In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica

Pan, Yan; Abd-Rashid, Badrul Amini; Ismail, Zakiah; Ismail, Rusli; Mak, Joon Wah; Pook, Peter C.K.; Er, Hui Meng; Ong, Chin Eng

doi:10.1016/j.jep.2010.05.002

Cited by 43 publications

(31 citation statements)

References 20 publications

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“…While a significant inhibition was observed for asiatic acid, C. asiatica ethanol, and dichloromethane extracts, implying involvement of semipolar constituents from C. asiatica in the effect. However, an inhibitory effect of asiatic acid on CYP was observed only when substrates for CYP isoforms are taken together with high asiatic acid content [84]. Interestingly, C. asiatica has no inhibitory effect on the activities of CYP450 isoforms at concentrations up to 1000 mg/kg/day [57].…”

Section: Discussionmentioning

confidence: 99%

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Duggina

Kalla

Varikasuvu³

et al. 2015

J Physiol Biochem

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This study was designed to investigate the protective effects of the centella triterpene saponins (EXT) on cyclophosphamide (CYP)-induced hepatotoxicity and immunosuppression in rats. The phytochemical profile of EXT was analyzed for centella saponins by using high-performance liquid chromatographic (HPLC). Therapeutic efficacy of EXT (250 mg/kg/day p.o) on hematological profile of blood, liver function markers, and cytokine profiles in CYP (10 mg/kg/day p.o)-treated rats. In addition, weights of immune organs (spleen and thymus) and histopathological changes in the liver, intestine, and spleen were also evaluated. The active principles in EXT were identified as madecassoside, asiaticoside, and asiatic acid by HPLC analysis. Upon administration of EXT, enhanced levels of glutamate pyruvate transaminase, alkaline phosphatase, and lipid peroxidation were found reduced while the levels of reduced glutathione and hematological parameters and relative weights of immune organs were restored to normal in CYP-treated rats. The hepatic mRNA level of TNF-α, which was increased during CYP administration, was significantly decreased by the EXT treatment. The decreased levels of mRNA expression of other cytokines like IFN-γ, IL-2, GM-CSF, after CYP treatment, were also found elevated upon administration of the EXT. Histopathological examination of the intestine, liver, and spleen indicated that the extract could attenuate the CYP-induced hepatic and immune organ damage. These results indicated that EXT modulated the immune and hepatic system function of rats against CYP-induced immunosuppression and hepatotoxicity by restoring the cytokine production, antioxidant system, and multiorgan injury. Thus, triterpene saponins may provide protective and/or therapeutic alternative against the immune-mediated liver diseases.

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Section: Discussionmentioning

confidence: 99%

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Duggina

Kalla

Varikasuvu³

et al. 2015

J Physiol Biochem

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“…The inhibition of CYP enzymes can result in clinical drug interactions whereby the systemic exposure to one drug that is cleared primarily via CYP-mediated biotransformation is elevated when coadministered with a second drug that inhibits this activity. Except for chemical drugs, natural products can also inhibit CYP enzymes (He and Edeki 2004;Pan et al 2010). Co-administration of herbal medicines and synthetic drugs was prevalent in the clinical regimens.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes

Guo

et al. 2011

Eur J Drug Metab Pharmacokinet

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Wogonin, derived from the root of Scutellaria baicalensis, is a popular herb for its anticancer, anti-inflammatory, neuroprotective and anti-convulsant effects. The purpose of this study was to investigate the effect of wogonin on human hepatic cytochrome P450s (CYP450s) in vitro. Isoform-specific substrate probes of CYP1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 were incubated in human liver microsomes with or without wogonin. IC(50) and K (i) values were estimated and the types of inhibition were determined. Wogonin was a potent, competitive inhibitor of CYP1A2 (K (i) = 0.24 μM), and a weak inhibitor of CYP2C19 (IC(50) = 101.10 μM), but was not able to inhibit CYP2C9, CYP2D6, CYP2E1 and CYP3A4 (IC(50) > 200 μM). Wogonin could inhibit the activity of CYP1A2 and CYP2C19 with varying potency, while it is a strong inhibitor of CYP1A2. These findings suggested that it was necessary to study the potential pharmacokinetic drug interaction in vivo.

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“…In an in vitro study, inhibition of CYP2C9, 2D6 and 3A4 were reported (Pan et al, 2010), but its clinical importance remains uncertain.…”

Section: Gotu Cola (Centella Asiatica)mentioning

confidence: 99%

Clinical applications of herbal medicines for anxiety and insomnia; targeting patients with bipolar disorder

Baek

Nierenberg

Kinrys

2014

Aust N Z J Psychiatry

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Objectives: Patients with bipolar disorder frequently continue to experience residual anxiety and insomnia between mood episodes. In real-world practice, patients increasingly self-prescribe alternative medicines. Methods:We reviewed case reports, open-label, and placebo-controlled trials investigating the use of herbal medicines to treat anxiety and insomnia, and discussed their potential applications for bipolar disorder.Results: Eleven herbal medicines that have been studied in human subjects are included in this review. Mechanisms of action, efficacy, side effects, and drug-drug interactions are discussed. Based on currently available evidence, valerian seems to be the most promising candidate for insomnia and anxiety in bipolar disorder. Conclusions:Adjunctive herbal medicines may have the potential to alleviate these symptoms and improve the outcomes of standard treatment, despite limited evidence. Physicians need to have a more in-depth understanding of the evidence of benefits, risks, and drug interactions of alternative treatments.

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In vitro modulatory effects on three major human cytochrome P450 enzymes by multiple active constituents and extracts of Centella asiatica

Cited by 43 publications

References 20 publications

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: its possible mechanisms of action

Inhibitory effects of wogonin on catalytic activity of cytochrome P450 enzyme in human liver microsomes

Clinical applications of herbal medicines for anxiety and insomnia; targeting patients with bipolar disorder

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