signal-regulated kinase (ERK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was found to be overexpressed and linked to poor prognosis in HCC. Thus, to identify possible nature compound that can suppress ERK/NF-κB may be benefit to HCC patient. Magnolol, a natural compound derived from herbal plant Magnolia officinalis, has been recognized as a liver protection and antitumor reagent. However, whether magnolol-inhibited HCC progression correlates with disruption of ERK/NF-κB signaling is remained unclear. In this studies, we performed SK-Hep1/luc2 HCC bearing animal model to investigate the anticancer efficacy and mechanism of magnolol on tumor progression. Tumor size and tumor growth rate were dramatically suppressed after treatment of magnolol. In addition, expression of phospho-ERK (p-ERK), NF-κB p65 (Ser536), and tumor progression-associated proteins, such as matrix metallopeptidase 9 (MMP-9), vascular endothelial growth factor (VEGF), X-linked inhibitor of apoptosis protein (XIAP), and CyclinD1 were all significantly decreased by magnolol. Most important, major extrinsic and intrinsic apoptosis signaling factors, including active caspase-8 and caspase-9 were both enhanced by magnolol. This study indicated that apoptosis induction through extrinsic/intrinsic pathways and blockage of ERK/NF-κB activation were associated with magnolol-inhibited tumor progression in HCC in vivo.

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PMID: 

J Toxicol Sci. 2019 ;44(11):753-758. PMID: 31708532

Abstract Title: 

Magnolol protects PC12 cells from hydrogen peroxide or 6-hydroxydopamine induced cytotoxicity.

Abstract: 

Magnoliae Cortex contains a range of bioactive components including terpenes (e.g.α-, β- and γ-eudesmol), phenylpropanoids (e.g. honokiol and magnolol) and alkaloids (e.g. magnocurarine). We recently reported that pretreatment of PC12 cells with Magnoliae Cortex extract significantly suppresses cytotoxicity induced by HOor 6-hydroxydopamine (6-OHDA) through the induction of drug-metabolizing and antioxidant enzymes. In this study, we investigated whether honokiol and magnolol, which are known to be active components of Magnoliae Cortex, induce drug-metabolizing enzymes and antioxidant enzymes in PC12 cells. We also examined the cytoprotective effect of honokiol and magnolol against HOor 6-OHDA induced cell death in PC12 cells. Our results revealed that honokiol and magnolol induced both NAD(P)H:quinone oxidoreductase 1 (NQO1) and catalase enzyme activities in a concentration-dependent manner. Pretreatment of PC12 cells with magnolol suppressed toxicity induced by HOor 6-OHDA. However, pretreatment of PC12 cells with honokiol showed only a suppressive effect on toxicity induced by HO. Our results suggest that the cytoprotective effect of Magnoliae Cortex extract on PC12 cells is mainly attributable to magnolol and only partially to honokiol.

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PMID: 

Curr Diab Rep. 2019 Aug 1 ;19(9):73. Epub 2019 Aug 1. PMID: 31368026

Abstract Title: 

Nutritional Supplementation for the Prevention and/or Treatment of Gestational Diabetes Mellitus.

Abstract: 

PURPOSE OF REVIEW: Gestational diabetes mellitus (GDM) is a common pregnancy complication that has short- and long-term health implications for both the mother and child. While lifestyle modifications, insulin therapy, and oral agents such as metformin are effective, they can be difficult to adhere to, and there remain concerns over long-term effects of oral agents on the infant. Further, GDM has no proven preventive strategies, which could be more effective than treatment postdiagnosis. Nutritional supplements are an appealing, potentially safer, and better tolerated alternative to pharmaceuticals to treat and/or prevent GDM. Here, we review the existing evidence for nutritional supplementation for treatment and prevention of GDM.RECENT FINDINGS: There is limited evidence that myo-inositol, vitamins D and B6, magnesium, selenium, zinc, fatty acids, and probiotics might be beneficial for the prevention or treatment of GDM. There are very few studies for each nutrient, and the existing studies tend to have few participants. Where multiple studies of a nutrient exist, often those studies were conducted within the same country, limiting the generalizability of the findings, or alternatively there was no consensus across findings. There is limited evidence that nutritional supplementation of myo-inositol, vitamins D and B6, magnesium, selenium, zinc, fatty acids, and probiotics could improve glycemic control or prevent GDM. Our understanding is constrained by the small number of studies, small sample sizes in most studies, and by lack of consistency across findings. Further large, high-quality, randomized controlled trials are required to determine the efficacy of nutritional supplements to treat or prevent GDM.

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PMID: 

Eur J Appl Physiol. 2019 Oct 17. Epub 2019 Oct 17. PMID: 31624951

Abstract Title: 

One week of magnesium supplementation lowers IL-6, muscle soreness and increases post-exercise blood glucose in response to downhill running.

Abstract: 

PURPOSE: Magnesium supplementation modulates glucose metabolism and inflammation, which could influence exercise performance and recovery. This study investigated the effect of magnesium intake on physiological responses and performance during eccentric exercise and recovery.METHODS: Nine male recreational runners completed a counterbalanced, double-blind, placebo-controlled, cross-over study, registered at ClinicalTrial.gov. Participants consumed low magnesium diets and were supplemented with 500 mg/day of magnesium (SUP) or placebo (CON) for 7 days prior to a 10 km downhill (- 10%) running time trial (TT), separated by a 2-week washout period. At baseline and 24 h post-TT, maximal muscle force was measured. Interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R) and creatine kinase (CK) were measured at rest, 0 h, 1 h and 24 h post-TT. Muscle soreness was measured at the previous times plus 48 h and 72 h post. Glucose and lactate were measured during the TT.RESULTS: The main effect of condition was detected for IL-6 (SUP: 1.36 ± 0.66 vs CON: 2.06 ± 1.14 pg/ml) (P 

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