Pharmacokinetic study of phyllanthin and hypophyllanthin after oral administration to rats

Abstract

Objective: The present study was carried out to develop a sensitive and cost effective HPLC method for the determination of bioactive lignans (phyllanthin and hypophyllanthin) and its application in a pharmacokinetic study. Methods: Identification of lignan compounds on C-18 column was monitored at a range of 199-400nm using photodiode array detector (PDA) with methanol-water (66:34, v/v) as mobile phase at a flow rate of 1ml/min. Carbamazepine was used as internal standard. Results: From the developed method LOD and LOQ values were found to be 56.14ng/ml and 169.99ng/ml for phyllanthin, and 56.04ng/ml and 169.82ng/ml for hypophyllanthin. The validated RP-HPLC method herein was applied for pharmacokinetic studies and C max (ng/ml) values for administered three oral doses (2.5, 5 and 10mg/kg) of phyllanthin and hypophyllanthin were 0.28±0.06, 0.53±0.16, 0.98±0.22 and 0.68±0.76, 1.35±0.23, 2.45±0.33, respectively. Conclusion: In conclusion, developed HPLC-PDA method effectively determined the phyllanthin and hypophyllanthin in various solvent and plasma samples. This method was successfully applied in conducting their oral pharmacokinetic studies.

A New LC/MS/MS Method for the Analysis of Phyllanthin in Rat Plasma and its Application on Comparative Bioavailability of Phyllanthin in Different Formulations after Oral Administration in Rats

“…In our method, the LLOQ was only 0.5 ng/ mL, compare with HPLC-FD method, 10 the LOQ was 4.88 ng/mL, our method was almost 10 times more sensitive than this HPLC-FD method. In the report of Madhukiran et al 11 , the LOQ of phyllanthin was up to 169.99 ng/mL wih the use of HPLC-PDA, our method demonstrated up to 340 times more sensistive than HPLC-PDA method.…”

“…6 Furthermore, phyllanthin is known to possess immunomodulatory 7 , nephroprotective 8 , and anticancer 9 properties. Pharmacokinetic study of phyllanthin after oral administration to rats showed that phyllathin can be absorbable via GI tract 10,11 , however, the bioavailability of phyllanthin was only 0.62% in rat 12 . Because the content of phyllanthin in herb or herb extract is very low, and this herbal drug was used as a total extract, not a single pure compound of phyllanthin, it is important to quantitate such a low level of phyllanthin in the blood.…”

“…Because the content of phyllanthin in herb or herb extract is very low, and this herbal drug was used as a total extract, not a single pure compound of phyllanthin, it is important to quantitate such a low level of phyllanthin in the blood. There are several methods for the quatitative analysis of phyllanthin from rat plasma such as HPLC-fluorescence detection 10,12 , HPLC with PDA detection method 11,12 , and however, these methods Long, et al: A New LC/MS/MS Method for the Analysis of Phyllanthin in Rat Plasma and its Application on Comparative Bioavailability of Phyllanthin in Different Formulations after Oral Administration in Rats showed high LOQ and the analysis time is long (up to 30 minutes). 10,11 In our study, we try to develop a new, simple and rapid LC/MS/MS method for the analysis of phyllanthin in rat plasma and reduce the LOQ of phyllanthin to detect even trace level of phyllanthin in rat plasma.…”

Pharmacological activities and mechanisms of action of hypophyllanthin: A review

“…Van Thanh et al (2014Thanh et al ( ) et al, 2013Parvathaneni et al, 2014b;Van Thanh et al, 2014), hepatoprotective (Syamasundar et al, 1985;Harish and Shivanandappa, 2006;Rajkapoor et al, 2008;Taesotikul et al, 2011;Srirama et al, 2012;Subramanian et al, 2019;Wahyuni et al, 2019), anti-hyperuricemic (Murugaiyah and Chan, 2006), vascular tension (Hussain et al, 1995;Inchoo et al, 2011), estrogenic (Islam et al, 2008a) and anti-allergic activities (Abd Rani et al, 2021).…”

“…In vivo and in vitro studies on the pharmacological activities of hypophyllanthin include immunomodulation, anti-inflammatory, anticancer, hepatoprotective, anti-hyperuricemic, vascular tension, and anti-allergic activities. Figure 3 ; Tables 2 , 3 shows the various pharmacological activities of hypophyllanthin as a major component in the extracts of Phyllanthus species such as immunomodulation ( Jantan et al, 2014 ; Harikrishnan et al, 2018a ; Harikrishnan et al, 2018b ; Harikrishnan et al, 2018c ), anti-inflammatory ( Rachmilewitz et al, 1989 ; Mali et al, 2011 ; Kandhare et al, 2013 ; Chopade and Sayyad, 2015 ; Ilangkovan et al, 2015 ; Pradit et al, 2015 ; Wu et al, 2019 ), anticancer ( Somanabandhu et al, 1993 ; Islam et al, 2008b ; Sukhaphirom et al, 2013 ; Parvathaneni et al, 2014b ; Van Thanh et al, 2014 ), hepatoprotective ( Syamasundar et al, 1985 ; Harish and Shivanandappa, 2006 ; Rajkapoor et al, 2008 ; Taesotikul et al, 2011 ; Srirama et al, 2012 ; Subramanian et al, 2019 ; Wahyuni et al, 2019 ), anti-hyperuricemic ( Murugaiyah and Chan, 2006 ), vascular tension ( Hussain et al, 1995 ; Inchoo et al, 2011 ), estrogenic ( Islam et al, 2008a ) and anti-allergic activities ( Abd Rani et al, 2021 ).…”