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Type :thesis
Subject :QH Natural history
Main Author :Azam Muzafar Ahmad Mokhtar
Title :Histological effects of Aqueous extract from Aquilaria malaccensis and Aquilaria subintegra towards ICR mice
Place of Production :Tanjong Malim
Publisher :Fakulti Sains dan Matematik
Year of Publication :2022
Corporate Name :Universiti Pendidikan Sultan Idris
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Abstract : Universiti Pendidikan Sultan Idris
The study was conducted to investigate the acute toxicity of aqueous extract from Aquilaria malaccensis (AMAE) and Aquilaria subintegra (ASAE) leaves and their histological effects on several organ in ICR mice. Comparison between both extracts was included in order to determine which toxicity is more potent. A total of 156 ICR mice was used in this study consisted of 78 male and 78 female with the age of 12 weeks old. The mice were divided into 13 groups containing 12 mice (6 males and 6 females) in each group. 12 groups orally received one type of extract either AMAE or ASAE with only one type concentration. The concentrations used were 4000, 5000, 6000, 7000, 8000, 9000 mg/kg body weight. One group on the other hand act as the control and treated with distilled water. Extract administration was conducted only once on the first day. Mice body weight and organ weight were compared and analyzed using one-way ANOVA and evaluation of abnormalities in term of appearance and behavioral were conducted. After the 14th day, mice undergone euthanisation approved by UPSI ethics committee (reference number: 2021-0002-03) in order to conduct histological analysis on their organs which were liver, kidney and stomach. Evaluation on their cellular structure were also conducted. Results showed significant differences in both AMAE and ASAE male mice body weight. AMAE also showed higher significant difference when compared with ASAE using t-test. On top of that, all treated mice displayed drowsiness and their fur seems to be affected, primarily AMAE and ASAE female mice face fur which appeared to be balding. Faeces condition in some AMAE treatment groups also showed abnormalities. In terms of histological evaluation, mice liver, kidney and stomach tissues were also affected. Some liver’s portal vein and sinusoids in AMAE treatment were filled with blood. All treated mice glomerulus expanded while some glomeruli burst in AMAE treatment. All treated mice mucosa length reduced and some gastric glands in AMAE treatment showed abnormal changes. Therefore, it can be stated that both Aquilaria malaccensis and Aquilaria subintegra is toxic due to the adverse effects it caused on mice appearance, behaviour and organ tissues. Furthermore, Aquilaria malaccensis showed more adverse reactions compared to Aquilaria subintegra indicating higher toxicity. This implicates that both Aquilaria malaccensis and Aquilaria subintegra can be toxic and unsafe if being use in a higher concentration.

References

Abba S, Omotoso O Dare, & Faculty of Basic Medical Sciences, Department of Anatomy, College of Health Sciences, Kogi State University Anyigba, Nigeria. (2018). Hemorrhagic Centrolobar Necrosis and Cytoplasmic Vacuolation of the Hepatocytes in Syzygium Guineense Chronic Treated Mice. International Journal of Anatomy and Applied Physiology, 99–102. https://doi.org/10.19070/2572-7451-1800018 

Abdul Razak, R. N. H., Ismail, F., Md Isa, M. L., Abdul Wahab, A. Y., Muhammad, H., Ramli, R., & Raja Ismail, R. A. S. (2019). Ameliorative Effects of Aquilaria malaccensis Leaves Aqueous Extract on Reproductive Toxicity Induced by Cyclophosphamide inMaleRats. Malaysian Journal of Medical Sciences,26(1), 44– 57. https://doi.org/10.21315/mjms2019.26.1.4 

Abera, B. (2014). Medicinal plants used in traditional medicine by Oromo people, Ghimbi District,Southwest Ethiopia. Journal of Ethnobiology and Ethnomedicine,10(1), 40. https://doi.org/10.1186/1746-4269-10-40 

Abeysekera, R. A., Wijetunge, S., Nanayakkara, N., Wazil, A. W. M.,Ratnatunga, N. V. I., Jayalath, T., & Medagama, A. (2015).Starfruit toxicity:A cause of both acute kidney injury and chronic kidney disease: a reportof two cases. BMC Research Notes, 8(1), 796. https://doi.org/10.1186/s13104-015-1640-8 

Abid, R., & Mahmood, R. (2018). Acute and sub-acute oral toxicity of ethanol extract of Cassia fistula fruit in male rats. Avicenna Journal of Phytomedicine, (Online First). https://doi.org/10.22038/ajp.2018.11615 

Acharzo, A. K., Bodhankar, S., Mohan, & Thakurdesai, P.(2015). Acuteand repeated doses (28 days)oral toxicity study of glycosidesbased standardizedfenugreek seed extract in laboratory mice. Regulatory Toxicology and Pharmacology, 72(2), 323–334. https://doi.org/10.1016/j.yrtph.2015.05.003 

Adamson, R. H. (2016). The acute lethal dose 50 (LD50) of caffeine in albino rats. Regulatory Toxicology and Pharmacology, 80, 274–276. https://doi.org/10.1016/j.yrtph.2016.07.011 

Ahmed, M., & Azmat, A. (2014). Acute toxicity (lethal dose 50 calculation) and histopathological effects of methanolic extract of Berberis vulgaris in mice. World J. Pharmacol. Res., 3, 1439–1448. 

Aimi Zafirah, Lee, S. Y., & Mohamed, R. (2017). Pharmacological properties of agarwood tea derived from Aquilaria (Thymelaeaceae) leaves: An emerging contemporary herbal drink. Journal of Herbal Medicine, 10, 37–44. https://doi.org/10.1016/j.hermed.2017.06.002 

Aimi Zafirah, Tajuddin, S. N., Runglawan, S., Chaveerach, A., UH, A., MN, M., & Mohamed, R. (2018). Chemical constituents and toxicity effects of leaves from several agarwood tree species (Aquilaria). JOURNAL OF TROPICAL FOREST SCIENCE, 30(3), 342–353. https://doi.org/10.26525/jtfs2018.30.3.342353 

Ajani, E., Sabiu, S., Bamisaye, F., Ibrahim, S., & Salau, B. (2015). Evaluation of the Acute and Sub-acute Toxicity Effects of Ethanolic Leaves Extract of Lagenaria brevifolia (Bitter gourd) on Hepatic and Renal Function of Rats. European Journal of Medicinal Plants, 5(2), 210–219. https://doi.org/10.9734/EJMP/2015/13400 

Ajao, M. Y., & Akindele, A. J. (2013). Anxiolytic and sedative properties of hydroethanolic extract of Telfairia occidentalis leaves in mice.Revista Brasileira de Farmacognosia, 23(2), 301–309. https://doi.org/10.1590/S0102-695X2012005000138 

Akter, S., Islam, M. T., Zulkefeli, M., & Khan, S. I. (2013). Agarwood production-a multidisciplinary field to be explored in Bangladesh. International Journal of Pharmaceutical and Life Sciences, 2(1), 22–32. 

Alam, J., Mujahid, Md., Badruddeen, Jahan, Y., Bagga, P., & Rahman, Md. A. (2017). Hepatoprotective potential of ethanolic extract of Aquilaria agallocha leaves against paracetamol induced hepatotoxicity in SD rats. Journal of Traditional and Complementary Medicine, 7(1), 9–13. https://doi.org/10.1016/j.jtcme.2015.12.006 

Alebachew, M., Kinfu, Y., Makonnen, E., Bekuretsion, Y., Urga, K., & Afework, M. (2015). Toxicological evaluation of methanol leaves extract of Vernonia bipontini Vatke in blood, liver and kidney tissues of mice. African Health Sciences, 14(4), 1012. https://doi.org/10.4314/ahs.v14i4.33 

Ali, H. S., Caballero, C. E., Maunting, N. G., Patricio, M. J. S., & Reyes, L. D. D. (2014). The Effect of Peperomia pellucida (Shiny Bush) Leaf Crude Extract on the Body Temperature of Boiled Milk-Induced Male White Mice. Advancing Pharmacy Research, 1(1). 

Anisuzzman, Md., Hasan, Md. M., Acharzo, A. K., Das, A. K., & Rahman, S. (2017). In Vivo and In Vitro Evaluation of Pharmacological Potentials of Secondary Bioactive Metabolites of Dalbergia candenatensis Leaves. Evidence-Based Complementary and Alternative Medicine, 2017, 1–10. https://doi.org/10.1155/2017/5034827 

Aniszewski, T. (2015). Alkaloids: Chemistry, biology, ecology, and applications (Second). Elsevier. 

Arantes-Rodrigues, R., Henriques, A., Pinto-Leite, R., Faustino-Rocha, A., Pinho-Oliveira, J., Teixeira-Guedes, C., …Oliveira,P. A. (2012). The effects of repeated oral gavage on the health of male CD-1 mice. Lab Animal, 41(5), 129–134. https://doi.org/10.1038/laban0512-129 

Arsad, S., Esa, N., & Hamzah, H. (2014). Histopathologic Changes in Liver and Kidney Tissues from Male Sprague Dawley Rats Treated with Rhaphidophora Decursiva (Roxb.) Schott Extract. Journal of Cytology & Histology, s4(01). https://doi.org/10.4172/2157-7099.S4-001 

Asma Wil, Adila Omar, Noorhuda Awang@Ibrahim, & Saiful Tajuddin. (2014). In Vitro Antioxidant Activity andPhytochemical Screening of A. Malaccensis Leaf Extracts. Journal of Chemical and Pharmaceutical Research, 6(12), 688–693. 

Assouly, P. (2018). Hair Loss Associated With Cucurbit Poisoning. JAMA Dermatology, 154(5), 617. https://doi.org/10.1001/jamadermatol.2017.6128 

Azwanida. (2015). A Review on the Extraction Methods Use in Medicinal Plants, Principle, Strength and Limitation. Medicinal & Aromatic Plants, 04(03). https://doi.org/10.4172/2167-0412.1000196 

Bahrani, H.,Mohamad, J., Paydar,M., & Rothan, H. (2014). Isolation and Characterisation of Acetylcholinesterase Inhibitors from Aquilaria subintegra for the Treatment of Alzheimer’s Disease (AD). Current Alzheimer Research, 11(2), 206–214. https://doi.org/10.2174/1567205011666140130151344 

Balch, P. A. (2010). Prescription for nutritional healing: The A-to-Z guide to supplements. New York: Avery. 

Barden, A., Awang, N., Mulliken, T., & Song, M. (2000). Heart of the matter: Agarwood use and trade and CITES implementation for Aquilaria malaccensis. Cambridge, UK: TRAFFIC International. Retrieved from https://portals.iucn.org/library/efiles/documents/Traf-072.pdf 

Basit, S. A., Stone, C. D., & Gish, R. (2015). Portal Vein Thrombosis. Clinics in Liver Disease, 19(1), 199–221. https://doi.org/10.1016/j.cld.2014.09.012 

Bassam Abdul Rasool Hassan. (2012). Medicinal Plants (Importance and Uses). Pharmaceutica Analytica Acta,03(10). https://doi.org/10.4172/2153-2435.1000e139 

Becker, B. N. (1996). Ginseng-Induced Diuretic Resistance. JAMA: The Journal of the American Medical Association, 276(8), 606. https://doi.org/10.1001/jama.1996.03540080028021 

Bian, X., Chi, L., Gao, B., Tu, P., Ru, H., & Lu, K. (2017). The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLOS ONE, 12(6), e0178426. https://doi.org/10.1371/journal.pone.0178426 

Bönninghoff, R., Schwenke, K., Keese, M., Magdeburg, R., Bitter-Suermann, H., Otto, M., … Sturm, J. (2012). Effect of different liver resection methods on liver damage and regenerationfactorsVEGFand FGF-2 in mice. Canadian Journal of Surgery, 55(6), 389–393. https://doi.org/10.1503/cjs.007911 

Bregman, C. L., Adler, R. R., Morton, D. G., Regan, K. S., & Yano, B. L. (2003). Recommended TissueList for Histopathologic Examination inRepeat-Dose Toxicity and Carcinogenicity Studies: A Proposal of the Society of Toxicologic Pathology (STP). Toxicologic Pathology, 31(2), 252–253. https://doi.org/10.1080/01926230390183751 

Burch, J. B., Augustine, A. D., Frieden, L. A., Hadley, E., Howcroft, T. K., Johnson, R., … Wise, B. C. (2014). Advances in Geroscience: Impact on Healthspan and Chronic Disease. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 69(Suppl 1), S1–S3. https://doi.org/10.1093/gerona/glu041 

Campos-Vega, R., & Oomah, B. D. (2013). Chemistry and classification of phytochemicals. In B. K. Tiwari, N. P. Brunton, & C. S. Brennan (Eds.), Handbook of Plant Food Phytochemicals (pp. 5–48). Oxford: John Wiley & Sons Ltd. https://doi.org/10.1002/9781118464717.ch2 

Carro-Juárez, M., Franco, M. Á., & Rodríguez-Peña, M. de L. (2014). Increase of the Ejaculatory Potency by the Systemic Administration of Aqueous Crude Extracts of Cihuapatli ( Montanoa Genus) Plants in Spinal Male Rats. Journal of Evidence-Based Complementary & Alternative Medicine, 19(1), 43–50. https://doi.org/10.1177/2156587213510006 

Chapman, K., Sewell, F., Allais, L., Delongeas, J.-L., Donald, E., Festag, M., … Robinson, S. (2013). A globalpharmaceutical company initiative: An evidence-based approach to define the upperlimit of body weight lossin shortterm toxicity studies. Regulatory Toxicology and Pharmacology, 67(1), 27–38. https://doi.org/10.1016/j.yrtph.2013.04.003 

Chebaibi, M., Bousta, D., Chbani, L., Ez zoubi, Y., Touiti, N., & Achour, S. (2019). Acute toxicity of plants mixture used in traditional treatment of edema and colic renal in Morocco. Scientific African, 6, e00152. https://doi.org/10.1016/j.sciaf.2019.e00152 

Chen, Kuo, Yang, Chien, Chu, Huang, … Chen. (2014). Identification of cucurbitacins and assembly of a draft genome for Aquilaria agallocha. BMC Genomics, 15(1), 578. https://doi.org/10.1186/1471-2164-15-578 

Chen, S., Lalazar, G., Barak, O., Adar, T., Doviner, V., & Mizrahi, M. (2012). Protein-Loosing Entropathy Induced by Unique Combination of CMV and HP in an Immunocompetent Patient. Case Reports in Medicine, 2012, 1–4. https://doi.org/10.1155/2012/361892 

Chinedu, E., Arome, D., & Ameh, F. (2013). A new method for determining acute toxicity in animal models. Toxicology International, 20(3), 224. https://doi.org/10.4103/0971-6580.121674 

Chowdhury, M., Hussain, M. D., Chung, S.-O., Kabir, E., & Rahman, A. (2016). Agarwood manufacturing: A multidisciplinary opportunity for economy of Bangladesh-a review. Agricultural Engineering International: CIGR Journal, 18(3), 171–178. 

Chukwuebuka, N., Kelechi, A., Nwanneamaka, E., & Stephen, U. (2018). Toxicity Studies and Phytochemical Screening of Aqueous Extractof Cissus aralioidesPlant. Journal of Advances in Medical and Pharmaceutical Sciences, 17(1), 1–7. https://doi.org/10.9734/JAMPS/2018/41425 

Cole, T. B., Coburn, J., Dao, K., Roqué, P., Chang, Y.-C., Kalia, V., … Costa, L. G. (2016). Sex and genetic differences in the effects of acute diesel exhaust exposure on inflammation and oxidative stress in mouse brain. Toxicology, 374, 1–9. https://doi.org/10.1016/j.tox.2016.11.010 

Colerangle, J. B. (2017). Preclinical Development of Nononcogenic Drugs (Small and Large Molecules). In A Comprehensive Guide to Toxicology in Nonclinical Drug Development (pp. 659–683). Elsevier. https://doi.org/10.1016/B978-0-12-803620­4.00025-6 

Cook, H. C. (1997). Origins of ... Tinctorial methods in histology. Journal of Clinical Pathology, 50(9), 716–720. https://doi.org/10.1136/jcp.50.9.716 

Costa, J. P., Ferreira, P. B., De Sousa, D. P., Jordan, J., & Freitas, R. M. (2012). Anticonvulsant effectof phytolin a pilocarpine model in mice.Neuroscience Letters, 523(2), 115–118. https://doi.org/10.1016/j.neulet.2012.06.055 

Cremades, A., Sanchez-Capelo, A., Monserrat, A., Monserrat, F., & Peñafiel, R. (2003). Effects of potassium deficiency on potassium, polyaminesand amino acids in mouse tissues. Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 134(3), 647–654. https://doi.org/10.1016/S1095-6433(02)00369-0 

Dahham, S., Tabana, Y., Iqbal, M., Ahamed, M., Ezzat, M., Majid, A., & Majid, A.(2015). The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene ß-Caryophyllene from the Essential Oil of Aquilariacrassna. Molecules,20(7), 11808– 11829. https://doi.org/10.3390/molecules200711808 

Dalen, J. E. (1998). “Conventional” and “Unconventional” Medicine: Can They Be Integrated? Archives of Internal Medicine, 158(20), 2179. https://doi.org/10.1001/archinte.158.20.2179 

Dar, R. A., Shahnawaz, M., & Qazi, P. H. (2017). General overview of medicinal plants: A review. The Journal of Phytopharmacology, 6(6),349–351. 

Debelo, N., & Afework, M. (2016). Assessment of Hematological, Biochemical and Histopathological Effects of Acute and Sub-chronic Administration of the Aqueous LeavesExtract of Thymus schimperiin Rats. Journal of Clinical Toxicology,06(02). https://doi.org/10.4172/2161-0495.1000286 

Doke, S. K., & Dhawale, S. C. (2015). Alternatives to animal testing: A review. Saudi Pharmaceutical Journal, 23(3), 223–229. https://doi.org/10.1016/j.jsps.2013.11.002 

Duke, J. A., Telatnik, M. A., & Duke, P.-A. K. (2007). Herbs of the Bible: 2000 years of plant medicine. Warsaw, Ind.: Whitman Publications. 

Eaton, D. L., & Gallagher, E. P. (2010). Comprehensive Toxicology (2nd ed.). Elsivier. 

Ekeanyanwu, R. C., & Njoku, O. U. (2014). Acute and subacute oral toxicity study on the flavonoid rich fraction of Monodora tenuifolia seed in albino rats. Asian Pacific Journal of Tropical Biomedicine, 4(3), 194–202. https://doi.org/10.1016/S2221­1691(14)60231-8 

Ekor, M. (2014). The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Frontiers in Pharmacology, 4. https://doi.org/10.3389/fphar.2013.00177 

Elliott, R. (2005). Mechanisms of genomic and non-genomic actions of carotenoids. Biochimica et Biophysica Acta (BBA) -Molecular Basis of Disease, 1740(2), 147– 154. https://doi.org/10.1016/j.bbadis.2004.12.009 

El-Soud, N. A. (2010). Herbal Medicine in Ancient Egypt. Journal of Medicinal Plants Research, 4(2), 082–086. https://doi.org/10.5897/JMPR09.013 

Elvin-Lewis, M. (2001). Should we be concerned about herbal remedies. Journal of Ethnopharmacology, 75(2–3), 141–164. https://doi.org/10.1016/S0378­8741(00)00394-9 

Erhirhie, E. O., Ihekwereme, C. P., & Ilodigwe, E. E. (2018). Advances in acute toxicity testing: Strengths, weaknesses and regulatory acceptance. Interdisciplinary Toxicology, 11(1), 5–12. https://doi.org/10.2478/intox-2018-0001 

Esfandiarpour, I., Farajzadeh, S., & Abbaszadeh, M. (2008). Evaluation of serum iron and ferritin levels in alopecia areata. Dermatology Online Journal, 14(3). 

Ezeja, Anaga, & Asuzu. (2014). Acute and sub-chronic toxicity profile of methanol leaf extract of Gouanialongipetala inrats. Journal of Ethnopharmacology,151(3), 1155– 1164. https://doi.org/10.1016/j.jep.2013.12.034 

Faisal, R., Shinwari, L., Aziz, I., & Khalil, A. T. (2019). Therapeutic andAdverseEffectsof Commonly Used Medicinal Plants: Standardization and Quality Assurance.Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, 56(3), 1-9-1–9. 

Faqi (Ed.). (2017). A comprehensive guide to toxicology in nonclinical drug development (Second edition). Amsterdam: Academic Press is an imprint of Elsevier. 

Fatemeh Jamshidi-Kia, Zahra Lorigooini, & Hossein Amini-Khoei. (2018). Medicinal plants: Pasthistory and future perspective. Journal of Herbmed Pharmacology, 7(1), 1–7. https://doi.org/10.15171/jhp.2018.01 

Fauzi Elias, Husni Ibrahim, & Wan Rusmawati Wan Mahamod. (2017). A Review on the Malaysian Aquilaria species in Karas Plantation and Agarwood Production. International Journal of Academic Research in Business and Social Sciences, 7(4), 1021–1029. https://doi.org/10.6007/IJARBSS/v7-i4/2911 

Feng, J., Yang, X.-W., & Wang, R.-F. (2011). Bio-assay guided isolation and identification of a-glucosidase inhibitors from the leaves of Aquilaria sinensis. Phytochemistry, 72(2–3), 242–247. https://doi.org/10.1016/j.phytochem.2010.11.025 

Fischer, A. H., Jacobson, K. A., Rose, J., & Zeller, R. (2008). Hematoxylin and Eosin Staining of Tissue and Cell Sections. Cold Spring Harbor Protocols, 2008(6), pdb.prot4986-pdb.prot4986. https://doi.org/10.1101/pdb.prot4986 

Fogelson, A. L., & Neeves, K. B.(2015). Fluid Mechanics of Blood Clot Formation. Annual Review of Fluid Mechanics, 47(1), 377–403. https://doi.org/10.1146/annurev-fluid­010814-014513 

Gad, S. C. (2014). Rodents model for toxicity testing and biomarkers. In Biomarkers in Toxicology (pp. 7–69). Elsevier. https://doi.org/10.1016/B978-0-12-404630­6.00002-6 

Gao, Y., Wang, T., Wang, G., Li, G., Sun, C.,Jiang, Z., … Cho, S. (2019). Preclinical safety of ginsenoside compound K: Acute, and 26-week oral toxicity studies in mice and rats. Food and Chemical Toxicology, 131, 110578. https://doi.org/10.1016/j.fct.2019.110578 

Gautam, M. K., & Goel, R. K. (2014). Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies. Journal of Toxicology, 2014, 1–9. https://doi.org/10.1155/2014/135654 

George, P. (2011). Concerns regarding the safety and toxicity of medicinal plants-An overview. Journal of Applied Pharmaceutical Science, 1(6), 40–44. 

Ghan, S. Y., Chin, J. H., Thoo, Y. Y., Yim, H. S., & Ho, C. W. (2016). Acute oral toxicity study of Aquilaria crassna and a-tocopherol in mice. International Journal of Pharmaceutical Sciences and Research, 7(4), 1456–1461. 

Golub, M. S., Hogrefe, C. E., Germann, S. L., Tran, T. T., Beard, J. L., Crinella, F. M., & Lonnerdal, B. (2005). Neurobehavioral evaluation of rhesus monkey infants fed cow’s milk formula, soy formula, or soy formula with added manganese. Neurotoxicology and Teratology, 27(4), 615–627. https://doi.org/10.1016/j.ntt.2005.04.003 

Goudah, A., Abdo-El-Sooud, K., & Yousef, M. A. (2015). Acute and subchronic toxicity assessment model of Ferula assa-foetida gum in rodents. Veterinary World, 8(5), 584–589. https://doi.org/10.14202/vetworld.2015.584-589 

Guo, J., Wang, W., Fang, H., Liu, Q., Zhang, W., Yin, D., … Liu, H. (2002). Agarofuan derivatives, their preparation, pharmaceutical composition containing them and their use as medicine. 

Gupta, P. K. (2016). Fundamentals of toxicology: Essential concepts and applications. India : Amsterdam; Boston: BSPublications ; Elseiver/AP, Academic Press is an imprint of Elsevier. 

Hamada, C. (2018). Statistical analysis for toxicity studies. Journal of Toxicologic Pathology, 31(1), 15–22. https://doi.org/10.1293/tox.2017-0050 

Hamidpour, M., Hamidpour, R., Hamidpour, S., & Shahlari, M. (2014). Chemistry, Pharmacology, and Medicinal Property of Sage (Salvia) toPrevent and Cure Illnesses such asObesity,Diabetes, Depression, Dementia, Lupus, Autism, HeartDisease, and Cancer. Journal of Traditional and Complementary Medicine, 4(2), 82–88. https://doi.org/10.4103/2225-4110.130373 

Haschek, W. M., Rousseaux, C. G., & Wallig, M. A. (2010). Fundamentals of toxicologic pathology (2nd ed). Amsterdam: Elsevier. 

Hashim, Y. Z.-Y., Phirdaous, A., & Azura, A. (2014). Screening of anticancer activity from agarwood essential oil. Pharmacognosy Research, 6(3), 191. https://doi.org/10.4103/0974-8490.132593 

Hassanzadeh-Taheri, M., Hosseini, M., Salimi, M., Moodi, H., & Dorranpour, D. (2018). Acute and Sub-Acute Oral Toxicity Evaluation of Astragalus hamosus Seedpod Ethanolic Extract in Wistar Rats. Pharmaceutical Sciences, 24(1), 23–30. https://doi.org/10.15171/PS.2018.05 

Hau, J., & Schapiro, S. J. (Eds.). (2011). Handbook of laboratory animal science (3rd ed). Boca Raton, FL: CRC Press. 

Hommos, M. S., Zeng, C., Liu, Z., Troost, J. P., Rosenberg, A. Z., Palmer, M., … Rule, A.D. (2018). Global glomerulosclerosis with nephrotic syndrome; the clinical importance of age adjustment. Kidney International, 93(5), 1175–1182. https://doi.org/10.1016/j.kint.2017.09.028 

Hori, T., Ohashi, N., Chen, F., Baine, A.-M. T., Gardner, L. B., Jermanus, S., & Nguyen, J. 

H. (2011). Simple and sure methodology for massive hepatectomy in the mouse. Annals of Gastroenterology, 24(4), 307–318. 

Huang, Chen, Yu, Zhou, & Ning.(2016). Effects of different ratios of Aquilaria sinensis leaf meal on the growth performance, slaughterperformance and nutrients digestibility of broiler. China Feed, 11, 36–42. 

Huang, Xiao, Burton-Freeman, B. M., & Edirisinghe, I. (2016). Chemical Changes of Bioactive Phytochemicals during Thermal Processing. In Reference Module in Food Science (p. B9780081005965031000). Elsevier. https://doi.org/10.1016/B978-0-08­100596-5.03055-9 

Iannaccone, P. M., & Jacob, H. J. (2009). Rats! Disease Models & Mechanisms,2(5–6), 206– 210. https://doi.org/10.1242/dmm.002733 

ICH Harmonised TripartiteGuideline. (2009). Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals M3 (R2). Presented at the International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use. 

Iizuka, R., Kawakami, K., Izawa, N., & Chiba, K. (2009). Phenols produced by gutbacteria affect the skinin hairless mice. Microbial Ecology in Health and Disease,21(1), 50– 56. https://doi.org/10.1080/08910600802688910 

Inamul Haq. (2004). Safety ofmedicinal plants. Pak J Med Res, 43(4), 203–210. 

International Agency for Research on Cancer (Ed.). (2002). Some traditional herbal medicines, some mycotoxins, naphthalene and styrene: This publication represents the views and expert opinions of an IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, which met in Lyon, 12 -19 February 2002. Lyon: IARC. 

Iwu, M. M. (2014). Handbook of African Medicinal Plants (0 ed.). CRC Press. https://doi.org/10.1201/b16292 

Jamison, D. T., Breman, J. G., Measham, A. R., Alleyne, G., Claeson, M., Evans, D. B., … Mills, A. (2006). Complementary and Alternative Medicine. In Disease Control Priorities in Developing Countries. 2nd edition. (2nd ed., pp. 1281–1291). Washington, DC: The World Bank Group. 

Jangra, A., Lukhi, M. M., Sulakhiya, K., Baruah, C. C., & Lahkar, M. (2014). Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. European Journal of Pharmacology, 740, 337–345. https://doi.org/10.1016/j.ejphar.2014.07.031 

Jefferson, J. A., & Shankland, S. J. (2014). The Pathogenesis of Focal Segmental Glomerulosclerosis. Advances in Chronic Kidney Disease, 21(5), 408–416. https://doi.org/10.1053/j.ackd.2014.05.009 

Jegathambigai Naidu, Rusli Ismail, & Sreenivasan Sasidharan. (2014). Acute Oral Toxicity and Brine Shrimp Lethality of Methanol Extract of Mentha Spicata L (Lamiaceae). Tropical Journal of Pharmaceutical Research, 13(1), 101. https://doi.org/10.4314/tjpr.v13i1.15 

Jennette, J. C., Olson, J. L., Silva, F. G., D’Agati, V., & Heptinstall, R. H. *1920-* (Eds.). (2015). Heptinstall’s pathology of the kidney: Includes interactive eBook with complete content (Seventh edition). Philadelphia [u.a. ]:Wolters Kluwer. 

Jiang, S., & Tu, P.-F. (2011). Effects of 95% ethanol extract of Aquilariasinensis leaves on hyperglycemia in diabeticdb/db mice. Journal of Chinese Pharmaceutical Sciences, 20(6). https://doi.org/10.5246/jcps.2011.06.079 

Jimenez-Garcia, S. N., Vazquez-Cruz, M. A., Garcia-Mier, L., Contreras-Medina, L. M., Guevara-González, R. G., Garcia-Trejo, J. F., & Feregrino-Perez, A. A. (2018). Phytochemical and PharmacologicalProperties of Secondary Metabolites in Berries. In Therapeutic Foods (pp. 397–427). Elsevier. https://doi.org/10.1016/B978-0-12­811517-6.00013-1 

Jingcheng Dong. (2013). The Relationship between Traditional Chinese Medicine and Modern Medicine.Evidence-Based Complementary and Alternative Medicine,2013, 1–10. https://doi.org/10.1155/2013/153148 

Kacew, S., Yi, P., & Lu, F. C. (2013). Lu’s basic toxicology: Fundamentals, target organs, and risk assessment. Retrieved from http://www.crcnetbase.com/isbn/9781841849546 

Kakino, M., & Hara,H. (2016). PharmacologicalEffects of Aquilariaspp.Leaves and Their Chemical Constituents. In R. Mohamed (Ed.), Agarwood (pp. 125–136). Singapore: Springer Singapore. https://doi.org/10.1007/978-981-10-0833-7_8 

Kakino, M., Tazawa, S., Maruyama, H., Tsuruma, K., Araki, Y., Shimazawa, M., & Hara,H. (2010). Laxative effects of agarwood on low-fiber diet-induced constipation in rats. BMC Complementary and Alternative Medicine, 10(1), 68. https://doi.org/10.1186/1472-6882-10-68 

Kamonwannasit, S., Nantapong, N., Kumkrai, P., Luecha, P., Kupittayanant, S., & Chudapongse, N. (2013). Antibacterial activity of Aquilaria crassna leaf extract against Staphylococcus epidermidis by disruption of cell wall. Annals of Clinical Microbiology and Antimicrobials, 12(1), 20. https://doi.org/10.1186/1476-0711-12­20 

Karmaus, A., Fitzpatrick,J., Allen, D., Patlewicz, G., Kleinstreuer, N., &Casey, W. (2018). Variability of LD50 Values from Rat Oral Acute Toxicity Studies: Implications for Alternative Model Development. Society of Toxicology, San Antonio, TX, 3, 11–15. 

Kelly, K. (2009). Early civilizations: Prehistoric times to 500 C.E. NewYork, NY: Factson File. 

Kerr, R. W. (2015). Herbalism Through the Ages. San Jose, CA: Supreme Grand Lodge Of The Ancient and Mystical Order Rosae Crucis. Retrieved from https://f5db1a33c5d48483c689­1033844f9683e62055e615f7d9cc8875.ssl.cf5.rackcdn.com/Herbalism%20Through %20the%20Ages%20-%20Ralph%20Whiteside%20Kerr.pdf 

Khalil, A. S., Rahim, A. A., Taha, K. K., & Abdallah, K. B. (2013). Characterization of methanolicextracts of agarwood leaves. Journal of Applied and Industrial Sciences, 1(3), 78–88. 

Kim, J. E., Nam, J. H., Cho, J. Y., Kim, K. S., & Hwang, D. Y. (2017). Annual tendency of researchpapersused ICR miceas experimental animals in biomedical research fields. Laboratory Animal Research, 33(2), 171–178. https://doi.org/10.5625/lar.2017.33.2.171 

Kisby, G. E., Fry, R. C., Lasarev, M. R., Bammler, T. K., Beyer, R. P., Churchwell, M., … Spencer, P. S. (2011). The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner. PLoS ONE, 6(6), e20911. https://doi.org/10.1371/journal.pone.0020911 

Kleisiaris, C. F., Sfakianakis, C., & Papathanasiou, I. V. (2014). Health care practices in ancient Greece: The Hippocratic ideal. Journal of Medical Ethics and History of Medicine, 7. 

Knecht, D. A., LaFleur, R. A., Kahsai, A. W., Argueta, C. E., Beshir, A. B., & Fenteany, G. (2010). Cucurbitacin I Inhibits Cell Motility by Indirectly Interfering with Actin Dynamics. PLoS ONE, 5(11), e14039. https://doi.org/10.1371/journal.pone.0014039 

Krieger, R. I. (Ed.). (2010). Hayes’ handbook of pesticide toxicology (Third edition). Amsterdam ; Boston: Elsevier/AP. 

Kuete, V. (Ed.). (2014). Toxicological survey of african medicinal plants (First edition). Amsterdam Boston Heidelberg London New York Oxford Paris San Diego San Francisco Singapore Sydney Tokyo: Elsevier. 

Kumar, G., & Kiernan, J. (2010). Special Stains and H & E (Second). California: Dako. 

Kumphune, S., Prompunt, E., Phaebuaw, K., Sriudwong, P., Pankla, R., & Thongyoo, P. (2011). Anti-inflammatory effects of the ethyl acetate extract of Aquilaria crassna inhibits LPS-induced tumour necrosis factor-alpha production by attenuating P38 MAPK activation. International Journal of Green Pharmacy, 5(1), 43. https://doi.org/10.4103/0973-8258.82099 

Lalitha, Sripathi, S., & Jayanthi. (2012). Acute toxicity study of extracts of Eichhornia Crassipes (Mart.) Solms. Asian Journal of Pharmaceutical and Clinical Research, 5(4), 59–61. 

Lambert, R. (2009). Breeding strategies for maintaining colonies of laboratory mice. TJ Laboratory. 

Law Kim Sooi & Soon Lean Keng. (2013). Herbal Medicines: Malaysian Women’s Knowledgeand Practice. Evidence-Based Complementary and Alternative Medicine, 2013, 1–10. https://doi.org/10.1155/2013/438139 

Lee, S. Y., & Mohamed, R. (2016). The Origin and Domestication of Aquilaria, an Important Agarwood-Producing Genus. Tropical Forestry, 1–20. https://doi.org/10.1007/978­981-10-0833-7_1 

Li, B. S., Pasch, M. C., & Maibach,H. I. (2018).Hair Disorders Induced byExternal Factors. In S. M. John, J. D. Johansen, T. Rustemeyer, P. Elsner, & H. I. Maibach (Eds.), Kanerva’s Occupational Dermatology (pp. 1–25). Cham: Springer International Publishing. https://doi.org/10.1007/978-3-319-40221-5_26-2 

Li, Jiang, &Mei. (2013). Comparative study on the effect of Aquilaria sinensis leaf tea and agarwood on promoting small intestine propulsion. Asia-Pacific Tradit. Med, 9(6), 24–25. 

Li, Shi, & Guo. (2017). Acute and SubacuteOral Toxicity Evaluation of Eriobotrya japonica Leaf Triterpene Acids inICR Mice. Evidence-Based Complementary and Alternative Medicine, 2017, 1–9. https://doi.org/10.1155/2017/4837839 

Lin, C.-C., Chan, T. Y. K., & Deng, J.-F. (2004). Clinical features and management of herb-induced aconitine poisoning. Annals of Emergency Medicine, 43(5), 574–579. https://doi.org/10.1016/j.annemergmed.2003.10.046 

Lissiman, E., Bhasale, A. L., & Cohen, M. (2014). Garlic for the common cold. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD006206.pub4 

Liu, C., Zheng, Y., Xu, W., Wang, H., & Lin, N. (2014). Rhubarb Tannins Extract Inhibits the Expression of Aquaporins 2 and 3 in Magnesium Sulphate-Induced Diarrhoea Model. BioMed Research International, 2014, 1–14. https://doi.org/10.1155/2014/619465 

Liu, Chen, Yang, Zhang, Wei, Meng, … Chen. (2013). Whole-tree Agarwood-Inducing Technique: An Efficient Novel Technique forProducing High-Quality Agarwood in Cultivated Aquilaria sinensis Trees. Molecules, 18(3), 3086–3106. https://doi.org/10.3390/molecules18033086 

Liyana Zulkifle, Adila Omar, Tajuddin, S. N., & Shaari, R. (2013). Antidiabetic Activities of Malaysian Agarwood (Aquilaria SPP) Leaves Extract. Antidiabetic Activities of Malaysian Agarwood (Aquilaria SPP) Leaves Extract. Presented at the Cenference on Industry-Acedemia Joint Initiatives in Biotechnology, University Malaysia Pahang, Malaysia. 

Liyana Zulkifle, Amalina Sabri, Adila Omar, Rosly Shaari, & Saiful Nizam Tajuddin. (2018). Acute and sub-chronic toxicity studyof Aquilariamalaccensis leaves extract in Sprague-Dawley rats. Chemistry of Advanced Materials, 3(1), 8–15. 

Loha, M., Mulu, A., Abay, S. M., Ergete, W., & Geleta, B. (2019). Acute and Subacute Toxicity of Methanol Extract of Syzygium guineense Leaveson the Histology of the Liverand Kidney and Biochemical Compositions of Blood in Rats. Evidence-Based Complementary and Alternative Medicine, 2019, 1–15. https://doi.org/10.1155/2019/5702159 

López-Sampson, A., & Page, T. (2018). History of Use and Trade of Agarwood. Economic Botany, 72(1), 107–129. https://doi.org/10.1007/s12231-018-9408-4 

Mamat, M.F., Yacob, M. R., Fui, L. H., & Rdam, A. (2010). Costsand Benefits Analysis of Aquilaria Species on Plantation forAgarwood Production in Malaysia. International Journal of Business and Social Science, 1(2), 162–174. 

Martini, N. D., Katerere, D. R. P., & Eloff, J. N. (2004). Biological activity of five antibacterial flavonoids from Combretum erythrophyllum (Combretaceae). Journal of Ethnopharmacology, 93(2–3), 207–212. https://doi.org/10.1016/j.jep.2004.02.030 

Maryam Farooqui, Mohamed Azmi Hassali, Aishah Knight Abdul Shatar, Muhammad AslamFarooqui, FahadSaleem,Noman ul Haq,& CheNoriah Othman.(2016). Use of complementary and alternative medicines among Malaysian cancer patients: A descriptive study. Journal of Traditional and Complementary Medicine, 6(4), 321– 326. https://doi.org/10.1016/j.jtcme.2014.12.008 

Maxwelll, L. P., John, C., Noel, N., Steven, S., & Naanlep, M. (2007). The histopathologic effects of Securidaca longepedunculata on heart, liver, kidney and lungs of rats. African Journal of Biotechnology, 6(5), 591–595. 

Maynard, R.L., Downes,N., & Finney, B. (2015). Histological techniques: An introduction for beginners in toxicology. Retrieved from https://nls.ldls.org.uk/welcome.html?ark:/81055/vdc_100035370566.0x000001 

Mehra, A., Bajpai, O.,& Joshi, H. (2014). Diversity,utilization andsacred values of ethno­medicinal plants of Kumaun Himalaya. Tropical Plant Research, 1(3), 80–86. 

Mei, Q., Li, H., Lin, H., Wu, X., Liang, L., Yang, H., & Lan, Z. (2013). Comparative study on hypoglycemic effect between Aquilaria sinensis leaves and agarwood. Lishizhen Med. Mat. Med. Res, 24, 1606–1607. 

Mengesha, G. G. (2016). Ethnobotanical survey of medicinal plants used in treating human and livestock health problems in ManduraWoreda of BenishangulGumuz, Ethiopia. Adv Med Plant Res, 4(1), 11–26. 

Mikail, H. G. (2018). Phytochemical screening, elemental analysis and acute toxicity of aqueous extract of Allium sativum L. bulbs in experimental rabbits. Journal of Medicinal Plants Research, 4(4), 322–326. 

Miller, M. A. (2001). Gender-Based Differences in the Toxicity of Pharmaceuticals—The Food and Drug Administration’s Perspective. International Journal of Toxicology, 20(3), 149–152. https://doi.org/10.1080/109158101317097728 

More, B. (2016). Overview of Medicine-Its Importance and Impact. DJ International Journal Medical Research, 1(1), 1–8. https://doi.org/10.18831/djmed.org/2016011001 

Mrvos, R., Dean, B. S., & Krenzelok, E. P. (1991). Philodendron/Dieffenbachia Ingestions: Are They a Problem? Journal of Toxicology: Clinical Toxicology, 29(4), 485–491. https://doi.org/10.3109/15563659109025745 

Mulhern, S.,Stroube, W., & Jacobs, R. (1986). Alopecia induced in youngmice by exposure to excess dietary zinc. Experientia, 42(5), 551–553. 

Murphy, S. J., Smith, P., Shaivitz, A. B., Rossberg, M. I., & Hurn, P. D. (2001). The effect of brief halothane anesthesia during daily gavage on complications and body weight in rats. Contemporary Topics in Laboratory Animal Science, 40(2), 9–12. 

Musumeci, G. (2014). Past, present and future: Overview on histology and histopathology. Journal of Histology and Histopathology, 1(1), 5. https://doi.org/10.7243/2055­091X-1-5 

Najafi, S. (2013). Phytochemical screening and antibacterial activity of leaf extract of Ziziphus mauritiana Lam. International Research Journal of Applied and Basic Sciences, 4(10), 3274–3276. 

Nath, P., & Yadav, A. (2015). Acute and sub-acute oral toxicity assessment of the methanolic extract from leaves of Hibiscus rosa-sinensis L. in mice. Journal of Intercultural Ethnopharmacology, 4(1), 70. https://doi.org/10.5455/jice.20141028021746 

Nor Azah, Chang, Mailina, Abu Said, Abd. Majid J., Saidatul Husni, …Nik Yasmin. (2008). Comparisonof Chemical Profiles of Selected GaharuOils from Peninsular Malaysia. The Malaysian Journal of Analytical Sciences, 12(2), 338–340. 

Nur Hidayat Che Musa, Haniza Hanim Mohd Zain, & Husni Ibrahim. (2018). Aphrodisiac properties of Aquilaria malaccensis leaves aqueous extract in ICR mice. Journal of Research in Pharmacy, 23(1), 130–140. https://doi.org/10.12991/jrp.2018.117 

Nur Hidayat Che Musa, Haniza Hanim Mohd Zain, Husni Ibrahim, & Nor Nasibah Mohd Jamil. (2019). Evaluation of Acute and Sub-acute Oral Toxicity Effect of Aquilaria malaccensis Leaves Aqueous Extract in Male ICR Mice. Natural Product Sciences, 25(2), 157. https://doi.org/10.20307/nps.2019.25.2.157 

O’Connor, A., & O’Moráin, C. (2014). Digestive Function of the Stomach. Digestive Diseases, 32(3), 186–191. https://doi.org/10.1159/000357848 

Ogbuehi, I. H., Ebong, O. O., & Obianime, A. W. (2015). Oral acute toxicity (LD50) study of different solvent extracts of Abrus precatorius Linn leaves in wistar rats. Eur. J. Exp. Biol, 5, 18–25. 

Okugawa, H., Ueda, R., Matsumoto, K., Kawanishi, K., & Kato, A. (1993). Effects of Agarwood Extracts on the Central Nervous System in Mice. Planta Medica, 59(01), 32–36. https://doi.org/10.1055/s-2006-959599 

OMS. (2009). The WHO recommended classification of pesticides by hazard and guidelines to classifications 1992-1993. Ginebra: World Health Organization. 

Onwusonye, J. C., Uwakwe, A. A., Iwuanyanwu, P., & Iheagwam, U. (2014). Oral acute toxicity (LD50) study of methanol extract of Annona senegalensis leaf in albino mice. Sky J. Biochem. Res, 3(5), 46–48. 

Organisation forEconomic Co-operation and Development. (2008a).Test No. 407: Repeated dose 28-day oral toxicity study in rodents. Paris: OECD Publishing. Retrieved from https://doi.org/10.1787/9789264070691-fr 

Organisation for Economic Co-operation and Development. (2008b). Test No. 425: Acute Oral Toxicity: Up-and-Down Procedure. Paris: OECD Publishing. https://doi.org/10.1787/9789264071049-en 

Pagadala, P., Shankar, M. V., & Kutty, K. (2019). Feeding Behaviour and its Association with Stress:A Review. JOURNAL OF CLINICAL AND DIAGNOSTIC RESEARCH. https://doi.org/10.7860/JCDR/2019/40508.12725 

Paramitha, D., Ulum, M. F., Purnama, A., Wicaksono, D. H. B., Noviana, D., & Hermawan, 

H. (2017). Monitoring degradation products and metal ions in vivo. In Monitoring and Evaluation of Biomaterials and their Performance In Vivo (pp. 19–44). Elsevier. https://doi.org/10.1016/B978-0-08-100603-0.00002-X 

Parashar, U.D., Johnson, H., Steele, A. D., & Tate, J. E. (2016). Health Impactof Rotavirus Vaccination in Developing Countries: Progressand Way Forward. Clinical Infectious Diseases, 62(suppl 2), S91–S95. https://doi.org/10.1093/cid/civ1015 

Parker, V., Wong, A. bert H., Boon, H. S., & Seeman, M. V. (2001). Adverse Reactions to St John’s Wort. The Canadian Journal of Psychiatry, 46(1), 77–79. https://doi.org/10.1177/070674370104600112 

Peters, E. M. J., Arck, P. C., & Paus, R. (2006). Hair growth inhibition bypsychoemotional stress: A mouse model for neural mechanisms in hair growth control. Experimental Dermatology, 15(1), 1–13. https://doi.org/10.1111/j.0906-6705.2005.00372.x 

Petrovska,B. (2012).Historicalreview of medicinal plants' usage. Pharmacognosy Reviews, 6(11), 1. https://doi.org/10.4103/0973-7847.95849 

Phirdaous Abbas, Yumi Zuhanis Has-Yun Hashim, Azura Amid, Hamzah Mohd Salleh, Parveen Jamal, & Irwandi Jaswir. (2013). Anti-cancer Potential of Agarwood Distillate. Anti-Cancer Potential of Agarwood Distillate, 41–44. International Islamic University Malaysia (USIM), Malaysia: Journal of Pure and Applied Microbiology 8. 

Phirdaous Abbas, Yumi Zuhanis Has-Yun Hashim, & Hamzah Mohd Salleh. (2018). CYTOTOXIC EFFECTS AND RESPONSE SURFACE OPTIMIZATION OF SOLVENT EXTRACTION OF CRUDE EXTRACTS FROM Aquilaria subintegra UNINFECTED BRANCH. Science Heritage Journal, 2(2), 10–15. https://doi.org/10.26480/gws.02.2018.10.15 

Pizzo, F., Gadaleta, D., Lombardo, A., Nicolotti, O., & Benfenati, E. (2015). Identification of structural alerts for liver and kidney toxicity using repeated dose toxicity data. Chemistry Central Journal, 9(1), 62. https://doi.org/10.1186/s13065-015-0139-7 

Plonka, P. M., Handjiski, B., Popik, M., Michalczyk, D., & Paus, R. (2005). Zinc as an ambivalent but potent modulator of murine hair growth in vivo-preliminary observations. Experimental Dermatology, 14(11), 844–853. https://doi.org/10.1111/j.1600-0625.2005.00365.x 

Porwal, M., Khan, N., & Maheshwari, K. (2017). Evaluation of Acute and Subacute Oral Toxicity Induced by Ethanolic Extract of Marsdenia tenacissima Leaves in Experimental Rats. Scientia Pharmaceutica, 85(3), 29. https://doi.org/10.3390/scipharm85030029 

Prakash, B. (Ed.). (2020).Functional and preservative properties of phytochemicals.London San Diego, CA Cambridge, MA Oxford: Academic Press, an imprint of Elsevier. 

Pranakhon, R., Pannangpetch, P., & Aromdee, C. (2011). Antihyperglycemic activity of agarwood leaf extracts inSTZ-induced diabetic rats and glucose uptakeenhancement activity in rat adipocytes. Songklanakarin Journal of Science & Technology, 33(4), 405–410. 

Pratibha Thakur, Suravi Shrivastava, Renu Shrivastava, & Vinoy Shrivastava. (2018). IMPAIRMENT OF OVARIAN BIOCHEMICAL CONTENTS AND ENZYMES ACTIVITIES DURING POTASSIUM BROMATE (KBRO3-) INTOXICATION IN ALBINO MICE MUS MUSCULUS. INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES AND RESEARCH, 9(12), 5357–5362. 

Premaratna, R., Weerasinghe, M. S., Premawardana, Nuwan. P., & de Silva, H. J. (2015). Gloriosa superba poisoning mimicking an acute infection-a case report. BMC Pharmacology and Toxicology,16(1),27. https://doi.org/10.1186/s40360-015-0029­6 

Prussin, C. (2013). Eosinophil Cell–Cell Communication. In Eosinophils in Health and Disease (pp. 329–390). Elsevier. https://doi.org/10.1016/B978-0-12-394385­9.00011-0 

Rahman, H., Eswaraiah, M. C., & Dutta, A. M. (2016). Anti-arthritic activity of leaves and oil of Aquilaria agallocha. The Saudi Journal of Life Sciences, 1, 34–43. 

Randriamiharisoa, M. N., Kuhlman, A. R., Jeannoda, V., Rabarison, H., Rakotoarivelo, N., Randrianarivony, T., … Bussmann, R. W. (2015). Medicinal plants sold in the markets of Antananarivo, Madagascar. Journal of Ethnobiology and Ethnomedicine, 11(1), 60. https://doi.org/10.1186/s13002-015-0046-y 

Redzuan Razak, Suzanah Rahman, Asmah Hamdan, Roszaman Ramli, Lokman Md Isa, Hussin Muhammad,& Nik Fakhuruddin Nik Hassan. (2018).Evaluation of acute and sub-acute oral toxicity of the aqueous extract of Aquilaria malaccensis leaves in SpragueDawley rats. Asia Pacific Journal of Molecular Biology and Biotechnology, 27(1), 20–32. https://doi.org/10.35118/apjmbb.2019.027.1.03 

Régent, D., Croisé-Laurent, V., Mathias, J., Fairise, A., Ropion-Michaux, H., & Proust, C. (2010). Acute Gastritis and Enteritis. In P. Taourel (Ed.), CT of the Acute Abdomen (pp. 239–271). Berlin, Heidelberg: Springer Berlin Heidelberg. https://doi.org/10.1007/174_2010_84 

Rosidah, Yam, M. F., Sadikun, A., Ahmad, M., Akowuah, G. A., & Asmawi, Mohd. Z. (2009). Toxicology evaluation of standardized methanol extract of Gynura procumbens. Journal of Ethnopharmacology, 123(2), 244–249. https://doi.org/10.1016/j.jep.2009.03.011 

Roy, Ukil, & Lyndem. (2016). Acute and sub-acute toxicity studies on the effect of Senna alata in Swiss Albino mice. Cogent Biology, 2(1). https://doi.org/10.1080/23312025.2016.1272166 

Rutidosperma, C. (2018). Evaluation of Sedative and Hypnotic Activities of Ethanolic Extract of Leavesof Cleome Rutidosperma DC.(Capparidaceae)inMice. Journal of Pharmaceutics and Therapeutics, 4(1), 215–223. 

Saad Sabbar Dahham, Mohamed B. Khadeer Ahamed, Sultan Mohamad Saghir, Fouad Saleih Alsuede, Muhammad Adnan Iqbal, & Amin Malik Shah Abdul Majid. (2014). Bioactive essential oils from Aquilaria crassna for cancer prevention and treatment. https://doi.org/10.13140/2.1.3315.7125 

Said, F., & Kamaluddin, M. T. (2016). Theodorus 2016 Efficacy of the Aquilaria malaccensis leaves active fraction in glucose uptake in skeletal muscle on diabetic wistar rats. International Journal of Health Sciences and Research, 6(7), 162–167. 

Saïdana, D., Mahjoub, S., Boussaada, O., Chriaa, J., Mahjoub, M. A., Chéraif, I., … Helal, A. N. (2008). Antibacterial and Antifungal Activities of the Essential Oils of Two Saltcedar Species from Tunisia. Journal of the American Oil Chemists’ Society, 85(9), 817–826. https://doi.org/10.1007/s11746-008-1251-9 

Sánchez, B., Casalots-Casado, J., Quintana, S., Arroyo, A., Martín-Fumadó, C., & Galtés, I. (2012). Fatal manganese intoxicationdue to an error in the elaboration of Epsom salts for a liver cleansing diet. Forensic Science International, 223(1–3), e1–e4. https://doi.org/10.1016/j.forsciint.2012.07.010 

Sandler, B., & Aronson, P. (1993). Yohimbine-induced cutaneous drug eruption, progressive renal failure, and lupus-like syndrome. Urology, 41(4), 343–345. https://doi.org/10.1016/0090-4295(93)90592-X 

Satishprakash Shukla. (2017). SIGNIFICANCE OF DIFFERENCE BETWEEN MEANS. https://doi.org/10.13140/RG.2.2.21228.97924 

Sattayasai, J., Bantadkit, J., Aromdee, C., Lattmann, E., & Airarat, W. (2012). Antipyretic, analgesic and anti-oxidative activities of Aquilaria crassna leaves extract in rodents. Journal of Ayurveda and Integrative Medicine, 3(4), 175. https://doi.org/10.4103/0975-9476.104427 

Satyapa, Vilasrao Kadam, & Rumi Ghosh. (2008). Hepatoprotective Activity of Livobond A Polyherbal Formulation Against CCl4 Induced Hepatotoxicity in Rats. International Journal of Pharmacology, 4(6), 472–476. https://doi.org/10.3923/ijp.2008.472.476 

Serra, I., Yamamoto, M., Calvo, A., Cavada, G., Báez, S., Endoh, K., … Tajima, K. (2002). Association of chili pepper consumption, low socioeconomic status and longstanding gallstones with gallbladder cancer in a Chilean population: Gallstones and Gallbladder Cancer in Chile. International Journal of Cancer, 102(4), 407–411. https://doi.org/10.1002/ijc.10716 

Shakya, A. K. (n.d.). Medicinal Plants: Future Source of New Drugs. International Journal of Herbal Medicine, 4(4), 2016. https://doi.org/10.13140/rg.2.1.1395.6085 

Shatoor. (2011). Acute and Sub-acute Toxicity of Crataegus Aronia Syn. Azarolus (L.) Whole Plant Aqueous Extract in Wistar Rats. American Journal of Pharmacology and Toxicology, 6(2), 37–45. https://doi.org/10.3844/ajptsp.2011.37.45 

Singh. (2015). Medicinal plants: A review. Journal of Plant Sciences, 3(1–1), 50–55. https://doi.org/10.11648/j.jps.s.2015030101.18 

Singh, T., Sinha, N., & Singh, A. (2013). Biochemical and histopathological effects on liver due to acute oral toxicity of aqueous leaf extract of Ecliptaalba on female Swiss albino mice. Indian Journal of Pharmacology, 45(1), 61. https://doi.org/10.4103/0253-7613.106437 

Slaoui, M., & Fiette, L. (2011). Histopathology Procedures: From Tissue Sampling to Histopathological Evaluation. In J.-C. Gautier (Ed.), Drug Safety Evaluation (Vol. 691, pp. 69–82). Totowa, NJ: Humana Press. https://doi.org/10.1007/978-1-60761­849-2_4 

Stubblefield, W. A., McKee, R. H., Kapp, R. W., & Hinz, J. P. (1989). An evaluation of the acute toxic properties of liquids derived from oil sands. Journal of Applied Toxicology, 9(1), 59–65. https://doi.org/10.1002/jat.2550090111 

Subasinghe, & Hettiarachchi. (2013). Agarwood resin production and resin quality of Gyrinops walla Gaertn. International Journal of Agricultural Sciences, 3(1), 357– 262. https://doi.org/10.13140/2.1.4907.8405 

Subramanian, K., Sankaramourthy, D., & Gunasekaran, M. (2018). Toxicity StudiesRelated to Medicinal Plants. In Natural Products and Drug Discovery (pp. 491–505). Elsevier. https://doi.org/10.1016/B978-0-08-102081-4.00018-6 

Subramanion Jothy, Zuraini Zakaria, Yeng Chen, Yee Ling Lau, Lachimanan Yoga Latha, & Sreenivasan Sasidharan. (2011). Acute Oral Toxicity of Methanolic Seed Extract of Cassia fistula in Mice. Molecules, 16(6), 5268–5282. https://doi.org/10.3390/molecules16065268 

Sultana, N., Al-Khatib, A., & Kadir, M. (2014). Review on Some Malaysian Traditional Medicinal Plants with Therapeutic Properties. Journal of Basic & Applied Sciences, 10, 149–159. https://doi.org/10.6000/1927-5129.2014.10.20 

Sundberg, J. P., Boggess, D., Silva, K. A., McElwee, K. J., King, L. E., Li, R., … Cox, G. A. (2003). Major Locus on Mouse Chromosome 17 and Minor Locus on Chromosome 9 are Linked with Alopecia Areata in C3H/HeJ Mice. Journal of Investigative Dermatology, 120(5), 771–775. https://doi.org/10.1046/j.1523­1747.2003.12135.x 

Sutrisni, N., Soewandhi, S., Adnyana, I., & Sasongko, L. (2019). Acute and Subchronic (28­day) Oral Toxicity Studies on the Film Formulation of k-Carrageenan and Konjac Glucomannan for Soft Capsule Application. Scientia Pharmaceutica, 87(2), 9. https://doi.org/10.3390/scipharm87020009 

Suwannasing. (2012). Anti-ischemic effect of ethyl acetate extract of Aquilaria crassna by attenuation of p38-MAPK activation. Journal of Applied Pharmaceutical Science, 2(10), 026–030. https://doi.org/10.7324/JAPS.2012.21005 

Taiwo & Joel. (2015). Acute toxicity and histopathological assessment of methanol extract of Cleome viscosa (Linn.) whole plant. Journal of Medicinal Plants Research,9(11), 360–369. https://doi.org/10.5897/JMPR2014.5756 

Takemoto, H., Ito, M., Shiraki, T., Yagura, T., & Honda, G. (2007). Sedative effects of vapor inhalation of agarwood oil and spikenard extract and identification of their active components. Journal of Natural Medicines, 62(1), 41–46. https://doi.org/10.1007/s11418-007-0177-0 

Tamizhazhagan, V. (2017). Histological Methods in Life Science. International Journal of Biomedical Materials Research, 5(6), 68. https://doi.org/10.11648/j.ijbmr.20170506.11 

Tan, C. S., Isa, N. M., Ismail, I., & Zainal, Z. (2019). Agarwood Induction: Current Developments and Future Perspectives. Frontiers in Plant Science, 10, 122. https://doi.org/10.3389/fpls.2019.00122 

Teo, S., Stirling, D., Thomas, S., Hoberman, A., Kiorpes, A., & Khetani, V. (2002). A 90­day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in Sprague–Dawley rats. Toxicology, 179(3), 183–196. https://doi.org/10.1016/S0300­483X(02)00338-4 

Thakur, M., Singh, K., & Khedkar, R. (2020). Phytochemicals. In Functional and Preservative Properties of Phytochemicals (pp. 341–361). Elsevier. https://doi.org/10.1016/B978-0-12-818593-3.00011-7 

Traesel, G. K., de Souza, J. C., de Barros, A. L., Souza, M. A., Schmitz, W. O., Muzzi, R. M., … Arena, A. C. (2014). Acute and subacute (28 days) oral toxicity assessment of the oil extracted from Acrocomia aculeata pulp in rats. Food and Chemical Toxicology, 74, 320–325. https://doi.org/10.1016/j.fct.2014.10.026 

Ugochukwu, S. C., Uche, A., & Ifeanyi, O. (2013). Preliminary phytochemical screening of different solvent extracts of stem bark and roots of Dennetia tripetala G. Baker. Asian Journal of Plant Science and Research, 3(3), 10–13. 

Wang. (2008). Determination of Genkwanin in the leaves of Aquilaria sinensis(Lour.) Gilg with HPLC. Guiding J. Trad. Chin. Med. Pharm, 14, 69–70. 

Wang, Li, Luo, Zhao, Ma, & Liu. (2018). GC-MS Study of the Chemical Components of Different Aquilariasinensis(Lour.) Gilgorgansand Agarwood from DifferentAsian Countries. Molecules, 23(9), 2168. https://doi.org/10.3390/molecules23092168 

Wang, Yan, Niu, Li, Lin, Liu, … Li. (2014). Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase. Pharmaceutical Biology, 52(1), 68–73. https://doi.org/10.3109/13880209.2013.814691 

Ward, H. A., Kuhnle, G. G., Mulligan, A. A., Lentjes, M. A.,Luben, R. N., & Khaw, K.-T. (2010). Breast, colorectal, and prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition-Norfolk in relation to phytoestrogen intake derived from an improved database. American Journal of Clinical Nutrition, 91(2), 440–448. https://doi.org/10.3945/ajcn.2009.28282 

Watson, R. R., Gerald, J. K., & Preedy, V. R. (Eds.). (2011). Nutrients, dietary supplements, and nutriceuticals: Cost analysis versus clinical benefits. New York: Humana Press. 

Wesam Kooti, Maryam Moradi, Sara Ali-Akbari,Majid Asadi-Samani, & Damoon Ashtary-Larky. (2015). Therapeutic and pharmacological potential of Foeniculum vulgare Mill: A review. Journal of HerbMed Pharmacology, 4(1), 1–9. 

Wider, B., Pittler, M. H., & Ernst, E. (2015). Feverfew for preventing migraine. Cochrane Database of Systematic Reviews. https://doi.org/10.1002/14651858.CD002286.pub3 

World Health Organization (Ed.). (1999). WHO Monographs on Selected Medicinal Plants. Geneva: World Health Organization. 

World Health Organization. (2002). The General Design Of Non-Clinical Safety (Toxicity) Testing Programmes For Pharmaceuticals In International Guidelines. In Non-Clinical Safety Testing (pp. 27–30). Geneza, Switzerland: World Health Organization. Retrieved from https://www.who.int/tdr/publications/documents/safety_handbook.pdf 

Wu, Li, Mei, Lin, Liang,Yang, &Lan. (2013). A comparativestudyontheasthma effect of Aquilaria leaves and agarwood. Pharm. Today, 23, 346–347. 

Wu, Q., Tanaka, H., Hirukawa, T., Endoh, M., & Fukagawa, M. (2012). Characterization and quantification of proliferating cell patterns in endocapillary proliferation.Nephrology Dialysis Transplantation, 27(8), 3234–3241. https://doi.org/10.1093/ndt/gfr797 

Wu, Zhu, Lin, Chen, Yao, & Liao. (2012). The active ingredient for hypolipidemic effect in Aquilaria sinensis leaves. Chinese Phamacertical Association. Proceedings of the National Symposium on the Twelfth Chinese Medicine and Natural Medicine, 2–4. Beijing. 

Xie, R., Xu, J., Xiao, Y., Wu, J., Wan, H., Tang, B., … Yang,S. (2017). Calcium Promotes Human Gastric Cancer via a Novel Coupling of Calcium-Sensing Receptor and TRPV4 Channel. Cancer Research, 77(23), 6499–6512. https://doi.org/10.1158/0008-5472.CAN-17-0360 

Yi, P., Kacew, S., Kim, H., & Lu, F. C. (Eds.). (2018). Lu’s basic toxicology: Fundamentals, target organs, and risk assessment (Seventh edition). Boca Raton:CRC Press, Taylor & Francis Group. 

Yuslianti, E.R., M. Bachtia, B., F. Suniart, D., &B. Sutjiat, A. (2016). Effect of Rambutan Honey (Nephelium lappaceum) Acute Administration on Mortality, Body Weight, Toxicity Symptoms and Relative Organ Weight of Swiss Websters Mice. Research Journal of Toxins, 8(1), 1–7. https://doi.org/10.3923/rjt.2016.1.7 

Zakaria, Y., Azlan, N. Z., Fakhuruddin, N., Hassan, N., & Muhammad, H. (2016). Phytochemicals and acute oral toxicity studies of the aqueous extract of Vernonia amygdalina from state of Malaysia. Journal of Medicinal Plants Studies, 4(3), 1–5. 

Zeman, T., Buchtová, M., Docekal, B., Míšek, I., Navrátil, J., Mikuška, P., … Vecera, Z. (2015). Organ weight changes in mice after long-term inhalation exposure to manganese oxides nanoparticles. Journal of Physics: Conference Series, 617, 012018. https://doi.org/10.1088/1742-6596/617/1/012018 

Zhao, Y.-L., Su, M., Shang, J.-H., Wang, X., Njateng, G. S. S., Bao, G.-L., … Luo, X.-D. (2020). Acute and Chronic Toxicity of Indole Alkaloids from Leaves of Alstonia scholaris (L.) R. Br. In Mice and Rats. Natural Products and Bioprospecting, 10(2), 77–88. https://doi.org/10.1007/s13659-020-00237-1 

Zhong, M., Liu, Y., Liu, J., Di, D., Xu, M., Yang, Y., … Liu, J. (2014). Isocorydine Derivatives and Their Anticancer Activities. Molecules, 19(8), 12099–12115. https://doi.org/10.3390/molecules190812099 

Zhou, M., Wang, H., Suolangjiba, Kou, J., & Yu, B. (2008). Antinociceptive and anti-inflammatory activities of Aquilaria sinensis (Lour.)Gilg. Leaves extract. Journal of Ethnopharmacology, 117(2), 345–350. https://doi.org/10.1016/j.jep.2008.02.005 

Zhou, Yang, & Wang. (2016). Higher cytotoxicity and genotoxicity of cultivated versus natural agarwood incense smoke. Environmental Chemistry Letters, 14(4), 501–506. https://doi.org/10.1007/s10311-016-0567-1 

 


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