medtigo Journal of Pharmacology

|Literature Review

| Volume 1, Issue 1

Anti-Inflammatory Effects of Zingiber officinale: A Comprehensive Review of Its Bioactive Compounds and Therapeutic Potential

Author Affiliations

medtigo J Pharmacol. Published Date: Sep 24, 2024.

https://doi.org/10.63096/medtigo3061113

Abstract

Zingiber officinale is commonly known as ginger, which has been extensively studied for its anti-inflammatory properties. Numerous studies have demonstrated ginger’s efficacy in mitigating inflammation through its bioactive compounds such as 6-gingerol, 6-shogaols, and zingerone, which modulate the key inflammatory pathways. These compounds inhibit cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) by reducing the production of pro-inflammatory mediators like prostaglandins and leukotrienes. Ginger has demonstrated efficacy in treating several inflammatory diseases, such as rheumatoid arthritis, ulcerative colitis, and psoriasis, through inhibitory effects on nuclear factor-kappa B (NF-κB) and changes in oxidative stress. Both clinical and preclinical studies have suggested that ginger is effective in the treatment of inflammation and is comparable to NSAIDs, but has fewer side effects, particularly concerning the gastrointestinal tract. Some of the research findings that were reported demonstrated the effectiveness of ginger in fighting inflammation. However, large-scale clinical trials are still required to establish the therapeutic efficacy of ginger in inflammatory diseases.

Keywords

Zingiber officinale, Ginger, Anti-inflammatory properties, Bioactive compounds, 6-gingerol, 6-shogaol, Zingerone, Pro-inflammatory mediators, Prostaglandins, Leukotrienes

Introduction

Zingiber officinale is a flowering plant native to Southeast Asia and is highly valued for its rhizome, which is used as both a spice and a traditional medicine.[1] Ginger has numerous health benefits, particularly its anti-inflammatory and antioxidant properties. In recent decades, scientific research has increasingly focused on understanding the mechanisms underlying ginger’s therapeutic effects, especially its role in managing inflammatory conditions.[2]

Ginger has been used in various traditional medicine systems, including Ayurveda, Traditional Chinese Medicine (TCM), and Unani, for centuries. Traditionally, it has been used in the management of several diseases, such as digestive disorders like nausea and pain.[3] The use of ginger as an anti-inflammatory drug is quite remarkable since traditional healers have been using ginger for the treatment of arthritis and other respiratory ailments and other inflammatory diseases.[4]

The therapeutic effects of ginger are largely attributed to its rich content of bioactive compounds, which include gingerols, shogaols, and zingerone. Of these, 6-gingerol is the most predominant and is thus referred to as the major bioactive compound.[5]

Inhibition of Cyclooxygenase and Lipoxygenase Pathways:
Gingerols and shogaols inhibit key enzymes involved in the inflammatory process, such as cyclooxygenase-2 (COX-2) and lipoxygenase (LOX). COX-2 is an enzyme responsible for the formation of pro-inflammatory prostaglandins, while LOX contributes to the production of leukotrienes, which are another group of inflammatory mediators. By inhibiting these enzymes, ginger reduces the synthesis of these pro-inflammatory compounds, thereby mitigating inflammation.[6]

Modulation of Nuclear Factor-kappa B (NF-κB) Pathway:
The NF-κB pathway is significant in modulating the inflammatory cascade through its action on the genes encoding cytokines, chemokines, and adhesion molecules associated with the immune response. It has been established that ginger extracts, especially the 6-gingerol, can prevent NF-κB activation, which has inflammatory cytokines, for instance, TNF-α, IL-1β, and IL6. This inhibition of the NF-κB signalling pathway is one of the most widely explained ways through which ginger exhibits anti-inflammatory properties.[7]

Antioxidant Activity:
Ginger possesses potent antioxidant properties, which further contribute to its therapeutic effects. Oxidative stress which is characterized by the excessive production of reactive oxygen species (ROS) is a key driver of inflammation and is involved in the pathogenesis of various chronic inflammatory diseases.[8] Ginger’s bioactive compounds scavenge free radicals and upregulate the body’s endogenous antioxidant defenses, thereby reducing oxidative stress and its associated inflammatory damage.[9]

Clinical Applications:
Several clinical and preclinical investigations have been conducted to examine the effects of ginger in the treatment and prevention of different forms of inflammation. Ginger has been observed to have the potential to reduce the symptoms of osteoarthritis through the inflammation and degeneration of joints. Randomised controlled trials have shown a significant reduction of pain and stiffness among patients with osteoarthritis of the knee after supplementation with ground ginger, proving its promising prospect for being a natural replacement for NSAIDs.

Safety and Tolerability:
Ginger is known to be harmless when consumed in moderate portions by most people. In the clinical trials, few side effects have been described, mostly nausea and vomiting, mainly gastrointestinal manifestations. However, taking large amounts of ginger or ginger supplements can bring some side effects, such as stomach irritation, heartburn, or an allergic response. Hence, it is important to take ginger in controlled portions and in consultation with physicians, particularly in cases where the patient has an underlying illness or is taking other medicines.[10]

Methodology

Data Sources and Search Strategy:
A comprehensive literature review was conducted on the anti-inflammatory effects of Zingiber officinale (ginger) using the PubMed database by covering studies from 2000 to 2024. The search employed specific keywords and MeSH terms. The review included articles published in English that encompassed both preclinical and clinical studies.

Inclusion Criteria:
The review included studies that investigated the anti-inflammatory effects of ginger in human subjects or animal models. Eligible studies involved the administration of ginger or its bioactive components either alone or in combination therapy and compared these effects to placebo, no treatment, or standard anti-inflammatory treatments like NSAIDs. Outcomes of interest included measurable markers of inflammation (e.g., TNF-α, IL-6), clinical symptoms (e.g., pain, swelling), and molecular pathways (e.g., COX-2, NF-κB). The review encompassed various study designs, including randomized controlled trials, cohort studies, case-control studies, cross-sectional studies, and preclinical studies.[11]

Exclusion Criteria:
Studies were excluded if they did not specifically focus on ginger’s effects on inflammation or lacked clear, measurable inflammation-related outcomes. Review articles and meta-analyses were excluded from the primary analysis to prevent data duplication, though they were used for background information. Non-English studies and those published before 2000 were excluded to avoid translation errors and ensure relevance.[12]

Data Extraction:
Data extraction was performed independently by two reviewers to reduce bias and focus on study characteristics, intervention details, and outcomes. Key findings, which include the statistical significance of ginger’s anti-inflammatory effects, were recorded. The quality of each study was assessed using tools like the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale for observational studies.[13]

Data Synthesis:
The extracted data were synthesized using a narrative approach with a focus on identifying patterns and trends in the anti-inflammatory effects of ginger. The results were categorized based on the type of inflammatory condition studied, the specific bioactive compounds of ginger investigated, and the molecular pathways targeted.[14] Where possible, the quantitative data from RCTs were summarized using meta-analytic techniques to provide an overall estimate of the effect size.[15]

Results

Effects of Ginger Supplementation in Type 2 Diabetes:
Mahluji et al. (2013) investigated the anti-inflammatory effects of ginger (Zingiber officinale) supplementation on pro-inflammatory markers in type 2 diabetes (DM2) patients.[16]

The randomized, double-blind, placebo-controlled trial involved 64 DM2 patients, divided into ginger and placebo groups. Over two months, the ginger group received two tablets of ginger daily, and blood samples were taken to measure levels of pro-inflammatory cytokines (TNF-α and IL-6) and the acute-phase protein hs-CRP.

Ginger significantly reduced TNF-α (P = 0.006), IL-6 (P = 0.02), and hs-CRP (P = 0.012) levels in the ginger group compared to baseline.

A significant reduction in TNF-α (15.3 ± 4.6 vs. 19.6 ± 5.2; P = 0.005) and hs-CRP (2.42 ± 1.7 vs. 2.56 ± 2.18; P = 0.016) was observed in the ginger group compared to the placebo group after adjusting for covariates.

However, changes in IL-6 levels were not statistically significant between groups (7.9 ± 2.1 vs. 7.8 ± 2.9; P > 0.05).

Effects of Ginger Root Extract and Diclofenac on Acute Inflammation:
Boarescu et al. (2024) the authors examined the synergistic effects of ginger root capsule extract (GRCE) in combination with diclofenac sodium (D) on acute inflammation in an animal model.[17]

The study aimed to evaluate how GRCE at doses of 100 mg/kg and 200 mg/kg body weight (b.w.) alone, or in combination with a low dose (5 mg/kg b.w.) of diclofenac, impacted carrageenan-induced acute inflammation (AI). The results revealed that:

The combination of GRCE (200 mg/kg b.w.) with diclofenac sodium resulted in the highest inhibition of inflammation, reducing edema by up to 95% after 24 hours.

GRCE alone did not exhibit significant anti-inflammatory effects, but in combination with diclofenac, it greatly enhanced the reduction of tissue inflammatory changes.

Both doses of GRCE combined with diclofenac significantly lowered plasma and tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) by up to 55% (p ≤ 0.0317).

The combination also reduced serum and tissue levels of COX-2 by up to 71% (p ≤ 0.0371), showing a marked reduction in the molecular markers of inflammation.

Effects of Aqueous Ginger Extract on Cholesterol, Triglycerides, and Inflammatory Markers in Rat:
In the study by Thomson et al. (2002), the effects of aqueous ginger extract (Zingiber officinale) on serum cholesterol, triglycerides, and the production of thromboxane-B₂ (TXB₂) and prostaglandin-E₂ (PGE₂) were investigated in rats.[18]

Ginger at a high dose (500 mg/kg) significantly reduced serum PGE₂ and TXB₂ levels when administered orally. However, intraperitoneal (IP) administration only significantly lowered PGE₂, not TXB₂.

A low dose (50 mg/kg) of ginger did not significantly affect TXB₂ levels but did cause notable changes in PGE₂ when administered orally.

High-dose ginger (500 mg/kg) led to a significant reduction in serum cholesterol, while at a low dose, significant cholesterol reduction was only observed with IP administration.

Triglyceride levels remained unaffected by both low and high doses of ginger.

Authors Year Study design Population Intervention Statistical significance
Sepide Mahluji et al. 2013 Randomized, double-blind, placebo-controlled trial 64 type 2 diabetes patients Ginger group: 2 tablets daily; Placebo group TNF-α, IL-6, hs-CRP: Significant
Ioana Boarescu et al.                            2024 Preclinical study Rats GRCE (100 mg/kg and 200 mg/kg) alone or with diclofenac (5 mg/kg) Cytokines, COX-2: Significant
Thomson et al., 2002 Experimental study Rats Aqueous ginger extract at low (50 mg/kg) and high (500 mg/kg) doses PGE₂, TXB₂: Significant (high dose)

Table 1: Summary of Studies on the Anti-Inflammatory Effects and Clinical Applications of Ginger

Discussion

The study by Mahluji et al. (2013) provides compelling evidence of the anti-inflammatory effects of ginger (Zingiber officinale) supplementation in patients with type 2 diabetes (DM2).[19] This randomized, double-blind, placebo-controlled trial involved 64 DM2 patients who were assigned to either a ginger or placebo group. Over two months, the ginger group received a daily dose of two tablets of ginger, and various pro-inflammatory markers were assessed, including TNF-α, IL-6, and hs-CRP.[20]

The results indicated that ginger supplementation led to significant reductions in TNF-α (P = 0.006), IL-6 (P = 0.02), and hs-CRP (P = 0.012) levels compared to baseline measures. Specifically, there was a notable reduction in TNF-α from 19.6 ± 5.2 to 15.3 ± 4.6 (P = 0.005) and hs-CRP from 2.56 ± 2.18 to 2.42 ± 1.7 (P = 0.016) in the ginger group compared to the placebo group. These findings underscore the potential of ginger as an adjunctive therapy for managing inflammation in DM2 patients, where chronic inflammation is a significant factor.

Despite these promising results, the study found no significant difference in IL-6 levels between the ginger and placebo groups (P > 0.05). This discrepancy highlights a nuanced aspect of ginger’s anti-inflammatory effects, suggesting that while it may modulate certain inflammatory markers, its impact on IL-6 might be less pronounced or require different dosing or duration to achieve significance.[21]

Complementing these findings, Boarescu et al. (2024) explored the synergistic effects of ginger root capsule extract (GRCE) combined with diclofenac sodium in an animal model of acute inflammation.[22] Their study demonstrated that the combination of GRCE (200 mg/kg body weight) and a low dose of diclofenac (5 mg/kg body weight) led to a significant reduction in edema by up to 95% after 24 hours. Furthermore, this combination therapy significantly lowered plasma and tissue levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and COX-2, highlighting the enhanced anti-inflammatory potential of GRCE when used alongside conventional anti-inflammatory medications.

Thomson et al. (2002) investigated the effects of aqueous ginger extract on lipid profiles and inflammatory markers in rats.[23] Their findings showed that high doses of ginger (500 mg/kg) significantly reduced serum levels of PGE₂ and TXB₂, both of which are involved in inflammation and thrombosis. This reduction in inflammatory markers was observed primarily with oral administration, while intraperitoneal administration had different effects on TXB₂ and PGE₂ levels. These results support the notion that ginger can modulate inflammatory pathways, though the route and dosage of administration play critical roles in its effectiveness.

Mahluji et al. (2013) and other studies demonstrate ginger’s potential to reduce inflammation in various contexts, but the variability in findings across different studies and conditions underscores the need for more robust research.[24] Continued investigation into optimal dosages, administration routes, and combinations with other therapies will be crucial in fully elucidating ginger’s therapeutic potential and enhancing its clinical applications.

Limitations and Future Directions for Research on Zingiber officinale
Limitations:
Variability in Study Designs and Methodologies: Most research done on ginger includes variation in their approach, such as: dose, form of ginger used (fresh, purified ginger, pills, etc), and the period of treatment. This can tend to increase the variability and make it difficult to come up with comparison results as presented by different researchers.

Sample Size and Generalizability: It has been established that many clinical trials have limited sample sizes, and this influences the statistics and applicability of the research findings. Small sample sizes lead to type I and type II errors, and the results are not generalizable to the whole population.[25]

Methodological Limitations: Common drawbacks that are typical for the presented studies are the following: poor blinding, insufficient randomisation, and short follow-up. These limitations can also influence the results and bring some bias into the process.[26]

Inconsistent Outcome Measures: Several investigations employ dissimilar success criteria of ginger’s help in fighting inflammation in human beings, including biomarkers and clinical end points, such as TNF-α, IL-6, and hs-CRP. This inconsistency makes the aggregation of results and the establishment of conclusions more challenging.

Lack of Standardization: Heterogeneous preparation and concentration of ginger employed in the scientific investigations have varied effects, hence the differences in efficacy. Due to differences in preparing ginger and extracting its active components, the bioavailability may differ and consequently influence the results and their implications.[27]

Future Directions
Mechanistic Studies: The published data on the interaction of ginger with inflammatory and antioxidant signaling pathways are extensive, but the molecular targets have not been clearly elucidated. To direct future studies, researchers should pay more attention to determining the specific signaling cascades through which bioactive compounds of ginger, including [6]-gingerol and [6]-shogaol, exert their effects. A further insight into the modulation of its action with pro-inflammatory cytokines such as TNF-α, IL-6, as well as antioxidant response elements including Nrf2, on certain chronic diseases, including RA, cardiovascular diseases, and neurodegenerative disorders.[28]

Clinical Trials: Despite the numerous positive findings in various small-scale clinical trials, further large-scale trials in multiple centres, RCTs in conditions such as nausea (especially in chemotherapy-induced nausea), IBS, osteoarthritis, and metabolic syndromes are still needed. It would be important that the dosages, routes, and forms (fresh, dried, extracts, etc.) that are used in these trials be standardized to implement the findings from the laboratory in clinical practice.[29]

Pharmacokinetics and Bioavailability: Another disadvantage of ginger in the treatment of various diseases is the low solubility of its active components. Subsequent studies should explore ways of improving the bioavailability and disposition of the gingerols and the shogaols.[30] Diverse drug delivery systems based on nanotechnology, such as nanoemulsions and liposomes, can enhance the pharmacokinetic properties, bioavailability, and therapeutic effect of ginger extracts.

Ginger and Gut Microbiota: There is emerging evidence on the effects of ginger use on gut health, which has elicited interest. Further research could explore how ginger influences the composition of the gut microbiome and whether the herb could be beneficial as an adjunct therapy for disorders associated with gut imbalances, including IBD and obesity.

Cancer Research: Few experimental investigations have been conducted that have shown that ginger possesses anticancer properties via the following ways: apoptosis, angiogenesis, and metastasis. Further research is required to determine the efficacy of ginger in cancer prevention and treatment by examining specific types of cancer, the interaction of ginger with standard 5-FU and other anti-cancerous drugs, and ginger’s effect on cancer stem cells.

Conclusion

In conclusion, the studies provide strong evidence supporting the anti-inflammatory effects of Zingiber officinale. It showed that ginger supplementation has the potential for the management of chronic low-grade inflammation in patients with T2DM by decreasing TNF-α, IL-6, and hs-CRP concentrations, the critical markers of inflammation. This supports the findings of other studies suggesting that ginger’s active components, such as 6-gingerol and 6-shogaols, suppress inflammatory signaling by down-regulating enzymes and decreasing the secretion of inflammatory agents like COX-2 and LOX.

These findings are further supported by Boarescu, who conducted a comparative study that established that ginger root capsule extract (GRCE) when used in conjunction with diclofenac sodium has a better anti-inflammatory response in an animal model. These changes demonstrated that this combination therapy had a marked reduction in edema and other pro-inflammatory cytokines, highlighting the possible synergistic role of ginger in the application of conventional anti-inflammatory agents. On the other hand, Thomson et al. (2002) reported that high doses of ginger reduced levels of inflammatory mediators such as PGE₂ and TXB₂ in rat models, which underscores the importance of the dose and route of administration when considering ginger’s effectiveness.

On average, prior literature emphasizes ginger as an anti-inflammatory agent; however, inconsistencies in findings and methodological realities suggest the need for improvement in the studies. Subsequent research should be directed toward the optimal dosing, the route of administration, and investigating multifaceted therapeutic processes. Over time, ginger can emerge as a useful supplement for treating multiple inflammation-related disease states if there is sufficient and reliable data to back up its use and effectiveness.

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Acknowledgments

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Author Information

Corresponding Author:
Sonam Shashikala B V
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India
Email: venkateshsonams@gmail.com

Co-Authors:
Samatha Ampeti
Department of Pharmacology
Kakatiya University, University College of Pharmaceutical Sciences, Warangal, TS, India
Email: ampetisamatha9@gmail.com

Mansi Srivastava
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India
Email: srivastavamansi811@gmail.com

Shubham Ravindra Sali
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India
Email: shubhamsali42@gmail.com

Raziya Begum Sheikh
Independent Researcher, Department of Content
medtigo India Pvt Ltd, Pune, India
Email: raziya.pharma@gmail.com

Authors Contributions

The author contributed to the conceptualization, investigation, and data curation by acquiring and critically reviewing the selected articles and was involved in the writing – original Draft preparation and writing –  review & editing to refine the manuscript.

Not applicable

Conflict of Interest Statement

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Guarantor

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DOI

https://doi.org/10.63096/medtigo3061113

Cite this Article

Sonam SBV, Samatha A, Mansi S, Shubham RS, Raziya BS. Anti-Inflammatory Effects of Zingiber officinale: A Comprehensive Review of Its Bioactive Compounds and Therapeutic Potential. medtigo J Pharmacol. 2024;1(1):e3061113. doi:10.63096/medtigo3061113 Crossref

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