Prospects for Pharmaceutical of Zingiber officinale Extracts and Fractions by Analysis of the Chemical Markers, Safety Profile, Anti-Lipoxygenase, and Analgesic Activity: http://.www.doi.org/10.26538/tjnpr/v7i2.11

Zinna Marie P. Rasonabe; Charlene G. Tiausas; Jannelle D. Cruz; Francheska Areza

Authors

Zinna Marie P. Rasonabe Synnovate Pharma Corporation, Unilab Pharma Campus, 4024 Biñan, Laguna, Philippines
Charlene G. Tiausas Synnovate Pharma Corporation, Unilab Pharma Campus, 4024 Biñan, Laguna, Philippines
Jannelle D. Cruz Synnovate Pharma Corporation, Unilab Pharma Campus, 4024 Biñan, Laguna, Philippines
Francheska Areza Synnovate Pharma Corporation, Unilab Pharma Campus, 4024 Biñan, Laguna, Philippines

Keywords:

Analgesic, Anti-inflammatory, Acute oral toxicity, Liquid chromatography-tandem mass spectrometry, High-performance liquid chromatography, Zingiber officinale

Abstract

Ginger (Zingiber officinale) has gained recognition for its flavoring uses and its numerous health benefits. Ginger can be used in functional foods and nutraceuticals alone or combined with other herbal plants. This study aims to validate the pharmaceutical potential of the Zingiber officinale variety from the Philippines by examining the chemical composition, acute oral toxicity, anti lipoxygenase, and analgesic activities of its extracts and fractions. 6, 8, 10-Gingerols and 6, 8, 10-Shogaols were identified by high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) in methanol and hexane extracts. Acute oral toxicity in mice indicated the median lethal dose (LD50) of methanol and hexane extracts of Zingiber officinale, and the 1% IPA-hexane and 50% IPA-hexane fractions obtained by solid phase extraction (SPE) was greater than 2000 mg/kg body weight. The 1% IPA-hexane fraction altered the behavioral pattern of the animals. The anti-inflammatory activity was analyzed by lipoxygenase (LOX) inhibition assay. The IC50 value for the inhibitory action of crude methanol extract on LOX was 218.00 µg/mL. The crude hexane extract IC50 value was 57.40 µg/mL. SPE fractionation of hexane extracts resulted in higher IC50 values; 72.14 µg/mL for the 1% IPAhexane fraction and 98.65 µg/mL for the 50% IPA-hexane fraction. Through in-vitro suppression of LOX, the hexane crude extracts showed more effective anti-inflammatory properties. The analgesic effect was measured using acetic acid-induced writhing in mice. All doses of the methanol and hexane extract inhibited writhing by a percentage ranging from 91-100%. The SPE fractions of the hexane extract have 78-99% inhibition. Both extracts and fractions demonstrated strong analgesic effects in the mice models.

References

Han YA, Song CW, Koh WS, Yon GH, Kim YS, Ryu SY, Kwon HJ, Lee KH. Anti-inflammatory effects of the Zingiber officinale roscoe constituent 12-dehydrogingerdione in lipopolysaccharide-stimulated Raw 264.7 cells. Phytother Res. 2013; 27(8):1200-1205.

Kizhakkayil J, Sasikumar B. Diversity, characterization and utilization of ginger: A review. Plant Genet. Resour. Characterisation Util. 2011; 9(3):64-477.

Johnson JB, Mani JS, White S, Brown P, Naiker M. Current Research in Food Science Pungent and volatile constituents of dried Australian ginger. Curr. Res. Food Sci. 2021; 4:612-618.

Mao QQ, Xu XY, Cao SY, Gan RY, Corke H, Beta T, Li HB.Bioactive compounds and bioactivities of ginger (zingiber officinale roscoe). Foods. 2019; 8(6):1-21.

Prasad S, Tyagi AK. Ginger and its constituents: Role in prevention and treatment of gastrointestinal cancer. Gastroenterol. Res. Pract. 2015; 2015:142979.

Yeh HY, Chuang CH, Chen HC, Wand CJ, Chena TL, Lin LY. Bioactive components analysis of two various gingers (Zingiber officinale Roscoe) and antioxidant effect of ginger extracts. LWT - Food Sci. Technol. 2014; 55(1):329-334.

Rupasinghe V, Gunathilake K. Recent perspectives on the medicinal potential of ginger. Bot. Targets Ther. 2015; 2015(5):55-63.

Siddiq IA, Martin O, Lawal, Usman, IN, Muhammad MB. Cardio-and-Hepatoprotective Benefits of Some Spices in Wistar Rats Induced with Metabolic Syndrome. Trop. J. Nat. Prod. Res. 2022; 6(10):1707-1714.

Pagano E, Souto EB, Durazzo A, Sharifi-Rad J, Lucarini M, Souto SB, Salehi B, Zam W, Montanaro V, Lucariello G, Izzo AA, Santini A, Romano B. Ginger (Zingiber officinale Roscoe) as a nutraceutical: Focus on the metabolic, analgesic, and anti-inflammatory effects. Phyther. Res. 2021; 35:2403-2417.

Fajrin FA, Nugroho AE, Nurrochmad A, Susilowati R. Ginger extract and its compound, 6-shogaol, attenuates painful diabetic neuropathy in mice via reducing TRPV1 and NMDAR2B expressions in the spinal cord. J. Ethnopharmacol. 2020; 249:112396.

Balberona AN, Noveno JJ, Angeles MGB, Santos RI, Cachin EJDJ, Cruz KGJ. Ethnomedicinal Plants Utilized by the Ilongot-Eǵongot Community of Bayanihan, Maria Aurora, Aurora, Philippines. Int. J. Agric. Technol. 2018; 14(2):145-159.

Baleta FN, Donato JG, Bolaños JM. Awareness, utilization and diversity of medicinal plants at Palanan, Isabela, Philippines J. Med. Plants Stud. 2016; 4(4):265-269.

Demayo CG, Olowa L. Ethnobotanical Uses of Medicinal Plants among the Muslim Maranaos in Iligan City. Adv. Environ. Biol. 2015; (7):204-215.

Lantz RC, Chen GJ, Sarihan M, Sólyom AM, Jolad SD, Timmermann BN. The effect of extracts from ginger rhizome on inflammatory mediator production. Phytomedicine. 2007; 14(2-3):123-128.

Putra ED, Nazliniwaty N, Syafruddin S, Nerdy, N. (2021). Component Analysis of White Ginger (Zingiber officinale Roscoe) Extract and Red Ginger (Zingiber officinale Rubra) Extract. Trop. J. Nat. Prod. Res. 2021; 5(9):1634-1637.

Mehrzadi S, Khalili H, Fatemi I, Malayeri A, Siahpoosh A, Goudarzi M. Zingerone Mitigates Carrageenan-Induced Inflammation Through Antioxidant and Anti-inflammatory Activities. Inflammation. 2021; 44(1):186-193.

Li J, Thangaiyan R, Govindasamy K, Wei J. Antiinflammatory and Anti-Apoptotic Effect of Zingiberene on IsoproterenolInduced Myocardial Infarction in Experimental Animals. Hum Exp Toxicol. 2020; 40(6):915-927.

Nishidono Y, Saifudin A, Nishizawa M, Fujita T, Nakamoto M, Tanaka K. Identification of the Chemical Constituents in Ginger (Zingiber officinale) Responsible for Thermogenesis. Nat. Prod. Commun. 2018; 13(7):869-873.

Park JS, Jung MY. Development of high-performance liquid chromatography-time-of-flight mass spectrometry for the simultaneous characterization and quantitative analysis of gingerol-related compounds in ginger products. J. Agric. Food Chem. 2012; 60(40):10015-10026.

Tao Y, Li W, Liang W, Van BRB. Identification and Quantification of Gingerols and Related Compounds in Ginger Dietary Supplements Using High-Performance Liquid Chromatography-Tandem Mass Spectrometry. J. Agric. Food Chem. 2009; 57(21):10014-10021.

de Lima RMT, Dos Reis AC, de Menezes APM, Santos JVO, Filho JWGO, Ferreira JRO, de Alencar MVOB, da Mata AMOF, Khan IN, Islam A, Uddin SJ, Ali ES, Islam MT, Tripathi S, Mishra SK, Mubarak MS, Melo-Cavalcante AAC. Protective and therapeutic potential of ginger (Zingiber officinale) extract and [6]-gingerol in cancer: A comprehensive review. Phytother Res. 2018; 32(10):1885-1907.

Yücel Ç, Karatoprak GŞ, Açıkara ÖB, Akkol EK, Barak TH, Sobarzo-Sánchez E, Aschner M, Shirooie S. Immunomodulatory and anti-inflammatory therapeutic potential of gingerols and their nanoformulations. Front Pharmacol. 2022; 13:902551.

Ley-Martínez JS, Ortega-Valencia JE, García-Barradas O, Jiménez-Fernández M, Uribe-Lam E, Vencedor-Meraz CI, Oliva-Ramírez J. Active Compounds in Zingiber officinale as Possible Redox Inhibitors of 5-Lipoxygenase Using an In Silico Approach. Int. J. Mol. Sci. 2022; 23(11):6093.

Ali BH, Blunden G, Tanira MO, Nemmar A. Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): a review of recent research. Food Chem. Toxicol. 2008; 46(2):409-420.

Semwal RB, Semwal DK, Combrinck S, Viljoen AM. Gingerols and shogaols: important nutraceutical principles from ginger. Phytochemistry. 2015; 117:554-568.

Wohlmuth H, Leach DN, Smith MK, Myers SP. Gingerol content of diploid and tetraploid clones of ginger (Zingiber officinale Roscoe). J. Agric. Food Chem. 2005; 53(14):5772-5778.

Bischoff-Kont I, Fürst R. Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes. Pharmaceuticals. 2021; 14(6):571.

Flynn DL, Rafferty MF, Boctor AM. Inhibition of human neutrophil 5-lipoxygenase activity by gingerdione, shogaol, capsaicin and related pungent compounds. Prostaglandins, Leukot. Med. 1986; 24(2-3):195-198.

Weidner MS, Sigwart K. Investigation of the teratogenic potential of a Zingiber officinale extract in the rat. Reprod. Toxicol. 2001; 15(1):1575-1580.

Wilkinson JM. Effect of ginger tea on the fetal development of Sprague–Dawley rats. Reprod. Toxicol. 2000; 14(6):507-512.

Chrubasik S, Pittler MH. Roufogal BD. Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles. Phytomedicine. 2005; 12(9):684-701.

Zick SM, Djuric Z, Ruffin MT, Litzinger AJ, Normolle DP, Alrawi S, Feng MR, Brenner DE. Pharmacokinetics of 6-gingerol, 8-gingerol, 10-gingerol and 6-shogaol and conjugate metabolites in healthy human subjects. Cancer Epidemiol. Biomark. Prev. 2008; 17(8):1930-1936.

Sánchez-Mateo CC, Bonkanka CX, Hernández-Pérez M, Rabanal RM. Evaluation of the analgesic and topical antiinflammatory effects of Hypericum reflexum L. fil. J. Ethnopharmacol. 2006; 107(1):116.

Young HY, Luo YL, Cheng HY, Hsieh WC, J Liao JC, Peng WH. Analgesic and anti-inflammatory activities of [6]-gingerol. J. Ethnopharmacol. 2005; 96(1-2):207-210.

Suekawa M, Ishige A, Yuasa K, Sudo K, Aburada M, Hosoya E. Pharmacological studies on ginger. I. Pharmacological actions of pungent constitutents, (6)-gingerol and (6)-shogaol. J Pharmacobiodyn. 1984;7(11):836-848.