| Reference | 1. Anticancer Agents Med Chem. 2019 Oct 14. doi: 10.2174/1871521409666191014164742.
[Epub ahead of print]
<br>
Morin Inhibits Ovarian Cancer Growth through Inhibition of NF-κB Signaling
Pathway.
<br>
Xu M(1), Zhang Y(1).
<br>
Author information: <br>
(1)Department of Gynecology and Obstetrics, Liaocheng People`s Hospital, No. 67
of Dongchang West Road, Liaocheng 252000, Shandong, China.
<br>
BACKGROUND & OBJECTIVE: Ovarian cancer has the highest mortality in gynecological
tumors with no effective therapeutic drugs as a result of drug-resistance for
long-term utilization. Morin has been reported to possess powerful anti-tumor
effects in several cancers. The present study aims to investigate whether Morin
could influence ovarian cancer growth and the underlying mechanisms.<br>
METHODS: Morin was administered to cultured cells in vitro and formed tumors in
vivo. MTT and colony formation assays were conducted to explore the effects of
Morin on proliferation and colony formation of OVCAR3 and SKOV3 ovarian cancer
cells. Western blot, RT-qPCR, immunofluorescence as well as ELISA were used to
detect protein and mRNA expression of target factors. Tumor formation was
performed to investigate the tumorigenesis ability of drug-treated cells.<br>
RESULTS: The proliferation and colony size of OVCAR3 and SKOV3 were significantly
decreased after Morin administration. The expression of NF-κB and inflammatory
cytokines IL6/8 induced by TNF-α can be inhibited by Morin. Furthermore, Morin
inhibited the volume of ovarian cancer tumor in nude mice.<br>
CONCLUSION: Morin effectively alleviates ovarian cancer growth, inhibits
inflammatory response and reduces tumor size via modulation of NF-κB pathway.
<br><br>
2. Front Pharmacol. 2019 Sep 20;10:1089. doi: 10.3389/fphar.2019.01089. eCollection
2019.
<br>
Morin Hydrate Inhibits TREM-1/TLR4-Mediated Inflammatory Response in Macrophages
and Protects Against Carbon Tetrachloride-Induced Acute Liver Injury in Mice.
<br>
Li X(1), Yao Q(2), Huang J(3), Jin Q(2), Xu B(2), Chen F(2), Tu C(2).
<br>
Author information: <br>
(1)Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai,
China.
(2)Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan
University, Shanghai, China.
(3)Department of Gastroenterology and Hepatology, Zhongshan Hospital Qingpu
Branch, Fudan University, Shanghai, China.
<br>
This study aims to investigate the protective effects of morin hydrate (MH)
against acute liver injury induced by carbon tetrachloride (CCl4) in mice and to
elucidate the possible molecular mechanism of action. Mice were pretreated with
MH (50 mg/kg body weight) or vehicle by oral gavage once daily for 5 days,
followed by intraperitoneal injection of a single dose of CCl4 (1 ml/kg in olive
oil). Mice were sacrificed 24 h later; the blood and liver samples were harvested
for analysis. We also used the model of lipopolysaccharide (LPS)-stimulated
RAW264.7 macrophages in vitro and examined the effects of MH and its mechanism of
action on the inflammatory response. Our results revealed that MH remarkably
attenuated liver histopathological alterations, serum transaminases, hepatocytes
death, and inflammatory response induced by CCl4. Importantly, MH reduced
expression of the triggering receptor expressed on myeloid cells-1 (TREM-1) and
toll-like receptor 4 (TLR4) both in vivo and in vitro experiments. This
inhibitory effect MH on expression of the TREM-1 and TLR4 in cell culture was
further heightened after TREM-1 knockdown with small interfering RNA (siRNA).
Moreover, MH dramatically suppressed the inhibitor of kappa B α (IκBα)
degradation and subsequent nuclear factor-kappa B (NF-κB) p65 translocation into
the nucleus and NF-κB-mediated cytokines, such as tumor necrosis factor α
(TNF-α), interleukin (IL)-1β, and IL-6. Additionally, MH also ameliorated
CCl4-induced oxidative stress by enhancing the nuclear factor erythroid 2-related
factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expression in the injured livers.
Taken together, MH has hepatoprotective activity, and this effect may be elicited
by attenuating macrophage-mediated inflammatory responses via inhibition
TREM-1/TLR4/NF-κB signaling and by regulating hepatic oxidative stress via
enhancement Nrf2/HO-1 antioxidant pathway.
<br><br>
3. Eur J Pharmacol. 2019 Oct 12;865:172734. doi: 10.1016/j.ejphar.2019.172734. [Epub
ahead of print]
<br>
Morin hydrate inhibits platelet activation and clot retraction by regulating
integrin αIIbβ3, TXA2, and cAMP levels.
<br>
Nam GS(1), Lee KS(1), Nam KS(2).
<br>
Author information: <br>
(1)Department of Pharmacology and Intractable Disease Research Center, School of
Medicine, Dongguk University, Gyeongju, Gyeongsangbuk-do, 38066, Republic of
Korea.
(2)Department of Pharmacology and Intractable Disease Research Center, School of
Medicine, Dongguk University, Gyeongju, Gyeongsangbuk-do, 38066, Republic of
Korea. Electronic address: [email protected].
<br>
Morin hydrate is an active constituent of Morus alba L, Prunus dulcis, and
Cudrania tricuspidata and has been reported to inhibit platelet activation in
vivo and in vitro, but no reports have been issued on its regulation of αIIbβ3, a
platelet-specific integrin and thromboxane A2 (TXA2), positive feedback molecule.
In this study, we investigated the anti-platelet activity of morin hydrate in
collagen- and thrombin-induced human platelets and attempted to identify the
mechanism responsible for integrin αIIbβ3 activation and TXA2 generation. Our
results demonstrated that morin hydrate (25-100 μM) inhibited collagen- and
thrombin-induced platelet aggregation, granule secretion (P-selectin expression,
ATP, and serotonin release), calcium mobilization, TXA2 production, integrin
αIIbβ3 activation, and clot retraction. Additionally, morin hydrate attenuated
the phosphorylations of phospholipase Cγ2 (PLCγ2), cytosolic phospholipase A2
(cPLA2), phosphoinositide 3-kinase (PI3K), Akt, c-Jun N-terminal kinase (JNK),
and extracellular signal-regulated kinase (ERK), and enhanced the
phosphorylations of inositol trisphosphate receptor (IP3 receptor) and cyclic
adenosine monophosphate (cAMP) generation. However, it had no effect on the
coagulation pathway. Taken together, these observations indicate morin hydrate
inhibits platelet-mediated thrombosis by down-regulating TXA2 production and
integrin αIIbβ3 activation, and by upregulating cAMP generation, and thus,
inhibits clot retraction. These results suggest morin hydrate may have
therapeutic potential as a treatment for platelet-activation-related diseases.
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