This work was carried out between March 2020 - July 2026. Chemical composition and biological activities of Heliotropium indicum L. (Indian heliotrope) are deeply explored in this work. The analysis highlights the predominance of pyrrolizidine alkaloids, as well as the significant presence of triterpenoids, sterols, flavonoids and polyamines. These compounds are responsible for a wide range of biological activities, mainly including antioxidant, anti-inflammatory, wound healing, antimicrobial, hypolipidemic and antitumor effects. Focus has been placed on structure-activity relationships (SAR), particularly in pyrrolizidines, triterpenoids and sterols, to demonstrate the influence of structural elements such as double bonds, hydroxyl and ester groups on biological activity and toxicity of these compounds. The study also shows that complexation with cyclodextrins, in particular for amyrins, is one of the promising strategies aimed at improving the bioavailability of compounds. Despite its therapeutic potential, the use of Heliotropium indicum L. remains limited by the well-documented toxicity of pyrrolizidines, notably liver toxicity and genotoxicity. This review highlights the need for targeted studies on standardized extracts and isolated compounds, in order to optimize the benefit/risk ratio and to support a rational integration of compounds from this plant into modern therapeutics.
References
[1]
Ghori, M.K., Ghaffar？, M.A., Hussa？n, S.N., Manzoor, M., Az？z, M. and Sarwer, W. (2016) Ethnopharmacological, Phytochemical and Pharmacognostic Potential of Genus Heliotrop？um L. Turkish Journal of Pharmaceutical Sciences, 13, 143-168. https://doi.org/10.5505/tjps.2016.20591
[2]
Gopinathan, M. and Balasubramanian, M. (2020) A Review on the Pharmacological Potential of the Genus Heliotropium (Boraginaceae). European Journal Pharmaceutical and Medical Research, 7, 462-471.
[3]
Ghosh, P., Das, P., Das, C., Mahapatra, S. and Chatterjee, S. (2018) Morphological Characteristics and Phytopharmacological Detailing of Hatishur (Heliotropium indicum Linn.): A Concise Review. Journal of Pharmacognosy and Phytochemistry, 7, 1900-1907.
[4]
Roeder, E. and Wiedenfeld, H. (2013) Plants Containing Pyrrolizidine Alkaloids Used in the Traditional Indian Medicine—Including Ayurveda. Die Pharmazie, 68, 83-92. https://doi.org/10.31083/ph.2013.2706
[5]
Pandey, D.P., Singh, J.P., Roy, R., Singh, V.P. and Pandey, V.B. (1996) Constituents of Heliotropium indicum. Oriental Journal of Chemistry, 12, 321-322. http://www.orientjchem.org/?p=37865
[6]
Hartmann, M. (2003) 5 Sterol Metabolism and Functions in Higher Plants. In: Daum, G., Ed., Topics in Current Genetics, Springer, 183-211. https://doi.org/10.1007/978-3-540-40999-1_6
[7]
Hartmann, T. and Ober, D. (2000) Biosynthesis and Metabolism of Pyrrolizidine Alkaloids in Plants and Specialized Insect Herbivores. In: Leeper, F.J. and Vederas, J.C., Eds., Topics in Current Chemistry, Springer, 207-243. https://doi.org/10.1007/3-540-48146-x_5
[8]
Chunthorng-Orn, J., Dechayont, B., Phuaklee, P., Prajuabjinda, O., Juckmeta, T. and Itharat, A. (2016) Cytotoxic, Anti-Inflammatory and Antioxidant Activities of Helotropium indicum Extracts. Journal of the Medical Association of Thailand, 99, S102-S109.
[9]
Kyei, S., Koffuor, G.A., Ramkissoon, P., Afari, C. and Asiamah, E.A. (2015) The Claim of Anti-Cataract Potential of Heliotropium indicum: A Myth or Reality? Ophthalmology and Therapy, 4, 115-128. https://doi.org/10.1007/s40123-015-0042-2
[10]
Wani, P.A., Tolu, A.M. and Wahid, S. (2018) Antioxidant, Antimicrobial and Antibiotic Resistance Modifying Effect of Heliotropium indicum. Biocatalysis and Agricultural Biotechnology, 15, 113-118. https://doi.org/10.1016/j.bcab.2018.05.018
[11]
Dodehe, Y., Barthelemy, A., Calixte, B., Jean, D.N., Allico, J.D. and Nelly, F. (2011) Isolation of Wound Healing Compounds from Heliotropium indicum. Journal of Applied Pharmaceutical Science, 1, 102-106.
[12]
Kugelman, M., Liu, W.C., Axelrod, M., McBride, T.J. and Rao, K.V. (1976) Indicine-N-Oxide: The Antitumor Principle of Heliotropium indicum. Lloydia: A Journal of Natural Products, 39, 125-128.
[13]
Torres Ovalle, J.D., Gama, J.M.M. and Torres Garcia, O.A. (2022) Systematic Review of the Phytochemical Compounds Use of Heliotropium indicum Taking Advantage of Its Advantage in Modern Medicine. Journal of Applied Biotechnology & Bioengineering, 9, 132-136. https://doi.org/10.15406/jabb.2022.09.00300
[14]
Pandey, V., Singh, J., Rao, Y. and Acharya, S. (1982) Isolation and Pharmacological Action of Heliotrine, the Major Alkaloid of Heliotropium indicumseeds. Planta Medica, 45, 229-233. https://doi.org/10.1055/s-2007-971378
[15]
Mattocks, A.R. (1967) Minor Alkaloids of Heliotropium indicum L. Journal of the Chemical Society C: Organic, 2, 329-331. https://doi.org/10.1039/j39670000329
[16]
Birecka, H., Frohlich, M.W. and Glickman, L.M. (1983) Free and Esterified Necines in Heliotropium Species from Mexico and Texas. Phytochemistry, 22, 1167-1171. https://doi.org/10.1016/0031-9422(83)80214-3
[17]
Souza, J.S.N., Machado, L.L., Pessoa, O.D.L., Braz-Filho, R., Overk, C.R., Yao, P., et al. (2005) Pyrrolizidine alkaloids from Heliotropium indicum. Journal of the Brazilian Chemical Society, 16, 1410-1414. https://doi.org/10.1590/s0103-50532005000800019
[18]
Rahman, M.A., Mia, M. and Shahid, I. (2011) Pharmacological and Phytochemical Screen Activities of Roots of Heliotropium indicum Linn. Pharmacologyonline, 1, 185-192.
[19]
Adetuyi, B.O., Adebisi, O.A., Awoyelu, E.H., Adetuyi, O.A. and Ogunlana, O.O. (2020) Phytochemical and Toxicological Effect of Ethanol Extract of Heliotropium indicum on Liver of Male Albino Rats. Letters in Applied NanoBioscience, 10, 2085-2095.
[20]
Basak, M. and Dey, B.K. (2016) Phytochemical and Antipyretic Potential of Ethanolic Leaf Extract of Heliotropium indicum L. Journal of Applied Pharmaceutical Research, 4, 6-10. https://www.japtronline.com/index.php/joapr/article/view/61
[21]
Mohammad, S.A., Nabi, S.A., Marella, S., Thandaiah, K.T., Kumar, M.V.J. and Rao, C.A. (2014) Phytochemical Screening and Antihyperglycemic Activity of Heliotropium indicum Whole Plant in Streptozotocin induced Diabetic Rats. Journal of Applied Pharmaceutical Science, 4, 65-71.
[22]
Sahu, A.K., Meher, C.P., Meher, A. and Shankar, B. (2019) Heliotropium indicum: Pharmacognostical, Physicochemical and Phytochemical Approaches. Journal of Pharmaceutical and Advanced Research, 2, 464-468.
[23]
Oluwatoyin, S.M., Illeogbulam, N.G. and Joseph, A. (2011) Phytochemical and Antimicrobial Studies on the Aerial Parts of Heliotropium indicum Linn. https://www.cabidigitallibrary.org/doi/full/10.5555/20113163784
[24]
Osungunna, M.O. and Adedeji, K.A. (2011) Phytochemical and Antimicrobial Screening of Methanol Extract of Heliotropium indicum Leaf. Journal of Microbiology and Antimicrobials, 3, 213-216.
[25]
da Silva Júnior, W.F., Bezerra de Menezes, D.L., de Oliveira, L.C., Koester, L.S., Oliveira de Almeida, P.D., Lima, E.S., et al. (2019) Inclusion Complexes of Β and HP β-Cyclodextrin with Α, Β Amyrin and in Vitro Anti-Inflammatory Activity. Biomolecules, 9, Article 241. https://doi.org/10.3390/biom9060241
[26]
Kyei, S., Koffuor, G.A., Ramkissoon, P., Ameyaw, E.O. and Asiamah, E.A. (2016) Anti-Inflammzatory Effect of Heliotropium indicum Linn on Lipopolysaccharide-Induced Uveitis in New Zealand White Rabbits. International Journal of Ophthalmology, 9, 528-535.
[27]
Kumar, M.S., Chaudhury, S. and Balachandran, S. (2014) In Vitro Callus Culture of Heliotropium indicum Linn. for Assessment of Total Phenolic and Flavonoid Content and Antioxidant Activity. Applied Biochemistry and Biotechnology, 174, 2897-2909. https://doi.org/10.1007/s12010-014-1235-1
[28]
Dash, G.K. and Abdullah, M.S. (2013) A Review on Heliotropium indicum L. (Boraginaceae). International Journal of Pharmaceutical Sciences and Research, 4, 1253-1258.
[29]
Joshi, R.K. (2020) GC-MS Analysis of Volatile Organic Constituents of Traditionally Used Medicinal Plants from the Western Ghats of India: Blumea lanceolaria (Roxb.) Druce., Heliotropium indicum L. and Triumfetta rhomboidea Jacq. Journal of the Mexican Chemical Society, 64, 74-82. https://doi.org/10.29356/jmcs.v64i2.1093
[30]
Faleye, B.C., Bamisaye, F.A. and Fatoki, T.H. (2023) GC-MS Characterization and Computational Assessment of Phytochemicals in Heliotropium indicum Ethanolic Leaves Extract. Journal of Complementary and Alternative Medical Research, 22, 1-10. https://doi.org/10.9734/jocamr/2023/v22i1447
[31]
Sulaimon, O.F., Ibrahim, A., Abiodun, S.L., Muhammad, F.A., Morufu Eyitayo Balogun, M.G. and Adetoyi, A.Z. (2024) Evaluation of the Antidiarrheal Activity of the Heliotropium indicum (Indian Heliotrope) Methanol Leaf Extract and Formulation into Oral Suspensions. Journal of Research in Complementary Medicine, 1, 73-80. https://doi.org/10.5455/jrcm.20240624082058
[32]
Afroz Shoily, M.S., Islam, M.E., Rasel, N.M., Parvin, S., Barmon, J., Hasan Aqib, A., et al. (2025) Unveiling the Biological Activities of Heliotropium indicum L. Plant Extracts: Anti-Inflammatory Activities, GC-MS Analysis, and In-Silico Molecular Docking. Scientific Reports, 15, Article No. 3285. https://doi.org/10.1038/s41598-024-79559-w
[33]
Shoily, S.A., Parvin, M.S., Kazi, M., Aqib, A.H., Hossain, M.S., Ahmed, R., Rafi, R.H., Barmon, J., Uddin, M.N. and Islam, M.E. (2026) Phytochemical Profiling and Computational Docking Studies Revealing the Potential Anticancer and Antioxidant Properties of Heliotropium indicum L. Scientifica, 2026, Article ID: 1079290.
[34]
Wijesinghe, U., Thiripuranathar, G., Menaa, F., Iqbal, H., Razzaq, A. and Almukhlifi, H. (2021) Green Synthesis, Structural Characterization and Photocatalytic Applications of ZnO Nanoconjugates Using Heliotropium indicum. Catalysts, 11, Article 831. https://doi.org/10.3390/catal11070831
[35]
Zhao, Y., Xia, Q., Yin, J.J., Lin, G. and Fu, P.P. (2011) Photoirradiation of Dehydropyrrolizidine Alkaloids—Formation of Reactive Oxygen Species and Induction of Lipid Peroxidation. Toxicology Letters, 205, 302-309. https://doi.org/10.1016/j.toxlet.2011.06.020
[36]
Schoental, R. (1968) Toxicology and Carcinogenic Action of Pyrrolizidine Alkaloids. Cancer Research, 28, 2237-2246.
[37]
Kalyan, S.B., Jasmin Sajni, R., Karthik, R., Raamamurthy, J., Christina, A. and Sasikumar, S. (2007) Anti-Inflammatory and Anti-Nociceptive Activities of Heliotropium indicum Linn. in Experimental Animal Models. Pharmacology Online, 3, 438-445.
[38]
Srinivas, K., Rao, M.E.B. and Rao, S.S. (2000) Anti-Inflammatory Activity of Heliotropium indicum Linn. and Leucas Aspera Spreng. In Albino Rats. Indian Journal of Pharmacology, 32, 37-38. https://www.cabidigitallibrary.org/doi/full/10.5555/20000311183
[39]
Boye, A., Koffuor, G.A., Amoateng, P., Ameyaw, E.O. and Abaitey, A.K. (2012) Analgesic Activity and Safety Assessment of Heliotropium indicum Linn. (Boraginaceae) in Rodents. International Journal of Pharmacology, 8, 91-100. https://doi.org/10.3923/ijp.2012.91.100
[40]
Singh, B. and Sharma, R.A. (2019) Pyrrolizidine Alkaloids and Their Biological Properties from Indian Heliotropium Species. Current Bioactive Compounds, 15, 3-18. https://doi.org/10.2174/1573407213666171120163307
[41]
Adelaja, A.A., Ayoola, M.D., Otulana, J.O., Akinola, O.B., Olayiwola, A. and Ejiwunmi, A.B. (2008) Evaluation of the Histo-Gastroprotective and Antimicrobial Activities of Heliotropium indicum Linn (Boraginaceae). The Malaysian Journal of Medical Sciences, 15, 22-30.
[42]
Sifat, N., Zihad, S.M.N.K., Lovely, F., Rouf, R., Shajib, G.M.A., Alam, M.A., et al. (2020) Supplementation of Heliotropium indicum Linn Attenuates Obesity and Associated Metabolic Disorders in High‐Carbohydrate‐High‐Fat Diet‐Induced Obese Rats. Journal of Food Biochemistry, 44, e13444. https://doi.org/10.1111/jfbc.13444
[43]
Goyal, N. and Sharma, S. (2014) Bioactive Phytoconstituents and Plant Extracts from Genus Heliotropium. International Journal of Green Pharmacy, 8, Article 217.
[44]
Ramamurthy, V. and Krishnaveni, S. (2014) Larvicidal Efficacy of Leaf Extracts of Heliotropium indicum and Mukia maderaspatana against the Dengue Fever Mosquito Vector Aedes Aegypti. Journal of Entomology and Zoology Studies, 2, 40-45.
[45]
Mourin, N.A., Sharmin, T., Chowdhury, S.R., Islam, F., Rahman, M.S. and Rashid, M.A. (2013) Evaluation of Bioactivities of Heliotropium indicum, a Medicinal Plant of Bangladesh. The Pharma Innovation Journal, 2, 217-221.
[46]
Moreira, R., Pereira, D.M., Valent？o, P. and Andrade, P.B. (2018) Pyrrolizidine Alkaloids: Chemistry, Pharmacology, Toxicology and Food Safety. International Journal of Molecular Sciences, 19, Article 1668. https://doi.org/10.3390/ijms19061668
[47]
Sarkar, C., Mondal, M., Khanom, B., Hossain, M.M., Hossain, M.S., Sureda, A., et al. (2021) Heliotropium indicum L.: From Farm to a Source of Bioactive Compounds with Therapeutic Activity. Evidence-Based Complementary and Alternative Medicine, 2021, 1-21. https://doi.org/10.1155/2021/9965481
[48]
Silvestro, D., Andersen, T.G., Schaller, H. and Jensen, P.E. (2013) Plant Sterol Metabolism. Δ7-Sterol-C5-Desaturase (STE1/DWARF7), Δ5,7-Sterol-Δ7-Reductase (DWARF5) and Δ24-Sterol-Δ24-Reductase (DIMINUTO/DWARF1) Show Multiple Subcellular Localizations in Arabidopsis thaliana (Heynh) L. PLOS ONE, 8, e56429. https://doi.org/10.1371/journal.pone.0056429
[49]
Premnath, D. and Gomez, P. (2012) Antifungal and Antibacterial Activities of Chemical Constituents from Heliotropium indicum Linn. Plant. Drug Invention Today, 11, 564-568.
[50]
Samira, K., Laboni, F.R., Julie, A.S., Jalal, U. and Labu, Z.K. (2016) Biological Investigations of Medicinal Plants of Heliotropium indicum Indigenous to Bangladesh. Journal of Coastal Life Medicine, 4, 874-878.
[51]
Kandemir, N., ？elik, A., Shah, S.N. and Razzaq, A. (2020) Comparative Micro-Anatomical Investigation of Genus Heliotropium (Boraginaceae) Found in Turkey. Flora, 262, Article 151495. https://doi.org/10.1016/j.flora.2019.151495
[52]
Asumeng Ko, G., Boye, A., Amoateng, P., O. Ameyaw, E. and K. Abaitey, A. (2012) Investigating the Site of Action of an Aqueous Extract of Heliotropium indicum Linn (Boraginaceae) on Smooth Muscles. Research Journal of Pharmacology, 6, 12-19. https://doi.org/10.3923/rjpharm.2012.12.19
[53]
Schramm, S., K？hler, N. and Rozhon, W. (2019) Pyrrolizidine Alkaloids: Biosynthesis, Biological Activities and Occurrence in Crop Plants. Molecules, 24, Article 498. https://doi.org/10.3390/molecules24030498
[54]
Veda Vijaya, T., Sasi Kumar, S., Asokan, B.R., Sengottuvelu, S. and Jaikumar, S. (2015) Anticataract Activity of Ethanolic Extract of Heliotropium indicum Leaves on Galactose Induced Cataract in Rats. International Journal of Pharmacology and Toxicology, 5, 18-20.
[55]
Mahato, K., Kakoti, B.B., Borah, S. and Kumar, M. (2014) Evaluation of In-Vitro Anthelmintic Activity of Heliotropium indicum Linn. Leaves in Indian Adult Earthworm. Asian Pacific Journal of Tropical Disease, 4, S259-S262. https://doi.org/10.1016/s2222-1808(14)60451-5
[56]
Reddy, J.S., Rao, P.R. and Reddy, M.S. (2002) Wound Healing Effects of Heliotropium indicum, Plumbago Zeylanicum and Acalypha Indica in Rats. Journal of Ethnopharmacology, 79, 249-251. https://doi.org/10.1016/s0378-8741(01)00388-9
[57]
Bakar, B.W., Emmanuel, A.P., Samuel, A., Naomi, A.S. and Emelia, O.B. (2025) A Review of the Pharmacological Activities and Safety of Heliotropium indicum. Journal of Natural Remedies, 25, 1339-1452.
[58]
Straub, L.V., Mulder, P.P.J., Zuilhof, H., Gonzalez, F.P. and Righetti, L. (2025) Development of a High-Resolution Tandem Mass Spectral Library for Pyrrolizidine Alkaloids (PASL). Scientific Data, 12, Article No. 1654. https://doi.org/10.1038/s41597-025-05940-7
