Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: Implication of herb-drug interactions in COVID-19 pharmacotherapy

Zhang, Feng; Huang, Jinkun; Liu, Wei; Wang, Chao-Ran; Liu, Yanfang; Tu, Dong-Zhu; Liang, Xinmiao; Yang, Ling; Zhang, Weidong; Chen, Hongzhuan; Ge, Guang-Bo

doi:10.1016/j.fct.2021.111998

Cited by 38 publications

(32 citation statements)

References 42 publications

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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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“…Generally speaking, quality and safety standards of TCM formulas appear to be variable, thus limiting widespread acceptance outside China [187] . Finally, specific TCM formulas such as Qingfei Paidu decoction could significantly modulate the pharmacokinetics of CYP3A substrate-drugs via inhibition of CYP3A, which on one hand may be exploited to boost immunomodulating agents but raises the issue of potential clinically relevant drug interactions when using traditional preparations with uncertain potential to interfere with drugs used in COVID-19 treatment [188] .…”

Section: Traditional Chinese Medicine and Covid-19mentioning

confidence: 99%

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity

Spini

Giudice

Brancaleone

et al. 2021

Pharmacological Research

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Making gender bias visible allows to fill the gaps in knowledge and understand health records and risks of women and men. The coronavirus disease 2019 (COVID-19) pandemic has shown a clear gender difference in health outcomes. The more severe symptoms and higher mortality in men as compared to women are likely due to sex and age differences in immune responses. Age-associated decline in sex steroid hormone levels may mediate proinflammatory reactions in older adults, thereby increasing their risk of adverse outcomes, whereas sex hormones and/or sex hormone receptor modulators may attenuate the inflammatory response and provide benefit to COVID-19 patients. While multiple pharmacological options including anticoagulants, glucocorticoids, antivirals, anti-inflammatory agents and traditional Chinese medicine preparations have been tested to treat COVID-19 patients with varied levels of evidence in terms of efficacy and safety, information on sex-targeted treatment strategies is currently limited. Women may have more benefit from COVID-19 vaccines than men, despite the occurrence of more frequent adverse effects, and long-term safety data with newly developed vectors are eagerly awaited. The prevalent inclusion of men in randomised clinical trials (RCTs) with subsequent extrapolation of results to women needs to be addressed, as reinforcing sex-neutral claims into COVID-19 research may insidiously lead to increased inequities in health care. The huge worldwide effort with over 3,000 ongoing RCTs of pharmacological agents should focus on improving knowledge on sex, gender and age as pillars of individual variation in drug responses and enforce appropriateness.

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“…In vivo experiments showed (Zhang et al, 2021) that Qingfei Paidu decoction can affect the pharmacokinetics of CYP3A substrate drugs through the inactivation of CYP3A, which leads to the risk of disease treatment with CYP3A substrate drugs such as lopinavir.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review

Yang

Wang

et al. 2021

Front. Pharmacol.

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Coronavirus disease 2019 (COVID-19) is an emergent infectious pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and pathogenic. COVID-19 has rapidly swept across the world since it was first discovered in December 2019 and has drawn significant attention worldwide. During the early stages of the outbreak in China, traditional Chinese medicines (TCMs) were involved in the whole treatment process. As an indispensable part of TCM, Chinese patent medicines (CPMs) played an irreplaceable role in the prevention and treatment of this epidemic. Their use has achieved remarkable therapeutic efficacy during the period of medical observation and clinical treatment of mild, moderate, severe, and critical cases and during convalescence. In order to better propagate and make full use of the benefits of TCM in the treatment of COVID-19, this review will summarize the potential target of SARS-CoV-2 as well as the theoretical basis and clinical efficacy of recommended 22 CPMs by the National Health Commission and the Administration of TCM and local provinces or cities in the treatment of COVID-19. Additionally, the study will further analyze the drug composition, potential active ingredients, potential targets, regulated signaling pathways, and possible mechanisms for COVID-19 through anti-inflammatory and immunoregulation, antiviral, improve lung injury, antipyretic and organ protection to provide meaningful information about the clinical application of CPMs.

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Inhibition of drug-metabolizing enzymes by Qingfei Paidu decoction: Implication of herb-drug interactions in COVID-19 pharmacotherapy

Cited by 38 publications

References 42 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

Sex-tailored pharmacology and COVID-19: Next steps towards appropriateness and health equity

Potential Mechanisms of Action of Chinese Patent Medicines for COVID-19: A Review

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