PMID: 

Front Pharmacol. 2019 ;10:1003. Epub 2019 Sep 6. PMID: 31551793

Abstract Title: 

Berberine Ameliorates Spatial Learning Memory Impairment and Modulates Cholinergic Anti-Inflammatory Pathway in Diabetic Rats.

Abstract: 

Cognitive impairment caused by diabetes has been recognized. Berberine is well known for its resistance to peripheral lesions, but it is rarely used for the treatment of spatial learning and memory caused by diabetes. This study explored the mechanism of berberine to alleviate cognitive impairmentthe cholinergic anti-inflammatory and insulin signaling pathways.Morris water maze was used to appraise spatial learning and memory. Positron-emission tomography (PET) imaging was adopted to detect the transport of glucose, and blood/cerebrospinal fluid (CSF) glucose was checked using commercial blood glucose meter. Insulin level was measured by ELISA kit andβ-Amyloid (Aβ) formation was observed by Congo red staining. Western-blot was performed to appraise protein expression.We found that berberine rectified some aberrant changes in signal molecules concerning inflammation, and cholinergic and insulin signaling pathways in the hippocampus. Furthermore, CSF/blood glucose, inflammatory response or acetyl cholinesterase enzyme (AChE) activity were reduced by berberine. Additionally, acetylcholine levels were enhanced after berberine treatment in diabetic rats. Finally, Aβ formation in diabetic hippocampus was inhibited and spatial learning memory was ameliorated by berberine.In conclusion, berberine clears Aβ deposit and consequently ameliorates spatial learning memory impairmentthe activation of the cholinergic anti-inflammatory and insulin signaling pathways in diabetic rats.

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PMID: 

Dose Response. 2019 Jul-Sep;17(3):1559325819878537. Epub 2019 Sep 25. PMID: 31598118

Abstract Title: 

Astaxanthin Ameliorates the Lipopolysaccharides-Induced Subfertility in Mouse via Nrf2/HO-1 Antioxidant Pathway.

Abstract: 

The endotoxin lipopolysaccharide (LPS) exists in human semen, which is associated with reduced sperm quality. Studying the LPS-impaired spermatozoa motility and viability, and discovering effective therapeutic treatments have crucial importance. The time-course and dose-response experiments were performed to optimize the treatment dose and time of astaxanthin and LPS on mouse spermatozoa motility and viability. Sperm kinetics and morphology, reactive oxygen species production, in vitro fertilization, and developmental competence were examined to evaluate the protective effects of astaxanthin on spermatozoa after LPS exposure. The activity of nuclear factor erythroid 2-related factor-2/heme oxygenase 1 (Nrf2/HO-1) pathway was detected by quantitative reverse transcription polymerase chain reaction and Western blot. Astaxanthin improves LPS-impaired spermatozoa motility, viability, morphology, and activity; reduces LPS-induced spermatozoa oxidative stress; and alleviates LPS-impaired fertilization and embryo development through activating Nrf2/HO-1 antioxidant signaling pathway. Astaxanthin might be a potential treatment for LPS-induced subfertility.

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PMID: 

Diabetes Metab Syndr Obes. 2019 ;12:1717-1725. Epub 2019 Sep 3. PMID: 31564939

Abstract Title: 

Effect of berberine on the HPA-axis pathway and skeletal muscle GLUT4 in type 2 diabetes mellitus rats.

Abstract: 

Purpose: Activation of the hypothalamus-pituitary-adrenal (HPA) axis pathway is closely related to insulin resistance (IR), glucose, and lipid metabolism disorders in type 2 diabetes mellitus (T2DM). Berberine (BBR) has effect on regulating disorder of glucose and lipid metabolism in T2DM. In fact, activation of the HPA axis pathway is closely related to IR, glucose, and lipid metabolism disorders in T2DM. Here, we investigated whether the therapeutic effect of BBR on T2DM rats is acted through the HPA axis pathway.Methods: In this research, we investigated the effects of BBR on the HPA-axis pathway-related indicators and expression of skeletal muscle glucose transporter 4 (GLUT4) in the high-fat diet and streptozotocin-induced T2DM rats, and identify its possible mechanism of improving IR in T2DM.Results: BBR significantly reduced fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol in model rats. It also improved the abnormalities of the high-density lipoprotein cholesterol, the insulin resistance index, the insulin sensitivity index, glucagon, and insulin levels. BBR decreased levels of hypothalamic Orexin-A, the OX2R receptor, the corticotropin-releasing hormone, the pituitary and the plasma adrenocorticotropic hormone, as well as serum and urine corticosterone. At the same time, BBR increased mRNA and protein expressions of GLUT4 in skeletal muscles of model rats as well.Conclusion: Those results suggested that BBR can exert inhibition on the HPA-axis and increased skeletal muscle expression of GLUT4 proteins, which may be one of the important mechanisms in BBR to improve IR and regulating glucose and lipid metabolism in T2DM rats.

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PMID: 

J Pak Med Assoc. 2019 Aug ;69(Suppl 3)(8):S83-S87. PMID: 31603884

Abstract Title: 

Reno-protective effect of berberine.

Abstract: 

Objective: To assess the reno-protective effect of berberine on diclofenac-induced acute kidney injury in rats.Methods: The experimental study was conducted at the College of Medicine, Mustansiriya University, Baghdad, Iraq, from January to March 2018, and comprised Sprague Dawley male rats which were divided into 3 equal groups. Group1 rats were treated with distilled water plus normal saline for 14 days, Group2 rats were treated with distilled water plus diclofenac for 14 days and Group3 rats were treated with berberine plus diclofenac for 14 days. Parameters measured were blood urea, serum creatinine, serum malondialdehyde, superoxide dismutase, glutathione reductase, neutrophil gelatinase associated lipocalin, kidney injury molecules-1, Interleukin-18and cystatin-c. Anthropometric measurements and estimated glomerular filtration rate were also noted. SPSS 20 was used for data analysis.Results: Of the 30 rats, the three groups had 10(33.3%) each. Berberine reduced blood urea, serum creatinine, malondialdehyde, neutrophil gelatinase associated lipocalin, kidney injury molecules-1 and Interleukin-18 significantly compared to diclofenac-induced acute kidney injury (p

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PMID: 

Pak J Pharm Sci. 2019 Jul ;32(4):1663-1669. PMID: 31608888

Abstract Title: 

Antihyperalgesia potency of Zingiber officinale var. Rubrum in inflammatory and neuropathy-induced chronic pain condition in mice.

Abstract: 

Chronic inflammation and neuropathic pain are classified into chronic pain. Until now there are so many drugs that have been used for chronic pain but the effectiveness still lower. One of the plants that are commonly used for medicine in Indonesia is red ginger (Zingiber officinale var. rubrum). This study was aimed to analyze the component of red ginger oil and proved its antihyperalgesia potency in chronic pain using two models, inflammatory pain and neuropathy pain. Forty-eight mice were divided into 2 groups i.e. inflammatory and neuropathy. Each group was divided into 6 subgroups (@4 mice) i.e. for inflammatory model (sham, negative control, red ginger oil doses 100, 200, 400 and 600 mg/kg) and for neuropathy model (sham, negative control, red ginger oil doses 100, 200, 400 and 600 mg/kg). Inflammatory model was induced using Completed Freud's Adjuvant (CFA) 40 ml intraplantar. Neuropathy model was induced using Partial Sciatic Nerve Ligation (PSNL). At day-7, all groups were given orally treatment, once daily for seven days. The latency time toward thermal stimulus and plantar thickness were measured at day 0,1,3,5,7,8,10,12 and 14 after induction. Quality of red ginger oil was standardized by Indonesia standard (SNI 06-1312-1998). The red ginger oil compound was identified by GC/MS. The result showed that red ginger oil was qualified based on SNI 06-1312-1998. Red ginger oil 200 mg/kgBW and 400mg/kgBW administration in mice gave the best result in prolong the latency time toward thermal stimulus using hot plate and significantly different with inflammatory and neuropathy group. From GC/MS analysis, camphene was known as the highest compound of red ginger oil that might be important for its antihyperalgesia effect. The conclusion of this study that red ginger oil have antihyperalgesia activity in mice with chronic pain and could be developed further to be antihyperalgesia.

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PMID: 

J Food Biochem. 2019 Oct 14:e13076. Epub 2019 Oct 14. PMID: 31608477

Abstract Title: 

Zingiber officinale extract and omega-3 fatty acids ameliorate endoplasmic reticulum stress in a nonalcoholic fatty liver rat model.

Abstract: 

Endoplasmic reticulum (ER) stress was reported to play a major role in non-alcoholic fatty liver disease (NAFLD) induction and progression. Here, we study the effect of Zingiber officinale and omega-3 fatty acids on ER stress for treating NAFLD. Male Wistar rats were fed on a normal diet (control group) or high-fat diet (HFD) for 8 weeks. The HFD rats were later treated with vehicle, omega-3 or with Z. officinale extract. HFD group demonstrated significantly more body weight gain and higher plasma lipid profile, glucose, and hepatic enzymes. The expressions of lipogenic ChREBP and ER stress genes CHOP, XBP1, and GRP78 were increased. This was accompanied by intrahepatic fat accumulation visualized by hepatic morphology and H&E-stained sections. Treatment with Z. officinale and omega-3 fatty acids reverted these changes into a normal healthy state. From these results, we prove that both therapeutic approaches can be potential drugs for treating NAFLD besides other ER stress-associated diseases. PRACTICAL APPLICATIONS: The effect of Zingiber officinale extract and omega-3 fatty acid on ER stress associated with NAFLD was investigated. The results revealed that Z. officinale extract and omega-3 fatty acids significantly inhibited ER stress and intrahepatic fat accumulation with the upper hand for Z. officinale extract. Both can be used as future promising therapies for the treatment of NAFLD patients and also treating different diseases that involve ER stress as a pathological modulator like diabetes mellitus, Alzheimer's disease, Parkinson's disease, and cancer.

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PMID: 

Nutrients. 2019 Sep 6 ;11(9). Epub 2019 Sep 6. PMID: 31500218

Abstract Title: 

Omega-3 Polyunsaturated Fatty Acids PreventInfection by Inducing Autophagy via AMPK Activation.

Abstract: 

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms ininfection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of-infected macrophages with DHA resulted in colocalization ofparasitophorous vacuoles with autophagosomes and reduced intracellular survival of. The autophagic and anti-effects induced by DHA were mediated by AMP-activated protein kinase (AMPK) signaling. Importantly, BMDMs isolated from Fat-1 transgenic mice, a well-known animal model capable of synthesizingω3-PUFAs from ω6-PUFAs, showed increased activation of autophagy and AMPK, leading to reduced intracellular survival ofwhen compared with wild-type BMDMs. Moreover, Fat-1 transgenic mice exhibited lower cyst burden in the brain following infection with the avirulent strain ME49 than wild-type mice. Collectively, our results revealed mechanisms by which endogenousω3-PUFAs and DHA controlinfection and suggest thatω3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites.

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PMID: 

Microb Pathog. 2019 Sep 16 ;137:103751. Epub 2019 Sep 16. PMID: 31536800

Abstract Title: 

Is Toxoplasma gondii a potential risk factor for Alzheimer's disease? A systematic review and meta-analysis.

Abstract: 

Toxoplasmosis is a major public health concern due to neurotropic nature and role in the development of mental and behavioral disorders. Alzheimer's disease (AD) is an important nervous disease that results in the reduction of the amount of beta-amyloid plaque deposition and irreversible loss of neurons in the brain. Although a few studies evaluated the association between AD and toxoplasmosis, the present study as a systematic review and meta-analysis of published studies investigated the possible association between Toxoplasma gondii (T. gondii) and AD. A systematic literature search was conducted using seven electronic databases from the inception to 25th of November 2018 with no restriction of language that looked at toxoplasmosis (as an exposure) and AD (as a disease). The random effect model was used to determine the total odds ratio (OR) and total p-value. Generally, eight studies containing 3239 subjects (360 patients and 2879 controls) met the eligibility criteria. Then, eight articles were used for meta-analysis with respect to inclusion and exclusion criteria. The results of the meta-analysis (random effect model) showed a common OR of 1.53 (95% CI: 1.07-2.18). Despite the fact that there was no evidence of publication bias (P = 0.079) using formal statistical test, the visual inspection of the funnel graph suggested that the observed effect was fueled mainly by three studies with large effects (and large standard errors). Moreover, the file-drawer effect (i.e. publishing mainly studies with positive results) might play a role in the phenomenon. Results of this meta-analytic study suggested that T. gondii can be considered a risk factor for the development of AD and exacerbation of its symptoms. However, the number of published relevant studies is still relatively low, and the risk of the presence of publication bias is relatively high. Therefore, the investigation of the clinically important question of the possible association between toxoplasmosis and AD definitively deserves further attention.

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