Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism

Zhang, Feng; Huang, Jinkun; He, Rong-Jing; Wang, Lu; Huo, Pengchao; Guan, Xiao-Qing; Fang, Sheng-Quan; Xiang, Yan-Wei; Jia, Shou-Ning; Ge, Guang-Bo

doi:10.1016/j.phymed.2020.153287

Cited by 32 publications

(21 citation statements)

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“…Herbs can interact significantly with chemical drug treatments via cytochrome P450 (CYP450) isoforms. 22,23 It is known that BBR is metabolized to 6-and 1′-hydroxy BBR by hepatic cytochrome P450 (CYP) 2C9 and CYP3A4, respectively. 24 1′-Hydroxy BBR is further metabolized to reactive intermediates and a series of glutathione adducts in human and mouse liver microsomes via formation of 1′,6-dihydorxy BBR, which is responsible for BBR-induced hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Efficacy and Reduced Hepatotoxicity by Combination of Gnaphalium affine Extract and Benzbromarone in the Treatment of Rats with Hyperuricemic Nephropathy

Liu

Yang

et al. 2021

Pharmaceutical Fronts

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Simultaneous oral intake of herbal medicine with chemical drugs may result in beneficial pharmacodynamic efficacy, including additive and synergistic effects with reduced toxicity. Gnaphalium affine D. Don (GAD) is a traditional Chinese Medicine that has been used for the management of hyperuricemia and gout. Benzbromarone (BBR) is one of the first-line drugs used for urate-lowering therapy in China but is toxic to the liver. The present study aimed to determine the effects of GAD and BBR, both alone and in co-treatment (with dosing interval of 1 hour), on chronic hyperuricemic nephropathy (HN) and hepatotoxicity in rats. Our data indicated that GAD significantly inhibited the elevation of serum uric acid, blood urea nitrogen, and creatinine levels in chronic HN rats at doses of 450 and 900 mg/kg/day. The rise in serum alanine aminotransferase and aspartate aminotransferase in BBR (or vehicle)-treated HN rats was significantly reduced by pre- (or post)-administration of GAD (450 mg/kg/day). The q-value >1.15 (by Jin method) indicated synergistic effects of co-treatments of BBR (50 mg/kg) with GAD (450 mg/kg). The synergistic beneficial effects were validated by comparison of BBR alone at a dose of clinical usage (4.5 mg/kg/day, in two divided doses) and BBR + GAD at half dose plus half dose (2.25 + 225 mg/kg/day) or half dose plus full dose (2.25 + 450 mg/kg/day). In conclusion, co-treatment with GAD and BBR holds promise for the management of hyperuricemia and gout.

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Section: Discussionmentioning

confidence: 99%

Enhanced Efficacy and Reduced Hepatotoxicity by Combination of Gnaphalium affine Extract and Benzbromarone in the Treatment of Rats with Hyperuricemic Nephropathy

Liu

Yang

et al. 2021

Pharmaceutical Fronts

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“…In addition, it also has assorted pharmacological effects, e.g., antibacterial (Wang et al, 2010;, insecticidal (Imam, 2013), antidepressant (Min et al, 2018), inhibiting abnormal excitation of uterine smooth muscle (Wang et al, 2014), anti-prostate cancer cells (Atmaca et al, 2020), promoting wound healing (Ocsel et al, 2012) and hepatoprotective (Suzek et al, 2016), which will not be discussed in this article. (Wang et al, 2012b;Gurbuz et al, 2013;Peng et al, 2013) Carvone (Wang et al, 2012b;Peng et al, 2012;Peng et al, 2013) (-)-α-Terpineol Gurbuz et al ( 2013) Terpinen-4-ol (Peng et al, 2012;Gurbuz et al, 2013) Linalool oxide (Furanoid) (Wang et al, 2012b;Gurbuz et al, 2013;Peng et al, 2013) α-Pinene (Wang et al, 2012b;Peng et al, 2012;Gurbuz et al, 2013;Peng et al, 2013;Park 2014) β-pinene (Wang et al, 2012b;Peng et al, 2012;Gurbuz et al, 2013; Huang et al, 2019) Pentacyclic triterpenoids Oleanic acid Wang et al, 2020b;Wang et al, 2020c;Zhang et al, 2020) Oleanonic acid Wang et al, 2020b;Wang et al, 2020c;Zhang et al, 2020) Betulinic acid (Wang et al, 2020b;Wang et al, 2020c;Zhang et al, 2020) Corosolic acid (Wang et al, 2020b;Wang et al, 2020c;…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Storax, A Promising Botanical Medicine for Treating Cardio-Cerebrovascular Diseases: A Review

Yuan

et al. 2021

Front. Pharmacol.

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In recent years, the incidence and mortality of cardio-cerebrovascular diseases have been increasing year by year, which has become global burden and challenge. Based on the holistic thinking of “brain disease affects the heart” and “heart disease affects the brain,” as well as the characteristics of multi-target and multi-path effects of Chinese medicine, Chinese medicine is more advantageous in the treatment of cardio-cerebrovascular diseases. As a botanical medicine, storax is known for its resuscitation, filth avoidance and pain-relieving effects in the treatment of cardio-cerebrovascular diseases. By reviewing and collating the relevant domestic and international literature in the past 10 years, we have sorted out an overview of the medicinal parts, traditional uses and chemical composition of storax. For the first time, based on the idea of “cerebral and cardiac simultaneous treatment,” the pharmacological activities and mechanisms of heart and brain protection of storax for treating cardio-cerebrovascular diseases were summarized and analyzed, showing that storax has the pharmacological effects of anti-cerebral ischemia, regulation of blood-brain barrier, bidirectional regulation of the central nervous system, anti-myocardial ischemia, anti-arrhythmia, anti-thrombosis and anti-platelet aggregation. It mainly exerts its protective effects on the brain and heart through mechanisms such as inhibition of inflammatory immune factors, anti-oxidative stress, anti-apoptosis, pro-neovascularization and regulation of NO release. On the basis of the current findings and limitations, the future research strategies and perspectives of storax are proposed, with a view to providing a reference for further application and development of this medicine, as well as contributing new thoughts and visions for the clinical application of “treating brain-heart synchronously”.

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“…P450 inhibition assays were carried out in 200 μL reaction mixtures, which included phosphate-buffered saline (PBS, 100 mM, pH 7.4), each substrate for a target P450, NADPH-generating system (10 mM of G-6-P, 1.0 unit/mL of G-6-PDH, 1.0 mM of β-NADP + , 4.0 mM of MgCl 2 ), HLMs or RLMs, along with HEJG, or each herbal extract or some major constituents in these herbs [ 32 , 33 ]. Notably, Herba Schizonepetae oil is a key material for preparing Jingyin granules, while water extracts of other individual herbs were used for preparing Jingyin granules.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of drug-metabolizing enzymes by Jingyin granules: implications of herb–drug interactions in antiviral therapy

et al. 2021

Self Cite

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Jingyin granules, a marketed antiviral herbal medicine, have been recommended for treating H1N1 influenza A virus infection and Coronavirus disease 2019 (COVID-19) in China. To fight viral diseases in a more efficient way, Jingyin granules are frequently co-administered in clinical settings with a variety of therapeutic agents, including antiviral drugs, anti-inflammatory drugs, and other Western medicines. However, it is unclear whether Jingyin granules modulate the pharmacokinetics of Western drugs or trigger clinically significant herb–drug interactions. This study aims to assess the inhibitory potency of the herbal extract of Jingyin granules (HEJG) against human drug-metabolizing enzymes and to clarify whether HEJG can modulate the pharmacokinetic profiles of Western drug(s) in vivo. The results clearly demonstrated that HEJG dose-dependently inhibited human CES1A, CES2A, CYPs1A, 2A6, 2C8, 2C9, 2D6, and 2E1; this herbal medicine also time- and NADPH-dependently inhibited human CYP2C19 and CYP3A. In vivo tests showed that HEJG significantly increased the plasma exposure of lopinavir (a CYP3A-substrate drug) by 2.43-fold and strongly prolonged its half-life by 1.91-fold when HEJG (3 g/kg) was co-administered with lopinavir to rats. Further investigation revealed licochalcone A, licochalcone B, licochalcone C and echinatin in Radix Glycyrrhizae , as well as quercetin and kaempferol in Folium Llicis Purpureae , to be time-dependent CYP3A inhibitors. Collectively, our findings reveal that HEJG modulates the pharmacokinetics of CYP substrate-drug(s) by inactivating CYP3A, providing key information for both clinicians and patients to use herb–drug combinations for antiviral therapy in a scientific and reasonable way.

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Herb-drug interaction between Styrax and warfarin: Molecular basis and mechanism

Cited by 32 publications

References 50 publications

Enhanced Efficacy and Reduced Hepatotoxicity by Combination of Gnaphalium affine Extract and Benzbromarone in the Treatment of Rats with Hyperuricemic Nephropathy

Enhanced Efficacy and Reduced Hepatotoxicity by Combination of Gnaphalium affine Extract and Benzbromarone in the Treatment of Rats with Hyperuricemic Nephropathy

Storax, A Promising Botanical Medicine for Treating Cardio-Cerebrovascular Diseases: A Review

Inhibition of drug-metabolizing enzymes by Jingyin granules: implications of herb–drug interactions in antiviral therapy

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