Methanol extract of Isodon ternifolius (D. Don) KUDO leaves has antimicrobial and antioxidant activities but no neuroprotective activity.

Aruna Chanu Hijam; Arunkumar Singh Koijam; Reena Haobam

doi:10.52756/ijerr.2024.v39spl.016

Authors

Aruna Chanu Hijam Department of Biotechnology, Manipur University, Canchipur, Imphal-795003, Manipur, India https://orcid.org/0000-0002-5614-6039
Arunkumar Singh Koijam Insect Bioresources Laboratory, Animal Bioresources Programme, Institute of Bioresources & Sustainable Development, Department of Biotechnology, Govt. of India, Takyelpat, Imphal-795001, Manipur, India https://orcid.org/0000-0001-5778-4932
Reena Haobam Department of Biotechnology, Manipur University, Canchipur, Imphal-795003, Manipur, India https://orcid.org/0000-0002-2994-9493

DOI:

https://doi.org/10.52756/ijerr.2024.v39spl.016

Keywords:

Bactericidal, free radicals’ quencher, fungicidal, neurotoxicity, phytochemicals

Abstract

Isodon ternifolius (D. Don) KUDO is a medicinal plant traditionally used by the indigenous people of Manipur, India, as a room fumigant and a means to ward off evil spirits. The current study was designed to assess the antimicrobial, antioxidant, and neuroprotective properties of I. ternifolius. The dried leaves of I. ternifolius were heat extracted with methanol (ME) and screened for phytochemical constituents. The antimicrobial activity was investigated against pathogenic microbes. In-vitro antioxidant activity was assessed by 2-deoxyribose, 2, 2´-Azinobis-3-ethylbenzo-Thiozoline-6-sulphonate (ABTS), and 1, 1-Diphenyl-2-Picrylhydrazyl (DPPH) assay methods. The endogenous reactive oxygen species (ROS) level on SH-SY5Y cells was detected using 2?,7?-Dichlorofluorescein diacetate (DCF-DA). The neuroprotective activity of ME was studied in rotenone-treated SH-SY5Y cells. ME was observed to have substantial antimicrobial potential against four pathogenic bacterial strains - B. subtilis, Streptococcus, K. pneumoniae and E. aerogenes and also revealed antifungal activity against C. albicans. ME also showed potent free radical quenching activity in chemical and cell-culture-based DCF-DA assays and possesses high phenolic and flavonoid contents. However, ME did not show neuroprotective activity in rotenone-treated SH-SY5Y cells.

References

Acharya, C.K., Khan, N.K., & Madhu, N.R. (2022a). A Comparative GC-MS Analysis of Bioactive Compounds in Ethyl Acetate Fruit Extract of Phyllanthus emblica L. (Gaertn.) Growing in Two Phyto-geographically Contrasting Regions of West Bengal, India. Journal of Plant Science and Research, 38(1), 343–355. https://doi.org/10.32381/JPSR.2022.38.01.37

Acharya, C.K., Khan, N.S., & Madhu, N.R. (2022b). Traditional Phyto-therapeutic uses by Tribal People in Western Sundarbans: Henry Island, Fredric Island and Bakkhali, West Bengal, India. Journal of Plant Science and Research, 38(2), 513–523. https://doi.org/10.32381/JPSR.2022.38.02.8

Aimond, A., Calabro, K., Audoin, C., Olivier, E., Dutot, M., Buron, P., Rat, P., Laprévote, O., Prado, S., Roulland, E., Thomas, O. P., & Genta-Jouve, G. (2020). Cytotoxic and anti-inflammatory effects of ent-kaurane derivatives isolated from the alpine plant Sideritis hyssopifolia. Molecules (Basel, Switzerland), 25(3), 589. https://doi.org/10.3390/molecules25030589

Bagchi, B. (2021). Diversity and antimicrobial activity of endophytic fungi from Combretum sp. collected in monsoon from three regions. International Journal of Experimental Research and Review, 24, 1–9. https://doi.org/10.52756/ijerr.2021.v24.001

Bee, B., Jat, R., & Ahmad, S. (2023). Fabrication of microspheres and characterization of antimicrobial and anti-inflammatory activity isolated fraction from total alcoholic extract of Cassia fistula (Linn.) in carrageenan-Type-IV induced inflammatory rats. International Journal of Experimental Research and Review, 32, 246–259. https://doi.org/10.52756/ijerr.2023.v32.021

Bhalodia, N. R., & Shukla, V. J. (2011). Antibacterial and antifungal activities from leaf extracts of Cassia fistula l.: An ethnomedicinal plant. Journal of Advanced Pharmaceutical Technology & Research, 2(2), 104–109. https://doi.org/10.4103/2231-4040.82956

Bhatta, K., Samal, H., & Mohanty, P. (2023). Isozyme profiling of Antioxidant Enzyme in Macrotyloma uniflorum. International Journal of Experimental Research and Review, 36, 156–165. https://doi.org/10.52756/ijerr.2023.v36.015a

Biswas, K., Basu, J., Ghosh, A., & Giri, P. (2016). Study of rhizospheric bacterial population of Azadirachta indica (Neem) of North 24 Parganas district of West Bengal for bioprospective consideration. International Journal of Experimental Research and Review, 6, 62–66.

Bouayed, J., & Bohn, T. (2010). Exogenous antioxidants-Double-edged swords in cellular redox state: Health beneficial effects at physiologic doses versus deleterious effects at high doses. Oxidative Medicine and Cellular Longevity, 3(4), 228–237. https://doi.org/10.4161/oxim.3.4.12858

Chang, C. C., Yang, M. H., Wen, H. M., & Chern, J. C. (2002). Estimation of total flavonoid content in propolis by two complementary colorimetric methods. Journal of Food and Drug Analysis, 10(3), 178–182. https://doi.org/10.38212/2224-6614.2748

Collin, F. (2019). Chemical basis of reactive oxygen species reactivity and involvement in neurodegenerative diseases. International Journal of Molecular Sciences, 20(10), 2407. https://doi.org/10.3390/ijms20102407

Deng, J., Qin, L., & Zhou, Z. (2023). Network Pharmacology and Molecular Docking Reveal the Mechanism of Isodon ternifolius (D. Don) Kudo Against Liver Fibrosis. Drug Design, Development and Therapy, 17, 2335-2351. https://doi.org/10.2147/DDDT.S412818

Dey-Ray, S., Dutta, S., Sengupta, P., Madhu, N.R., Das, N., Ray, S., Kolesarova, A., Roychoudhury, S. (2024). Elucidation of anti-inflammatory activity of a new cyclic alkaloid compound from root bark of Ziziphus nummularia (Aubrev.): in vitro, in silico and in vivo studies. Journal of Microbiology, Biotechnology and Food Sciences, 13(5), e10564. https://doi.org/10.55251/jmbfs.10564

Dhanalakshmi, C., Manivasagam, T., Nataraj, J., Justin Thenmozhi, A., & Essa, M. M. (2015). Neurosupportive Role of vanillin, a natural phenolic compound, on rotenone induced neurotoxicity in SH-SY5Y neuroblastoma cells. Evidence-Based Complementary and Alternative Medicine: eCAM, 2015, 626028. https://doi.org/10.1155/2015/626028

Ding, C., Ding, Y., Chen, H., Zhou, J., (2017). Chapter 5 - Chemistry and bioactivity of ent-kaurene diterpenoids. In: Atta-ur-Rahman (eds). Studies in natural products chemistry. Vol. 54. Elsevier. pp. 141-197. https://doi.org/10.1016/B978-0-444-63929-5.00005-X.

El-hawary, S. S., El-sofany, R. H., Abdel-Monem, A. R., Ashour, R. S., & Sleem, A. A. (2012). Polyphenolics content and biological activity of Plectranthus amboinicus (Lour.) Spreng growing in Egypt (Lamiaceae). Pharmacognosy Journal, 4(32), 45–54. https://doi.org/10.5530/pj.2012.32.9

Elshamy, A. I., Mohamed, T. A., Swapana, N., Kasai, Y., Noji, M., Efferth, T., Imagawa, H., Hegazy, M. F., & Umeyama, A. (2023). Ternifolipyrons A-J: new cytotoxic α-pyrones from Isodon ternifolius (D. Don) Kudô. RSC Advances, 13(29), 19710–19720. https://doi.org/10.1039/d3ra03146b

Gauri, S., Bera, C., Bhattacharyya, R., & Mandal, S. (2016). Identification of an antimicrobial peptide from large freshwater snail (Lymnaea stagnalis): activity against antibiotics resistant Staphylococcus epidermidis. Int. J. Exp. Res. Rev., 2, 5–9. https://doi.org/10.52756/ijerr.2016.v2.002

Gebicki, J. M., & Nauser, T. (2021). Fast Antioxidant Reaction of Polyphenols and Their Metabolites. Antioxidants (Basel, Switzerland), 10(8), 1297. https://doi.org/10.3390/antiox10081297

Ghosh, S., Nahar, N., Dasgupta, D., Sarkar, B., Biswas, P., Chakraborty, R., Acharya, C.K., Jana, S.K., Madhu, N.R. (2022). Socioeconomic Disparity in Health of Rural Communities in the Himalayan Foothills: Mahananda Wildlife Sanctuary, West Bengal. Chettinad Health City Medical Journal. 11(2), 9–18.

Gonçalves, T. B., Braga, M. A., de Oliveira, F. F., Santiago, G. M., Carvalho, C. B., Brito e Cabral, P., de Melo Santiago, T., Sousa, J. S., Barros, E. B., do Nascimento, R. F., & Nagao-Dias, A. T. (2012). Effect of subinihibitory and inhibitory concentrations of Plectranthus amboinicus (Lour.) Spreng essential oil on Klebsiella pneumoniae. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 19(11), 962–968. https://doi.org/10.1016/j.phymed.2012.05.013

Gou, L. L., Hu, K., Yang, Q., Li, X. N., Sun, H. D., Xiang, C. L., & Puno, P. T. (2019). Structurally diverse diterpenoids from Isodon ternifolius collected from three regions. Tetrahedron, 75(19), 2797–2806. https://doi.org/10.1016/j.tet.2019.03.056

Gou, L. L., Hu, K., Yang, Q., Li, X. N., Sun, H. D., Xiang, C. L., Puno, P. T. (2019). Structurally diverse diterpenoids from Isodon ternifolius collected from three regions. Tetrahedron, 75(19), 2797–2806. https://doi.org/10.1016/j.tet.2019.03.056

Gurgel, A. P., da Silva, J. G., Grangeiro, A. R., Oliveira, D. C., Lima, C. M., da Silva, A. C., Oliveira, R. A., & Souza, I. A. (2009). In vivo study of the anti-inflammatory and antitumor activities of leaves from Plectranthus amboinicus (Lour.) Spreng (Lamiaceae). Journal of Ethanopharmacology, 125(2), 361–363. https://doi.org/10.1016/j.jep.2009.07.006

Hore, P., & Bhaben, T. (2023). Toxic Effect of 2,4-D on Cytology of Vigna radiata (L.) Wilczek”. International Journal of Experimental Research Review, 30, 276–281. https://doi.org/10.52756/ijerr.2023.v30.025.

Huang, W., Liang, Y., Wang, J., Li, G., Wang, G., Li, Y., & Chung, H. Y. (2016). Anti-angiogenic activity and mechanism of kaurane diterpenoids from Wedelia chinensis. Phytomedicine: International Journal of Phytotherapy and Phytopharmacology, 23(3), 283–292. https://doi.org/10.1016/j.phymed.2015.12.021

Husain, S., Hillmann, K., Hengst, K., & Englert, H. (2023). Effects of a lifestyle intervention on the biomarkers of oxidative stress in non-communicable diseases: A systematic review. Frontiers in Aging, 4, 1085511. https://doi.org/10.3389/fragi.2023.1085511

Ibrahim, T. S., Khongorzul, P., Muyaba, M., & Alolga, R. N. (2023). Ent-kaurane diterpenoids from the Annonaceae family: a review of research progress and call for further research. Frontiers in Pharmacology, 14, 1227574. https://doi.org/10.3389/fphar.2023.1227574

Jakkana, V., & Yamala, S. (2024). Isolation, Identification and in-Silico Characterization of Bioactive Peptide from the Venom Sac of Conus inscriptus. International Journal of Experimental Research and Review, 38, 1–14. https://doi.org/10.52756/ijerr.2024.v38.001

Kiran, T., Otlu, O. & Karabulut, A. (2023). Oxidative stress and antioxidants in health and disease. Journal of Laboratory Medicine, 47(1), 1–11. https://doi.org/10.1515/labmed-2022-0108.

Li, X., Xiao, W., Pu, J., Ban, L., Shen, Y., Weng, Z., Li, S., & Sun, H. (2006). Cytotoxic ent-kaurene diterpenoids from Isodon phyllostachys. Phytochemistry, 67(13), 1336–1340. https://doi.org/10.1016/j.phytochem.2006.05.002

Liao, Y. J., Bai, H. Y., Li, Z. H., Zou, J., Chen, J. W., Zheng, F., Zhang, J. X., Mai, S. J., Zeng, M. S., Sun, H. D., Pu, J. X., & Xie, D. (2014). Longikaurin A, a natural ent-kaurane, induces G2/M phase arrest via downregulation of Skp2 and apoptosis induction through ROS/JNK/c-Jun pathway in hepatocellular carcinoma cells. Cell Death & Disease, 5(3), e1137. https://doi.org/10.1038/cddis.2014.66

Liu, M., Wang, W. G., Sun, H. D., & Pu, J. X. (2017). Diterpenoids from Isodonspecies: an update. Natural Product Reports, 34(9), 1090–1140. https://doi.org/10.1039/C7NP00027H

Maiti, A., Madhu, N.R., & Manna, C. K. (2010). Ethnomedicine used by the tribal people of the district Purulia, W. B., India in controlling fertility: and experimental study. Pharmacologyonline. 1, 783–802.

Maiti, A., Madhu, N.R., & Manna, C. K. (2013). Natural products traditionally used by the tribal people of the Purulia district, West Bengal, India for the abortifacient purpose. International Journal of Genuine Medicine, 3(2), e14:1–4.

Mathew, S., Abraham, T. E., & Zakaria, Z. A. (2015). Reactivity of phenolic compounds towards free radicals under in vitro conditions. Journal of Food Science and Technology, 52(9), 5790–5798. https://doi.org/10.1007/s13197-014-1704-0

Meade-Tollin, L. C., Wijeratne, E. M. K., Cooper, D., Guild, M., Jon, E., Fritz, A., Zhou, G., Whitesell, L., Liang, J., Gunatilaka, A. A. L. (2004). Ponicidin and oridonin are responsible for the antiangiogenic activity of Rabdosia rubescens, a constituent of the herbal supplement PC SPES. Journal of Natural Products, 67(1), 2–4. https://doi.org/10.1021/np0304114.

Mohamed, E. A. A., Muddathir, A. M., & Osman, M. A. (2020). Antimicrobial activity, phytochemical screening of crude extracts, and essential oils constituents of two Pulicaria spp. growing in Sudan. Scientific Reports, 10(1), 17148. https://doi.org/10.1038/s41598-020-74262-y

Munteanu, I. G., & Apetrei, C. (2021). Analytical Methods Used in Determining Antioxidant Activity: A Review. International Journal of Molecular Sciences, 22(7), 3380. https://doi.org/10.3390/ijms22073380

Nasim, N., Sandeep, I.S. & Mohanty, S. (2022). Plant-derived natural products for drug discovery: current approaches and prospects. The Nucleus: An International Journal of Cytology and Allied Topics, 65(3), 399-411. https://doi.org/10.1007/s13237-022-00405-3

Park, H. R., Lee, H., Park, H., Jeon, J. W., Cho, W. K., & Ma, J. Y. (2015). Neuroprotective effects of Liriope platyphylla extract against hydrogen peroxide-induced cytotoxicity in human neuroblastoma SH-SY5Y cells. BMC Complementary and Alternative Medicine, 15, 171. https://doi.org/10.1186/s12906-015-0679-3

Pham, M. Q., Le, T. T. H., Do, T. T., To, D. C., Pham, Q. L., & Nguyen, P. H. (2020). PTP1B inhibitors from Isodon ternifolius collected in Vietnam. Vietnam Journal of Science and Technology, 58(5), 533-540. https://doi.org/10.15625/2525-2518/58/5/15012

Putra, L. S., Sukweenadhi, J., Nathania, C., Wibowo, E. S., Buschle-Diller, G., & Marianti Purwanto, M. G. (2022). Comparative study of polyphenolic compound extraction from empty palm fruit bunches and sugarcane pulp. Heliyon, 8(2), e08951. https://doi.org/10.1016/j.heliyon.2022.e08951

Rami, N., Kulkarni, B., Chibber, S., Jhala, D., Parmar, N., & Trivedi, K. (2023). In vitro antioxidant and anticancer potential of Annona squamosa L. Extracts against breast cancer. Int. J. Exp. Res. Rev., 30, 264–275. https://doi.org/10.52756/ijerr.2023.v30.024

Rauf, A., Muhammad, N., Khan, A., Uddin, N., Muhammad, A., & Barkatullah. (2012). Antibacterial and phytotoxic profile of selected Pakistani medicinal plants. World Applied Sciences Journal 20(4), 540–544. https://doi.org/10.5829/idosi.wasj.2012.20.04.1718.

Re, R., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., & Rice-Evans, C. (1999). Antioxidant activity: applying an improved ABTS radical cation decolorization assay. Free Radical Biology and Medicine, 26(9-10), 1231–1237. https://doi.org/10.1016/S0891-5849(98)00315-3

Rudrapal, M., Khairnar, S. J., Khan, J., Dukhyil, A. B., Ansari, M. A., Alomary, M. N., Alshabrmi, F. M., Palai, S., Deb, P. K., & Devi, R. (2022). Dietary Polyphenols and Their Role in Oxidative stress-induced human diseases: Insights into protective effects, antioxidant potentials and mechanism(s) of action. Frontiers in Pharmacology, 13, 806470. https://doi.org/10.3389/fphar.2022.806470

Rudrapal, M., Khairnar, S. J., Khan, J., Dukhyil, A. B., Ansari, M. A., Alomary, M. N., Alshabrmi, F. M., Palai, S., Deb, P. K., & Devi, R. (2022). Dietary polyphenols and their role in oxidative stress-induced human diseases: insights into protective effects, antioxidant potentials and mechanism(s) of action. Frontiers in Pharmacology, 13, 806470. https://doi.org/10.3389/fphar.2022.806470

Sacchetti, G., Maietti, S., Muzzoli, M., Scaglianti, M., Manfredini, S., Radice, M., & Bruni, R. (2005). Comparative evaluation of 11 essential oils of different origin as functional antioxidants, antiradicals and antimicrobials in foods. Food Chemistry, 91(4), 621–632. https://doi.org/10.1016/j.foodchem.2004.06.031

Saeed, F., Afzaal, M., Tufail, T., & Ahmad, A. (2019). Use of natural antimicrobial agents: A safe preservation approach. IntechOpen. https://doi.org/10.5772/intechopen.80869

Sarkar, B., Bhattacharya, P., Yen Chen, C., Maity, J., & Biswas, T. (2022). A comprehensive characterization and therapeutic properties in ripened Noni fruits (Morinda citrifolia L.). Int. J. Exp. Res. Rev., 29, 10–32. https://doi.org/10.52756/ijerr.2022.v29.002

Sarkar, B., Biswas, P., Acharya, C.K., Ghorai, S.K., Nahar, N., Jana, S.K., Ghosh, S., Sarkar, D., Behera, B., & Madhu, N.R. (2021). Knowledge of Traditional Indian Medicinal Plants for the Management of COPD. Chettinad Health City Medical Journal.10(4), 184–189. https://doi.org/10.36503/chcmj10(4)-05

Sarkar, B., Kotal, H.N., Giri, C.K., Mandal, A., Hudait, N., Madhu, N.R., Saha, S., Basak, S.K., Sengupta, J., & Ray, K. (2024). Detection of a bibenzyl core scaffold in 28 common mangrove and associate species of the Indian Sundarbans: potential signature molecule for mangrove salinity stress acclimation. Frontiers of Plant Science, 14, 1291805. https://doi.org/10.3389/fpls.2023.1291805

Sarker, U., & Oba, S. (2020). Polyphenol and flavonoid profiles and radical scavenging activity in leafy vegetable Amaranthus gangeticus. BMC Plant Biology, 20, 499. https://doi.org/10.1186/s12870-020-02700-0

Shimada, K., Fujikawa, K., Yahara, K., & Nakamura, T. (1992). Antioxidative properties of xanthin on autoxidation of soybean oil in cyclodextrin emulsion. Journal of Agricultural and Food Chemistry, 40(6), 945–948. https://doi.org/10.1021/jf00018a005

Shipley, M. M., Mangold, C. A., & Szpara, M. L. (2016). Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line. Journal of Visualized Experiments: Jove, (108), 53193. https://doi.org/10.3791/53193

Singleton, V. L., Orthofer, R., & Lamuela‐Raventos, R. M. (1999). Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin‐Ciocalteu reagent. Methods in Enzymology, 299, 152–178. https://doi.org/10.1016/S0076-6879(99)99017-1

Sun, Y., Qiao, Y., Liu, Y., Zhou, J., Wang, X., Zheng, H., Xu, Z., Zhang, J., Zhou, Y., Qian, L., Zhang, C., & Lou, H. (2021). Ent-kaurane diterpenoids induce apoptosis and ferroptosis through targeting redox resetting to overcome cisplatin resistance. Redox Biology, 43, 101977.

https://doi.org/10.1016/j.redox.2021.101977

Thirugnanasampandan, R. & Jayakumar, R. (2009). Cytotoxic and anticarcinogenic activity of the ent-kaurene diterpenoid, melissoidesin, from Isodon wightii (Bentham) H. Hara. Natural Product Research, 23(16), 1499–1506. https://doi.org/10.1080/14786410802632812

Thirugnanasampandan, R., Jayakumar, R., Narmatha Bai, V., Martin, E., & Rajendra Prasad, K. J. (2008). Antiacetylcholinesterase and antioxidant ent-Kaurene diterpenoid, melissoidesin from Isodon wightii (Bentham) H. Hara. Natural Product Research, 22(8), 681–688. http://dx.doi.org/10.1080/14786410801990625

Tomic, A., Petrovic, S., Pavlovic, M., Trajkovski, B., Milenkovic, M., Bozic, D., & Niketic, M. (2009). Antimicrobial and antioxidant properties of methanol extracts of two Anthamanta turbith subspecies. Pharmaceutical Biology, 47(4), 314–319. https://doi.org/10.1080/13880200902748452

Turkoglu, S., Turkoglu, I., Kahyaoğlu, M., & Çeli̇k, S. (2010). Determination of antimicrobial and antioxidant activities of Turkish endemic Ajuga chamaepitys (L.) Schreber subsp. euphratica P.H. Davis (Lamiaceae). Journal of Medicinal Plants Research, 4, 1260–1268. https://api.semanticscholar.org/CorpusID:86621474

Ullah, A., Munir, S., Badshah, S. L., Khan, N., Ghani, L., Poulson, B. G., Emwas, A. H., & Jaremko, M. (2020). Important flavonoids and their role as a therapeutic agent. Molecules (Basel, Switzerland), 25(22), 5243. https://doi.org/10.3390/molecules25225243

Verma, M., S., kotwal, S., & Kumar, A. (2024). Exploring the Influence of Arbuscular Mycorrhizal Symbology on the Antioxidant Potential of Liverwort Asterella multiflora: A Comprehensive Study on Rhizoid and Thallus Anatomy. International Journal of Experimental Research and Review, 37(Special Vol), 109–119. https://doi.org/10.52756/ijerr.2024.v37spl.009

Yuan, Y., Du, Y., Hu, X. Y., Liu, M. Y., Du, J. K., Liu, X. M., Yu, H. E., Wang, T. Z., Pu, J. X., Zhong, Q., & Zou, Q. F. (2017). Longikaurin A, a natural ent-kaurane, suppresses stemness in nasopharyngeal carcinoma cells. Oncology Letters, 13(3), 1672–1680. https://doi.org/10.3892/ol.2017.5625

Zhang, H. L., Zhang, Y., Yan, X. L., Xiao, L. G., Hu, D. X., Yu, Q., & An, L. K. (2020). Secondary metabolites from Isodon ternifolius (D. Don) Kudo and their anticancer activity as DNA topoisomerase IB and Tyrosyl-DNA phosphodiesterase 1 inhibitors. Bioorganic & Medicinal Chemistry, 28(11), 115527. https://doi.org/10.1016/j.bmc.2020.115527

Zhu, J., Lian, J., Wang, X., Wang, R., Pang, X., Xu, B., Wang, X., Li, C., Ji, S., & Lu, H. (2023). Role of endogenous and exogenous antioxidants in risk of six cancers: evidence from the Mendelian randomization study. Frontiers in Pharmacology, 14, 1185850. https://doi.org/10.3389/fphar.2023.1185850

Zou, J., Du, X., Pang, G., Shi, Y. M., Wang, W. G., Zhan, R., Kong, L. M., Li, X. N., Li, Y., Pu, J. X., & Sun, H. D. (2012). Ternifolide A, a new diterpenoid possessing a rare macrolide motif from Isodon ternifolius. Organic Letters, 14(12), 3210–3213. https://doi.org/10.1021/ol3013205

Zou, Q. F., Du, J. K., Zhang, H., Wang, H. B., Hu, Z. D., Chen, S. P., Du, Y., Li, M. Z., Xie, D., Zou, J., Sun, H. D., Pu, J. X., & Zeng, M. S. (2013). Anti-tumour activity of longikaurin A (LK-A), a novel natural diterpenoid, in nasopharyngeal carcinoma. Journal of Translational Medicine, 11, 200. https://doi.org/10.1186/1479-5876-11-200.