INTRODUCTION
Antimicrobial activity is the process of killing or preventing the growth of the microbes that cause infectious diseases (Wang et al., 2017). Nowadays, there are various antimicrobial agents available to treat these diseases. These antimicrobial agents are divided into groups based on the mechanisms of the antimicrobial activity such as agents that prevent cell wall synthesis, those that depolarize the cell membrane, and those that inhibit protein and nucleic acid synthesis as well as metabolic pathways in bacteria (Reygaert, 2018). There are many available synthetic drugs that are used to treat infectious diseases but also have many side effects on the consumer. For example, chloramphenicol, an antimicrobial agent, is used to treat meningitis. This drug works by passing through the blood-brain barrier and is able to cause aplastic anemia (Mohsen et al., 2020). Besides, treatment with ribavirin has been shown to reduce the ribonucleic acid of the virus but is able to cause hemolytic anemia in the patient (McFee, 2020).
This medicinal plant has been used by humans for a long time to treat many ailments as well as other essential roles. Also, medicinal plants have been important medicines in all cultures and are a source of many traditional medicines that also contribute to modern medicines (Dar et al., 2017). In pursuit of new drug candidates, plant extracts and natural molecules from plants are being extensively analyzed (Harun et al., 2018, 2019, 2021). Plants have been used for more than 5,000 years as agents of vaccines, antimicrobials, analgesics, cardioprotective agents, and other medicines. Human beings have used natural substances in ancient history to combat pathogens. Currently, almost 70% to 90% peoples in developing countries applied herbs to treat various diseases. The strongest and most promising components of plants are secondary metabolites. More than half of the drugs authorized by the Food and Drug Administration use natural products and their derivatives (Anand et al., 2019). As an alternative for safer treatment and low risk of side effects, Zingiber officinale or ginger is famous in the community and is traditionally used to treat many diseases including infectious diseases and fever and also was used to boost immunity.
Zingiber officinale, a member of the family Zingiberaceae and a species of the genus Zingiber, has been well known as a medicinal herbal and spice product for a long time. This herb is abundantly cultivated for commercial purposes in India, Indochina, West Indies, Mexico, Southeast Asia, and other countries as well (Banerjee et al., 2011). Ginger has been traditionally used to reduce the symptoms of headaches, colds, nausea, pain, and emesis (Mao et al., 2019; Mohamad et al., 2019). In India, the preparation of fresh ginger juice mixed with fresh garlic juice and honey is a common practice for cough and asthma (Awang, 1992). In Southeast Asian countries such as Malaysia and Indonesia, women consume ginger soup after birth to make them hot and sweat (Mohammad and Hamed, 2012). Also, Z. officinale is a common component of traditional Chinese treatments for respiratory infections (Chang et al., 2013) and also remedies for atonic dyspepsia and colic (Keys, 1985). Based on a study by Safa et al. (2020), Z. officinale-based tablets increased the recovery rate of clinical symptoms as well as the improvement of clinical and preclinical features in patients admitted with severe acute respiratory syndrome due to COVID-19 infection. Zingiber officinale and its bioactive compounds showed a variety of biological activities including antimicrobial (Aaisha et al., 2020; Elmowalid et al., 2019), antioxidant, antiarthritic (Murugesan et al., 2020), antitumor (Liao et al., 2020), anti-inflammatory, antithrombotic (Thomson et al., 2002), and hypoglycemic (Ojewole, 2006) effects. Zingiber officinale also contains many natural organic materials such as 6-gingerol, 6-shogoal, and 6-paradol that promote its biological activities.
There are numerous previous studies related to the structure–activity relationship of bioactive compounds who isolated from Z. officinale and their effects on biological activity. The study by Yamauchi et al. (2019) who isolated 13 bioactive compounds from the methanol extract of the Z. officinale rhizomes and further assessed their effects on the extracellular melanogenesis inhibitory activity. The findings showed that gingerols promoted the highest inhibitory activity of extracellular melanogenesis as compared to other vanilloid compounds. They suggest that elongation of the carbon chain as well as the carbonyl and hydroxyl groups on the carbon chain played an important role in this effect. Another study by Masuda et al. (2004) who investigated the antioxidant properties of the gingerol-related compounds and diarylheptanoid isolated from the rhizomes of ginger. The results suggested that the alkyl chain substitution of dehydrogingerdiones is able to contribute to the radical scavenging effects of autoxidation of oils as compared with gingerol-related compounds.
The pharmacological validation of the antimicrobial effect of Z. officinale is quite restricted, and several existing review publications on this plant have not been focused on this activity. Therefore, this study aimed to conduct a systematic assessment of all available data (years 2000–2020) to determine the effects of Z. officinale on antimicrobial activities. Therefore, it is crucial to prove the community’s belief in traditionally consuming this herb as a treatment for infectious diseases by conducting a systematic review and meta-analysis on Z. officinale’s antimicrobial activities.
METHODOLOGY
This systematic review was carried out in accordance with the principles of the Cochrane Collaboration framework and was described following the guideline by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses declaration.
Search strategies and study selection
From 2000 until 2020, an electronic search for original articles was done using two selected electronic databases which were PubMed and Science Direct. The selection of these two databases was based on the ability to get full access to the related articles from our institution. The strategic search terms were Z. officinale or ginger plus antimicrobial activities or effect of Z. officinale or ginger on antimicrobial activities. The papers that were included in the study are research that involved the use of the extract or bioactive compound of Z. officinale which contained the antimicrobial outcomes (in vivo, in vitro, or clinical studies). The papers that did not include the above criteria were excluded (Moher et al., 2009). The study selection was performed by following the steps in Figure 1.
Data extraction and quality assessment
The data were extracted using standard data extraction from the two selected databases (PubMed and Science Direct) from 2000 to 2020. The extracted data included the tested substances, antimicrobial properties, method used to test the antimicrobial properties, tested microorganism, model used, tested dose, results (using tested substances), and comparison with positive controls.
The quality of the included studies was assessed using the Cochrane risk of bias tool. Sequence generation, allocation concealment, incomplete outcome data, selective reporting, other sources of bias, and overall risk of bias were evaluated. The risk of bias assessment using the Cochrane risk of bias assessment is displayed in Table 1.
Statistical analysis
The analysis of the antimicrobial effects of Z. officinale was conducted by comparing the data for the individual function test (treated with Z. officinale) with its comparator (positive control) [standardized mean difference (SMD) with a confidence interval (CI) at 95%]. Meanwhile, the I2-statistic was used to assess the heterogeneity value. The direction of effects, amount, and power of heterogeneity evidence affect the value of the threshold of I2. Substantial heterogeneity means an I2 value of more than 50%. All the statistical analyses were done using the RevMan software (edition 5.4).
RESULTS
The database search resulted in the discovery of 363 articles. Because there was no duplication, none of the articles were removed. There were 96 titles, abstracts, and keywords evaluated in all. Nineteen of the full-text research articles were reviewed from the screened titles, abstracts, and keywords, and all the papers were included in the systematic review. The flow of study selection for the antimicrobial activities is presented in Figure 2. After analyzing the 19 included studies, 10 studies (52.63%) had sufficient data for the comparison between Z. officinale and positive control while 9 other studies (47.37%) did not have sufficient data for this. All the information on the antimicrobial activities of this plant (model and method used, tested substances, tested microorganisms, results, tested dose, and comparison with control) is summarized in Table 2.
Figure 1. The flow chart of study selection (Moher et al., 2009 ). “n” is the number of papers. [Click here to view] |
The quality assessment of the data is presented in Table 3. Fifteen studies (78.94%) showed a low possibility of bias. Four studies (21.05%) were indistinguishable. Despite the fact that all studies claimed that they were randomized controlled trials, two studies showed an unclear risk of bias for “sequence generation” due to a lack of description of the sequence generation methods. Two other studies showed an indistinguishable possibility of bias for “allocation concealment” because the explanation for the “allocation concealment” method was not present.
The antimicrobial-related outcome was categorized into overall outcomes, inhibition zone, and minimum inhibition concentration (MIC) for the meta-analysis. Qualitative analysis of heterogeneity for the “overall outcome” findings is shown in Figure 3. An analysis specifically done on the qualitative visual method of the findings suggests variability present between the studies. The individual study point evaluations of the effect of treatment (green squares) are on the same line of the upright axis, representing similar treatment amount effects between studies. The prediction of the effect on the study treatment of the population showed the difference value as presented at the horizontal lines in the figure, and the result suggests the presence of heterogeneity. The I2-value that presented the quantitative tests of heterogeneity was 100% and suggests there was study variability (i.e., heterogeneity).
Table 1. The Cochrane risk of bias assessment. [Click here to view] |
Qualitative analysis of heterogeneity for the “inhibition zone” findings is shown in Figure 4. Observational analysis of the results suggests there is between-study variability. The individual study point evaluations of the effect of treatment (green squares) are on both sides. However, they are not located on the upright axis, representing a modification in treatment amount effect between studies. Meanwhile, the prediction of the effects of the study treatment of the population showed the difference value as presented at the horizontal lines in the figure, and the result suggests the presence of heterogeneity. The I2 value was 99% and suggests that there was study variability (i.e., heterogeneity).
Furthermore, an observational analysis of the MIC result suggests medium between-study-group variability, as shown in Figure 5. Based on the figure, the location of the green squares showed similar approximation of the amount of the treatment effects for the groups. However, there was a similar prediction for the effect of population treatment groups, as illustrated by the CIs for the groups overlapping each other in the figure, suggesting there is medium heterogeneity. The I2-value was 34%. This quantitative result suggests medium between-study variability (i.e., heterogeneity).
Figure 2. Detailed flow diagram of study selection for antimicrobial activities (Moher et al., 2009 ). [Click here to view] |
Based on the data of the included studies, 19 studies described the antimicrobial activities of Z. officinale, but only 4 had satisfactory data for further proceeding with meta-analysis. The four studies were considered in a specific area for the purpose of determining the antimicrobial effects of Z. officinale. The domains included: 1) overall effect outcomes, 2) inhibition zone, and 3) MIC. For the overall outcome and inhibition zone, the I2-values were 100% and 99%, respectively. The results presented high heterogeneity between the parameters included in this study. For the MIC, the I2 value was 34%, which means there was medium heterogeneity. There was a significant difference between Z. officinale and positive controls on the MIC [SMD: 0.0201 (CI; 0.0166–0.0235), I2 = 34%], while there was no significant difference between Z. officinale and positive controls for the overall outcome and inhibition zone [overall outcome SMD: −0.6003 (95% CI; −0.7092 to −0.4913), I2 = 100%: inhibition zone SMD: 0.8771 (CI; −8.1288 to 9.8829), I2 = 99%]. All the results are presented in Table 4.
DISCUSSION
The results of preliminary research employing the disc diffusion approach reported that the methanol extract of Z. officinale exhibited antibacterial potentials against pathogenic bacteria such as Escherichia coli, Pseudomonas aeruginosa, Pasteurella multocida, Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, and Proteus mirabilis. In this study, the methanol extract of Z. officinale showed antibacterial activities with an inhibition zone of 10–15 mm (Chakraborty et al., 2014). In addition, the similar extract of Z. officinale presented a broad range of inhibition towards P. aeruginosa, Streptococcus mutans, and Streptococcus sobrinus. The researcher used the agar well diffusion and agar diffusion methods to figure out these antibacterial activities, and the outcome exhibited that the methanol extract at doses of 0.2 and 2 mg/ml suppressed most major inhibitory capabilities against those microorganisms (Babaeekhou and Ghane, 2020; Chakotiya et al., 2017). The ethanol extract of Z. officinale was able to inhibit the growth of many microorganisms including E. coli, P. multocida, B. subtilis, and S. aureus on the basis of the disc diffusion method. The inhibition zone by the ethanol extract ranged from 10.6 to 15.7 mm (Abdul Qadir et al., 2017; Chakraborty et al., 2014). The ethanol extract also presented significant antibacterial properties by inhibiting the growth of the enterococcal species, Enterobacter species, Proteus species, and Klebsiella species on the basis of the agar well diffusion method and serial tube dilution technique. The ethanol extract (0.025–100 mg/ml) was able to inhibit microorganism growth with inhibition zones ranging from 4 to 20 mm (Karuppiah and Rajaram, 2012; Revati et al., 2015). In addition, the acetone extract also showed promising outcomes in inhibiting the growth of some microorganisms such as E. coli, P. multocida, S. aureus, K. pneumoniae, B. subtilis, P. aeruginosa, and P. mirabilis (Abdul Qadir et al., 2017; Chakraborty et al., 2014).
Table 2. Antimicrobial activities of crude extracts, bioactive fraction, and compounds derived from Z. officinale. [Click here to view] |
Table 3. The quality assessment of the data included in the study. [Click here to view] |
Figure 3. Qualitative and quantitative analysis of heterogeneity for “overall outcome” findings (CI: confidence interval). [Click here to view] |
Figure 4. Qualitative and quantitative analysis of heterogeneity for “inhibition zone” findings (CI: confidence interval). [Click here to view] |
Figure 5. Qualitative and quantitative analysis of heterogeneity for “mean inhibitory concentration” findings (CI: confidence interval). [Click here to view] |
The Z. officinale root essential oils exhibited effective inhibitors for pathogens (Silva et al., 2018). Ginger essential oil (GEO) was effective against Gram-positive and Gram-negative bacteria. Essential oil at concentrations of 0.01 and 50 mg/ml inhibited the growth of both Gram-positive and Gram-negative bacteria with inhibition zones ranging from 6 to 22.33 mm (Imane et al., 2020; Snuossi et al., 2016). On the basis of the agar diffusion method, GEO (300 mg/ml) inhibited the growth of S. aureus, Listeria monocytogenes, Salmonella typhimurium, and P. aeruginosa. In addition, GEO also revealed antifungal activity by inhibiting Penicillium citrinum, E. coli, and Penicillium chrysogenum through broth dilution antifungal susceptibility testing (Sharifzadeh et al., 2016). Susceptibility testing of GEO against Mycobacterium tuberculosis and nontuberculous mycobacteria presented significant results at the concentration of 0.25 mg/ml with an MIC value of 0.25 mg/ml (Baldin et al., 2019).
A finding by Chang et al. (2013) showed that the hot water extract of ginger was able to reduce the infection rate of the human respiratory syncytial virus (HRSV) by 50% at a dose of 0.3 mg/ml. Ginger nanofiber (GNF) is a product from the remains after ginger oil and oleoresins are extracted from the ginger. The research conducted by Jacob et al. (2019) stated that the bacterial susceptibility of GNF by the agar diffusion assay was 0.013 mg/ml against Bacillus cereus, 0.012 mg/ml against E. coli, 0.018 mg/ml against S. aureus, and 0.031 mg/ml against S. typhimurium. The phenolic extract also showed a significant antibacterial property against S. aureus, K. pneumoniae, P. mirabilis, E. coli, and Helicobacter pylori on the basis of the agar well diffusion, agar diffusion, and conventional broth dilution methods. The dose of 0.05 mg/ml on the agar well produced inhibition zones ranging from 16 to 25 mm with MICs ranging from 1.59 to 2.2 mg/ml while the dose of 0.01 mg/ml in the conventional broth dilution and agar produced a 20 mm inhibition zone and an MIC value of 0.049 mg/ml (Saleh et al., 2018; Siddaraju and Dharmesh, 2007).
Table 4. The meta-analysis of the effect of Z. officinale on antimicrobial activities. [Click here to view] |
The crude extract of ginger inhibits the growth of S. mutans at a dosage of 2 mg/ml with an inhibition zone of 7.65 mm. Meanwhile, the aqueous extract of ginger inhibits S. mutans at a similar concentration with an inhibition zone of 14.02 mm, which is higher than the crude extract. The finding showed that the aqueous extract of ginger is more effective than the crude extract in inhibiting the growth of S. mutans (Jain et al., 2015). The ginger compounds ([6]-dehydrogingerdione, [6]-shogaol, [10]-gingerol, and [6]-gingerol) derived from ginger display good antibacterial properties against extensively drug-resistant Acinetobacter baumannii when using the broth microdilution method (MIC value: 0.132–0.347 mg/ml) (Wang et al., 2010). A further experiment was done on the basis of the alamarBlue assay to test gingerol against the M. tuberculosis drug-sensitive and drug-resistant clinical strains. Gingerol at a dose of 0.025 mg/ml inhibits the growth of the drug-sensitive and drug-resistant clinical strains of M. tuberculosis with MIC values ranging from 0.0015 to 0.05 mg/ml (Bhaskar et al., 2020).
The concentrations of Z. officinale in previous papers included in this study were different with a range of 0.01 to 300 mg/ml. Variation in Z. officinale extract concentrations was also observed, which included four studies that used the methanol extract ranging from 0.03 to 100 mg/ml, six studies that used the ethanol extract ranging from 0.03 to 300 mg/ml, five studies that used the essential oil ranging from 0.01 to 300 mg/ml, and two studies that used acetone ranging from 0.03 to 100 mg/ml and two studies that used the crude extract ranging from 2 to 5 mg/ml. Additionally, the concentration of Z. officinale in some of the included studies was unclear. Hence, there is insufficient evidence to support the antimicrobial activity of Z. officinale. The SMD is used to measure the antimicrobial activities of Z. officinale across the included studies. SMD converts data from different scales to a common scale which causes the original information for each measurement of the included studies to be missing. However, the value of SMD is able to provide a significant level of the effect of Z. officinale when compared to the positive controls (Higgins and Green, 2011). The result of the meta-analysis for the mean inhibitory concentration displays that the effects of the positive controls in the previous research selected in this study were more effective than the effects of the Z. officinale extract [SMD: 0.0201 (CI; 0.0166–0.0235), I2 = 34%]. However, the previous reports showed that Z. officinale were more effective than its selective positive control. These findings included in the study that used GNF showed an MIC value higher than that of ampicillin which were 0.031 and 0.012 mg/ml, respectively (Jacob et al., 2019). Secondly, the study that used the methanol, n-hexane, and ethyl acetate extracts of ginger at a dose of 2 mg/ml presented higher inhibition zones than that of penicillin (40 mg/ml) (Babaeekhou and Ghane, 2020). The other related study was conducted by Baldin et al. (2019) who demonstrated that GEO (0.25 mg/ml) has a higher MIC value than isoniazid and ciprofloxacin. The results might be because of insufficient relevant data from these studies to be included in the meta-analysis.
CONCLUSION
In a nutshell, the overall findings revealed that the Z. officinale extracts and bioactive compounds have antimicrobial activities similar to the positive controls for antimicrobial analysis related to the overall outcome and inhibition zone [overall outcome SMD: −0.6003 (95% CI; −0.7092 to −0.4913), I2 = 100%, inhibition zone SMD: 0.8771 (CI; −8.1288 to 9.8829), I2 = 99%]. However, the verification of the Z. officinale as an antimicrobial agent still needs further study with more available data from several other databases.
LIST OF ABBREVIATIONS
B. subtilis: Bacillus subtilis; CI: Confidence interval; GEO: Ginger essential oil; GNF: Ginger nanofiber; E. coli: Escherichia coli; K. pneumonia: Klebsiella pneumoniae; L. monocytogenes: Listeria monocytogenes; MIC: Minimum inhibition concentration; M. tuberculosis: Mycobacterium tuberculosis; P. aeruginosa: Pseudomonas aeruginosa; P. multocida: Pasteurella multocida; P. mirabilis: Proteus mirabilis; S. aureus: Staphylococcus aureus; SMD: Standardized mean difference; S. typhimurium: Salmonella typhimurium; Z. officinale: Zingiber officinale
CONFLICTS OF INTEREST
The authors declared no conflicts of interest.
FUNDING
There is no funding to report.
AUTHOR CONTRIBUTIONS
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work. All the authors are eligible to be an author as per the international committee of medical journal editors (ICMJE) requirements/guidelines.
ETHICAL APPROVALS
This study does not involve experiments on animals or human subjects.
DATA AVAILABILITY
All data generated and analyzed are included within this research article.
PUBLISHER’S NOTE
This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.
REFERENCES
Aaisha SA, Fatema AA, Khaloud MA, Hany MY, Wafa MA, Syed NHA, Shah AK. Essential oil from the rhizomes of the Saudi and Chinese Zingiber officinale cultivars: comparison of chemical composition, antibacterial and molecular docking studies. J King Saud Univ, 2020; 32(8):3343–50. CrossRef
Abdul Qadir M, Shahzadi SK, Bashir A, Munir A, Shahzad S. Evaluation of phenolic compounds and antioxidant and antimicrobial activities of some common herbs. Int J Anal Chem, 2017; 2017:3475738. CrossRef
Anand U, Jacobo-Herrera N, Altemimi A, Lakhssassi N. A comprehensive review on medicinal plants as antimicrobial therapeutics: potential avenues of biocompatible drug discovery. Metabolites, 2019; 9(11):258. CrossRef
Awang DVC. Ginger. Can Pharm J, 1992; 7:309–11.
Babaeekhou L, Ghane M. Antimicrobial activity of ginger on cariogenic bacteria: molecular networking and molecular docking analyses. J Biomol Struct Dyn, 2020; 39:2164–75. CrossRef
Baldin VP, Scodro BLR, Fernandez CM, Ieque AL, Caleffi-Ferracioli KR, Dias Siqueira VL, de Almeida AL, Gonçalves JE, Garcia Cortez DA, Cardoso RF. Ginger essential oil and fractions against Mycobacterium spp. J Ethnopharmacol, 2019; 244:112095. CrossRef
Banerjee S, Mullick HI, Banerjee J. Zingiber officinale: a natural gold. Int J Pharm Bio Sci, 2011; 2(1):283–94.
Bhaskar A, Kumari A, Singh M, Kumar S, Kumar S, Dabla A, Chaturvedi S, Yadav V, Chattopadhyay D, Prakash DV. [6]-Gingerol exhibits potent anti-mycobacterial and immunomodulatory activity against tuberculosis. Int Immunopharmacol, 2020; 87(6):106809. CrossRef
Chakotiya AS, Tanwar A, Narula A, Sharma RK. Zingiber officinale: its antibacterial activity on Pseudomonas aeruginosa and mode of action evaluated by flow cytometry. Microb Pathog, 2017; 107:254–60. CrossRef
Chakraborty B, Nath A, Saikia H, Sengupta M. Bactericidal activity of selected medicinal plants against multidrug resistant bacterial strains from clinical isolates. Asian Pac J Trop Med, 2014; 7(S1):435–41. CrossRef
Chang JS, Wang KC, Yeh CF, Shieh DE, Chiang LC. Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines. J Ethnopharmacol, 2013; 145(1):146–51. CrossRef
Dar RA, Shahnawaz M, Qazi PH, Qazi H. General overview of medicinal plants: a review. J Phytopharmacol, 2017; 6(6):91–3. CrossRef
Elmowalid GA, El-Hamid MIA, El-Wahab AMA, Atta M, El-Naser GA, Attia AM. Garlic and ginger extracts modulated broiler chicks innate immune responses and enhanced multidrug resistant Escherichia coli O78 clearance. Comp Immunol Microbiol Infect Dis, 2019; 66:101334. CrossRef
Harun NH, Ahmad WANW, Suppian R. Immunostimulatory effects of Asiatic acid and madecassoside on the phagocytosis activities of macrophages cell lines (J774A.1). J Appl Pharm Sci, 2021; 11(11):104–11. CrossRef
Harun NH, Septama AW, Wan Ahmad WAN, Suppian R. The potential of Centella asiatica (Linn.) Urban as an anti-microbial and immunomodulator agent: a review. Nat Prod Sci, 2019; 25(2):92–102. CrossRef
Harun NH, Ahmad WANW, Suppian R. The effects of individual and combination of Asiatic acid and madecassoside derived from Centella asiatica (Linn.) on the viability percentage and morphological changes of mouse macrophage cell lines (J774A.1). J Appl Pharm Sci, 2018; 8(11):109–15. CrossRef
Hasan S, Danishuddin M, Khan AU. Inhibitory effect of Zingiber officinale towards Streptococcus mutans virulence and caries development: in vitro and in vivo studies. BMC Microbiol, 2015; 15(1):1–14. CrossRef
Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.1.0. The Cochrane Collaboration, 2011. Available via www.handbook.cochrane.org
Imane NI, Fouzia H, Azzahra LF, Ahmed E, Ismail G, Idrissa D, Mohamed KH, Sirine F, L’Houcine O, Noureddine B. Chemical composition, antibacterial and antioxidant activities of some essential oils against multidrug resistant bacteria. Eur J Integr Med, 2020; 35:101074. CrossRef
Jacob J, Peter G, Thomas S, Haponiuk JT, Gopi S. Chitosan and polyvinyl alcohol nanocomposites with cellulose nanofibers from ginger rhizomes and its antimicrobial activities. Int J Biol Macromol, 2019; 129:370–6. CrossRef
Jain I, Jain P, Bisht D, Sharma A, Srivastava B, Gupta N. Comparative evaluation of antibacterial efficacy of six indian plant extracts against Streptococcus mutans. J Clin Diagn Res, 2015; 9(2):50–3. CrossRef
Karuppiah P, Rajaram S. Antibacterial effect of Allium sativum cloves and Zingiber officinale rhizomes against multiple-drug resistant clinical pathogens. Asian Pac J Trop Biomed, 2012; 2(8):597–601. CrossRef
Keys JD. Chinese herbs. 3rd edition, Charles E Tuttle Company, Inc., Tokyo, Japan, pp 77–8, 1985.
Liao DW, Cheng C, Liu JP, Zhao LY, Huang DC, Chen GT. Characterization and antitumor activities of polysaccharides obtained from ginger (Zingiber officinale) by different extraction methods. Int J Biol Macromol, 2020; 152(6):894–903. CrossRef
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):185. CrossRef
Masuda Y, Kikuzaki H, Hisamoto M, Nakatani N. Antioxidant properties of gingerol related compounds from ginger. BioFactors, 2004; 21:293–6. CrossRef
McFee RB. Middle east respiratory syndrome (MERS) coronavirus. Dis Mon, 2020; 66(9) :101053. CrossRef
Mohamad HS, Sun W, Cheng Q. Clinical aspects and health benefits of ginger (Zingiber officinale) in both traditional Chinese medicine and modern industry. Acta Agric Scand Soil Plant Sci, 2019; 69:546–56. CrossRef
Mohammad SM, Hamed HK. Ginger (Zingiber officinale): a review. J Med Plants Res, 2012; 6(26):4255–8. CrossRef
Moher D, Liberati A, Tetzlaff J, Altman DG, Altman D, Antes G, Atkins D, Barbour V, Barrowman N, Berlin JA, Clark J, Clarke M, Cook D, D’Amico R, Deeks JJ, Devereaux PJ, Dickersin K, Egger M, Ernst E, Tugwell P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med, 2009; 6(7) :339:b2535. CrossRef
Mohsen S, Dickinson JA, Somayaji R. Update on the adverse effects of antimicrobial therapies in community practice. Can Fam Phys, 2020; 66(9):651–9.
Murugesan S, Venkateswaran MR, Jayabal S, Periyasamy S. Evaluation of the antioxidant and anti-arthritic potential of Zingiber officinale Rosc. by in vitro and in silico analysis. South Afri J Bot, 2020; 130:45–53. CrossRef
Ojewole JAO. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol extract of Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. Phytother Res, 2006; 20(9):764–72. CrossRef
Revati S, Bipin C, Chitra PB, Minakshi B. In vitro antibacterial activity of seven Indian spices against high level gentamicin resistant strains of enterococci. Arch Med Sci, 2015; 11(4):863–8. CrossRef
Reygaert CW. An overview of the antimicrobial resistance mechanisms of bacteria. AIMS Microbiol, 2018; 4(3):482–501. CrossRef
Safa O, Hassaniazad M, Davoodian P, Dadvand H, Hassanipour S, Fathalipor M. Effects of ginger on clinical manifestations and paraclinical features of patients with severe acute respiratory syndrome due to COVID-19: a structured summary of a study protocol for a randomized controlled trial. Trials, 2020; 21:841. CrossRef
Saleh RM, Kabli SA, Al-Garni SM, Al-Ghamdi MA, Abdel-Aty AM, Mohamed SA. Solid-state fermentation by Trichoderma viride for enhancing phenolic content, antioxidant and antimicrobial activities in ginger. Lett Appl Microbiol, 2018; 67(2):161–7. CrossRef
Sharifzadeh A, Jebeli JA, Shokri H, Abbaszadeh S, Keykhosravy K. Evaluation of antioxidant and antifungal properties of the traditional plants against foodborne fungal pathogens. J Mycol Med, 2016; 26(1):e11–7. CrossRef
Siddaraju MN, Dharmesh SM. Inhibition of gastric H+,K+-ATPase and Helicobacter pylori growth by phenolic antioxidants of Zingiber officinale. Mol Nutr Food Res, 2007; 51(3):324–32. CrossRef
Silva FT, Cunha KF, Fonseca LM, Antunes MD, Halal SLM, Fiorentini AM, Zavareze ER, Dias ARG. Action of ginger essential oil (Zingiber officinale) encapsulated in proteins ultrafine fibers on the antimicrobial control in situ. Int J Biol Macromol, 2018; 118:107–15. CrossRef
Snuossi M, Trabelsi N, Taleb SB, Dehmeni A, Flamini G. Laurus nobilis, Zingiber officinale and Anethum graveolens essential oils: composition, antioxidant and antibacterial activities against bacteria isolated from fish and shellfish. Molecules, 2016; 21(10) :1414. CrossRef
Thomson M, Al-Qattan KK, Al-Sawan SM, Alnaqeeb MA, Ali KM. The use of ginger (Zingiber officinale Rosc.) as a potential anti-inflammatory and antithrombotic agent. Prostaglandins Leukot Essent FattyAcids, 2002; 67(6):475–8. CrossRef
Wang HM, Chen CY, Chen HA, Huang WC, Lin WR, Chen TC, Lin CY, Chien HJ, Lu PL, Lin CM, Chen YH. Zingiber officinale (ginger) compounds have tetracycline-resistance modifying effects against clinical extensively drug-resistant Acinetobacter baumannii. Phytother Res, 2010; 24(12):1825–30. CrossRef
Wang L, Hu C, Shao L. The antimicrobial activity of nanoparticles: present situation and prospects for the future, 2017; 12:1227–49. CrossRef
Yamauchi K, Natsume M, Yamaguchi K, Batubara I, Mitsunaga T. Structure-activity relationship for vanilloid compounds from extract of Zingiber officinale var rubrum rhizomes: effect on extracellular melanogenesis inhibitory activity. Med Chem Res, 2019; 28:1402–12. CrossRef