Journal of Multidisciplinary Applied Natural Science
an Open Access Journal
Scopus CiteScore 2025
2.1
Calculated on 05 May, 2025
SJR 2025
0.25
Powered by scimagojr.com
an Open Access Journal
2.1
Calculated on 05 May, 2025
0.25
Powered by scimagojr.com
https://doi.org/10.47352/jmans.2774-3047.377
Bujaningrum Ega Agustina
Berna Elya
Roshamur Cahyan Forestrania
Husniati Husniati
Kratom (Mitragyna speciosa Korth.) is widely used in Southeast Asia, and vein-color phenotypes (red, white, green) are traditionally and commercially associated with different intended uses and perceived effects. Although phytochemical variation among kratom products has been reported, direct comparison of Kalimantan vein-color phenotypes that links standardized alkaloid metrics to a defined anti-inflammatory enzyme target remains limited. Since 15-lipoxygenase (15-LOX) contributes to the formation of pro-inflammatory lipid mediators and is implicated in chronic inflammatory conditions, its inhibition provides a relevant biochemical endpoint to screen anti-inflammatory potential. This study characterized the alkaloid profiles and mitragynine content of red-, white-, and green-vein kratom leaves from Kalimantan and evaluated their in vitro 15-LOX inhibitory activity. GC–MS and LC–HRMS indicated broadly similar alkaloid fingerprints across phenotypes, dominated by mitragynine with accompanying constituents, including 7-hydroxymitragynine, paynantheine and the speciogynine/speciociliatine isomeric pair. Mitragynine content in crude methanolic extracts ranged from 22.96 ± 0.24 to 43.87 ± 0.96 mg g⁻¹ extract (white > green > red; p < 0.0001), whereas alkaloid extracts contained 177.44 ± 0.70 to 258.21 ± 1.00 mg g⁻¹ extract (red > green > white; p < 0.0001). In the 15-LOX assay, baicalein showed the strongest inhibition (IC₅₀ = 9.72 ± 0.07 µg mL⁻¹), followed by mitragynine (28.38 ± 0.39 µg mL⁻¹) and alkaloid extracts (red: 53.01 ± 0.39; green: 56.29 ± 0.79; white: 59.91 ± 0.92 µg mL⁻¹), while crude methanolic extracts exhibited weak activity (IC₅₀ > 100 µg mL⁻¹). Overall, Kalimantan vein-color phenotypes share a common monoterpenoid indole alkaloid core profile but differ quantitatively in mitragynine levels and 15-LOX inhibitory potency, supporting further mechanistic and translational investigations.
[1] S. D. Löfstrand, Å. Krüger, S. G. Razafimandimbison, and B. Bremer. (2014). "Phylogeny And Generic Delimitations In The Sister Tribes Hymenodictyeae And Naucleeae (Rubiaceae)". Systematic Botany. 39 (1): 304-315. 10.1600/036364414X678116.
DOI: https://doi.org/10.1600/036364414X678116[2] L. S. L. Chua. (2001). In: "Plant Resources Of South-East Asia (PROSEA)". Bogor: PROSEA Foundation.
[3] R. Nilus, F. Lee Ying, and A. Hastie. (2011). "Species Selection Trial In Burnt Peat Swamp Vegetation In Southwest Coast Of Sabah, Malaysia". Proceedings Of The International Symposium Rehabilitation Of Tropical Rainforest Ecosystems.
[4] E. Cinosi. (2015). "Following The Roots Of Kratom (Mitragyna Speciosa): The Evolution Of An Enhancer From A Traditional Use To Increase Work And Productivity In Southeast Asia To A Recreational Psychoactive Drug In Western Countries". BioMed Research International. 2015 : 1-11. 10.1155/2015/968786.
DOI: https://doi.org/10.1155/2015/968786[5] T. Nakaphan, M. Teerachaisakul, S. Puttum, K. Sompimai, and P. Nootim. (2016). "Traditional Use Of Kratom (Mitragyna Speciosa Korth) Among Folk Healers In Southern Thailand". Journal Of Thai Traditional And Alternative Medicine. 14 (3): 274-285.
[6] L. Flores-Bocanegra. (2020). "The Chemistry Of Kratom (Mitragyna Speciosa): Updated Characterization Data And Methods To Elucidate Indole And Oxindole Alkaloids". Journal Of Natural Products. 83 (7): 2165-2177. 10.1021/acs.jnatprod.0c00257.
DOI: https://doi.org/10.1021/acs.jnatprod.0c00257[7] D. A. Todd. (2020). "Chemical Composition And Biological Effects Of Kratom (Mitragyna Speciosa): In Vitro Studies With Implications For Efficacy And Drug Interactions". Scientific Reports. 10 : 19158. 10.1038/s41598-020-76119-w.
DOI: https://doi.org/10.1038/s41598-020-76119-w[8] F. Kurniawati, D. Fitria, A. R. U. Nainggolan, and P. A. Wardani. (2023). "Identifikasi Dan Karakterisasi Tanaman Kratom Melalui Pendekatan Profil Kandungan Senyawa Penanda Secara LC-HRMS QToF Dan Penetapan Nilai Retention Index Secara GCMS". Eruditio: Indonesia Journal Of Food And Drug Safety. 3 (1): 79-90. 10.54384/eruditio.v3i1.141.
DOI: https://doi.org/10.54384/eruditio.v3i1.141[9] P. K. Manwill. (2022). "Kratom (Mitragyna Speciosa) Validation: Quantitative Analysis Of Indole And Oxindole Alkaloids Reveals Chemotypes Of Plants And Products". Planta Medica. 88 (9-10): 838-852. 10.1055/a-1795-5876.
DOI: https://doi.org/10.1055/a-1795-5876[10] M. Zhang, A. Sharma, F. León, B. A. Avery, C. R. McCurdy, and B. J. Pearson. (2022). "Plant Growth And Phytoactive Alkaloid Synthesis In Kratom (Mitragyna Speciosa) In Response To Varying Radiance". PLoS One. 17 : e0259326. 10.1371/journal.pone.0259326.
DOI: https://doi.org/10.1371/journal.pone.0259326[11] S. I. Rahmawati. (2024). "Dual Anti-Inflammatory Activities Of COX-2/5-LOX Driven By Kratom Alkaloid Extracts In Lipopolysaccharide-Induced RAW 264.7 Cells". Scientific Reports. 14 (1): 28993. 10.1038/s41598-024-79229-x.
DOI: https://doi.org/10.1038/s41598-024-79229-x[12] H. Takayama. (2004). "Chemistry And Pharmacology Of Analgesic Indole Alkaloids From The Rubiaceous Plant, Mitragyna Speciosa". Chemical And Pharmaceutical Bulletin. 52 (8): 916-928. 10.1248/cpb.52.916.
DOI: https://doi.org/10.1248/cpb.52.916[13] H. Takayama, M. Kurihara, M. Kitajima, I. M. Said, and N. Aimi. (1998). "New Indole Alkaloids From The Leaves Of Malaysian Mitragyna Speciosa". Tetrahedron. 54 (29): 8433-8440. 10.1016/S0040-4020(98)00464-5.
DOI: https://doi.org/10.1016/S0040-4020(98)00464-5[14] K. Ng and T. Ha. (2024). "Extraction And Detection Of Mitragynine In Kratom Leaves By High-Performance Liquid Chromatography". Natural Product Research. 1-6. 10.1080/14786419.2024.2331602.
DOI: https://doi.org/10.1080/14786419.2024.2331602[15] A. Bayu. (2024). "An In Vitro Examination Of Whether Kratom Extracts Enhance The Cytotoxicity Of Low-Dose Doxorubicin Against A549 Human Lung Cancer Cells". Molecules. 29 (6): 1404. 10.3390/molecules29061404.
DOI: https://doi.org/10.3390/molecules29061404[16] V. Novianry, P. Astuti, and Andriani. (2024). "Comparative Analysis Of Mitragynine Content In Kratom Leaves (Mitragyna Speciosa Korth) From Kabupaten Kapuas Hulu Using HPLC Method". Sciscitatio. 5 (2): 87-93. 10.21460/sciscitatio.2024.52.183.
DOI: https://doi.org/10.21460/sciscitatio.2024.52.183[17] A. Janthongkaw. (2023). "Effect Of Green And Red Thai Kratom (Mitragyna Speciosa) On Pancreatic Digestive Enzymes (Alpha-Glucosidase And Lipase) And Acetyl-Carboxylase 1 Activity: A Possible Therapeutic Target For Obesity Prevention". PLoS One. 18 (9): e0291738. 10.1371/journal.pone.0291738.
DOI: https://doi.org/10.1371/journal.pone.0291738[18] M. Masriani, P. Melania, R. Muharini, A. H. Alimuddin, and R. P. Sartika. (2024). "Total Phenolic And Flavonoids Content, And Antioxidant Activity Of Kratom (Mitragyna Speciosa Korth.) Leaf Ethanol Extract". Jurnal Natural. 24 (1): 16-21. 10.24815/jn.v24i1.33125.
DOI: https://doi.org/10.24815/jn.v24i1.33125[19] N. Nawaka, M. Lertcanawanichakul, S. Porntadavity, B. Pussadhamma, and N. Jeenduang. (2025). "Kratom Leaf Extracts Exert Hypolipidaemic Effects Via The Modulation Of PCSK9 And LDLR Pathways In HepG2 Cells". Scientific Reports. 15 (1): 15696. 10.1038/s41598-025-00711-1.
DOI: https://doi.org/10.1038/s41598-025-00711-1[20] G. Huisman, M. Menke, O. Grundmann, R. Schreiber, and N. Mason. (2023). "Examining The Psychoactive Differences Between Kratom Strains". International Journal of Environmental Research and Public Health. 20 (14): 6425. 10.3390/ijerph20146425.
DOI: https://doi.org/10.3390/ijerph20146425[21] R. Syarma, K. Masitoh, and S. Setyawati. (2023). "Karakteristik Dan Pengetahuan Masyarakat Desa Entibab Tentang Pemanfaatan Tumbuhan Kratom (Mitragyna Speciosa) Di Kabupaten Kapuas Hulu". Jurnal Hutan Lestari. 11 (1): 75-80. 10.26418/jhl.v11i1.60416.
DOI: https://doi.org/10.26418/jhl.v11i1.60416[22] M. G. Netea. (2017). "A Guiding Map For Inflammation". Nature Immunology. 18 (8): 826-831. 10.1038/ni.3790.
DOI: https://doi.org/10.1038/ni.3790[23] N. Mukhopadhyay, A. Shukla, P. N. Makhal, and V. R. Kaki. (2023). "Natural Product-Driven Dual COX-LOX Inhibitors: Overview Of Recent Studies On The Development Of Novel Anti-Inflammatory Agents". Heliyon. 9 (3): e14569. 10.1016/j.heliyon.2023.e14569.
DOI: https://doi.org/10.1016/j.heliyon.2023.e14569[24] O. R. Kolawole and K. Kashfi. (2025). "Reprogramming Inflammation: Mechanisms And Therapeutic Targeting Of Eicosanoids And Pro-Resolving Mediators". European Journal of Pharmacology. 1003 : 177924. 10.1016/j.ejphar.2025.177924.
DOI: https://doi.org/10.1016/j.ejphar.2025.177924[25] L. Morici, E. Allémann, O. Jordan, and I. Nikolić. (2025). "Promising LOX Proteins For Cartilage-Targeting Osteoarthritis Therapy". Pharmacological Research. 212 : 107627. 10.1016/j.phrs.2025.107627.
DOI: https://doi.org/10.1016/j.phrs.2025.107627[26] J. A. Boyce. (2022). "The Role Of 15 Lipoxygenase 1 In Asthma Comes Into Focus". Journal Of Clinical Investigation. 132 (1). 10.1172/JCI155884.
DOI: https://doi.org/10.1172/JCI155884[27] G. Feugray. (2022). "Determination Of Lipoxygenase, CYP450, And Non-Enzymatic Metabolites Of Arachidonic Acid In Essential Hypertension And Type 2 Diabetes". Metabolites. 12 (9): 859. 10.3390/metabo12090859.
DOI: https://doi.org/10.3390/metabo12090859[28] J. W. Chen. (2025). "12/15-Lipoxygenase Mediates Disturbed Flow-Induced Endothelial Dysfunction And Atherosclerosis". Molecular Medicine. 31 (1): 257. 10.1186/s10020-025-01297-0.
DOI: https://doi.org/10.1186/s10020-025-01297-0[29] L. Boffa, C. Ghè, A. Barge, G. Muccioli, and G. Cravotto. (2018). "Alkaloid Profiles And Activity In Different Mitragyna Speciosa Strains". Natural Product Communications. 13 (9): 1111-1116. 10.1177/1934578X1801300904.
DOI: https://doi.org/10.1177/1934578X1801300904[30] H. M. Salim, Choirotussanijjah, E. S. Awwalia, and I. P. Alam. (2022). "Anti-Inflammatory Effects And Potential Mechanisms Of Mitragyna Speciosa Methanol Extract On λ-Karagenan-Induced Inflammation Model". Bali Medical Journal. 11 (3): 1172-1175. 10.15562/bmj.v11i3.3535.
DOI: https://doi.org/10.15562/bmj.v11i3.3535[31] Z. Utar, M. I. A. Majid, M. I. Adenan, M. F. A. Jamil, and T. M. Lan. (2011). "Mitragynine Inhibits The COX-2 mRNA Expression And Prostaglandin E2 Production Induced By Lipopolysaccharide In RAW264.7 Macrophage Cells". Journal of Ethnopharmacology. 136 (1): 75-82. 10.1016/j.jep.2011.04.011.
DOI: https://doi.org/10.1016/j.jep.2011.04.011[32] N. Tohar, J. A. Shilpi, Y. Sivasothy, S. Ahmad, and K. Awang. (2019). "Chemical Constituents And Nitric Oxide Inhibitory Activity Of Supercritical Carbon Dioxide Extracts From Mitragyna Speciosa Leaves". Arabian Journal of Chemistry. 12 (3): 350-359. 10.1016/j.arabjc.2016.09.005.
DOI: https://doi.org/10.1016/j.arabjc.2016.09.005[33] A. Kafo, R. Elsalami, and M. Hassan. (2024). "Mitragyna Speciosa Korth. Downregulates Macrophage Inflammatory Responses By Inhibiting TLR-4 And Increasing IL-10 Production". İstanbul Journal Of Pharmacy. 54 (3): 350-358. 10.26650/IstanbulJPharm.2024.1424150.
DOI: https://doi.org/10.26650/IstanbulJPharm.2024.1424150[34] S. Tuntiyasawasdikul, J. Junlatat, P. Tabboon, E. Limpongsa, and N. Jaipakdee. (2024). "Mitragyna Speciosa Ethanolic Extract: Extraction, Anti-Inflammatory, Cytotoxicity, And Transdermal Delivery Assessments". Industrial Crops And Products. 208 : 117909. 10.1016/j.indcrop.2023.117909.
DOI: https://doi.org/10.1016/j.indcrop.2023.117909[35] A. Listiyani, B. Elya, and N. Puspitasari. (2017). "Antioxidant Activity And Lipoxygenase Enzyme Inhibitory Assay With Total Flavonoids Content From Garcinia Hombroniana Pierre Stem Bark Extract". Pharmacognosy Journal. 9 (2): 276-279. 10.5530/pj.2017.2.47.
DOI: https://doi.org/10.5530/pj.2017.2.47[36] T. Karunakaran, Y. S. Goh, R. Santhanam, V. Murugaiyah, M. H. A. Bakar, and S. Ramanathan. (2022). "RP-HPLC-DAD Analysis Of Mitragynine Content In Mitragyna Speciosa Korth. (Ketum) Leaf Extracts Prepared Using Ultrasound Assisted Extraction Technique And Their Cytotoxicity". Separations. 9 (11): 345. 10.3390/separations9110345.
DOI: https://doi.org/10.3390/separations9110345[37] S. N. I. Mutiara, M. Masriani, R. Muharini, A. Sapar, and R. Rasmawan. (2023). "Comparison Of Extraction Variations On Mitragynine Level Of Three Variants Of Kratom Leaves (Mitragyna Speciosa Korth)". EduChemia: Jurnal Kimia Dan Pendidikan. 8 (1): 113. 10.30870/educhemia.v8i1.21184.
DOI: https://doi.org/10.30870/educhemia.v8i1.21184[38] B. E. Agustina, B. Elya, and R. C. Forestrani. (2025). "Environmental And Physiological Determinants Of Growth And Phytochemical Variation In Kratom (Mitragyna Speciosa): A Review". Journal Of Horticulture And Postharvest Research. 8 (4): 561-580. 10.22077/jhpr.2025.9870.1557.
[39] V. M. Sipoloni, M. C. Bassicheto, M. V. de Oliveira, A. B. dos S. de Souza, G. M. Alves, and T. A. M. Veiga. (2025). "Nonconventional Techniques In Plant Alkaloid Extraction: A Decade Of Progress (2014-2023)". Chemistry & Biodiversity. 22 (8). 10.1002/cbdv.202403225.
DOI: https://doi.org/10.1002/cbdv.202403225[40] Tanti, C. A. Lalangi, E. Arfiyani, W. Ningtias, and E. N. Maulida. (2021). "Mitragynine Percentages Of Various Kratom Variants Seized In Indonesia: A Quantitative Analysis Using Liquid Chromatography-Photo Diode Array Detector". International Journal of Applied Pharmaceutics. 13 (5): 252-256. 10.22159/ijap.2021v13i5.41910.
DOI: https://doi.org/10.22159/ijap.2021v13i5.41910[41] T. Limpanuparb, R. Noorat, and Y. Tantirungrotechai. (2019). "In Silico Investigation Of Mitragynine And 7-Hydroxymitragynine Metabolism". BMC Research Notes. 12 (1). 10.1186/s13104-019-4461-3.
DOI: https://doi.org/10.1186/s13104-019-4461-3[42] N. Sengnon. (2023). "Seasonal And Geographic Variation In Alkaloid Content Of Kratom (Mitragyna Speciosa (Korth.) Havil.) From Thailand". Plants. 12 (4): 949. 10.3390/plants12040949.
DOI: https://doi.org/10.3390/plants12040949[43] S. Phongprueksapattana, W. Putalun, N. Keawpradub, and J. Wungsintaweekul. (2008). "Mitragyna Speciosa: Hairy Root Culture For Triterpenoid Production And High Yield Of Mitragynine By Regenerated Plants". Zeitschrift Für Naturforschung C. 63 (9-10): 691-698. 10.1515/znc-2008-9-1014.
DOI: https://doi.org/10.1515/znc-2008-9-1014[44] R. Veeramohan. (2023). "Comparative Metabolomics Analysis Reveals Alkaloid Repertoires In Young And Mature Mitragyna Speciosa (Korth.) Havil. Leaves". PLoS One. 18 (3): e0283147. 10.1371/journal.pone.0283147.
DOI: https://doi.org/10.1371/journal.pone.0283147[45] K. Matsumoto. (2004). "Antinociceptive Effect Of 7-Hydroxymitragynine In Mice: Discovery Of An Orally Active Opioid Analgesic From The Thai Medicinal Herb Mitragyna Speciosa". Life Sciences. 74 (17): 2143-2155. 10.1016/j.lfs.2003.09.054.
DOI: https://doi.org/10.1016/j.lfs.2003.09.054[46] A. C. Kruegel. (2019). "7-Hydroxymitragynine Is An Active Metabolite Of Mitragynine And A Key Mediator Of Its Analgesic Effects". ACS Central Science. 5 (6): 992-1001. 10.1021/acscentsci.9b00141.
DOI: https://doi.org/10.1021/acscentsci.9b00141[47] E. C. Berthold. (2022). "The Lack Of Contribution Of 7-Hydroxymitragynine To The Antinociceptive Effects Of Mitragynine In Mice: A Pharmacokinetic And Pharmacodynamic Study". Drug Metabolism And Disposition. 50 (2): 158-167. 10.1124/dmd.121.000640.
DOI: https://doi.org/10.1124/dmd.121.000640[48] D. W. Indriani. (2025). "Serotonin Release Mediates Analgesia Via Opioidergic System And Withdrawal Symptoms In Chronic Kratom Extract-Treated Mice". BMC Complementary Medicine And Therapies. 25 (1): 205. 10.1186/s12906-025-04947-2.
DOI: https://doi.org/10.1186/s12906-025-04947-2[49] M. Zhang. (2025). "Alkaloid Biosynthesis In Medicinal Crop Kratom (Mitragyna Speciosa) Varies With Postharvest, Genetic, And Seasonal Factors". Frontiers In Plant Science. 16 : 1653916. 10.3389/fpls.2025.1653916.
DOI: https://doi.org/10.3389/fpls.2025.1653916[50] K. Kim. (2023). "Biosynthesis Of Kratom Opioids". New Phytologist. 240 (2): 757-769. 10.1111/nph.19162.
DOI: https://doi.org/10.1111/nph.19162[51] C. Schotte. (2023). "Directed Biosynthesis Of Mitragynine Stereoisomers". Journal of the American Chemical Society. 145 (9): 4957-4963. 10.1021/jacs.2c13644.
DOI: https://doi.org/10.1021/jacs.2c13644[52] N. J. Y. Chear. (2021). "Exploring The Chemistry Of Alkaloids From Malaysian Mitragyna Speciosa (Kratom) And The Role Of Oxindoles On Human Opioid Receptors". Journal Of Natural Products. 84 (4): 1034-1043. 10.1021/acs.jnatprod.0c01055.
DOI: https://doi.org/10.1021/acs.jnatprod.0c01055[53] T. Karunakaran, B. Vicknasingam, and M. C. Chawarski. (2025). "Phytochemical Analysis Of Water And Ethanol Liquid Extracts Prepared Using Freshly Harvested Leaves Of Mitragyna Speciosa (Korth.)". Natural Product Research. 39 (15): 4480-4487. 10.1080/14786419.2024.2362428.
DOI: https://doi.org/10.1080/14786419.2024.2362428[54] S. Parthasarathy. (2013). "A Simple HPLC-DAD Method For The Detection And Quantification Of Psychotropic Mitragynine In Mitragyna Speciosa (Ketum) And Its Products For The Application In Forensic Investigation". Forensic Science International. 226 (1-3): 183-187. 10.1016/j.forsciint.2013.01.014.
DOI: https://doi.org/10.1016/j.forsciint.2013.01.014[55] N. Izzati. (2021). "HPLC Method For Mitragynine And 7-Hydroxymitragynine Determination In Mitragyna Speciosa". Transactions Of The Malaysian Society Of Plant Physiology. 28 : 251-255.
[56] Tanti, Y. Harahap, T. Rahmania, R. Pangsibidang, O. Nursanti, S. Tuba, C. Tonggo, M. Tambunan, C. Andriyani, Maimunah, P. Heryani, W. Ningtias, and M. Luther. (2023). "Development And Validation Of The Quantification Method For Mitragynine And 7-Hydroxy Mitragynine In Kratom Plant Using High-Performance Liquid Chromatography-Photodiode Array". Azerbaijan Medical Journal. 62 (9): 4653-4660.
[57] F. G. Kocanci, S. Nigdelioglu Dolanbay, and B. Aslim. (2022). "Comparison Of Three Different Protocols Of Alkaloid Extraction From Glaucium Corniculatum Plant". International Journal Of Secondary Metabolite. 9 (1): 43-51. 10.21448/ijsm.980171.
DOI: https://doi.org/10.21448/ijsm.980171[58] F. León, E. Habib, J. E. Adkins, E. B. Furr, C. R. McCurdy, and S. J. Cutler. (2009). "Phytochemical Characterization Of The Leaves Of Mitragyna Speciosa Grown In USA". Natural Product Communications. 4 (7): 907-910. 10.1177/1934578X0900400705.
DOI: https://doi.org/10.1177/1934578X0900400705[59] S. U. Edi, U. S. Y. V. Indrawati, and J. Junaidi. (2024). "Characterization Of Physicochemical Properties And Heavy Metals Content Of Soils Under Kratom (Mitragyna Speciosa) Cultivation, Kapuas Hulu District, Indonesia". Indian Journal Of Agricultural Research. 58 (Special Issue): 1109-1114. 10.18805/IJARe.AF-845.
DOI: https://doi.org/10.18805/IJARe.AF-845[60] B. Rossalinda, A. Astina, and T. Palupi. (2024). "Respon Pertumbuhan Bibit Kratom Terhadap Jenis Tanah Yang Berbeda [Response Of Kratom Seedlings Growth To Different Soil Types]". Jurnal Sains Pertanian Equator. 13 (2): 576. 10.26418/jspe.v13i2.77021.
DOI: https://doi.org/10.26418/jspe.v13i2.77021[61] W. Phromchan, I. Defri, C. Saensano, A. Chookaew, R. Chiarawipa, and S. Sriwiriyajan. (2024). "Morphological And Physiological Properties Of Kratom (Mitragyna Speciosa) Leaves: Macronutrients, Phytochemicals, Antioxidants, And Mitragynine Content". Plant Science Today. 762-770. 10.14719/pst.2991.
DOI: https://doi.org/10.14719/pst.2991[62] C. J. K. Simamora, K. P. Utomo, Jumiati, M. Pramulya, and N. Wahyuni. (2025). "Evaluation Of Growth Position And Root Associative Microbes Of Mitragyna Speciosa On The Production Of Psychoactive, Mitragynine And Alkaloids". Notulae Scientia Biologicae. 17 (1): 12281. 10.55779/nsb17112281.
DOI: https://doi.org/10.55779/nsb17112281[63] S. Kaewchompoo, P. Temkitthawon, K. Phumlek, N. Waranuch, N. Ngamdokmai, and K. Ingkaninan. (2025). "Cosmeceutical Potential Of Mitragyna Speciosa (Kratom): Anti-Adipogenic And Antioxidant Properties Of Extracts And Mitragynine". Molecules. 30 (21): 4256. 10.3390/molecules30214256.
DOI: https://doi.org/10.3390/molecules30214256[64] H. Sadeghian and A. Jabbari. (2016). "15-Lipoxygenase Inhibitors: A Patent Review". Expert Opinion On Therapeutic Patents. 26 (1): 65-88. 10.1517/13543776.2016.1113259.
DOI: https://doi.org/10.1517/13543776.2016.1113259[65] J. Z. Haeggström and C. D. Funk. (2011). "Lipoxygenase And Leukotriene Pathways: Biochemistry, Biology, And Roles In Disease". Chemical Reviews. 111 (10): 5866-5896. 10.1021/cr200246d.
DOI: https://doi.org/10.1021/cr200246d[66] P. Singh, Y. Arif, E. Miszczuk, A. Bajguz, and S. Hayat. (2022). "Specific Roles Of Lipoxygenases In Development And Responses To Stress In Plants". Plants. 11 (7): 979. 10.3390/plants11070979.
DOI: https://doi.org/10.3390/plants11070979[67] Y. Benatzy, M. A. Palmer, and B. Brüne. (2022). "Arachidonate 15-Lipoxygenase Type B: Regulation, Function, And Its Role In Pathophysiology". Frontiers in Pharmacology. 13. 10.3389/fphar.2022.1042420.
DOI: https://doi.org/10.3389/fphar.2022.1042420[68] F. J. Papatheofanis and W. E. M. Lands. (1985). In: "Biochemistry Of Arachidonic Acid Metabolism". Boston, MA: Springer US. 9-39. 10.1007/978-1-4613-2597-0_2.
DOI: https://doi.org/10.1007/978-1-4613-2597-0_2[69] Z. Xu, H. Du, A. Manyande, and S. Xiong. (2024). "A Comprehensive Investigation On The Interaction Between Jaceosidin, Baicalein And Lipoxygenase: Multi-Spectroscopic Analysis And Computational Study". Spectrochimica Acta Part A: Molecular And Biomolecular Spectroscopy. 304 : 123423. 10.1016/j.saa.2023.123423.
DOI: https://doi.org/10.1016/j.saa.2023.123423[70] A. Sardar. (2022). "Identification Of Novel Diclofenac Acid And Naproxen Bearing Hydrazones As 15-LOX Inhibitors: Design, Synthesis, In Vitro Evaluation, Cytotoxicity, And In Silico Studies". Arabian Journal of Chemistry. 15 (12): 104300. 10.1016/j.arabjc.2022.104300.
DOI: https://doi.org/10.1016/j.arabjc.2022.104300[71] A. Mujawah, A. Rauf, S. Bawazeer, A. Wadood, H. A. Hemeg, and S. Bawazeer. (2023). "In-Vitro Antioxidant, Lipoxygenase Inhibitory, And In-Vivo Muscle Relaxant Potential Of The Extract And Constituent Isolated From Diospyros Kaki (Japanese Persimmon)". Heliyon. 9 (3): e13816. 10.1016/j.heliyon.2023.e13816.
DOI: https://doi.org/10.1016/j.heliyon.2023.e13816[72] C. D. Sadik, H. Sies, and T. Schewe. (2003). "Inhibition Of 15-Lipoxygenases By Flavonoids: Structure-Activity Relations And Mode Of Action". Biochemical Pharmacology. 65 (5): 773-781. 10.1016/S0006-2952(02)01621-0.
DOI: https://doi.org/10.1016/S0006-2952(02)01621-0[73] J. D. Deschamps, V. A. Kenyon, and T. R. Holman. (2006). "Baicalein Is A Potent In Vitro Inhibitor Against Both Reticulocyte 15-Human And Platelet 12-Human Lipoxygenases". Bioorganic & Medicinal Chemistry. 14 (12): 4295-4301. 10.1016/j.bmc.2006.01.057.
DOI: https://doi.org/10.1016/j.bmc.2006.01.057[74] I. Arief and E. Kurnianto. (2022). "Identification Of Active Compound From Mitragyna Speciosa Leave As Antiinflammation Agent: In Silico Study". Acta Chimica Asiana. 5 (2): 218-223. 10.29303/aca.v5i2.139.
DOI: https://doi.org/10.29303/aca.v5i2.139[75] M. Lončarić, I. Strelec, T. Moslavac, D. Šubarić, V. Pavić, and M. Molnar. (2021). "Lipoxygenase Inhibition By Plant Extracts". Biomolecules. 11 (2): 152. 10.3390/biom11020152.
DOI: https://doi.org/10.3390/biom11020152[76] D. Yuan. (2009). "Anti-Inflammatory Effects Of Rhynchophylline And Isorhynchophylline In Mouse N9 Microglial Cells And The Molecular Mechanism". International Immunopharmacology. 9 (13-14): 1549-1554. 10.1016/j.intimp.2009.09.010.
DOI: https://doi.org/10.1016/j.intimp.2009.09.010[77] R. G. Geetha and S. Ramachandran. (2021). "Recent Advances In The Anti-Inflammatory Activity Of Plant-Derived Alkaloid Rhynchophylline In Neurological And Cardiovascular Diseases". Pharmaceutics. 13 (8): 1170. 10.3390/pharmaceutics13081170.
DOI: https://doi.org/10.3390/pharmaceutics13081170[78] C. Zhang. (2023). "Rhynchophylline Alleviates Neuroinflammation And Regulates Metabolic Disorders In A Mouse Model Of Parkinson's Disease". Food & Function. 14 (7): 3208-3219. 10.1039/D2FO02939A.
DOI: https://doi.org/10.1039/D2FO02939A[79] S. A. Garba. (2025). "Identification Of The Anti-Epileptic Effect Of Speciogynine Through Molecular Network-Aided Metabolite Profiling Of M. Speciosa Alkaloids Using Zebrafish". Fitoterapia. 184 : 106667. 10.1016/j.fitote.2025.106667.
DOI: https://doi.org/10.1016/j.fitote.2025.106667[80] A. S. Alford, H. L. Moreno, M. M. Benjamin, C. F. Dickinson, and M. T. Hamann. (2025). "Exploring The Therapeutic Potential Of Mitragynine And Corynoxeine: Kratom-Derived Indole And Oxindole Alkaloids For Pain Management". Pharmaceuticals. 18 (2): 222. 10.3390/ph18020222.
DOI: https://doi.org/10.3390/ph18020222