What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism

Yu, Ziwei; Chen, Ziqiang; Li, Qijuan; Yang, Ke; Huang, Zecheng; Wang, Wenjun; Zhao, Siyu; Hu, Huiling

doi:10.1080/03602532.2020.1853151

Cited by 14 publications

(12 citation statements)

References 124 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The metabolism of Hac and DHac shows similarities with that of other STLs, e.g., alantolactone, isoalantolactone, costunolide and dehydrocostus lactone [36,37]. In a review on the pharmacokinetics of different STLs, phase I and phase II metabolism of STLs were described to be extensive, which agrees with our results [38]. For example, the phase The metabolism of Hac and DHac shows similarities with that of other STLs, e.g., alantolactone, isoalantolactone, costunolide and dehydrocostus lactone [36,37].…”

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 90%

“…For example, the phase The metabolism of Hac and DHac shows similarities with that of other STLs, e.g., alantolactone, isoalantolactone, costunolide and dehydrocostus lactone [36,37]. In a review on the pharmacokinetics of different STLs, phase I and phase II metabolism of STLs were described to be extensive, which agrees with our results [38]. For example, the phase I metabolic reactions hydroxylation, hydration and desaturation, as well as the phase II metabolic reactions GSH conjugation, Cys conjugation and methylation, were observed in our experiments and also in a pharmacokinetic study of costunolide and dehydrocostus lactone by Peng et al [36].…”

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 90%

“…Related to this, the exocyclic methylene group of the α,β-unsaturated lactone moiety of alantolactone and isoalantolactone was described to be their major metabolic target [37]. This Michael acceptor system was also highlighted as a major metabolism region in the above-mentioned review on the pharmacokinetics of different STLs [38]. Our results are consistent with this conclusion, because Michael acceptor systems are also the major metabolic targets in case of Hac and DHac.…”

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 88%

“…These experiments yielded 24 metabolites in total, including GSH mono-and di-conjugates (16,17,19,20,21,22), degradation products of the former (18, 26, 27, 32), water conjugates (33,34), a methylated water conjugate (35) and combinations thereof (23, 24, 25, 28, 29, 30, 31). Furthermore, hydroxides (36, 37), 1 water conjugated hydroxide (38) and 1 hydrogenated metabolite (39 = DHac) were formed. 23), methylated GSH-water conjugates (24, 25) and a Hac-GSH-CysGly conjugate (18) were detected.…”

Section: Combined Phase I and Phase Ii Metabolismmentioning

confidence: 99%

See 3 more Smart Citations

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

et al. 2022

View full text Add to dashboard Cite

Arnica tincture is a herbal medicinal preparation with anti-inflammatory activity which is used traditionally for the topical treatment of blunt injuries as well as rheumatic muscle and joint complaints. Its main bioactive constituents are sesquiterpene lactones (STLs) of the helenalin and 11α,13-dihydrohelenalin types. Besides the mentioned activity, the tincture and its isolated STLs have antileishmanial activity. In a recent in vivo study, a treatment with Arnica tincture cured cutaneous Leishmaniasis (CL) in a golden hamster model. CL is a neglected tropical disease affecting more than two million people every year, for which new treatments are urgently needed. In order to use Arnica tincture on open CL lesions of human patients, it is important to know how the constituents are metabolized. Therefore, in vitro metabolism experiments with liver microsomes of different species (rat, pig and human) were performed with the Arnica STLs helenalin acetate and 11α,13-dihydrohelenalin acetate. Phase I and phase II metabolism experiments were performed, as well as a combination of both. Glutathione conjugation plays a major role in the metabolism of these STLs, as could be expected based on previous reports on their reactivity. Besides glutathione conjugates, several other metabolites were formed, e.g., water conjugates and hydroxides. Our results show for the first time a detailed picture of the metabolism of Arnica STLs. The fast and extensive formation of glutathione conjugates makes it unlikely that low absorbed levels of these compounds, as expected after dermal absorption from Arnica tincture, which could be of toxicological concern.

show abstract

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 90%

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 90%

Section: Esi-ms Fragmentation Of Hac ([M+h]supporting

confidence: 88%

Section: Combined Phase I and Phase Ii Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

et al. 2022

View full text Add to dashboard Cite

show abstract

“…To sum up, the main factors causing unstable absorption of andrographolide include efflux transporters (P‐gp) and their own metabolic effects. α‐β‐ unsaturated lactone moiety has intense metabolic activity, which plays an important role in the phase I (oxidation, reduction, hydrolysis) mediated by CYP450s (mainly CYP3A4) and phase II (conjugation) metabolism mediated by uridine diphosphate glucuronyltransferase (UGT) (UGT1A3, UGT1A4, UGT2B4 and UGT2B7) (Yu et al, 2021). In future, drug metabolizing enzyme probe, cell pharmacokinetics, mass spectrometry‐based metabonomics and other innovative technologies will provide prodigious technical support for the in‐depth pharmacokinetic research of andrographolide.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

Zeng

Wei

Zhou

et al. 2021

Phytotherapy Research

View full text Add to dashboard Cite

Andrographis paniculata (Burm. f.) Wall. ex Nees, a renowned herb medicine in China, is broadly utilized in traditional Chinese medicine (TCM) for the treatment of cold and fever, sore throat, sore tongue, snake bite with its excellent functions of clearing heat and toxin, cooling blood and detumescence from times immemorial. Modern pharmacological research corroborates that andrographolide, the major ingredient in this traditional herb, is the fundamental material basis for its efficacy. As the main component of Andrographis paniculata (Burm. f.) Wall. ex Nees, andrographolide reveals numerous therapeutic actions, such as antiinflammatory, antioxidant, anticancer, antimicrobial, antihyperglycemic and so on. However, there are scarcely systematic summaries on the specific mechanism of disease treatment and pharmacokinetics. Moreover, it is also found that it possesses easily ignored security issues in clinical application, such as nephrotoxicity and reproductive toxicity. Thereby it should be kept a lookout over in clinical. Besides, the relationship between the efficacy and security issues of andrographolide should be investigated and evaluated scientifically. In this review, special emphasis is given to andrographolide, a multifunctional natural terpenoids, including its pharmacology, pharmacokinetics, toxicity and pharmaceutical researches. A brief overview of its clinical trials is also presented. This review intends to systematically and comprehensively summarize the current researches of andrographolide, which is of great significance for the development of andrographolide clinical products. Noteworthy, those un‐cracked issues such as specific pharmacological mechanisms, security issues, as well as the bottleneck in clinical transformation, which detailed exploration and excavation are still not to be ignored before achieving integration into clinical practice. In addition, given that current extensive clinical data do not have sufficient rigor and documented details, more high‐quality investigations in this field are needed to validate the efficacy and/or safety of many herbal products.

show abstract

An improved strategy for identification and annotation of easily in‐sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example

Ding

Zhang

et al. 2023

Rapid Comm Mass Spectrometry

View full text Add to dashboard Cite

Rationale: Diterpene lactones (DL) in Andrographis paniculata (AP) are known as "natural antibiotics" for their excellent antibacterial activity. During mass spectrometry (MS) analysis, the hydroxyl groups in the AP DL skeleton are prone to neutral loss of H 2 O, producing high in-source fragment peaks and affecting the characterization of these components.Methods: Mass tags were applied during the MS data acquisition step, and special adduct ion form was used to guide the data processing and characterization steps.Besides, the total number of characterized AP DLs significantly increased when combining the number of neutrally lost H 2 O from AP DLs, incorporating information on the diagnostic ions, and adopting molecular networks generated with the Global Natural Products Social Molecular Networking database.Results: Ninety-nine DLs, comprising 6 monohydroxyl groups, 20 dihydroxyl groups, 27 trihydroxy groups, and 46 DLs with more than 3 hydroxyl groups, were characterized from AP. In addition, based on the characteristic fragments in the product ions (C 3 H 4 , Δm/z = 40.03 Da), it could be assumed that 90 DLs had the C19-OH structure among the identified DLs. The current study provides a new approach for collecting, processing, and characterizing MS analysis of natural DLs prone to in-source fragmentation.Conclusions: MS characterization of AP DLs was significantly improved, and many potential new compounds were identified in AP. This characterization provides new methods for the purification and identification of AP DLs.

show abstract

What dominates the changeable pharmacokinetics of natural sesquiterpene lactones and diterpene lactones: a review focusing on absorption and metabolism

Cited by 14 publications

References 124 publications

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

In Vitro Metabolism of Helenalin Acetate and 11α,13-Dihydrohelenalin Acetate: Natural Sesquiterpene Lactones from Arnica

Andrographolide: A review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches

An improved strategy for identification and annotation of easily in‐sourced dissociation diterpene lactones from plant natural products: Taking Andrographis paniculata (Burm. f.) as an example

Contact Info

Product

Resources

About