ABSTRACT:
Boswellia serrata, a prominent medicinal plant in traditional Ayurvedic medicine, has garnered significant attention for its potential antiangiogenic properties. Angiogenesis, the formation of new blood vessels, is a critical process in various biological functions and diseases. Dysregulated angiogenesis is a key factor in conditions such as cancer, inflammatory diseases, diabetic retinopathy, and cardiovascular disorders. This review comprehensively examines the phytochemical composition, pharmacokinetics, and mechanisms underlying the antiangiogenic effects of Boswellia serrata extracts, particularly focusing on its primary bioactive constituents, boswellic acids. These acids, especially 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-beta-boswellic acid (KBA) exhibit potent inhibitory effects on angiogenesis and inflammation by targeting key enzymes and signaling pathways. The review highlights these findings, emphasizing the promise of Boswellia serrata extracts as natural therapeutic agents that could complement or even provide alternatives to conventional therapies for angiogenesis-related diseases. These extracts offer a potentially safer and more accessible option for improving patient outcomes, particularly in conditions where excessive angiogenesis is a driving factor.
Cite this article:
Jyoti Kumari, M P Chopra. A Review of Phytochemical and Antiangiogenesis Activity of Boswellia Serrata Extract. Research Journal of Pharmacy and Technology. 2025;18(6):2890-2. doi: 10.52711/0974-360X.2025.00416
Cite(Electronic):
Jyoti Kumari, M P Chopra. A Review of Phytochemical and Antiangiogenesis Activity of Boswellia Serrata Extract. Research Journal of Pharmacy and Technology. 2025;18(6):2890-2. doi: 10.52711/0974-360X.2025.00416 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-6-69
REFERENCES:
1. M.K. Kakkar, S. Singh, T. Behl, S. Singh, N. Sharma, Hema, M. Sachdeva, Update on the role of Angiogenesis in Diabetes associated Nephropathy, Res J Pharm Technol (2021). https://api.semanticscholar.org/CorpusID:237670575.
2. A.C. Dudley, A.W. Griffioen, Pathological angiogenesis: mechanisms and therapeutic strategies., Angiogenesis 26 (2023) 313–347. https://doi.org/10.1007/s10456-023-09876-7.
3. J. Tímár, S. Paku, J. Tóvári, B. Döme, [Rationale of antiangiogenic therapy]., Magy Onkol 50 (2006) 141–151.
4. M.P. Vinod, M.Kr. Singh, M. Pradhan, S.Kr. Iyer, D.K. Tripathi, Phytochemical constituents and pharmacological activities of Betula alba Linn. - a review., Int J Pharmtech Res 4 (2012) 643–647. https://api.semanticscholar.org/CorpusID:83642457.
5. R. Narasimhan, M. Sathiyamoorthy, Phytochemical Screening and Antioxidant Studies in the Pulp Extracts of Cucurbita maxima, Asian Journal of Pharmaceutical Research 6 (2016) 1–4. https://api.semanticscholar.org/CorpusID:90721737.
6. K. Yadav, D. Singh, M.R. Singh, Development and characterization of corticosteroid loaded lipid carrier system for psoriasis, Res J Pharm Technol 14 (2021) 966–970. https://doi.org/10.5958/0974-360X.2021.00172.4.
7. D. Singh, M. Pradhan, S. Shrivastava, S.N. Murthy, M.R. Singh, Chapter 11 - Skin autoimmune disorders: lipid biopolymers and colloidal delivery systems for topical delivery, in: A.M.B.T.-N. in G.F. and C. Grumezescu (Ed.), William Andrew Publishing, 2016: pp. 257–296. https://doi.org/https://doi.org/10.1016/B978-0-323-42868-2.00011-5.
8. Z. Hoseinkhani, F. Norooznezhad, M. Rastegari-Pouyani, K. Mansouri, Medicinal Plants Extracts with Antiangiogenic Activity: Where Is the Link?, Adv Pharm Bull 10 (2020) 370–378. https://doi.org/10.34172/apb.2020.045.
9. F. Iram, S.A. Khan, A. Husain, Phytochemistry and potential therapeutic actions of Boswellic acids: A mini-review, Asian Pac J Trop Biomed 7 (2017) 513–523. https://doi.org/https://doi.org/10.1016/j.apjtb.2017.05.001.
10. R. Ramasubramaniaraja, Pharmacognostical Phytochemical Including GC-MS Investigation of Ethanolic Leaf Extracts of Abutilon indicum (Linn), Asian Journal of Pharmaceutical Analysis 1 (2011) 88–92. https://api.semanticscholar.org/CorpusID:85639171.
11. Y. Qurishi, A. Hamid, P.R. Sharma, Z.A. Wani, D.M. Mondhe, S.K. Singh, M.A. Zargar, S.S. Andotra, B.A. Shah, S.C. Taneja, A.K. Saxena, PARP cleavage and perturbance in mitochondrial membrane potential by 3-α-propionyloxy-β-boswellic acid results in cancer cell death and tumor regression in murine models., Future Oncol 8 (2012) 867–881. https://doi.org/10.2217/fon.12.68.
12. M.Z. Siddiqui, Boswellia serrata, a potential antiinflammatory agent: an overview., Indian J Pharm Sci 73 (2011) 255–261. https://doi.org/10.4103/0250-474X.93507.
13. D. Kosolapov, P. Jáč, P. Riasová, J. Poušková, M. Polášek, L. Nováková, Advances and Challenges in the Analysis of Boswellic Acids by Separation Methods, Crit Rev Anal Chem (2024). https://doi.org/10.1080/10408347.2024.2312502.
14. E.A. Ragab, M.F. Abd El-Wahab, A.S. Doghish, R.M. Salama, N. Eissa, S.F. Darwish, The journey of boswellic acids from synthesis to pharmacological activities, Naunyn Schmiedebergs Arch Pharmacol 397 (2024) 1477–1504. https://doi.org/10.1007/s00210-023-02725-w.
15. M.K. Senghani, P.M. Patel, Pharmacognostic and Phytochemical Study of Oleo Gum Resin from Boswellia serrata, Research Journal of Pharmacognosy and Phytochemistry 5 (2013) 244–250. https://api.semanticscholar.org/CorpusID:73741697.
16. J. Liu, X. Yin, C. Kou, R. Thimmappa, X. Hua, Z. Xue, Classification, biosynthesis, and biological functions of triterpene esters in plants, Plant Commun 5 (2024) 100845. https://doi.org/https://doi.org/10.1016/j.xplc.2024.100845.
17. N.K. Roy, D. Parama, K. Banik, D. Bordoloi, A.K. Devi, K.K. Thakur, G. Padmavathi, M. Shakibaei, L. Fan, G. Sethi, A.B. Kunnumakkara, An Update on Pharmacological Potential of Boswellic Acids against Chronic Diseases., Int J Mol Sci 20 (2019). https://doi.org/10.3390/ijms20174101.
18. D. Obiștioiu, A. Hulea, I. Cocan, E. Alexa, M. Negrea, I. Popescu, V. Herman, I.M. Imbrea, G. Heghedus-Mindru, M.A. Suleiman, I. Radulov, F. Imbrea, Boswellia Essential Oil: Natural Antioxidant as an Effective Antimicrobial and Anti-Inflammatory Agent., Antioxidants (Basel) 12 (2023). https://doi.org/10.3390/antiox12101807.
19. U. Siemoneit, L. Tausch, D. Poeckel, M. Paul, H. Northoff, A. Koeberle, J. Jauch, O. Werz, Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts., Planta Med 83 (2017) 1020–1027. https://doi.org/10.1055/s-0043-107884.
20. G. Mannino, A. Occhipinti, M.E. Maffei, Quantitative Determination of 3-O-Acetyl-11-Keto-βBoswellic Acid (AKBA) and Other Boswellic Acids in Boswellia sacra Flueck (syn. B. carteri Birdw) and Boswellia serrata Roxb., Molecules 21 (2016). https://doi.org/10.3390/molecules21101329.
21. A. Giacosa, A. Riva, G. Petrangolini, P. Allegrini, T. Fazia, L. Bernardinelli, G. Peroni, M. Rondanelli, Positive Effects of a Lecithin-Based Delivery Form of Boswellia serrata Extract in Acute Diarrhea of Adult Subjects., Nutrients 14 (2022). https://doi.org/10.3390/nu14091858.
22. J. Hüsch, J. Bohnet, G. Fricker, C. Skarke, C. Artaria, G. Appendino, M. Schubert-Zsilavecz, M. Abdel-Tawab, Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome(®)) of Boswellia extract., Fitoterapia 84 (2013) 89–98. https://doi.org/10.1016/j.fitote.2012.10.002.
23. A. Tambe, P. Mokashi, N. Pandita, Ex-vivo intestinal absorption study of boswellic acid, cyclodextrin complexes and poloxamer solid dispersions using everted gut sac technique., J Pharm Biomed Anal 167 (2019) 66–73. https://doi.org/10.1016/j.jpba.2018.12.018.
24. A. Rajabian, M. Farzanehfar, H. Hosseini, F.L. Arab, A. Nikkhah, Boswellic acids as promising agents for the management of brain diseases, Life Sci 312 (2023) 121196. https://doi.org/https://doi.org/10.1016/j.lfs.2022.121196.
25. M. Abdel-Tawab, O. Werz, M. Schubert-Zsilavecz, Boswellia serrata: an overall assessment of in vitro, preclinical, pharmacokinetic and clinical data., Clin Pharmacokinet 50 (2011) 349–369. https://doi.org/10.2165/11586800-000000000-00000.
26. T. Rastogi, D.S. Ghorpade, U.A. Deokate, S.S. Khadabadi, Studies on Antimicrobial Activity of Boswellia serrata, Moringa oleifera and Vitex negundo: A comparison, Research Journal of Pharmacognosy and Phytochemistry 1 (2009) 75–77. https://api.semanticscholar.org/CorpusID:86869344.
27. Mohd.Y. Khan, I. Aziz, B. Bihari, H. Kumar, M. Roy, V.K. Verma, A Review-Phytomedicines Used in Treatment of Diabetes, Asian Journal of Pharmaceutical Research 4 (2014) 135–154. https://api.semanticscholar.org/CorpusID:74466269.
28. M.S.N. Hohmann, R.D.R. Cardoso, F.A. Pinho-Ribeiro, J. Crespigio, T.M. Cunha, J.C. Alves-Filho, R. V da Silva, P. Pinge-Filho, S.H. Ferreira, F.Q. Cunha, R. Casagrande, W.A. Verri Jr., 5-Lipoxygenase Deficiency Reduces Acetaminophen-Induced Hepatotoxicity and Lethality, Biomed Res Int 2013 (2013) 627046. https://doi.org/https://doi.org/10.1155/2013/627046.
29. M. Pradhan, A. Alexander, Ajazuddin, Development and validation of a robust RP-HPLC method for analysis of calcipotriol in pharmaceutical dosage form, Res J Pharm Technol 12 (2019) 579–583. https://doi.org/10.5958/0974-360X.2019.00103.3.
30. K. Yadav, M. Pradhan, D. Singh, M.R. Singh, Targeting autoimmune disorders through metal nanoformulation in overcoming the fences of conventional treatment approaches, in: N. Rezaei (Ed.), Translational Autoimmunity, Academic Press, 2022: pp. 361–393. https://doi.org/10.1016/b978-0-12-824390-9.00017-7.
31. M. Mehta, H. Dureja, M. Garg, Development and optimization of boswellic acid-loaded proniosomal gel, Drug Deliv 23 (2016) 3072–3081. https://doi.org/10.3109/10717544.2016.1149744.
32. M.Y. Khan, I. Aziz, I. Ahmad, M. Roy, V.K. Verma, A Natural Cure to Arthritis by Phytomedicines- A Review, Asian Journal of Research in Pharmaceutical Science 5 (2015) 216–220. https://api.semanticscholar.org/CorpusID:74459603.
33. W. Zeng, Y. Song, R. Wang, R. He, T. Wang, Neutrophil elastase: From mechanisms to therapeutic potential., J Pharm Anal 13 (2023) 355–366. https://doi.org/10.1016/j.jpha.2022.12.003.
34. H.P.T. Ammon, Boswellic Acids and Their Role in Chronic Inflammatory Diseases., Adv Exp Med Biol 928 (2016) 291–327. https://doi.org/10.1007/978-3-319-41334-1_13.
35. E.A. Ragab, M.F. Abd El-Wahab, A.S. Doghish, R.M. Salama, N. Eissa, S.F. Darwish, The journey of boswellic acids from synthesis to pharmacological activities., Naunyn Schmiedebergs Arch Pharmacol 397 (2024) 1477–1504. https://doi.org/10.1007/s00210-023-02725-w.
36. B. Neha, J. Honey, B. Ranjan, B. Mukesh, Pharmacognostical and preliminary phytochemical investigation of Acorus calamus linn., Asian Journal of Pharmaceutical Research 2 (2012) 39–42. https://api.semanticscholar.org/CorpusID:88354367.
37. M.-A. Bjornsti, S.H. Kaufmann, Topoisomerases and cancer chemotherapy: recent advances and unanswered questions., F1000Res 8 (2019). https://doi.org/10.12688/f1000research.20201.1.
38. P.N. Nesargikar, B. Spiller, R. Chavez, The complement system: history, pathways, cascade and inhibitors., Eur J Microbiol Immunol (Bp) 2 (2012) 103–111. https://doi.org/10.1556/EuJMI.2.2012.2.2.
39. M. Noris, G. Remuzzi, Overview of complement activation and regulation., Semin Nephrol 33 (2013) 479–492. https://doi.org/10.1016/j.semnephrol.2013.08.001.
40. A. Kapil, N. Moza, Anticomplementary activity of Boswellic acids — An inhibitor of C3-convertase of the classical complement pathway, Int J Immunopharmacol 14 (1992) 1139–1143. https://doi.org/https://doi.org/10.1016/0192-0561(92)90048-P.
41. A.N. Ivanov, Yu.R. Chabbarov, Mechanisms of Physiological Angiogenesis, J Evol Biochem Physiol 59 (2023) 914–929. https://doi.org/10.1134/S0022093023030237.
42. M. Kretschmer, D. Rüdiger, S. Zahler, Mechanical Aspects of Angiogenesis., Cancers (Basel) 13 (2021). https://doi.org/10.3390/cancers13194987.
43. J.-H. Jeong, U. Ojha, Y.M. Lee, Pathological angiogenesis and inflammation in tissues., Arch Pharm Res 44 (2021) 1–15. https://doi.org/10.1007/s12272-020-01287-2.
44. F. Radmanesh, H. Sadeghi Abandansari, M.H. Ghanian, S. Pahlavan, F. Varzideh, S. Yakhkeshi, M. Alikhani, S. Moradi, T. Braun, H. Baharvand, Hydrogel-mediated delivery of microRNA-92a inhibitor polyplex nanoparticles induces localized angiogenesis., Angiogenesis 24 (2021) 657–676. https://doi.org/10.1007/s10456-021-09778-6.
45. D. La Mendola, M.L. Trincavelli, C. Martini, Angiogenesis in Disease., Int J Mol Sci 23 (2022). https://doi.org/10.3390/ijms231810962.
46. I. V Maiborodin, V. V Morozov, Y. V Markevich, V.A. Matveeva, L. V Artem’eva, A.L. Matveev, G.A. Chastikin, Y. V Seryapina, Acceleration of Angiogenesis after Paravasal Injection of Mesenchymal Stem Cells at the Site of Modeled Venous Thrombosis., Bull Exp Biol Med 159 (2015) 128–133. https://doi.org/10.1007/s10517-015-2907-8.
47. A.P. Veith, K. Henderson, A. Spencer, A.D. Sligar, A.B. Baker, Therapeutic strategies for enhancing angiogenesis in wound healing., Adv Drug Deliv Rev 146 (2019) 97–125. https://doi.org/10.1016/j.addr.2018.09.010.
48. F.H. Al-Ostoot, S. Salah, H.A. Khamees, S.A. Khanum, Tumor angiogenesis: Current challenges and therapeutic opportunities, Cancer Treat Res Commun 28 (2021) 100422. https://doi.org/https://doi.org/10.1016/j.ctarc.2021.100422.
49. L. Mosteo, J. Storer, K. Batta, E.J. Searle, D. Duarte, D.H. Wiseman, The Dynamic Interface Between the Bone Marrow Vascular Niche and Hematopoietic Stem Cells in Myeloid Malignancy., Front Cell Dev Biol 9 (2021) 635189. https://doi.org/10.3389/fcell.2021.635189.
50. V.L. Trivedi, R. Soni, P. Dhyani, P. Sati, S. Tejada, A. Sureda, W.N. Setzer, A. Faizal Abdull Razis, B. Modu, M. Butnariu, J. Sharifi-Rad, Anti-cancer properties of boswellic acids: mechanism of action as anti-cancerous agent., Front Pharmacol 14 (2023) 1187181. https://doi.org/10.3389/fphar.2023.1187181.
51. T. Sharma, S. Jana, Boswellic acids as natural anticancer medicine: Precious gift to humankind, J Herb Med 20 (2020) 100313. https://doi.org/https://doi.org/10.1016/j.hermed.2019.100313.
52. S. Elnawasany, Y.A. Haggag, S.M. Shalaby, N.A. Soliman, A.A. EL Saadany, M.A.A. Ibrahim, F. Badria, Anti-cancer effect of nano-encapsulated boswellic acids, curcumin and naringenin against HepG-2 cell line, BMC Complement Med Ther 23 (2023) 270. https://doi.org/10.1186/s12906-023-04096-4.
53. H. Alipanah, P. Zareian, Anti-cancer properties of the methanol extract of Boswellia serrata gum resin: Cell proliferation arrest and inhibition of angiogenesis and metastasis in BALB/c mice breast cancer model TT -, Physiol-Pharmacol 22 (2018) 183–194. http://ppj.phypha.ir/article-1-1400-en.html.
54. T. Ranjbarnejad, M. Saidijam, S. Moradkhani, R. Najafi, Methanolic extract of Boswellia serrata exhibits anti-cancer activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells, Prostaglandins Other Lipid Mediat 131 (2017) 1–8. https://doi.org/https://doi.org/10.1016/j.prostaglandins.2017.05.003.
55. N. Gupta, S. Mansoor, A. Sharma, A. Sapkal, J. Sheth, P. Falatoonzadeh, B. Kuppermann, M. Kenney, Diabetic retinopathy and VEGF., Open Ophthalmol J 7 (2013) 4–10. https://doi.org/10.2174/1874364101307010004.
56. M. Bertocchi, G. Isani, F. Medici, G. Andreani, I. Tubon Usca, P. Roncada, M. Forni, C. Bernardini, Anti-Inflammatory Activity of Boswellia serrata Extracts: An In Vitro Study on Porcine Aortic Endothelial Cells., Oxid Med Cell Longev 2018 (2018) 2504305. https://doi.org/10.1155/2018/2504305.
57. O. Guarino, C. Iovino, V. Di Iorio, A. Rosolia, I. Schiavetti, M. Lanza, F. Simonelli, Anatomical and Functional Effects of Oral Administration of Curcuma Longa and Boswellia Serrata Combination in Patients with Treatment-Naïve Diabetic Macular Edema, J Clin Med 11 (2022). https://doi.org/10.3390/jcm11154451.
58. M. Lulli, M. Cammalleri, I. Fornaciari, G. Casini, M. Dal Monte, Acetyl-11-keto-β-boswellic acid reduces retinal angiogenesis in a mouse model of oxygen-induced retinopathy, Exp Eye Res 135 (2015) 67–80. https://doi.org/https://doi.org/10.1016/j.exer.2015.04.011.
59. S. Saraswati, M. Pandey, R. Mathur, S.S. Agrawal, Boswellic acid inhibits inflammatory angiogenesis in a murine sponge model, Microvasc Res 82 (2011) 263–268. https://doi.org/https://doi.org/10.1016/j.mvr.2011.08.002.
60. L. Deveza, J. Choi, F. Yang, Therapeutic angiogenesis for treating cardiovascular diseases., Theranostics 2 (2012) 801–814. https://doi.org/10.7150/thno.4419.
61. M. Chen, M. Wang, Q. Yang, M. Wang, Z. Wang, Y. Zhu, Y. Zhang, C. Wang, Y. Jia, Y. Li, A. Wen, Antioxidant effects of hydroxysafflor yellow A and acetyl-11-keto-β-boswellic acid in combination on isoproterenol-induced myocardial injury in rats., Int J Mol Med 37 (2016) 1501–1510. https://doi.org/10.3892/ijmm.2016.2571.
62. I. Serbian, R.K. Wolfram, L. Fischer, A. Al‐Harrasi, R. Csuk, Hydroxylated boswellic and glycyrrhetinic acid derivatives: synthesis and cytotoxicity, Mediterranean Journal of Chemistry (2018). https://api.semanticscholar.org/CorpusID:92791358.
63. Y. Wang, Y. Sun, C. Wang, X. Huo, P. Liu, C. Wang, B. Zhang, L. Zhan, H. Zhang, S. Deng, Y. Zhao, X. Ma, Biotransformation of 11-keto-β-boswellic acid by Cunninghamella blakesleana., Phytochemistry 96 (2013) 330–336. https://doi.org/10.1016/j.phytochem.2013.07.018.
64. D. Chaturvedi, P.K. Dwivedi, A.K. Chaturvedi, N. Mishra, H.H. Siddiqui, V. Mishra, Semisynthetic hybrids of boswellic acids: a novel class of potential anti-inflammatory and anti-arthritic agents, Medicinal Chemistry Research 24 (2015) 2799–2812. https://doi.org/10.1007/s00044-015-1331-y.
65. A. Koeberle, A. Henkel, M. Verhoff, L. Tausch, S. König, D. Fischer, N. Kather, S. Seitz, M. Paul, J. Jauch, O. Werz, Triterpene Acids from Frankincense and Semi-Synthetic Derivatives That Inhibit 5-Lipoxygenase and Cathepsin G., Molecules 23 (2018). https://doi.org/10.3390/molecules23020506.
66. S.A.F. Morad, M. Schmid, B. Büchele, H.-U. Siehl, M. El Gafaary, O. Lunov, T. Syrovets, T. Simmet, A novel semisynthetic inhibitor of the FRB domain of mammalian target of rapamycin blocks proliferation and triggers apoptosis in chemoresistant prostate cancer cells., Mol Pharmacol 83 (2013) 531–541. https://doi.org/10.1124/mol.112.081349.
67. P. Ravanan, S.K. Singh, G.S. Rao, P. Kondaiah, Growth inhibitory, apoptotic and anti-inflammatory activities displayed by a novel modified triterpenoid, cyano enone of methyl boswellates., J Biosci 36 (2011) 297–307. https://doi.org/10.1007/s12038-011-9056-7.