Protective Effects of Salacca zalacca Peel Extract on Oxidative and Inflammatory Liver Injury Biomarkers in CCl4-Induced Rats
DOI:
https://doi.org/10.48048/tis.2026.12785Keywords:
Salacca zalacca peel extract, CCl₄, SGPT, TNF-α, SOD, HepatoprotectionAbstract
Salacca zalacca peel extract (SPE) contains phenolic and flavonoid compounds with reported antioxidant and anti-inflammatory properties, but in vivo evidence from liver injury models remains limited. This study evaluated the effects of SPE on biomarkers in CCl₄-induced liver injury in Wistar rats by measuring serum alanine aminotransferase (SGPT), TNF-α, and superoxide dismutase (SOD). Thirty rats were divided into 5 groups: Healthy controls, 2% CCl₄-treated controls (C-), 3.6 mg/kg NAC-treated controls (C+), and CCl₄-induced rats treated with low (400 mg/kg BW/day) and high (600 mg/kg BW/day) doses of SPE for 14 days. SPE was administered orally following CCl₄ induction. SGPT levels were measured by spectrophotometry, and TNF-α and SOD levels were analyzed using ELISA. Compared to CCl₄ controls, SPE groups showed significantly reduced SGPT and TNF-α levels and elevated SOD activity (p < 0.005), indicating improved markers of hepatocellular injury, inflammation, and antioxidant status. The high-dose SPE group exhibited the greatest effect. In conclusion, SPE administration demonstrated antioxidant and anti-inflammatory benefits by lowering SGPT and TNF-α while increasing SOD levels.
HIGHLIGHTS
- Ethanolic Salacca zalacca peel extract protects against CCl₄-induced liver injury in Wistar rats.
- The extract reduces SGPT and TNF-α levels and improves antioxidant enzyme activity.
- High phenolic and flavonoid contents contribute to antioxidant and anti-inflammatory effects.
- Liver protection is associated with improved oxidative stress and inflammatory status.
- Salacca zalacca peel shows potential as a natural hepatoprotective agent from agricultural waste.
GRAPHICAL ABSTRACT
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J Vrba, B Papoušková, K Lněničková, P Kosina, V Křen and J Ulrichová. Metabolism of 2,3-dehydrosilybin A and 2,3-dehydrosilybin B: A study with human hepatocytes and recombinant UDP-glucuronosyltransferases and sulfotransferases. Antioxidants 2021; 10(6), 954.
X Meng, GY Tang, PH Liu, CJ Zhao, Q Liu and HB Li. Antioxidant activity and hepatoprotective effect of 10 medicinal herbs on CCl4 -induced liver injury in mice. World Journal of Gastroenterology 2020; 26(37), 5629-5645.
C Lee, S Yoon and JO Moon. Kaempferol suppresses carbon tetrachloride-induced liver damage in rats via the MAPKs/NF-κB and AMPK/Nrf2 signaling pathways. International Journal of Molecular Sciences 2023; 24(8), 6900.
Y Ibn ElAchaouia, A Mahmoudi, D Dallali, R Marrakchi, G Marti, M Chamkha, S Sayadi and A Noureddine. UHPLC-HRMS-MS analysis, antioxidant and hepatoprotective effects of methanolic extracts from Ficus carica L., leaves and stem barks against acute CCl4 -induced liver damage. Natural Product Research 2025. https://doi.org/10.1080/14786419.2025.2498075
S Munakarmi, L Chand, HB Shin, KY Jang and YJ Jeong. Indole-3-carbinol derivative DIM mitigates carbon tetrachloride-induced acute liver injury in mice by inhibiting inflammatory response, apoptosis and regulating oxidative stress. International Journal of Molecular Sciences 2020; 21(6), 2048.
L Sun, Y Zhang, S Wen, Q Li, R Chen, X Lai, Z Zhang, Z Zhou, Y Xie, X Zheng, K Zhang, D Li and S Sun. Extract of Jasminum grandiflorum L. alleviates CCl4-induced liver injury by decreasing inflammation, oxidative stress and hepatic CYP2E1 expression in mice. Biomedicine & Pharmacotherapy 2022; 152, 113255.
FT Johra, S Hossain, P Jain, AT Bristy, T Emran, R Ahmed, SM Sharker, AK Bepari and HM Reza. Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in Long Evans rats. Scientific Reports 2023; 13(1), 9909.
MM Erdogan, MA Erdogan, S Koc, A Yalcin, A Turk and EA Yetkin. Hepatoprotective effects of N-acetylcysteine on liver injury by irisin upregulation and oxidative stress reduction in diabetic rats. Egyptian Liver Journal 2023; 13(1), 33.
B Wang, S Cui, B Mao, Q Zhang, F Tian, J Zhao, X Tang and W Chen. Cyanidin alleviated CCl4-induced acute liver injury by regulating the Nrf2 and NF-κB signaling pathways. Antioxidants 2022; 11(12), 2383.
D Emad, AMA Bayoumi, SM Gebril, DME Ali and S Waz. Modulation of keap-1/Nrf2/HO-1 and NF-ĸb/caspase-3 signaling pathways by dihydromyricetin ameliorates sodium valproate-induced liver injury. Archives of Biochemistry and Biophysics. 2024; 758, 110084.
P Hlásná Čepková, M Jágr, D Janovská, V Dvořáček, A Kotrbová Kozak and I Viehmannová. Comprehensive mass spectrometric analysis of snake fruit: Salak (Salacca zalacca). Journal of Food Quality 2021; 2021, 6621811.
AAIM Padmiswari, NT Wulansari, KB Harditya and SD Megayanti. Antioxidant activity test of salak bali peel extract (Salacca zalacca var. amboinensis) against brain cells of male mice (Mus musculus L.) induced by alloxan. Jurnal Pijar Mipa 2025; 20(1), 35-39.
Y Zhou, C Qian, Y Tang, M Song, T Zhang, G Dong, W Zheng, C Yang, C Zhong, A Wang, Y Zhao and Y Lu. Advance in the pharmacological effects of quercetin in modulating oxidative stress and inflammation related disorders. Phytotherapy Research 2023; 37(11), 4999-5016.
H Khotimah, SN Alita, D Aninditha, A Weningtyas, WE Prima, U Kalsum, M Rahayu, D Handayani and SK Nandar. Ethanolic extract of Salacca zalacca peel reduce IL-1β and apoptosis in high glucose induced zebrafish embryo. GSC Biological and Pharmaceutical Sciences 2021; 16(3), 024-033.
RM Hussein, DM Sawy, MA Kandeil and HS Farghaly. Chlorogenic acid, quercetin, coenzyme Q10 and silymarin modulate Keap1-Nrf2/heme oxygenase-1 signaling in thioacetamide-induced acute liver toxicity. Life Sciences 2021; 277, 119460.
W Widowati, D Dani, V Vera and VA Yuninda. Antioxidant and antiaging potential of salak fruit extract (Salacca zalacca (Gaert.) Voss). Majalah Obat Tradisional 2023; 28(3), 230-236.
PH Čepková, M Jágr, D Janovská, V Dvořáček, AK Kozak and I Viehmannová. Comprehensive mass spectrometric analysis of snake fruit: Salak (Salacca zalacca). Journal of Food Quality 2021; 2021, 662811.
F Aghababaei and M Hadidi. Recent advances in potential health benefits of quercetin. Pharmaceuticals 2023; 16(7), 1020.
OJ Sul and SW Ra. Quercetin prevents LPS-induced oxidative stress and inflammation by modulating NOX2/ROS/NF-kB in lung epithelial cells. Molecules 2021; 26(22), 6949.
A Arhami, LT Djohan and H Rajagukguk. The effect of giving salak (Salacca Zalacca) bark extract on liver function and histopathological features of the liver of male wistar white rats obesity model. International Journal of Public Health Excellence 2024; 3(2), 607-616.
DY Putri, Y Yueniwati, S Utami, MFR Syaban, N Halid, PP Putra, SP Putri and H Khotimah. Salacca zalacca skin as a potential adjuvant for metabolic syndrome therapy: Integrative in vitro and computational approaches. Trends in Sciences 2024; 22(11), 10678.
S Utami, MFR Syaban, DY Putri, VAG Hose, H Khotimah and Y Yueniwati. Bioinformatics examination of quercetin from Salacca zalacca skin, fruit, and seed as a potent active compounds against hypercholesterolemia via PCSK9 inhibition. Trends in Sciences 2025; 22(4), 9237.
E Zubaidah, Y Hasfiani and H Sujuti. Physicochemical properties and anti-cancer activity of Javanese turmeric kombucha (Curcuma xanthorrhiza) against T47D cell line. Trends in Sciences 2025; 22(9), 10417.
E Girsang, C Ginting, I Lister, C Wijayanti, W Widowati and R Rizal. Antioxidant properties of Salacca zalacca (Gaertn.) voss peel ethanolic extract compared to chlorogenic acid. In: Proceedings of the 1st International Conference on Emerging Issues in Technology, Engineering and Science (ICE-TES 2021), Bandung, Indonesian, 2021, p. 87-94.
E Coyago-Cruz, G Méndez, J Zúñiga-Miranda, N Jami, R Acurio-Vásconez and J Heredia-Moya. Dynamics of bioactive compounds and their relationship with antioxidant and antimicrobial activity in the pulp, peel, and seeds of ‘salak’ during ripening. Foods 2025; 14, 3476.
JM Clarkson, JE Martin and DEF McKeegan. A review of methods used to kill laboratory rodents: Issues and opportunities. Laboratory Animals 2022; 56(5), 419-436.
DL Hickman. Minimal exposure times for irreversible euthanasia with carbon dioxide in mice and rats. Journal of The American Association for Laboratory Animal Science 2022; 61(3), 283-286.
MW Brunt, L Améndola and DM Weary. Attitudes of laboratory animal professionals and researchers towards carbon dioxide euthanasia for rodents and perceived barriers to change. Laboratory Animals 2021; 55(6), 531-539.
C Dai, X Zhang, J Lin and J Shen. Nootkatone supplementation ameliorates carbon tetrachloride-induced acute liver injury via the inhibition of oxidative stress, NF-κB pathways, and the activation of Nrf2/HO-1 pathway. Antioxidants 2023; 12(1), 194.
S Wang, W Li, W Liu, L Yu, F Peng, J Qin, L Pu, Y Tang, X Xie and C Peng. Total flavonoids extracted from Penthorum chinense Pursh mitigates CCl4-induced hepatic fibrosis in rats via inactivation of TLR4-MyD88-mediated NF-κB pathways and regulation of liver metabolism. Frontiers in Pharmacology 2023; 14, 1253013.
B Pandey, S Thapa, A Kaundinnyayana and S Panta. Hepatoprotective effects of Juglans regia on carbon tetrachloride‐induced hepatotoxicity: In silico/in vivo approach. Food Science & Nutrition 2024; 12(9), 6482-6497.
R Setyawaty, RB Aptuning and Dewanto. Preliminary studies on the content of phytochemical compounds on skin of salak fruit (Salacca zalacca). Pharmaceutical Journal of Indonesia 2020; 6(1), 1-6.
Mohammed, SM Saleh, M Siddiqui, S Mat So’Ad, S Murugesu, A Khatib and M Rahman. Antioxidant and α-glucosidase inhibitory activities and gas chromatography-mass spectrometry profile of salak (Salacca zalacca) fruit peel extracts. Pharmacognosy Research 2018; 10(4), 385.
Sukamto, KM Amalia and Sudiyono. Effect of drying temperature and wilting period on the physical and sensory properties of indonesian pondoh snake fruit (Salacca zalacca) powder. International Journal of Current Science Research and Review 2025; 08(5), 2439-2444.
DPB Suri, A Ningrum, MP Kurniawan, ZA Athaillah and Manikharda. Valorization of snake fruit (Salacca edulis R) seeds for coffee subtitutes: Impact of drying and roasting on bioactive compounds and sensory profile. Biocatalysis and Agricultural Biotechnology 2025; 66, 103613.
RK Saputri, A Al-Bari and DI Pramesti. Phytochemical screening and evaluation of transparent soap with addition of wedi snakefruit (Salacca zalacca) rind extract. In: Proceedings of the 4th Green Development International Conference (GDIC 2022), Jambi, Indonesia. 2023, p. 78-86.
PD Andina, D Indarto and LO Wardhani. Phytochemical and nutrient analysis of ethanol extract of Salak Pondoh (Sallaca Edulis Reinw) peel for the development of anti-obesity. Media Penelitian dan Pengembangan Kesehatan 2025; 35(2), 467-476.
D Pertiwi, AP Aulia, JW Wibowo, M Nisa, D Guscella and N Anggita. The effect of ethanol extract from Salacca zalacca (Gaertn.) voss peel on antioxidant and uric acid levels in hyperuricemia rats. Tropical Journal of Natural Product Research 2025; 9(4), 1706-1710.
National Agency of Drug and Food Control of the Republic of Indonesia. Regulation of the national agency of drug and food control number 20 of 2023 on guidelines for preclinical pharmacodynamic testing of traditional medicines. National Agency of Drug and Food Control of the Republic of Indonesia, Central Jakarta, Indonesia, 2023.
EJ Jo, E Bae, JH Yoon, JY Kim and JS Han. Comparison of murine retroorbital plexus and facial vein blood collection to mitigate animal ethics issues. Laboratory Animal Research 2021; 37(1), 12.
US Aguwa, CE Eze, BN Obinwa, SN Okeke, SF Onwuelingo, DI Okonkwo, DK Ogbuokiri, AE Agulanna, IJ Obiesie and AJ Umezulike. Comparing the effect of methods of rat euthanasia on the brain of wistar rats: Cervical dislocation, chloroform inhalation, diethyl ether inhalation and formalin inhalation. Journal of Advances in Medicine and Medical Research 2020; 32(17), 8-16.
G Ouais and DM Hassan. A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats. Anatomy & Cell Biology 2023; 56(4), 538-551.
X Yu, L Huang, C You and L Huang. Hepatoprotective Effects of Polysaccharide from Anoectochilus roxburghii (Wall.) Lindl. on Rat Liver Injury Induced by CCl4. Drug Design, Development and Therapy 2021; 15, 2885-2897.
N Iqbal, HM Zubair, MH Almutairi, M Abbas, MF Akhtar, L Aleya, M Kamel, A Saleem, Q Jabeen, S Noreen, MMFA Baig and MM Abdel-Daim. Hepatoprotective effect of Cordia rothii extract against CCl4-induced oxidative stress via Nrf2–NFκB pathways. Biomedicine & Pharmacotherapy 2022; 156, 113840.
J Juarros-Basterretxea, G Aonso-Diego, Á Postigo, P Montes-Álvarez, Á Menéndez-Aller and E García-Cueto. Post-hoc tests in 1-way ANOVA: The case for normal distribution. Methodology 2024; 20(2), 84-99.
I Touiss, S Ouahhoud, M Harnafi, S Khatib, O Bekkouch, S Amrani and H Harnafi. Toxicological evaluation and hepatoprotective efficacy of rosmarinic acid-rich extract from Ocimum basilicum L. Evidence-Based Complementary and Alternative Medicine 2021; 2021, 6676998.
S Sergazy, Z Shulgau, Y Kamyshanskiy, Z Zhumadilov, E Krivyh, A Gulyayev and M Aljofan. Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress. Heliyon 2023; 9(4), e15370.
NA Madbouly, DM Ali and AA Farid. Nanoparticles from grape seed extract inhibit inflammatory cytokines and ameliorate CCl4-induced hepatotoxicity. BMC Complementary Medicine and Therapies 2025; 25(1), 276.
N Ammar, H Hassan, H Abdallah, S Afifi, A Elgamal, A Farrag, A El-Gendy, M Farag and A Elshamy. Protective effects of naringenin from Citrus sinensis (var. Valencia) peels against CCl4-induced hepatic and renal injuries in rats assessed by metabolomics, histological and biochemical analyses. Nutrients 2022; 14(4), 841.
M Kim, SC Jee and JS Sung. Hepatoprotective effects of flavonoids against benzo[a]pyrene-induced oxidative liver damage along its metabolic pathways. Antioxidants 2024; 13(2), 180.
H Yousefi-Manesh, AR Dehpour, S Ansari-Nasab, S Hemmati, MA Sadeghi, RH Shahraki, S Shirooie, SM Nabavi, JG Nkuimi Wandjou, S Sut, G Caprioli, S Dall’Acqua and F Maggi. Hepatoprotective effects of standardized extracts from an ancient italian apple variety (Mela Rosa Dei Monti Sibillini) against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Molecules 2020; 25(8), 1816.
M Wang, L Zhao, Y Wang, C Zhang and H Li. Sugarcane molasses polyphenol extract attenuates alcohol-induced chronic liver damage via antioxidant, anti-inflammatory, and CYP2E1/Keap1/NF-κB pathway modulation. Nutrients 2025; 17(9), 1589.
D Wang, T Wang, Z Li, Y Guo and D Granato. Green tea polyphenols upregulate the Nrf2 signaling pathway and suppress oxidative stress and inflammation markers in D-galactose-induced liver aging in mice. Frontiers in Nutrition 2022; 9, 836112.
IF Machado, RG Miranda, DJ Dorta, AP Rolo and CM Palmeira. Targeting oxidative stress with polyphenols to fight liver diseases. Antioxidants 2023; 12(6), 1212.
GM Kondepudi, BG Rao and P Balakrishnaiah. Evaluation of hepatoprotective effects of selected fruit peel extracts and their poly herbal mixture on CCl4 induced hepatotoxicity: An in vivo study. Indian Drugs 2020; 57(9), 67-74.
R Li, W Yang, Y Yin, X Ma, P Zhang and K Tao. 4-OI attenuates carbon tetrachloride-induced hepatic injury via regulating oxidative stress and the inflammatory response. Frontiers in Pharmacology 2021; 12, 651444.
H Ali, A Jahan, S Samrana, A Ali, S Ali, N Kabir, A Ali, R Ullah, RA Mothana, BN Murtaza and M Kalim. Hepatoprotective potential of pomegranate in curbing the incidence of acute liver injury by alleviating oxidative stress and inflammatory response. Frontiers in Pharmacology 2021; 12, 694607.
TI Tithi, MdR Tahsin, J Anjum, TS Zaman, F Aktar, NB Bahar, S Tasnim, A Sultana, I Jahan, SS Afrin, T Akter, P Sen, FJ Koly, MdS Reza, JA Chowdhury, S Kabir, AA Chowdhury and S Amran. An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity. PLoS One 2023; 18(9), e0291125.
A Allameh, R Niayesh-Mehr, A Aliarab, G Sebastiani and K Pantopoulos. Oxidative stress in liver pathophysiology and disease. Antioxidants 2023; 12(9), 1653.
JS Park, N Rustamov and YS Roh. The roles of NFR2-regulated oxidative stress and mitochondrial quality control in chronic liver diseases. Antioxidants 2023; 12(11), 1928.
NA Mohamed, MAM Hashem, AM Alzahrani, AM Abdel-Moneim and HM Abdou. Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats. Journal of Pharmacy and Pharmacology 2021; 73(11), 1562-1570.
FC Liu, HC Lee, CC Liao, AH Chou and HP Yu. Role of NADPH oxidase-derived ROS-mediated IL-6/STAT3 and MAPK/NF-κB signaling pathways in protective effect of corilagin against acetaminophen-induced liver injury in mice. Biology 2023; 12, 334.
Q Zou, N Wang, Z Gao, H Xu, G Yang, T Zhang, Z Guo, Z Zhang, L Jia and X Chen. Antioxidant and hepatoprotective effects against acute CCl 4 ‐induced liver damage in mice from red‐fleshed apple flesh flavonoid extract. Journal of Food Science 2020; 85(10), 3618-3627.
K Yin, X Li, X Luo, Y Sha, P Gong, J Gu and R Tan. Hepatoprotective effect and potential mechanism of aqueous extract from Phyllanthus emblica on carbon-tetrachloride-induced liver fibrosis in rats. Evidence-Based Complementary and Alternative Medicine 2021; 2021, 5345821.
Y Lu, Y Hong, T Sun, F Li, Y Li, B Liu, W Wang and C Gao. Lycopus lucidus Turcz. extract ameliorates CCl4-induced liver damage by MAPK/Nrf2 signaling pathways and gut microbiota in mice. Journal of Functional Foods 2025; 128, 106834.
N Saadaoui, A Mathlouthi, A Zaiter, S El-Bok, M Mokni, M Harbi, N Ghanem-Boughanmi, A Dicko and M Ben-Attia. Phytochemical profiling, antioxidant potential and protective effect of leaves extract of tunisian Vitis vinifera autochthonous accessions against acute CCl4-injured hepatotoxicity in mice. Heliyon 2023; 9(5), e16377.
E Wani, T Nasihun and A Hussaana. The influence of continuous multi stage countercurrent extraction process (CMCE) propolis extract administration on superoxide dismutase activity and hepatocytes fibrosis degree (an experimental study on male wistar rats induced with carbon tetrachloride (CCl4)). Sains Medika 2020; 11(1), 42.
R Yi, Y Wei, F Tan, J Mu, X Long, Y Pan, W Liu and X Zhao. Antioxidant capacity-related preventive effects of shoumei (slightly fermented Camellia sinensis) polyphenols against hepatic injury. Oxidative Medicine and Cellular Longevity 2020; 2020, 9329356.
IG Ko, JJ Jin, L Hwang, SH Kim, CJ Kim, JH Han, S Lee, HI Kim, HP Shin and JW Jeon. Polydeoxyribonucleotide exerts protective effect against CCl4-induced acute liver injury through inactivation of NF-κB/MAPK signaling pathway in mice. International Journal of Molecular Sciences 2020; 21(21), 7894.
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