Anti-inflammatory Effect of Mangosteen (Garcinia mangostana L.) Peel Extract and its Compounds in LPS-induced RAW264.7 Cells

Wahyu Widowati; Lusiana Darsono; Jo Suherman; Nurul Fauziah; Maesaroh Maesaroh; Pande Putu Erawijantari

doi:10.20307/nps.2016.22.3.147

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Widowati, Darsono, Suherman, Fauziah, Maesaroh, and Erawijantari: Anti-inflammatory Effect of Mangosteen (Garcinia mangostana L.) Peel Extract and its Compounds in LPS-induced RAW264.7 Cells

Original Article

Natural Product Sciences 2016;22(3):147-153.

Published online: 17 January 2016

DOI: https://doi.org/10.20307/nps.2016.22.3.147

Anti-inflammatory Effect of Mangosteen (Garcinia mangostana L.) Peel Extract and its Compounds in LPS-induced RAW264.7 Cells

Wahyu Widowati^1,^∗, Lusiana Darsono¹, Jo Suherman¹, Nurul Fauziah², Maesaroh Maesaroh², Pande Putu Erawijantari²

¹Medical Research Center, Faculty of Medicine, Maranatha Christian University, Bandung 40164, West Java, Indonesia

²Biomolecular and Biomedical Research Center, Aretha Medika Utama, Bandung 40163, West Java, Indonesia

^∗Author for correspondence Wahyu Widowati, Faculty of Medicine, Maranatha Christian University, Bandung 40164, Indonesia. Tel: +62-819-1004-0010; E-mail: wahyu_w60@yahoo.com

Received 0 August 2016 Revised 0 August 2016 Accepted 0 August 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Inflammation plays an important role in host defense against external stimuli such as infection by pathogen, endotoxin or chemical exposure by the production of the inflammatory mediators that produced by macrophage. Anti-inflammatory factor is important to treat the dangers of chronic inflammation associated with chronic disease. This research aims to analyze the anti-inflammatory effects of Garcinia mangostana L. peel extract (GMPE), α-mangostin, and γ-mangostin in LPS-induced murine macrophage cell line (RAW 264.7) by inhibiting the production of inflammatory mediators. The cytotoxic assay of G. mangostana L. extract, α-mangostin, and γ-mangostin were performed by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) to determine the safe and non-toxic concentration in RAW 264.7 for the further assay. The concentration of inflammatory mediators (COX-2, IL-6, and IL-1β) were measured by the ELISA-based assay and NO by the nitrate/nitrite colorimetric assay in treated LPS-induced RAW 264.7 cells. The inhibitory activity was determined by the reducing concentration of inflammatory mediators in treated LPS-induced RAW 264.7 over the untreated cells. This research revealed that GMPE, α-mangostin, and γ-mangostin possess the anti-inflammatory effect by reducing COX-2, IL-6, IL-1β, and NO production in LPS-induces RAW 264.7 cells.

Keywords: Anti-inflammatory, GMPE, α-Mangostin, γ-Mangostin, Macrophages, Inflammatory mediator

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Fig. 1.

Chemical structure of (a) α-mangostin and (b) γ-mangostin.

Table 1.

Effect of GMPE and mangostins in various concentrations toward RAW 264.7 cell viability

Samples	Viability (%)
Control	100.00±0.00^def
GMPE 100 µg/mL	557.36±2.67^a
GMPE 75 µg/mL	558.13±1.69^a
GMPE 50 µg/mL	548.86±12.81^b
GMPE 25 µg/mL	102.49±8.14^efg
GMPE 20 µg/mL	100.80±4.45^def
GMPE 10 µg/mL	115.23±16.03^fgh
GMPE 5 µg/mL	123.10±12.93^h
α-mangostin 100 µM	585.81±4.75^cd
α-mangostin 75 µM	598.50±6.36^de
α-mangostin 50 µM	112.76±8.86^efgh
α-mangostin 25 µM	116.95±9.43^gh
γ-mangostin 100 µM	583.30±11.55^c
γ-mangostin 75 µM	597.23±3.70^cde
γ-mangostin 50 µM	103.38±6.54^efg
γ-mangostin 25 µM	105.34±5.43^efg

The data are presented as mean ± standard deviation. Different superscript letters (^{a,b,c,cd,cde,de,def,efg,efgh,fgh,gh,h}) in the same column (the viability among concentrations of the samples) are significant at p < 0.05 based on Duncan's post-hoc comparisons (p <0.05). The experiment was conducted in triplicate

Table 2.

Effect various concentrations of GMPE and mangostins toward COX-2 concentration in RAW 264.7 cell

Samples	COX-2
Samples	COX-2 concentration (ng/mL)	COX-2 inhibitory activity (%)
Negative control	0.81±0.03^a	72.93±0.97^f
Positive control	2.98±0.170^g	50.11±5.72^a
GMPE 20 µg/mL	1.35±0.18^b	54.59±6.09^e
GMPE 10 µg/mL	2.02±0.12^de	32.21±3.87^cd
GMPE 5 µg/mL	2.16±0.07^ef	27.40±2.28^bc
α-mangostin 75 µM	1.43±0.08^b	52.13±2.61^e
α-mangostin 50 µM	1.75±0.12^c	41.16±4.00^d
α-mangostin 25 µM	2.06±0.05^de	30.87±1.78^bc
γ-mangostin 75 µM	1.89±0.03^cd	36.58±0.89^cd
γ-mangostin 50 µM	1.98±0.03^d	33.56±1.16^cd
γ-mangostin 25 µM	2.31±0.03^f	22.48±0.89^b

The data are presented as mean ± standard deviation. Different superscript letters (^{a,b,bc,c,cd,d,de,e,f}) in the same coloumn (among various concentrations of GMPE, mangostins in COX-2 concentrations and inhibitory activity) are significant at p < 0.05 based on Duncan's post-hoc comparisons (p < 0.05). The experiment was conducted in triplicate

Table 3.

Effect various concentrations of GMPE and mangostins toward IL-6 concentration in RAW 264.7 cell

Samples	IL-6
Samples	IL-6 concentration (pg/mL)	IL-6 inhibitory activity (%)
Negative control	176.57±5.14^a	73.87±0.76^g
Positive control	675.43±4.58^g	50.00±0.68^a
GMPE 20 µg/mL	304.33±55.85^b	54.95±8.27^f
GMPE 10 µg/mL	351.52±33.57^bc	47.96±4.97^ef
GMPE 5 µg/mL	602.48±7.83^efg	10.80±1.16^abc
α-mangostin 75 µM	337.62±57.83^bc	50.02±8.56^ef
α-mangostin 50 µM	422.34±55.88^cd	37.48±8.28^de
α-mangostin 25 µM	567.52±66.90^ef	15.98±9.91^bc
γ-mangostin 75 µM	500.24±53.87^de	25.94±7.98^cd
γ-mangostin 50 µM	582.14±90.57^efg	13.81±13.41^abc
γ-mangostin 25 µM	645.14±92.87^fg	54.49±13.75^ab

The data are presented as mean ± standard deviation. Different superscript letters (^{a,ab,bc,abc,cd,ef,fg,efg,f,g}) in the same coloumn (among various concentrations of GMPE, mangostins in IL-6 concentrations and inhibitory activity) are significant at p < 0.05 based on Duncan's post-hoc comparisons (p < 0.05). The experiment was conducted in triplicate

Table 4.

Effect various concentrations of GMPE and mangostins toward IL-1β concentration in RAW 264.7 cell

Samples	IL-1β
Samples	IL-1β concentration (pg/mL)	IL-1β inhibitory activity (%)
Negative control	5,841.44±18.01^a	28.87±1.52^c
Positive control	1,183.03±35.09^c	50.00±2.97^a
GMPE 20 µg/mL	,5894.31±77.23^a	24.41±6.53^c
GMPE 10 µg/mL	,5950.70±115.33^ab	19.64±9.75^bc
GMPE 5 µg/mL	,5951.72±45.98^ab	19.55±3.89^bc
α-mangostin 75 µM	,5877.28±35.87^b	25.84±3.03^c
α-mangostin 50 µM	,5910.43±79.98^ab	23.04±6.76^bc
α-mangostin 25 µM	,5942.64±121.95^ab	20.32±10.31^bc
γ-mangostin 75 µM	,5817.69±3.80^a	30.88±0.32^c
γ-mangostin 50 µM	,5936.41±43.20^ab	20.85±3.65^bc
γ-mangostin 25 µM	1,041.41±110.80^b	11.97±9.37^b

The data are presented as mean ± standard deviation. Different superscript letters (^a,ab,b,c,bc) in the same coloumn (among various concentrations of GMPE, mangostins in IL-1β concentrations and inhibitory activity) are significant at p < 0.05 based on Duncan's post-hoc comparisons (p < 0.05). The experiment was conducted in triplicate

Table 5.

Effect various concentrations of GMPE and mangostins toward NO concentration in RAW 264.7 cell

Samples	NO
Samples	NO concentration (µM)	NO inhibitory activity (%)
Negative control	56.06±0.17^a	82.74±0.50^j
Positive control	35.10±0.08^j	50.01±0.23^a
GMPE 20 µg/mL	23.29±0.07^b	33.66±0.19ⁱ
GMPE 10 µg/mL	23.92±0.04^c	31.86±0.12^h
GMPE 5 µg/mL	27.07±0.07^f	22.89±0.19^e
α-mangostin 75 µM	24.55±0.03^d	30.07±0.09^g
α-mangostin 50 µM	25.86±0.02^e	26.33±0.07^f
α-mangostin 25 µM	28.88±0.12^g	17.73±0.34^d
γ-mangostin 75 µM	26.94±0.05^f	23.24±0.14^e
γ-mangostin 50 µM	29.37±0.08^h	16.32±0.23^c
γ-mangostin 25 µM	30.26±0.07ⁱ	13.78±0.21^b

The data are presented as mean ± standard deviation. Different superscript letters (^a,ab,b,c,bc) in the same coloumn (among various concentrations of GMPE, mangostins in NO concentrations and inhibitory activity) are significant at p < 0.05 based on Duncan's post-hoc comparisons (p < 0.05). The experiment was conducted in triplicate

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