PMID: 

Bioinformation. 2019 ;15(9):657-665. Epub 2019 Oct 13. PMID: 31787815

Abstract Title: 

Effect of Myristica fragrans extract on total body composition in cafeteria diet induced obese rats.

Abstract: 

It is of interest to evaluate the effect of Myristica fragrans on body composition of cafeteria diet induced obese rats. Thirty rats (150-160g) grouped into 5 and each group contains 6 rats. Group-1 was normal control and 2-5 groups were fed with cafeteria diet for 15 weeks to induce obesity. From 16th week to 25th week test drugs were given as mentioned in the experimental protocol. Body weight, BMI, changes in body composition was measured by TOBEC, adipose tissue weights, organ weights, abdominal circumference were measured according to standard methods. After 70days of treatment with MFE 200mg/kg, 400mg/kg Body weight reduced by 9.29%, 12.87% respectively. BMI was also decreased. Abdominal circumference, total fat percentage, organ weights, was substantially reduced. At 400mg/kg of MFE has shown maximum potentiality when compared with 200mg/kg. Orlistat 50mg was used as standard drug. Tetrahydrofuran, flavonoids, saponins, present in Myristica fragrans has shown anti obesity activity. Our findings explain the potentiality of phytochemicals as a potent anti obesity agent, provide scientific evidence for its traditional use and suggest the possible mechanism of action.

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PMID: 

J Med Food. 2016 Oct ;19(10):952-960. Epub 2016 Aug 26. PMID: 27564381

Abstract Title: 

Hepatoprotective Activity of an Herbal Composition, MAP, a Standardized Blend Comprising Myristica fragrans, Astragalus membranaceus, and Poria cocos.

Abstract: 

Historically, botanicals have been reported to possess good antioxidative activities as demonstrated by their free radical scavenging property rendering their usage in liver protection. In this study, we describe the potential use of MAP, a standardized blend comprising three extracts from Myristica fragrans, Astragalus membranaceus, and Poria cocos, in ameliorating chemically induced acute liver toxicities. Acetaminophen (APAP) and carbon tetrachloride (CCl)-induced acute liver toxicity models in mice were utilized. Hepatic functional tests from serum collected at T24, histopathology analysis, and merit of blending three standardized extracts were evaluated. MAP administered at doses of 150-400 mg/kg showed statistically significant and dose-correlated inhibitions of serum alanine aminotransferase (ALT) ranging from 30.8% (P ≤ .05) to 88.1% (P = .0001) in the APAP and 66.9% (P = .002) to 83.7% (P = .0002) in the CClmodels, respectively. Moreover, MAP resulted in up to 75.7%, 60.9%, and 33.3% reductions in serum aspartate aminotransferase (AST), bile acid, and total bilirubin, respectively. Mice treated with oral doses of composition of MAP at 300 mg/kg showed statistically significant reduction in hepatocyte necrosis when compared with vehicle control. Unexpected synergistic protection of liver damage was also observed. Therefore, the composition, MAP, could be potentially utilized as an effective hepatic detoxifying agent for the protection of liver damage.

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PMID: 

Bioorg Chem. 2017 02 ;70:94-99. Epub 2016 Nov 23. PMID: 27912907

Abstract Title: 

Bioactivity-guided isolation of anti-inflammatory triterpenoids from the sclerotia of Poria cocos using LPS-stimulated Raw264.7 cells.

Abstract: 

Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (-)-pinoresinol (7) and protocatechualdehyde (8). The structures of the isolated compounds were determined by spectroscopic analysis, includingH andC NMR spectra, and LC/MS analysis. The anti-inflammatory activities of the isolates were evaluated by estimating their effect on the production of nitric oxide (NO) and prostaglandin E(PGE) in LPS-stimulated Raw264.7 as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compounds 1-5 inhibited NO production and iNOS expression in LPS-stimulated Raw264.7 cells. Among them, compound 1 exerted the highest anti-inhibitory activity and reduced PGElevels via downregulation of COX-2 protein expression. The findings of this study provide experimental evidence that the sclerotia of P. cocos are a potential source of natural anti-inflammatory agents for use in pharmaceuticals and functional foods. Furthermore, the most active compound 1, seco-lanostane triterpenoid, could be a promising lead compound for the development of novel anti-inflammatory agents.

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PMID: 

Chin J Integr Med. 2017 Dec ;23(12):916-922. Epub 2016 Dec 29. PMID: 28035538

Abstract Title: 

Effect of Poria cocos hydroethanolic extract on treating adriamycin-induced rat model of nephrotic syndrome.

Abstract: 

OBJECTIVE: To evaluate the effect of Poria cocos (Schw.) Wolf hydroethanolic extract (PHE) against nephrotic syndrome (NS) in rats and to identify the potential active components from PHE.METHODS: The high content compounds were isolated and purified by using column chromatography followed by preparative highperformance liquid chromatography (p-HPLC). Forty male Wistar rats with adriamycin (ADR)-induced NS were randomly divided into 5 groups, 8 in each group: model control group, positive control group (with prednisone treatment), PHE low-dose group, PHE middle-dose group and PHE high-dose group. Another 8 rats were recruited as vehicle control group. All rats received the intragastric administration of corresponding drugs or saline for 30 days. During the experimental period, rats' behavior and appearance were observed and recorded daily, and their body weights were recorded weekly. After treatment, 24-h urine samples were collected to evaluate the urine protein and urine creatinine (Ucr); then the rats were sacrificed to collect carotid blood and to determine the levels of serum total protein (TP), albumin (Alb), globulin (Glo), total cholesterol (TC) and cytokine interlukin-4 (IL-4).RESULTS: Six acidic components were isolated and identified from the PHE section: pachymic acid, 15α-hydroxydehydrotumulosic acid, trametenolic acid, dehydropachymic acid, 3β-hydroxy-lanosta-7,9(11), 24-trien-21-oic-acid and dehydroeburicoic acid. Compared with the model control group, the urine protein content were significantly decreased in the PHE treatment groups and positive control group(P

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PMID: 

Cells. 2018 Aug 24 ;7(9). Epub 2018 Aug 24. PMID: 30149516

Abstract Title: 

Cytotoxic Constituents from the Sclerotia ofagainst Human Lung Adenocarcinoma Cells by Inducing Mitochondrial Apoptosis.

Abstract: 

Previous studies have revealed the antitumor potential ofWolf against a broad spectrum of cancers. However, the biological activity ofagainst lung cancer, which is known as the leading cause of cancer mortality worldwide, and its underlying chemical and molecular basis, remain to be investigated. We aimed to evaluate the in vitro cytotoxicity oftoward human lung adenocarcinoma cells with differentstatuses, to identify the bioactive constituents of, and explicate the molecular mechanisms underlying the cytotoxicity of these constituents in human lung adenocarcinoma cells. An EtOH extract of the sclerotia ofexhibited cytotoxicity toward four human lung cancer cell lines: A549, H1264, H1299, and Calu-6, regardless of theirstatus. Chemical investigation of the extract resulted in the isolation of two triterpenoids, dehydroeburicoic acid monoacetate () and acetyl eburicoic acid (); a sterol, 9,11-dehydroergosterol peroxide (); and a diterpenoid, dehydroabietic acid (). All of the isolated compounds were cytotoxic to the lung adenocarcinoma cell lines, exhibiting ICvalues ranging from 63.6μM to 171.0 μM at 48 h of treatment. The cytotoxicity of the extract and the isolated compounds were found to be mediated by apoptosis, and accompanied by elevated Bax expression and/or Bcl-2 phosphorylation along with caspase-3 activation. Our data demonstrate that the sclerotium ofand its four bioactive constituents (⁻) exert cytotoxicity against human lung adenocarcinoma cells, regardless of theirstatus, by inducing apoptosis associated with mitochondrial perturbation, and proposing the potential to employin the treatment of lung cancer.

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PMID: 

Int J Biol Macromol. 2018 Dec ;120(Pt B):1696-1704. Epub 2018 Sep 26. PMID: 30267822

Abstract Title: 

Antidepressant and immunosuppressive activities of two polysaccharides from Poria cocos (Schw.) Wolf.

Abstract: 

Pursuit of novel effective antidepressants is an urgent task. Poria cocos (Schw.) Wolf (PCW) is a traditional herb with antidepressant effects. Polysaccharides designated PCWPW and PCWPS were purified from PCW by DEAE-52 cellulose chromatography. Their structures were characterized using physicochemical and spectral methods. Chemical analysis indicated that PCWPW (37,154 Da) and PCWPS (186,209 Da) were mainly composed of mannose, glucose, galactose and fucose. Their antidepressant activities were evaluated by tail suspension test (TST), forced swimming test (FST) with chronic unpredictable mild stress (CUMS) model mice. To investigate the antidepressant mechanism, the neuroprotective and immunomodulation effects were assessed by MTT method. Results showed that PCWPW and PCWPS possess obvious antidepressant effects and can suppress ConA-stimulated T cell proliferation in a dose-dependent manner. In addition, PCWPS could protect the PC12 cells from HO-induced damage and suppress LPS-induced B cell proliferation. These findings implied that PCWPW and PCWPS might be a candidate for developing antidepressant or immunosuppressive agents in food and pharmaceutical industries.

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PMID: 

Bioorg Med Chem Lett. 2017 07 1 ;27(13):2881-2885. Epub 2017 Apr 27. PMID: 28487074

Abstract Title: 

Protective effect of lanostane triterpenoids from the sclerotia of Poria cocos Wolf against cisplatin-induced apoptosis in LLC-PK1 cells.

Abstract: 

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These resultsindicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

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PMID: 

Int J Biol Macromol. 2018 Jul 15 ;114:137-142. Epub 2018 Mar 20. PMID: 29572139

Abstract Title: 

Hepatoprotective effects exerted by Poria Cocos polysaccharides against acetaminophen-induced liver injury in mice.

Abstract: 

Our study was to investigate the potential pharmacological activity of Poria Cocos polysaccharides (PCP) against acetaminophen (APAP)-induced liver injury in mice. PCP-dosed mice were used to conducting biochemical assays of serological liver enzyme (ALT), lactate dehydrogenase (LD), inflammatory cytokines (TNF-α, IL-6), and immunoassays for functional proteins in the livers. Consequently, APAP-exposed mice resulted in elevated levels of ALT, LD, TNF-α, IL-6 in sera. Interestingly, PCP-dosed mice exhibited reduced ALT, LD and inflammatory cytokines in blood. Inflammatory infiltration and cell death in liver tissue were decreased following by PCP treatments. Furthermore, immunofluorescence staining showed that AKR7A, c-Jun, Bcl-2-positive cells were increased in PCP-dosed livers in mice, while Bax-labeled cells were decreased. In addition, hepatocellular down-regulated NF-κBp65, IkBα expressions were observed dose-dependently in PCP-dosed livers in mice. Taken together, the current findings indicate that Poria Cocos polysaccharides exert pharmacological bioeffects against APAP-induced liver injury in mice, and the underlying molecular mechanism is associated to suppressing inflammatory response and apoptosis in liver cells.

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PMID: 

Biomed Pharmacother. 2018 Jun ;102:865-873. Epub 2018 Apr 5. PMID: 29710543

Abstract Title: 

Molecular mechanism of Poria cocos combined with oxaliplatin on the inhibition of epithelial-mesenchymal transition in gastric cancer cells.

Abstract: 

PURPOSE: Natural product Poria cocos possesses antitumor effect. This study will explore the molecular mechanism of Poria cocos combined with chemotherapy in the inhibition of gastric cancer cell EMT process.METHODS: The experiment was divided into blank control group, Poria cocos group, oxaliplatin group and Poria cocos combined with oxaliplatin group. Scratch and Transwell assay were used to detect cell migration and invasion respectively. RT-qPCR and Western Blot analyses were used to detect mRNA and protein expression of the epithelial-mesenchymal transition (EMT) related factors including Snail, Twist, Vimentin, E-cadherin and N-cadherin respectively. Morphologic assessment was performed with HPIAS-1000 automated image analysis system.RESULTS: The migration and invasion abilities of gastric cancer cells in the Poria cocos combined with oxaliplatin group were significantly decreased (P 

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PMID: 

J Cell Biochem. 2019 May ;120(5):7482-7488. Epub 2018 Oct 30. PMID: 30378160

Abstract Title: 

Antihepatotoxic benefits of Poria cocos polysaccharides on acetaminophen-lesioned livers in vivo and in vitro.

Abstract: 

In our previous study, preliminary data indicates that Poria cocos polysaccharides (PCP) shows beneficial hepatoprotection against acetaminophen (APAP)-induced liver injury in mice. However, biological molecular mechanism warrants to be further discussed. In current study, a number of biochemical tests and immunoassays were subjected to respective PCP-dosed mice in vivo and liver cells in vitro. As a result, PCP-treated mice showed reduced contents of inflammatory cytokines (tumor necrosis factor [TNF]-β and TNFsR-I), enzymological molecules (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase [LDL]), and heat shock protein 90 (Hsp90) after APAP exposure. Additionally, immunostaining assays exhibited that lowered-positive cells of cleaved-caspase-3, cleaved-poly ADP ribose polymerase, and Hsp90-labeled cells in PCP-treated livers were observed, and increased cluster of differentiation 29 (CD29), CD73-positive cells in the spleen were detected. Further, PCP-treated mouse liver cells resulted in increased cell growth, reduced LDL level. Increased proliferating cellnuclear antigen (PCNA), P38 mitogen-activated protein kinase (MAPK)-labeled cells and decreased Hsp90-positive cells in APAP-exposed liver cells were observed dose-dependently after PCP cotreatments. Collectively, our present experimental findings elucidate that PCP beneficially play hepatoprotective effects against APAP-lesioned liver cells in vivo and in vitro, potentially through the molecular mechanisms of suppressing cell death, reducing hepatocellular inflammatory stress and Hsp90 bioactivity.

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