Palm Fruit Bioactive Complex (PFBc), a Source of Polyphenols, Demonstrates Potential Benefits for Inflammaging and Related Cognitive Function

Cognitive function is a key aspect of healthy aging. Inflammation associated with normal aging, also called inflammaging is a primary risk factor for cognitive decline. A diet high in fruits and vegetable and lower in calories, particularly a Mediterranean Diet, may lower the risk of age-related cognitive decline due in part to the associated high intake of antioxidants and polyphenols. A phenolic, Palm Fruit Bioactive complex (PFBc) derived from the extraction process of palm oil from oil palm fruit (Elaeis guineensis), is reported to offset inflammation due to its high antioxidant, especially vitamin E, and polyphenol content. The benefit is thought to be achieved via the influence of antioxidants on gene expression. It is the purpose of this comprehensive review to discuss the etiology, including gene expression, of mild cognitive impairment (MCI) specific to dietary intake of antioxidants and polyphenols and to focus on the potential impact of nutritional interventions specifically PFBc has on MCI. Several in vitro, in vivo and animal studies support multiple benefits of PFBc especially for improving cognitive function via anti-inflammatory and antioxidant mechanisms. While more human studies are needed, those completed thus far support the benefit of consuming PFBc to enhance cognitive function via its anti-inflammatory antioxidant functions.

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Mitoprotective Effects of Centella asiatica (L.) Urb.: Anti-Inflammatory and Neuroprotective Opportunities in Neurodegenerative Disease

Frontiers in Pharmacology ◽

10.3389/fphar.2021.687935 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jia Hui Wong ◽

Anna M. Barron ◽

Jafri Malin Abdullah

Keyword(s):

Neurodegenerative Disease ◽

Healthy Aging ◽

Brain Aging ◽

Antioxidant Properties ◽

Centella Asiatica ◽

Asiatic Acid ◽

Wide Range ◽

Anti Inflammatory

Natural products remain a crucial source of drug discovery for accessible and affordable solutions for healthy aging. Centella asiatica (L.) Urb. (CA) is an important medicinal plant with a wide range of ethnomedicinal uses. Past in vivo and in vitro studies have shown that the plant extract and its key components, such as asiatic acid, asiaticoside, madecassic acid and madecassoside, exhibit a range of anti-inflammatory, neuroprotective, and cognitive benefits mechanistically linked to mitoprotective and antioxidant properties of the plant. Mitochondrial dysfunction and oxidative stress are key drivers of aging and neurodegenerative disease, including Alzheimer’s disease and Parkinson’s disease. Here we appraise the growing body of evidence that the mitoprotective and antioxidative effects of CA may potentially be harnessed for the treatment of brain aging and neurodegenerative disease.

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Modulation of Glial Responses by Furanocembranolides: Leptolide Diminishes Microglial Inflammation in Vitro and Ameliorates Gliosis In Vivo in a Mouse Model of Obesity and Insulin Resistance

Marine Drugs ◽

10.3390/md18080378 ◽

2020 ◽

Vol 18 (8) ◽

pp. 378

Author(s):

Miriam Corraliza-Gómez ◽

Amalia B. Gallardo ◽

Ana R. Díaz-Marrero ◽

José M. de la Rosa ◽

Luis D’Croz ◽

...

Keyword(s):

Mouse Model ◽

Microglial Cells ◽

Obese Mouse ◽

Neurodegenerative Process ◽

Age Related ◽

Bv2 Cells ◽

Anti Inflammatory ◽

Inflammatory Molecules

Neurodegenerative diseases are age-related disorders caused by progressive neuronal death in different regions of the nervous system. Neuroinflammation, modulated by glial cells, is a crucial event during the neurodegenerative process; consequently, there is an urgency to find new therapeutic products with anti-glioinflammatory properties. Five new furanocembranolides (1−5), along with leptolide, were isolated from two different extracts of Leptogorgia sp., and compound 6 was obtained from chemical transformation of leptolide. Their structures were determined based on spectroscopic evidence. These seven furanocembranolides were screened in vitro by measuring their ability to modulate interleukin-1β (IL-1β) production by microglial BV2 cells after LPS (lipopolysaccharide) stimulation. Leptolide and compounds 3, 4 and 6 exhibited clear anti-inflammatory effects on microglial cells, while compound 2 presented a pro-inflammatory outcome. The in vitro results prompted us to assess anti-glioinflammatory effects of leptolide in vivo in a high-fat diet-induced obese mouse model. Interestingly, leptolide treatment ameliorated both microgliosis and astrogliosis in this animal model. Taken together, our results reveal a promising direct biological effect of furanocembranolides on microglial cells as bioactive anti-inflammatory molecules. Among them, leptolide provides us a feasible therapeutic approach to treat neuroinflammation concomitant with metabolic impairment.

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Effects of Berries on High-Fat Diet-Induced Inflammation

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_082 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 449-449

Author(s):

Patricia Perez ◽

Desiree Wanders ◽

Hannah Land ◽

Kathryn Chiang ◽

Rami Najjar ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Inflammatory Markers ◽

In Vitro Study ◽

Vitro Study ◽

In Vivo Study ◽

High Fat ◽

Anti Inflammatory

Abstract Objectives Studies suggest that inflammation mediates the link between obesity and its comorbidities including type 2 diabetes and cardiovascular disease. Hence, there is a demand for effective alternative or complementary approaches to treat obesity-associated inflammation. The objective of this study was to determine whether consumption of blackberries (BL) and raspberries (RB) alone or in combination reduce obesity-induced inflammation. Methods In Vitro Study: RAW 264.7 macrophages were pretreated with either BL, RB, or BL + RB, each at a final concentration of 200 µg/mL for 2 h. LPS (1 ng/mL) was then added to the media for 16 h. mRNA expression of inflammatory cytokines was measured. In Vivo Study: Five-week-old mice were acclimated to a low-fat low-sucrose (LFLS) diet for one week after which mice were randomized 10 per group to one of five groups: 1) LFLS, 2) high-fat high-sucrose (HFHS), 3) HFHS + 10% BL, 4) HFHS + 10% RB, or 5) HFHS + 5% BL + 5% RB. Expression of inflammatory markers was measured in the liver as well as epididymal and inguinal white adipose tissue. Results In Vitro Study: Each berry alone and in combination suppressed the LPS-induced increase in inflammatory markers, with the combination (BL + RB) having the greatest effect. The combination suppressed LPS-induced expression of Ccl2, Tnfa, F4/80, and Il6 by 3.7−, 5.3−, 5.3−, and 4.4-fold, respectively. In Vivo Study: Gene expression analysis indicated that berry consumption had no significant effect on proinflammatory (Ccl2, Il1b, Tnfa, Il6, Itgam) or anti-inflammatory (Adipoq, Arg1, Mgl1) markers in adipose tissue depots or liver. However, relatively low gene expression of inflammatory markers in the tissues indicates that the mice fed the HFHS diet failed to develop a robust inflammatory state. Conclusions BL and RB have direct anti-inflammatory effects on immune cells. Initial analysis indicates that consumption of BL and RB has no significant effects on markers of inflammation in a diet-induced mouse model of obesity. However, it is possible that the relatively low levels of inflammation in these mice masked the anti-inflammatory potential of BL and RB. Ongoing analysis will provide additional insights into the effects of BL and RB on inflammation in these tissues. Funding Sources Lewis Foundation Award.

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Mesenchymal Stem Cell Therapy Ameliorates Metabolic Dysfunction and Restores Fertility in a PCOS Mouse Model Through Interleukin-10

10.21203/rs.3.rs-444566/v1 ◽

2021 ◽

Author(s):

Rishi Man Chugh ◽

Hang-soo Park ◽

Abdeljabar El Andaloussi ◽

Amro Elsharoud ◽

Sahar Esfandyari ◽

...

Keyword(s):

Gene Expression ◽

Polycystic Ovary ◽

Therapeutic Option ◽

Interleukin 10 ◽

Reproductive Age ◽

Metabolic Dysfunction ◽

Mesenchymal Stem Cell Therapy ◽

Anti Inflammatory

Abstract Background: Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in reproductive-age women. Excessive inflammation and elevated androgen production from ovarian theca cells are key features of PCOS. Human bone marrow mesenchymal stem cells (BM-hMSC) and their secreted factors (secretome) exhibit robust anti-inflammatory capabilities in various biological systems. We evaluated the therapeutic efficacy of BM-hMSC and its secretome in both in vitro and in vivo PCOS models.Methods: For in vitro experiment, we treated conditioned media from BM-hMSC to androgen producing H293R cells, and analyzed androgen producing gene expression. For in vivo experiment, BM-hMSC were implanted into Letrozole (LTZ) induced mouse PCOS model. BM-hMSC effect in androgen producing cells or PCOS model mice was assessed by monitoring cell proliferation (immunohistochemistry), steroidogenic gene expression (quantitative real-time polymerase chain reaction [qRT-PCR] and Western blot, animal tissue assay (H&E staining), and fertility by pup delivery.Results: BM-hMSC significantly downregulate steroidogenic gene expression, curb inflammation, and restore fertility in treated PCOS animals. The anti-inflammatory cytokine interleukin-10 (IL-10) played a key role in mediating the effects of BM-hMSC in our PCOS models. We demonstrated that BM-hMSC treatment was improve in metabolic and reproductive markers in our PCOS model and able to restore fertility. Conclusion: Our study demonstrates for the first time the efficacy of intra-ovarian injection of BM-hMSC or its secretome to treat PCOS-related phenotypes, including both metabolic and reproductive dysfunction. This approach may represent a novel therapeutic option for women with PCOS. Our results suggest that BM-hMSC can reverse PCOS-induced inflammation through IL-10 secretion. BM-hMSC might be a novel and robust therapeutic approach for PCOS treatment.

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Identification of reference genes for RT-qPCR data normalisation in aging studies

Scientific Reports ◽

10.1038/s41598-019-50035-0 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Lourdes González-Bermúdez ◽

Teresa Anglada ◽

Anna Genescà ◽

Marta Martín ◽

Mariona Terradas

Keyword(s):

Gene Expression ◽

Reference Genes ◽

Quantitative Polymerase Chain Reaction ◽

Expression Levels ◽

Qpcr Data ◽

Age Related ◽

Specific Subset ◽

Aging Studies

Abstract Aging is associated with changes in gene expression levels that affect cellular functions and predispose to age-related diseases. The use of candidate genes whose expression remains stable during aging is required to correctly address the age-associated variations in expression levels. Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) has become a powerful approach for sensitive gene expression analysis. Reliable RT-qPCR assays rely on the normalisation of the results to stable reference genes. Taken these data together, here we evaluated the expression stability of eight frequently used reference genes in three aging models: oncogene-induced senescence (OIS), in vitro and in vivo aging. Using NormFinder and geNorm algorithms, we identified that the most stable reference gene pairs were PUM1 and TBP in OIS, GUSB and PUM1 for in vitro aging and GUSB and OAZ1 for in vivo aging. To validate these candidates, we used them to normalise the expression data of CDKN1A, APOD and TFRC genes, whose expression is known to be affected during OIS, in vitro and in vivo aging. This study demonstrates that accurate normalisation of RT-qPCR data is crucial in aging research and provides a specific subset of stable reference genes for future aging studies.

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Bacopa monnierias an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/615384 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 24

Author(s):

Tamara Simpson ◽

Matthew Pase ◽

Con Stough

Keyword(s):

Oxidative Stress ◽

Cognitive Function ◽

Neuronal Cell Death ◽

Neuronal Cell ◽

Bacopa Monnieri ◽

Aging Brain ◽

Resonance Spectroscopy ◽

Age Related

The detrimental effect of neuronal cell death due to oxidative stress and mitochondrial dysfunction has been implicated in age-related cognitive decline and neurodegenerative disorders such as Alzheimer’s disease. The Indian herbBacopa monnieriis a dietary antioxidant, with animal andin vitrostudies indicating several modes of action that may protect the brain against oxidative damage. In parallel, several studies using the CDRI08 extract have shown that extracts ofBacopa monnieriimprove cognitive function in humans. The biological mechanisms of this cognitive enhancement are unknown. In this review we discuss the animal studies andin vivoevidence forBacopa monnierias a potential therapeutic antioxidant to reduce oxidative stress and improve cognitive function. We suggest that future studies incorporate neuroimaging particularly magnetic resonance spectroscopy into their randomized controlled trials to better understand whether changes in antioxidant statusin vivocause improvements in cognitive function.

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Resveratrol Derivative-Rich Melinjo Seed Extract Attenuates Skin Atrophy inSod1-Deficient Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2015/391075 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 10

Author(s):

Kenji Watanabe ◽

Shuichi Shibuya ◽

Yusuke Ozawa ◽

Naotaka Izuo ◽

Takahiko Shimizu

Keyword(s):

Gene Expression ◽

Skin Diseases ◽

Human Study ◽

Seed Extract ◽

Protective Effects ◽

Oxidative Damages ◽

Age Related ◽

Skin Damages

The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (Gnetum gnemonLinn) seed extract (MSE) contains trans-resveratrol (RSV) and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in theSod1−/−mice. Furthermore, MSE and RSV normalized gene expression ofCol1a1andp53and upregulated gene expression ofSirt1in skin tissues.In vitroexperiments revealed that RSV significantly promoted the viability ofSod1−/−fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generationin vivoandin vitroleading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.

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Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813205115 ◽

2018 ◽

Vol 115 (45) ◽

pp. 11625-11630 ◽

Cited By ~ 16

Author(s):

María Díaz-Moreno ◽

Tomás Armenteros ◽

Simona Gradari ◽

Rafael Hortigüela ◽

Laura García-Corzo ◽

...

Keyword(s):

Healthy Aging ◽

Late Onset ◽

Hippocampal Neurogenesis ◽

Bmp Signaling ◽

In Vitro Assays ◽

Age Related ◽

Samp8 Mice ◽

The Brain

Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer’s disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain’s natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.

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Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10

Blood ◽

10.1182/blood-2002-02-0538 ◽

2003 ◽

Vol 101 (2) ◽

pp. 729-738 ◽

Cited By ~ 196

Author(s):

Dominique Berrebi ◽

Stefano Bruscoli ◽

Nicolas Cohen ◽

Arnaud Foussat ◽

Graziella Migliorati ◽

...

Keyword(s):

Gene Expression ◽

Leucine Zipper ◽

Nuclear Factor Κb ◽

Interleukin 10 ◽

Delayed Type Hypersensitivity ◽

Glucocorticoid Treatment ◽

Inflammatory Protein ◽

Anti Inflammatory

Glucocorticoids and interleukin 10 (IL-10) prevent macrophage activation. In murine lymphocytes, glucocorticoids induce expression of glucocorticoid-induced leucine zipper (GILZ), which prevents the nuclear factor κB (NF-κB)–mediated activation of transcription. We investigated whether GILZ could account for the deactivation of macrophages by glucocorticoids and IL-10. We found that GILZ was constitutively produced by macrophages in nonlymphoid tissues of humans and mice. Glucocorticoids and IL-10 stimulated the production of GILZ by macrophages both in vitro and in vivo. Transfection of the macrophagelike cell line THP-1 with the GILZ gene inhibited the expression of CD80 and CD86 and the production of the proinflammatory chemokines regulated on activation normal T-cell expressed and secreted (CCL5) and macrophage inflammatory protein 1α (CCL3). It also prevented toll-like receptor 2 production induced by lipopolysaccharide, interferonγ, or an anti-CD40 mAb, as well as NF-κB function. In THP-1 cells treated with glucocorticoids or IL-10, GILZ was associated with the p65 subunit of NF-κB. Activated macrophages in the granulomas of patients with Crohn disease or tuberculosis do not produce GILZ. In contrast, GILZ production persists in tumor-infiltrating macrophages in Burkitt lymphomas. Therefore, GILZ appears to play a key role in the anti-inflammatory and immunosuppressive effects of glucocorticoids and IL-10. Glucocorticoid treatment stimulates GILZ production, reproducing an effect of IL-10, a natural anti-inflammatory agent. The development of delayed-type hypersensitivity reactions is associated with the down-regulation of GILZ gene expression within lesions. In contrast, the persistence of GILZ gene expression in macrophages infiltrating Burkitt lymphomas may contribute to the failure of the immune system to reject the tumor.

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Study of Osteoarthritis Treatment with Anti-Inflammatory Drugs: Cyclooxygenase-2 Inhibitor and Steroids

BioMed Research International ◽

10.1155/2015/595273 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 25

Author(s):

Hongsik Cho ◽

Andrew Walker ◽

Jeb Williams ◽

Karen A. Hasty

Keyword(s):

Gene Expression ◽

Type Ii Collagen ◽

Cartilage Degradation ◽

Cyclooxygenase 2 ◽

Cox Inhibitor ◽

Inflammatory Drugs ◽

Cox 2 ◽

Anti Inflammatory

Patients with osteoarthritis (OA), a condition characterized by cartilage degradation, are often treated with steroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) selective NSAIDs. Due to their inhibition of the inflammatory cascade, the drugs affect the balance of matrix metalloproteinases (MMPs) and inflammatory cytokines, resulting in preservation of extracellular matrix (ECM). To compare the effects of these treatments on chondrocyte metabolism, TNF-αwas incubated with cultured chondrocytes to mimic a proinflammatory environment with increasing production of MMP-1 and prostaglandin E2 (PGE2). The chondrocytes were then treated with either a steroid (prednisone), a nonspecific COX inhibitor NSAID (piroxicam), or a COX-2 selective NSAID (celecoxib). Both prednisone and celecoxib decreased MMP-1 and PGE-2 production while the nonspecific piroxicam decreased only the latter. Both prednisone and celecoxib decreased gene expression of MMP-1 and increased expression of aggrecan. Increased gene expression of type II collagen was also noted with celecoxib. The nonspecific piroxicam did not show these effects. The efficacy of celecoxibin vivowas investigated using a posttraumatic OA (PTOA) mouse model.In vivo, celecoxib increases aggrecan synthesis and suppresses MMP-1. In conclusion, this study demonstrates that celecoxib and steroids exert similar effects on MMP-1 and PGE2 productionin vitroand that celecoxib may demonstrate beneficial effects on anabolic metabolismin vivo.

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