Research Article
Evaluation of Anti-HIV-1 Integrase and Anti-Inflammatory
Activities of Compounds from Betula alnoides Buch-Ham
Prapaporn Chaniad ,
1
Teeratad Sudsai,
1
Abdi Wira Septama,
2
Arnon Chukaew,
3
and Supinya Tewtrakul
4
1
School of Medicine, Walailak University, Nakhon Si ammarat 80160, ailand
2
Research Center for Chemistry, Indonesian Institute of Sciences, Kawasan Puspitek Serpong, Tangerang Selatan, Banten 15314,
Indonesia
3
Chemistry Department, Faculty of Science and Technology, Suratthani Rajabhat University, Surat ani 84100, ailand
4
Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat-Yai, Songkhla 90112, ailand
Correspondence should be addressed to Prapaporn Chaniad; prapaporn.ch@wu.ac.th
Received 13 February 2019; Revised 28 April 2019; Accepted 8 May 2019; Published 2 June 2019
Academic Editor: P. Patrignani
Copyright©2019PrapapornChaniadetal.isisanopenaccessarticledistributedundertheCreativeCommonsAttribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is
properly cited.
Betula alnoides is a medicinal plant in ai traditional longevity preparations. e crude extracts of this plant possess various
biological activities. However, the isolated compounds from this plant have no reports of anti-HIV-1 integrase (IN) activity.
erefore, the present study aims to investigate the anti-HIV-1 integrase and anti-inflammatory effects of isolated compounds
fromthisplantandpredicttheinteractionofcompoundswithintegraseactivesites.Fromthebioassay-guidedfractionationofthe
ethanol extract of B. alnoides stems using chromatographic techniques, five pentacyclic triterpenoid compounds were obtained.
eyarebetulinicacid( 1),betulin(2),lupeol(3),oleanolicacid(4),andursolicacid(5).Compound 2 exhibitedthemostpotent
inhibitoryactivityagainstHIV-1IN,withanIC
50
valueof17.7 μM.PotentialinteractionsofcompoundswithINactivesiteswere
investigated using computational docking. e results indicated that active compounds interacted with Asp64, a residue par-
ticipating in 3′-processing, and r66, His67, and Lys159, residues participating in strand-transfer reactions of the integration
process. Regarding anti-inflammatory activity, all compounds exerted significant inhibitory effects on LPS-induced nitric oxide
production (IC
50
< 68.7 μM). us, this research provides additional scientific support for the use of B. alnoides in traditional
medicine for the treatment of HIV patients.
1. Introduction
Human immunodeficiency virus (HIV) infection remains a
major global public health crisis. In 2017, there were ap-
proximately 36.9 million people living with HIV, with 1.8
millionpeoplebecomingnewlyinfectedand940,000people
died from HIV-related causes globally [1]. e infection
leads to a progressive immunodeficiency due to the de-
pletion of CD4+ T-cells and increased susceptibility to
opportunistic infections as a result of their immunocom-
promised state [2]. HIV infection is also associated with a
rapid and intense release of a variety of cytokines, which is
associated with relatively high levels of inflammation [3].
Integration of transcribed viral DNA into the host chro-
mosomeismediatedbytheintegrase(IN)enzymewhichisa
key enzyme for viral integration of the reverse-transcribed
viralDNAintothehostcellgenome,anessentialstepinthe
HIV life cycle [4]. e integration requires two catalytic
reactions, referred to as 3′-processing and DNA strand
transfer [5]. e full-length IN structure consists of three
functionaldomains.eN-terminaldomain,residues1–51,
contains a conserved HCCHZn
2+
-binding motif. e cata-
lytic core domain, residues 52–210, contains the catalytic
triad characterized by Asp64, Asp116, and Glu152. e
C-terminal domain, residues 220–288, contributes to
DNA binding [6]. Currently, only three IN inhibitors,
Hindawi
Advances in Pharmacological Sciences
Volume 2019, Article ID 2573965, 11 pages
https://doi.org/10.1155/2019/2573965