Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers

Hongxian, Pang; Xue, Wei; Ai, Shi; Li, Min; Li, Yang; Cao, Guoying; Yan, Bin; Fan, Daiming; Xiao, Wei; He, Guo‐Wei; Du, Guanhua; Hu, Xin; Cheng, Gang

doi:10.1007/s40261-016-0418-7

Cited by 71 publications

(43 citation statements)

References 29 publications

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“…1). Importantly, two phase I clinical trials of baicalein in healthy Chinese adult volunteers have been completed (Li et al, 2014;Pang et al, 2016) and confirmed that baicalein is safe and well tolerated by healthy subjects. Thus, all of these properties indicate that the therapeutic implications of baicalein may prove successful in slowing or even halting further progression of CNS neurodegenerative diseases.…”

Section: Resultsmentioning

confidence: 88%

“…The accumulation index varied from 1.66 to 2.07 for baicalein and from 1.68 to 2.45 for baicalin. In conclusion, in dose range of 200-800 mg, multiple-dose oral baicalein administration was safe and well tolerated, dose proportionality was inconclusive, and no serious accumulation of baicalein was observed (Pang et al, 2016).…”

Section: Clinical Trials Of Baicaleinmentioning

confidence: 78%

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Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Zhao

Hölscher

2017

CNS Drugs

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Alzheimer's disease and Parkinson's disease are the two most common, progressive central neurodegenerative diseases affecting the population over the age of 60 years. Apart from treatments that temporarily improve symptoms, there is no medicine currently available to inhibit or reverse the progression of Alzheimer's disease and Parkinson's disease. In traditional Chinese medicine, the root of Scutellaria baicalensis Georgi is a classic compatible component in the decoction of herbal medicine used for treating central nervous system diseases. Modern pharmacokinetic studies have confirmed that baicalein (5,6,7-trihydroxyflavone) is a major bioactive flavone constituent root of S. baicalensis Georgi. Studies showed that baicalein possesses a range of key pharmacological properties, such as reducing oxidative stress, anti-inflammatory properties, inhibiting aggregation of disease-specific amyloid proteins, inhibiting excitotoxicity, stimulating neurogenesis and differentiation action, and anti-apoptosis effects. Based on these properties, baicalein shows therapeutic potential for Alzheimer's disease and Parkinson's disease. In this review, we summarize the pharmacological protective actions of baicalein that make it suitable for the treatment of Alzheimer's disease and Parkinson's disease, and discuss the potential mechanisms underlying the effects.

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Section: Resultsmentioning

confidence: 88%

Section: Clinical Trials Of Baicaleinmentioning

confidence: 78%

Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Zhao

Hölscher

2017

CNS Drugs

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“…This suggests baicalein to be considered as solid treatment tool for neurodegenerative diseases including PD. Importantly, baicalein is safe and sufficiently well tolerated by healthy volunteers as evidenced by two phase I clinical trials based on Chinese healthy adult volunteers [74,75]. Therefore, the abovementioned properties of baicalein indicate its potential therapeutic implications in slowing down/ halting the progression of PD.…”

Section: Resultsmentioning

confidence: 99%

“…In 2016, another study in Chinese subjects based on placebo-controlled, single-center, and double-blind parallel group investigated the pharmacokinetics, safety, and tolerability of baicalein following multiple-ascending-dose protocol [75]. Volunteers were randomly divided to get placebo treatment (n = 2 per dose regimen) or baicalein (n = 8 per dose regimen).…”

Section: Clinical Trials With Baicaleinmentioning

confidence: 99%

Therapeutic Potential of Baicalein in Parkinson’s Disease: Focus on Inhibition of α-Synuclein Oligomerization and Aggregation

Javed¹,

Ojha²

2020

Synucleins - Biochemistry and Role in Diseases

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Parkinson's disease (PD) is the most common neurodegenerative diseases, which affects the people in old age. The neuropathological symptoms of PD include the degeneration of dopaminergic neurons in the substantia nigra pars compacta, and presence of intracellular inclusions of α-synuclein (α-syn) aggregates. α-Syn, a natively unfolded protein, has been found to play a key role in PD pathology. Several mechanistic studies revealed the numerous aspects of α-syn fibrillation and aggregation process that lead to dopaminergic neurodegeneration in PD. Till to date, there is no complete cure of PD, but some therapeutic agents are able to halt the disease progression. Scutellaria baicalensis Georgi is a traditional Chinese medicine commonly used to treat the central nervous system diseases. Recently, it has been confirmed that root of S. baicalensis Georgi contains baicalein (5,6,7-trihydroxyflavone) as a major bioactive flavone constituent. Baicalein possess numerous pharmacological properties such as antiaggregation of amyloid proteins including α-syn, antioxidant, anti-inflammatory, and antiapoptotic. In the light of these properties, baicalein has potential therapeutic efficacy for PD. In this chapter, we explored the pharmacological protective actions of baicalein against α-syn fibrillation and aggregation that make it suitable for PD treatment and also discussed the possible mechanisms underlying the effects.

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“…Baicalein and oroxylin A (a methylated metabolite of baicalein in human body; Figure b; Zhang et al, ), active flavonoids extracted from the plant Scutellaria baicalensis Georgi radix, contain multiple hydroxyl and/or methoxyl substituents on their B‐rings (Figure b; Lu, Guo, & Zhao, ; Wang et al, ). Moreover, substantial biotransformation between baicalein or oroxylin A and their corresponding glycosides (baicalin and oroxylin A 7‐O‐β‐D‐glucuronide, respectively) was found in human body (Figure b; Pang et al, ; Zhang et al, ). These glycosides also contain the key structural features of inhibiting CYP1B1 (Figure b); however, their inhibitory effects have not been studied.…”

Section: Introductionmentioning

confidence: 99%

Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1‐mediated carcinogenic estradiol metabolite formation

Song

et al. 2019

Phytotherapy Research

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4-OHE2) from 17β-estradiol plays an important role in the progression of human breast cancer, while the biotransformation of 17β-estradiol to 2-hydroxyestradiol mediated by cytochrome P450 1A1 (CYP1A1) is considered as a less harmful pathway. In this study, inhibitory effects of flavonoids baicalein and oroxylin A, a metabolite of baicalein in human body, on CYP1A1 and 1B1 activities were investigated in vitro. The inhibition intensities of baicalein and oroxylin A towards CYP1B1 were greater than towards CYP1A1 with a mixed mechanism. In addition, oroxylin A showed a stronger inhibitory effect than baicalein towards the CYP1B1-mediated 17β-estradiol 4-hydroxylation, with the IC 50 values of 0.0146 and 2.27 μM, respectively. Docking studies elucidated that oroxylin A had a stronger binding affinity than baicalein for CYP1B1. In MCF-7 cells, compared with baicalein-treated groups, oroxylin A with lower doses decreased and increased the formation of 4-OHE2 and 2-hydroxyestradiol, respectively, with a preferential induction of mRNA of CYP1A1 over CYP1B1. In conclusion, this study demonstrated that oroxylin A showed a stronger inhibitory effect than baicalein on CYP1B1-mediated 4-OHE2 formation in MCF-7 cells, providing crucial implications for their possibly preventive/therapeutic potential against breast cancer via inhibition of CYP1B1, particularly of oroxylin A.

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Multiple-Ascending-Dose Pharmacokinetics and Safety Evaluation of Baicalein Chewable Tablets in Healthy Chinese Volunteers

Abstract: In dose range of 200-800 mg, multiple-dose oral baicalein administration was safe and well tolerated, dose proportionality was inconclusive, and no serious accumulation of baicalein was observed.

Cited by 71 publications

References 29 publications

Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Therapeutic Potential of Baicalein in Alzheimer’s Disease and Parkinson’s Disease

Therapeutic Potential of Baicalein in Parkinson’s Disease: Focus on Inhibition of α-Synuclein Oligomerization and Aggregation

Oroxylin A, a methylated metabolite of baicalein, exhibits a stronger inhibitory effect than baicalein on the CYP1B1‐mediated carcinogenic estradiol metabolite formation

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