Current Research On Pharmacological and Toxicological of Croton tiglium Linn.
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Abstract
Croton tiglium L., commonly known as Purging Croton and classified under the Euphorbiaceae family, has been traditionally used in Thai medicine as a potent purgative to treat colic, asthma, cough, phlegm, lymphatic disorders, cathartic, blood disorders, and parasitic infections. The seeds of Croton tiglium are incorporated in various formulations for treating symptoms resembling cancer. The chemical composition of the seeds includes oil (30.00-56.00%), carbohydrates (16.15%), proteins (16.00%), fibers (8.25%), and ash (3.60%). Key chemical constituents of the seeds are phorbol esters such as Phorbol-12-myristate-13-acetate, along with alkaloids, fatty acids, and amino acids. Phorbol esters exhibit a range of pharmacological activities, including antifungal, antiviral, antibacterial, laxative, vaccine adjuvant and anti-inflammatory properties. Notably, they demonstrate significant anticancer properties, effectively inhibiting the growth of cancer cells, including liver cancer, leukemia, lung cancer, prostate cancer, breast cancer, and gastric cancer. The inhibitory concentrations (IC50) of these compounds are typically within the micromolar range. Despite its medicinal potential, the presence of phorbol-12-myristate-13-acetate (PMA) poses a major drawback due to its toxicity and role as a tumor promoter. Various methods have been developed to reduce the toxicity of Croton tiglium seeds, effectively lowering PMA levels. However, comprehensive data on the reduction of carcinogenic promotion activity is still lacking. If these detoxification methods can be proven to effectively reduce both PMA levels and its carcinogenic promotion activity, Croton tiglium could emerge as a promising herbal alternative for cancer treatment. Recent discoveries highlight the potential of phorbol esters as Protein kinase C (PKC) activators that inhibit specific PKC isoforms linked to cancer inhibition. The development of cancer therapies targeting specific PKC isoforms is currently a significant area of interest.
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References
Beyer J, Esser H-J, Eurlings M, Vanwelzen P. A revision of the genus Croton (Euphorbiaceae) in Sumatra (Indonesia). Blumea. 2023;68(1):1-25.
Zhang X-l, Khan AA, Wang L-x, Yu K, Li F, Wang M-k. Four new phorbol diesters from Croton tiglium and their cytotoxic activities. Phytochem Lett. 2016;16:82-86.
Wang JF, Yang SH, Liu YQ, Li DX, He WJ, Zhang XX, et al. Five new phorbol esters with cytotoxic and selective anti-inflammatory activities from Croton tiglium. Bioorg Med Chem Lett. 2015;25(9):1986-1989.
Li C, Wu X, Sun R, Zhao P, Liu F, Zhang C. Croton tiglium Extract Induces Apoptosis via Bax/Bcl-2 Pathways in Human Lung Cancer A549 Cells. Asian Pac J Cancer Prev. 2016;17(11):4893-4898.
Zhang T, Liu Z, Sun X, Liu Z, Zhang L, Zhang Q, et al. Botany, traditional uses, phytochemistry, pharmacological and toxicological effects of Croton tiglium Linn.: a comprehensive review. J Pharm Pharmacol. 2022;74(8):1061-1084.
กระทรวงสาธารณสุข. ยาควบคุมพิเศษ. ราชกิจจานุเบกษา เล่มที่ 95 ตอนที่ 68 วันที่ 4 กรกฎาคม 2521 2521. p. 2072-2075.
Lin SC, Lin CC, Li S, Lin WY, Lehman CW, Bracci NR, et al. Alleviation of Collagen-Induced Arthritis by Crotonoside through Modulation of Dendritic Cell Differentiation and Activation. Plants (Basel). 2020;9(11).
Lin HC, Kuo YL, Lee WJ, Yap HY, Wang SH. Antidermatophytic Activity of Ethanolic Extract from Croton tiglium. Biomed Res Int. 2016;2016:3237586.
Ahmed S, Riaz M, Malik A, Shahid M. Effect of seed extracts of Withania somnifera, Croton tiglium and Hygrophila auriculata on behavior and physiology of Odontotermes obesus (Isoptera, Termitidae). Biologia. 2007;62(6):770-773.
Salatino A, Salatino MLF, Negri G. Traditional uses, chemistry and pharmacology of Croton species (Euphorbiaceae). J Braz Chem Soc 2007;18:11-33.
Liu Z, Gao W, Zhang J, Hu J. Antinociceptive and Smooth Muscle Relaxant Activity of Croton tiglium L Seed: An In-vitro and In-vivo Study. Iran J Pharm Res. 2012;11(2):611-620.
Department of Thai Traditional and Alternative Medicine. Handbook in Thai traditional pharmacy for preparing herbal ingredient. Nonthaburi: The War Veterans Organization of Thailand Under Royal Patronage His majesty the King; 2014.
Kongkum A, Caichompoo W, Nualkaew S. Amount of Phorbol-12-myristate-13-acetate (PMA) in Croton tiglium L. Seed Before and After Treatment using Methods of Thai Traditional Medicine. J Sci Technol MSU. 2013;33(1):19-25.
Aboulthana WM, Youssef A, El-Feky AM, Ibrahim NE-S, Seif MM, Hassan AK. Evaluation of antioxidant efficiency of Croton tiglium L. seeds extracts after incorporating silver nanoparticles. Egypt J Chem. 2019;62(2):181-200.
Kim M-S, Kim H-R, So H-S, Lee Y-R, Moon H-C, Ryu D-G, et al. Crotonis fructus and its constituent, croton oil, stimulate lipolysis in OP9 adipocytes. Evid Based Complement Alternat Med. 2014;2014.
Akbar S. Croton tiglium L. (Euphorbiaceae). Handbook of 200 Medicinal Plants: A Comprehensive Review of Their Traditional Medical Uses and Scientific Justifications. Cham: Springer International Publishing; 2020. p. 741-747.
Yu L, Wu X, Chen M, Huang H, He Y, Wang H, et al. The Effects and Mechanism of YK-4-279 in Combination with Docetaxel on Prostate Cancer. Int J Med Sci. 2017;14(4):356-366.
Matsuya Y, Yu Z, Yamamoto N, Mori M, Saito H, Takeuchi M, et al. Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity. Bioorg Med Chem. 2005;13(14):4383-4388.
El-Mekkawy S, Meselhy MR, Nakamura N, Hattori M, Kawahata T, Otake T. Anti-HIV-1 phorbol esters from the seeds of Croton tiglium. Phytochemistry. 2000;53(4):457-464.
Pillai NR. Gastro intestinal effects of Croton tiglium in experimental animals. Anc Sci Life. 1999;18(3-4):205-209.
Hu J, Gao W-Y, Gao Y, Ling N-S, qi H, Liu C-X. M3 muscarinic receptor- and Ca2+ influx-mediated muscle contractions induced by croton oil in isolated rabbit jejunum. Journal of ethnopharmacology. 2010;129:377-380.
Oh DR, Kang HW, Kim JR, Kim S, Park IK, Rhee JH, et al. PMA induces vaccine adjuvant activity by the modulation of TLR signaling pathway. Mediators Inflamm. 2014;2014:406514.
Weiss A, Wiskocil RL, Stobo JD. The role of T3 surface molecules in the activation of human T cells: a two-stimulus requirement for IL 2 production reflects events occurring at a pre-translational level. J Immunol. 1984;133(1):123-128.
Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49-63.
Matias D, Bessa C, Simões MF, Reis CP, Saraiva L, Rijo P. Natural products as lead protein kinase c modulators for cancer therapy. Studies in natural products chemistry. 2016;50:45-79.
Baird WM, Boutwell RK. Tumor-promoting activity of phorbol and four diesters of phorbol in mouse skin. Cancer Res. 1971;31(8):1074-1079.
Upadhyay RR. Tumour-promoting diterpene esters of the plant family Euphorbiaceae. 1996.
Raick AN, Thumm K, Chivers BR. Early effects of 12-O-tetradecanoyl-phorbol-13-acetate on the incorporation of tritiated precursor into DNA and the thickness of the interfollicular epidermis, and their relation to tumor promotion in mouse skin. Cancer Res. 1972;32(7):1562-1568.
Van Duuren BL, Sivak A. Tumor-promoting agents from Croton tiglium L. and their mode of action. Cancer Res. 1968;28(11):2349-2356.
Van Duuren BL. Tumor-promoting agents in two-stage carcinogenesis. Prog Exp Tumor Res. 1969;11:31-68.
Pal PK, Nandi MK, Singh NK. Detoxification of Croton tiglium L. seeds by Ayurvedic process of Śodhana. Ancient science of life. 2014;33(3):157-161.