Vol.2, No.2, 79-81 (2010) Health
Copyright © 2010 Openly accessible at http://www.scirp.org/journal/HEALTH/
Escin may exert a synergistic anti-inflammatory
effect with glucocorticoids
Lei-Ming Zhang, Tian Wang, Hua-Ying Fan, Xin Yu, Bing Han, Mei Zhu, Feng-Hua Fu
Department of Pharmacology, School of Pharmacy, Yantai University, Yantai, China; fufenghua@sohu.com
Received 16 October 2009; revised 15 December 2009; accepted 17 December 2009.
Escin is a natural mixture of triterpenoid as-
ponin isolated from the seed of the horse
chestnut and demonstrates anti-oedematous
and anti-inflammatory effects. As yet, the pre-
cise mechanisms by which escin exerts its anti-
inflammatory effects remain unclear. The data
from current studies indicate that the anti-in-
flammatory properties of escin were attributed
to its ability to reduce the adhesiveness of neu-
trophils and the associated release of inflam-
matory mediators; its ability to decrease hista-
minic and serotoninergic activities; its ability to
inhibit phospholipase A2; its ability to decrease
nuclear factor-κ B activation and down-regulate
the expression of tumor necrosis factor-α. All
these effects are similar to glucocorticoids. Mo-
reover, escin depends on adrenal glands to ex-
ert its anti-inflammatory effects. Also, our recent
research showed that the serum corticosterone
level in mice did not increase after a 7-day in-
travenous injection of escin. The results sup-
port the hypothesis that escin may exert a syn-
ergistic anti-inflammatory effect with glucocor-
ticoids. Confirming this hypothesis will play a
role in elucidating the anti-inflammatory mech-
anisms of escin.
Keywords: Escin; Glucocorticoids; Inflammation;
Escin, the major active principle from Aesculus hippo-
castanum (Hippocastanaceae), the horse chestnut tree,
possesses diverse biochemical and pharmacological ac-
tions. It has been reported that escin has anti-oedematous,
anti-inflammatory, and venotonic effects [1], and which
currently has wide clinical use. Accumulated experi-
mental evidence also suggests that escin exerts anti-
oedematous and anti-inflammatory effects. Escin has
been shown to be effective in preventing the formation
of oedema in models of inflammation that reproduce the
initial exudative phase, such as oedema induced in the
paw by a series of irritative agents [2]. Additionally,
escin shows a significant inhibition not only of the in-
crease of capillary permeability induced by acetic acid,
but also of the adhesion formation in animal model [3].
However, the anti-inflammatory mechanisms of escin
are still unclear.
The studies showed that escin could attenuate brain in-
jury, down-regulate the protein expressions of intercel-
lular adhesion molecule (ICAM)-1 and E-selectin, and
reduce the adhesiveness and migration of neutrophils [2,
4]. According to Matsuda [5], the anti-inflammatory
effects of escin are mainly dependent on their anti-his-
taminic and antiserotoninergic activities. Another re-
search [6] reported that escin dose-dependently pre-
vented the hypoxia-induced activation of human endo-
thelial cells, as evidenced by the inhibition of hy-
poxia-increased phospholipase A2, an enzyme responsi-
ble for the release of precursors of inflammatory media-
tors. In addition, escin can well alleviate the formation
of inflammatory edema by blocking the increase in per-
meability through enhancing generation of prostaglandin
F2α [7]. Escin could significantly inhibit nuclear fac-
tor-κ B (NF-κ B) activation and down-regulate the ex-
pression of tumor necrosis factor-α (TNF-α), alleviating
brain edema in traumatic brain injured rats [8].
The experiments listed above characterized that escin
has potent anti-inflammatory effects and its anti-in-
flammatory mechanisms are similar to glucocorticoids
(GCs) [9-11]. Additionally, an intriguing finding was
that the anti-inflammatory effects of escin disappeared
following adrenalectomy [12]. It suggests that the anti-
inflammatory effects of escin depend on GCs. However,
our recent research showed the serum corticosterone
level in mice did not increase after a 7-day intravenous
L. M. Zhang et al. / HEALTH 2 (2010) 79-81
SciRes Copyright © 2010 Openly accessible at http://www.scirp.org/journal/HEALTH/
injection of escin [13]. In another study, we further
found escin to be a safe and potent anti-inflammatory
drug with long effective anti-inflammation and without
immunosuppression [14].
It is well known that GCs possess both anti-inflam-
matory and immunosuppressive effects. The anti-in-
flammatory and immunosuppressive effects of GCs rely
on several molecular mechanisms, including direct ef-
fects on gene expression by the binding of glucocorti-
coid receptors (GR) to GC-responsive elements (i.e., the
induction of annexin I and MAPK phosphatase 1), indi-
rect effects on gene expression through the interactions
of GR with other transcription factors (i.e., NF-κB and
activator protein 1), and GR–mediated effects on sec-
ond-messenger cascades (i.e., the PI3K–Akt–eNOS
pathway) [15]. Unfortunately, because some of these
mechanisms are also involved in physiologic signaling
rather than inflammatory signaling, the therapeutic ef-
fects of GCs in inflammation are often accompanied by
clinically significant side effects.
Based on the aforementioned data, we hypothesize that
escin may exert a synergistic anti-inflammatory effect
with GCs, which could explain the relationship de-
scribed between escin and its anti-inflammatory mecha-
nism, and the molecular mechanisms of the synergistic
anti-inflammatory effect between escin and GCs may be
derived from amplification of endogenous GC action
through affecting GR or other elements in the signaling
pathways. In fact, this hypothesis is not difficult to test.
We can design experiments to confirm whether the com-
bination of escin with GCs, which alone had no anti-
nflammatory action in rodent animals by adrenalectomy,
can greatly inhibit inflammation after the administration
of physiological dose corticosterone. However, the dif-
ficulty in conducting these studies is how to precisely
discover the molecular mechanisms of synergistic anti-
inflammatory effects between escin and GCs, that is, to
determine escin how to affect the GC signaling pathway,
from GR to other elements [15].
GCs are widely used to treat inflammatory diseases.
However, GCs has multiple effects to inhibit the immune
system and it is also associated with an increased sus-
ceptibility to infection and a risk for reactivation of la-
tent tuberculosis. If our hypothesis could be proved cor-
rect, escin has its own virtue compared with GCs, as
escin is not only a safe and potent anti-inflammatory dr
ug, but also an anti-gastric ulcer agent [16]. Furthermore,
it is easy to obtain and can be taken orally and venously
with less side effects and complications. In conclusion,
escin is a promising anti-inflammatory drug, promising
wide clinical use within the population.
This study was supported by the National Natural Science Foundation
of China (No.30772760), the 11th Five Years Key Programs for Sci-
ence and Technology Development of China (No. 2008ZX09202-008),
and Shandong Province Natural Science Foundation (No. Y2008C51).
All authors declare that there are no conflicts of interest.
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