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Fulltext Subacute oral toxicity study of ethanolic leaves extracts of Strobilanthes crispus in rats

Lim KT, Lim V, Chin JH

Asian Pac J Trop Biomed, 2012 Dec;2(12):948-52.
PMID: 23593574 DOI: 10.1016/S2221-1691(13)60005-2

To examine the oral toxicity of repeated dosing of Strobilanthes crispus (S. crispus) ethanol leaves extract on the liver and kidney functions in Sprague Dawley rats.
Fulltext Safety and Efficacy of Dietary Epigallocatechin Gallate Supplementation in Attenuating Hypertension via Its Modulatory Activities on the Intrarenal Renin-Angiotensin System in Spontaneously Hypertensive Rats

Parn KW, Ling WC, Chin JH, Lee SK

Nutrients, 2022 Nov 01;14(21).
PMID: 36364864 DOI: 10.3390/nu14214605

This study aimed to identify the no-observed-adverse-effect level (NOAEL) of dietary epigallocatechin gallate (EGCG) supplementation and its possible antihypertensive and nutrigenomics effects in modulating intrarenal renin-angiotensin system (RAS) gene expression in spontaneously hypertensive rats (SHR). EGCG (50, 250, 500 or 1000 mg/kg b.w. i.g., once daily) was administered to SHR for 28 days. All the SHR survived with no signs of systemic toxicity. Increased alanine aminotransferase (ALT), aspartate aminotransferase (AST) and thiobarbituric acid reactive substances (TBARS) were evident in SHR supplemented with 500 and 1000 mg/kg b.w. but not in those supplemented with lower doses of EGCG. Subsequently, the NOAEL of EGCG was established at 250 mg/kg b.w., and the same protocol was replicated to assess its effects on blood pressure and renal RAS-related genes in SHR. The systolic blood pressure (SBP) of the EGCG group was consistently lower than the control group. The mRNA levels of cortical Agtr2 and Ace2 and medullary Agtr2, Ace and Mas1 were upregulated while medullary Ren was downregulated in EGCG group. Statistical analysis showed that SBP reduction was associated with the changes in medullary Agtr2, Ace, and Ren. Dietary EGCG supplementation exhibits antihypertensive and nutrigenomics effects through activation of intrarenal Ace and Agtr2 and suppression of Ren mediators, while a high dose of EGCG induced liver damage in SHR. In future clinical studies, liver damage biomarkers should be closely monitored to further establish the safety of the long-term use of EGCG.
UHPLC-MS/MS standardized extract of Vernonia amygdalina leaf inhibits CYP2C9 and CYP3A4 activities in hepatic cells of control and streptozotocin-induced diabetic rats

Sabbagh BA, Palanirajan VK, Chew YL, Chin JH, Ahmad M, Akowuah GA

Drug Metab Pers Ther, 2024 Dec 01;39(4):231-241.
PMID: 39658558 DOI: 10.1515/dmpt-2024-0005

OBJECTIVES: Vernonia amygdalina Del. is a perennial tropical shrub from Asteraceae. The fresh leaf of V. amygdalina is consumed as a vegetable due to its medicinal and nutritional properties. The present study focused on the quantification of bioactive compounds, luteolin-7-O-glucoside, luteolin-7-O-glucuronide, and 1,5-O-dicaffeoylquinic acid from aqueous leaf extract of V. amygdalina. The study also aims to investigate the effects of the aqueous leaf extract of V. amygdalina on cytochrome P450 2C9 (CYP2C9), and cytochrome P450 3A4 (CYP3A4) in hepatic cells of control and diabetic rats.
METHODS: The quantification of the bioactive compounds was conducted using ultra-high-performance liquid chromatography multiple reactions monitoring tandem mass spectrometry (UHPLC-MS/MS-MRM) technique. The effect of the extract on CYP2C9 and CYP3A4 activities was determined using a fluorometric screening kit according to the manufacturer's instructions.
RESULTS: The three bioactive compounds were detected and quantified in the aqueous leaf extract. Results showed that the content of luteolin-7-O-glucuronide (47 μg/mg) was the highest followed by luteolin-7-O-glucoside (3.5 μg/mg) and 1,5-O-dicaffeoylquinic acid (1.07 μg/mg). The extract showed an inhibitory effect on CYP3A4 and CYP2C9 enzyme activities in control and diabetic rats.
CONCLUSIONS: The UHPLC-MS/MS-MRM method is sensitive and reliable for the quality control of V. amygdalina leaf extract. The inhibitory effect of the extract suggests that concomitant use of V. amygdalina leaf preparations with conventional drugs metabolized and eliminated from the body by CYP3A4 and CYP2C9 enzymes may lead to possible interaction.

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