1) Mycelia component of Phellinus Linteus showed useful activity for the treatment of allergic disease and cancer. International Journal for Medicinal Mushrooms Issue 3 A Study of Pharmacological Components from Submerged Culture Mycelia of Phellinus linteus (Berk. et Curt.) Teng Tomoyuki Nakamura Applied Fungi Institute, IBI Corporation, 7841 Anayama-cyo, Nirasaki-shi, Yamanashi 407-0263; and Faculty of Engineering, Yamanashi University, 4-3-11 Takeda, Kofu-shi, Yamanashi 400-8511, Japan Yukihito Akiyama Applied Fungi Institute, IBI Corporation, 7841 Anayama-cyo, Nirasaki-shi, Yamanashi 407-0263, Japan ABSTRACT Phellinus linteus is apolypore of class Hymenomycetes and a heart-rot fungus occurring especially in groves of Morus bombycis Koidz. In Japan this fungus has been named Meshimakobu because it was found mainly in Meshima of the Danjo Islands in Nagasaki Prefecture. In Chinese medicine it has been called Souou and is used as a medicinal ingredient. About 30 years ago, certain pharmacological effects of this fungus were examined, and it was revealed that this fungus exhibited the highest antitumor activity among the Hymenomycetes mushrooms (Ikekawa et al., 1968). In this study, we found some biological activities of the mycelia extract and succeeded in isolation and structure-determination of the active principles in the extract (Nakamura et al., 2000, 2002). The results are as follows: The scavenging activity of superoxide anion radicals of the extracts was detected. As a result, caffeic acid was isolated as an antioxidant (Nakamura et al., 2002). The IC50 of this principle was 3.05 μg/mL (16.9 μM). This was the first report in which caffeic acid was isolated from mushroom mycelia. It was proposed that caffeic acid may partly contribute to the pharmacological activity of Ph. Linteus. The anti-allergic activity of the extracts was demonstrated by in vivo assay using NC/Nga/mice. Oral administration of mycelial extracts of Ph. Linteus exerted type-I allergy suppressive effects by inhibiting the production of serum IgE and inhibiting the formation of dermatitis-like skin lesions. Hot-water extracts of the mycelia was more active than the culture filtrates. The antitumor activity of the extracts was examined by using Sarcoma 180/mice, p.o. As a result, all the fractions of Ph. Linteus mycelia showed antitumor activity in the solid tumors implanted in mice. The highest antitumor activity (81.2%) was observed in the protein/glucan complex obtained by the precipitation of 24% NaOH extract at pH 6.0. The protein/glucan complex consisted of 39.3% polysaccharide and 49.4% protein. Its 13C and 1H NMR data showed that the main glucan part of the complex was primarily α-1,3-glucan chains (Nakamura et al., 2004). It was demonstrated that the mycelia component of Ph. Linteus showed useful activity for the treatment of allergic disease and cancer. These two diseases are recognized as very serious illnesses in Japan. The antioxidant activity (superoxide scavenging activity) of the mycelia component may contribute to keeping people’s health. http://www.dl.begellhouse.com/journals/708ae68d64b17c52,0d0f121956dd501b,7338d68f6da330c3.html __________________________________________________ 2) Phellinus Linteus and lung cancer Molecular Carcinogenesis Volume 46, Issue 2, pages 144–154, February 2007 Modulation of lung cancer growth arrest and apoptosis by Phellinus Linteus Jinjin Guo1, Tongbo Zhu1, LeaAnn Collins1, Zhi-Xiong J. Xiao2, Sung-Hoon Kim3, Chang-Yan Chen1,* 1 Department of Pathology, Boston University School of Medicine, Boston, Massachusetts 2 Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 3 Laboratory of Angiogenesis and Chemoprevention, Graduate School of East-West Medical Science, Kyunghee University, South Korea *Department of Pathology, K522, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118. Abstract The PhellinusLinteus (PL) mushroom has been shown to possess anti-tumor properties. Through influencing lymphocytes, PL indirectly augments the host's immune system against cancer cells. PL has also been demonstrated to reduce tumor proliferation. However, the mechanisms of PL against malignant growth have not yet been fully explored. In this study, we report that PL mediates the following two activities in mouse and human lung cancer cells: cell-cycle arrest at a low concentration of PL and apoptosis in response to a high dose of PL. After exposure to a low dose of PL, G1 growth arrest occurred in the lung cancer cells. The negative growth control mediated by PL is evidenced by the decrease of the activities of cyclin-dependent kinases CDK2, 4, and 6. In contrast, at high doses, PL-induced lung cancer cells to undergo apoptosis in a dose-dependent fashion. This was evidenced by DNA fragmentation, caspase activation, and loss of clonogenecity in the lung cancer cells, all of which were lacking in the lung cancer cells treated with low concentrations of PL as well as the normal mouse lung epithelial cells exposed to either low or high concentrations of PL. The addition of the caspase inhibitor Z-VADfmk completely suppressed PL-induced apoptosis. Furthermore, the low dose of PL was able to synergize with doxorubicin to induce apoptosis in the lung cancer cells. Thus, our findings suggest that PL regulates two responses in the lung cancer cells: cell-cycle arrest and apoptosis http://onlinelibrary.wiley.com/doi/10.1002/mc.20275/abstract?deniedAccessCustomisedMessage=&userIsAuthenticated=false __________________________________________________ 3) Phellinus Linteus and liver cancer Journal of Gastroenterology and Hepatology Volume 20, Issue 3, pages 488–492, March 2005 Spontaneous regression of a large hepatocellular carcinoma with skull metastasis SOON WOO NAM, JOON-YEOL HAN*, JIN IL KIM, SOO HEON PARK, SE HYUN CHO, NAM IK HAN, JIN MO YANG, JAE KWANG KIM, SANG WOOK CHOI, YOUNG SUK LEE, KYU WON CHUNG, HEE SIK SUN Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea *Dr Jool-Yeol Han, Catholic University of Korea, Seoul, Korea. Email: firstname.lastname@example.org Abstract Spontaneous regression of hepatocellular carcinoma (HCC) is a rare phenomenon. This case of a 65-year-old Korean man with HCC and metastatic frontal bone mass that regressed after radiotherapy for frontal bone mass without any other therapeutic modalities is described. The clinical diagnosis of HCC was made because of the presence of a liver mass on abdominal computed tomography (CT) scan, high serum α-fetoprotein value and tissue diagnosis on frontal bone biopsy. The patient refused any other recommended treatments, but accepted the radiation therapy due to a painful frontal bone mass, and ingested mushroom called Phellinus linteus for one and a half years. Ten months after radiation therapy, he experienced a reduction in size of the frontal bone mass and improvement of lesions in the liver, sternum and ribs. The patient is alive and in good condition without any symptoms or tumor aggravation in August 2002. It was concluded that a rare case of spontaneous regression of HCC had occurred. __________________________________________________ 4) Phellinus linteus and Breast Cancer British Journal of Cancer (2008) 98, 1348–1356. Published online 25 March 2008 Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling D Sliva, A Jedinak, J Kawasaki, K Harvey and V Slivova Abstract The antitumour activity of a medicinal mushroom Phellinus linteus (PL), through the stimulation of immune system or the induction of apoptosis, has been recently described. However, the molecular mechanisms responsible for the inhibition of invasive behaviour of cancer cells remain to be addressed. In the present study, we demonstrate that PL inhibits proliferation (anchorage-dependent growth) as well as colony formation (anchorage-independent growth) of highly invasive human breast cancer cells. The growth inhibition of MDA-MB-231 cells is mediated by the cell cycle arrest at S phase through the upregulation of p27Kip1 expression. Phellinus linteus also suppressed invasive behaviour of MDA-MB-231 cells by the inhibition of cell adhesion, cell migration and cell invasion through the suppression of secretion of urokinase -plasminogen activator from breast cancer cells. In addition, PL markedly inhibited the early event in angiogenesis, capillary morphogenesis of the human aortic endothelial cells, through the downregulation of secretion of vascular endothelial growth factor from MDA-MB-231 cells. These effects are mediated by the inhibition of serine-threonine kinase AKT signalling, because PL suppressed phosphorylation of AKT at Thr308 and Ser473 in breast cancer cells. Taken together, our study suggests potential therapeutic effect of PL against invasive breast cancer. http://www.nature.com/bjc/journal/v98/n8/abs/6604319a.html _____________________________________________________________________________ 5) Phellinus linteus and prostate cancer1 British Journal of Cancer (2006) 95, 282–288. Phellinus linteus sensitises apoptosis induced by doxorubicin in prostate cancer L Collins, T Zhu, J Guo, Z J Xiao and C-Y Chen Abstract It has been demonstrated that the Phellinus linteus (PL) mushroom, which mainly consists of polysaccharides, possesses antitumour activity. The mechanisms of PL against malignant growth remain unknown. The anticancer drug doxorubicin (Dox) has been shown to induce apoptosis via initiating a caspase cascade. In this investigation, we tested the effect of PL on Dox-induced apoptosis in prostate cancer LNCaP cells. We showed that PL or Dox, at relatively low doses, does not induce apoptosis in the cells. However, combination treatment with low doses of PL and Dox results in a synergistic effect on the induction of apoptosis. In this apoptotic process, caspases 8, 3 and BID are cleaved, and the addition of caspase inhibitor z-VADfmk completely blocks apoptosis. In addition, JNK is activated in response to PL or the combination treatment in LNCaP cells. The suppression of JNK partially inhibits the induction of apoptosis elicited by the co-treatment. These findings indicate that PL has a synergistic effect with Dox to activate caspases in prostate cancer LNCaP cells. Our study also suggests that PL has therapeutic potential to augment the magnitude of apoptosis induced by antiprostate cancer drugs. http://www.nature.com/bjc/journal/v95/n3/full/6603277a.html ____________________________________________________________________________ 6) Phellinus linteus and prostate cancer2 PLoS ONE 5(3): e9885. doi:10.1371/journal.pone.0009885 Phellinus Linteus Extract Sensitizes Advanced Prostate Cancer Cells to Apoptosis in Athymic Nude Mice Takanori Tsuji, Wei Du, Takashi Nishioka, Lihua Chen, Daisuke Yamamoto, Chang Yan Chen* Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, United States of America Abstract Phellinus linteus (PL) mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009885 7) Phellinus linteus and prostate cancer3 Urologia Internationalis 2004, Vol. 73, No. 2 Dramatic Remission of Hormone Refractory Prostate Cancer Achieved with Extract of the Mushroom, Phellinus linteus Shibata Y, Kurita S, Okugi H, Yamanaka H Department of Urology, Gunma University School of Medicine, Maebashi, Gunma, Japan. email@example.com Abstract: At present, there is no distinctly effective treatment for hormone refractory prostate cancer. We describe a hormone refractory prostate cancer patient with rapidly progressive bone metastasis who showed dramatic response to intake of an extract from the mushroom, Phellinus linteus. http://www.ncbi.nlm.nih.gov/pubmed/15331908 ____________________________________________________________________________ 8) Anti-tumor Activity Bioscience, Biotechnology, and Biochemistr Vol. 68 (2004) No. 4 P 868-872 Fractionation and Anti-tumor Activity of the Mycelia of Liquid-cultured Phellinus linteus *Tomoyuki NAKAMURA1) 2), *Seiichi MATSUGO2), *Yasuyuki UZUKA2), *Sumitaka MATSUO3), *Hirokazu KAWAGISHI4) 1) Applied Fungi Institute, IBI Corporation 2) Division of Applied Biological Sciences, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi 3) Allied Health Sciences, Department of Pharmacology, Kitasato University 4) Faculty of Agriculture, Shizuoka University Abstract All the fractions of Phellinus linteus mycelia showed anti-tumor activity toward solid tumors planted in mice. The highest anti-tumor activity of 81.2% was observed in the protein–glucan complex obtained by precipitating the 24% NaOH extract at pH 6.0. This protein–glucan complex consisted of 39.3% polysaccharide and 49.4% protein. Its 13C- and 1H-NMR data showed that the main glucan part of the complex was simple α-1,3-glucan chains. https://www.jstage.jst.go.jp/article/bbb/68/4/68_4_868/_article __________________________________________________________________________ 9) Phellinus linteus can inhibit tumor growth wih adriamycin Immunopharmacology Volume 41, Issue 2, February 1999, Pages 157–164 The inhibitory effect of polysaccharides isolated from Phellinuslinteus on tumor growth and metastasis Sang Bae Han, Chang Woo Lee,Young Jin Jeon, Nam Doo Hong, Ick Dong Yoo, Kyu-Hwan Yang, Hwan Mook Kim Abstract It was previously reported that polysaccharides (PL) isolated from Phellinuslinteus strongly stimulated cell-mediated and humoral immunity. This study was undertaken to investigate the immunochemotherapeutic activity of PL against tumor growth and metastasis. PL alone significantly prolonged the survival rate of B16F10-implanted mice, inhibited tumor growth in NCI-H23-implanted nude mice, and reduced the frequency of pulmonary metastasis of B16F10 melanoma. Adriamycin significantly inhibited tumor growth, but only slightly inhibited metastasis. The combination therapy with PL and adriamycin was more effective in inhibiting tumor growth, but not metastasis. PL did not induce direct toxicity in cancer cells, which is characteristic of immunotherapeutics. In conclusion, PL might be of use in immunochemotherapy of cancer because of its effective activities on tumor growth and metastasis through the immunopotentiation of the patients without toxicity. https://www.jstage.jst.go.jp/article/bpb/26/6/26_6_823/_article ___________________________________________________________________________ 10) Phellinus linteus inhibits melanoma cell metastasis International ImmunopharmacologyVolume 6, Issue 4, April 2006, Pages 697–702 Acidic polysaccharide from Phellinuslinteus inhibits melanoma cell metastasis by blocking cell adhesion and invasion Sang-Bae Han, Chang Woo Lee, Jong Soon Kang, Yeo Dae Yoon, Ki Hoon Lee, Kiho Lee, Song-Kyu Park, Hwan Mook Kim, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oundong, Yusong, Taejon 305-333, South Korea Abstract The acidic polysaccharide (PL) from Phellinuslinteus is an immunostimulator that has therapeutic activity against cancers. Here, we show that PL markedly inhibits melanoma cell metastasis in mice, and report that PL directly inhibits cancer cell adhesion to and invasion through the extracellular matrix, but that it has no direct effect on cancer cell growth. In addition, we found that PL increased macrophage NO production. These results suggest that PL has two antimetastatic functions, i.e., it acts as an immunopotentiator and as a direct inhibitor of cancer cell adhesion. http://www.sciencedirect.com/science/article/pii/S1567576905002894 ___________________________________________________________________________ 11) Phellinus linteus protects pancreatic β-cells Biomedical and Life Sciences Archives of Pharmacal ResearchVolume 33, Number 6 (2010), 853-861, Hispidin produced from Phellinus linteus protects pancreatic β-cells from damage by hydrogen peroxide Jae Soon Jang, Jong Seok Lee, Jung Hyun Lee, Duck Soo Kwon, Keun Eok Lee, Shin Young Lee and Eock Kee Hong Abstract Phellinus linteus, which is a traditional medicinal mushroom used in Asian countries for the treatment of various diseases, has attracted a lot of attention due to its antioxidant, anti-inflammatory, anti-mutagenicity, and cell-mediated immunity properties in addition to its ability to inhibit tumor growth and metastasis. However, the antidiabetic efficacy of P. linteus has not yet been examined. In this study, hispidin from P. linteus exhibited quenching effects against DPPH radicals, superoxide radicals, and hydrogen peroxide in a dose-dependent manner. Intracellular reactive oxygen species scavenging activity of hispidin was approximately 55% at a concentration of 30 μM. In addition, hispidin was shown to inhibit hydrogen peroxide-induced apoptosis and increased insulin secretion in hydrogen peroxide-treated cells. These combined results indicate that hispidin may act as an antidiabetic and that this property occurs through preventing β-cells from the toxic action of reactive oxygen species in diabetes. http://www.springerlink.com/content/w218712557866703/ _______________________________________________________________________ 12) Phellinus linteus and Antioxidant polyphenols Journal of Applied MicrobiologyVolume 104, Issue 6, pages 1824–1832, June 2008 Antioxidant polyphenols from the mycelial culture of the medicinal fungi Inonotus xeranticus and Phellinus linteus J.-Y. Jung, I.-K. Lee, S.-J. Seok, H.-J. Lee, Y.-H. Kim, B.-S. Yun Abstract Aims: The medicinal fungi Inonotus xeranticus and Phellinus linteus in the family Hymenochaetaceae have been used as traditional medicines for the treatment of various diseases. However, the compound responsible for the antioxidant activity is still unknown. Therefore, this study was conducted to characterize the antioxidant substances present in cultured broths made from these fungi. Methods and Results: Antioxidant fractions of the cultured broths obtained from I. xeranticus and P. linteus were analysed using reversed-phase HPLC, which revealed several peaks that exhibited a potent free radical scavenging activity. To identify these antioxidant peaks, an I. xeranticus strain was mass-cultured, and the cultured broth was separated using antioxidant activity-guided fractionation. Four major active substances were purified and identified as hispidin and its dimers, 3,14′-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan based on spectroscopic analyses. All compounds exhibited a significant scavenging activity against these radical species in a concentration-dependent manner. Conclusions: Antioxidant substances found in the cultured broths of the medicinal fungi I. xeranticus and P. linteus were identified as hispidin and its dimers, 3,14′-bihispidinyl, hypholomine B, and 1,1-distyrylpyrylethan. Significance and Impact of the Study: Polyphenol antioxidants were isolated from the cultured broth of the medicinal fungi I. xeranticus and P. linteus and identified based on extensive spectroscopic analyses. These compounds exhibited a strong antioxidant activity. http://www.ncbi.nlm.nih.gov/pubmed/18266700 _____________________________________________________________________________ 13) Phellinus linteus and its anti-inflammatory and anti-allergic properties Evidence-Based Complementary and Alternative Medicine Volume 2(2005) Issue 3, Pages 369-374 Inhibition of IgE-dependent Mouse Triphasic Cutaneous Reaction by a Boiling Water Fraction Separated from Mycelium of Phellinus linteus Naoki Inagaki1, Tomonori Shibata1, Tomokazu Itoh1, Tomohiro Suzuki2, Hiroyuki Tanaka1, Tomoyuki Nakamura3, Yukihito Akiyama3, Hirokazu Kawagishi2 and Hiroichi Nagai1 1 Department of Pharmacology, Gifu Pharmaceutical University, Gifu, 2 Department of Applied Biological Chemistry, Faculty of Agriculture, Shizuoka University, Shizuoka Japan 3 Applied Fungi Institute, IBI Corporation, Yamanashi, Japan Abstract Phellinus linteus, a mushroom, contains constituents that exhibit potent antitumor effects through activating immune cells. Recently, anti-inflammatory and anti-allergic properties of P. linteus extracts have also been implicated. In the present study, therefore, we separated the constituents of mycelium of P. linteus into five fractions—chloroform-soluble (CF), ethyl acetate-soluble (EA), methanolsoluble(AE), water-soluble (WA) and boiling water-soluble (BW) fractions—and examined their suppressive effects on the IgE-dependent mouse triphasic cutaneous reaction. The triphasic reaction was induced in the ear of BALB/c mice passively sensitized with anti-dinitrophenol IgE by painting with 2,4-dinitrofluorobenzene 24 h later. Ear swelling appeared triphasically with peak responses at 1 h, 24 h and 8 days after the challenge. ME, WA and BW given orally at a dose of 100 mg kg_1 significantly inhibited the first and second phase ear swelling, andBW also inhibited the third phase response. CF only inhibited the second phase. The inhibition by BW was the most potent and almost dose-dependent at doses of 30–300 mg kg_1. BW also inhibited vascular permeability increase caused by passive cutaneous anaphylaxis and histamine, and ear swelling caused by tumor necrosis factor-a. In contrast, BW apparently potentiated the production of interleukin-4 and interferon-g from anti-CD3-stimulated mouse splenocytes. These results indicate that BW derived from mycelium of P. linteus contains some constituents with anti-allergic as well as immunopotentiating properties. http://www.hindawi.com/journals/ecam/2005/973270/abs/ __________________________________________________ 14) Phellinuslinteus and inflammation Journal of EthnopharmacologyVolume 93, Issue 1, July 2004, Pages 141–146 Anti-inflammatory and related pharmacological activities of the n-BuOH subfraction of mushroom Phellinuslinteus Sun-Hyoung Kima, Yun-Seon Songb, Seung-Kook Kimc, Byung-Chul Kimc, Chang-Jin Limc, Eun-Hee Parka, a College of Pharmacy, Sookmyung Women’s University, Cheongpa-dong, Yongsan, Seoul 140-742, South Korea b Bioanalysis and Biotransformation Research Center, Korea Institute of Science and Technology, P.O. Box 131, Seoul 130-650, South Korea c Division of Life Sciences, Kangwon National University, Chuncheon 200-701, South Korea Abstract This study aimed to elucidate the anti-inflammatory and related activities of mushroom Phellinuslinteus. The results show that the EtOH extract of Phellinuslinteus (PLE) dose-dependently inhibited the mouse ear edema induced by croton oil. Among PLE subfractions, the n-BuOH subfraction showed highest anti-inflammatory activity in croton oil-induced ear edema test. The n-BuOH subfraction also showed highest inhibitory activity on the chick embryo chorioallantoic membrane (CAM) angiogenesis in a dose-dependent manner. PLE could significantly reduce the number of writhing induced by acetic acid in mice, indicating that PLE possesses potent antinociceptive effect mediated by its anti-inflammatory activity. Mycelial extract of six different Phellinus strains were found to contain anti-angiogenic activity in the CAM assay. These results suggest that Phellinuslinteus has anti-inflammatory and antinociceptive activities, in addition to its anti-angiogenic activity. __________________________________________________ 15) Phellinus linteus and rheumatoid arthritis Biological and Pharmaceutical Bulletin Vol. 26 (2003) No. 6 P 823-831 Oral Administration of Proteoglycan Isolated from Phellinus linteus in the Prevention and Treatment of Collagen-Induced Arthritis in Mice Gi-Young Kim, Seung-Hoon Kim, Sue-Yun Hwang, Ho-Youn Kim, Yeong-Min Park, Soon-Kew Park, Min-Ki Lee, Sang-Hwa Lee, Tae-Ho, Lee, Jae-Dong Lee Abstract To examine whether oral administration of proteoglycan derived from Phellinus linteus, which is known as the medicinal mushroom, can prevent or treat collagen-induced arthritis (CIA) in mice as experimental model of autoimmune disease. CIA was induced by intradermal injection of type II collagen (CII) emulsified with complete freund's adjuvant (CFA) into the base of the tail (on day 7) followed by a booster injection on day 21 into the footfad. To examine the ability of proteoglycan to effect the inhibition of CIA, doses of proteoglycan were orally administered on day 0 (pre-administration) or day 28 (post-administration) at two groups. The inhibition of CIA by oral administration of proteoglycan was associated with decrease in anti-CII IgG and IgG2a antibodies (Abs) as well as varying kinds of cytokines including IL-12, TNF-α, and IFN-γ. The results showed that administration of proteoglycan was followed by decrease of CIA of the mice in pre- and post-administration groups. Our findings suggest that immunomodulating proteoglycan isolated from P. linteus may be crucially involved in the prevention and treatment of autoimmune joint inflammation such as rheumatoid arthritis, although no definite role of anti-CII Abs in the human disease has been established. https://www.jstage.jst.go.jp/article/bpb/26/6/26_6_823/_article ____________________________________________________________________________ 16) Phellinus linteus is effective for atopic dermatitis BMC Complementary and Alternative Medicine 2012, 12:159 Immunomodulatory effect of water soluble extract separated from mycelium of Phellinus linteus on experimental atopic dermatitis JI-Sun Hwang (firstname.lastname@example.org) Ho-Keun Kwon (email@example.com) Jung-Eun Kim (firstname.lastname@example.org) Jeonghae Rho (email@example.com) Sin-Hyeog Im (firstname.lastname@example.org) Abstract Background Complementary and alternative medicine (CAM) is becoming a popular treatment for modulating diverse immune disorders. Phellinus linteus (P. linteus) as one of the CAMs has been used to modulate cancers, inflammation and allergic activities. However, little evidence has been shown about its underlying mechanism of action by which it exerts a beneficial role in dermatological disease in vivo. In this study, we examined the immunomodulatory effects of P. linteus on experimental atopic dermatitis (AD) and elucidated its action mechanism. Methods The immunomodulatory effect of total extract of P. linteus on IgE production by human myeloma U266B1 cells was measured by ELISA. To further identify the effective components, P. linteus was fractionated into methanol soluble, water soluble and boiling water soluble extracts. Each extract was treated to U266B1 cells and primary B cells to compare their inhibitory effects on IgE secretion. To test the in vivo efficacy, experimental atopic dermatitis (AD) was established by alternative treatment of DNCB and house dust mite extract into BALB/c mice. Water soluble extract of P. linteus (WA) or ceramide as a positive control were topically applied to ears of atopic mouse every day for 2 weeks and progression of the disease was estimated by the following criteria: (a) ear thickness, clinical score, (b) serum total IgE, IgG and mite specific IgE level by ELSIA, (c) histological examination of ear tissue by H&E staining and (d) cytokine profile of total ear cells and CD4+ T cells by real time PCR and ELSIA. Results Treatment of total extracts of P. linteus to U266B1 inhibited IgE secretion. Among the diverse extracts of P. linteus, water soluble extract of P. linteus (WA) significantly reduced the IgE production in primary B cells and B cell line U266B1. Moreover, treatment of WA reduced AD symptoms such as ear swelling, erythema, and dryness and decreased recruitment of lymphocyte into the inflamed site. Interestingly WA treatment significantly reduced IgE level without affecting IgG levels and also down-regulated the levels of pathogenic cytokines (IL-4, IL-13, IL-12 and IFN-gamma) and chemokines (CCL17 and CCL22) involved in AD development. Conclusions Our study indicates that protective effect of water soluble extract of P. linteus in atopic dermatitis is mediated by inhibiting IgE production and expression of AD associated pathogenic cytokines as well as chemokines, suggesting the beneficial effect of P. linteus to modulate allergic skin disease. ____________________________________________________________________________ 17) Phellinus linteus inhibits Cholesterol Gallstone Formation. Nippon Shokuhin Kagaku Kogaku Kaishi Vol. 53, No. 5, 268-274 (2006) Effects of Dietary Phellinus linteus on Cholesterol Gallstone Formation in Mice Toshiro Watanabe*, ** Miho Inoue*, Taduko Uno*, Tapan Kumar Mazumder*, Shiro Nagai* and Keisuke Tsuji** *YAEGAKI Technology Development Laboratories, YAEGAKI Bio-industry, Inc., Hayashida, Himeji, Hyogo 679-4298 ** School of Human Science and Environment, University of Hyogo, Shinzaike-honcho, Himeji, Hyogo 670-009 Abstract This study was carried out to clarify the effects of Phellinus linteus fruit body (PL-F) or mycelia (PL-M) powder on gallstone formation in mice fed a cholesterol-cholate diet. Male ICR mice were fed diets containing 0.5% cholesterol and 0.25% Na-cholate for 21, 28 or 35 days. Animals fed with a cholesterolcholate diet showed higher incidence of cholesterol gallstone formation than those fed with PL-F or PL-M powder diet, for 21 days test. Gallstone formation in mice was not further suppressed by extending the feeding period to 28 or 35 days. On the other hand, addition of PL-M to the diet caused significantly lower serum atherogenic index and liver total cholesterol (TC) levels than the PL-F or PL-M free diets. Fecal excretion of TC and bile acid (BA) were increased by PL-F or PL-M feeding. With each PL-F or PL-M diet, TC/BA ratio in the gall bladder was lower than that with the control diet. Hot water extract of the PL-M fractions were found to be the most effective in preventing the formation of gallstones in mice fed with cholesterol diets and this effect was almost equal to that of the whole PL-M powder.