Page 15 - ITPS-7-2

INNOSC Theranostics and
Pharmacological Sciences Novel pharmacologic therapies for SAH

Mc1r expression and PI3K phosphorylation reversed these Ppar-δ mRNA, which corresponded to lower TNF-α and
effects. In conclusion, the study demonstrates that NDP- IL-1β levels . The administration of a PPAR-γ inhibitor
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MSH activation of Mc1r ameliorates oxidative stress and prevented the decrease in TNF-α and IL-1β in the groups
neuronal apoptosis through the PI3K/Akt/Nrf2-signaling treated with glycyrrhizin. Glycyrrhizin was linked to the
pathway in the context of ICH in mice . production of PPARs, especially PPAR-γ, and exhibited
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NDP-MSH, an analog of α-melanocyte-stimulating anti-inflammatory effects on SAH-induced vasospasm
hormone (α-MSH), was investigated for its anti- overall, indicating its potential use in treating inflammation
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inflammatory potential in microglial cells through and vasospasm in SAH .
melanocortin receptor 4 (MC4R). In the pertinent study, 4.5. Proteasomes (HMGB1 and Purpurogallin)
NDP-MSH treatment induced the upregulation of the
M2a/M2c marker Ag1 and reduced the M2b marker Research into the causes of SAH, specifically immediate
Il-4rα and Tlr4 expression in microglia . Furthermore, and delayed neuroinflammation, has been spurred by the
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it inhibited the nuclear translocation of NF-κB subunits catastrophic consequences of SAH. This process involves
p65 and c-Rel induced by lipopolysaccharide. NDP-MSH a complex role played by T-cell infiltration during SAH.
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effectively reduced TNF-α release triggered by TLR2 and According to a study examining this process, purpurogallin
TLR4 agonists, while TLR-induced IL-10 release remained demonstrates potential in mitigating early inflammation
unaffected . Moreover, NDP-MSH inhibited TLR2- and subsequent stimulation of HMGB1 in a mouse
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induced high mobility group box 1 (HMGB1) translocation model of SAH. This suggests that the natural polyphenol
and phagocytic activity. These results highlight the potential purpurogallin may hold therapeutic promise for treating
of melanocortins, particularly NDP-MSH, in attenuating and preventing SAH-induced vasospasm. Nevertheless, the
pro-inflammatory mechanisms and promoting M2-like work is constrained by its inherent limitations, warranting
polarization in microglia, offering a promising avenue for the necessity for future research to consider variables such as
immunomodulation in neuroinflammatory disorders . SAH-induced vascular remodeling and the current paucity
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of comprehensive mechanistic evidence .
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4.4. Glycyrrhizic acid Rhinacanthin-C (RCT-C) demonstrates
In a study involving a rat model of SAH , the aim was to neuroprotective properties by decreasing cleaved
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investigate the therapeutic potential of glycyrrhizic acid caspase-3 and caspase-9a, mitigating apoptosis. Its anti-
(GA) in reducing cerebral vasospasm and to elucidate inflammatory effect is evident in the RCT-C groups, as
the underlying mechanisms. Three groups of male rats indicated by the decreased expression of HMGB-1 mRNA
were established: GA, SAH, and control. The GA and and protein. Importantly, the administration of HMGB-1
SAH groups received intraperitoneal injections of GA recombinant protein counteracts the neuroprotective and
(10 mg/kg) and normal saline (10 mg/kg), respectively, and immunosuppressive effects of RCT-C. This finding suggests
underwent experimental cerebral vasospasm induction. that RCT-C influences the HMGB-1 pathway and mitigates
Following SAH, GA therapy significantly enhanced cerebral brain apoptosis in the context of SAH pathogenesis .
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function . In comparison to the SAH group, the basilar In the basilar artery of SAH rat models, HMGB1 is
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artery in the GA group exhibited a considerable decrease released from smooth muscle cells through a dynamic
in vascular wall thickness and a noticeable increase in process . Anti-HMGB1 monoclonal antibodies
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diameter. Furthermore, in comparison to the SAH group, (mAb) efficiently blocked this cascade of events, which
GA therapy resulted in a significant reduction in Hmgb1 included the migration of HMGB1, upregulation of
expression and a decrease in the mRNA expression of Il-1β, receptors constricting blood vessels, and the presence of
Il-6, and Tnf-α but an increase in Il-10 expression. These inflammation-linked chemicals. The use of anti-HMGB1
results imply that GA may prevent cerebral vasospasm mAb contributed to the relaxation of blood vessel
after SAH by inhibiting the expression of HMGB1 and the constriction in the context of SAH. This treatment approach
subsequent generation of inflammatory cytokines . successfully interrupted the sequence by neutralizing
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In a mouse model of SAH, a separate study investigated extracellular HMGB1, preventing inflammatory responses,
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the effects of glycyrrhizin on pro-inflammatory cytokines alleviating severe blood vessel constriction in the basilar
and peroxisome proliferator-activated receptors (PPARs). artery, and ultimately decreasing brain damage caused by
The study unveiled morphological alterations in the basilar insufficient blood flow, thereby improving neurological
arteries and decreased PPAR-γ and PPAR-δ protein levels symptoms. These results suggest that anti-HMGB1 mAb
in the SAH groups. Treatment with glycyrrhizin boosted therapy can effectively disrupt the series of events triggered
the expression of Ppar-γ mRNA and protein, as well as by SAH .
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Volume 7 Issue 2 (2024) 9 doi: 10.36922/itps.2019