Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Quantification of Flavonoids in Alpinia officinarum Hance. via HPLC and Evaluation of its Cytotoxicity on Human Prostate Carcinoma (LNCaP) and Breast Carcinoma (MCF-7) Cells

Author(s): Sohrab Kazemi , Farideh Asadi, Ladan Barari, Payam Morakabati, Maryam Jahani, Seyede Narges Mousavi Kani, Farangiz Soorani, Fatemeh Kolangi and Zahra Memariani*

Volume 22, Issue 4, 2022

Published on: 06 July, 2021

Page: [721 - 730] Pages: 10

DOI: 10.2174/1871520621666210706142157

Price: $65

Abstract

Background: Various plant species have been shown to be effective in the prevention or adjuvant therapy of cancer. Alpinia officinarum and its main phytochemicals have also been the subject of several studies for their anticancer properties.

Objective: The objective of this study is to analyze the extracts of A. officinarum to quantify flavonoids and to evaluate the growth inhibitory effects of the extracts on MCF-7 and LNCaP cells.

Methods: A. officinarum aqueous and hydroalcoholic extracts were analyzed by using High-Performance Liquid Chromatography (HPLC) for the quantification of three flavonoid compounds. Then, MCF-7, LNCaP, and fibroblast cells were treated with several concentrations (25, 50, 100, 200, and 400 μg/mL) of extracts (24, 48 and 72h). Cell viability was assessed using an MTT assay. Flow cytometry was conducted to evaluate apoptosis.

Results: Galangin and kaempferol (3.85 and 1.57 mg/g dry extract) were quantified, respectively, in hydroalcoholic and aqueous extracts using a validated method. The hydroalcoholic extract significantly decreased the viability of MCF-7 (IC50: 43.45μg/mL for 48h) and LNCaP cells (IC50: 168 μg/mL for 48h). The aqueous extract reduced cancer cell viability by more than 50% only at 200 and 400 μg/mL (72 h). Treatment of primary fibroblasts with both extracts showed no significant decrease in cell viability (25-100 μg/mL; 24 and 48h). The hydroalcoholic extract induced a significant increase in apoptotic cells in both MCF-7 and LNCaP cells.

Conclusion: Obtained results demonstrated the cytotoxicity of A. officinarum through apoptosis induction in two cancer cell lines. Further investigations are required to determine the underlying apoptotic cell death mechanisms induced by A. officinarum in cancerous cells.

Keywords: Adjuvant therapy, anti-cancer, chemoprevention, galangin, kaempferol, lesser galangal, medicinal plants, persian medicine.

Graphical Abstract

[1]
Süntar, I. Importance of ethnopharmacological studies in drug discovery: role of medicinal plants. Phytochem. Rev., 2020, 19, 1199-1209.
[http://dx.doi.org/10.1007/s11101-019-09629-9]
[2]
Zhao, Q.; Luan, X.; Zheng, M.; Tian, X.H.; Zhao, J.; Zhang, W.D.; Ma, B.L. Synergistic mechanisms of constituents in herbal extracts during intestinal absorption: focus on natural occurring nanoparticles. Pharmaceutics, 2020, 12(2), 128.
[http://dx.doi.org/10.3390/pharmaceutics12020128] [PMID: 32028739]
[3]
Kolangi, F.; Memariani, Z.; Bozorgi, M.; Mozaffarpur, S.A.; Mirzapour, M. Herbs with potential nephrotoxic effects according to the traditional Persian medicine: review and assessment of scientific evidence. Curr. Drug Metab., 2018, 19(7), 628-637.
[http://dx.doi.org/10.2174/1389200219666180404095849] [PMID: 29623832]
[4]
Lichota, A.; Gwozdzinski, K. Anticancer activity of natural compounds from plant and marine environment. Int. J. Mol. Sci., 2018, 19(11), 3533.
[http://dx.doi.org/10.3390/ijms19113533] [PMID: 30423952]
[5]
Yin, S-Y. Therapeutic applications of herbal medicines for cancer patients. Evid.-based Complem. And Alternat. Med., 2013, 2013,302426.
[http://dx.doi.org/10.1155/2013/302426]
[6]
Lin, S-R.; Chang, C.H.; Hsu, C.F.; Tsai, M.J.; Cheng, H.; Leong, M.K.; Sung, P.J.; Chen, J.C.; Weng, C.F. Natural compounds as potential adjuvants to cancer therapy: preclinical evidence. Br. J. Pharmacol., 2020, 177(6), 1409-1423.
[http://dx.doi.org/10.1111/bph.14816] [PMID: 31368509]
[7]
Ullah, N. Green tea phytocompounds as anticancer: a review. Asian Pac. J. Trop. Dis., 2016, 6(4), 330-336.
[http://dx.doi.org/10.1016/S2222-1808(15)61040-4]
[8]
Syed, D.N.; Chamcheu, J.C.; Adhami, V.M.; Mukhtar, H. Pomegranate extracts and cancer prevention: molecular and cellular activities. Anticancer. Agents Med. Chem., 2013, 13(8), 1149-1161.
[http://dx.doi.org/10.2174/1871520611313080003] [PMID: 23094914]
[9]
Dinicola, S. Anticancer effects of grape seed extract on human cancers: a review. J. Carcinog. Mutagen. S, 2014, 8(005)
[10]
Honmore, V.S.; Kandhare, A.D.; Kadam, P.P.; Khedkar, V.M.; Sarkar, D.; Bodhankar, S.L.; Zanwar, A.A.; Rojatkar, S.R.; Natu, A.D. Isolates of Alpinia officinarum Hance as COX-2 inhibitors: evidence from anti-inflammatory, antioxidant and molecular docking studies. Int. Immunopharmacol., 2016, 33, 8-17.
[http://dx.doi.org/10.1016/j.intimp.2016.01.024] [PMID: 26849772]
[11]
Zhang, W.; Luo, J.; Kong, L-Y. The genus Alpinia: a review of its phytochemistry and pharmacology. World J. Tradit. Chin. Med., 2016, 2, 26-41.
[http://dx.doi.org/10.15806/j.issn.2311-8571.2015.0026]
[12]
Mahjour, M.; Khoushabi, A.; Noras, M. Herbal Remedies for Cancer based on Persian Medicine.In:Traditional and Integrative Medicine; Tehran University of Medical Sciences: Tehran, 2018, pp. 196-206.
[13]
Ghosh, S.; Rangan, L. Alpinia: the gold mine of future therapeutics. 3 Biotech,, 2013, 3(3), 173-185.
[http://dx.doi.org/10.1007/s13205-012-0089-x]
[14]
Houghton, P.; Fang, R.; Techatanawat, I.; Steventon, G.; Hylands, P.J.; Lee, C.C. The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods, 2007, 42(4), 377-387.
[http://dx.doi.org/10.1016/j.ymeth.2007.01.003] [PMID: 17560325]
[15]
Lee, C.C.; Houghton, P. Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer. J. Ethnopharmacol., 2005, 100(3), 237-243.
[http://dx.doi.org/10.1016/j.jep.2005.01.064] [PMID: 15888378]
[16]
Suja, S.; Chinnaswamy, P. Inhibition of in vitro cytotoxic effect evoked by Alpinia galanga and Alpinia officinarum on PC - 3 cell line. Anc. Sci. Life, 2008, 27(4), 33-40.
[PMID: 22557284]
[17]
Lee, H-S. Anti-proliferative effect of the rhizome extract of Alpinia officinarum on cultured human tumor cell lines. Korean J. Pharmacogn., 2008, 39(4), 347-351.
[18]
Ghil, S. Antiproliferative activity of Alpinia officinarum extract in the human breast cancer cell line MCF-7. Mol. Med. Rep., 2013, 7(4), 1288-1292.
[http://dx.doi.org/10.3892/mmr.2013.1305] [PMID: 23404367]
[19]
Alasmary, F.; Assirey, E.A.; El-Meligy, R.M.; Awaad, A.S.; El-Sawaf, L.A.; Allah, M.M.; Alqasoumi, S.I. Analysis of Alpina officinarum Hance, chemically and biologically. Saudi Pharm. J., 2019, 27(8), 1107-1112.
[http://dx.doi.org/10.1016/j.jsps.2019.09.007] [PMID: 31885470]
[20]
Motiur Rahman, A.F.M.; Lu, Y.; Lee, H.J.; Jo, H.; Yin, W.; Alam, M.S.; Cha, H.; Kadi, A.A.; Kwon, Y.; Jahng, Y. Linear diarylheptanoids as potential anticancer therapeutics: synthesis, biological evaluation, and structure-activity relationship studies. Arch. Pharm. Res., 2018, 41(12), 1131-1148.
[http://dx.doi.org/10.1007/s12272-018-1004-8] [PMID: 29397550]
[21]
An, N.; Zou, Z.M.; Tian, Z.; Luo, X.Z.; Yang, S.L.; Xu, L.Z. Diarylheptanoids from the rhizomes of Alpinia officinarum and their anticancer activity. Fitoterapia, 2008, 79(1), 27-31.
[http://dx.doi.org/10.1016/j.fitote.2007.07.001] [PMID: 17916414]
[22]
Wei, N.; Zhou, Z.; Wei, Q.; Wang, Y.; Jiang, J.; Zhang, J.; Wu, L.; Dai, S.; Li, Y. A novel diarylheptanoid-bearing sesquiterpene moiety from the rhizomes of Alpinia officinarum. Nat. Prod. Res., 2016, 30(20), 2344-2349.
[http://dx.doi.org/10.1080/14786419.2016.1185716] [PMID: 27222912]
[23]
Chien, S-T.; Shi, M.D.; Lee, Y.C.; Te, C.C.; Shih, Y.W. Galangin, a novel dietary flavonoid, attenuates metastatic feature via PKC/ERK signaling pathway in TPA-treated liver cancer HepG2 cells. Cancer Cell Int., 2015, 15(1), 15.
[http://dx.doi.org/10.1186/s12935-015-0168-2] [PMID: 25698902]
[24]
Liu, D.; You, P.; Luo, Y.; Yang, M.; Liu, Y. Galangin induces apoptosis in MCF-7 human breast cancer cells through mitochondrial pathway and phosphatidylinositol 3-Kinase/Akt inhibition. Pharmacology, 2018, 102(1-2), 58-66.
[http://dx.doi.org/10.1159/000489564] [PMID: 29879712]
[25]
Imran, M.; Salehi, B.; Sharifi-Rad, J.; Aslam Gondal, T.; Saeed, F.; Imran, A.; Shahbaz, M.; Tsouh Fokou, P.V.; Umair Arshad, M.; Khan, H.; Guerreiro, S.G.; Martins, N.; Estevinho, L.M. Kaempferol: a key emphasis to its anticancer potential. Molecules, 2019, 24(12), 2277.
[http://dx.doi.org/10.3390/molecules24122277] [PMID: 31248102]
[26]
Tambunan, A.P.; Bahtiar, A.; Tjandrawinata, R.R. Influence of extraction parameters on the yield, phytochemical, TLC-densitometric quantification of quercetin, and LC-MS profile, and how to standardize different batches for long term from Ageratum conyoides L. leaves. Pharmacogn. J., 2017, 9(6)
[http://dx.doi.org/10.5530/pj.2017.6.121]
[27]
Kolangi, F.; Shafi, H.; Memariani, Z.; Kamalinejad, M.; Bioos, S.; Jorsaraei, S.G.A.; Bijani, A.; Shirafkan, H.; Mozaffarpur, S.A. Effect of Alpinia officinarum Hance rhizome extract on spermatogram factors in men with idiopathic infertility: a prospective double-blinded randomised clinical trial. Andrologia, 2019, 51(1),e13172.
[http://dx.doi.org/10.1111/and.13172] [PMID: 30378695]
[28]
Denizot, F.; Lang, R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J. Immunol. Methods, 1986, 89(2), 271-277.
[http://dx.doi.org/10.1016/0022-1759(86)90368-6] [PMID: 3486233]
[29]
Ferrari, M.; Fornasiero, M.C.; Isetta, A.M. MTT colorimetric assay for testing macrophage cytotoxic activity in vitro. J. Immunol. Methods, 1990, 131(2), 165-172.
[http://dx.doi.org/10.1016/0022-1759(90)90187-Z] [PMID: 2391427]
[30]
Lee, J-J.; Lee, J.H.; Yim, N.H.; Han, J.H.; Ma, J.Y. Application of galangin, an active component of Alpinia officinarum Hance (Zingiberaceae), for use in drug-eluting stents. Sci. Rep., 2017, 7(1), 8207.
[http://dx.doi.org/10.1038/s41598-017-08410-2] [PMID: 28811550]
[31]
Jiao, H. Chromatographic fingerprint analysis and quantitative evaluate the rhizomes of Alpinia officinarum Hance (lesser galangal). J. Chin. Pharmaceut. Sci., 2019, 28(10), 728-738.
[32]
Zhang, J-Q. Simultaneous quantification of seventeen bioactive components in rhizome and aerial parts of Alpinia officinarum Hance using LC-MS/MS. Anal. Methods, 2015, 7(12), 4919-4926.
[http://dx.doi.org/10.1039/C5AY00647C]
[33]
Su, Y.; Chen, Y.; Liu, Y.; Yang, Y.; Deng, Y.; Gong, Z.; Chen, J.; Wu, T.; Lin, S.; Cui, L. Antiosteoporotic effects of Alpinia officinarum Hance through stimulation of osteoblasts associated with antioxidant effects. J. Orthop. Translat., 2015, 4, 75-91.
[http://dx.doi.org/10.1016/j.jot.2015.09.009] [PMID: 30035068]
[34]
Tao, L. HPLC analysis of bioactive flavonoids from the rhizome of Alpinia officinarum. S. Afr. J. Bot., 2006, 72(1), 163-166.
[http://dx.doi.org/10.1016/j.sajb.2005.06.007]
[35]
Nair, C. Antioxidant capacity and radioprotective properties of the flavonoids galangin and kaempferide isolated from Alpinia galanga L.(Zingiberaceae) against radiation induced cellular DNA damage. Int. J. Radiat. Res., 2013, 11(2), 81-89.
[36]
Patel, R.K.; Trivedi, P.D. Design-of-experiment approach for the development and validation of a high-performance thin-layer chromatography method for the simultaneous estimation of berberine chloride and galangin in Tinospora cordifolia M. and Alpinia galanga L. and their herbal formulations. JPC, 2018, 31(6), 451-459.
[http://dx.doi.org/10.1556/1006.2018.31.6.5]
[37]
Mpalantinos, M. Biologically active flavonoids and kava pyrones from the aqueous extract of Alpinia zerumbet. Phytother. Res., 1998, 12(6), 442-444.
[38]
Elzaawely, A.A.; Xuan, T.D.; Tawata, S. Essential oils, kava pyrones and phenolic compounds from leaves and rhizomes of Alpinia zerumbet (Pers.) BL Burtt. & RM Sm. and their antioxidant activity. Food Chem., 2007, 103(2), 486-494.
[http://dx.doi.org/10.1016/j.foodchem.2006.08.025]
[39]
Victório, C.P.; Lage, C.L.S.; Kuster, R.M. Flavonoid extraction from Alpinia zerumbet (Pers.) Burtt et Smith leaves using different techniques and solvents. Eclét. Quím., 2009, 34(1), 19-24.
[http://dx.doi.org/10.1590/S0100-46702009000100003]
[40]
Dai, D.N. Antimicrobial activity and chemical constituents of essential oil from the leaves of Alpinia globosa and Alpinia tonkinensis. J. Essent. Oil Bearing Plants, 2020, 23(2), 322-330.
[http://dx.doi.org/10.1080/0972060X.2020.1752816]
[41]
Song, W.; Yan, C.Y.; Zhou, Q.Q.; Zhen, L.L. Galangin potentiates human breast cancer to apoptosis induced by TRAIL through activating AMPK. Biomed. Pharmacother., 2017, 89, 845-856.
[http://dx.doi.org/10.1016/j.biopha.2017.01.062] [PMID: 28282786]
[42]
Haddad, A.Q.; Venkateswaran, V.; Viswanathan, L.; Teahan, S.J.; Fleshner, N.E.; Klotz, L.H. Novel antiproliferative flavonoids induce cell cycle arrest in human prostate cancer cell lines. Prostate Cancer Prostatic Dis., 2006, 9(1), 68-76.
[http://dx.doi.org/10.1038/sj.pcan.4500845] [PMID: 16314891]
[43]
Lee, D-H.; Szczepanski, M.; Lee, Y.J. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem. Pharmacol., 2008, 75(12), 2345-2355.
[http://dx.doi.org/10.1016/j.bcp.2008.03.013] [PMID: 18455702]
[44]
Kang, G-Y.; Lee, E.R.; Kim, J.H.; Jung, J.W.; Lim, J.; Kim, S.K.; Cho, S.G.; Kim, K.P. Downregulation of PLK-1 expression in kaempferol-induced apoptosis of MCF-7 cells. Eur. J. Pharmacol., 2009, 611(1-3), 17-21.
[http://dx.doi.org/10.1016/j.ejphar.2009.03.068] [PMID: 19356725]
[45]
Yi, X.; Zuo, J.; Tan, C.; Xian, S.; Luo, C.; Chen, S.; Yu, L.; Luo, Y. Kaempferol, a flavonoid compound from gynura medica induced apoptosis and growth inhibition in MCF-7 breast cancer cell. Afr. J. Tradit. Complement. Altern. Med., 2016, 13(4), 210-215.
[http://dx.doi.org/10.21010/ajtcam.v13i4.27] [PMID: 28852738]
[46]
Da, J. Kaempferol promotes apoptosis while inhibiting cell proliferation via androgen-dependent pathway and suppressing vasculogenic mimicry and invasion in prostate cancer. Analytical. Cellular. Pathology., 2019, 2019,1907698.
[http://dx.doi.org/10.1155/2019/1907698]
[47]
Caesar, L.K.; Cech, N.B. Synergy and antagonism in natural product extracts: when 1 + 1 does not equal 2. Nat. Prod. Rep., 2019, 36(6), 869-888.
[http://dx.doi.org/10.1039/C9NP00011A] [PMID: 31187844]

Rights & Permissions Print Cite
© 2025 Bentham Science Publishers | Privacy Policy
Request history8.2.27PHP Version376msRequest Duration28MBMemory UsageGET article/{article_id}/{param?}Route
  • warninglog[23:19:56] LOG.warning: Optional parameter $article_id declared before required parameter $request i...
  • warninglog[23:19:57] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • warninglog[23:19:57] LOG.warning: trim(): Passing null to parameter #1 ($string) of type string is deprecated ...
  • warninglog[23:19:57] LOG.warning: Function strftime() is deprecated in /home/alphaeurekaselec/public_html/stor...
  • Booting (123ms)time
  • Application (253ms)time
  • 1 x Application (67.23%)
    253ms
    1 x Booting (32.76%)
    123ms
    14 templates were rendered
    • articlearticle.blade.php#?blade
    • includes.article_top_bannerarticle_top_banner.blade.php#?blade
    • includes.article_referencearticle_reference.blade.php#?blade
    • export_citation_formexport_citation_form.blade.php#?blade
    • includes.article_bottom_bannerarticle_bottom_banner.blade.php#?blade
    • includes.inc_related_journalsinc_related_journals.blade.php#?blade
    • includes.inc_related_ebooksinc_related_ebooks.blade.php#?blade
    • includes.journal_rightmenujournal_rightmenu.blade.php#?blade
    • includes.journal_right_bannerjournal_right_banner.blade.php#?blade
    • layouts.appapp.blade.php#?blade
    • layouts._login_access_login_access.blade.php#?blade
    • layouts._header_header.blade.php#?blade
    • layouts._main_menu_main_menu.blade.php#?blade
    • layouts._footer_menu_footer_menu.blade.php#?blade
    uri
    GET article/{article_id}/{param?}
    middleware
    web, check_user_access
    controller
    App\Http\Controllers\ArticleController@GetArticleDetails
    namespace
    App\Http\Controllers
    where
    as
    article
    file
    app/Http/Controllers/ArticleController.php:1974-2510
    36 statements were executed, 4 of which were duplicates, 32 unique. Show only duplicated169ms
    • Connection Establishedalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 9. middleware::check_user_access:24
      • 10. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 11. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address (ip_address,visitor_agent,visitor_count, created_on,updated_on) VALUES ('51592399','',1,1739834396,1739834396) ON DUPLICATE KEY UPDATE visitor_count=visitor_count + 1, updated_on=1739834396
      1.4msalphaeurekaselec_live_10_06_2022UserAccessCheck.php#24
      Backtrace
      • 11. middleware::check_user_access:24
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • INSERT INTO visitor_ip_address_detail (ip_address,visitor_url,visitor_count, created_on,updated_on) VALUES ('51592399','/article/116495',1,1739834396,1739834396)
      190μsalphaeurekaselec_live_10_06_2022UserAccessCheck.php#27
      Backtrace
      • 11. middleware::check_user_access:27
      • 12. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 14. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 15. vendor/laravel/framework/src/Illuminate/Foundation/Http/Middleware/VerifyCsrfToken.php:88
    • (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_trail WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_journal_volume_token WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_trail WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_ebook_volume_token WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_trail WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_issue_token WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_trail WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_article_token WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_trail WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_chapter_token WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) union (select `user_id`, `to_ip`, `from_ip` from (select user_id, to_ip, from_ip FROM user_access_disease_corporate WHERE to_ip >= 51592399 ORDER BY to_ip ASC LIMIT 1) as `tjv` where `from_ip` <= 51592399) limit 1
      14.03msalphaeurekaselec_live_10_06_2022UserAccess.php#784
      Bindings
      • 0: 51592399
      • 1: 51592399
      • 2: 51592399
      • 3: 51592399
      • 4: 51592399
      • 5: 51592399
      • 6: 51592399
      • 7: 51592399
      • 8: 51592399
      • 9: 51592399
      • 10: 51592399
      • 11: 51592399
      • 12: 51592399
      • 13: 51592399
      • 14: 51592399
      • 15: 51592399
      Backtrace
      • 14. app/Models/UserAccess/UserAccess.php:784
      • 15. middleware::check_user_access:114
      • 16. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Middleware/SubstituteBindings.php:50
      • 18. vendor/laravel/framework/src/Illuminate/Pipeline/Pipeline.php:183
    • SELECT at.type_name, p.copyright, p.publisher_location,m.month,y.year, a.publish_on, a.nid article_nid,a.article_id, a.pmid, a.issue_id, a.title, a.abstract,a.podcast,a.altmetric_score,a.altmetric_url,a.kudos_url, a.page_count, a.first_page, a.elocator, a.last_page, i.publication_date, a.file_name, a.file_path, a.doi, a.is_epub,a.epub_type, a.volume_id, a.is_uploaded, a.editor_choice, a.is_epub, j.image_file_name, a.article_no, a.art_type AS article_type, a.supplementary_filename,a.html_filename,a.prc_filename,a.epub_filename, a.graph_abs_lg_filename, a.graph_abs_sm_filename, a.oa_image_lg_filename, a.oa_image_sm_filename, j.journal_banner,a.animated_abstract,a.erratum_in,a.erratum_for, (CASE WHEN a.issue_id =0 THEN j.epub_price ELSE j.price END) AS sell_price, j.epub_price, j.nid AS jour_nid, j.title AS journal_title, j.issn, j.eissn,j.journal_id, j.subtitle AS jour_subtitle, v.volume_id,v.volume_name AS volume, v.year_id, i.title AS issue, i.month_id ,i.type issue_type, j.subtitle,j.formerly_title, ac.subtitle AS epub_title,a.crossmark_enabled,a.text_mining_urls,a.license_urls,a.created, a.receivedate, a.revisedate, a.acceptdate,js.js_title FROM article a LEFT JOIN article_section ac ON a.is_epub = ac.art_sec_id LEFT JOIN journal_section js ON a.js_id = js.js_id LEFT JOIN article_type at ON a.art_type = at.art_type_id LEFT JOIN issue i ON a.issue_id = i.issue_id LEFT JOIN month m ON m.id = i.month_id LEFT JOIN volume v ON v.volume_id = a.volume_id INNER JOIN year y ON y.id = v.year_id INNER JOIN journal j ON j.journal_id = a.journal_id INNER JOIN publisher p ON p.publisher_id = j.publisher_id WHERE a.article_id=116495
      660μsalphaeurekaselec_live_10_06_2022Article.php#408
      Backtrace
      • 11. app/Models/Article.php:408
      • 12. app/Http/Controllers/ArticleController.php:2515
      • 13. app/Http/Controllers/ArticleController.php:2035
      • 14. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 15. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `journal` where `journal_id` = 1 limit 1
      810μsalphaeurekaselec_live_10_06_2022Journal.php#64
      Bindings
      • 0: 1
      Backtrace
      • 14. app/Models/Journal.php:64
      • 15. app/Http/Controllers/ArticleController.php:2516
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and sj.journal_id!=1 group by `j`.`nid`) as `aggregate_table`
      1.17msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 16. app/Models/Subject.php:200
      • 17. app/Http/Controllers/ArticleController.php:2517
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select j.nid as journal_nid,j.flyer_link,j.title ,j.issn,j.eissn,j.keyword, j.journal_id as journal_id, j.subtitle, j.image_file_name,j.description,j.journal_insight_url,j.doi from `subject_journal` as `sj` inner join `journal` as `j` on `j`.`journal_id` = `sj`.`journal_id` where j.journal_status=1 and subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and sj.journal_id!=1 group by `j`.`nid` order by `j`.`journal_id` asc limit 10 offset 0
      1.05msalphaeurekaselec_live_10_06_2022Subject.php#200
      Backtrace
      • 14. app/Models/Subject.php:200
      • 15. app/Http/Controllers/ArticleController.php:2517
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select count(*) as aggregate from (select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid`) as `aggregate_table`
      3.53msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 16. app/Models/Subject.php:220
      • 17. app/Http/Controllers/ArticleController.php:2518
      • 18. app/Http/Controllers/ArticleController.php:2035
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 20. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select v.nid as volume_id,e.nid,e.title,v.issn,v.eissn,v.isbn,v.eisbn,e.ebook_id, v.image_file_name,v.file_path,v.flyer_link,v.ebook_volume_id, v.volume_name,v.doi,v.year_id,v.introduction from `subject_ebook` as `se` inner join `ebook` as `e` on `e`.`ebook_id` = `se`.`ebook_id` inner join `ebook_volume` as `v` on `v`.`ebook_id` = `se`.`ebook_id` inner join `year` as `y` on `y`.`id` = `v`.`year_id` where subject_id IN (SELECT subject_id FROM subject_journal WHERE journal_id=1) and v.ebook_status='1' and y.year > 2020 group by `v`.`nid` order by `v`.`ebook_volume_id` desc limit 10 offset 0
      2.85msalphaeurekaselec_live_10_06_2022Subject.php#220
      Backtrace
      • 14. app/Models/Subject.php:220
      • 15. app/Http/Controllers/ArticleController.php:2518
      • 16. app/Http/Controllers/ArticleController.php:2035
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `keywords` where `article_id` = '116495'
      1msalphaeurekaselec_live_10_06_2022Keywords.php#43
      Bindings
      • 0: 116495
      Backtrace
      • 13. app/Models/Keywords.php:43
      • 14. app/Http/Controllers/ArticleController.php:2519
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select * from `article_citation` where `article_id` = '116495'
      2.54msalphaeurekaselec_live_10_06_2022Article.php#1570
      Bindings
      • 0: 116495
      Backtrace
      • 13. app/Models/Article.php:1570
      • 14. app/Http/Controllers/ArticleController.php:2520
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select CONCAT_WS(' ',au.first_name, ' ', ifnull(au.initials,''), ' ', au.last_name) as authors, CONCAT(au.last_name, IFNULL(CONCAT(' ', au.initials), ''), ' ', au.first_name) AS authorsRIS, CONCAT_WS(' ',au.last_name, ' ', ifnull(au.initials,''), ' ', au.first_name) as authorsCiteAs, CONCAT_WS(' ',au.first_name, IFNULL(CONCAT(' ', au.initials), ''), IFNULL(CONCAT(' ', au.last_name), '')) as authorsmodal , `au`.*, `af`.`ror_id`, `af`.`institution`, `af`.`department`, `af`.`country`, `af`.`city`, `af`.`address`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.institution,','),''), ifnull(concat(af.department,','),''), ifnull(concat(af.address,','),''), ifnull(concat(af.city,','),''), ifnull(concat(af.country,','),''), ifnull(concat(af.postal_code,','),''), ifnull(concat(af.phone,','),''), ifnull(concat(af.fax,','),''))) SEPARATOR '|')) as `author_affiliation`, (GROUP_CONCAT(TRIM(BOTH ', ' FROM CONCAT(ifnull(concat(af.web_view,','),''))) SEPARATOR '|')) as `web_view` from `author` as `au` left join `author_affiliation` as `af` on `au`.`author_id` = `af`.`author_id` where `au`.`article_id` = '116495' group by `au`.`author_id` order by `au`.`article_id` asc, `au`.`sequence` asc
      2.26msalphaeurekaselec_live_10_06_2022Author.php#86
      Bindings
      • 0: 116495
      Backtrace
      • 13. app/Models/Author.php:86
      • 14. app/Http/Controllers/ArticleController.php:2533
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      270μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2535
      • 15. app/Http/Controllers/ArticleController.php:2035
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
    • select `subtitle` from `journal` where `continues_publication_journal` = 1
      580μsalphaeurekaselec_live_10_06_2022Article.php#1960
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/Article.php:1960
      • 14. app/Http/Controllers/ArticleController.php:2062
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • Select j.subtitle, v.volume_id as volume_id,v.year_id,y.year as year,v.volume_name, v.total_no_of_issues, i.issue_id as issue_id,i.title as issue, i.publication_date as issue_pub_date from journal j join volume v on j.journal_id = v.journal_id join issue i on v.volume_id = i.volume_id join article a on a.issue_id = i.issue_id join year y on v.year_id = y.id where j.journal_id = 1 and i.is_uploaded = 1 order by v.volume_name+0 desc, i.title+0 desc limit 1
      35.37msalphaeurekaselec_live_10_06_2022Issue.php#298
      Backtrace
      • 11. app/Models/Issue.php:298
      • 12. app/Http/Controllers/ArticleController.php:2068
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 1 and a.journal_id = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      50.48msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2070
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select a.nid,a.publish_on, a.pmid,a.article_id,a.doi,j.journal_id,j.subtitle,v.volume_name,a.volume_id as volume_id, a.issue_id,a.title,first_page, last_page, page_count,abstract,ifnull(is_abstract,"y"),asec.title as article_section,at.type_name as article_type_name, a.article_id as ArticleID ,is_epub,epub_price,epub_type,a.created, y.year from `article` as `a` left join `article_section` as `asec` on `asec`.`art_sec_id` = `a`.`is_epub` left join `article_type` as `at` on `at`.`art_type_id` = `a`.`art_type` left join `journal` as `j` on `j`.`journal_id` = `a`.`journal_id` inner join `volume` as `v` on `a`.`volume_id` = `v`.`volume_id` inner join `year` as `y` on `v`.`year_id` = `y`.`id` where a.article_status != "W" and a.is_epub = 4 and a.journal_id = 1 and a.is_uploaded = 1 group by `a`.`article_id` order by `a`.`publish_on` desc
      25.15msalphaeurekaselec_live_10_06_2022Article.php#528
      Backtrace
      • 13. app/Models/Article.php:528
      • 14. app/Http/Controllers/ArticleController.php:2071
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select pdf, html, epub, prc from `article_metrics` where `article_id` = 116495 limit 1
      240μsalphaeurekaselec_live_10_06_2022Article.php#744
      Bindings
      • 0: 116495
      Backtrace
      • 14. app/Models/Article.php:744
      • 15. app/Http/Controllers/ArticleController.php:2091
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from content_by_diseases where content_id = 116495 and content_type = 'article' order by status desc limit 1
      250μsalphaeurekaselec_live_10_06_2022Article.php#751
      Backtrace
      • 11. app/Models/Article.php:751
      • 12. app/Http/Controllers/ArticleController.php:2094
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `node_meta` where `nid` = 194515 limit 1
      180μsalphaeurekaselec_live_10_06_2022Meta.php#30
      Bindings
      • 0: 194515
      Backtrace
      • 14. app/Models/Meta.php:30
      • 15. app/Http/Controllers/ArticleController.php:2101
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `bo`.* from `bundle_offer` as `bo` where `bo`.`bundle_status` = 'A' order by `bo`.`bundle_id` desc
      190μsalphaeurekaselec_live_10_06_2022BundleOffer.php#57
      Bindings
      • 0: A
      Backtrace
      • 13. app/Models/BundleOffer.php:57
      • 14. app/Http/Controllers/ArticleController.php:2108
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `tbl_ht_submission` as `h` where `h`.`subtitle` = 'ACAMC' and (h.proposal_closing_date = 0 OR TO_DAYS(FROM_UNIXTIME(h.proposal_closing_date)) >= TO_DAYS(NOW())) order by `h`.`manuscript` asc
      270μsalphaeurekaselec_live_10_06_2022Article.php#2025
      Bindings
      • 0: ACAMC
      Backtrace
      • 13. app/Models/Article.php:2025
      • 14. app/Http/Controllers/ArticleController.php:2112
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '116495' and content_type = 'a' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      400μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2186
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '11296' and content_type = 'i' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      370μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2207
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select count(*) as total_count, content_type_access_id as access_type from journal_access where content_type_id = '3166' and content_type = 'v' and ( (from_date <= CURDATE() and to_date >= CURDATE() and perpetual= 0) or (from_date is null and to_date is null and perpetual= 1) )
      300μsalphaeurekaselec_live_10_06_2022ContentAccess.php#647
      Backtrace
      • 11. app/Models/ContentAccess.php:647
      • 12. app/Http/Controllers/ArticleController.php:2231
      • 13. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 14. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"volume" as access_level,"" as issue_id,"" as article_id from `user_access_journal_volume_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.volume_id = 3166)
      15.9msalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2272
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11296) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11296) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"issue" as access_level,j.issue_id,"" as article_id from `user_access_issue_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.issue_id = 11296)
      580μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2297
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116495) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116495) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"article" as access_level, j.issue_id, j.article_id from `user_access_article_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 51592399 and j.to_ip >=51592399 )) and ((j.from_date <= 1739834397 and j.to_date >= 1739834397 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.article_id = 116495)
      550μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ArticleController.php:2329
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `first_page` < '721' and is_uploaded = 1 and issue_id = 11296 order by cast(first_page as SIGNED) desc limit 1
      600μsalphaeurekaselec_live_10_06_2022Article.php#1819
      Bindings
      • 0: 721
      Backtrace
      • 14. app/Models/Article.php:1819
      • 15. app/Http/Controllers/ArticleController.php:2470
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select * from `article` where `last_page` > '730' and is_uploaded = 1 and issue_id = 11296 order by cast(first_page as SIGNED) asc limit 1
      520μsalphaeurekaselec_live_10_06_2022Article.php#1831
      Bindings
      • 0: 730
      Backtrace
      • 14. app/Models/Article.php:1831
      • 15. app/Http/Controllers/ArticleController.php:2472
      • 16. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 17. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `language_id` from `multilanguage` where `short_code` = 'en'
      170μsalphaeurekaselec_live_10_06_2022ArticleController.php#2497
      Bindings
      • 0: en
      Backtrace
      • 14. app/Http/Controllers/ArticleController.php:2497
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 18. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select `source_lang_label`, `target_lang_label` from `multilanguage_labels` where `target_lang_id` = 1
      190μsalphaeurekaselec_live_10_06_2022MultiLanguage.php#23
      Bindings
      • 0: 1
      Backtrace
      • 13. app/Models/MultiLanguage.php:23
      • 14. app/Http/Controllers/ArticleController.php:2498
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select `id` from `multilanguage_article` where `article_id` = 116495 limit 1
      2.31msalphaeurekaselec_live_10_06_2022ArticleController.php#2506
      Bindings
      • 0: 116495
      Backtrace
      • 16. app/Http/Controllers/ArticleController.php:2506
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 18. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 19. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
      • 20. vendor/laravel/framework/src/Illuminate/Routing/Route.php:206
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 1 and `b`.`banner_from_date` <= 1739834397 and `b`.`banner_to_date` >= 1739834397 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.07msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1739834397
      • 4: 1739834397
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` inner join `journal` as `j` on `j`.`journal_id` = `bd`.`content_id` where `b`.`banner_journal` = 1 and `bd`.`content_type` = 'J' and `bd`.`content_id` = 1 and `b`.`banner_from_date` <= 1739834397 and `b`.`banner_to_date` >= 1739834397 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.08msalphaeurekaselec_live_10_06_2022Banner.php#95
      Bindings
      • 0: 1
      • 1: J
      • 2: 1
      • 3: 1739834397
      • 4: 1739834397
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:95
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='089122a2f588e4c24349f806d79535f8'
      200μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._header:260
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\MultiLanguage
    1MultiLanguage.php#?
        _token
        wjXAy5QoMqwiQLKAJPBqgMAcR7daqov4NDpLMrWY
        uc_cart_id
        089122a2f588e4c24349f806d79535f8
        _previous
        array:1 [ "url" => "http://alpha.eurekaselect.com/article/116495" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /article/116495
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
        array:9 [ "cookie" => array:1 [ 0 => "wayfindertarget=eyJpdiI6IlpIYTRUVFVMeWlvUjFjaURqdE12bnc9PSIsInZhbHVlIjoiejlvNW1nVE1pTnI1enZOd0d1anhOeE9nNE80bFA2SmFUL1FQUmpQQjFKNHRaWlBsMmxtejJhMGdqSjRzQlJ4NSIsIm1hYyI6ImQ3ZDc1MWZkM2Y2NTc3MzExYTI2NTI2MDU5YjY5ZjY0MjQ4NmM4YTVhODg4MGZlYWQ5ODVhMjcwMmMwYmEwODciLCJ0YWciOiIifQ%3D%3Dwayfindertarget=eyJpdiI6IlpIYTRUVFVMeWlvUjFjaURqdE12bnc9PSIsInZhbHVlIjoiejlvNW1nVE1pTnI1enZOd0d1anhOeE9nNE80bFA2SmFUL1FQUmpQQjFKNHRaWlBsMmxtejJhMGdqSjRzQlJ4NSIs" ] "accept-encoding" => array:1 [ 0 => "gzip, deflate" ] "accept" => array:1 [ 0 => "text/html,application/xhtml+xml,application/xml;q=0.9,image/avif,image/webp,image/apng,*/*;q=0.8,application/signed-exchange;v=b3;q=0.7" ] "user-agent" => array:1 [ 0 => "Mozilla/5.0 AppleWebKit/537.36 (KHTML, like Gecko; compatible; ClaudeBot/1.0; +claudebot@anthropic.com)" ] "upgrade-insecure-requests" => array:1 [ 0 => "1" ] "cache-control" => array:1 [ 0 => "no-cache" ] "pragma" => array:1 [ 0 => "no-cache" ] "connection" => array:1 [ 0 => "keep-alive" ] "host" => array:1 [ 0 => "alpha.eurekaselect.com" ] ]
        request_cookies
        0 of 0
        array:1 [ "wayfindertarget" => null ]
        response_headers
        0 of 0
        array:5 [ "content-type" => array:1 [ 0 => "text/html; charset=UTF-8" ] "cache-control" => array:1 [ 0 => "no-cache, private" ] "date" => array:1 [ 0 => "Mon, 17 Feb 2025 23:19:57 GMT" ] "set-cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjhwU1VPVU1senRZbHVscDkzQzNMNHc9PSIsInZhbHVlIjoiVkZIOGZPcURPbFZQMnpNdUZNVjBvUVYwLzdzZEFGT0N2MW5ubFdGOHhHWS83UmphNHVRSjEvRVZxamlVaWl3RHJub0tUREd6dVBCOFlNdHppd2VsNFoyYUpXbm5vcVUwWThuTE9SWWY2NzhzRjBua0VRM01MQnhneGdDTXRpTXAiLCJtYWMiOiI0OGYyZTMxMDMwYzY4OTlmZTc0NTVhM2RlNmNkOWI5MTg2ZWNjMWExYzI0ZmQ2NDE5ZjNkYmQ5MWYzZGQ3MGIxIiwidGFnIjoiIn0%3D; expires=Thu, 20 Feb 2025 11:19:57 GMT; Max-Age=216000; path=/; secure; samesite=laxXSRF-TOKEN=eyJpdiI6IjhwU1VPVU1senRZbHVscDkzQzNMNHc9PSIsInZhbHVlIjoiVkZIOGZPcURPbFZQMnpNdUZNVjBvUVYwLzdzZEFGT0N2MW5ubFdGOHhHWS83UmphNHVRSjEvRVZxamlVaWl3RHJub0tUR" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZibEdkaVN0VjdxVFRwZjR1VDRFdVE9PSIsInZhbHVlIjoiRm03RE1BK3FBUFNvOWpQS2NZMXJUcnpseDFzZ3ZGbkU1b09jeEtvcUJkc2FHZnJrVVdrWm40cE1XZFRDZlRCeUVXQmNveXA2S2tSSlNpbTBiUzFQaWRxenFCNEFjanFuUVRXMTNQYXVkOU4zWjZzOC9McHd6d3FFZ0ZVZEl1a28iLCJtYWMiOiIxYzJjNzMxOTA3MTBkNmZhYzRiYWYyNWIwMmQ3MGM0ZmYwMWFlODRiYWE3Njk2NGMwMGRjNWM0YzFlOGU5YTMyIiwidGFnIjoiIn0%3D; path=/; secure; httponly; samesite=laxalphaeurekaselectnet_session=eyJpdiI6InZibEdkaVN0VjdxVFRwZjR1VDRFdVE9PSIsInZhbHVlIjoiRm03RE1BK3FBUFNvOWpQS2NZMXJUcnpseDFzZ3ZGbkU1b09jeEtvcUJkc2FHZnJrVVdrWm40cE1" ] "Set-Cookie" => array:2 [ 0 => "XSRF-TOKEN=eyJpdiI6IjhwU1VPVU1senRZbHVscDkzQzNMNHc9PSIsInZhbHVlIjoiVkZIOGZPcURPbFZQMnpNdUZNVjBvUVYwLzdzZEFGT0N2MW5ubFdGOHhHWS83UmphNHVRSjEvRVZxamlVaWl3RHJub0tUREd6dVBCOFlNdHppd2VsNFoyYUpXbm5vcVUwWThuTE9SWWY2NzhzRjBua0VRM01MQnhneGdDTXRpTXAiLCJtYWMiOiI0OGYyZTMxMDMwYzY4OTlmZTc0NTVhM2RlNmNkOWI5MTg2ZWNjMWExYzI0ZmQ2NDE5ZjNkYmQ5MWYzZGQ3MGIxIiwidGFnIjoiIn0%3D; expires=Thu, 20-Feb-2025 11:19:57 GMT; path=/; secureXSRF-TOKEN=eyJpdiI6IjhwU1VPVU1senRZbHVscDkzQzNMNHc9PSIsInZhbHVlIjoiVkZIOGZPcURPbFZQMnpNdUZNVjBvUVYwLzdzZEFGT0N2MW5ubFdGOHhHWS83UmphNHVRSjEvRVZxamlVaWl3RHJub0tUR" 1 => "alphaeurekaselectnet_session=eyJpdiI6InZibEdkaVN0VjdxVFRwZjR1VDRFdVE9PSIsInZhbHVlIjoiRm03RE1BK3FBUFNvOWpQS2NZMXJUcnpseDFzZ3ZGbkU1b09jeEtvcUJkc2FHZnJrVVdrWm40cE1XZFRDZlRCeUVXQmNveXA2S2tSSlNpbTBiUzFQaWRxenFCNEFjanFuUVRXMTNQYXVkOU4zWjZzOC9McHd6d3FFZ0ZVZEl1a28iLCJtYWMiOiIxYzJjNzMxOTA3MTBkNmZhYzRiYWYyNWIwMmQ3MGM0ZmYwMWFlODRiYWE3Njk2NGMwMGRjNWM0YzFlOGU5YTMyIiwidGFnIjoiIn0%3D; path=/; secure; httponlyalphaeurekaselectnet_session=eyJpdiI6InZibEdkaVN0VjdxVFRwZjR1VDRFdVE9PSIsInZhbHVlIjoiRm03RE1BK3FBUFNvOWpQS2NZMXJUcnpseDFzZ3ZGbkU1b09jeEtvcUJkc2FHZnJrVVdrWm40cE1" ] ]
        session_attributes
        0 of 0
        array:5 [ "_token" => "wjXAy5QoMqwiQLKAJPBqgMAcR7daqov4NDpLMrWY" "uc_cart_id" => "089122a2f588e4c24349f806d79535f8" "_previous" => array:1 [ "url" => "http://alpha.eurekaselect.com/article/116495" ] "_flash" => array:2 [ "old" => [] "new" => [] ] "PHPDEBUGBAR_STACK_DATA" => [] ]
        ClearShow all
        Date ↕MethodURLData
        #12025-02-17 23:19:57GET/article/116495414361