Sensitivity analyses were performed to assess any undue influences of individual studies on the overall effect estimates, by systematically removing each individual study from the meta-analysis and recalculating the effect estimate from the remaining studies.

Publication bias was examined through visual inspection of funnel plots and quantitatively evaluated by Begg's and Egger's tests. Meta-regressions and assessment of publication bias were performed on STATA 12 StataCorp, College Station, Texas.

Figure 1 shows the flow of the literature. We identified publications, of which were excluded on the basis of title and abstract. Of the 45 potential relevant studies that were retrieved and fully reviewed, 30 were further excluded. Table 1 displays the characteristics of the included trials.

Nine Non-diabetes trials included subjects with essential hypertension 1 trial , pre-diabetes 2 trials , and those that were otherwise healthy 4 trials.

The median age of the study population was 51 years IQR: All but one trial [32] were carried out in outpatient settings. Eleven trials Two trials All the trials used encapsulated powder forms of ginseng as the intervention.

Thirteen trials The median follow-up was 8 weeks IQR: 8— The median MQS among the available trials was 8 IQR: 7—10 Table S2. Of those trials which received low scores, the elements contributing to the low scores were poor description of randomization and treatment protocol, nonconsecutive or poorly described patient selection, high drop-out rates, and the absence of an intention-to-treat analysis.

The Cochrane Risk of Bias Tool showed that 9 trials Six trials Fourteen trials Ten trials Figure 2 shows the effect of ginseng supplementation on FBG. The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trials [18].

P values are for Generic Inverse Variance random effects models. Heterogeneity remained significant, and could not be explained away by any of the subgroup analyses.

Figure 3 shows the effect of ginseng supplementation on FPI. No difference in effect estimate was identified by diabetes status. Sensitivity analyses did not alter the direction or significance of effect estimates nor modify heterogeneity; and a priori subgroup analyses did not reveal significant effect modification by any subgroup under both dichotomous and continuous models Figure S3 and Table S3.

Figure 4 shows the effect of ginseng supplementation on HbA1c. Paired analyses were applied to all crossover trial [18]. The overall heterogeneity in the results was not affected by the individual removal of any studies. No linear associations between baseline HbA1c or follow-up duration and reductions in HbA1c were found by continuous meta-regression analyses Table S3.

Figure 5 shows the effect of ginseng supplementation on HOMA-IR. Sensitivity analyses did not alter the direction or significance of effect estimates nor modify heterogeneity; and a priori subgroup analyses did not reveal significant effect modification by any subgroup under both dichotomous and continuous models.

Figure S5 and Table S3. However, this was not confirmed by either Egger's or Begg's tests Figure S6. An aggregate analyses of 16 RCTs in participants showed that ginseng supplementation significantly lowered FBG.

Ginseng intakes decreased FBG by 0. Although there was no significant overall effect of ginseng on FPI, HbA1c, or HOMA-IR, a priori subgroup analyses did show a significant HbA1c benefit in parallel trials compared to crossover trials. Greater reductions in FBG were also observed in people with diabetes than those without diabetes.

Our findings add to those from previous systematic reviews in this area. Two recent systematic reviews assessing the efficacy and safety of ginseng reported promising, but inconclusive evidence for its application in moderating glucose metabolism [12] , [13]. However, another earlier systematic review and meta-analysis failed to show a FBG-lowering effect of ginseng supplementation [14].

One reason for these inconsistencies may relate to differences in their eligibility criteria. Whereas the earlier systematic review included only RCTs that investigated the effect of Korean red ginseng in subjects with T2DM with either acute treatment administrations or treatment durations of least 12 weeks, we included trials which investigated the effect of any ginseng species in people with or without diabetes over at least 4 weeks.

Despite having more inclusive criteria for ginseng species, diabetes status, and follow-up, we did not find any significant effect modification by any of these criteria with the exception of diabetes status.

Diabetes status partially explained the heterogeneity in the overall analysis for FBG. Participants with diabetes had a greater reduction in FBG than participants without diabetes.

In line with this subgroup effect, our continuous meta-regression analyses showed that increases in baseline FBG were linearly associated with FBG reductions on the ginseng interventions, further supporting the notion that ginseng supplementation may generate a greater benefit in individuals with higher FBG levels.

It is unclear why the improvements in HbA1c were restricted to parallel trials only. One explanation may be an inadequate washout period between treatments in crossover designs, as it has been shown that ginseng metabolites may remain in the body for up to 10 weeks after treatment has ended [33].

Another explanation may relate to the glycemic control of the participants. It is a well understood phenomenon that the higher baseline HbA1c levels, the greater the fall with anti-hyperglycemic agents [34].

As most of the trials included participants with relatively good glycemic control in people with diabetes median HbA1c 7. These observations are line with findings from previous clinical trials supporting both the proposed insulin sensitizing and insulin secreting mechanisms for Panax ginseng and Panax quinquefolius respectively in the amelioration of hyperglycemia in T2DM [9] , [29].

The mechanisms underlying ginseng's hypoglycemic activity remain unclear. A growing database of cell culture and animal studies indicate that ginseng may alleviate hyperglycemia by enhancing pancreatic β-cell function and reducing insulin resistance [38].

Collectively, these investigations offer preliminary but plausible explanations for the anti-diabetic potency of the two ginseng species in the clinical trials of this meta-analysis. Assessment of the safety and tolerability of ginseng was not possible in this systematic review and meta-analysis, as only 4 of the 16 trials reported safety parameters among which a consistent safety parameter did not exist [9] , [27] , [29] , [30].

Markers used in evaluating ginseng's safety included hepatic, renal, haemostatic, blood pressure function, comprehensive blood tests, and number of adverse events, none of which reported any difference in adverse events relative to the control.

This parallels findings of several systematic reviews investigating the efficacy and safety of ginseng, where it was concluded that while its efficacy remains questionable, it appears to be generally safe [12] , [37] , [39].

Due to the nature of the intervention used in the trials, we could not eliminate the possibility of an effect modification by source of funding. Hence, following a post hoc analysis, no effect of funding source was found for any of the endpoints.

Several limitations of this systematic review and meta-analysis should be acknowledged. often uncharacterized extracts of these varieties , precluding calculation of ginseng dose equivalents.

Second, the high variability in ginsenoside composition along with poor standardization of the ginsenoside profile continues to add complexity to the assessment of ginseng's glycemic benefits, as it has been shown that the anti-hyperglycemic efficacy of ginseng varies across species and is correlated to its ginsenoside composition [40].

To date, the optimal ratio of the most prominent bioactive components of ginseng, the ginsenosides, needed to ensure reproducible glucose lowering effects and product quality, has not been fully determined, necessitating a demand for better ginseng standardization.

Third, information on the ginsenoside profile was not given by most of the trials, complicating the corroboration of a corresponding ginsenoside profile across studies that demonstrated effective findings.

In conclusion, aggregate data analyses of controlled clinical trials show evidence for a modest yet significant benefit of ginseng in improving FBG in people with and without diabetes. Although ginseng did show advantages for HbA1c in parallel trials, the overall lack of an effect on HbA1c and persistent unexplained heterogeneity among the effect estimates from the available trials creates some uncertainty as to the long-term benefits of ginseng supplementation on glycemic control.

The uncertainty points to several methodological limitations including the short duration of the trials, the well-controlled glycemia of participants at baseline, and the use of unstandardized ginseng preparations with potentially varying potencies.

To provide more precise estimates of ginseng's long term effectiveness and address the unexplained heterogeneity, longer term, large scale, RCTs of the effect of ginseng preparations on HbA1c are warranted. Finally, given the promising effects of ginseng on FBG demonstrated herein, further research in this area is sensible, with a particular focus in investigating its potential glycemic-lowering components such as the unexamined non-saponins.

Risk of bias assessment for included trials by the Cochrane risk of bias tool. Forest plots of subgroup analyses investigating the effect of ginseng on fasting blood glucose. Forest plots of subgroup analyses investigating the effect of ginseng on fasting plasma insulin.

Forest plots of subgroup analyses investigating the effect of ginseng on glycated hemoglobin. Forest plots of subgroup analyses investigating the effect of ginseng on homeostasis model assessment of insulin resistance.

Search strategy for studies assessing the effect of ginseng on glycemic control in randomized controlled trials. Continuous meta-regression analysis for the effect of ginseng on glycemic parameters. We thank Ms. Evelyn Wong and Ms. Shana Kim for providing assistance with the translations of the non-English articles.

Analyzed the data: ES VH AC RdS VJ. Wrote the paper: ES. Developed the search strategy, conducted the search, performed data analysis and interpretation, drafted, revised, and finalized the manuscript: ES. Conception and design of the project: VV JS. Analysis and interpretation of data: VV JS.

Critical revision of the manuscript: VV JS DJ RdS AC VH VJ VD EJ SBM. Supervision: VV. Design of the project: DJ. Interpretation of data: RdS. Statistical analysis: RdS. Assistance in the search, extraction of data, data interpretation: AC VH VJ EJ SBM. Extraction of study characteristics and data from each included study: VD.

Approved the final manuscript for publication and agreed to be accountable for all aspects of the work: ES JS VD AC VH VJ DJ SBM RdS EJ VV. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Importance Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.

Objective To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes.

Data sources MEDLINE, EMBASE, CINAHL and the Cochrane Library through July 3, Data extraction Relevant data were extracted by 2 independent reviewers. Conclusions Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. Trial Registration ClinicalTrials.

gov NCT Introduction Diabetes is reaching epidemic proportions globally, with rates continually rising in both the developed and developing countries [1]. Methods Our meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions [15]. Data sources and searches MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of RCTs were searched from inception through 3 July , using a comprehensive search strategy Table S1.

Data extraction and quality assessment Data were reviewed and extracted by two independent reviewers E. Results Search results Figure 1 shows the flow of the literature. Download: PPT.

Figure 1. Flow of the literature search for the effect of ginseng on glycemic outcomes FBG, FPI, HbA1c, and HOMA-IR. Trial characteristics Table 1 displays the characteristics of the included trials. Table 1. Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes.

Fasting Blood Glucose Figure 2 shows the effect of ginseng supplementation on FBG. Figure 2. Forest plots of controlled clinical trials investigating the effect of ginseng on FBG. Fasting Plasma Insulin Figure 3 shows the effect of ginseng supplementation on FPI.

Figure 3. Forest plots of controlled clinical trials investigating the effect of ginseng on fasting plasma insulin. Glycated Hemoglobin Figure 4 shows the effect of ginseng supplementation on HbA1c.

Figure 4. Forest plots of controlled clinical trials investigating the effect of ginseng on glycated hemoglobin. Homeostasis model assessment of insulin resistance Figure 5 shows the effect of ginseng supplementation on HOMA-IR.

Figure 5. Forest plots of controlled clinical trials investigating the effect of ginseng on homeostasis model assessment of insulin resistance. Discussion and Conclusions An aggregate analyses of 16 RCTs in participants showed that ginseng supplementation significantly lowered FBG. Supporting Information.

Figure S1. s DOC. Figure S2. s DOCX. Figure S3. Figure S4. Figure S5. Figure S6. Table S1. Table S2. Study Quality Assessment by the Heyland MQS. Table S3. Checklist S1. PRISMA Checklist. Acknowledgments We thank Ms. Author Contributions Analyzed the data: ES VH AC RdS VJ.

References 1. King H, Aubert RE, Herman WH Global burden of diabetes, — prevalence, numerical estimates, and projections. Diabetes Care — View Article Google Scholar 2. Levy P The current unmet need in type 2 diabetes mellitus: addressing glycemia and cardiovascular disease.

Postgrad Med 7— View Article Google Scholar 3. Tackett KL, Jones MC Complementary and Alternative Medicines for the Treatment of Diabetes. Journal of Pharmacy Practice — ISSN print ISSN online. Endocrine Abstracts.

Prev Next. Endocrine Abstracts 56 P DOI: The effects of Korean red ginseng on diabetic complications and glucose modulation in type 2 diabetic patients.

Author affiliations. Yonsei University College of Medicine, Gangnam Severance Hospital, Seoul, Republic of Korea. Volume 56 Prev Next. Summary Abstract Book Programme Volume Editors Abstracts.

Article tools. My recent searches. My recently viewed abstracts. The effects of Korean red ginseng on diabetic complications and glucose modulation in type 2 diabetic patients Authors. Woo Ahn Chul Endocrine Abstracts Google Scholar Pub Med.

Hye Kim Jung Endocrine Abstracts Google Scholar Pub Med. Park Kahui Endocrine Abstracts Google Scholar Pub Med. Bae Lee Sang Endocrine Abstracts Google Scholar Pub Med. Sun Nam Ji Endocrine Abstracts Google Scholar Pub Med. Kang Shinae Endocrine Abstracts Google Scholar Pub Med. Suk Park Jong Endocrine Abstracts Google Scholar Pub Med.

The median follow-up was 8 weeks IQR: 8— The median MQS among the available trials was 8 IQR: 7—10 Table S2. Of those trials which received low scores, the elements contributing to the low scores were poor description of randomization and treatment protocol, nonconsecutive or poorly described patient selection, high drop-out rates, and the absence of an intention-to-treat analysis.

The Cochrane Risk of Bias Tool showed that 9 trials Six trials Fourteen trials Ten trials Figure 2 shows the effect of ginseng supplementation on FBG. The diamond represents a pooled effect estimate. Paired analyses were applied to all crossover trials [18].

P values are for Generic Inverse Variance random effects models. Heterogeneity remained significant, and could not be explained away by any of the subgroup analyses.

Figure 3 shows the effect of ginseng supplementation on FPI. No difference in effect estimate was identified by diabetes status. Sensitivity analyses did not alter the direction or significance of effect estimates nor modify heterogeneity; and a priori subgroup analyses did not reveal significant effect modification by any subgroup under both dichotomous and continuous models Figure S3 and Table S3.

Figure 4 shows the effect of ginseng supplementation on HbA1c. Paired analyses were applied to all crossover trial [18]. The overall heterogeneity in the results was not affected by the individual removal of any studies.

No linear associations between baseline HbA1c or follow-up duration and reductions in HbA1c were found by continuous meta-regression analyses Table S3. Figure 5 shows the effect of ginseng supplementation on HOMA-IR.

Sensitivity analyses did not alter the direction or significance of effect estimates nor modify heterogeneity; and a priori subgroup analyses did not reveal significant effect modification by any subgroup under both dichotomous and continuous models.

Figure S5 and Table S3. However, this was not confirmed by either Egger's or Begg's tests Figure S6. An aggregate analyses of 16 RCTs in participants showed that ginseng supplementation significantly lowered FBG. Ginseng intakes decreased FBG by 0. Although there was no significant overall effect of ginseng on FPI, HbA1c, or HOMA-IR, a priori subgroup analyses did show a significant HbA1c benefit in parallel trials compared to crossover trials.

Greater reductions in FBG were also observed in people with diabetes than those without diabetes. Our findings add to those from previous systematic reviews in this area.

Two recent systematic reviews assessing the efficacy and safety of ginseng reported promising, but inconclusive evidence for its application in moderating glucose metabolism [12] , [13].

However, another earlier systematic review and meta-analysis failed to show a FBG-lowering effect of ginseng supplementation [14]. One reason for these inconsistencies may relate to differences in their eligibility criteria. Whereas the earlier systematic review included only RCTs that investigated the effect of Korean red ginseng in subjects with T2DM with either acute treatment administrations or treatment durations of least 12 weeks, we included trials which investigated the effect of any ginseng species in people with or without diabetes over at least 4 weeks.

Despite having more inclusive criteria for ginseng species, diabetes status, and follow-up, we did not find any significant effect modification by any of these criteria with the exception of diabetes status.

Diabetes status partially explained the heterogeneity in the overall analysis for FBG. Participants with diabetes had a greater reduction in FBG than participants without diabetes. In line with this subgroup effect, our continuous meta-regression analyses showed that increases in baseline FBG were linearly associated with FBG reductions on the ginseng interventions, further supporting the notion that ginseng supplementation may generate a greater benefit in individuals with higher FBG levels.

It is unclear why the improvements in HbA1c were restricted to parallel trials only. One explanation may be an inadequate washout period between treatments in crossover designs, as it has been shown that ginseng metabolites may remain in the body for up to 10 weeks after treatment has ended [33].

Another explanation may relate to the glycemic control of the participants. It is a well understood phenomenon that the higher baseline HbA1c levels, the greater the fall with anti-hyperglycemic agents [34].

As most of the trials included participants with relatively good glycemic control in people with diabetes median HbA1c 7. These observations are line with findings from previous clinical trials supporting both the proposed insulin sensitizing and insulin secreting mechanisms for Panax ginseng and Panax quinquefolius respectively in the amelioration of hyperglycemia in T2DM [9] , [29].

The mechanisms underlying ginseng's hypoglycemic activity remain unclear. A growing database of cell culture and animal studies indicate that ginseng may alleviate hyperglycemia by enhancing pancreatic β-cell function and reducing insulin resistance [38].

Collectively, these investigations offer preliminary but plausible explanations for the anti-diabetic potency of the two ginseng species in the clinical trials of this meta-analysis. Assessment of the safety and tolerability of ginseng was not possible in this systematic review and meta-analysis, as only 4 of the 16 trials reported safety parameters among which a consistent safety parameter did not exist [9] , [27] , [29] , [30].

Markers used in evaluating ginseng's safety included hepatic, renal, haemostatic, blood pressure function, comprehensive blood tests, and number of adverse events, none of which reported any difference in adverse events relative to the control.

This parallels findings of several systematic reviews investigating the efficacy and safety of ginseng, where it was concluded that while its efficacy remains questionable, it appears to be generally safe [12] , [37] , [39].

Due to the nature of the intervention used in the trials, we could not eliminate the possibility of an effect modification by source of funding. Hence, following a post hoc analysis, no effect of funding source was found for any of the endpoints.

Several limitations of this systematic review and meta-analysis should be acknowledged. often uncharacterized extracts of these varieties , precluding calculation of ginseng dose equivalents.

Second, the high variability in ginsenoside composition along with poor standardization of the ginsenoside profile continues to add complexity to the assessment of ginseng's glycemic benefits, as it has been shown that the anti-hyperglycemic efficacy of ginseng varies across species and is correlated to its ginsenoside composition [40].

To date, the optimal ratio of the most prominent bioactive components of ginseng, the ginsenosides, needed to ensure reproducible glucose lowering effects and product quality, has not been fully determined, necessitating a demand for better ginseng standardization.

Third, information on the ginsenoside profile was not given by most of the trials, complicating the corroboration of a corresponding ginsenoside profile across studies that demonstrated effective findings.

In conclusion, aggregate data analyses of controlled clinical trials show evidence for a modest yet significant benefit of ginseng in improving FBG in people with and without diabetes. Although ginseng did show advantages for HbA1c in parallel trials, the overall lack of an effect on HbA1c and persistent unexplained heterogeneity among the effect estimates from the available trials creates some uncertainty as to the long-term benefits of ginseng supplementation on glycemic control.

The uncertainty points to several methodological limitations including the short duration of the trials, the well-controlled glycemia of participants at baseline, and the use of unstandardized ginseng preparations with potentially varying potencies.

To provide more precise estimates of ginseng's long term effectiveness and address the unexplained heterogeneity, longer term, large scale, RCTs of the effect of ginseng preparations on HbA1c are warranted.

Finally, given the promising effects of ginseng on FBG demonstrated herein, further research in this area is sensible, with a particular focus in investigating its potential glycemic-lowering components such as the unexamined non-saponins. Risk of bias assessment for included trials by the Cochrane risk of bias tool.

Forest plots of subgroup analyses investigating the effect of ginseng on fasting blood glucose. Forest plots of subgroup analyses investigating the effect of ginseng on fasting plasma insulin.

Forest plots of subgroup analyses investigating the effect of ginseng on glycated hemoglobin. Forest plots of subgroup analyses investigating the effect of ginseng on homeostasis model assessment of insulin resistance. Search strategy for studies assessing the effect of ginseng on glycemic control in randomized controlled trials.

Continuous meta-regression analysis for the effect of ginseng on glycemic parameters. We thank Ms. Evelyn Wong and Ms. Shana Kim for providing assistance with the translations of the non-English articles.

Analyzed the data: ES VH AC RdS VJ. Wrote the paper: ES. Developed the search strategy, conducted the search, performed data analysis and interpretation, drafted, revised, and finalized the manuscript: ES.

Conception and design of the project: VV JS. Analysis and interpretation of data: VV JS. Critical revision of the manuscript: VV JS DJ RdS AC VH VJ VD EJ SBM. Supervision: VV. Design of the project: DJ.

Interpretation of data: RdS. Statistical analysis: RdS. Assistance in the search, extraction of data, data interpretation: AC VH VJ EJ SBM. Extraction of study characteristics and data from each included study: VD.

Approved the final manuscript for publication and agreed to be accountable for all aspects of the work: ES JS VD AC VH VJ DJ SBM RdS EJ VV. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Article Authors Metrics Comments Media Coverage Reader Comments Figures. Abstract Importance Despite the widespread use of ginseng in the management of diabetes, supporting evidence of its anti-hyperglycemic efficacy is limited, necessitating the need for evidence-based recommendations for the potential inclusion of ginseng in diabetes management.

Objective To elucidate the effect of ginseng on glycemic control in a systematic review and meta-analysis of randomized controlled trials in people with and without diabetes. Data sources MEDLINE, EMBASE, CINAHL and the Cochrane Library through July 3, Data extraction Relevant data were extracted by 2 independent reviewers.

Conclusions Ginseng modestly yet significantly improved fasting blood glucose in people with and without diabetes. Trial Registration ClinicalTrials. gov NCT Introduction Diabetes is reaching epidemic proportions globally, with rates continually rising in both the developed and developing countries [1].

Methods Our meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions [15]. Data sources and searches MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of RCTs were searched from inception through 3 July , using a comprehensive search strategy Table S1.

Data extraction and quality assessment Data were reviewed and extracted by two independent reviewers E. Results Search results Figure 1 shows the flow of the literature. Download: PPT. Figure 1. Flow of the literature search for the effect of ginseng on glycemic outcomes FBG, FPI, HbA1c, and HOMA-IR.

Trial characteristics Table 1 displays the characteristics of the included trials. Table 1. Characteristics of Studies Investigating the Effect of Ginseng on Glycemic Outcomes. Fasting Blood Glucose Figure 2 shows the effect of ginseng supplementation on FBG. Trends in alternative medicine use in the United States, results of a follow-up national survey.

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UK Prospective Diabetes Study UKPDS Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes UKPDS See More About Diabetes Diabetes and Endocrinology. Select Your Interests Select Your Interests Customize your JAMA Network experience by selecting one or more topics from the list below.

Save Preferences. Privacy Policy Terms of Use. This Issue. Citations View Metrics. Among the 28 ginsenosides, PPT, Rh1, Rh2, Rh4, Ro, Rg1, and PPD interacted with more targets, BP, and signaling pathways.

We speculated that these seven saponins might play a significant role in managing DM. A comparison with the literature, molecular docking, and molecular dynamics simulation showed the authenticity and reliability of our results.

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College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, , China. National and Local Joint Engineering Research Center for Ginseng Breeding and Development, Changchun, , China. Key Laboratory of Biotechnology and Bioresources Utilization, Ministry of Education, Dalian Minzu University, Dalian, , Liaoning, China.

Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun, China. You can also search for this author in PubMed Google Scholar. Author contributions W. and Z. conceived and designed the study, M.

wrote the manuscript, M. corrected the manuscript, M. acquisition of data, K. contributed tools. All data were generated in-house, and no paper mill was used.

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Subjects Plant sciences Systems biology. Abstract A large body of literature has shown that ginseng had a role in diabetes mellitus management. Introduction Diabetes mellitus DM is a non-communicable metabolic disease characterized by chronic hyperglycemia. Construction and analysis of the protein—protein interaction PPI network We inputted the intersection targets into STRING Gene ontology and Kyoto encyclopedia of genes and genomes pathway enrichment analysis All intersecting targets were analyzed for Gene Ontology GO and Kyoto Encyclopedia of Genes and Genomes KEGG enrichment by the Bioconductor cluster analyzer of R 4.

Molecular dynamics simulation After the docking studies were completed, the active ingredients with the good binding ability to the protein were further evaluated for their stability in the binding pocket using the amber18 software package to run ns molecular dynamics of protein-compound conjugates.

Investigation of binding affinity using molecular mechanics Poisson—Boltzmann surface area MM-PBSA The relative binding energy of a protein—ligand complex is popularly used in MD simulations and thermodynamic computations.

Table 1 The ginsenosides and their information. Full size table. Figure 1. Full size image. Figure 2. Table 2 The 9 core targets of detailed information on the screening.

Figure 3.