An overview of betulin: botanical source, derivatives and biological potential: Mini Review
DOI:
https://doi.org/10.18006/2025.13(1).11.28Keywords:
Betulin, Botanical Sources, Derivatives, Biological activities, TriterpenoidAbstract
This review aims to provide insight into and summarize the potential of betulin and its derivatives as important pharmaceutical molecules, including their underlying mechanisms of action. This investigation compiles comprehensive scientific data regarding betulin as a botanical raw material for industrial and pharmaceutical applications. Betulin, a natural pentacyclic lupane-triterpenoid, exhibits diverse biological activities, addressing metabolic dysfunctions, infectious diseases, cardiovascular disorders, and carcinogenic activity. The extraction of betulin from natural sources, mainly birch bark, is relatively simple and cost-effective, making it an attractive compound for the pharmaceutical and cosmetic industries. This study lists 93 plant sources of betulin and explores its repurposing as an effective therapeutic agent. It highlights its potential as an antiviral, anti-inflammatory, anticancer, and hepatoprotective compound, emphasizing the benefits of derivatizing betulin with various groups or moieties, such as imidazole carboxylic ester, hemisuccinate, hemiphthalate, nicotinate, acetylbetulin-28-o-triphenylphosphonium, succinyl, and 3-substituted glutaryl. The information gathered comes from various sources, including plant databases, Google Scholar, PubMed, ethnobotanical references, and classical texts.
References
Abyshev, A. Z., Agaev, E. M., & Guseinov, A. B. (2007). Studies of the chemical composition of birch bark extracts (Cortex betula) from the Betulaceae family. Pharmaceutical Chemistry Journal, 41(8), 419-423. DOI: https://doi.org/10.1007/s11094-007-0091-5
Adepoju, F. O., Duru, K. C., Li, E., Kovaleva, E. G., & Tsurkan, M. V. (2023). Pharmacological potential of betulin as a multitarget compound. Biomolecules, 13(7), 1105. DOI: https://doi.org/10.3390/biom13071105
Aguiar, R. M., David, J. P., & David, J. M. (2005). Unusual naphthoquinones, catechin and triterpene from Byrsonima microphylla. Phytochemistry, 66(19), 2388-2392. DOI: https://doi.org/10.1016/j.phytochem.2005.07.011
Akihisa, T., Takamine, Y., Yoshizumi, K., Tokuda, H., Kimura, Y., et al. (2002). Microbial transformations of two lupane-type triterpenes and anti-tumor-promoting effects of the transformation products. Journal of natural products, 65(3), 278-282. DOI: https://doi.org/10.1021/np010424m
Alakurtti, S., Mäkelä, T., Koskimies, S., & Yli-Kauhaluoma, J. (2006). Pharmacological properties of the ubiquitous natural product betulin. European Journal of Pharmaceutical Sciences, 29(1), 1-13. DOI: https://doi.org/10.1016/j.ejps.2006.04.006
Amiri, S., Dastghaib, S., Ahmadi, M., Mehrbod, P., Khadem, F., Behrouj, H., & Ghavami, S. (2020). Betulin and its derivatives as novel compounds with different pharmacological effects. Biotechnology advances, 38, 107409. DOI: https://doi.org/10.1016/j.biotechadv.2019.06.008
Atkinson, M. D. (1992). Betula pendula Roth (B. verrucosa Ehrh.) and B. pubescens Ehrh. Journal of Ecology, 80(4), 837-870. DOI: https://doi.org/10.2307/2260870
Baratto, L. C., Porsani, M. V., Pimentel, I. C., Netto, A. B. P., Paschke, R., & Oliveira, B. H. (2013). Preparation of betulinic acid derivatives by chemical and biotransformation methods and determination of cytotoxicity against selected cancer cell lines. European journal of medicinal chemistry, 68, 121-131. DOI: https://doi.org/10.1016/j.ejmech.2013.07.012
Bebenek, E., Chodurek, E., Orchel, A., Dzierzewicz, Z., & Boryczka, S. (2015). Antiproliferative activity of novel acetylenic derivatives of betulin against G-361 human melanoma cells. Acta Poloniae Pharmaceutica, 72(4), 699-703.
Bębenek, E., Chrobak, E., Rzepka, Z., & Wrześniok, D. (2022). New Betulin Derivatives with Nitrogen Heterocyclic Moiety—Synthesis and Anticancer Activity In Vitro. Biomolecules, 12(10), 1540. DOI: https://doi.org/10.3390/biom12101540
Bergelin, E., & Holmbom, B. (2008). Reactions and distribution of birch extractives in kraft pulp oxygen delignification. Journal of Wood Chemistry and Technology, 28(4), 261-269. DOI: https://doi.org/10.1080/02773810802452600
Bhandari, P., Shrestha, K. K., Kunwar, R. M., Bussmann, R. W., & Paniagua-Zambrana, N. Y. (2020). Lyonia ovalifolia (Wall.) Drude Ericaceae. In: R. Kunwar, H. Sher, R.W. Bussmann (Eds.) Ethnobotany of the Himalayas. Ethnobotany of Mountain Regions (pp 1-8). Springer, Cham. https://doi.org/10.1007/978-3-030-45597-2_145-1 DOI: https://doi.org/10.1007/978-3-030-45597-2_145-1
Bhat, A. T., Prabhukumar, K. M., & Rana, T. S. (2024). Lectotypification of four names in the genus Gymnosporia (Celastraceae). Phytotaxa, 645(3), 286-293. DOI: https://doi.org/10.11646/phytotaxa.645.3.8
Blondeau, D., St‐Pierre, A., Bourdeau, N., Bley, J., Lajeunesse, A., & Desgagné‐Penix, I. (2020). Antimicrobial activity and chemical composition of white birch (Betula papyrifera Marshall) bark extracts. Microbiologyopen, 9(1), e00944. DOI: https://doi.org/10.1002/mbo3.944
Boparai, A., Niazi, J., Bajwa, N., & Singh, P. A. (2017). Betulin a pentacyclic tri–terpenoid: an hour to rethink the compound. Open Access Journal of Translational Medicine & Research, 1(2), 53-59. DOI: https://doi.org/10.15406/oajtmr.2017.01.00012
Boryczka, S., Bębenek, E., Wietrzyk, J., Kempińska, K., Jastrzębska, M., Kusz, J., & Nowak, M. (2013).Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin. Molecules, 18(4), 4526-4543. DOI: https://doi.org/10.3390/molecules18044526
Chen, H., Xiao, H., & Pang, J. (2020). Parameter optimization and potential bioactivity evaluation of a betulin extract from white birch bark. Plants, 9(3), 392. DOI: https://doi.org/10.3390/plants9030392
Chowdhury, S., Mukherjee, T., Chowdhury, S. R., Sengupta, S., Mukhopadhyay, S., Jaisankar, P., & Majumder, H. K. (2014). Disuccinyl betulin triggers metacaspase-dependent endonuclease G-mediated cell death in unicellular protozoan parasite Leishmania donovani. Antimicrobial agents and chemotherapy, 58(4), 2186-2201. DOI: https://doi.org/10.1128/AAC.02193-13
Chrobak, E., Jastrzębska, M., Bębenek, E., Kadela-Tomanek, M., Marciniec, K., et al. (2021). Molecular structure, in vitro anticancer study and molecular docking of new phosphate derivatives of betulin. Molecules, 26(3), 737. DOI: https://doi.org/10.3390/molecules26030737
Ci, X., Zhou, J., Lv, H., Yu, Q., Peng, L., & Hua, S. (2017). Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism. Cell death & disease, 8(5), e2798-e2798. DOI: https://doi.org/10.1038/cddis.2017.39
Cichewicz, R. H., & Kouzi, S. A. (2004).Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Medicinal research reviews, 24(1), 90-114. DOI: https://doi.org/10.1002/med.10053
Csuk, R., Barthel, A., Schwarz, S., Kommera, H., & Paschke, R. (2010). Synthesis and biological evaluation of antitumor-active γ-butyrolactone substituted betulin derivatives. Bioorganic & medicinal chemistry, 18(7), 2549-2558. DOI: https://doi.org/10.1016/j.bmc.2010.02.042
Csuk, R., Sczepek, R., Siewert, B., & Nitsche, C. (2013). Cytotoxic betulin-derived hydroxypropargylamines trigger apoptosis. Bioorganic & medicinal chemistry, 21(2), 425-435. DOI: https://doi.org/10.1016/j.bmc.2012.11.016
de Figueiredo, P. T. R., Duarte, M. C., Cordeiro, L. V., de Menezes, R. P. B., Lima, E. D. O., et al. (2024). Sesquiterpenes alkaloids from Maytenus distichophylla (Celastraceae). Quimica nova, 47(4),e-20230123. DOI: https://doi.org/10.21577/0100-4042.20230123
Desta, G. T., Ferede, Y. A., Zewdu, W. S., Adugna, B. Y., Arega, T., & Alemu, M. A. (2022). Validation of Antidiabetic and Antihyperlipidemic Effects of 80% Methanolic Extract of the Lonchocarpus laxiflorusLeaves in Streptozotocin‐Induced Diabetic Swiss Albino Mice. Evidence‐Based Complementary and Alternative Medicine, 2022(1), 8411851. DOI: https://doi.org/10.1155/2022/8411851
Dhadse, P., & Saxena, J. (2024). Formulation and Evaluation of Phytosomes of Pterocarpus santalinus Extract. International Journal for Research in Applied Science and Engineering Technology, 12, 450-457. DOI: https://doi.org/10.22214/ijraset.2024.57964
Drąg-Zalesińska, M., Drąg, M., Poręba, M., Borska, S., Kulbacka, J., & Saczko, J. (2017). Anticancer properties of ester derivatives of betulin in human metastatic melanoma cells (Me-45). Cancer Cell International, 17, 1-7. DOI: https://doi.org/10.1186/s12935-016-0369-3
Eberle, L. V., Tsisak, A. О., Radaieva, I. M., & Kazantseva, А. S. (2023). Analysis of phenolic compounds in black walnut (Juglans nigra L.) fruit extract using high-performance liquid chromatography. Farmatsevtychnyizhurnal, (2), 49-57. DOI: https://doi.org/10.32352/0367-3057.2.23.06
Fujun, M. A., Qiujun, W., Junling, D. O. N. G., Yi, Y., Wenjia, W., Defei, Y., & Bainian, S. (2015). Buxus leaves from the Oligocene of Guangxi, China and their biogeographical significance. Acta Geologica Sinica‐English Edition, 89(5), 1453-1469. DOI: https://doi.org/10.1111/1755-6724.12557
Fulda, S. (2008). Betulinic acid for cancer treatment and prevention. International journal of molecular sciences, 9(6), 1096-1107. DOI: https://doi.org/10.3390/ijms9061096
George, S., Duraisamy, M., Venugopalan, R., & Kalaiselvan, D. (2023).Neuroprotective Effect of Mallotusphilippensis Extract in Streptozotocin Induced Diabetic Neuropathy in Rats. Research Journal of Pharmacy and Technology, 16(10), 4649-4657. DOI: https://doi.org/10.52711/0974-360X.2023.00756
Ghaffari Moghaddam, M., Ahmad, B. H., & Samzadeh-Kermani, A. (2012). Biological activity of betulinic acid: a review. Pharmacology & Pharmacy, 3(02), 119-123. DOI: https://doi.org/10.4236/pp.2012.32018
Grishko, V. V., Tolmacheva, I. A., Nebogatikov, V. O., Galaiko, N. V., Nazarov, A. V., Dmitriev, M. V., & Ivshina, I. B. (2017). Preparation of novel ring-A fused azole derivatives of betulin and evaluation of their cytotoxicity. European Journal of Medicinal Chemistry, 125, 629-639. DOI: https://doi.org/10.1016/j.ejmech.2016.09.065
Grymel, M., Pastuch-Gawołek, G., Lalik, A., Zawojak, M., Boczek, S., Krawczyk, M., & Erfurt, K. (2020). Glycoconjugation of betulin derivatives using copper-catalyzed 1, 3-dipolar azido-alkyne cycloaddition reaction and a preliminary assay of cytotoxicity of the obtained compounds. Molecules, 25(24), 6019. DOI: https://doi.org/10.3390/molecules25246019
Guo, N., Chen, Z., Cao, S. Q., & Shang, F. D. (2024). Sophora japonica L. bioactives: Chemistry, sources, and processing techniques. Food Frontiers, 5(3), 1166-1187. DOI: https://doi.org/10.1002/fft2.367
Gupta, M., Mazumder, U. K., Siva, K. T., Gomathi, P., & Sambath, K. R. (2004). Antioxidant and hepatoprotective effects of Bauhinia racemosa against paracetamol and carbon tetrachloride induced liver damageinrats. Iranian Journal of Pharmacology and Therapeutics, 3, 12-20.
Gupta, P. C., Sharma, N., & Rao, C. V. (2012). Pharmacognostic studies of the leaves and stem of Careyaarborea Roxb. Asian Pacific journal of tropical biomedicine, 2(5), 404-408. DOI: https://doi.org/10.1016/S2221-1691(12)60065-3
Hayek, E. W., Jordis, U., Moche, W., & Sauter, F. (1989). A bicentennial of betulin. Phytochemistry, 28(9), 2229-2242. DOI: https://doi.org/10.1016/S0031-9422(00)97961-5
He, P., Hua, H., Tian, W., Zhu, H., Liu, Y., & Xu, X. (2020). Holly (Ilex latifolia Thunb.) polyphenols extracts alleviate hepatic damage by regulating ferroptosis following diquat challenge in a piglet model. Frontiers in Nutrition, 7, 604328. DOI: https://doi.org/10.3389/fnut.2020.604328
Holonec, L., Ranga, F., Crainic, D., Truta, A., & Socaciu, C. (2012).Evaluation of betulin and betulinic acid content in birch bark from different forestry areas of Western Carpathians. NotulaeBotanicaeHortiAgrobotanici Cluj-Napoca, 40(2), 99-105. DOI: https://doi.org/10.15835/nbha4027967
Hossain, M. H., Hassan, M. M., Jahan, I. A., Nimmi, I., & Islam, A. (2012).Antidiarrhoeal activity, nitric oxide scavenging and total tannin content from the bark of Ceriops decandra (griff.) Ding hou. International Journal of Pharmaceutical Sciences and Research, 3, 1306-1311.
Hu, J., Herbohn, J., Chazdon, R. L., Baynes, J., & Vanclay, J. K. (2020). Long-term growth responses of three Flindersia species to different thinning intensities after selective logging of a tropical rainforest. Forest Ecology and Management, 476, 118442. DOI: https://doi.org/10.1016/j.foreco.2020.118442
Hu, S. Y. (1949). The genus Ilex in China. Journal of the Arnold Arboretum, 30(3), 233-344. DOI: https://doi.org/10.5962/bhl.part.18050
Huang, H. C., Shen, C. C., Chen, C. F., Wu, Y. C., & Kuo, Y. H. (2000). A novel agarofuran sesquiterpene, celahin D from Celastrus hindsiiBenth. Chemical and pharmaceutical bulletin, 48(7), 1079-1080. DOI: https://doi.org/10.1248/cpb.48.1079
Hwang, B. Y., Chai, H. B., Kardono, L. B., Riswan, S., Farnsworth, N. R., et al. (2003). Cytotoxic triterpenes from the twigs of Celtis philippinensis. Phytochemistry, 62(2), 197-201. DOI: https://doi.org/10.1016/S0031-9422(02)00520-4
Induja, M. S., Anuradha, A., Mulasseri, S., Jadav, R., Aneaus, S., Karthic, A., &Arjumand, T. (2024). Oleander Leaf: Fatal poisoning in children. Current Science (00113891), 126(2).
Jäger, S., Winkler, K., Pfüller, U., & Scheffler, A. (2007). Solubility studies of oleanolic acid and betulinic acid in aqueous solutions and plant extracts of Viscum album L. Planta medica, 73(02), 157-162. DOI: https://doi.org/10.1055/s-2007-967106
Jia, L. I., Xiao, M. E. N. G., Chengyue, Y. I. N., Zhang, L., Bin, L. I. N., et al. (2023). Antimalarial and neuroprotectiveent-abietanediterpenoids from the aerial parts of Phlogacanthus curviflorus. Chinese Journal of Natural Medicines, 21(8), 619-630. DOI: https://doi.org/10.1016/S1875-5364(23)60464-9
Kaingu, C. K., Oduma, J. A., & Kanui, T. (2012). Preliminary investigation of contractile activity of Ricinus communis and Euclea divinorum extracts on isolated rabbit uterine strips. Journal of ethnopharmacology, 142(2), 496-502. DOI: https://doi.org/10.1016/j.jep.2012.05.026
Kamagaté, M., Koffi, C., Kouamé, N. M., Akoubet, A., Alain, N., Yao, R., & Die, H. (2014). Ethnobotany, phytochemistry, pharmacology and toxicology profiles of Cassia siamea Lam. The Journal of Phytopharmacology, 3(1), 57-76. DOI: https://doi.org/10.31254/phyto.2014.3109
Kaur, P., Arora, S., & Singh, R. (2022). Isolation, characterization and biological activities of betulin from Acacia nilotica bark. Scientific Reports, 12(1), 9370. DOI: https://doi.org/10.1038/s41598-022-13338-3
Khusnutdinova, E. F., Petrova, A. V., Apryshko, G. N., Kukovinets, O. S., & Kazakova, O. B. (2018). Synthesis and cytotoxicity of indole derivatives of betulin, erythrodiol, and uvaol. Russian Journal of Bioorganic Chemistry, 44, 322-329. DOI: https://doi.org/10.1134/S1068162018030081
Kislitsyn, A. N. (1994). Ekstraktivnyeveshchestvaberesty: vydelenie, sostav, svoistva, primenenie [Birch bark extractives: isolation, composition, properties, application]. Khimiiadrevesiny—Wood chemistry, 3, 3-28.
Kommera, H., Kaluđerović, G. N., Bette, M., Kalbitz, J., Fuchs, P., et al. (2010). In vitro anticancer studies of α-and β-d-glucopyranose betulin anomers. Chemico-biological interactions, 185(2), 128-136. DOI: https://doi.org/10.1016/j.cbi.2010.02.038
Krasutsky, P. A. (2006). Birch bark research and development. Natural Product Reports, 23(6), 919-942. DOI: https://doi.org/10.1039/b606816b
Krol, S. K., Bębenek, E., Sławińska-Brych, A., Dmoszyńska-Graniczka, M., Boryczka, S., & Stepulak, A. (2020). Synthetic betulin derivatives inhibit growth of glioma cells in vitro. Anticancer Research, 40(11), 6151-6158. DOI: https://doi.org/10.21873/anticanres.14635
Kubba, A., Tillequin, F., Koch, M., Litaudon, M., & Deguin, B. (2005). Iridoids, lignan, and triterpenes from Osmanthuscymosus. Biochemical systematics and ecology, 33(3), 305-307. DOI: https://doi.org/10.1016/j.bse.2004.06.008
Laavola, M., Haavikko, R., Hämäläinen, M., Leppänen, T., Nieminen, R., et al. (2016). Betulin derivatives effectively suppress inflammation in vitro and in vivo. Journal of natural products, 79(2), 274-280. DOI: https://doi.org/10.1021/acs.jnatprod.5b00709
Laiolo, J., Graikioti, D. G., Barbieri, C. L., Joray, M. B., Antoniou, A. I., et al. (2024). Novel betulin derivatives as multidrug reversal agents targeting P-glycoprotein. Scientific Reports, 14(1), 70. DOI: https://doi.org/10.1038/s41598-023-49939-9
Lall, N., Weiganand, O., Hussein, A. A., & Meyer, J. J. M. (2006). Antifungal activity of naphthoquinones and triterpenes isolated from the root bark of Eucleanatalensis. South African Journal of Botany, 72(4), 579-583. DOI: https://doi.org/10.1016/j.sajb.2006.03.005
Lee, S. J., Hossaine, M. A., & Park, S. C. (2016). A potential anti-inflammation activity and depigmentation effect of Lespedeza bicolor extract and its fractions. Saudi Journal of Biological Sciences, 23(1), 9-14. DOI: https://doi.org/10.1016/j.sjbs.2015.01.016
Lesellier, E., Destandau, E., Grigoras, C., Fougère, L., & Elfakir, C. (2012). Fast separation of triterpenoids by supercritical fluid chromatography/evaporative light scattering detector. Journal of Chromatography A, 1268, 157-165. DOI: https://doi.org/10.1016/j.chroma.2012.09.102
Li, Y., Liu, X., Jiang, D., Lin, Y., Wang, Y., et al. (2016). Betulin induces reactive oxygen species-dependent apoptosis in human gastric cancer SGC7901 cells. Archives of pharmacal research, 39, 1257-1265. DOI: https://doi.org/10.1007/s12272-016-0761-5
Lin, H., Jiang, X., Qian, C., Zhang, Y., Meng, X., et al. (2024). Genome-Wide Identification, Characterization, and Expression Analysis of the HD-Zip Gene Family in Lagerstroemia for Regulating Plant Height. Genes, 15(4), 428. DOI: https://doi.org/10.3390/genes15040428
Linde, H. H. (1965). Die alkaloide aus Melodinus australis (F. MUELLER) PIERRE (Apocynaceae). Helvetica Chimica Acta, 48(8), 1822-1842. DOI: https://doi.org/10.1002/hlca.19650480803
Ma, W., Lv, C., Jiang, D., Kang, C., & Zhao, D. (2020). The complete chloroplast genome sequence of Euphorbia lathyris L.(Euphorbiaceae). Mitochondrial DNA Part B, 5(3), 3660-3662. DOI: https://doi.org/10.1080/23802359.2020.1832601
Magid, A.A., Voutquenne-Nazabadioko, L., Bontemps, G., Litaudon, M., Lavaud, C. (2008). Tyrosinase inhibitors and sesquiterpene diglycosides from Guioa villosa. Planta Medica, 74(1), 55-60. DOI: https://doi.org/10.1055/s-2007-993780
Mahajan, G., & Chauhan, B. S. (2024).Novel use pattern of pendimethalin for annual ryegrass (Lolium rigidum Gaudin) control in wheat and barley. Frontiers in Agronomy, 5, 1341880. DOI: https://doi.org/10.3389/fagro.2023.1341880
Manzoor, M. A., Xu, Y., Lv, Z., Xu, J., Wang, Y., et al. (2024). Comparative genomics of N-acetyl-5-methoxytryptamine members in four Prunus species with insights into bud dormancy and abiotic stress responses in Prunus avium. Plant Cell Reports, 43(4), 89. DOI: https://doi.org/10.1007/s00299-024-03184-0
Melani, I. R., Wafi, M. F., Riandinata, M. R., Halim, P. A. R., Muti'ah, R., & Santosaningsih, D. (2023). Potential Inhibition of Melaleuca leucadendron L. Compounds Against the NSP5 SARS CoV-2 Protein. Indonesian Journal of Cancer Chemoprevention, 13(3), 195-206. DOI: https://doi.org/10.14499/indonesianjcanchemoprev13iss3pp195-206
Mhamdi, S., Yahia, K.B., Montpied, P., Brendel, O., & Dreyer, E. (2023).Inter-specific differences in architectural and morphological traits on seedlings of cork oak (Quercus suber L.), zeen oak (Quercus canariensis Willd.) and their hybrid Afares oak (Quercus afares Pomel) growing in the greenhouse. IOBC-WPRS Bulletin, 168, 49-54.
Mishra, S. N., Tomar, P. C., & Lakra, N. (2007).Medicinal and food value of Capparis—a harsh terrain plant. The Indian Journal of Traditional Knowledge, 6(1), 230-238.
Ning, K. Q., Meng, D. L., Lou, L. L., & Li, X. (2013). Chemical constituents from the Jasminum lanceolarium Roxb. Biochemical Systematics and Ecology, 51, 297-300. DOI: https://doi.org/10.1016/j.bse.2013.09.016
Orchel, A., Chodurek, E., Jaworska-Kik, M., Paduszyński, P., Kaps, A., et al. (2021). Anticancer activity of the acetylenic derivative of betulin phosphate involves induction of necrotic-like death in breast cancer cells in vitro. Molecules, 26(3), 615. DOI: https://doi.org/10.3390/molecules26030615
Orzalesi, G., Mezzetti, T., Rossi, C., & Bellavita, V. (1970). Pentacyclic triterpenoids from Euclea kellau. Plantamedica, 18(05), 30-36. DOI: https://doi.org/10.1055/s-0028-1099801
Öz, U. (2021). Anatomy of Carlina corymbosa L., Carthamus dentatus Vahl. And Picnomon acarna (L.) Cass.(Asteraceae). Celal Bayar University Journal of Science, 17(2), 215-222. DOI: https://doi.org/10.18466/cbayarfbe.785328
Peraza-Sánchez, S. R., Poot-Kantún, S., Toores-Tapia, L. W., May-Pat, F., Simá-Polanco, P., & Cedillo-Rivera, R. (2005). Screening of Native Plants from Yucatan for Anti–Giardia lamblia Activity. Pharmaceutical biology, 43(7), 594-598. DOI: https://doi.org/10.1080/13880200500301720
Pratima, H., Shiraguppi, A., Joojagar, P., Shah, K., Cheeraladinni, S. S., et al. (2024). Phytochemical profile and hepatoprotective potentiality of Phyllanthus genus: a review. Journal of Pharmacy and Pharmacology, 77(2):189-205. DOI: https://doi.org/10.1093/jpp/rgae040
Rastogi, S., Pandey, M. M., & Rawat, A. K. S. (2015). Medicinal plants of the genus Betula—Traditional uses and a phytochemical–pharmacological review. Journal of ethnopharmacology, 159, 62-83. DOI: https://doi.org/10.1016/j.jep.2014.11.010
Rorato, D., Araujo, M., Dutra, A., Turchetto, F., Tabaldi, L., & Mieth, P. (2018).Seed analysis and seedling production of Matayba elaeagnoides Radlk. Floresta e Ambiente, 25, e20160043. DOI: https://doi.org/10.1590/2179-8087.004316
Rzepka, Z., Bębenek, E., Chrobak, E., & Wrześniok, D. (2022).Synthesis and anticancer activity of indole-functionalized derivatives of betulin. Pharmaceutics, 14(11), 2372. DOI: https://doi.org/10.3390/pharmaceutics14112372
Sajini, R. J., & Chamundeeswari, D. (2023).Ixoraspecies: A Review on chemical constituents and Pharmacological activities. Latin American Journal of Pharmacy: A Life Science Journal, 42(3), 1000-1024.
Saleem, H., Htar, T. T., Naidu, R., Zengin, G., Locatelli, M., Tartaglia, A., & Ahemad, N. (2020). Phytochemical composition and enzyme inhibition studies of Buxus papillosa CK Schneid. Processes, 8(7), 757. DOI: https://doi.org/10.3390/pr8070757
Salin, O., Alakurtti, S., Pohjala, L., Siiskonen, A., Maass, V., Maass, M., &Vuorela, P. (2010). Inhibitory effect of the natural product betulin and its derivatives against the intracellular bacterium Chlamydia pneumoniae. Biochemical pharmacology, 80(8), 1141-1151. DOI: https://doi.org/10.1016/j.bcp.2010.06.051
Santos, R. C., Salvador, J. A., Marín, S., Cascante, M., Moreira, J. N., & Dinis, T. C. (2010). Synthesis and structure–activity relationship study of novel cytotoxic carbamate and N-acylheterocyclic bearing derivatives of betulin and betulinic acid. Bioorganic & medicinal chemistry, 18(12), 4385-4396. DOI: https://doi.org/10.1016/j.bmc.2010.04.085
Sharma, M., Chopra, S., & Prasad, S. B. (2015). Guazuma tomentosa: A valuable medicinal plant. International Journal of Pharmacognosy and Phytochemical Research, 7(1), 197-200.
Shen, C. C., Ni, C. L., Huang, Y. L., Huang, R. L., & Chen, C. C. (2004). Furanolabdane Diterpenes from Hypoestes purpurea. Journal of natural products, 67(11), 1947-1949. DOI: https://doi.org/10.1021/np0497402
Šiman, P., Filipová, A., Tichá, A., Niang, M., Bezrouk, A., & Havelek, R. (2016). Effective method of purification of betulin from birch bark: The importance of its purity for scientific and medicinal use. PloS one, 11(5), e0154933. DOI: https://doi.org/10.1371/journal.pone.0154933
Singh, P. A., Brindavanam, N. B., Kimothi, G. P., Verma, R., & Aeri, V. (2016).A validated HPLC method for the determination of betulin in the stem bark of Tectona grandis Linn. International Journal of Pharmaceutical Sciences and Research, 7(2), 719.
So, H. M., Eom, H. J., Lee, D., Kim, S., Kang, K. S., et al. (2018). Bioactivity evaluations of betulin identified from the bark of Betula platyphylla var. japonica for cancer therapy. Archives of pharmacal research, 41, 815-822. DOI: https://doi.org/10.1007/s12272-018-1064-9
Şoica, C. M., Dehelean, C. A., Peev, C., Aluas, M., Zupkó, I., KásaJr, P., &Alexa, E. (2012). Physico-chemical comparison of betulinic acid, betulin and birch bark extract and in vitro investigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell lines. Natural product research, 26(10), 968-974. DOI: https://doi.org/10.1080/14786419.2010.545352
Spivak, A. Y., Keiser, J., Vargas, M., Gubaidullin, R. R., Nedopekina, D. A., Shakurova, E. R., & Odinokov, V. N. (2014). Synthesis and activity of new triphenylphosphonium derivatives of betulin and betulinic acid against Schistosoma mansoni in vitro and in vivo. Bioorganic & medicinal chemistry, 22(21), 6297-6304. DOI: https://doi.org/10.1016/j.bmc.2014.07.014
Stöcklin, W., De Silva, L.B., Geissman, T.A.(1969). Constituents of Holacanthaemoryi. Phytochemistry, 8(8),1565-9. DOI: https://doi.org/10.1016/S0031-9422(00)85931-2
Szakiel, A., Paczkowski, C., & Huttunen, S. (2012).Triterpenoid content of berries and leaves of bilberry Vaccinium myrtillus from Finland and Poland. Journal of Agricultural and Food Chemistry, 60(48),11839-49. DOI: https://doi.org/10.1021/jf3046895
Szlasa, W., Ślusarczyk, S., Nawrot-Hadzik, I., Abel, R., Zalesińska, A., et al. (2023). Betulin and its derivatives reduce inflammation and COX-2 activity in macrophages. Inflammation, 46(2), 573-583. DOI: https://doi.org/10.1007/s10753-022-01756-4
Szuster-Ciesielska, A., Plewka, K., Daniluk, J., & Kandefer-Szerszeń, M. (2011). Betulin and betulinic acid attenuate ethanol-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS), cytokine (TNF-α, TGF-β) production and by influencing intracellular signaling. Toxicology, 280(3), 152-163. DOI: https://doi.org/10.1016/j.tox.2010.12.006
Takibayeva, A. T., Zhumabayeva, G. K., Bakibaev, A. A., Demets, O. V., Lyapunova, M. V., et al. (2023). Methods of analysis and identification of betulin and its derivatives. Molecules, 28(16), 5946. DOI: https://doi.org/10.3390/molecules28165946
Tang, J., Jones, S. A., Jeffery, J. L., Miranda, S. R., Galardi, C. M., et al. (2014). Synthesis and biological evaluation of macrocyclized betulin derivatives as a novel class of anti-HIV-1 maturation inhibitors. The Open Medicinal Chemistry Journal, 8, 23. DOI: https://doi.org/10.2174/1874104501408010023
Tang, J., Zou, R., Wei, X., & Li, D. (2023). Complete chloroplast genome sequences of five Ormosia Species: Molecular structure, comparative analysis, and phylogenetic analysis. Horticulturae, 9(7), 796. DOI: https://doi.org/10.3390/horticulturae9070796
Tchatchoua, D. T., & Aravanopoulos, F. A. (2015). Selection strategy for Chestnut (Castanea sativa Mill.) families originating from contrasting European populations. Open Journal of Forestry, 5(05), 489. DOI: https://doi.org/10.4236/ojf.2015.55042
Tolstikov, G. A., Flekhter, O. B., Shultz, E. E., Baltina, L. A., & Tolstikov, A. G. (2005). Betulin and its derivatives: Chemistry and biological activity. Chemistry for sustainable development, 13(1), 1-29.
Tsepaeva, O. V., Nemtarev, A. V., Abdullin, T. I., Grigor’eva, L. R., Kuznetsova, E. V., et al. (2017). Design, synthesis, and cancer cell growth inhibitory activity of triphenylphosphonium derivatives of the triterpenoid betulin. Journal of natural products, 80(8), 2232-2239. DOI: https://doi.org/10.1021/acs.jnatprod.7b00105
Tykheev, Z. A., Anenkhonov, O. A., Zhigzhitzhapova, S. V., Taraskin, V. V., Radnaeva, L. D., & Zhang, F. (2020). Do Compositions of Lipid Fraction Correspond to Species Differentiation in Bupleurum L.(Apiaceae)?. Plants, 9(11), 1407. DOI: https://doi.org/10.3390/plants9111407
Ur’yash, V. F., Kokurina, N. Y., Larina, V. N., Kashtanov, E. A., & Gruzdeva, A. E. (2014). Physicochemical properties of Betulin and CO 2 extract from birch bark. Russian Journal of Physical Chemistry B, 8, 1100-1109. DOI: https://doi.org/10.1134/S1990793114080181
Veloso, C. C., Bitencourt, A. D., Cabral, L. D., Franqui, L. S., Dias, D. F., et al. (2010). Pyrostegia venusta attenuate the sickness behavior induced by lipopolysaccharide in mice. Journal of Ethnopharmacology, 132(1), 355-358. DOI: https://doi.org/10.1016/j.jep.2010.07.053
Vieira, S. F., Ferreira, H., & Neves, N. M. (2020). Antioxidant and anti-inflammatory activities of cytocompatible Salvia officinalis extracts: A comparison between traditional and Soxhlet extraction. Antioxidants, 9(11), 1157. DOI: https://doi.org/10.3390/antiox9111157
Wang, J., Wu, J., Han, Y., Zhang, J., Lin, Y., et al. (2022). Synthesis and biological evaluation of novel betulin derivatives with aromatic hydrazone side chain as potential anticancer agents. Journal of the Brazilian Chemical Society, 33(03), 227-237. DOI: https://doi.org/10.21577/0103-5053.20210140
White, J. F., & Bernstein, D. I. (2003). Key pollen allergens in North America. Annals of Allergy, Asthma & Immunology, 91(5), 425-435. DOI: https://doi.org/10.1016/S1081-1206(10)61509-8
Wirtu, S. F., Mishra, A. K., Jule, L. T., & Ramaswamy, K. (2024). Ocimum basilicum and Ocimum americanum: A Systematic Literature Review on Chemical Compositions and Antimicrobial Properties. Natural Product Communications, 19(4), 1934578X241247640. DOI: https://doi.org/10.1177/1934578X241247640
Wu, J., Wang, J., Han, Y., Lin, Y., Wang, J., & Bu, M. (2021).Synthesis and cytotoxic activity of novel betulin derivatives containing hydrazide-hydrazone moieties. Natural Product Communications, 16(10), 1934578X211055345. DOI: https://doi.org/10.1177/1934578X211055345
Wu, Q., Li, H., Qiu, J., & Feng, H. (2014). Betulin protects mice from bacterial pneumonia and acute lung injury. Microbial pathogenesis, 75, 21-28. DOI: https://doi.org/10.1016/j.micpath.2014.08.005
Xiong, J., Kashiwada, Y., Chen, C. H., Qian, K., Morris-Natschke, S. L., Lee, K. H., &Takaishi, Y. (2010). Conjugates of betulin derivatives with AZT as potent anti-HIV agents. Bioorganic & medicinal chemistry, 18(17), 6451-6469. DOI: https://doi.org/10.1016/j.bmc.2010.06.092
Ye, Z., Zhang, H., Lin, X., Huang, S., Zou, S., & Zou, X. (2024). Effect of Biochar Using N, P, and K Fertilisers on Growth and Quality of Lithocarpus litseifolius. Agronomy, 14(4), 728. DOI: https://doi.org/10.3390/agronomy14040728
Zhang, H., Ding, J., Holstein, N., & Wang, N. (2023). Betula mcallisteri sp. nov.(sect. Acuminatae, Betulaceae), a new diploid species overlooked in the wild and in cultivation, and its relation to the widespread B. luminifera. Frontiers in Plant Science, 14, 1113274. DOI: https://doi.org/10.3389/fpls.2023.1113274
Zhang, L., Ma, Z., Wang, R., & Zhu, M. (2021).Synthesis and characterization of methacrylate-functionalized betulin derivatives as antibacterial comonomer for dental restorative resins. ACS Biomaterials Science & Engineering, 7(7), 3132-3140. DOI: https://doi.org/10.1021/acsbiomaterials.1c00563
Zhang, L., Mao, R., Bi, H., Shen, J., Wang, Y., & Li, M. (2020).Characterization of the complete chloroplast genome of Hoveniaacerba (Rhamnaceae). Mitochondrial DNA Part B, 5(1), 934-935. DOI: https://doi.org/10.1080/23802359.2020.1714492
Zhou, Z., Zhu, C., Cai, Z., He, L., Zhao, F., Lou, X., & Qi, X. (2018). Betulin induces cytochrome c release and apoptosis in colon cancer cells via NOXA. Oncology letters, 15(5), 7319-7327. DOI: https://doi.org/10.3892/ol.2018.8183
Zhu, H. (2002). A revision of the genus Lasianthus (Rubiaceae) from China. Systematics and Geography of Plants, 72(2)63-110.
Zia-Ul-Haq, M., Stanković, M. S., Rizwan, K., & De Feo, V. (2013).Grewiaasiatica L., a food plant with multiple uses. Molecules, 18(3), 2663-2682. DOI: https://doi.org/10.3390/molecules18032663
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