PMID: 

World J Gastroenterol. 2019 Sep 14 ;25(34):5120-5133. PMID: 31558861

Abstract Title: 

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver diseasethe Sirt1/AMPK and NF-κB signaling pathways.

Abstract: 

BACKGROUND: Allyl isothiocyanate (AITC), a classic anti-inflammatory and antitumorigenic agent, was recently identified as a potential treatment for obesity and insulin resistance. However, little is known about its direct impact on the liver.AIM: To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease (commonly referred to as NAFLD).METHODS: To establish a mouse and cellular model of NAFLD, C57BL/6 mice were fed a high fat diet (HFD) for 8 wk, and AML-12 cells were treated with 200μM palmitate acid for 24 h. For AITC treatment, mice were administered AITC (100 mg/kg/d) orally and AML-12 cells were treated with AITC (20 μmol/L).RESULTS: AITC significantly ameliorated HFD-induced weight gain, hepatic lipid accumulation and inflammation. Furthermore, serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice. Mechanistically, AITC significantly downregulated the protein levels of sterol regulatory element-binding protein 1 (SREBP1) and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation, as well as the upstream mediators Sirtuin 1 (Sirt1) and AMP-activated protein kinase α (AMPKα), in the livers of HFD-fed mice. AITC also attenuated the nuclear factor kappa B (NF-κB) signaling pathway. Consistently, AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cellsthrough the Sirt1/AMPK and NF-κB signaling pathways. Importantly, further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKα in AML-12 cells.CONCLUSION: AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway. Therefore, AITC is a potential therapeutic agent for NAFLD.

read more

PMID: 

Life Sci. 2020 Feb 15 ;243:117291. Epub 2020 Jan 9. PMID: 31927049

Abstract Title: 

Allyl isothiocyanate treatment alleviates chronic obstructive pulmonary disease through the Nrf2-Notch1 signaling and upregulation of MRP1.

Abstract: 

AIMS: Chronic obstructive pulmonary disease (COPD) is a disease with high morbidity and mortality worldwide, which can cause serious social and economic burdens. Allyl isothiocyanate (AITC) is one of the most common natural isothiocyanates and has been shown to have anti-inflammatory and antioxidant biological activities. The purpose of this study was to investigate whether AITC regulated Multidrug resistance-associated protein 1 (MRP1), reactive oxide species (ROS) and reduced glutathione (GSH) levels via Nrf2 and Notch1 signaling pathways to treat COPD and whether there was an interaction between these two pathways.MAIN METHODS: Lung function indexes and histopathological changes in mice were determined by lung function instrument and HE staining, respectively. The protein expression was analyzed using immunohistochemistry and Western blotting. The mRNA expression was measured by RT-PCR in human bronchial epithelial cell line 16HBE. The contents of ROS, GSH and GSSG were detected by kits in 16HBE cells.KEY FINDINGS: The protein expression of Notch1, Hes1, MRP1, Nrf2, and HO-1 in lung tissues of WT mice and untransfected cells were significantly down-regulated in COPD, then significantly ameliorated in treatment groups. The protein expression of MRP1, Notch1 and Hes1 in lung tissues of Nrf2mice were markedly reduced. There was a significant reduction in expression of Nrf2, HO-1 and MRP1 in si-Notch1 transfected cells. Pretreatment with AITC markedly improved oxidative stress and GSH-redox disorder in COPD.SIGNIFICANCE: Our study demonstrates that there is a potential interaction between Nrf2 and Notch1 signaling pathways during treatment of COPD.

read more

PMID: 

Int J Mol Sci. 2019 Oct 9 ;20(20). Epub 2019 Oct 9. PMID: 31600887

Abstract Title: 

Glucosinolate-Degradation Products as Co-Adjuvant Therapy on Prostate Cancer in Vitro.

Abstract: 

Glucosinolate-degradation products (GS-degradation products) are believed to be responsible for the anticancer effects of cruciferous vegetables. Furthermore, they could improve the efficacy and reduce side-effects of chemotherapy. The aim of the present study was to determine the cytotoxic effects of GS-degradation products on androgen-insensitive human prostate cancer (AIPC) PC-3 and DU 145 cells and investigate their ability to sensitize such cells to chemotherapeutic drug Docetaxel (DOCE). Cells were cultured under growing concentrations of allyl-isothiocyanate (AITC), sulforaphane (SFN), 4-pentenyl-isothiocyanate (4PI), iberin (IB), indole-3-carbinol (I3C), or phenethyl-isothiocyanate (PEITC) in absence or presence of DOCE. The anti-tumor effects of these compounds were analyzed using the trypan blue exclusion, apoptosis, invasion and RT-qPCR assays and confocal microscopy. We observed that AITC, SFN, IB, and/or PEITC induced a dose- and time-dependent cytotoxic effect on PC-3 and DU 145 cells, which was mediated, at least, by apoptosis and cell cycle arrest. Likewise, we showed that these GS-degradation products sensitized both cell lines to DOCE by synergic mechanisms. Taken together, our results indicate that GS-degradation products can be promising compounds as co-adjuvant therapy in prostate cancer.

read more

Contrary to what mass mainstream media would have you assume, coronaviruses aren’t uncharted territory. In fact, human coronaviruses are responsible for 15-30% of common colds each year

PMID: 

J Ethnopharmacol. 2019 Apr 6 ;233:41-46. Epub 2018 Dec 30. PMID: 30599220

Abstract Title: 

In vitro studies on anti-inflammatory activities of kiwifruit peel extract in human THP-1 monocytes.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Kiwifruit is native to eastern China and many are the references about the consumption of fruits and fruits extracts of the Actinidia plants in Chinese traditional medicine as therapeutic food supplements to prevent and/or counteract numerous disorders including inflammation-related diseases like cancer.AIM OF THE STUDY: Aim of the present work was to obtain a kiwifruit peel extract, rich in polyphenols, and to explore the anti-inflammatory potential by analyzing its capability to target multiple pathways involved in monocyte-mediated inflammatory response.MATERIALS AND METHODS: The extract was obtained from the fruit peel of Actinidia deliciosa (A.Chev.) C.F.Liang&A.R.Ferguson, cv Hayward and characterized by HPLC-DAD-ESI-MS. Lipopolysaccharide-stimulated THP-1 monocytes were used as a model of human inflammation in vitro.RESULTS: Analytical data evidenced that procyanidins resulted the main polyphenols present in the extract, representing the 92% w/w of the total. The extract inhibited the production of inflammatory molecules such as IL-6, IL-1β, TNF-α pro-inflammatory cytokines, HMGB1 danger signal and granzyme B serine protease by activated monocytes. In particular, an inhibitory activity of 81%, 68%, 63%, 76% and 60% on the extracellular release of IL-6, IL-1β, TNF-α, HMGB1 and granzyme B, respectively, was observed by western blotanalysis. Moreover, the extract prevented STAT3 activation and promoted autophagy.CONCLUSIONS: The reported findings demonstrated a strong and broad anti-inflammatory profile of the kiwifruit peel extract, which makes it a promising preventive and therapeutic natural ingredient for nutraceutical, cosmetic and pharmaceutical formulations to counteract multiple inflammatory disorders.

read more

PMID: 

Food Sci Biotechnol. 2020 Jan ;29(1):131-140. Epub 2019 Nov 25. PMID: 31976135

Abstract Title: 

Britton var. frutescens leaves attenuate dextran sulfate sodium-induced acute colitis in mice and lipopolysaccharide-stimulated angiogenic processes in human umbilical vein endothelial cells.

Abstract: 

The aim of the current study was to investigate whether the leaves ofBritton var. frutescens (PL), a frequently consumed vegetable in Korea, attenuate dextran sulfate sodium (DSS)-induced acute colitis in mice and lipopolysaccharide (LPS)-stimulated angiogenic processes in human umbilical vein endothelial cells (HUVEC). In DSS-treated mice, dietary supplementation with PL mitigated DAI and colon shortening. The dietary PL also reduced colonic levels of inflammatory and angiogenic mediators, such as interleukin-1β, interleukin-6, monocyte chemoattractant protein-1, macrophage inflammatory protein-2, leukotriene B, inducible nitric oxide synthase, cyclooxygenase-2, basic fibroblast growth factor, and intercellular adhesion molecule-1 (ICAM-1). Treatment of HUVEC with ethanol extract of PL attenuated LPS-stimulated increases in ICAM-1 levels, monocyte adhesion, invasion, and tube formation. This study suggests that dietary PL effectively inhibited DSS-induced acute colitis in mice, and its anti-angiogenic activities may partially contribute to the inhibition.

read more

PMID: 

J Ethnopharmacol. 2019 Dec 28 ;251:112529. Epub 2019 Dec 28. PMID: 31891797

Abstract Title: 

Actinidia Chinensis Planch Root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting the DLX2/TARBP2/JNK/AKT pathway.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies have confirmed that traditional Chinese herbs exert potential anti-tumor effects. Actinidia Chinensis Planch root has been used as a traditional Chinese medicine (TCM) for thousands of years. However, the mechanism of anti-tumor effects of Actinidia Chinensis Planch root has not been clearly clarified.AIM OF THE STUDY: To explore the molecular biological mechanisms underlying the inhibitory effect of Actinidia Chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC).MATERIALS AND METHODS: In our previous study, we used mRNA chip analyses to identify genes regulated by acRoots. Further analyses of altered genes led to the identification of a key regulator of genes that responds to acRoots. We explored the effects of acRoots on the proliferation and invasion of HCC cells via cell counting as well as transwell assays, and further explored the molecular mechanisms underlying the effects of acRoots on HCC cells using qRT-PCR, western blot, and Chip-PCR.RESULTS: Increasing the concentration of acRoots as well as prolonging its action time enhanced the inhibitory activity of acRoots as well as its cytotoxicity against HCC cells. High TARBP2 expression in HCC cells, which is associated with advanced-stage HCC and poor prognoses in HCC patients, was downregulated by treatment with acRoots. Furthermore, acRoots inhibited proliferation, invasion, and epithelial-to-mesenchymal transition by downregulating TARBP2 expression. HCC cells with higher TARBP2 expression were more sensitive to acRoots. The expression of TARBP2 and DLX2 in HCC patients and HCC cell lines was significantly positively correlated, and DLX2 as a transcription factor may promote TARBP2 expression, thereby further activating the JNK/AKT signaling pathway leading to the inhibition of HCC.CONCLUSIONS: acRoots inhibited the malignant behavior of HCC cells by inhibiting TARBP2 expression, which is affected by the transcription factor DLX2, leading to a reduction in JNK/AKT signaling pathway activation.

read more

PMID: 

Nutr Res. 2016 11 ;36(11):1231-1242. Epub 2016 Sep 30. PMID: 27865618

Abstract Title: 

Actinidia arguta supplementation protects aorta and liver in rats with induced hypercholesterolemia.

Abstract: 

There are no published results focusing on the study of hardy kiwifruit as a supplementation to the atherogenic diet. We hypothesized that hardy kiwifruit (Actinidia arguta (A. arguta)) from Poland possess better pro-healthy action than two Asian varieties (Hayward and Bidan). We tested this hypothesis by measuring the metabolic reactions of rats loaded with 1% cholesterol and supplemented with 5% of hardy kiwifruit (A. arguta), Hayward, or Bidan in their diets. The experiment was performed on 71 male Wistar rats. Cholesterol showed a significant impact on the rise of liver somatic index, while lipid profile improved by decreasing the levels of TC, LDL-C, TC/HDL-C, AI, TG, and increasing HDL-C in the serum of rats (P

read more

PMID: 

J Ethnopharmacol. 2018 Mar 1 ;213:159-165. Epub 2017 Nov 21. PMID: 29174375

Abstract Title: 

Actinidia arguta extract attenuates inflammasome activation: Potential involvement in NLRP3 ubiquitination.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Actinidia arguta (A. arguta) has been widely used in Asian countries as a traditional medicinal herb to treat inflammation-related diseases, such as gastritis, bronchitis, and arthritis.AIM OF THE STUDY: The inhibitory effect of A. arguta leaves' extract (AA) on inflammasome activation was investigated to verify its traditional use in treating inflammation-related diseases.MATERIALS AND METHODS: Bone marrow-derived macrophages (BMDMs) primed by lipopolysaccharide (LPS) were activated by selective inflammasome stimulators, and the effect of AA on inflammasome activation was investigated. A monosodium urate crystal (MSU)-induced peritonitis mouse model was used to study the in vivo efficacy of AA on inflammasome activation.RESULTS: In the in vitro study, AA regulated NLRP3 ubiquitination and apoptosis-associated speck-like protein containing a CARD (ASC) oligomerization, leading to the inhibition of NLRP3 inflammasome-mediated interleukin (IL)-1β secretion. The inhibitory effect of AA on inflammasome activation in vitro was further confirmed in vivo using an MSU-induced peritonitis mouse model.CONCLUSION: AA provided scientific evidence, substantiating the traditional claims for its use in the treatment of inflammation and inflammation-mediated metabolic disorders, including gout.

read more