PMID: 

Nutr Res. 2019 Oct 24 ;73:58-66. Epub 2019 Oct 24. PMID: 31841748

Abstract Title: 

Gallic acid regulates adipocyte hypertrophy and suppresses inflammatory gene expression induced by the paracrine interaction between adipocytes and macrophages in vitro and in vivo.

Abstract: 

Obesity-induced chronic inflammation in adipose tissue plays a critical role in the development of insulin resistance and various lifestyle-related diseases. Although gallic acid (GA) is known to exert protective effects on obesity-related complications, its function in adipose tissue inflammation has not been elucidated. Recently, we reported that GA exerts protective effects against inflammation. To test our hypothesis that the anti-inflammatory effect of GA partially contributes to the improvement of metabolic diseases, we examined the effect of GA on inflammation caused by adipocyte-macrophage crosstalk in obesity. We showed that GA enhanced adipocyte differentiation in 3 T3-L1 adipocytes. Consistent with the enhancement of adipogenesis, GA decreased the gene expression of monocyte chemoattractant protein-1 and increased that of adiponectin and the upstream mediator peroxisome proliferator-activated receptor gamma. GA also reduced inflammatory mediator expression induced by the co-culture of 3 T3-L1 adipocytes with RAW 264 macrophages. Diet-induced obese mice treated with GA showed decreased serum cholesterol levels and adipocyte size, and improved insulin sensitivity without changes in body weight. Moreover, GA-treated mice had decreased expression of interleukin-6, inducible nitric oxide synthase, cyclooxygenase-2, F4/80, and sterol regulatory element binding transcription factor-1 in their adipose tissue. These results indicate that GA suppresses adipocyte hypertrophy and inflammation caused by the interaction between adipocytes and macrophages, thereby improving metabolic disorders such as insulin resistance and dyslipidemia.

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PMID: 

Biochem Biophys Res Commun. 2019 Dec 9. Epub 2019 Dec 9. PMID: 31831179

Abstract Title: 

Mid infrared light treatment attenuates cognitive decline and alters the gut microbiota community in APP/PS1 mouse model.

Abstract: 

Alzheimer's disease (AD) as the first most neurodegenerative disease in the elderly still has no effective therapy, suggesting that the intervention toolbox for AD should be expanded. One newly developed strategy involves the use of photobiomodulation, such as near infrared or far infrared light, which has proven to attenuate AD-associated pathology. However, the efficacy of mid infrared light (MIR) in treating AD is under investigated. With this in mind, we assessed the benefits of MIR light of peak wavelength 7.7-10 μm treatment on APP/PS1 transgenic mice. We found that APP/PS1 mice treated with MIR light had improved learning and memory abilities and reduced amyloid-β (Aβ) plaque load in the brain. We also surprisingly found that the gut microbiota composition in APP/PS1 mice treated with MIR light returned to normal (wild type mice) levels. Together, these findings suggested a novel non-invasive and promising avenue for AD treatment via photobiomodulation, and also proposed that future target for AD might be the gut microbiota via the brain-gut-skin axis.

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PMID: 

Exp Ther Med. 2019 Sep ;18(3):1914-1920. Epub 2019 Jul 1. PMID: 31410154

Abstract Title: 

inhibits itch-associated histamine and IL-31 production in stimulated mast cells.

Abstract: 

(Myrrh) is widely recognized for its anti-inflammatory and antimicrobial properties, which are utilized for the treatment of oral ulcers, gingivitis, sinusitis, glomerulonephritis, brucellosis and a variety of skin disorders. The current study aimed to assess whether myrrh modulates itch-associated interleukin (IL)-31 cytokine production and histamine release in stimulated human mast cells (HMC-1). To realize this, molecular biology techniques including real-time quantitiative PCR, western blotting and ELISA were employed. The results indicated that Myrrh successfully suppressed phorbol myristate acetate and calcium ionophore-stimulated mRNA expression, and reduced the production of IL-31 in HMC-1 cells. In addition, myrrh served as a suppressor of extracellular signal-regulated kinase and NF-κB activation, indicating its mechanism in the prevention of HMC-1 cell IL-31 production. Myrrh also prevented the release of histamine in HMC-1 cells. Whilst the present study awaitssupport, the pharmacological actions of myrrh provide new indications as to its potential applicability for itch treatment, which cannot be treated with histamine receptor blockers alone.

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PMID: 

Phytomedicine. 2019 Nov ;64:152924. Epub 2019 Apr 9. PMID: 31465983

Abstract Title: 

Guggulipid ameliorates adjuvant-induced arthritis and liver oxidative damage by suppressing inflammatory and oxidative stress mediators.

Abstract: 

BACKGROUND: Arthritis is a common degenerative joint disease characterized by deterioration of articular cartilage, subchondral bone, and associated with immobility, pain and inflammation. The incessant action of reactive oxygen species (ROS) during progressive arthritis causes severe oxidative damage to vital organs and circulatory system.PURPOSE: In this study we investigated the ability of guggulipid (GL), a lipid rich extract from the gum resin of the plant Commiphora whighitii to suppress the progressive arthritis and associated liver oxidative stress both in vivo and in vitro.STUDY DESIGN/METHODS: The anti-arthritic ability of GL was demonstrated in vitro using IL-1β stimulated bovine nasal cartilage model and in vivo Freund's complete adjuvant-induced arthritic rat model. Collagen/proteoglycan degradation and pro-inflammatory mediators were monitored in the harvested culture medium of nasal cartilage by estimating the levels of matrix metalloproteinases (MMPs), hydroxy proline, glycosaminoglycans and inflammatory mediators. Further, anti-arthritic ability of GL was evaluated in vivo by measuring enzymatic and non-enzymatic mediators of cartilage degradation, inflammation and oxidative stress markers.RESULTS: GL significantly inhibited the IL-1β stimulated cartilage degradation in vitro by mitigating the MMPs activity, collagen degradation and secretion of pro-inflammatory mediators. Further, GL significantly reduced the adjuvant-induced paw swelling and body weight loss in vivo. GL remarkably reduced the MMPs and hyaluronidases activities in serum and bone homogenate along with altered hematological parameters. GL also mitigated the elevated bone resorbing enzymes cathepsins, exoglycosidases and phosphatases. Additionally, GL effectively mitigated ROS and oxidative stress-mediators recuperating the altered serum/liver oxidative stress and liver damage incurred during arthritic progression.CONCLUSION: In summary, the study clearly demonstrates the protective efficacy of GL against arthritis and its associated oxidative stress, particularly, liver oxidative damage. Hence, GL could be a potential alternative and complementary medicine to treat inflammatory joint diseases.

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PMID: 

Avicenna J Phytomed. 2019 Sep-Oct;9(5):454-464. PMID: 31516859

Abstract Title: 

The anti-diabetic and antioxidant effects of a combination of,andin diabetic rats.

Abstract: 

Objective: Effects ofandethanolic extracts andhydro-ethanolic extract combination were evaluated in streptozotocin (STZ)-induced diabetic rats.Materials and Methods: Male Wistar rats (n=48) were randomly assigned into: control; diabetic; diabetic+metformin (300 mg/kg); diabetic+dose 1 of herbal combination (438 mg/kg of+214 mg/kg of+857 mg/kg of); diabetic+dose 2 (642 mg/kg of+214 mg/kg of+642 mg/kg of); and diabetic+dose 3 (857 mg/kg of+438 mg/kg of+1714 mg/kg t of). All treatments were given orally by gavage. Diabetes was induced by STZ (60 mg/kg, i.p.). At the end of study (day 28), blood glucose, insulin and lipid profile; as well as hepatic malondialdehyde (MDA) and thiol content, and superoxide dismutase (SOD) and catalase (CAT) activities were determined.Results: In diabetic rats, plasma glucose, triglycerides (TG), total cholesterol (TC), and LDL-C, as well as hepatic MDA levels were elevated but plasma HDL-C and insulin, and hepatic thiol content and SOD and CAT activities were reduced compared to control (p

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PMID: 

Planta Med. 2019 Nov ;85(16):1225-1232. Epub 2019 Oct 7. PMID: 31590195

Abstract Title: 

Virucidal Effect of Guggulsterone Isolated from Commiphora gileadensis.

Abstract: 

, locally known as becham, is a plant used in traditional Arabian medicine for treating headache, constipation, stomach, joint pain, and inflammatory disorders. Several studies have reported its antibacterial properties; however, no study has demonstrated its antiviral activity. This study aimed to evaluate the antiviral activity ofas well as to isolate its active compound and investigate its mode of action. This activity was evaluated using 4 viruses, herpes simplex virus type 2 (HSV-2), respiratory syncytial virus type B (RSV-B), coxsackie virus B type 3, and adenovirus type 5 by performing the plaque reduction assay and the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays for enveloped and nonenveloped viruses, respectively. The methanol extract ofleaves only showed antiviral activity against enveloped viruses with a selectivity index of 11.19 and 10.25 for HSV-2 and RSV-B, respectively. The study of the mechanism underlying antiviral activity demonstrated a virucidal effect by direct contact with these target viruses. The active compound, isolated using bio-guided assays involving TLC, was identified as guggulsterone by HPLC-diode array detection coupled with electrospray ionization mass spectrometry. Guggulsterone is an antagonist of the bile acid receptor and a modulator of cholesterol metabolism; however, its antimicrobial properties have been reported for the first time in this study.

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PMID: 

Int J Mol Med. 2019 Nov 1. Epub 2019 Nov 1. PMID: 31746354

Abstract Title: 

Honokiol antagonizes doxorubicin‑induced cardiomyocyte senescence by inhibiting TXNIP‑mediated NLRP3 inflammasome activation.

Abstract: 

Senescence of cardiomyocytes is considered a key factor for the occurrence of doxorubicin (Dox)‑associated cardiomyopathy. The NOD‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome is reported to be involved in the process of cellular senescence. Furthermore, thioredoxin‑interactive protein (TXNIP) is required for NLRP3 inflammasome activation and is considered to be a key component in the regulation of the pathogenesis of senescence. Studies have demonstrated that pretreatment with honokiol (Hnk) can alleviate Dox‑induced cardiotoxicity. However, the impact of Hnk on cardiomyocyte senescence elicited by Dox and the underlying mechanisms remain unclear. Thepresent study demonstrated that Hnk was able to prevent Dox‑induced senescence of H9c2 cardiomyocytes, indicated by decreased senescence‑associated β‑galactosidase (SA‑β‑gal) staining, as well as decreased expression of p16INK4A and p21. Hnk also inhibited TXNIP expression and NLRP3 inflammasome activation in Dox‑stimulated H9c2 cardiomyocytes. When TXNIP expression was enforced by adenovirus‑mediated gene overexpression, the NLRP3 inflammasome was activated, which led to inhibition of the anti‑inflammation and anti‑senescence effects of Hnk on H9c2 cardiomyocytes under Doxtreatment. Furthermore, adenovirus‑mediated TXNIP‑silencing inhibited the NLRP3 inflammasome. Consistently, TXNIP knockdown enhanced the anti‑inflammation and anti‑senescence effects of Hnk on H9c2 cardiomyocytes under Dox stimulation. In summary, Hnk was found to be effective in protectingcardiomyocytes against Dox‑stimulated senescence. This protective effect was mediated via the inhibition of TXNIP expression and the subsequent suppression of the NLRP3 inflammasome. These results demonstrated that Hnk may be of value as a cardioprotective drug by inhibiting cardiomyocyte senescence.

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PMID: 

Anticancer Res. 2019 Dec ;39(12):6555-6565. PMID: 31810921

Abstract Title: 

Honokiol Is a Potential Therapeutic Agent and Has a Synergistic Effect With 5-FU in Human Urothelial Cell Carcinoma Cells.

Abstract: 

BACKGROUND/AIM: Honokiol is a biphenolic component of the bark of Magnolia, and has been shown to exert several activities, including anti-depressant, anti-emetic, anti-oxidative, anti-thrombotic, anti-angiogenesis, anti-anxiolytic, anti-inflammatory and anti-tumor effects.MATERIALS AND METHODS: The anti-tumor activities of honokiol and its synergistic effect with 5-fluorouracil (5-FU) in human urothelial cell carcinoma (UCC) cells were investigated.RESULTS: Honokiol significantly suppressed the proliferation of UCC cells in a dose- and time-dependent manner. Moreover, honokiol inhibited the tumorigenesis of UCC cells in vitro. In addition, honokiol induced cell cycle arrest at G/Gphase and caused apoptosis of UCC cells through the intrinsic pathway. Importantly, we demonstrated that honokiol potentiated the cytotoxic effect of 5-FU, and displayed a synergistic effect with 5-FU in UCC cells.CONCLUSION: Honokiol causes growth inhibition, tumorigenesis suppression, cell cycle arrest, apoptosis, and importantly has a synergistic effect with 5-FU in human UCC cells. Therefore, this agent displays a therapeutic potential for treating human UCC.

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PMID: 

Biomolecules. 2019 Dec 6 ;9(12). Epub 2019 Dec 6. PMID: 31817770

Abstract Title: 

Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation.

Abstract: 

Honokiol is a natural biphenolic compound extracted from traditional Chinese medicinespecies, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.

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PMID: 

Microb Pathog. 2019 Dec 11 ;139:103924. Epub 2019 Dec 11. PMID: 31837416

Abstract Title: 

Antimicrobial activity of eugenol against carbapenem-resistant Klebsiella pneumoniae and its effect on biofilms.

Abstract: 

A preliminary study found that eugenol expressed an antibacterial activity against Klebsiella pneumoniae. However, the mechanism of action of eugenol against K. pneumoniae still remains unexplored. The aim of this study was to gain further insight into the antibacterial effect of eugenol against carbapenem-resistant Klebsiella pneumoniae (CRKP) and possible mode of action. Here, minimum inhibitory concentration (MIC) of eugenol against CRKP strains was determined using the agar dilution method. Moreover, variations in intracellular ATP concentration, intracellular pH (pH), membrane potential and membrane integrity were measured to evaluate the effect of eugenol on cell membrane. Besides, changes in cell structure and biofilm formation of CRKP as well as biofilm-associated cell damage were determined using field emission scanning electron microscope (FESEM), transmission electron microscope (TEM) and confocal laser scanning microscopy (CLSM). Finally, gene expression of biofilm-related biosynthesis was investigated. The results showed that MICs of eugenol against four tested CRKP were 0.2 mg/mL. Eugenol damaged the cell membrane of CRKP, as evidenced by decreased intracellular ATP concentration, reduced pHand cell membrane hyperpolarization, coupled with enhanced membrane permeability. Furthermore, eugenol compromised cell structure and induced loss of intracellular components of CRKP. Additionally, eugenol inhibited biofilm formation and inactivated biofilm CRKP cells. Finally, eugenol presented strong inhibitory effects on biofilm formation and biofilm-associated gene expression, and inactivated CRKP cells growing in biofilms. These findings suggest that eugenol exhibits antimicrobial effect against CRKP strains and could be potentially used to control CRKP-related infections.

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