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In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae)

Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vi...

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Published in:Journal of ethnopharmacology 2023-01, Vol.301, p.115828-115828, Article 115828
Main Authors: Alam, Fiaz, Hanif, Muhammad, Rahman, Asad ur, Ali, Sayyad, Jan, Saeed
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description Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P  0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p 
doi_str_mv 10.1016/j.jep.2022.115828
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Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 μg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 μg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine. [Display omitted] •Gaultherias are traditional medicines in Himalaya.•Gaultherias are rich in salicylates.•Extract and salicylate rich fraction relieved analgesia, inflammation and pyrexia in vivo.•Extract and salicylate rich fraction inhibit LOX and COX in vitro.•Gaultherin docked well in sito.]]></description><identifier>ISSN: 0378-8741</identifier><identifier>EISSN: 1872-7573</identifier><identifier>DOI: 10.1016/j.jep.2022.115828</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Analgesic ; Cyclooxygenase ; Gaultheria ; Inflammation ; Lipoxygenase ; Molecular docking</subject><ispartof>Journal of ethnopharmacology, 2023-01, Vol.301, p.115828-115828, Article 115828</ispartof><rights>2022 Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c330t-280b1faa20cd4f14ddd99b496d1ca8ab1ffd74c2956d3eeeb695dfdee73703ec3</citedby><cites>FETCH-LOGICAL-c330t-280b1faa20cd4f14ddd99b496d1ca8ab1ffd74c2956d3eeeb695dfdee73703ec3</cites><orcidid>0000-0003-4717-086X ; 0000-0003-2411-6510</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids></links><search><creatorcontrib>Alam, Fiaz</creatorcontrib><creatorcontrib>Hanif, Muhammad</creatorcontrib><creatorcontrib>Rahman, Asad ur</creatorcontrib><creatorcontrib>Ali, Sayyad</creatorcontrib><creatorcontrib>Jan, Saeed</creatorcontrib><title>In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae)</title><title>Journal of ethnopharmacology</title><description><![CDATA[Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 μg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 μg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine. [Display omitted] •Gaultherias are traditional medicines in Himalaya.•Gaultherias are rich in salicylates.•Extract and salicylate rich fraction relieved analgesia, inflammation and pyrexia in vivo.•Extract and salicylate rich fraction inhibit LOX and COX in vitro.•Gaultherin docked well in sito.]]></description><subject>Analgesic</subject><subject>Cyclooxygenase</subject><subject>Gaultheria</subject><subject>Inflammation</subject><subject>Lipoxygenase</subject><subject>Molecular docking</subject><issn>0378-8741</issn><issn>1872-7573</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNp9kc2KFDEUhYMo2I4-gLssR-hq81PVqcKVDOM4MCCIrsPt5MZOk6qUSbqh3spHNDXt2lUO99zvcMMh5D1nO874_uNpd8J5J5gQO867XvQvyIb3SjSqU_Il2TCp-qZXLX9N3uR8Yowp3rIN-fM40YsvKW6pX9UlUpjsqrMP3kSKFwhnKD5ONLrqQfiF2ZttlcU3fnIBxhFKTMv2mXwez0vC4g0FU3xNX1Y0Q81bAhSkyZsjdWl1a6xLcaQPcA7liMkDLasd5-MSAtDvcQlIb-_rDAwCfnhLXjkIGd_9e2_Izy_3P-6-Nk_fHh7vPj81RkpWGtGzA3cAghnbOt5aa4fh0A57yw30UD1nVWvE0O2tRMTDfuiss4hKKibRyBtye82dU_x9xlz06LPBetOE8Zy1UKITjEvW11V-XTUp5pzQ6Tn5EdKiOdNrO_qkazt6bUdf26nMpyuD9Q8Xj0ln43EyaH1CU7SN_j_0X56DnJI</recordid><startdate>20230130</startdate><enddate>20230130</enddate><creator>Alam, Fiaz</creator><creator>Hanif, Muhammad</creator><creator>Rahman, Asad ur</creator><creator>Ali, Sayyad</creator><creator>Jan, Saeed</creator><general>Elsevier B.V</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4717-086X</orcidid><orcidid>https://orcid.org/0000-0003-2411-6510</orcidid></search><sort><creationdate>20230130</creationdate><title>In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae)</title><author>Alam, Fiaz ; Hanif, Muhammad ; Rahman, Asad ur ; Ali, Sayyad ; Jan, Saeed</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-280b1faa20cd4f14ddd99b496d1ca8ab1ffd74c2956d3eeeb695dfdee73703ec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Analgesic</topic><topic>Cyclooxygenase</topic><topic>Gaultheria</topic><topic>Inflammation</topic><topic>Lipoxygenase</topic><topic>Molecular docking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alam, Fiaz</creatorcontrib><creatorcontrib>Hanif, Muhammad</creatorcontrib><creatorcontrib>Rahman, Asad ur</creatorcontrib><creatorcontrib>Ali, Sayyad</creatorcontrib><creatorcontrib>Jan, Saeed</creatorcontrib><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>Alam, Fiaz</au><au>Hanif, Muhammad</au><au>Rahman, Asad ur</au><au>Ali, Sayyad</au><au>Jan, Saeed</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae)</atitle><jtitle>Journal of ethnopharmacology</jtitle><date>2023-01-30</date><risdate>2023</risdate><volume>301</volume><spage>115828</spage><epage>115828</epage><pages>115828-115828</pages><artnum>115828</artnum><issn>0378-8741</issn><eissn>1872-7573</eissn><abstract><![CDATA[Medicinal properties of Gaultheria have been used in traditional medicine to treat pain and inflammation. Hence, the purpose of this study was to evaluate the analgesic, antipyretic, and anti-inflammatory properties of Gaultheria trichophylla Royle extract and salicylate-rich fraction in vivo, in vitro, and in silico. In vivo analgesic, antipyretic, and anti-inflammatory of extract and a salicylate-rich fraction (at doses of 100, 200, 300, and 150 mg/kg) were assessed using healthy albino mice employing acetic acid-induced writhing, tail immersion test, carrageenan-induced inflammation, and croton oil-induced edema. For in vitro testing of extracts COX and LOX enzyme inhibition assays were used. Molecular docking studies were conducted for in silico testing of the inhibitory activity of the dominant compound Gaultherin against COX and LOX. G-EXT 200 and 300 and G-SAL 150 mg/kg reduced pyrexia significantly (P < 0.05 and P < 0.01). G-EXT-200, 300, and G-SAL 150 reduce the writing to a significant level (p > 0.05, p < 0.01). G-EXT 200 and 300 and G-SAL 150 mg/kg doses the analgesic effect was significant (p > 0.05, p > 0.01) and was comparable to tramadol. G-EXT 100 200, 300 mg/kg showed 43.8%, 47.94% and 56% respectively. G-SAL 150 mg, rich in salicylates, showed maximum inhibition of 65.75% next to standard drug diclofenac with 76.7% inhibition. G-EXT 100 and 200 mg/kg dose showed significant (p < 0.05) reduction in ear edema. With 300 mg/kg dose the effect was more (61.89%, p < 0.01). The salicylate-rich fraction G-SAL and Celecoxib showed an almost similar effect (p < 0.01). Significance inhibition was shown in the COX-2 test (G-EXT 39.70 and G-SAL 77.20 IC50 μg/ml) and in the 5-LOX test (G-EXT 28.3 and G-SAL 39.70 IC50 μg/ml). The preliminary in silico results suggest that the investigated compound showed excellent inhibitory activity against COX and LOX enzymes as evident from the free binding energy. Molecular docking revealed that Gaultherin binds well in the COX and LOX enzyme catalytic region. The extract and salicylate-rich fraction obtained from G. trichophylla showed significant analgesic, anti-inflammatory, and antipyretic effects in vivo, in vitro, and in silico assays that support its use in traditional medicine. [Display omitted] •Gaultherias are traditional medicines in Himalaya.•Gaultherias are rich in salicylates.•Extract and salicylate rich fraction relieved analgesia, inflammation and pyrexia in vivo.•Extract and salicylate rich fraction inhibit LOX and COX in vitro.•Gaultherin docked well in sito.]]></abstract><pub>Elsevier B.V</pub><doi>10.1016/j.jep.2022.115828</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-4717-086X</orcidid><orcidid>https://orcid.org/0000-0003-2411-6510</orcidid></addata></record>
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source ScienceDirect Freedom Collection 2022-2024
subjects Analgesic
Cyclooxygenase
Gaultheria
Inflammation
Lipoxygenase
Molecular docking
title In vitro, in vivo and in silico evaluation of analgesic, anti-inflammatory, and anti-pyretic activity of salicylate rich fraction from Gaultheria trichophylla Royle (Ericaceae)
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