Lactobacillus murinus Improved the Bioavailability of Orally Administered Glycyrrhizic Acid in Rats

Abstract

Intestinal microbiota has been extensively studied in the context of host health benefit, and it has recently become clear that the gut microbiota influences drug pharmacokinetics and correspondingly efficacy. Intestinal microbiota dysbiosis is closely related with liver cirrhosis, especially the depletion of Lactobacillus. Therefore, the bioavailability of orally administered glycyrrhizic acid (GL) was speculated to be influenced under a pathological state. In the present study, L. murinus was isolated and screened for GL bioconversion capacity in vitro. Compared with Lactobacillus rhamnosus and Lactobacillus acidophilus, L. murinus was chosen for further investigation because it has the highest biotransformation rate. Our results showed that L. murinus could significantly improve the translocation of GL on Caco-2 cell models. Meanwhile, L. murinus was observed to have the ability to bind with the surface of Caco-2 cells and prominently downregulate the transporter gene expression level of multidrug resistance gene 1 (MDR1) and multidrug resistance protein 2 (MRP2), which were involved in the efflux of drugs. Furthermore, L. murinus was selected to be orally administred into rats in healthy and liver cirrhosis groups by a daily gavage protocol. Our data highlighted that supplements of L. murinus significantly improved the bioavailability of orally administered GL in rats, especially under a pathological condition, which may provide a novel strategy for improving the clinical therapeutic effect of liver protective drugs.

Constituents, Pharmacokinetics, and Pharmacology of Gegen-Qinlian Decoction

“…ACAG protected against 2,4,6-trinitrobenzene sulfonic acid-induced colitis through anti-inflammatory and antioxidant effects (Xu B.-L. et al, 2015). However, the constituents in ACAG, such as puerarin (Li et al, 2014a), daidzin (Murota et al, 2002), baicalin (Wu et al, 2014), berberine (Liu et al, 2016), and glycyrrhizic acid (Yuan et al, 2020), have poor solubility, permeability, or metabolic stability; thus, improving their oral bioavailability is challenging.…”

The influence of the gut microbiota on the bioavailability of oral drugs

“…Yuan et al. 42 reported that Lactobacillus murinus could enhance the bioavailability of oral administered glycyrrhizic acid (GL) by significantly downregulating the efflux transporter gene expression level of multidrug resistance gene 1 ( MDR1 ) and multidrug resistance protein 2 (MRP2) in vitro . They also found that the supplements of L. murinus could prominently increase the bioavailability of GL in rats with liver cirrhosis, indicating a potential strategy for enhancing the efficacy of liver protective drugs in the clinical treatment.…”

“…In addition, it may also offer us many innovative ideas of the drug delivery system design, especially the design of colon-targeted drug delivery systems. Herein, we provide a review to document the recent discoveries of the possible interactions of the gut microbiota, host and oral drugs by which the bioavailability may be affected (as shown in Table 1 24 , 25 , 26 , 28 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ) and make suggestions for further research in this field.…”

Combined Nasal, Oropharyngeal Povidone Iodine Plus Glycyrrhizic Acid Sprays, Accelerate Clinical and Laboratory Recovery and Reduces Household Transmission of SARS-CoV-2: A Randomized Placebo-Controlled Clinical Trial

“…The environment created by tissue culture could mimic the nasal and oral mucosa to a great extent. For instance, oral glycyrrhizic acid is converted to glycyrrhetic acid (more toxic) by intestinal commensal bacteria, where glycyrrhizic acid itself becomes indetectable in the plasma ( 11 , 12 ).…”