Pharmacokinetics and Tissue Distribution of Coumarins from Tagetes lucida in an LPS-Induced Neuroinflammation Model

Abstract

Tagetes lucida has been widely used as a folk remedy in illnesses associated with the central nervous system and inflammatory ailments. Among the chemical compounds that stand out in the plant against these conditions are coumarins, such as 7-O-prenylscopoletin (PE), scoparone (SC), dimethylfraxetin (DF), herniarin (HR), and 7-O-prenylumbelliferone (PU), considered potential anti-neuroinflammatory compounds. Therefore, the relationship between the therapeutic effect and the dose can be evaluated through pharmacokinetic–pharmacodynamic (PK–PD) studies under a model of neuroinflammation induced by lipopolysaccharide (LPS). Nonetheless, accomplishing those studies requires an accurate and robust analytical method for the detection of these compounds in different biological matrices of interest. Due to the above, in the present study, a bioanalytical method was established by HPLC–DAD-UV for the simultaneous quantification of the coumarins present in the hexane extract of T. lucida, which was able to determine the temporal concentration profiles of each of the coumarins in the plasma, brain, kidney, and spleen samples of healthy and damaged mice. Coumarins showed an increase in plasma concentrations of up to three times in the neuroinflammation model, compared to healthy mice, so it was possible to quantify the therapeutic agents in the main target organ, the brain. The ability of compounds to cross the blood–brain barrier is an advantage in the treatment of diseases associated with neuroinflammation processes that can be studied in future PK–PD evaluations.

Dose-Effect Determination of a Neuroprotector Fraction Standardized in Coumarins of Tagetes lucida and Bioavailability

“…Finally, it was established that the standardized coumarin content in mg/g of extract was equal to previously reported, using the same HPLC parameters that were described in the mentioned work [ 21 ]. Briefly, a Waters 2695 separation equipment coupled to a UV-VIS detector (Waters 2696) was used to carry out a 30 min run with a gradient elution composed of an aqueous solution of trifluoroacetic acid at 0.5% and acetonitrile ( Table S1 ).…”

“…A hexanic extract from Tagetes lucida was obtained as described in our previous work [ 21 ]. Briefly, dry milled plant material collected in Xochitepec, Morelos, Mexico identified with the voucher No.…”

“…The aggregate was centrifuged at 14,000 rpm for 10 min and the organic layer was separated and filtered into new tubes to be brought to dryness. For HPLC-UV analysis, samples were resuspended in methanol and 10 µL of sample was injected into the system, as indicated in HPLC-DAD-UV handling conditions section by Santibáñez et al [ 21 ].…”

“…During the new herbal drug development, pharmacokinetic (PK) studies become essential to providing information on the prediction of the distribution, metabolism, and excretion of the chemical participants. As has been tested with the bioactive fraction obtained from the T. lucida hexanic extract, administered at a dose of 10 mg/kg, carried out in our previous study [ 21 ]. Nonetheless, it is important to establish the relationship between different doses and the exposure of the molecules at the site of action to evaluate the properties and therapeutic efficacy, through biological tests, that the herbal drug has at different concentrations to the binding target [ 22 , 23 , 24 ].…”

Nephroprotective Activity of Papaloquelite (Porophyllum ruderale) in Thioacetamide-Induced Injury Model

“…These phenolic acids and flavanols were identified by a direct comparison of the retention time of each peak, with the respective analytical standard and their contents shown in Table 3. Peaks of Rt at 8.42 and 11.058 min in the chromatogram were not identified; however, their UV light spectra showed absorption bands characteristic of caffeic acid derivatives and coumarins, respectively (Figure 7) [34,35].…”