PMID: 

J Agric Food Chem. 2019 Jul 29. Epub 2019 Jul 29. PMID: 31322351

Abstract Title: 

Pelargonidin-3–glucoside Derived from Wild Raspberry Exerts Antihyperglycemic Effect by Inducing Autophagy and Modulating Gut Microbiota.

Abstract: 

Increasing evidence indicates that anthocyanins exert beneficial effects on type 2 diabetes (T2D), but the underlying mechanism remains unclear. Herein, the hyperglycemia-lowering effect of Pg3G derived from wild raspberry was investigated on high-glucose/high-fat (HG+HF)-induced hepatocytes and/diabetic mice. Our results indicated that Pg3G promoted glucose uptake in HG+HF-induced hepatocytes. Moreover, Pg3G induced autophagy, whereas autophagy inhibitors blocked the hypoglycemic effect of Pg3G. Transcriptional factor EB (TFEB) was found to be linked to Pg3G-induced autophagy. In vivo study showed that Pg3G treatment contributed to the improvement of glucose tolerance, insulin sensitivity, and induction of autophagy. Furthermore, Pg3G not only modified the gut microbiota composition, as indicated by an increased abundance of, and elevated Bacteroidetes/Firmicutes ratio, but also strengthened the intestinal barrier integrity. This study unveils a novel mechanism that Pg3G attenuates hyperglycemia through inducing autophagy and modulating gut microbiota, which implicates a potential nutritional intervention strategy for T2D.

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PMID: 

J Ethnopharmacol. 2013 Jul 9 ;148(2):403-10. Epub 2013 Apr 21. PMID: 23612421

Abstract Title: 

Urinary metabonomic study of the surface layer of Poria cocos as an effective treatment for chronic renal injury in rats.

Abstract: 

ETHNOPHARMACOLOGICAL RELEVANCE: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus. The epidermis of the sclerotia ("Fu-Ling-Pi"in Chinese) is used as a diuretic and traditionally used for promoting urination and reduce edema.AIM OF THE STUDY: Traditional Chinese medicines (TCM) treat many diseases through multi-components, multi-ways and multi-targets. However, the molecular mechanisms of TCM are not yet well understood. In the present work, ultra performance liquid chromatography-based metabonomics analysis was applied to investigate the urinary metabolite profiling of the renoprotective effect of FLP on adenine-induced chronic kidney disease (CKD) rat model and involved possible mechanism.MATERIAL AND METHODS: A metabonomic approach based on ultra performance liquid chromatography coupled with quadrupole time-of-flight high-sensitivity mass spectrometry and a novel mass spectrometry(Elevated Energy) data collection technique was developed. The resulting dataset was analyzed by principal component analysis and partial least squares discriminant analysis. The identification of all potential biomarkers was performed using reference standard by comparing their mass spectra, MS(E) fragments information, isotopic pattern and MassLynx i-FIT algorithm.RESULTS: By partial least squares-discriminate analysis, 15 biomarkers in rat urine were identified and 11 of them were related to the pathway of adenine metabolism and amino acid metabolism. Among these biomarkers, eight biomarkers like adenine, L-acetylcarnitine, 8-hydroxyadenine, hypoxanthine, creatine, methionine, phytosphingosine and phenylalanine were reversed to the control level in FLP-treated group and six biomarkers like 2,8-dihydroxyadenine, indole-3-carboxylic acid, 3-methyldioxyindole, ethyl-N2-acetyl-L-argininate, 3-O-methyldopa and xanthurenic acid were reversed to high control group by FLP, which indicates that the urinary metabolic pattern significantly changed after FLP treatment.CONCLUSIONS: Our study indicates that FLP treatment can ameliorate CKD by intervening in some dominating metabolic pathways, such as adenine metabolism and amino acid metabolism. The metabonomic results not only supplied a systematic view of the development and progression of CKD and mechanism studies of FLP but also provided the theoretical basis for the prevention or treatment of CKD.

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PMID: 

Int J Oncol. 2013 Jun ;42(6):1869-74. Epub 2013 Apr 16. PMID: 23588713

Abstract Title: 

Triterpenes from Poria cocos suppress growth and invasiveness of pancreatic cancer cells through the downregulation of MMP-7.

Abstract: 

Poria cocos is a medicinal mushroom that is widely used in traditional Asian medicine. Here, we show that a characterized mixture of triterpenes extracted from P. cocos (PTE) and three purified triterpenes: pachymic acid (PA), dehydropachymic acid (DPA) and polyporenic acid C (PPAC) suppress the proliferation of the human pancreatic cancer cell lines Panc-1, MiaPaca-2, AsPc-1 and BxPc-3. Moreover, the most effective compound, PA, only slightly affects theproliferation of HPDE-6 normal pancreatic duct epithelial cells. The anti-proliferative effects of PTE on BxPc-3 cells are mediated by the cell cycle arrest at G0/G1 phase. DNA microarray analysis demonstrated that PTE significantly downregulates the expression of KRAS and matrix metalloproteinase-7(MMP-7) in BxPc-3 cells. In addition, PTE and PA suppress the invasive behavior of BxPc-3 cells. The inhibition of invasiveness by PTE and PA was associated with the reduction of MMP-7 at the protein level and the role of MMP-7 further confirmed by the gene silencing of MMP-7 which also suppressedthe invasiveness of BxPc-3 cells. In conclusion, triterpenes from P. cocos demonstrate anticancer and anti-invasive effects on human pancreatic cancer cells and can be considered as new therapeutic agents in the treatment of pancreatic cancer.

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PMID: 

BMC Complement Altern Med. 2014 Mar 15 ;14:101. Epub 2014 Mar 15. PMID: 24628870

Abstract Title: 

Ethanol extract of Poria cocos reduces the production of inflammatory mediators by suppressing the NF-kappaB signaling pathway in lipopolysaccharide-stimulated RAW 264.7 macrophages.

Abstract: 

BACKGROUND: Poria cocos Wolf, a medicinal fungus, is widely used in traditional medicines in East Asian countries owing to its various therapeutic potentials. Although several studies have demonstrated the anti-inflammatory activity of this fungus, its underlying mechanisms have not yet been clearly defined.METHODS: In the present study, we have demonstrated the anti-inflammatory effects of ethanol extract of P. cocos (EEPC) in lipopolysaccaride (LPS)-stimulated RAW 264.7 macrophages. As inflammatory parameters, the productions of nitric oxide (NO), prostaglandin E2 (PGE2), interleukin (IL)-1β and tumor necrosis factor (TNF)-α were evaluated. We also examined the EEPC's effect on the nuclear factor-kappaB (NF-κB) signaling pathway.RESULTS: Our results indicated that EEPC exhibits a potent inhibitory effect on NO production and inhibits PGE2 release in LPS-induced macrophages without affecting cell viability. EEPC also significantly attenuated LPS-induced secretion of inflammatory cytokines IL-1β and TNF-α. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1β, and TNF-α was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-κB, as well as the nuclear translocation of the NF-κB p65, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IκB) degradation.CONCLUSIONS: Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1β, and TNF-α through inactivation of the NF-κB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.

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PMID: 

Oncol Rep. 2015 Nov ;34(5):2533-40. Epub 2015 Sep 8. PMID: 26353048

Abstract Title: 

Induction of apoptosis by an ethanol extract of Poria cocos Wolf. in human leukemia U937 cells.

Abstract: 

Poria cocos Wolf., which belongs to the Polyporaceae family, has been widely used as an Oriental traditional herbal medicine for centuries. Its sclerotium has been reported to possess a wide spectrum of pharmacological activities, including free-radical scavenging, anti-viral, anti-microbial, anti-inflammatory and anticancer activities. However, the cellular and molecular mechanisms of apoptosis induction by P. cocos in human cancer cells are poorly understood. In the present study, we investigated the pro-apoptotic potential of an ethanol extract of P. cocos sclerotium (EEPC) in human leukemiaU937 cells in vitro. We found that EEPC induced anti-proliferative effects in U937 cells in a concentration- and time-dependent manner, which was due to apoptotic induction, as evident from morphological changes and flow cytometric assays. EEPC-induced apoptosis of U937 cells was associated with an increase in the Bax:Bcl-2 ratio, the release of cytochrome c to the cytosol, and a decrease in the expression of an inhibitor of the apoptosis family of proteins. The events were accompanied by activation of caspase-8, -9 and -3, and cleaved poly(ADP-ribose) polymerase, suggesting the involvement of both the intrinsic and extrinsic apoptotic cascades. In addition, the overexpression of Bcl-2 caused a significant attenuation of EEPC-induced caspase activation, degradation of PARP, and the collapse of mitochondrial membrane potential, and thereby reversed EEPC-induced cell apoptosis and growth inhibition. Collectively, these data provide insights into the molecular mechanisms underlying EEPC-induced apoptosis in U937 cells, suggesting that EEPC may be a new therapeutic option for the treatment of leukemia.

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PMID: 

Int J Biol Macromol. 2016 Feb ;83:103-10. Epub 2015 Nov 19. PMID: 26601761

Abstract Title: 

Antioxidant property of water-soluble polysaccharides from Poria cocos Wolf using different extraction methods.

Abstract: 

Poria cocos Wolf is a popular traditional medicinal plant that has invigorating activity. Water-soluble polysaccharides (PCPs) are its main active components. In this study, four different methods were used to extract PCPs, which include hot water extraction (PCP-H), ultrasonic-assisted extraction (PCP-U), enzyme-assisted extraction (PCP-E) and microwave-assisted extraction (PCP-M). Their chemical compositions and structure characterizations were compared. In vitro antioxidant activities were studied on the basis of DPPH radical, hydroxyl radical, reducing power and metal chelating ability. The results showed that PCPs were composed of mannose, glucose, galactose, and arabinose, and had typical IR spectra characteristics of polysaccharides. Compared with other PCPs, PCP-M had lower neutral sugar content, higher mannose content and higher uronic acid content. The molecular weight were determined as PCP-E

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PMID: 

Pharm Biol. 2016 Nov ;54(11):2528-2535. Epub 2016 May 9. PMID: 27159135

Abstract Title: 

Antiepileptic activity of total triterpenes isolated from Poria cocos is mediated by suppression of aspartic and glutamic acids in the brain.

Abstract: 

CONTEXT: Triterpenes from Poria cocos Wolf (Polyporaceae) have been used to treat various diseases in traditional Chinese medicine. However, the antiepileptic effects and mechanism are not fully understood.OBJECTIVE: The objective of this study is to investigate the antiepileptic properties of total triterpenes (TTP) from the whole P. cocos.MATERIALS AND METHODS: The ethanol extract TTP was identified by HPLC fingerprint analysis. Male ICR mice were gavaged (i.g.) with TTP (5, 20, 80 or 160 mg/kg) or reference drugs twice a day for 7 d. Antiepileptic activities of TTP were evaluated by maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizures in mice for 30 and 60 min, respectively. Locomotor activity and Rota-rod tests were performed for 60 min and 5 min, respectively. The levels of glutamic acid (Glu), aspartic acid (Asp), γ-aminobutyric acid (GABA) and glycine (Gly) in convulsive mice were estimated. The chronic epileptic model of Wistar rats was built to measure expressions of glutamate decarboxylase 65 (GAD65) and GABAin rat brain after TTP treatment.RESULTS: The LCof TTP (i.g.) was above 6 g/kg. TTP (5-160 mg/kg) protected mice against MES- and PTZ-induced convulsions at 65.0% and 62.5%, respectively, but have no effect on rota-rod treadmill; TTP (20-160 mg/kg) significantly reduced the locomotor activities, shortened the onset of pentobarbital sodium-induced sleep; TTP decreased Glu and Asp levels in convulsive mice, but increased the GAD65 and GABAexpressions in chronic epileptic rats at doses usage.DISCUSSION AND CONCLUSION: TTP extracted from P. cocos possessed potential antiepileptic properties and is a candidate for further antiepileptic drug development.

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PMID: 

Mediators Inflamm. 2016 ;2016:3472608. Epub 2016 Jun 29. PMID: 27445434

Abstract Title: 

Regulatory T Cell Induced by Poria cocos Bark Exert Therapeutic Effects in Murine Models of Atopic Dermatitis and Food Allergy.

Abstract: 

The prevalence of allergic disorders including atopic dermatitis (AD) and food allergy (FA) has increased dramatically in pediatric populations, but there is no effective drug available for their management. Therefore, trials are required for the development of safe therapeutic agents such as herbal medicines. We determined whether orally administered Poria cocos bark (PCB) extract could exert immunosuppressive effects on allergic and inflammatory symptoms of AD and FA. For both AD, which was induced using house dust mite extract, and FA, which was induced by exposure to ovalbumin, model mice were orally treated with PCB extract for 62 days and 18 days, respectively. We also investigated the inductive effect of PCB extract on the generation and maintenance of Foxp3(+)CD4(+) regulatory T cells (Tregs). The symptoms of AD and FA were ameliorated by the administration of PCB extract. Furthermore, PCB extract inhibited the Th2-related cytokines and increased the population of Foxp3(+)CD4(+) Tregs in both AD and FA models. In ex vivo experiments, PCB extract promoted the functional differentiation of Foxp3(+)CD4(+) Tregs, which is dependent on aryl hydrocarbon receptor activation. Thus, PCB extract has potential as an oral immune suppressor for the treatment of AD and FA through the generation of Tregs.

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PMID: 

Folia Morphol (Warsz). 2019 May 7. Epub 2019 May 7. PMID: 31063201

Abstract Title: 

Ameliorative effect of Myristica fragrans (nutmeg) extract on oxidative status and histology of pancreas in alloxan induced diabetic rats.

Abstract: 

BACKGROUND: Many traditional treatments have been recommended in the alternative system of medicine for the treatment of diabetes mellitus. The aim of this study was to assess oxidative stress and histological changes in the pancreas of alloxan-induced diabetic rats following Myristica fragrans seed (nutmeg) extract treatment.MATERIALS AND METHODS: Forty-eight male Wistar rats weighing 200-250 g were randomly divided into six groups of eight rats each. Group I, non-diabetic rats; group II, diabetic rats; groups III, IV and V, diabetic rats given orally nutmeg extract at levels of 50, 100 and 200 mg/kg, respectively; and group VI, diabetic rats given orally metformin (100 mg/kg). The experiment lasted for 28 days.RESULTS: Data showed that nutmeg extract (100 and 200 mg/kg) significantly decreased the blood glucose levels and increased the levels of serum insulin in diabetic rats. Administration of nutmeg extract to diabetic rats reduced oxidative stress and improved the antioxidant activities in pancreatic tissue. Histopathologic results of treated groups revealed marked improvement in the morphology of the pancreas compared with the control diabetic group. In addition, number of pancreatic islets and percent ofβ-cells increased significantly in these groups in comparison with diabetic untreated group.CONCLUSIONS: These results suggest that nutmeg extract has potent antidiabetic andβ-cell protection activities in alloxan induced diabetic rats, possibly via its antioxidant properties.

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PMID: 

An Acad Bras Cienc. 2019 Jun 19 ;91(2):e20181044. Epub 2019 Jun 19. PMID: 31241706

Abstract Title: 

Evaluation of Gastro-protective Activity of Myristica fragrans on Ethanol-induced Ulcer in Albino Rats.

Abstract: 

Myristica fragrans seeds are traditionally used to treat dyspepsia, vomiting and abdominal pain. The purpose of this study was to investigate the protective effect of Myristica fragrans in ethanol induced gastric ulcer. Study was carried out on rats, divided into four groups; negative control, positive control, standard drug control, and Myristicafragrans extract treated rats. The pH, ulcer index, acidity values and histopathological examination of stomach were evaluated. Myristica fragrans significantly (P

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