PMID: 

Eur J Pediatr. 2013 Feb ;172(2):171-7. Epub 2012 Oct 11. PMID: 23052615

Abstract Title: 

Sixty-four children with persistent itching nodules and contact allergy to aluminium after vaccination with aluminium-adsorbed vaccines-prognosis and outcome after booster vaccination.

Abstract: 

UNLABELLED: Persistent itching subcutaneous nodules and aluminium (Al) allergy have been described after vaccination with Al-adsorbed vaccines but are considered rare. Little is known about the prognosis. Sixty-four children with itching nodules following vaccination with diphtheria-tetanus-pertussis (DTP) vaccines currently used in Sweden (Infanrix® and Pentavac®) were spontaneously reported to the authors from 1999 and followed for up to 12 years. The median duration of itching was 5 years in the 44 children who were free or almost free from symptoms at the latest follow-up. Typical findings were a long interval between vaccination and onset of symptoms (months or years) and intensified itching during intercurrent infections. Contact allergy to aluminium was demonstrated in 60/63 children (95 %). Neither the incidence nor differences between the two vaccines can be estimated from this study, but vaccine-induced itching nodules areprobably more common than hitherto realised. The median interval between onset of symptoms and diagnosis was 8 months in a region where nurses were educated to recognise the condition compared to 2 years in other regions. Booster vaccination with DTP-polio was postponed or declined by 15/40 families in fear for new problems. Out of 25 children who received a booster dose, only two had new itching nodules.CONCLUSION: Intensely itching subcutaneous nodules (vaccination granulomas) and contact allergy to aluminium may occur after primary vaccination with the two most commonly used DTP vaccines in Europe. The condition is probably underreported. Symptoms may last for at least 4-5 years but eventually seem to subside.

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PMID: 

Prog Mol Biol Transl Sci. 2019 ;163:263-296. Epub 2019 Apr 1. PMID: 31030751

Abstract Title: 

Molecular basis for Poria cocos mushroom polysaccharide used as an antitumor drug in China.

Abstract: 

Poria cocos is an edible mushroom known as"Fuling"in Chinese, which belongs to the fungus family of Polyporaceae. Poria cocos has been used as a Chinese traditional medicine for>2000 years. Indications for using it include promoting urination, to invigorate the spleen function, and to calm the mind. The bioactive components in Poria cocos include polysaccharides, triterpenoids, fatty acids, sterols, enzymes, etc. Poria cocos polysaccharide (PCP) accounts for 84% by weight among all constituents in the dried sclerotium. Biochemical and pharmacological studies reveal that PCP is the major bioactive component in Poria cocos and has a wide range of biological activities including antitumor, immunomodulation, anti-inflammation, anti-oxidation, anti-aging, anti-hepatitis, anti-diabetes, and anti-hemorrhagic fever effects. As a result,"Poria cocos polysaccharide oral solution"was developed and sold as an over-the-counter health supplement since 1970s. In 2015,"Polysaccharidum of Poria cocos oral solution"was approved as a drug by Chinese Food and Drug Administration (SFDA) for treating multiple types of cancers, hepatitis, and other diseases alone or during chemo- or radiation therapy for cancer patients. In this article, biochemical, preclinical and clinical studies of Poria cocos polysaccharide from 74 independent studies during the past 46 years (1970-2018) based on PubMed, VIP (Chongqing VIP Chinese Scientific Journals Database), CNKI (China National Knowledge Infrastructure), and Wanfang database searches are summarized. The structure, pharmacological effects, clinical efficacy, immune regulatory molecular mechanisms, and toxicity of PCP are deliberated to provide the data basis for PCP to serve as a clinically used antitumor drug.

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PMID: 

Zhongguo Zhong Yao Za Zhi. 2019 Jul ;44(13):2835-2840. PMID: 31359698

Abstract Title: 

[Isolation of homogeneous polysaccharide from Poria cocos and effect of its sulfated derivatives on migration of human breast cancer MDA-MB-231 cells].

Abstract: 

SATB1 plays a crucial role in the invasion and metastasis of breast cancer,and inhibition of SATB1 expression can effectively control breast cancer metastasis. In this study,homogeneous polysaccharides were isolated from Poria cocos and their sulfated derivatives were prepared to screen out the polysaccharide compositions with inhibitory effects on SATB1 expression. Smal-molecule components were removed from P. cocos by ethanol extraction,and P. cocos crude polysaccharide PPS was obtained by water extraction and ethanol precipitation. Then PPS was successively separated by DEAE Sepharose fast flow anion-exchange and Superdex-75 gel permeation chromatographic steps to give PPSW-1. The structure of PPSW-1 was identified and its sulfated derivatives were prepared. Then their inhibitory effects on human breast cancer MDA-MB-231 cells were investigated. A kind of polysaccharide,PPSW-1 with inhibitory effect on human breast cancer MDA-MB-231 cells,was obtained from P. cocos,with a relative molecular weight of 3. 06×104,and structure of 1,6-branched 1,3-α-D-galactan. PPSW-1 and its sulfated derivative Sul-W-1 showed good inhibitory effect on cells migration,and the water solubility of Sul-W-1 was better than that of PPSW-1. In addition,it was found that polysaccharide of P. cocos and its sulfated derivativecan inhibit expression of SATB1. In this study,a kind of homogeneous polysaccharide with inhibitory effect on human breast cancer MDA-MB-231 cells was isolated from P. cocos,and its sulfated derivative with similar efficacy but better solubility was prepared,laying the foundation for the substance basis study of P. cocos.

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PMID: 

J Agric Food Chem. 2019 Oct 2 ;67(39):10871-10879. Epub 2019 Sep 23. PMID: 31517482

Abstract Title: 

16α-Hydroxytrametenolic Acid fromImproves Intestinal Barrier Function Through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway.

Abstract: 

This study evaluated the effect of triterpenoids from edible mushroomon intestinal epithelium integrity and revealed the transcriptional regulatory pathways that underpin restorative mechanisms in the gut. Based on computational docking studies, transcriptional activation experiments and glucocorticoid receptor (GR) protein immunofluorescence localization assays in cultured cells, 16α-hydroxytrametenolic acid (HTA) was discovered as a novel GR agonist in this study. HTA ameliorates TNF-α-induced Caco-2 monolayer intestinal epithelial barrier damage and suppressed activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), which attenuated downstream IκB and nuclear factor kappa-B (NF-κB) phosphorylation through GR activation. Moreover, HTA prevented NF-κB translocation into the nucleus and binding to its cis-element and suppressed lipopolysaccharide-induced downstream NO production and pro-inflammatory cytokines at both protein and mRNA expressionlevels. In conclusion, HTA fromimproves intestinal barrier function through a GR-mediated PI3K/Akt/NF-κB signaling pathway and may be potentially exploited as a supportive dietary therapeutic strategy for restoring gut health.

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PMID: 

Int J Mol Sci. 2019 Sep 27 ;20(19). Epub 2019 Sep 27. PMID: 31569635

Abstract Title: 

Wolf Extract Ameliorates Hepatic Steatosis through Regulation of Lipid Metabolism, Inhibition of ER Stress, and Activation of Autophagy via AMPK Activation.

Abstract: 

Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)-palmitic and oleic acid-and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.

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PMID: 

Nanomedicine. 2020 Jan ;23:102095. Epub 2019 Oct 25. PMID: 31669856

Abstract Title: 

Co-delivery of Poria cocos extract and doxorubicin as an 'all-in-one' nanocarrier to combat breast cancer multidrug resistance during chemotherapy.

Abstract: 

Recent studies have indicated that multidrug resistance (MDR) can significantly limit the effects of conventional chemotherapy. In this study, PT (Pachymic acid and dehydrotumulosic acid) are the two major triterpenoid components purified and identified in P. cocos. A liposomal co-delivery system encapsulating doxorubicin (DOX) and PT was prepared. Notably, the mechanism of PT reversed P-glycoprotein (P-gp) mediated MDR mainly relied on the inhibition of the P-gp function, which further decreased the levels of P-gp and caveolin-1 proteins. In drug-resistant MCF cells, co-administration with 5 μg/ml PT significantly enhanced sensitivity of DOX. Finally, liposome-mediated co-delivery with PT significantly improved the anti-tumor effect of DOX in tumor-bearing mice when compared to other single therapy groups. In conclusion, this study showed for the first time that DOX and PT act synergistically as an"all-in-one"treatment to reverse MDR during tumor treatment and, thus, should be studied further for a wide range of anti-cancer applications.

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PMID: 

Int Immunopharmacol. 2020 Jan 13 ;80:106173. Epub 2020 Jan 13. PMID: 31945610

Abstract Title: 

Poria cocos polysaccharides attenuated ox-LDL-induced inflammation and oxidative stress via ERK activated Nrf2/HO-1 signaling pathway and inhibited foam cell formation in VSMCs.

Abstract: 

Oxidative stress, inflammation, and foam cell formation in vascular smooth muscle cells (VSMCs) are considered to play crucial roles in the pathogenesis of atherosclerosis. Poria cocos polysaccharides (PCP) has been shown to possess anti-inflammatory, antitumor and anti-oxidative properties. In this study we explored the effects of PCP on ox-LDL-induced inflammation, oxidative stress and foam cell formation in VSMCs. PCP significantly attenuated ox-LDL-induced oxidative stress, as evidenced by the decreased reactive oxygen species (ROS) and MDA levels, and the increased SOD activity in VSMCs. PCP suppressed the induction effect of ox-LDL on inflammatory cytokines and inflammatory mediators. PCP also substantially inhibited VSMCs foam cell formation and intracellular lipids accumulation. Mechanistically, PCP suppressed ox-LDL-induced up-regulation of LOX-1, which is responsible for ox-LDL uptake. Western blotting suggested that PCP activated ERK1/2 signaling pathway, increased Nrf2 translocated from cytoplasm to nucleus and heme oxygenase-1 (HO-1) expression. Up-regulation of PCP on Nrf2/HO-1 signaling was reversed by pretreatment with ERK inhibitor PD98059, indicating the involvement of ERK in PCP activation of Nrf2/HO-1 signaling. In conclusion, these results demonstrated that PCP exerted its protection against oxidative stress and inflammation via the ERK/Nrf2/HO-1 signaling pathway and that PCP may be a promising candidate for the therapy of atherosclerosis.

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PMID: 

J Ethnopharmacol. 2020 Jan 9. Epub 2020 Jan 9. PMID: 31926986

Abstract Title: 

Poria cocos water extract ameliorates the behavioral deficits induced by unpredictable chronic mild stress in rats by down-regulating inflammation.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos is a medicinal mushroom of the Polyporaceae family with antioxidant and anti-inflammatory activities, which has been used for its sedative, diuretic and tonic effects in traditional medicine for several hundred years.AIM OF STUDY: Considering that depression is an inflammatory related mental disease, this study investigated the antidepressant-like effects of water extract of P. cocos in a rodent animal model.MATERIALS AND METHODS: Rats that were exposed to a forced swimming test (FST) for 28 consecutive days, and unpredictable chronic mild stress (UCMS) for five weeks underwent treatment with P. cocos water extract (PCW) (doses: 100, 300 and 900 mg/kg body weight [bw]; administered by gavage). Dopamine (DA), serotonin (5-HT) and their metabolites in the frontal cortex of rats were measured.RESULTS: Our results firstly showed that sucrose preference during the UCMS paradigm was increased and immobility time in the FST was reduced with administration of PCW. In addition, PCW significantly attenuated UCMS-induced turnover rate of DA and 5-HT in the frontal cortex. Moreover, PCW inhibited UCMS-induced activated inflammatory response, reflected by reduced expression in the frontal cortex of p38, NF-κB and TNF-α.CONCLUSIONS: Our results strongly suggest that PCW exhibits a potent antidepressant-like effect via regulation of monoaminergic neurotransmission and inactivation of inflammation, and that P. cocos may be considered as a traditional herbal potential medicine for the treatment of depression.

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PMID: 

Molecules. 2016 Aug 31 ;21(9). Epub 2016 Aug 31. PMID: 27589714

Abstract Title: 

Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts andα-Glucosidase Inhibitory Activities of Different Fractionations.

Abstract: 

Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak(®) cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC50 = 15.4-69.5 μg/mL), which were higher than that of positive control acarbose (IC50 = 383.2 μg/mL). Four purified compounds 1-4 exerted α-glucosidase inhibitory activities, with IC50 values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved.

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PMID: 

Evid Based Complement Alternat Med. 2016 ;2016:6093783. Epub 2016 Sep 14. PMID: 27703489

Abstract Title: 

Myricitrin Protects against Doxorubicin-Induced Cardiotoxicity by Counteracting Oxidative Stress and Inhibiting Mitochondrial Apoptosis via ERK/P53 Pathway.

Abstract: 

Doxorubicin (Dox) is one of the most effective and widely used anthracycline antineoplastic antibiotics. Unfortunately, the use of Dox is limited by its cumulative and dose-dependent cardiac toxicity. Myricitrin, a natural flavonoid which is isolated from the ground bark of, has recently been found to have a strong antioxidative effect. This study aimed to evaluate the possible protective effect of myricitrin against Dox-induced cardiotoxicity and the underlying mechanisms. An in vivo investigation in SD rats demonstrated that myricitrin significantly reduced the Dox-induced myocardial damage, as indicated by the decreases in the cardiac index, amelioration of heart pathological injuries, and decreases in the serum cardiac enzyme levels. In addition, in vitro studies showed that myricitrin effectively reduced the Dox-induced cell toxicity. Further study showed that myricitrin exerted its function by counteracting oxidative stress and increasing the activities of antioxidant enzymes. Moreover, myricitrin suppressed the myocardial apoptosis induced by Dox, as indicated by decreases in the activation of caspase-3 and the numbers of TUNEL-positive cells, maintenance of the mitochondrial membrane potential, and increase in the Bcl-2/Bax ratio. Further mechanism study revealed that myricitrin-induced suppression of myocardial apoptosis relied on the ERK/p53-mediated mitochondrial apoptosis pathway.

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