22.16 Allergic Encephalomyelitis
Multiple sclerosis (MS), an inflammatory T cell facilitated autoimmune complication of CNS (Ridderstad Wollberg et al. 2014). In clinical MS patients and
Experimental Allergic Encephalomyelitis (EAE) preclinical model, T leukocytes
transmigrate from the bloodstream into the CNS to attack myelin sheath encircling
nerve fibers (Zozulya and Wiendl 2008). Autoreactive CD4+ and CD8 + T cells
were considered as the key driver events in EAE models, indicating important
immunopathologic features of MS (Friese and Fugger 2005; Lassmann and Bradl
2017). In highly proliferative cells, such as activated T lymphocytes, increased de
novo pyrimidine biosynthesis by Human Dihydroorotate dehydrogenase can enable
their superior growth capacity (Quéméneur et al. 2003), thereby inhibiting this
enzyme serve the purpose. The scientists’ result showed that piperine is a potent,
direct DHODH inhibitor with an IC 50 value of 0.88 ± 0.04 lM. Meanwhile,
piperine effectively reduced T cell proliferation through DHODH inhibition in vitro,
suggesting a potential role of piperine in immune function modulating.
Furthermore, piperine treatment significantly reduced immune cell infiltration in
central nervous tissue and resultant remission of EAE symptoms. The 13.2–15.8 h
terminal half-life (t 1/2 ) for elimination of piperine (Ren and Zuo 2019) is largely
shorter than A771726. Since DHODH is a main functional target of EAE, we
corroborated the efficacy of piperine in MS model by inhibiting DHODH activity,
although it remains to be investigated in the future whether other proteins were
involved in the therapeutic effect of piperine in EAE (Liu et al. 2020).
22.17 Memory Enhancer and Restoration of Myelin
Damage
Piperine enhanced remembrance damage in lysolecithin-stimulated demyelination
model by mitigating astrocytes initiation, iNOS, and provocative cytokines
appearance level by enhancing total antioxidant capability in demyelination situation. Also, Piperine amplified the level of IL10, Foxp3, and antioxidant gene
markers. Piperine upgraded the myelin restoration progression by intensifying the
amount of MBP and BDNF (Roshanbakhsh et al. 2020).
22.18 Effect on Carbamazepine Metabolism
Carbamazepine (CBZ) is a drug of choice to treat different type of seizures. It works
for seizure control in the dose range of 4–12 lg/ml in human plasma. Increase in
concentration may cause side effects such as diplopia, nystagmus, and aplastic
anemia (Bialer et al. 1998). Carbamazepine-10, 11-epoxide (CBZE), a metabolic
770
N. Sachan et al.
Multiple sclerosis (MS), an inflammatory T cell facilitated autoimmune complication of CNS (Ridderstad Wollberg et al. 2014). In clinical MS patients and
Experimental Allergic Encephalomyelitis (EAE) preclinical model, T leukocytes
transmigrate from the bloodstream into the CNS to attack myelin sheath encircling
nerve fibers (Zozulya and Wiendl 2008). Autoreactive CD4+ and CD8 + T cells
were considered as the key driver events in EAE models, indicating important
immunopathologic features of MS (Friese and Fugger 2005; Lassmann and Bradl
2017). In highly proliferative cells, such as activated T lymphocytes, increased de
novo pyrimidine biosynthesis by Human Dihydroorotate dehydrogenase can enable
their superior growth capacity (Quéméneur et al. 2003), thereby inhibiting this
enzyme serve the purpose. The scientists’ result showed that piperine is a potent,
direct DHODH inhibitor with an IC 50 value of 0.88 ± 0.04 lM. Meanwhile,
piperine effectively reduced T cell proliferation through DHODH inhibition in vitro,
suggesting a potential role of piperine in immune function modulating.
Furthermore, piperine treatment significantly reduced immune cell infiltration in
central nervous tissue and resultant remission of EAE symptoms. The 13.2–15.8 h
terminal half-life (t 1/2 ) for elimination of piperine (Ren and Zuo 2019) is largely
shorter than A771726. Since DHODH is a main functional target of EAE, we
corroborated the efficacy of piperine in MS model by inhibiting DHODH activity,
although it remains to be investigated in the future whether other proteins were
involved in the therapeutic effect of piperine in EAE (Liu et al. 2020).
22.17 Memory Enhancer and Restoration of Myelin
Damage
Piperine enhanced remembrance damage in lysolecithin-stimulated demyelination
model by mitigating astrocytes initiation, iNOS, and provocative cytokines
appearance level by enhancing total antioxidant capability in demyelination situation. Also, Piperine amplified the level of IL10, Foxp3, and antioxidant gene
markers. Piperine upgraded the myelin restoration progression by intensifying the
amount of MBP and BDNF (Roshanbakhsh et al. 2020).
22.18 Effect on Carbamazepine Metabolism
Carbamazepine (CBZ) is a drug of choice to treat different type of seizures. It works
for seizure control in the dose range of 4–12 lg/ml in human plasma. Increase in
concentration may cause side effects such as diplopia, nystagmus, and aplastic
anemia (Bialer et al. 1998). Carbamazepine-10, 11-epoxide (CBZE), a metabolic
770
N. Sachan et al.