Main Article Content
Abstract
Highlights:
1. This study determined the toxic effects of combining Caesalpinia sappan and Zingiber officinale extracts, as
people need to be aware of the potential side effects of these common herbal remedies for the treatment of
rheumatoid arthritis.
2. The combination of Caesalpinia sappan and Zingiber officinale extracts is efficacious and non-toxic as an antiarthritis treatment, hence, the ingredients can be upgraded to standardized herbal medicines and
phytopharmaceuticals.
Abstract
Sappanwood (Caesalpinia sappan) and red ginger (Zingiber officinale) are plant species that have been studied for their
efficacy in treating inflammation related to rheumatoid arthritis. This study aimed to examine the effects of combining
sappanwood and red ginger in order to determine the potential toxicity of the herbal extracts in medicine. The toxicity
testing was carried out in vivo using 32 Wistar strain male white rats (Rattus norvegicus) grouped into eight groups of four.
The rats were injected with complete Freund's adjuvant to induce a chronic inflammatory effect. The eight groups consisted
of the negative control group, the positive control group, the normal group, and five treatment groups. This study was
conducted by observing the animals for toxic symptoms and death to determine the safety of the extracts and drugs. The
observation results were analyzed using a one-way analysis of variance (p<0.05). The analysis results showed that weight
gain and relative organ weight among the groups had no significant differences (p>0.05). Microscopic examination of the
organ preparations observed under a light microscope revealed no significant changes or adverse effects in rats treated with
the extracts or drugs. In conclusion, a combination of sappanwood and red ginger ethanol extracts administered orally has
no toxic effect in rats injected with complete Freund's adjuvant.
Keywords
Article Details
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References
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- Amalia R, Tukiran, Suyatno, et al (2021). Arthritis assay on combination of red ginger (Zingiber Officinale) and secang wood (Caesalpinia Sappan) extract towards rat oedema induced by complete freund's adjuvant. Advances in Engineering Research 209, 584–589. doi: 10.2991/aer.k. 211215.099.
- Amna OF, Nooraain H, Noriham A, et al (2013). Acute and oral subacute toxicity study of ethanolic extract of cosmos caudatus leaf in sprague dawley rats. International Journal of Bioscience, Biochemistry and Bioinformatics 3, 301–305. doi: 10.7763/IJBBB.2013.V3.218.
- Aristyanti NPP, Wartini NM, Gunam IBW (2017). Rendemen dan karakteristik ekstrak pewarna bunga kenikir (Tagetes erecta L.) pada perlakuan jenis pelarut dan lama ekstraksi. J Rekayasa dan Manaj Agroindustri. Available at: https://ojs. unud.ac.id/index.php/jtip/article/view/34075.
- Attanayake AP, Jayatilaka KAPW, Pathirana C, et al (2013). Efficacy and toxicological evaluation of Coccinia grandis (Cucurbitaceae) extract in male Wistar rats. Asian Pacific Journal of Tropical Disease 3, 460–466. doi: 10.1016/S2222-1808(13) 60101-2.
- Barkia I, Ketata Bouaziz H, Sellami Boudawara T, et al (2020). Acute oral toxicity study on Wistar rats fed microalgal protein hydrolysates from Bellerochea malleus. Environmental Science and Pollution Research 27, 19087–19094. doi: 10.1007/s11356-018-4007-6.
- Berata IK, Winaya BO, Adi AAAM, et al (2015). Patologi Veteriner Umum, Ketiga.ed. Kardena IM. Swasta Nulus, Denpasar.
- Bronte V, Pittet MJ (2013). The spleen in local and systemic regulation of immunity. Immunity 39, 806–818. doi: 10.1016/j.immuni.2013.10.010.
- Bukke AN, Hadi FN, Produtur CS (2015). Comparative study of in vitro antibacterial activity of leaves, bark, heart wood and seed extracts of Caesalpinia sappan L. Asian Pacific Journal of Tropical Disease 5, 903–907. doi: 10.1016/S2222-1808(15)60954-9.
- Choudhary M, Kumar V, Malhotra H, et al (2015). Medicinal plants with potential anti-arthritic activity: Journal of Intercultural Ethnopharma cology 4, 147. doi: 10.5455/jice.20150313021918.
- Corsini A, Bortolini M (2013). Drug-induced liver injury: The role of drug metabolism and transport. The Journal of Clinical Pharmacology 53, 463–474. doi: 10.1002/jcph.23.
- Ezzat SM, Ezzat MI, Okba MM, et al. (2018). The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity. Journal of Ethno-pharmacology 214, 113–123. doi: 10.1016/j.jep.2017.12.019.
- Firestein GS, McInnes IB (2017). Immuno-pathogenesis of Rheumatoid Arthritis. Immunity 46, 183–196. doi: 10.1016/j.immuni. 2017.02.006.
- Fitmawati, Titrawani, Safitri W (2018). Struktur Histologi Hati Tikus Putih (Rattus norvegicus Berkenhout 1769) dengan Pemberian Ramuan Tradisional Masyarakat Melayu Lingga, Kepulauan Riau. EKOTONIA: Jurnal Penelitian Biologi, Botani, Zoologi dan Mikrobiologi 03, 11–19. doi: 10.33019/ekotonia.v3i1.753.
- Hidayat R, Bagus Putu Putra Suryana, Linda Kurniaty Wijaya, et al (2021). Indonesian rheumatology association (IRA) recommendations for diagnosis and management of rheumatoid arthritis. Indonesian Journal of Rheumatology 13, 322–443. doi: 10.37275/ijr.v13i1.173.
- Hidayati E, Berata IK, Samsuri S, et al (2018). Gambaran histopatologi limpa tikus putih yang diberi deksametason dan vitamin E. Buletin Veteriner Udayana 18. doi: 10.24843/bulvet. 2018.v10.i01.p03.
- Idang EO, Yemitan OK, Mbagwu HOC, et al (2019). Toxicological assessment of zingiber officinale roscoe (Ginger) root oil extracts in albino rats. Toxicology Digest 4, 108–119. Available at: https://www.researchgate.net/publication/331155817_Toxicological_Assessment_of_Zingiber_officinale_Roscoe_Ginger_Root_Oil_Extracts_in_Albino_rats.
- Jannah DR, Budijastuti W (2022). Gambaran histopatologi toksisitas ginjal tikus jantan (Rattus norvegicus) yang diberi sirup umbi yakon (Smallanthus sonchifolius). LenteraBio : Berkala Ilmiah Biologi 11, 238–246. doi: 10.26740/lenterabio.v11n2.p238-246.
- Jung EG, Han K Il, Hwang SG, et al. (2015). Brazilin isolated from caesalpinia sappan L. inhibits rheumatoid arthritis activity in a type-II collagen induced arthritis mouse model. BMC Complementary and Alternative Medicine. doi: 10.1186/s12906-015-0648-x.
- Kim KJ, Yoon KY, Yoon HS, et al (2015). Brazilein suppresses inflammation through inactivation of IRAK4-NF-kb pathway in LPS-induced Raw264.7 macrophage cells. International Journal of Molecular Sciences 16, 27589–27598. doi: 10.3390/ijms161126048.
- Kumar V, Abbas A, Aster J (2013). Robbins Basic Pathology, 9th Edition. Elsevier, Canada.
- Lees JG, White D, Keating BA, et al. (2020). Oxaliplatin-induced haematological toxicity and splenomegaly in mice ed. Palaniyandi S. PLoS One 15, e0238164. doi: 10.1371/journal.pone. 0238164.
- Martina SJ, Ramar LAP, Silaban MRI, et al. (2019). Antiplatelet effectivity between aspirin with honey on cardiovascular disease based on bleeding time taken on mice. Open Access Macedonian Journal of Medical Sciences 7, 3416–3420. doi: 10.3889/ oamjms.2019.431.
- Mbaveng AT, Kuete V (2017). Zingiber officinale. In Medicinal Spices and Vegetables from Africa: Therapeutic Potential Against Metabolic, Inflammatory, Infectious and Systemic Diseases, pp. 627–639. Elsevier Inc. doi: 10.1016/B978-0-12-809286-6.00030-3.
- Miller MA, Zachary JF (2017). Mechanisms and morphology of cellular injury, adaptation, and death. In Pathologic Basis of Veterinary Disease, pp. 2-43.e19. Elsevier. Available at: https://linking hub.elsevier.com/retrieve/pii/B9780323357753000011.
- Nirmal NP, Rajput MS, Prasad RGSV, et al (2015). Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review. Asian Pacific Journal of Tropical Medicine 8, 421–430. doi: 10.1016/j.apjtm.2015.05.014.
- Noh ASM, Chuan TD, Khir NAM, et al (2021). Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis ed. Di Paola R. PLoS One 16, e0260423. doi: 10.1371/journal. pone.0260423.
- Nurhidayah G, Tukiran, Suyatno, et al (2022). Anti-inflammatory activity combination of ethanol extract from sappan wood (Caesalpinia sappan L .) and red ginger rhizome (Zingeiber officinale Roxb.) against albumin denaturation inhibition. World Journal of Pharmaceutical Research (WJPR). doi: 10.20959/wjpr202216-26197.
- Panagopoulos PK, Lambrou GI (2018). Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic implications. Journal of Musculoskeletal & Neuronal Interactions18, 304–319. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6146189.
- Pereira CR-, Silva V, Costa VM, et al. (2019). Histological and toxicological evaluation, in rat, of a P-glycoprotein inducer and activator: 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5). EXCLI J 18, 697–722. doi: 10.17179/excli 2019-1675.
- Ping KY, Darah I, Chen Y, et al (2013). Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. BioMed Research International 2013, 1–14. doi: 10.1155/2013/ 182064.
- Rambod M, Nazarinia M, Raieskarimian F (2018). The prevalence and predictors of herbal medicines usage among adult rheumatoid arthritis patients: A case-control study. Complementary Therapies in Medicine 41, 220–224. doi: 10.1016/j.ctim.2018. 10.004.
- Ravikumar C (2014). Virulence factors of Acinetobacter spp View project Plastination. Journal of Pharmaceutical Sciences and Research. Available at: https://www.jpsr.pharmainfo.in/Documents/Volumes/Vol6Issue08/jpsr06081402.pdf.
- Sangi SMA (2016). Potential therapeutic agents for the treatment of fatty degeneration of liver and atheromatous plaques: An experimental study in rats. Pharmacognosy Magazine 12, 414. doi: 10.4103/0973-1296.191444.
- Suhita NLPR, Sudira IW, Winaya IBO (2013). Histopatologi ginjal tikus putih akibat pemberian ekstrak pegagan (Centella asiatica) peroral. Buletin Veteriner Udayana 5, 71–8. Available at: https://ojs.unud.ac.id/index.php/buletinvet/article/view/5741.
- Sunil D, Isloor AM, Shetty P, et al (2013). In vivo anticancer and histopathology studies of Schiff bases on Ehrlich ascitic carcinoma cells. Arabian Journal of Chemistry 6, 25–33. doi: 10.1016/j. arabjc.2010.12.016.
- Wang W, Dong Z, Zhang J, et al. (2019). Acute and subacute toxicity assessment of oxyclozanide in wistar rats. Frontiers in Veterinary Science. doi: 10.3389/fvets.2019.00294.
References
Al-Saadany HM, Hussein MS, Gaber RA, et al (2016). Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity. The Egyptian Rheumatologist 38, 1–7. doi: 10.1016/j.ejr.2015.01.001.
Amalia R, Tukiran, Suyatno, et al (2021). Arthritis assay on combination of red ginger (Zingiber Officinale) and secang wood (Caesalpinia Sappan) extract towards rat oedema induced by complete freund's adjuvant. Advances in Engineering Research 209, 584–589. doi: 10.2991/aer.k. 211215.099.
Amna OF, Nooraain H, Noriham A, et al (2013). Acute and oral subacute toxicity study of ethanolic extract of cosmos caudatus leaf in sprague dawley rats. International Journal of Bioscience, Biochemistry and Bioinformatics 3, 301–305. doi: 10.7763/IJBBB.2013.V3.218.
Aristyanti NPP, Wartini NM, Gunam IBW (2017). Rendemen dan karakteristik ekstrak pewarna bunga kenikir (Tagetes erecta L.) pada perlakuan jenis pelarut dan lama ekstraksi. J Rekayasa dan Manaj Agroindustri. Available at: https://ojs. unud.ac.id/index.php/jtip/article/view/34075.
Attanayake AP, Jayatilaka KAPW, Pathirana C, et al (2013). Efficacy and toxicological evaluation of Coccinia grandis (Cucurbitaceae) extract in male Wistar rats. Asian Pacific Journal of Tropical Disease 3, 460–466. doi: 10.1016/S2222-1808(13) 60101-2.
Barkia I, Ketata Bouaziz H, Sellami Boudawara T, et al (2020). Acute oral toxicity study on Wistar rats fed microalgal protein hydrolysates from Bellerochea malleus. Environmental Science and Pollution Research 27, 19087–19094. doi: 10.1007/s11356-018-4007-6.
Berata IK, Winaya BO, Adi AAAM, et al (2015). Patologi Veteriner Umum, Ketiga.ed. Kardena IM. Swasta Nulus, Denpasar.
Bronte V, Pittet MJ (2013). The spleen in local and systemic regulation of immunity. Immunity 39, 806–818. doi: 10.1016/j.immuni.2013.10.010.
Bukke AN, Hadi FN, Produtur CS (2015). Comparative study of in vitro antibacterial activity of leaves, bark, heart wood and seed extracts of Caesalpinia sappan L. Asian Pacific Journal of Tropical Disease 5, 903–907. doi: 10.1016/S2222-1808(15)60954-9.
Choudhary M, Kumar V, Malhotra H, et al (2015). Medicinal plants with potential anti-arthritic activity: Journal of Intercultural Ethnopharma cology 4, 147. doi: 10.5455/jice.20150313021918.
Corsini A, Bortolini M (2013). Drug-induced liver injury: The role of drug metabolism and transport. The Journal of Clinical Pharmacology 53, 463–474. doi: 10.1002/jcph.23.
Ezzat SM, Ezzat MI, Okba MM, et al. (2018). The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity. Journal of Ethno-pharmacology 214, 113–123. doi: 10.1016/j.jep.2017.12.019.
Firestein GS, McInnes IB (2017). Immuno-pathogenesis of Rheumatoid Arthritis. Immunity 46, 183–196. doi: 10.1016/j.immuni. 2017.02.006.
Fitmawati, Titrawani, Safitri W (2018). Struktur Histologi Hati Tikus Putih (Rattus norvegicus Berkenhout 1769) dengan Pemberian Ramuan Tradisional Masyarakat Melayu Lingga, Kepulauan Riau. EKOTONIA: Jurnal Penelitian Biologi, Botani, Zoologi dan Mikrobiologi 03, 11–19. doi: 10.33019/ekotonia.v3i1.753.
Hidayat R, Bagus Putu Putra Suryana, Linda Kurniaty Wijaya, et al (2021). Indonesian rheumatology association (IRA) recommendations for diagnosis and management of rheumatoid arthritis. Indonesian Journal of Rheumatology 13, 322–443. doi: 10.37275/ijr.v13i1.173.
Hidayati E, Berata IK, Samsuri S, et al (2018). Gambaran histopatologi limpa tikus putih yang diberi deksametason dan vitamin E. Buletin Veteriner Udayana 18. doi: 10.24843/bulvet. 2018.v10.i01.p03.
Idang EO, Yemitan OK, Mbagwu HOC, et al (2019). Toxicological assessment of zingiber officinale roscoe (Ginger) root oil extracts in albino rats. Toxicology Digest 4, 108–119. Available at: https://www.researchgate.net/publication/331155817_Toxicological_Assessment_of_Zingiber_officinale_Roscoe_Ginger_Root_Oil_Extracts_in_Albino_rats.
Jannah DR, Budijastuti W (2022). Gambaran histopatologi toksisitas ginjal tikus jantan (Rattus norvegicus) yang diberi sirup umbi yakon (Smallanthus sonchifolius). LenteraBio : Berkala Ilmiah Biologi 11, 238–246. doi: 10.26740/lenterabio.v11n2.p238-246.
Jung EG, Han K Il, Hwang SG, et al. (2015). Brazilin isolated from caesalpinia sappan L. inhibits rheumatoid arthritis activity in a type-II collagen induced arthritis mouse model. BMC Complementary and Alternative Medicine. doi: 10.1186/s12906-015-0648-x.
Kim KJ, Yoon KY, Yoon HS, et al (2015). Brazilein suppresses inflammation through inactivation of IRAK4-NF-kb pathway in LPS-induced Raw264.7 macrophage cells. International Journal of Molecular Sciences 16, 27589–27598. doi: 10.3390/ijms161126048.
Kumar V, Abbas A, Aster J (2013). Robbins Basic Pathology, 9th Edition. Elsevier, Canada.
Lees JG, White D, Keating BA, et al. (2020). Oxaliplatin-induced haematological toxicity and splenomegaly in mice ed. Palaniyandi S. PLoS One 15, e0238164. doi: 10.1371/journal.pone. 0238164.
Martina SJ, Ramar LAP, Silaban MRI, et al. (2019). Antiplatelet effectivity between aspirin with honey on cardiovascular disease based on bleeding time taken on mice. Open Access Macedonian Journal of Medical Sciences 7, 3416–3420. doi: 10.3889/ oamjms.2019.431.
Mbaveng AT, Kuete V (2017). Zingiber officinale. In Medicinal Spices and Vegetables from Africa: Therapeutic Potential Against Metabolic, Inflammatory, Infectious and Systemic Diseases, pp. 627–639. Elsevier Inc. doi: 10.1016/B978-0-12-809286-6.00030-3.
Miller MA, Zachary JF (2017). Mechanisms and morphology of cellular injury, adaptation, and death. In Pathologic Basis of Veterinary Disease, pp. 2-43.e19. Elsevier. Available at: https://linking hub.elsevier.com/retrieve/pii/B9780323357753000011.
Nirmal NP, Rajput MS, Prasad RGSV, et al (2015). Brazilin from Caesalpinia sappan heartwood and its pharmacological activities: A review. Asian Pacific Journal of Tropical Medicine 8, 421–430. doi: 10.1016/j.apjtm.2015.05.014.
Noh ASM, Chuan TD, Khir NAM, et al (2021). Effects of different doses of complete Freund's adjuvant on nociceptive behaviour and inflammatory parameters in polyarthritic rat model mimicking rheumatoid arthritis ed. Di Paola R. PLoS One 16, e0260423. doi: 10.1371/journal. pone.0260423.
Nurhidayah G, Tukiran, Suyatno, et al (2022). Anti-inflammatory activity combination of ethanol extract from sappan wood (Caesalpinia sappan L .) and red ginger rhizome (Zingeiber officinale Roxb.) against albumin denaturation inhibition. World Journal of Pharmaceutical Research (WJPR). doi: 10.20959/wjpr202216-26197.
Panagopoulos PK, Lambrou GI (2018). Bone erosions in rheumatoid arthritis: recent developments in pathogenesis and therapeutic implications. Journal of Musculoskeletal & Neuronal Interactions18, 304–319. Available at: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC6146189.
Pereira CR-, Silva V, Costa VM, et al. (2019). Histological and toxicological evaluation, in rat, of a P-glycoprotein inducer and activator: 1-(propan-2-ylamino)-4-propoxy-9H-thioxanthen-9-one (TX5). EXCLI J 18, 697–722. doi: 10.17179/excli 2019-1675.
Ping KY, Darah I, Chen Y, et al (2013). Acute and subchronic toxicity study of Euphorbia hirta L. methanol extract in rats. BioMed Research International 2013, 1–14. doi: 10.1155/2013/ 182064.
Rambod M, Nazarinia M, Raieskarimian F (2018). The prevalence and predictors of herbal medicines usage among adult rheumatoid arthritis patients: A case-control study. Complementary Therapies in Medicine 41, 220–224. doi: 10.1016/j.ctim.2018. 10.004.
Ravikumar C (2014). Virulence factors of Acinetobacter spp View project Plastination. Journal of Pharmaceutical Sciences and Research. Available at: https://www.jpsr.pharmainfo.in/Documents/Volumes/Vol6Issue08/jpsr06081402.pdf.
Sangi SMA (2016). Potential therapeutic agents for the treatment of fatty degeneration of liver and atheromatous plaques: An experimental study in rats. Pharmacognosy Magazine 12, 414. doi: 10.4103/0973-1296.191444.
Suhita NLPR, Sudira IW, Winaya IBO (2013). Histopatologi ginjal tikus putih akibat pemberian ekstrak pegagan (Centella asiatica) peroral. Buletin Veteriner Udayana 5, 71–8. Available at: https://ojs.unud.ac.id/index.php/buletinvet/article/view/5741.
Sunil D, Isloor AM, Shetty P, et al (2013). In vivo anticancer and histopathology studies of Schiff bases on Ehrlich ascitic carcinoma cells. Arabian Journal of Chemistry 6, 25–33. doi: 10.1016/j. arabjc.2010.12.016.
Wang W, Dong Z, Zhang J, et al. (2019). Acute and subacute toxicity assessment of oxyclozanide in wistar rats. Frontiers in Veterinary Science. doi: 10.3389/fvets.2019.00294.