How Valerian and Kava Extracts Affect Liver Enzymes and Protein Transporters

Jenn Hoskins
17th July, 2024

How Valerian and Kava Extracts Affect Liver Enzymes and Protein Transporters

This study demonstrates that herbal extracts from valerian (Valeriana officinalis) (left) and kava-kava (Piper methysticum) (right) can significantly increase the plasma concentration of conventional drugs by inhibiting their metabolism in the intestine.

Composite: Natural Science News / CC BY. [Sources]
Adapted from photos by:

Key Findings

  • Researchers at Universidade Federal de São João del-Rei found that valerian and kava-kava significantly increase the plasma concentration of the sedative midazolam when taken orally
  • The study showed that valerian and kava-kava inhibit the intestinal metabolism of midazolam, leading to higher drug levels in the blood without affecting its half-life
  • Kava-kava also increased the uptake of the drug fexofenadine in cells, suggesting it may affect drug transport mechanisms, unlike valerian
The recent study conducted by researchers at Universidade Federal de São João del-Rei investigated the interactions between traditional herbal medicines, specifically Valeriana officinalis (valerian) and Piper methysticum (kava-kava), and conventional drugs[1]. This research is pertinent given the increasing use of complementary and alternative medicine (CAM) in treating anxiety and other disorders[2][3]. The study aimed to understand how these herbal medicines affect the metabolism and efficacy of conventional drugs, using midazolam—a common sedative—as a test case. The researchers used male Wistar rats to explore the pharmacokinetic interactions between the herbal extracts and midazolam. They utilized High-Performance Liquid Chromatography (HPLC) to characterize the phytomedicines, ensuring precise measurement of their active components: valerenic acid in valerian and kavain in kava-kava. The study administered these herbal extracts orally, both alone and in combination with midazolam, to observe any changes in drug metabolism. The results were significant. When midazolam was administered orally, the presence of valerian and kava-kava extracts increased its maximum plasma concentration (Cmax) by 2- and 4-fold, respectively, compared to the control group. Additionally, the area under the plasma concentration versus time curve (AUC(0-∞)) was markedly enhanced—from 994.3 ± 152.3 ng.h/mL in the control group to 3041 ± 398 ng.h/mL with valerian and 4139 ± 373 ng.h/mL with kava-kava. Interestingly, these changes did not affect the half-life of midazolam, suggesting that the alterations were due to the inhibition of midazolam metabolism in the intestines rather than systemic changes. To further distinguish between presystemic (intestinal) and systemic effects, midazolam was also administered intravenously. The pharmacokinetics of midazolam remained unchanged with intravenous administration, confirming that the herbal extracts primarily inhibited intestinal metabolism. The study also examined the effects of these herbal extracts on the uptake of fexofenadine, a P-gp substrate, by Caco-2 cells. Kava-kava significantly increased the uptake of fexofenadine by 3.5-fold compared to the control, while valerian's effect was not statistically significant. This suggests that kava-kava might affect drug transport mechanisms, specifically P-glycoprotein (P-gp), which plays a role in drug absorption and distribution. These findings have important implications for the use of herbal medicines alongside conventional drugs. The inhibition of intestinal metabolism by valerian and kava-kava could lead to higher plasma levels of certain medications, potentially enhancing their effects or increasing the risk of side effects. This interaction is particularly relevant for patients using CAM for anxiety disorders, as highlighted in previous studies[2][3][4]. For example, kava-kava has been shown to be effective in reducing anxiety symptoms but carries warnings of hepatotoxicity[4]. Moreover, the study underscores the need for careful consideration of herbal and conventional drug interactions in clinical settings. Integrating traditional botanical products into primary healthcare requires a nuanced understanding of their pharmacological and toxicological profiles[5]. This research contributes to that understanding by providing concrete data on how valerian and kava-kava interact with conventional drugs. In summary, the study by the Universidade Federal de São João del-Rei provides valuable insights into the interactions between traditional herbal medicines and conventional drugs. By demonstrating that valerian and kava-kava can significantly alter the metabolism of midazolam, the research highlights the importance of monitoring and managing such interactions in clinical practice. This knowledge is crucial for developing integrative healthcare models that safely and effectively incorporate both conventional and complementary treatments.

MedicineBiochemPlant Science

References

Main Study

1) Evaluation of the Effects of Extracts Containing Valeriana officinalis and Piper methysticum on the Activities of Cytochrome P450 3A and P-Glycoprotein.

Published 16th July, 2024

https://doi.org/10.1055/a-2360-4808

Related Studies

2) Use of complementary and alternative medicine in a large sample of anxiety patients.

https://doi.org/10.1016/j.psym.2011.11.009

3) Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence.

https://doi.org/10.1007/s40263-013-0059-9

4) The effectiveness and safety of Kava Kava for treating anxiety symptoms: A systematic review and analysis of randomized clinical trials.

https://doi.org/10.1016/j.ctcp.2018.09.003

5) Traditional Herbal Medicine in Mesoamerica: Toward Its Evidence Base for Improving Universal Health Coverage.

https://doi.org/10.3389/fphar.2020.01160


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