Vitex trifolia’s molecular anti-inflammatory effect: a review

Main Article Content

Ahmad Tamim Ghafari
Aisyah Hasyila Jahidin
Yuslina Zakaria
Mizaton Hazizul Hasan

Abstract

Inflammation is defined as a defensive response of the body against invading agents and harmful stimuli directly involved in the pathophysiology of various chronic diseases. Conventional anti-inflammatories have always been the first choice to treat and control inflammation and inflammation-related diseases. However, researchers have been searching for safer alternatives to conventional drugs with fewer possible side effects. Medicinal plants are considered potent alternatives to these drugs. Thus, understanding the molecular mechanisms of these plants and their biological targets can provide a new prospect for developing new anti-inflammatory agents with safer effects. Vitex trifolia belongs to the family Verbenaceae, a multipurpose medicinal plant, which can exhibit anti-inflammatory property. In recent literature, the plant was reported to have significant anti-inflammatory actions, including inhibitory effects on pro-inflammatory signaling pathways and mediators. Herein, the molecular anti-inflammatory effects of Vitex trifolia and its active components during inflammation have been reviewed.

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How to Cite
Tamim Ghafari, A., Hasyila Jahidin, A., Zakaria, Y., & Hazizul Hasan, M. (2021). Vitex trifolia’s molecular anti-inflammatory effect: a review. Science, Engineering and Health Studies, 15, 21010006. https://doi.org/10.14456/sehs.2021.56
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Editorials and Reviews

References

Abd Aziz, S. M., Low, C. N., Chai, L. C., Abd Razak, S. S. N., Selamat, J., Son, R., Sarker, M. Z. I., and Khatib, A. (2011). Screening of selected malaysian plants against several food borne pathogen bacteria. International Food Research Journal, 18(3), 1195-1201.

Abdul Hakeem, N. R. S., Md Yusof, N., Jahidin, A. H. Hasan, M. H., Mohsin, H. S., Abdul Wahab, I. (2016). Vitex species: review on phytochemistry and pouch design for nutritional benefits. Scientific Research Journal, 13(2), 15-28.

Adwas, A. A., Elsayed, A. S. I., Azab, A. E., and Quwaydir, A. (2019). Oxidative stress and antioxidant mechanisms in human body. Journal of Applied Biotechnology and Bioengineering, 6(1), 43-47.

Ahmed, A. U. (2011). An overview of inflammation: mechanism and consequences. Frontiers in Biology, 6(4), 274-281.

Alam, G., Wahyuono, S., Ganjar, I. G., Hakim, L., Timmerman, H., and Verpoorte, R. (2002). Tracheospasmolytic activity of viteosin-A and vitexicarpin isolated from Vitex trifolia. Planta Medica, 68(11), 1047-1049.

Anandan, R., Jayakar, B., Karar, B., Babuji, S., Manavalan, R., and Kumaf ethanolr, R. S. (2009). Effect of ethanol extract of flowers of Vitex trifolia Linn. on CCl4-induced hepatic injury in rats. Pakistan Journal of Pharmaceutical Sciences, 22(4), 391-394.

Ankalikar, A., and Viswanathswamy, A. H. (2017a). Effect of leaves of Vitex. trifolia Linn on different stages of inflammation. Indian Journal of Pharmaceutical Education and Research, 51(3), 461-471.

Ankalikar, A., and Viswanthswamy, A. H. (2017b). Effect of Vitex trifolia Linn and Solanum nigrum Linn on oxidative stress and inflammation. Indian Journal of Health Sciences and Biomedical Research, 10(3), 269-275.

Aoki, T., and Narumiya, S. (2012). Prostaglandins and chronic inflammation. Trends in Pharmacological Sciences, 33(6), 304-311.

Awaludin, S. M., Ahmad, N. A., Naidu, B. M., Yusof, M., Abd Razak, M. A., and Abdul Ghani, M. K. A. (2017). Prevalence of non-steroidal anti-inflammatory drugs (NSAIDs) use in Malaysian adults and associated factors: a population-based survey. Malaysian Journal of Public Health, 17(3), 58-65.

Aye, M. M., Aung, H. T., Sein, M. M., and Armijos, C. (2019). A review on the phytochemistry, medicinal properties and pharmacological activities of 15 selected Myanmar medicinal plants. Molecules, 24(2), 1-34.

Bao, F., Tang, R., Cheng, L., Zhang, C., Qiu, C., Yuan, T., Zhu, L., Li, H., and Chen, L. (2018). Terpenoids from Vitex trifolia and their anti-inflammatory activities. Journal of Natural Medicines, 72(2), 570-575.

Bello, M. O., Zaki, A. A., Aloko, S., Fasinu, P. S., Bello, E. O., Ajao, U. L., and Oguntoye, O. S. (2018). The genus Vitex: an overview of iridoids as chemotaxonomic marker. Journal of Basic and Applied Sciences, 7(4), 414-419.

Benly, P. (2015). Role of histamine in acute inflammation. Journal of Pharmaceutical Sciences and Research, 7(6), 373-376.

Borish, L. C., and Steinke, J. W. (2003). 2. Cytokines and chemokines. Journal of Allergy and Clinical Immunology, 111(2), 460-475.

Branco, A. C. C. C., Yoshikawa, F. S. Y., Pietrobon, A. J., and Sato, M. N. (2018). Role of histamine in modulating the immune response and inflammation. Mediators of Inflammation, 2018, 9524075.

Chan, E. W. C., Baba, S., Chan, H. T., Kainuma, M., and Tangeh, J. (2016). Medicinal plants of sandy shores: a short review on Vitex trifolia L. and Ipomoea pes-caprae (L.) R. Br. Indian Journal of Natural Products and Resources, 7(2), 107-115.

Chan, E. W. C., Wong, S. K., and Chan, H. T. (2018). Casticin from Vitex species: a short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 16(3), 147-152.

Chantaranothai, P. (2011). A revision of the genus Vitex (Lamiaceae) in Thailand. Tropical Natural History, 11(2), 91-118.

Chelombitko, M. A. (2018). Role of reactive oxygen species in inflammation: a minireview. Moscow University Biological Sciences Bulletin, 73, 199-202.

Chen, L., Deng, H., Cui, H., Fang, J., Zuo, Z., Deng, J., Li, Y., Wang, X., and Zhao, L. (2018a). Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 9(6), 7204-7218.

Chen, Y., Zhou, Z., and Min, W. (2018b). Mitochondria, oxidative stress and innate immunity. Frontiers in Physiology, 9(1487), 1-10.

Chinsembu, K. C. (2019). Chemical diversity and activity profiles of HIV-1 reverse transcriptase inhibitors from plants. Brazilian Journal of Pharmacognosy, 29(4), 504-528.

Cinelli, M. A., Do, H. T., Miley, G. P., and Silverman, R. B. (2020). Inducible nitric oxide synthase: regulation, structure, and inhibition. Medicinal Research Reviews, 40(1), 158-189.

Conegundes, J. L. M., da Silva, J. M., Freitas R. M., Fernandes, M. F., Pinto, N. C. C., de Almeida, M. A., Dib, P. R. B., Andrade, R, A., Rodrigues, M. N., Castañon, M. C. M. N., Macedo, G. C., Scio, E. (2020). Anti-inflammatory and antinociceptive activity of Siparuna guianensis Aublet, an Amazonian plant traditionally used by indigenous communities. Journal of Ethnopharmacology, 265(2021), 1-12.

De Oliveira, C. M. B., Sakata, R. K., Issy, A. M., Gerola, L. R., and Salomão, R. (2011). Cytokines and Pain. Revista Brasileira de Anestesiologia, 61(2), 255-265.

Dehsheikh, A. B., Sourestani, M. M., Dehsheikh, P. B., Vitalini, S., Iriti, M., and Mottaghipisheh, J. (2019). A comparative study of essential oil constituents and phenolic compounds of arabian lilac (Vitex trifolia var. Purpurea): an evidence of season effects. Foods, 8(2), 1-14.

Devi, W., R., and Singh, C., B. (2014). Chemical composition, anti-dermatophytic activity, antioxidant and total phenolic content within the leaves essential oil of Vitex trifolia. International Journal of Phytocosmetic and Natural Ingredients, 1(5), 1-5.

Dinarello, C. A. (2007). Historical insights into cytokines. European Journal of Immunology, 37(1), 34-45.

El-Kousy, S., Mohamed, M., and Mohamed, S. (2012). Phenolic and biological activities of Vitex trifolia aerials parts. Life Sciences Journal, 9(2), 670-677.

Fang, S. M., Liu, R., Li, L., Yao, J. L., Liu, E. W., Fan, G. W., Zhang, H., and Gao, X. M. (2018). Anti-inflammatory diterpenes from the fruits of Vitex trifolia L. var. simplicifolia Cham. Journal of Asian Natural Products Research, 21(10), 985-991.

Feghali, C. A., and Wright, T. M. (1997). Cytokines in acute and chronic inflammation. Frontiers in Bioscience, 2(4), 12-26.

Ferreira, V. L., Borba, H. H. L., Bonetti, A. de F., Leonart, L. P., and Pontarolo, R. (2018). Cytokines and interferons: types and functions. In Autoantibodies and Cytokines (Khan, W. A., ed.), pp. 65-87. London: IntechOpen Ltd.

Forrester, S. J., Kikuchi, D. S., Hernandes, M. S., Xu, Q., and Griendling, K. K. (2018). Reactive oxygen species in metabolic and inflammatory signaling. Circulation Research, 122(6), 877-902.

Garbi, M. I., Osman, E. E., Dahab, M. M., Koko, W. S., Kabbashi, A. S., Elegami, A. A., and Hamed., S. Y. (2015). Antigiardial, antiamoebic and cytotoxic activity of the leaves extracts of Vitex trifolia. Advancement in Medicinal Plant Research, 3(1), 1-7.

Ghafari, A. T., Jahidin, A. H., Zakaria, Y., and Hasan, M. H. (2020). Phytochemical screening and high-performance thin-layer chromatography quantification of Vitex trifolia leaves hydro-alcoholic extract: potential anti-inflammatory properties. Journal of Pharmaceutical Research International, 33(28A), 111-121.

Ghasemian, M., Owlia, S., and Owlia, M. B. (2016). Review of anti-inflammatory herbal medicines. Advances in Pharmacological Sciences, 2016, 1-11.

Goverdhan, P., and Bobbala, D. (2009). Anti-nociceptive and anti-inflammatory effects of the leaf extract of Vitex trifolia Linn. in experimental animals. Ethnobotanical Leaflets, 13, 65-72.

Hernandez, M. M., Heraso, C., Villarreal, M. L., Vargas-Arispuro, I., and Aranda, E. (1999). Biological activities of crude plant extracts from Vitex trifolia L. (Verbenaceae). Journal of Ethnopharmacology, 67(1), 37-44.

Hegazi, A. G., and Abdel-Rahman, E. H. (2015). Cytokines. Innovative Immunology, 1-38.

Holbrook, J., Lara-Reyna, S., Jarosz-Griffiths, H., and McDermott, M. F. (2019). Tumour necrosis factor signaling in health and disease. F1000Research, 28(8), 111.

Huang, M., Zhang, L., Zhou, F., Ma, X., Li, Z., Zhong, T., and Zhang, Y. (2016). A new ursane triterpenoid possessing cytotoxicity from the fruits of Vitex trifolia var. simplicifolia. Chemistry of Natural Compounds, 52(4), 660-663.

Hussain, T., Tan, B., Yin, Y., Blachier, F., Tossou, M. C. B., and Rahu, N. (2016). Oxidative stress and inflammation: what polyphenols can do for us? Oxidative Medicine and Cellular Longevity, 2016, 1-9.

Ikawati, Z., Wahyuono, S., and Maeyama, K. (2001). Screening of several indonesian medicinal plants for their inhibitory effect on histamine release from RBL-2H3 cells. Journal of Ethnopharmacology, 75(2-3), 249-256.

Jangwan, J. S., Aquino, R. P., Mencherini, T., Picerno, P., and Singh, R. (2014). Chemical constituents of ethanol extract of leaves and molluscicidal activity of crude extracts from Vitex trifolia Linn. Herba Polonica, 59(4), 19-32.

Kapoor, M., Martel-Pelletier, J., Lajeunesse, D., Pelletier, J. P., and Fahmi, H. (2011). Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nature Reviews Rheumatology, 7(1), 33-42.

Kasote, D. M., Katyare, S. S., Hegde, M. V., and Bae, H. (2015). Significance of antioxidant potential of plants and its relevance to therapeutic applications. International Journal of Biological Sciences, 11(8), 982-991.

Khanapure, S. P., Garvey, D. S., Janero, D. R., and Gordon Letts, L. (2007). Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Current Topics in Medicinal Chemistry, 7(3), 311-340.

Laxmikant, K. (2011a). Anti-inflammatory activity of Vitex trifolia Linn. (verbaneaceae) leaves extracts. International Journal of Pharmaceutical Sciences and Research, 2(8), 2037-2040.

Laxmikant, K. (2011b). Pharmacological review on Vitex trifolia Linn. (Verbaneaceae). Pharmacologyonline, 3, 858-863.

Laxmikant, K. (2012). Vitex trifolia Linn. (Verbaneaceae): A review on pharmacological and biological effects, isolated and known potential phytoconstituents of therapeutic importance. International Journal of Research in Pharmaceutical Sciences, 3(3), 441-445.

Laxmikant, K. (2014). Analgesic potential of Vitex trifolia Linn (verbaneacae). Asian Journal of Pharmaceutical and Clinical Research, 7(1), 157-159.

Lee, C., Lee, J. W., Jin, Q., Lee, H. J., Lee, S. J., Lee, D., Lee, M. K., Lee, C. K., Hong, J. T., Lee, M. K., and Hwang, B. Y. (2013). Anti-inflammatory constituents from the fruits of Vitex rotundifolia. Bioorganic and Medicinal Chemistry Letters, 23(21), 6010-6014.

Lee, G., Jung, K. H., Ji, E. S., and Bae, H. (2017). Pyranopyran-1,8-dione, an active compound from Vitices Fructus, attenuates cigarette-smoke induced lung inflammation in mice. International Journal of Molecular Sciences, 18(7), 110.

Lee, S. M., Lee, Y. J., Kim, Y. C., Kim, J. S., Kang, D. G., and Lee, H. S. (2012). Vascular protective role of vitexicarpin isolated from Vitex rotundifolia in human umbilical vein endothelial cells. Inflammation, 35(2), 584-593.

Liou, C. J., Cheng, C. Y., Yeh, K. W., Wu, Y. H., and Huang, W. C. (2018). Protective effects of casticin from Vitex trifolia alleviate eosinophilic airway inflammation and oxidative stress in a murine asthma model. Frontiers in Pharmacology, 9, 1-12.

Liou, C. J., Len, W. B., Wu, S. J., Lin, C. F., Wu, X. L., and Huang, W. C. (2014). Casticin inhibits COX-2 and iNOS expression via suppression of NF-κB and MAPK signaling in lipopolysaccharide-stimulated mouse macrophages. Journal of Ethnopharmacology, 158(2014), 310-316.

Liu, Z. G. (2005). Molecular mechanism of TNF signaling and beyond. Cell Research, 15(1), 24-27.

Luo, P., Xia, W., Morris-Natschke, S. L., Lee, K. H., Zhao, Y., Gu, Q., and Xu, J. (2017). Vitepyrroloids A–D, 2-cyanopyrrole-containing labdane diterpenoid alkaloids from the leaves of Vitex trifolia. Journal of Natural Products, 80(5), 1679-1683.

Mary, R. N. I., and Banu, N. (2015). Screening of antibiofilm and anti-quorum sensing potential of Vitex trifolia in Pseudomonas aeruginosa. International Journal of Pharmacy and Pharmaceutical Sciences, 7(8), 242-245.

Matsui, M., Adib-Conquy, M., Coste, A., Kumar-Roiné, S., Pipy, B., Laurent, D., and Pauillac, S. (2012). Aqueous extract of Vitex trifolia L. (Labiatae) inhibits LPS-dependent regulation of inflammatory mediators in RAW 264.7 macrophages through inhibition of nuclear factor kappa B translocation and expression. Journal of Ethnopharmacology, 143(1), 24-32.

Matsui, M., Kumar-Roine, S., Darius, H. T., Chinain, M., Laurent, D., and Pauillac, S. (2009). Characterisation of the anti-inflammatory potential of Vitex trifolia L. (labiatae), a multipurpose plant of the pacific traditional medicine. Journal of Ethnopharmacology, 126(3), 427-433.

Medzhitov, R. (2008). Origin and physiological roles of inflammation. Nature, 454, 428-435.

Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., and Malik, A. B. (2014). Reactive oxygen species in inflammation and tissue injury. Antioxidants and Redox Signaling, 20(7), 1126-1167.

Mogensen, T. H. (2009). Pathogen recognition and inflammatory signaling in innate immune defenses. Clinical Microbiology Reviews, 22(2), 240-273.

Mu, Y., Hao, W., and Li, S. (2019). Casticin protects against IL-1β-induced inflammation in human ortheoarthritis chodrocytes. European Journal of Pharmacology, 842, 314-320.

Nishina, A., Itagaki, M., Sato, D., Kimura, H., Hirai, Y., Phay, N., and Makishima, M. (2017). The Rosiglitazone-like effects of vitexilactone, a constituent from Vitex trifolia L. in 3T3-L1 preadipocytes. Molecules, 22(2), 1-13.

Nurul Amin, M., Siddiqui, S. A., Ibrahim, M., Lukman Hakim, M., Ahammed, M. S., Kabir, A., and Sultana, F. (2020). Inflammatory cytokine in the pathogenesis of cardiovascular disease and cancer. Medicine, 8, 1-12.

Nworu, C. S., and Akah, P. A. (2015). Anti-inflammatory medicinal plants and the molecular mechanisms underlying their activities. African Journal of Traditional, Complementary and Alternative Medicines, 12, 52-61.

Orwa, C., Mutua, A., Kindt, R., Jamnadass, R., and Anthony S. (2009). Agroforestree Database: a tree reference and selection guide version 4.0. [Online URL: http://www.worldagroforestry.org/sites/treedbs/treedatabases.asp] accessed on January 25, 2021.

Palm, N. W., and Medzhitov, R. (2009). Pattern recognition receptors and control of adaptive immunity. Immunological Reviews, 227(1), 221-233.

Pizzino, G., Irrera, N., Cucinotta, M., Pallio, G., Mannino, F., Arcoraci, V., Squadrito, F., Altavilla, D., and Bitto, A. (2017). Oxidative stress: harms and benefits for human health. Oxidative Medicine and Cellular Longevity, 2017, 1-13.

Placha, D. and Janpilek, J. (2021). Chronic inflammatory diseases, anti-inflammatory agents and their delivery nanosystems. Pharmaceutics, 13(1), 64.

Planas, A. M., Gorina, R., and Chamorro, Á. (2006). Signaling pathways mediating inflammatory responses in brain ischaemia. Biochemical Society Transactions, 34(6), 1267-1270.

Rani, A., and Sharma, A. (2013). The genus Vitex: a review. Pharmacognosy Reviews, 7(14), 188-198.

Ricciotti, E., and Fitzgerald, G. A. (2011). Prostaglandins and inflammation. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(5), 986–1000.

Roshene, R., and Ramesh, A. (2017). Cytokines. Journal of Pharmaceutical Sciences and Research, 9(5), 719-721.

Saklani, S., Mishra, A. P., Chandra, H., Atanassova, M. S., Stankovic, M., Sati, B., Shariati, M. A., Nigam, M., Khan, M. U., Plygun, S., Elmsellem, H., and Suleria, H. A. R. (2017). Comparative evaluation of polyphenol contents and antioxidant activities between ethanol extracts of Vitex negundo and Vitex trifolia L. leaves by different methods. Plants, 6(4), 1-11.

Salvemini, D., Ischiropoulos, H., and Cuzzocrea, S. (2003). Roles of nitric oxide and superoxide in inflammation. Methods in Molecular Biology, 225(2014), 291-303.

Serasanambati, M., and Chilakapati, S. R. (2016). Function of nuclear factor kappa B (NF-kB) in human diseases-a review. South Indian Journal of Biological Sciences, 2(4), 368-387.

Shahid, M., Tripathi, T., Sobia, F., Moin, S., Siddiqui, M., and Khan, R. A. (2009). Histamine, histamine receptors, and their role in immunomodulation: An updated systematic review. The Open Immunology Journal, 2, 9-41.

Stojković, N., Cekić, S., Ristov, M., Ristić, M., Đukić, D., Binić, M., and Virijević, D. (2015). Histamine and antihistamines. Acta Facultatis Medicae Naissensis, 32(1), 7-22.

Suchitra, M., and Cheriyan, B. V. (2018). Vitex trifolia: An ethnobotanical and pharmacological review. Asian Journal of Pharmaceutical and Clinical Research, 11(4), 12-14.

Sujarwo, W., Keim, A. P., Savo, V., Guarrera, P. M., and Caneva, G. (2015). Ethnobotanical study of Loloh: Traditional herbal drinks from Bali (Indonesia). Journal of Ethnopharmacology, 169, 34-48.

Szollosi, D. E., Manzoor, M. K., Aquilato, A., Jackson, P., Ghoneim, O. M., and Edafiogho, I. O. (2018). Current and novel anti-inflammatory drug targets for inhibition of cytokines and leucocyte recruitment in rheumatic diseases. Journal of Pharmacy and Pharmacology, 70(1), 18-26.

Tasneem, S., Liu, B., Li, B., Choudhary, M. I., and Wang, W. (2019). Molecular pharmacology of inflammation: medicinal plants as anti-inflammatory agents. Pharmacological Research, 139, 126-140.

Thalhamer, T., McGrath, M. A., and Harnett, M. M. (2008). MAPKs and their relevance to arthritis and inflammation. Rheumatology, 47(4), 409-414.

Thangam, E. B., Jemima, E. A., Singh, H., Baig, M. S., Khan, M., Mathias, C. B., Church, M. K., and Saluja, R. (2018). The role of histamine and histamine receptors in mast cell-mediated allergy and inflammation: the hunt for new therapeutic targets. Frontiers in Immunology, 9, 1873

Thenmozhi, S., Vibha, S., Dhanalakshmi, M., Manjuladevi, K., Diwedi, S. and Subasini, U. (2013). Evaluation of anthelmintic activity of Vitex trifolia Linn. leaves against Pheretima posthuma. International Journal of Pharmaceutical and Biological Archives 2013, 4(5), 878- 880.

Tiwari, N., Luqman, S., Masood, N., and Gupta, M. M. (2012). Validated high performance thin layer chromatographic method for simultaneous quantification of major iridoids in Vitex trifolia and their antioxidant studies. Journal of Pharmaceutical and Biomedical Analysis, 61(2012), 207-214.

Tsai, T. Y., Li, C. Y., Livneh, H., Lin, I. H., Lu, M. C., and Yeh, C. C. (2016). Decreased risk of stroke in patients receiving traditional Chinese medicine for vertigo: A population-based cohort study. Journal of Ethnopharmacology, 184(2016), 138-143.

Van Lap, H. (2013). Verbenaceae -Vitex trifolia. Flickr [Online URL: https://www.flickr.com/photos/35334437@N05/9800815094] accessed on April 18, 2021.

Vimalanathan, S., Ignacimuthu, S., and Hudson, J. B. (2009). Medicinal plants of Tamil Nadu (Southern India) are a rich source of antiviral activities. Pharmaceutical Biology, 47(5), 422-429.

Wang, P., Geng, J., Gao, J., Zhao, H., Li, J., Shi, Y., Yang, B., Xiao, C., Linghu, Y., Sun, X., Chen, X., Hong, L., Qin, F., Li, X., Yu, J. S., You, H., Yuan, Z., Zhou, D., Johnson, R. L., and Chen, L. (2019a). Macrophage achieves self-protection against oxidative stress-induced ageing through the Mst-Nrf2 axis. Nature Communications, 10(755), 1-16.

Wang, T., Fu, X., Chen, Q., Patra, J. K., Wang, D., Wang, Z., and Gai, Z. (2019b). Arachidonic acid metabolism and kidney inflammation. International Journal of Molecular Sciences, 20(15), 1-28.

Wee, H. N., Neo, S. Y., Singh, D., Yew, H. C., Qiu, Z. Y., Tsai, X. R. C., How, S. Y., Yip, K. Y. C., Tan, C. H., and Koh, H. L. (2020). Effects of Vitex trifolia L. leaf extracts and phytoconstituents on cytokine production in human u937 macrophages. BMC Complementary Medicine and Therapies, 20, 91.

Wu, Z., Li, W., Liu, G., and Tang, Y. (2018). Network-based methods for prediction of drug-target interactions. Frontiers in Pharmacology, 9, 1134.

Zhang, J. M., and An, J. (2009). Cytokines, inflammation and pain. International Anesthesiology Clinics, 45(2), 27-37.

Zheng, C. J., Zhu, J. Y., Yu, W., Ma, X. Q, Rahman, K., and Qin, L. P, (2013). Labdane-type diterpenoids from the fruits of Vitex trifolia. Journal of Natural Products, 76(2), 287-291.