Effect of Poria cocos on hypertonic stress-induced water channel expression and apoptosis in renal collecting duct cells

Department of Oriental Medicine and Professional Graduate School of Oriental Medicine, Wonkwang University, Iksan 570-749, Republic of Korea
Journal of ethnopharmacology (Impact Factor: 3). 03/2012; 141(1):368-76. DOI: 10.1016/j.jep.2012.02.048
Source: PubMed


A major physiological role of the kidney is to regulate body water and urine concentration. Aquaporin-2 (AQP2), a family of water channels, plays an important role in the urinary concentrating process and regulation of water balance in the kidney. The dried sclerotia of Poria cocos Wolf has been known to have a diuretic effect and used for the treatment of chronic edema and nephrosis.
This study was conducted to evaluate the inhibitory effect of the sclerotia of Poria cocos (WPC) on hypertonic stress-induced AQP2 expression and apoptosis in inner medullary collecting duct cell lines (IMCD-3).
Hypertonic stress was induced by 175mM NaCl. Inhibitory effect of WPC on hypertonic stress-induced AQP2 expression and apoptosis were determined by western blot, RT-PCR, and immunofluorescence.
Hypertonic stress (175mM NaCl) increased in the levels of AQP2 expression by hypertonicity in IMCD-3 cells. WPC attenuated the hypertonicity-induced increase in protein and mRNA levels of AQP2 in a concentration-dependent manner. Pretreatment with WPC attenuated hypertonicity-induced cell death. Hypertonicity increased serum- and glucocorticoid-inducible protein kinase (Sgk1) phosphorylation, however, WPC attenuated the hypertonicity-induced Sgk1 activation. Tonicity-responsive enhancer binding protein (TonEBP) mRNA was also recovered by WPC under hypertonic stress. Pretreatment with WPC presented the similar effect of PKA inhibitor which decreased hypertonic stress-induced AQP2 expression. Hypertonicity increased cAMP levels and the changes were blocked by WPC. On the other hand, hypertonic stress-induced Bax or caspase-3 expression was decreased by WPC, resulting in anti-apoptotic effect.
These results provided evidence that the beneficial effect of WPC in water balance against in vitro hypertonic stress of renal collecting ducts. In addition, WPC exhibits anti-apoptotic property response to hypertonic stress. Thus, these data suggests that WPC has benefit for the therapeutic approach to the inhibition of renal disorder.

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    • "W. extensa contains two principal groups of chemicals: the triterpene fraction and the polysaccharide fraction [35]. Modern phytochemical and pharmacological researches demonstrated that main active constituents such as triterpenoids and polysaccharides isolated from W. extensa had antioxidant, antitumor, anticancer, anti-inflammatory, nematicidal activities, antihypertonic stress effect, and antihyperglycemic property [36] [37] [38] [39] [40] [41] [42]. This species fungus has not only long been utilized to treat a wide variety of diseases, but also recently has attracted the attention of the pharmaceutical industry. "
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    ABSTRACT: The fungus species Wolfiporia extensa has a long history of medicinal usage and has also been commercially used to formulate nutraceuticals and functional foods in certain Asian countries. In the present study, a practical and promising method has been developed to discriminate the dried sclerotium of W. extensa collected from different geographical sites based on UV spectroscopy together with chemometrics methods. Characteristic fingerprint of low polar constituents of sample extracts that originated from chloroform has been obtained in the interval 250–400 nm. Chemometric pattern recognition methods such as partial least squares discriminant analysis (PLS-DA) and hierarchical cluster analysis (HCA) were applied to enhance the authenticity of discrimination of the specimens. The results showed that W. extensa samples were well classified according to their geographical origins. The proposed method can fully utilize diversified fingerprint characteristics of sclerotium of W. extensa and requires low-cost equipment and short-time analysis in comparison with other techniques. Meanwhile, this simple and efficient method may serve as a basis for the authentication of other medicinal fungi.
    Journal of Analytical Methods in Chemistry 12/2014; 2014. DOI:10.1155/2014/519424 · 0.79 Impact Factor
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    • "In the previous study, Poria cocos Wolf (Chinese Pinyin: Fu Ling, WPC) markedly inhibited AQP2 expression in response to hypertonic stress in vitro [18]; however, the possible benefits and mechanism of this have not been fully elucidated in nephrotic syndrome animal models. In this study, we used the same WPC that was used in the previous study. "
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    ABSTRACT: Nephrotic syndrome is associated with altered renal handling of water and sodium and changes in the levels of aquaporins (AQPs) and epithelial Na channels (ENaCs). The dried sclerotia of Poria cocos Wolf (WPC) have been used for treating chronic edema and nephrosis. We evaluated the effects of WPC on puromycin aminonucleoside- (PAN-) induced renal functional derangement and altered renal AQP2 and ENaC expression. In the nephrotic syndrome rat model, animals were injected with 75 mg/kg PAN and then treated with Losartan (30 mg·kg(-1) ·day(-1)) or WPC (200 mg·kg(-1) ·day(-1)) for 7 days. In the WPC group, proteinuria and ascites improved significantly. Plasma levels of triglyceride, total cholesterol, and low-density lipoprotein- (LDL-) cholesterol reduced significantly in the WPC group. In addition, the WPC group exhibited attenuation of the PAN-induced increase in AQP2 and ENaC α/β subunit protein and mRNA levels. WPC suppressed significantly PAN-induced organic osmolyte regulators, reducing serum- and glucocorticoid-inducible protein kinase (Sgk1) and sodium-myo-inositol cotransporter (SMIT) mRNA expression. Our results show that WPC improves nephrotic syndrome, including proteinuria and ascites, through inhibition of AQP2 and ENaC expression. Therefore, WPC influences body-fluid regulation via inhibition of water and sodium channels, thereby, improving renal disorders such as edema or nephrosis.
    Evidence-based Complementary and Alternative Medicine 08/2014; 2014:570420. DOI:10.1155/2014/570420 · 1.88 Impact Factor
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    • "In particular, this fungus is widely used in traditional medicine to treat chronic gastritis, acute gastroenteric catarrh, gastric atony, oedema, nephrosis, dizziness, nausea, and emesis [16,17]. Many previous studies have indicated that its extracts and components have a variety of biological activities such as anti-fungal and anti-bacterial [18], antioxidant [19-21], neuroprotective [22], anti-hypertonic [23], anti-inflammatory [17,24-26], anti-angiogenic [27,28], and anti-cancer effects [29,30]. However, the claimed benefits and their action mechanisms are not fully understood. "
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    ABSTRACT: 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. 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)-1beta and tumor necrosis factor (TNF)-alpha were evaluated. We also examined the EEPC's effect on the nuclear factor-kappaB (NF-kappaB) signaling pathway. 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-1beta and TNF-alpha. Additionally, LPS-induced expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, IL-1beta, and TNF-alpha was decreased by pre-treatment with EEPC at the transcriptional level. Moreover, EEPC clearly inhibited LPS-induced nuclear translocation of NF-kappaB p65 subunits, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IkappaB) degradation. Moreover, EEPC clearly suppressed the LPS-induced DNA-binding activity of NF-kappaB, as well as the nuclear translocation of the NF-kappaB p65, which correlated with EEPC's inhibitory effects on inhibitor kappaB (IkappaB) degradation. Taken together, our data indicates that EEPC targets the inflammatory response of macrophages via inhibition of iNOS, COX-2, IL-1beta, and TNF-alpha through inactivation of the NF-kappaB signaling pathway, supporting the pharmacological basis of P. cocos as a traditional herbal medicine for treatment of inflammation and its associated disorders.
    BMC Complementary and Alternative Medicine 03/2014; 14(1):101. DOI:10.1186/1472-6882-14-101 · 2.02 Impact Factor
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