PMID: 

J Cell Physiol. 2019 Oct 10. Epub 2019 Oct 10. PMID: 31602671

Abstract Title: 

Chlorogenic acid activates ERK1/2 and inhibits proliferation of osteosarcoma cells.

Abstract: 

Osteosarcoma (OS) is a very aggressive metastatic pediatric and adolescent tumor. Due to its recurrent development of chemotherapy resistance, clinical outcome for OS patients remains poor. Therefore, discovering more effective anticancer agents is needed. Chlorogenic acid (CGA) is a phenolic compound contained in plant-related products that modulates many cellular functions and inhibits cell proliferation in several cancer types. However, few evidence is available in OS. Here, we investigate the effects of CGA in U2OS, Saos-2, and MG-63 OS cells. By multiple approaches, we demonstrate that CGA acts as anticancer molecule affecting the cell cycle and provoking cell growth inhibition mainly by apoptosis induction. We also provide evidence that CGA strongly activates extracellular-signal-regulated kinase1/2 (ERK1/2). Strikingly, ERK1/2 inhibitor PD98059 sensitizes the cells to CGA. Altogether, our data enforce the evidence of the anticancer activity mediated by CGA and provide the rationale for the development of innovative therapeutic strategies in OS cure.

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PMID: 

Curr Neuropharmacol. 2019 Oct 21. Epub 2019 Oct 21. PMID: 31631820

Abstract Title: 

Pharmacologic overview of chlorogenic acid and its metabolites in chronic pain and inflammation.

Abstract: 

BACKGROUND: Natural phenolic compounds in medicinal herbs and dietary plants are antioxidants which play therapeutic or preventive roles in different pathological situations, such as oxidative stress and inflammation. One of the most studied phenolic compounds in the last decade is chlorogenic acid (CGA), which is a potent antioxidant found in certain foods and drinks.OBJECTIVE: This review focuses on the anti-inflammatory and antinociceptive bioactivities of CGA, and we describe putative mechanisms of action. Ethnopharmacological reports related to these bioactivities are also reviewed.MATERIALS AND METHODS: An electronic literature search was conducted by authors up to October 2019. Original articles were selected.RESULTS: CGA has been shown to reduce inflammation and modulate inflammatory and neuropathic pain in animal models.CONCLUSION: The consensus of the literature search was that systemic CGA may facilitate pain management via bolstering antioxidant defenses against inflammatory insults.

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PMID: 

Biomed Res Int. 2019 ;2019:5423703. Epub 2019 Sep 22. PMID: 31662982

Abstract Title: 

Chlorogenic Acid Attenuates Kidney Ischemic/Reperfusion Injury via Reducing Inflammation, Tubular Injury, and Myofibroblast Formation.

Abstract: 

Kidney ischemic/reperfusion (I/R) injury is the main cause of acute kidney injury (AKI) involving renal function deterioration, renal architecture damage, and inflammation. This condition may lead to kidney fibrosis with epithelial to mesenchymal transition (EMT) and myofibroblast formation. Inhibition of chronic effects of kidney I/R injury may provide effective strategies for treating AKI and chronic kidney diseases (CKDs). Chlorogenic acid (CGA) is recognized as a powerful antioxidant, with anti-inflammatory and antifibrotic properties in many conditions. However, the effect of CGA on kidney I/R injury has not been elucidated yet. Kidney I/R injury was performed on male Swiss background mice (I/R group, = 5, 3-4 months, 30-40 g) which underwent bilateral renal pedicles clamping for 30 minutes and then were euthanized on day three after operation. Three groups of I/R were treated with 3 different doses of CGA intraperitoneally for 2 days: 3.5 (I/R + CGA1 group), 7 (I/R + CGA2 group), and 14 (I/R + CGA3 group) mg/kg of body weight. Tubular injury was quantified based on Periodic Acid-Schiff staining, while reverse transcriptase PCR (RT-PCR) was performed to quantify mRNA expression of TGF-1, vimentin, SOD-1, TLR-4, TNF-α, NF-κB and MCP-1. Immunohistochemical staining was done to quantify proliferating cell nuclear antigen (PCNA), myofibroblast (-SMA), SOD-1 and macrophage (CD68) number. Kidney I/R demonstrated tubular injury and increased inflammatory mediator expression, macrophage number, and myofibroblast expansion. Meanwhile, histological analysis showed lower tubular injury with higher epithelial cell proliferation in CGA-treated groups compared to the I/R group. RT-PCR also revealed significantly lower TGF-1 and vimentin mRNA expressions with higher SOD-1 mRNA expression. CGA-treated groups also demonstrated a significantly lower macrophage and myofibroblast number compared to the I/R group. These findings associated with lower mRNA expression of TLR-4, TNF-α, NF-κB, and MCP-1 as inflammatory mediators in CGA groups. I/R + CGA3 represented the highest amelioration effect among other CGA-treated groups. CGA treatment attenuates kidney I/R injury through reducing inflammation, decreasing myofibroblast expansion, and inducing epithelial cells proliferation.

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PMID: 

Korean J Physiol Pharmacol. 2019 Nov ;23(6):501-508. Epub 2019 Oct 24. PMID: 31680772

Abstract Title: 

Effects of rosmarinic acid on immunoregulatory activity and hepatocellular carcinoma cell apoptosis intumor-bearing mice.

Abstract: 

Rosmarinic acid (RA) is a natural polyphenolic compound that exists in many medicinal species ofand. The previous studies have revealed that RA had therapeutic effects on hepatocellular carcinoma (HCC) in the-xenograft models by inhibiting the inflammatory cytokines and NF-κB p65 pathway in the tumor microenvironment. However, its molecular mechanisms of immunoregulation and pro-apoptotic effect in HCC have not been fully explored. In the present study, RA at 75, 150, and 300 mg/kg was given totumor-bearing mice via gavage once a day for 10 days. The results showed that RA can effectively inhibit the tumor growth through regulating the ratio of CD4/CD8and the secretion of interleukin (IL)-2 and interferon-γ, inhibiting the expressions of IL-6, IL-10 and signal transducer and activator of transcription 3, thereby up-regulatingandand down-regulating. The underlying mechanisms involved regulation of immune response and induction of HCC cell apoptosis. These results may provide a more comprehensive perspective to clarify the anti-tumor mechanism of RA in HCC.

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PMID: 

Nutrients. 2019 Sep 18 ;11(9). Epub 2019 Sep 18. PMID: 31540391

Abstract Title: 

Iron Fortification and Bioavailability of Chickpea (L.) Seeds and Flour.

Abstract: 

Iron (Fe) deficiency is one of the most common nutritional disorders, and is mainly due to insufficient intake of bioavailable Fe. Chickpea (L.) was examined as a potential vehicle for Fe fortification. Fortificants (FeSO·7HO (ferrous sulfate hepta-hydrate), FeSO·HO (ferrous sulfate mono-hydrate) and NaFeEDTA (ethylenediaminetetraacetic acid iron (iii) sodium salt)) were applied by a spraying and drying method. At 2000µg giron fortificant, the fortified split desi seeds (dal), desi flour and kabuli flour supplied 18-19 mg, 16-20 mg and 11-19 mg Fe per 100 g, respectively. The overall consumer acceptability using a nine-point hedonic scale for sensory evaluation demonstrated that NaFeEDTA-fortified cooked chickpea (soup and chapatti) scored the highest among the three fortificants. Lightness (L*), redness (a*) and yellowness (b*) of Fe-fortified products changed over time. However, no organoleptic changes occurred. Fe bioavailability was increased by 5.8-10.5, 15.3-25.0 and 4.8-9.0 ng ferritin mgprotein for cooked split desi seeds (soup), desi chapatti and kabuli chapatti, respectively, when prepared using Fe-fortified chickpea. Desi chapatti showed significantly higher Fe bioavailability than the other two. The increase in Fe concentration and bioavailability in fortified chickpea products demonstrated that these products could provide a significant proportion of the recommended daily Fe requirement.

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PMID: 

J Ethnopharmacol. 2019 Oct 19:112326. Epub 2019 Oct 19. PMID: 31639486

Abstract Title: 

Flavonoids extracted from mulberry (Morus alba L.) leaf improve skeletal muscle mitochondrial function by activating AMPK in type 2 diabetes.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaves have been widely applied to controlling blood glucose as an efficacious traditional Chinese medicine or salutary medical supplement. The extracts of mulberry leaf suppress inflammatory mediators and oxidative stress, protect the pancreaticβ-cells and modulate glucose metabolism in diabetic rats. Our previous studies and others have shown that mulberry leaf extract has excellent therapeutic effects on type 2 diabetes mellitus (T2DM), however, the underlying mechanism remains to be studied.AIM OF THE STUDY: Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of T2DM. The aim of this study was to investigate the effects and mechanisms of Mulberry leaf flavonoids (MLF) in L6 skeletal muscle cells and db/db mice.MATERIALS AND METHODS: L6 skeletal muscle cells were cultured and treated with/without MLF for in vitro studies. For in vivo studies, the db/db mice with/without MLF therapy were used.RESULTS: MLF and metformin significantly ameliorated muscle glucose uptake and mitochondrial function in L6 muscle cells. MLF also increased the phosphorylation of AMPK and the expression of PGC-1α, and upregulated the protein levels of m-GLUT4 and T-GLUT4. These effects were reversed by the AMPK inhibitor compound C. In db/db mice, MLF improve diabetes symptoms and insulin resistance. Moreover, MLF elevated the levels of p-AMPK and PGC-1α, raised m-GLUT4 and T-GLUT4 protein expression, and ameliorated mitochondrial function in skeletal muscle of db/db mice.CONCLUSIONS: MLF significantly improved skeletal muscle insulin resistance and mitochondrial function in db/db mice and L6 myocytes through AMPK-PGC-1α signaling pathway, and our findings support the therapeutic effects of MLF on type 2 diabetes.

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PMID: 

J Environ Pathol Toxicol Oncol. 2019 ;38(3):205-216. PMID: 31679308

Abstract Title: 

Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.

Abstract: 

Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.

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PMID: 

J Alzheimers Dis. 2019 Oct 29. Epub 2019 Oct 29. PMID: 31683483

Abstract Title: 

Effect of Chlorogenic Acids on Cognitive Function in Mild Cognitive Impairment: A Randomized Controlled Crossover Trial.

Abstract: 

BACKGROUND: Mild cognitive impairment (MCI) is a global-scale issue, due in large part to the rapidly growing elderly population. The main polyphenol contained in coffee beans, chlorogenic acid (CGA), improves attention in healthy individuals. The utility of CGAs for treating MCI, however, has not been evaluated.OBJECTIVE: To determine the effects of continuous CGA intake on cognitive function, especially attention, in patients diagnosed with MCI.METHODS: The study was a randomized controlled crossover trial including 34 patients with MCI. Participants were randomly divided into two groups: Those who first ingested a placebo beverage and those who first ingested an active beverage containing CGAs (553.6 mg/bottle) twice daily for 12 weeks. After a 4-week washout period, the subjects ingested the other beverage (i.e., placebo or active beverage) in the same manner. Endpoint measures included scores on the Japanese version of the Mini-Mental State Examination (MMSE), the Japanese version of the Alzheimer's Disease Assessment Scale-cognitive component (ADAS-cog) testing overall cognitive function, and the Japanese version of the Trail Making Test (TMT-A, TMT-B) testing attention, along with the results of blood tests to evaluate safety.RESULTS: In the TMT-B test, participants had a significantly reduced number of errors while ingesting the CGA beverage as compared with the placebo beverage (p 

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PMID: 

Food Chem Toxicol. 2019 Nov ;133:110796. Epub 2019 Aug 28. PMID: 31472226

Abstract Title: 

Red raspberry extract (Rubus idaeus L shrub) intake ameliorates hyperlipidemia in HFD-induced mice through PPAR signaling pathway.

Abstract: 

Effects of red raspberry extract (RRE) intake on hyperlipidemia mice induced by high-fat diet (HFD) were investigated in this study. After intragastric gavage of RRE for 8 weeks, the body weight and the adipose tissue mass of mice in RRE administration groups significantly (p 

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PMID: 

Nutrients. 2019 Oct 11 ;11(10). Epub 2019 Oct 11. PMID: 31614689

Abstract Title: 

Fermentation of Blackberry withJBMI F5 Enhance the Protection Effect on UVB-Mediated Photoaging in Human Foreskin Fibroblast and Hairless Mice through Regulation of MAPK/NF-κB Signaling.

Abstract: 

Chronic and extensive exposure of ultraviolet (UV)-irradiation causes human skin sunburn, inflammation, or photoaging, which is associated with downregulated collagen synthesis. This study investigated the effects of fermented blackberry (B., FBB) byJBMI F5 (LP) on UVB-induced photoaging in human foreskin fibroblast (Hs68) as well as in SKH-1 hairless mice. FBB pretreatment inhibited UVB-mediated type-1 procollagen degradation, matrix metalloproteinase (MMP)-1 and MMP-2 protein expression, and suppressed nuclear factor-κB (NF-κB) activation as well as mitogen-activated protein kinase (MAPK) phosphorylation in Hs68. In addition, FBB administration diminished the wrinkle formation in dorsal skin and epidermal thickening in UVB-irradiated hairless mice. Moreover, UVB-induced Type-1 procollagen reduction and antioxidant enzyme inactivation were reversed by FBB administration. These results suggest that FBB may have antiphotoaging effects on UVB-induced wrinkle formation by maintaining the extracellular matrix density in the dermis, which occurs via regulation of reactive oxygen species and related MAPK and NF-κB signaling. Therefore, FBB can be a potential candidate for protecting skin aging against UV irradiation.

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