Potential of Zingiber officinale var. Rubrum Extract in Inhibiting Helicobacter pylori in Chronic Gastritis Patients: A Pilot Study in Human Focusing on Inflammation, Oxidative Stress, and Quality of Life
DOI:
https://doi.org/10.48048/tis.2026.12656Keywords:
Red Ginger, Zingiber officinale, H. pyori, Gastritis, Chronic, Red Ginger, Zingiber officinale, H. pyori, Gastritis, ChronicAbstract
Helicobacter pylori infection is a major global public health problem. Although H. pylori eradication has been shown to reduce the incidence of gastric cancer, increasing resistance to standard antibiotic therapy decreases treatment success rates. Zingiber officinale var. Rubrum contains active compounds with anti-inflammatory and antioxidant thus potential as an adjuvant for inhibiting H. pylori. This study aimed to demonstrate and verify the effect of ZOR extract therapy on the inhibiting of H. pylori in patients with chronic gastritis. Study parameters included TNF-α, IL-6, IL-1β, MDA, and quality of life based on the SF-NDI. A randomized controlled trial with a pre-post test was conducted from July 2024 to June 2025 at Sebelas Maret University Hospital, Sukoharjo. Thirty patients with chronic ulcers due to H. pylori infection were divided equally into 3 groups: A positive control standard eradication therapy, treatment 1 with the addition of 500 mg ZOR capsules, and treatment 2 with the addition of 1 g ZOR capsules. The intervention lasted for 2 weeks. Parameters evaluated before and after the intervention included serum levels of TNF-α, IL-6, IL-1β, MDA, and quality of life using the SF-NDI. Statistical analysis used ANOVA/Kruskal Wallis test with a significance level of p < 0.05. ZOR supplementation at doses of 500 mg and 1 g reduced TNF-α levels. Administration of 1 g ZOR also reduced IL-6 and IL-1β levels between groups. The reduction in MDA was not significant. Quality of life scores were found primarily in the 500 mg and 1 g ZOR groups, with significant results p < 0.05. Zingiber officinale var. Rubrum supplementation can be applied as an adjuvant in H. pylori eradication therapy, potentially providing anti-inflammatory and antioxidant effects thus improving quality of life in patients with chronic gastric ulcers caused by H. pylori infection.
HIGHLIGHTS
- Red ginger adjuvant therapy reduces key inflammatory cytokines in pylori gastritis.
- Zingiber officinale Rubrum improves patient quality of life alongside standard care.
- Dose-dependent effects shown; 1g more effective reducing IL-6, IL-1β than 500 mg.
- Significant SF-NDI score improvement with ZOR supplementation vs. control.
- ZOR may provide anti-inflammatory support amid rising pylori antibiotic resistance.
GRAPHICAL ABSTRACT
Downloads
References
JKY Hooi, WY Lai, WK Ng, MMY Suen, FE Underwood, D Tanyingoh, P Malfertheiner, DY Graham, V Wong, JCY Wu, FKL Chan, JJY Sung, GG Kaplan and SC Ng. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology 2017; 153, 420-429.
H Maulahela, D Doohan, YAA Rezkhita, AF Syam, LA Waskito, CMA Savitri, M Richardo, A Rahman, YS Namara, H Shatri, A Sanityoso, GA Siregar, E Sudarmo and T Uchida. Helicobacter pylori prevalence in Indonesia: Higher infection risk in Eastern region population. F1000Research 2022; 11, 1581.
M Simadibrata and D Mustikarani. Prevalence and association of Helicobacter pylori infection in bowel disease at Dr. Cipto Mangunkusumo General National Hospital 2010-2021. The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy 2024; 24, 222.
SZ Molaoa. Prevalence of Helicobacter pylori infection and the incidence of the associated malignant and peptic ulcer disease at Nelson Mandela Academic Hospital: A retrospective analysis. Journal of Drug Assessment 2021; 10(1), 57-61.
S Diaconu, A Predescu, A Moldoveanu, CS Pop and C Fierbințeanu-Braticevici. Helicobacter pylori infection: Old and new. Journal of Medicine and Life 2017; 10(2), 112-117.
O Nestegard, B Moayeri, FA Halvorsen, T Tønnesen, SW Sørbye, E Paulssen, KM Johnsen, R Goll, JR Florholmen and KK Melby. Helicobacter pylori resistance to antibiotics before and after treatment: Incidence of eradication failure. PLoS One 2022; 17, e0265322.
S Mukjerjee and D Karati. A mechanistic view on phytochemistry, pharmacognostic properties, and pharmacological activities of phytocompounds present in Zingiber officinale: A comprehensive review. Pharmacological Research-Modern Chinese Medicine 2022; 5, 100173.
D Makmun, A Syam, H Maulahela, R Makmun, A Renaldi, S Simadibrata and A Abdullah. Konsensus nasional penatalaksanaan dispepsia dan infeksi Helicobacter pylori di Indonesia (revisi 2021) (in Indonesian). PIPInterna, Jakarta, Indonesia, 2022.
PSD Dewi and MT Ma’ruf. Sub-acute toxicity test of red ginger extract (Zingiber officinale var. rubrum) on mice (Mus musculus). Interdental Jurnal Kedokteran Gigi 2023; 19(1), 1-5.
C Zhang, A Rao, C Chen, Y Li, X Tan, J Long, X Wang, J Cai, J Huang, H Luo, C Li and Y Dang. Pharmacological activity and clinical application analysis of traditional Chinese medicine ginger from the perspective of one source and multiple substances. Chinese Medicine 2024; 19, 97.
S Zhang, X Kou, H Zhao, KK Mak, MK Balijepalli, MR Pichika and A Khan. Zingiber officinale var. rubrum: Red ginger’s medicinal uses. Molecules 2022; 27, 775.
RD Supu, A Diantini and J Levita. Red ginger (Zingiber officinale var. rubrum): Its chemical constituents, pharmacological activities and safety. Fitofarmaka Jurnal Ilmiah Farmasi 2019; 8, 23-29.
IG Arinton, P Samudro and S Soemohardjo. The Nepean dyspepsia index: Translation and validation in Indonesian language. Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy 2006; 7, 38-41.
F Jaber, S Alsakarneh, A Beran, T Alsharaeh, AJ Salahat, A Abdelshafi, I Mohamed, W Johnson, K Elfert, M Jaber, M Almeqdadi, M Ahmed, H Ghoz, WK Clarkston and JH Helzberg. Impact of Helicobacter pylori eradication on clinical and laboratory parameters in non-alcoholic fatty liver disease patients: A systematic review and meta-analysis of randomized controlled trials. Current Medical Science 2025; 45, 1-10.
AFT Rossi, JC Contiero, F da Silva Manoel-Caetano, FE Severino and AE Silva. Up-regulation of tumor necrosis factor-α pathway survival genes and of the receptor TNFR2 in gastric cancer. World Journal of Gastrointestinal Oncology 2019; 11(4), 281-294.
Y Raza, M Mubarak, MY Memon and MS Alsulaimi. Update on molecular pathogenesis of Helicobacter pylori-induced gastric cancer. World Journal of Gastrointestinal Pathophysiology 2025; 16(2), 107052.
H Sulzbach De Oliveira, V Biolchi, HR Medeiros, DBG Jantsch, Ln De Oliveira Becker Delving, R Reckziegel, MI Goettert, IS Brum and A Pozzobon. Effect of Helicobacter pylori on NFKB1, p38α and TNF-α mRNA expression levels in human gastric mucosa. Experimental and Therapeutic Medicine 2016; 11, 2365-2372.
D Hefni, Y Herdalina and N Suharti. Activity of red ginger extract (Zingiber officinale var. rubrum) against interleukin. International Conference on Contemporary Science and Clinical Pharmacy 2023; 15, 1.
T Sari, S Trisnadi and I Isradji. The effect of red ginger extract on TNF-α and malondialdehyde serum level. International Journal of Multidisciplinary Research and Analysis 2022; 5, 12.
F Ayustaningwarno, G Anjani, AM Ayu and V Fogliano. A critical review of ginger’s (Zingiber officinale) antioxidant, anti-inflammatory, and immunomodulatory activities. Frontiers in Nutrition 2024; 11, 1364836.
HW Jung, CH Yoon, KM Park, HS Han and YK Park. Hexane fraction of Zingiberis rhizoma crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway. Food and Chemical Toxicology 2009; 47, 1190-1197.
Yuandani, R Jantan, N Jalil and S Husain. Immunomodulatory effects and mechanisms of the extracts and secondary compounds of Zingiber and Alpinia species: A review. Frontiers in Pharmacology 2023; 14, 1222195.
XH Li, KCY McGrath, S Nammi, AK Heather and BD Roufogalis. Attenuation of liver pro-inflammatory responses by Zingiber officinale via inhibition of NF-kappa B activation in high-fat diet-fed rats. Basic & Clinical Pharmacology & Toxicology 2012; 110, 238-244.
N Aryaeian, M Mahmoudi, F Shahram, S Poursani, F Jamshidi and H Tavakoli. The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: A randomized controlled trial. Medical Journal of the Islamic Republic of Iran 2019; 33, 154.
D Amanda. 2022, Uji aktivitas imunomodulator ekstrak jahe merah (Zingiber officinale var. rubrum) terhadap tumor nekrosis faktor alfa mencit putih jantan (Mus musculus) dengan metode ELISA (in Indonesian). Bachelor’s Thesis. Universitas Andalas, Indonesia.
MY Song, SH Jeong, HJ Lee, H Kang and JY Kim. Steamed ginger extract exerts anti-inflammatory effects in Helicobacter pylori-infected gastric epithelial cells through inhibition of NF-κB. Journal of Cancer Prevention 2021; 26(4), 289-297
K Gaus, Y Huang, DA Israel, SL Pendland, BA Adeniyi and GB Mahady. Standardized ginger (Zingiber officinale) extract reduces bacterial load and suppresses acute and chronic inflammation in Mongolian gerbils infected with cagA+ Helicobacter pylori. Pharmaceutical Biology 2009; 47, 92-98.
L Zhong, H Tong, J Zhu and M Lv. Pharmacological effects of different ginger juices on the concurrent symptoms in animal models of functional dyspepsia: A comparative study. Food Science & Nutrition 2019; 7(7), 2205-2213.
W Saiah, H Halzoune, R Djaziri, K Tabani, EA Koceir and N Omari. Antioxidant and gastroprotective actions of butanol fraction of Zingiber officinale against diclofenac sodium-induced gastric damage in rats. Journal of Food Biochemistry 2018; 42, e12456.
M Morvaridzadeh, S Fazelian, S Agah, M Khazdouz, M Rahimlou, F Agh, E Potter, S Heshmati and J Heshmati. Effect of ginger (Zingiber officinale) on inflammatory markers: A systematic review and meta-analysis of randomized controlled trials. Cytokine 2020; 135, 155224.
B Yu, L Xiang, MP Peppelenbosch and GM Fuhler. Overlapping cytokines in H. pylori infection and gastric cancer: a tandem meta-analysis. Frontiers in Immunology 2023; 14, 1125658.
XC Yu, QQ Shao, J Ma, M Yu, C Zhang, L Lei, Y Zhou, WC Chen, W Zhang, XH Fang, YZ Zhu, G Wu, XM Wang, SY Han, PC Sun and SZ Ding. Family-based Helicobacter pylori infection status and transmission pattern in central China, and its clinical implications for related disease prevention. World Journal of Gastroenterology 2022; 28(28), 3706-3719.
XY Yuan, Y Zhang, X Zhao, A Chen and P Liu. IL-1β, an important cytokine affecting Helicobacter pylori-mediated gastric carcinogenesis. Microbial Pathogenesis 2023; 174, 105933.
H Yulma. 2022, Uji aktivitas imunomodulator ekstrak jahe merah (Zingiber officinale var. rubrum) terhadap IL-6 pada mencit putih jantan dengan metode ELISA (in Indonesian). Bachelor’s Thesis, Universitas Andalas, Indonesia.
F Zehsaz, N Farhangi and L Mirheidari. The effect of Zingiber officinale R. rhizomes (ginger) on plasma pro-inflammatory cytokine levels in well-trained male endurance runners. Central European Journal of Immunology 2014; 39(2), 174-180.
K Pázmándi, AG Szöllősi and T Fekete. The root causes behind the anti-inflammatory actions of ginger compounds in immune cells. Frontiers in Immunology 2024; 15, 1400956.
M Aliyu, FT Zohora, AU Anka, K Ali, S Maleknia, M Saffarioun and G Azizi. Interleukin-6 cytokine: An overview of the immune regulation, immune dysregulation, and therapeutic approach. International Immunopharmacology 2022; 111, 109130.
RP Semper, R Mejías-Luque, C Groß, F Anderl, A Müller, M Vieth, DH Busch, CP da Costa, J Ruland, O Groß and M Gerhard. Helicobacter pylori-induced IL-1β secretion in innate immune cells is regulated by the NLRP3 inflammasome and requires the Cag pathogenicity island. The Journal of Immunology 2014; 193(7), 3566-3576.
JH Kim, JH Chang, JH Yoon, SH Kwon, JH Bae and KS Kim. Gingerol suppresses interleukin-1β-induced MUC5AC gene expression in human airway epithelial cells. American Journal of Rhinology & Allergy 2009; 23, 385-391.
I Bischoff-Kont, T Primke, LS Niebergall, T Zech and R Fürst. Ginger constituent 6-shogaol inhibits inflammation- and angiogenesis-related cell functions in primary human endothelial cells. Frontiers in Pharmacology 2022; 13, 844767.
Y Song and J Chung. Zingerone-induced autophagy suppresses IL-1β production by increasing the intracellular killing of Aggregatibacter actinomycetemcomitans in THP-1 macrophages. Biomedicines 2023; 11, 2130.
LG Aregawi and C Zoltan. Ginger’s nutritional implication on gastrointestinal health. Clinical Nutrition Open Science 2025; 61, 1-13.
SJ Han, M Kim, VD D’Agati and HT Lee. 6-Shogaol protects against ischemic acute kidney injury by modulating NF-κB and heme oxygenase-1 pathways. American Journal of Physiology-Renal Physiology 2019; 317(3), F743-F756.
N Aryaeian, M Mahmoudi, F Shahram, S Poursani, F Jamshidi and H Tavakoli. The effect of ginger supplementation on IL2, TNFα, and IL1β cytokines gene expression levels in patients with active rheumatoid arthritis: a randomized controlled trial. Medical Journal of the Islamic Republic of Iran 2019; 33, 154.
H Maryam, S Azhar, MN Akhtar, A Asghar, F Saeed, H Ateeq, M Afzaal, N Akram, H Munir, W Anjum and MA Shah. Role of bioactive components of ginger in management of osteoarthritis: A review. International Journal of Food Properties 2023; 26, 1903-1913.
P Ballester, B Cerdá, R Arcusa, J Marhuenda, K Yamedjeu and P Zafrilla. Effect of ginger on inflammatory diseases. Molecules 2022; 27, 7223.
X Zhou, G Münch, H Wohlmuth, S Afzal, MH Kao, A Al-Khazaleh, M Low, D Leach and CG Li. Synergistic inhibition of pro-inflammatory pathways by ginger and turmeric extracts in RAW 264.7 cells. Frontiers in Pharmacology 2022; 13, 818166.
R Sotler, B Poljšak, R Dahmane, T Jukić, D Pavan Jukić, C Rotim, P Trebše and A Starc. Prooxidant activities of antioxidants and their impact on health. Acta Clinica Croatica 2019; 58, 726-736.
VS Chedea, LL Tomoiagǎ, ŞO Macovei, DC Mǎgureanu, ML Iliescu, IC Bocsan, AD Buzoianu, CM Voşloban and RM Pop. Antioxidant/pro-oxidant actions of polyphenols from grapevine and wine by-products - base for complementary therapy in ischemic heart diseases. Frontiers in Cardiovascular Medicine 2021; 8, 750508.
ME Giordano, R Caricato and MG Lionetto. Concentration dependence of the antioxidant and prooxidant activity of Trolox in HeLa cells: involvement in the induction of apoptotic volume decrease. Antioxidants 2020; 9, 1058.
K Jomova, D Valko, M Valko, S Ševčovičová, K Kuča, A Valent and Z Kovalčíková. Reactive oxygen species, toxicity, oxidative stress, and antioxidants: chronic diseases and aging. Archives of Toxicology 2023; 97, 2499-2574.
L Han, X Shu and J Wang. Helicobacter pylori-mediated oxidative stress and gastric diseases: A review. Frontiers in Microbiology 2022; 13, 811258.
G Yang, X Gao, L Jiang, X Sun, X Liu, M Chen, X Yao, Q Sun and S Wang. 6-Gingerol prevents MEHP-induced DNA damage in human umbilical vein endothelial cells. Human & Experimental Toxicology 2017; 36, 1177-1185.
S Wang, G Yang, L Jiang, C Zhang, F Xin, C Geng, X Sun and Y Yang. 6-Gingerol attenuates hydrogen peroxide-induced DNA damage in human umbilical vein endothelial cells. Food Science and Technology Research 2014; 20, 947-954.
B Ahmad, MU Rehman, I Amin, A Arif, S Rasool, SA Bhat, I Afzal, I Hussain, S Bilal and M ur Rahman Mir. A review on pharmacological properties of zingerone (4-(4-hydroxy-3-methoxyphenyl)-2-butanone). The Scientific World Journal 2015; 2015, 816364.
G Figueroa‐González, LI Quintas‐Granados, OD Reyes‐Hernández, IH Caballero‐Florán, SI Peña-Corona, H Cortés, G Leyva-Gómez, S Habtemariam and J Sharifi-Rad. Review of the anticancer properties of 6-shogaol: mechanisms of action in cancer cells and future research opportunities. Food Science & Nutrition 2024; 12(7), 4513-4533.
G Oboh, AJ Akinyemi and AO Ademiluyi. Antioxidant and inhibitory effect of red ginger (Zingiber officinale var. rubra) and white ginger (Zingiber officinale Roscoe) on Fe2+-induced lipid peroxidation in rat brain in vitro. Experimental and Toxicologic Pathology 2012; 64, 31-36.
M Afzal, I Kazmi, AM Quazi, SA Khan, A Zafar, FA Al-Abbasi, F Imam, KS Alharbi, SI Alzarea and N Yadav. 6-Shogaol attenuates traumatic brain injury-induced anxiety/depression-like behavior via inhibition of oxidative stress-influenced expressions of inflammatory mediators TNF-α, IL-1β, and BDNF: Insight into the mechanism. ACS Omega 2022; 7, 140-148.
M Rafeeq, HAS Murad, HM Abdallah and AM El-Halawany. Protective effect of 6-paradol in acetic acid-induced ulcerative colitis in rats. BMC Complementary Medicine and Therapies 2021; 21(1), 28.
P Baiubon, P Kunanusorn, P Khonsung, N Chiranthanut, A Panthong and C Rujjanawate. Gastroprotective activity of the rhizome ethanol extract of Zingiber simaoense YY Qian in rats. Journal of Ethnopharmacology 2016; 194, 571-576.
A Mestrovic, J Bozic, K Vukojevic and A Tonkic. Impact of different Helicobacter pylori eradication therapies on gastrointestinal symptoms. Medicina 2021; 57, 803.
A Shiotani, P Roy, H Lu and DY Graham. Helicobacter pylori diagnosis and therapy in the era of antimicrobial stewardship. Therapeutic Advances in Gastroenterology 2021; 14, 1-19.
H Matsumoto, A Shiotani and DY Graham. Current and future treatment of Helicobacter pylori infections. Helicobacter pylori in Human Diseases: Advances in Microbiology, Infectious Diseases and Public Health 2019; 11, 211-225.
A Gupta, S Shetty, S Mutalik, EM Mathew, A Jha, B Mishra, S Rajpurohit, G Ravi, M Saha and S Moorkoth. Treatment of H. pylori infection and gastric ulcer: Need for novel pharmaceutical formulation. Heliyon 2023; 9, e20406.
MN Bodagh, I Maleki and A Hekmatdoost. Ginger in gastrointestinal disorders: A systematic review of clinical trials. Food Science & Nutrition 2019; 7, 96-108.
Y Huang, MJ Patil, M Yu, P Liptak, BJ Undem, X Dong, G Wang and, S Yu. Effects of ginger constituent 6-shogaol on gastroesophageal vagal afferent C-fibers. Neurogastroenterology & Motility 2019; 31, e13585.
QQ Mao, XY Xu, SY Cao, RY Gan, H Corke, T Beta and HB Li. Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe). Foods 2019; 8, 185.
A Kabiraj and R Deshmukh. A review on Chinese herbal medicine used as carminative. Research-Modern Chinese Medicine 2024; 11, 100409.
G Chantharangsikul, W Kitpati, N Soonthornchareonnon, A Sailasuta, A Itharat and W Suvitayavat. Mucus secretion stimulation: a mechanism in gastroprotective effect of Zingiber officinale. Thai Journal of Pharmaceutical Sciences 2016; 40, 1-8.
NS Karampour, A Arzi, A Rezaie, M Pashmforoosh and F Kordi. Gastroprotective effect of zingerone on ethanol-induced gastric ulcers in rats. Medicina 2019; 55(3), 64.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
