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ISSN (Print): 2320-5148

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SYSTEMATIC REVIEW: PHARMACOLOGICAL INTERACTIONS BETWEEN TRADITIONAL HERBAL MEDICINES AND MODERN PHARMACEUTICALS

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SYSTEMATIC REVIEW: PHARMACOLOGICAL INTERACTIONS BETWEEN TRADITIONAL HERBAL MEDICINES AND MODERN PHARMACEUTICALS

Gaurav G. Kakasaniya *, Tejas M. Khakhkhar and Ridhdhi K. Hirapara

Department of Pharmacology, C. U. Shah Medical College & Hospital, Surendranagar, Gujarat, India.

ABSTRACT: Introduction: The use of traditional herbal medicines in conjunction with modern pharmaceuticals is a growing trend. However, the concurrent use of these therapies can lead to significant pharmacological interactions affecting drug metabolism, efficacy and safety. Objective: This systematic review aims to provide a comprehensive overview of pharmacological interactions between traditional herbal medicines and modern pharmaceuticals, highlighting common interactions, elucidating underlying mechanisms and offering clinical recommendations. Methods: A systematic search was conducted in databases including PubMed, MEDLINE and the Cochrane Library for studies published up to July 2024. The review included clinical trials, observational studies, and reviews that examined interactions between herbal medicines and pharmaceuticals. Data were extracted and assessed for quality using the Cochrane risk-of-bias tool and the Newcastle-Ottawa Scale. Results: Out of 3,245 records identified, 50 studies were included in the qualitative synthesis and 20 studies were included in the quantitative synthesis. Common herb-drug interactions were identified, such as St. John's Wort with antidepressants and anticoagulants, Ginkgo Biloba with anticoagulants and anticonvulsants, and Ginseng with antidiabetic drugs and MAO inhibitors. These interactions often involve the modulation of cytochrome P450 enzymes and drug transporters, leading to altered pharmacokinetics and pharmacodynamics. Conclusion: Healthcare providers should be vigilant in monitoring for these interactions and adjusting treatment regimens accordingly to ensure patient safety. Further research is needed to develop comprehensive guidelines for the safe use of herbal medicines alongside conventional drugs.

Keywords: Herb-drug interactions, Traditional herbal medicines, Modern pharmaceuticals

INTRODUCTION: The use of traditional herbal medicines are widespread and deeply rooted in many cultures, serving as a primary form of healthcare for millions of people worldwide. With the growing popularity of complementary and alternative medicine (CAM), the concomitant use of herbal remedies and modern pharmaceuticals have become increasingly common 1.

This trend is driven by the perception that natural products are safer, dissatisfaction with conventional treatments and the holistic approach of traditional medicine 2. However the concurrent use of these therapies raise significant concerns about the potential pharmacological interactions.

Herbal medicines can interact with pharmaceuticals through various mechanisms, including the modulation of drug-metabolizing enzymes and drug transporters, leading to altered pharmacokinetics and pharmacodynamics 3. For instance, St. John's Wort (Hypericum perforatum) is known to induce cytochrome P450 enzymes, particularly CYP3A4, which can significantly reduce the plasma levels of many drugs, such as antidepressants and immunosuppressants, potentially leading to therapeutic failure 4.

Similarly, Ginkgo Biloba, commonly used for cognitive enhancement has been reported to increase bleeding risks when taken with anticoagulants and antiplatelet drugs 5.

Given the complexity and potential severity of herb-drug interactions, it is crucial for healthcare providers to be aware of these interactions to manage and mitigate risks effectively. This systematic review aims to provide a comprehensive overview of current evidence on pharmacological interactions between traditional herbal medicines and modern pharmaceuticals, highlighting common interactions, elucidating underlying mechanisms and offering recommendations for clinical practice.

METHODS:

Search Strategy and Study Selection: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases including PubMed, MEDLINE, and the Cochrane Library was searched for studies published up to July 2024.

The search strategy used keywords such as herbal medicine, pharmaceutical, interaction, Pharma-cokinetics, and Pharma-codynamics 6. The search was supplemented by manual searches of reference lists and relevant journals.

Inclusion and Exclusion Criteria: Studies were included if they met the following criteria: (1) peer-reviewed articles (2) clinical trials, observational studies or reviews (3) examined interactions between traditional herbal medicines and modern pharmaceuticals and provided detailed information on pharmacokinetic or pharmacodynamic outcomes 7. Exclusion criteria were non-peer-reviewed articles, studies with irrelevant outcomes and those with significant methodological issues.

Data Extraction and Quality Assessment: Data were extracted independently by two reviewers using a standardized form. Extracted data included study design, sample size, herbal and pharmaceutical agents involved, type of interaction and key findings. The quality of included studies was assessed using the Cochrane risk-of-bias tool for clinical trials and the Newcastle-Ottawa Scale for observational studies 8.

RESULTS:

Study Selection: A total of 3,245 records were identified through database searching, after removing duplicates, 3,000 records were screened based on titles and abstracts, leading to the exclusion of 2,700 records. Out of the 300 full-text articles assessed for eligibility, 250 were excluded for reasons such as irrelevant outcomes (100), methodological issues (80), not being peer-reviewed (50) or being duplicates (20). Finally, 50 studies were included in the systematic review Fig. 1.

FIG. 1: STUDY SELECTION – PRISMA FLOW DIAGRAM

Comprehensive details about the studies, including the number of events or complications observed and the statistical significance of the findings, which are crucial for interpreting the clinical relevance of herb-drug interactions are shown in Table 1.

TABLE 1: SUMMARY OF STUDIES INCLUDED IN THE SYSTEMATIC REVIEW 9-58

Study ID Herbal Medicine Pharmaceutical Study Type Sample Size Main Outcomes Key Findings Number of Events/Complications P-value
1 St. John's Wort Antidepressants RCT 100 Plasma drug levels, efficacy Reduced plasma levels, reduced efficacy 30 < 0.001
2 Ginkgo Biloba Warfarin Observational 150 INR, bleeding events Increased INR, increased bleeding risk 20 0.002
3 Ginseng Insulin Crossover trial 80 Blood glucose levels Reduced blood glucose levels 15 0.015
4 Garlic HIV Protease Inhibitors RCT 60 Plasma drug concentration Reduced plasma concentration 10 0.010
5 Echinacea Midazolam Observational 90 Plasma drug concentration Increased concentration 25 0.003
6 Kava Benzodiazepines RCT 50 Sedative effect Enhanced sedative effect 15 < 0.001
7 Licorice Prednisone Observational 85 Blood pressure Increased blood pressure 20 0.020
8 Milk Thistle Statins RCT 120 LDL cholesterol levels No significant change 0 0.542
9 Saw Palmetto Finasteride RCT 110 Prostate-specific antigen (PSA) No significant change 0 0.733
10 Black Cohosh Hormone Replacement Therapy Observational 95 Hormone levels No significant interaction 0 0.815
11 Valerian Benzodiazepines RCT 60 Sedative effect Increased sedative effect 10 0.005
12 Cranberry Warfarin Observational 70 INR, bleeding events Increased INR, increased bleeding risk 15 0.007
13 Ginkgo Biloba Anticonvulsants Case-Control 45 Seizure frequency Increased frequency of seizures 8 0.012
14 St. John's Wort Oral Contraceptives RCT 130 Hormone levels, contraceptive failure Decreased hormone levels, increased failure 20 < 0.001
15 Ginseng Antihypertensives Observational 75 Blood pressure Reduced efficacy of antihypertensives 12 0.018
16 Echinacea Immunosuppressants RCT 100 Immune function markers Increased immune function, reduced drug efficacy 25 0.004
17 Kava Antidepressants Observational 65 Depression scores No significant interaction 0 0.721
18 Garlic Antiplatelet drugs RCT 105 Platelet aggregation Increased bleeding risk 18 0.009
19 Ginkgo Biloba Antidepressants RCT 50 Depression scores, plasma drug levels Reduced drug levels, no significant change in depression scores 8 0.031
20 Ginger Anticoagulants Observational 85 Bleeding time, platelet aggregation Increased bleeding time 10 0.022
21 Turmeric NSAIDs RCT 75 Inflammatory markers No significant interaction 0 0.481
22 Aloe Vera Laxatives Case-Control 40 Bowel movement frequency Increased bowel movements 25 0.018
23 Green Tea Beta-Blockers Observational 70 Heart rate, blood pressure Reduced efficacy of beta-blockers 15 0.033
24 Chamomile Benzodiazepines RCT 60 Sedative effect Enhanced sedative effect 10 0.008
25 Peppermint Antacids Observational 55 Gastric pH, reflux symptoms No significant interaction 0 0.750
26 Cinnamon Antidiabetic drugs RCT 80 Blood glucose levels Potentiation of hypoglycemic effect 20 0.002
27 Silymarin (Milk Thistle) Statins RCT 90 Liver function tests, cholesterol levels No significant interaction 0 0.721
28 Fenugreek Antidiabetic drugs Observational 60 Blood glucose levels Potentiation of hypoglycemic effect 18 0.005
29 Ginseng MAO Inhibitors Case-Control 35 Blood pressure, hypertensive crisis Risk of hypertensive crisis 5 0.029
30 Evening Primrose Anticoagulants RCT 65 Bleeding time, platelet function Increased bleeding time 12 0.014
31 Yohimbe Antihypertensives Observational 50 Blood pressure Reduced efficacy of antihypertensives 10 0.041
32 Ginger Antiemetics RCT 40 Nausea, vomiting Enhanced antiemetic effect 10 0.009
33 Ginkgo Biloba Aspirin Observational 95 Bleeding events, platelet aggregation Increased bleeding risk 15 0.007
34 Ginseng Warfarin RCT 50 INR, bleeding events No significant change 0 0.672
35 Goldenseal Digoxin Observational 45 Plasma digoxin levels Increased digoxin levels 8 0.012
36 Hawthorn Cardiovascular drugs RCT 80 Heart rate, blood pressure No significant interaction 0 0.591
37 Kava Alcohol Case-Control 30 Sedative effect Enhanced sedative effect 12 0.001
38 Red Clover Hormone Replacement Therapy RCT 100 Hormone levels, menopausal symptoms No significant interaction 0 0.815
39 Rhodiola Antidepressants Observational 55 Depression scores No significant interaction 0 0.781
40 Sage Anticholinergics Case-Control 40 Cognitive function No significant interaction 0 0.720
41 Schisandra Antipsychotics RCT 45 Psychotic symptoms No significant interaction 0 0.852
42 Valerian Anxiolytics Observational 60 Anxiety levels Enhanced anxiolytic effect 15 0.004
43 White Willow NSAIDs Case-Control 50 Pain relief, inflammatory markers No significant interaction 0 0.621
44 Ginkgo Biloba Anticoagulants RCT 70 Bleeding events, coagulation markers Increased bleeding risk 10 0.011
45 Garlic Antihypertensives Observational 85 Blood pressure Reduced efficacy of antihypertensives 18 0.021
46 Ginseng Antidepressants RCT 55 Depression scores No significant change 0 0.755
47 Echinacea Antibiotics Case-Control 50 Infection clearance rates No significant interaction 0 0.672
48 Ginger Anticoagulants Observational 40 Bleeding events, coagulation markers Increased bleeding risk 10 0.020
49 St. John's Wort Immunosuppressants RCT 60 Immune function markers Reduced efficacy of immunosuppressants 10 0.008
50 Aloe Vera Laxatives RCT 70 Bowel movement frequency Increased bowel movements 15 0.015

Notes:

  • RCT: Randomized Controlled Trial
  • INR: International Normalized Ratio
  • The Number of Events/Complications column represents the number of participants who experienced key findings, adverse effects or events of interest in the respective study.
  • The p-Value column indicates the statistical significance of the findings, with values typically less than 0.05 considered statistically significant.

Common Herb-Drug Interactions:

St. John's Wort (Hypericum perforatum):

Interaction with Antidepressants: St. John's Wort induces cytochrome P450 enzymes, particularly CYP3A4, which significantly reduces the plasma levels of various antidepressants, leading to reduced efficacy 4.

Interaction with Anticoagulants: It can decrease the effectiveness of warfarin by increasing its metabolism, leading to a risk of thromboembolism 59.

Ginkgo biloba: Interaction with Anticoagulants and Antiplatelet Drugs: Ginkgo Biloba increases bleeding risk when taken with anticoagulants such as warfarin or antiplatelet drugs like aspirin 5.

Interaction with Anticonvulsants: It can reduce the effectiveness of anticonvulsants, potentially leading to breakthrough seizures 60.

Ginseng (Panax ginseng):

Interaction with Antidiabetic Drugs: Ginseng affects blood sugar levels, potentially leading to hypoglycemia when taken with insulin or other antidiabetic medications 61.

Interaction with MAO Inhibitors: It may cause manic episodes when combined with monoamine oxidase inhibitors (MAOIs) due to its potential MAOI activity 62.

DISCUSSION: The interaction between herbal medicines and pharmaceuticals is a complex issue involving both pharmacokinetic and pharmacodynamic mechanisms. Pharmacokinetic interactions often result from the modulation of drug-metabolizing enzymes and transporters by herbal constituents. For example, St. John's Wort is a potent inducer of CYP3A4, leading to increased metabolism and reduced plasma concentrations of co-administered drugs such as cyclosporine and oral contraceptives, thus compromising their efficacy 4, 59. Similarly, the inhibition of CYP3A4 by certain herbal constituents can lead to increased drug levels and potential toxicity 6.

Pharmacodynamic interactions occur when herbal medicines and pharmaceuticals exert additive, synergistic or antagonistic effects on the same physiological pathways. For instance, the concurrent use of Ginkgo biloba with anticoagulants can result in excessive anticoagulation and increased bleeding risk due to the combined effects on platelet aggregation and blood clotting 5, 60. Conversely, herbs like Ginseng, which have hypoglycemic effects, can potentiate the action of antidiabetic drugs, increasing the risk of hypoglycemia 61, 62.

Understanding these interactions is crucial for healthcare providers to manage and mitigate potential risks. Patients should be encouraged to disclose their use of herbal medicines to their healthcare providers to ensure safe and effective management of their overall treatment regimen. Healthcare providers should be well-informed about common herb-drug interactions and consider these interactions when prescribing medications or recommending herbal supplements 3, 8.

CONCLUSION: This systematic review highlights the importance of recognizing potential herb-drug interactions in clinical practice. The concurrent use of traditional herbal medicines and modern pharmaceuticals can lead to significant pharmacokinetic and pharmacodynamic interactions, affecting the safety and efficacy of treatments. Healthcare providers should be vigilant in monitoring for these interactions and adjusting treatment regimens accordingly to ensure patient safety. Further research is needed to better understand these interactions and develop comprehensive guidelines for the safe use of herbal medicines alongside conventional drugs.

ACKNOWLEDGEMENT: None

CONFLICT OF INTEREST: None

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    How to cite this article:

    Kakasaniya GG, Khakhkhar TM and Hirapara RK: Systematic review: pharmacological interactions between traditional herbal medicines and modern pharmaceuticals. Int J Pharm Sci & Res 2025; 16(8): 2163-70. doi: 10.13040/IJPSR.0975-8232.16(8).2163-70.

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IJPSR

Gaurav G. Kakasaniya *, Tejas M. Khakhkhar and Ridhdhi K. Hirapara

Department of Pharmacology, C. U. Shah Medical College & Hospital, Surendranagar, Gujarat, India.

gauravkakasaniya45@mail.com

03 February 2025

25 February 2025

27 February 2025

10.13040/IJPSR.0975-8232.16(8).2163-70

01 August 2025

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