Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells
Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China. Aim of study: In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogen...
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| Veröffentlicht in: | Journal of ethnopharmacology 2012-06, Vol.141 (2), p.622-628 |
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| creator | Tsang, Ting-Fung Ye, Yan Tai, William Chi-Shing Chou, Gui-Xin Leung, Alexander Kai-Man Yu, Zhi-Ling Hsiao, Wen-Luan Wendy |
| description | Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China. Aim of study: In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogenic effect of QW in B16 cells.
Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60min of QW treatment.
The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW. |
| doi_str_mv | 10.1016/j.jep.2011.08.043 |
| format | Article |
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Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60min of QW treatment.
The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW.</description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2011.08.043</identifier><identifier>PMID: 21903156</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Animals ; B16 cells ; Bleaching Agents - pharmacology ; Blotting, Western ; cAMP-dependent protein kinase ; Cell Line, Tumor ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases - metabolism ; cytotoxicity ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal - pharmacology ; Intramolecular Oxidoreductases - metabolism ; Medicine, Chinese Traditional ; melanin ; Melanins - biosynthesis ; Melanogenesis ; melanoma ; Melanoma, Experimental - enzymology ; Melanoma, Experimental - pathology ; Mice ; mitogen-activated protein kinase ; Monophenol Monooxygenase - antagonists & inhibitors ; Monophenol Monooxygenase - metabolism ; Oxidoreductases - metabolism ; p38 MAPK ; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases - metabolism ; Phosphorylation ; PKA ; Plants, Medicinal ; Protein Kinase Inhibitors - pharmacology ; protein synthesis ; Qian-wang-hong-bai-san ; Signal Transduction - drug effects ; Skin Pigmentation - drug effects ; Spectrophotometry ; Time Factors ; Traditional Chinese medicine ; Tyrosinase ; Western blotting</subject><ispartof>Journal of ethnopharmacology, 2012-06, Vol.141 (2), p.622-628</ispartof><rights>2011 Elsevier Ireland Ltd</rights><rights>Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c377t-f0ebf25b084e985b9afbd4d771191dd4388fd3cf74329c02fa5754f9e734da963</citedby><cites>FETCH-LOGICAL-c377t-f0ebf25b084e985b9afbd4d771191dd4388fd3cf74329c02fa5754f9e734da963</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jep.2011.08.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>315,781,785,3551,27928,27929,45999</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21903156$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsang, Ting-Fung</creatorcontrib><creatorcontrib>Ye, Yan</creatorcontrib><creatorcontrib>Tai, William Chi-Shing</creatorcontrib><creatorcontrib>Chou, Gui-Xin</creatorcontrib><creatorcontrib>Leung, Alexander Kai-Man</creatorcontrib><creatorcontrib>Yu, Zhi-Ling</creatorcontrib><creatorcontrib>Hsiao, Wen-Luan Wendy</creatorcontrib><title>Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells</title><title>Journal of ethnopharmacology</title><addtitle>J Ethnopharmacol</addtitle><description>Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China. Aim of study: In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogenic effect of QW in B16 cells.
Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60min of QW treatment.
The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW.</description><subject>Animals</subject><subject>B16 cells</subject><subject>Bleaching Agents - pharmacology</subject><subject>Blotting, Western</subject><subject>cAMP-dependent protein kinase</subject><subject>Cell Line, Tumor</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</subject><subject>Cyclic AMP-Dependent Protein Kinases - metabolism</subject><subject>cytotoxicity</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drugs, Chinese Herbal - pharmacology</subject><subject>Intramolecular Oxidoreductases - metabolism</subject><subject>Medicine, Chinese Traditional</subject><subject>melanin</subject><subject>Melanins - biosynthesis</subject><subject>Melanogenesis</subject><subject>melanoma</subject><subject>Melanoma, Experimental - enzymology</subject><subject>Melanoma, Experimental - pathology</subject><subject>Mice</subject><subject>mitogen-activated protein kinase</subject><subject>Monophenol Monooxygenase - antagonists & inhibitors</subject><subject>Monophenol Monooxygenase - metabolism</subject><subject>Oxidoreductases - metabolism</subject><subject>p38 MAPK</subject><subject>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</subject><subject>p38 Mitogen-Activated Protein Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>PKA</subject><subject>Plants, Medicinal</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>protein synthesis</subject><subject>Qian-wang-hong-bai-san</subject><subject>Signal Transduction - drug effects</subject><subject>Skin Pigmentation - drug effects</subject><subject>Spectrophotometry</subject><subject>Time Factors</subject><subject>Traditional Chinese medicine</subject><subject>Tyrosinase</subject><subject>Western blotting</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuEzEQhlcIREPhAbiAjxy6wV57411xKhEtFZUAQc_WrD3OTrTxpmunUZ6HF8UhhSOXmcv3_xrNVxSvBZ8LLhbv1_M1bucVF2LOmzlX8kkxE42uSl1r-bSYcambstFKnBUvYlxzzrVQ_HlxVomWS1EvZsWvm9BTR4nGwEbPUo9sKxsGwbFvXy5ZpFWAgcKKbSH1ezhERpFBjKMlSOjYnlL_JwUhUbnBAcK4wkCWgU30QOlwrP1OEMo9hFXZj3l0QGWEcMGALXsKGJH1OHUwMD9Om90AF4wC-ygWzOIwxJfFMw9DxFeP-7y4u_r0c_m5vP16fbO8vC2t1DqVnmPnq7rjjcK2qbsWfOeU01qIVjinZNN4J63XSlat5ZWHWtfKt6ilctAu5Hnx7tS7ncb7HcZkNhSPF0DAcRdN_nldKaVbkVFxQu00xjihN9uJNjAdMnTkFmZtshtzdGN4Y7KbnHnzWL_rNuj-Jf7KyMDbE-BhNLCaKJq7H7lB8VyYVR6JDycC8xseCCcTLWGw6GhCm4wb6T8H_AbeLqkU</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>Tsang, Ting-Fung</creator><creator>Ye, Yan</creator><creator>Tai, William Chi-Shing</creator><creator>Chou, Gui-Xin</creator><creator>Leung, Alexander Kai-Man</creator><creator>Yu, Zhi-Ling</creator><creator>Hsiao, Wen-Luan Wendy</creator><general>Elsevier Ireland Ltd</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20120601</creationdate><title>Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells</title><author>Tsang, Ting-Fung ; Ye, Yan ; Tai, William Chi-Shing ; Chou, Gui-Xin ; Leung, Alexander Kai-Man ; Yu, Zhi-Ling ; Hsiao, Wen-Luan Wendy</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c377t-f0ebf25b084e985b9afbd4d771191dd4388fd3cf74329c02fa5754f9e734da963</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>B16 cells</topic><topic>Bleaching Agents - pharmacology</topic><topic>Blotting, Western</topic><topic>cAMP-dependent protein kinase</topic><topic>Cell Line, Tumor</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors</topic><topic>Cyclic AMP-Dependent Protein Kinases - metabolism</topic><topic>cytotoxicity</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drugs, Chinese Herbal - pharmacology</topic><topic>Intramolecular Oxidoreductases - metabolism</topic><topic>Medicine, Chinese Traditional</topic><topic>melanin</topic><topic>Melanins - biosynthesis</topic><topic>Melanogenesis</topic><topic>melanoma</topic><topic>Melanoma, Experimental - enzymology</topic><topic>Melanoma, Experimental - pathology</topic><topic>Mice</topic><topic>mitogen-activated protein kinase</topic><topic>Monophenol Monooxygenase - antagonists & inhibitors</topic><topic>Monophenol Monooxygenase - metabolism</topic><topic>Oxidoreductases - metabolism</topic><topic>p38 MAPK</topic><topic>p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors</topic><topic>p38 Mitogen-Activated Protein Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>PKA</topic><topic>Plants, Medicinal</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>protein synthesis</topic><topic>Qian-wang-hong-bai-san</topic><topic>Signal Transduction - drug effects</topic><topic>Skin Pigmentation - drug effects</topic><topic>Spectrophotometry</topic><topic>Time Factors</topic><topic>Traditional Chinese medicine</topic><topic>Tyrosinase</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tsang, Ting-Fung</creatorcontrib><creatorcontrib>Ye, Yan</creatorcontrib><creatorcontrib>Tai, William Chi-Shing</creatorcontrib><creatorcontrib>Chou, Gui-Xin</creatorcontrib><creatorcontrib>Leung, Alexander Kai-Man</creatorcontrib><creatorcontrib>Yu, Zhi-Ling</creatorcontrib><creatorcontrib>Hsiao, Wen-Luan Wendy</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of ethnopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tsang, Ting-Fung</au><au>Ye, Yan</au><au>Tai, William Chi-Shing</au><au>Chou, Gui-Xin</au><au>Leung, Alexander Kai-Man</au><au>Yu, Zhi-Ling</au><au>Hsiao, Wen-Luan Wendy</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells</atitle><jtitle>Journal of ethnopharmacology</jtitle><addtitle>J Ethnopharmacol</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>141</volume><issue>2</issue><spage>622</spage><epage>628</epage><pages>622-628</pages><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract>Qian-wang-hong-bai-san (QW), a Chinese herbal formula, is traditionally used as a skin whitening agent in China. Aim of study: In our previous screening assays, QW was identified as an effective tyrosinase inhibitor. In this study, we aim to investigate the underlying mechanism of the anti-melanogenic effect of QW in B16 cells.
Cytotoxicity of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity was determined based on the melanin content measured at 475nm with a microplate spectrophotometer. Protein expression was analyzed by Western blotting and quantified by Quantity One.
QW dose-dependently inhibited tyrosinase activity and decreased melanin content at 48h without significant cytotoxicity in B16 cells. Western blot analysis showed that QW treatment down-regulated the expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2 in a dose-dependent manner. At the same time, QW treatment for 48h inhibited IBMX-induced elevation of cellular melanin content and tyrosinase activity. However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and phospho-PKA was readily observed with 60min of QW treatment.
The anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These findings shed new light on the molecular mechanisms of the skin-whitening property of QW.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>21903156</pmid><doi>10.1016/j.jep.2011.08.043</doi><tpages>7</tpages></addata></record> |
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| ispartof | Journal of ethnopharmacology, 2012-06, Vol.141 (2), p.622-628 |
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| subjects | Animals B16 cells Bleaching Agents - pharmacology Blotting, Western cAMP-dependent protein kinase Cell Line, Tumor Cyclic AMP Response Element-Binding Protein - metabolism Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors Cyclic AMP-Dependent Protein Kinases - metabolism cytotoxicity Dose-Response Relationship, Drug Drugs, Chinese Herbal - pharmacology Intramolecular Oxidoreductases - metabolism Medicine, Chinese Traditional melanin Melanins - biosynthesis Melanogenesis melanoma Melanoma, Experimental - enzymology Melanoma, Experimental - pathology Mice mitogen-activated protein kinase Monophenol Monooxygenase - antagonists & inhibitors Monophenol Monooxygenase - metabolism Oxidoreductases - metabolism p38 MAPK p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors p38 Mitogen-Activated Protein Kinases - metabolism Phosphorylation PKA Plants, Medicinal Protein Kinase Inhibitors - pharmacology protein synthesis Qian-wang-hong-bai-san Signal Transduction - drug effects Skin Pigmentation - drug effects Spectrophotometry Time Factors Traditional Chinese medicine Tyrosinase Western blotting |
| title | Inhibition of the p38 and PKA signaling pathways is associated with the anti-melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16 cells |
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