endothelium, and consequences in vasoconstriction (Chatterjee et al. 2003;
Goligorsky et al. 2002; Ling et al. 1999). They reported that piperine gavage shields
kidney from 30-min ischemia and 24-h reperfusion influenced injuries in rat.
Piperine was ingested by gavage with 97% of absorption without any modification.
In the research, renal ischemia–reperfusion increased plasma creatinine and
urea-nitrogen concentrations. Given the contrary relationship between plasma creatinine concentration and glomerular filtration rate (GFR), it is likely that the rise in
the plasma creatinine and urea-nitrogen concentrations is because of the diminution
in GFR. It has been shown that different factors are at play in reducing GFR
following IR, among which, mention can be made of the back-leak of filtered
substances (due to damaged tubular epithelial cells), activation of tubuloglomerular
feedback because of increased NaCl (Mohammadi et al. 2019).
22.11 Anticonvulsant Mechanisms of Piperine
Experimental findings suggest that piperine considerably slowed down the onset of
seizures in the PTZ-induced seizure test, telling a potential involvement of
GABA A receptors. In addition, prolonged onset of seizures in picrotoxin and
strychnine-initiated piperine-treated seizure models, although deprived of upsetting
mortality, also indicates the involvement of GABAergic and glycinergic signaling
paths, possibly with a widely recognized downstream pathway. Certainly, piperine’s acute effect on cortical and hippocampal GABA estimate the prevalence that
piperine intervention has increased GABA levels in these areas and fits into the PTZ
experiment with its anticonvulsant influence. Earlier works indicate the involvement of GABA transmission in animal models with anticonvulsant responses of
piperine (Zaugg et al. 2010). In addition, da Cruz et al. study (2013) encourage our
results because it advocates that piperine enhances basal GABA and glycine
amounts in the brain (da Cruz et al. 2013). From the other hand, serotonergic
modulation in MES induced convulsions could be a potential mechanism for the
protective role (Browning et al. 1983). In fact, our acute study indicated that
piperine facilitated the release of serotonin in cortex and hippocampus (Li et al.
2007) which may result in increased seizure threshold and this facilitatory effect on
serotonin release (Pei 1983). Interestingly, piperine has provided effective protection in seizures provoked by BAYK-8644 (a glutamate receptor agonist dependent
on L-type voltage) (Gasior et al. 1995), in line with the PASS prediction that
piperine may affect L-type channels. Piperine modulatory impacts of the Ca
2+
channel have been reported earlier in in vitro studies utilizing rat hippocampal
neurons (Fu et al. 2010). In patch clamp tests, piperine merely poorly blocked
L-type channels. Piperine may reduce the inclination of BAYK-8644 to L-type
calcium channels allosterically, thus compensating for the difference between both
the in vitro and in vivo effects (Bukhari et al. 2013; D'Hooge et al. 1996; Mishra
et al. 2015). The dose-dependent anticonvulsant impact of piperine in the convulsions induced by MES mentioned the idea of piperine inhibiting sodium channel
22 Piperine: Sources, Properties, Applications …
767
Goligorsky et al. 2002; Ling et al. 1999). They reported that piperine gavage shields
kidney from 30-min ischemia and 24-h reperfusion influenced injuries in rat.
Piperine was ingested by gavage with 97% of absorption without any modification.
In the research, renal ischemia–reperfusion increased plasma creatinine and
urea-nitrogen concentrations. Given the contrary relationship between plasma creatinine concentration and glomerular filtration rate (GFR), it is likely that the rise in
the plasma creatinine and urea-nitrogen concentrations is because of the diminution
in GFR. It has been shown that different factors are at play in reducing GFR
following IR, among which, mention can be made of the back-leak of filtered
substances (due to damaged tubular epithelial cells), activation of tubuloglomerular
feedback because of increased NaCl (Mohammadi et al. 2019).
22.11 Anticonvulsant Mechanisms of Piperine
Experimental findings suggest that piperine considerably slowed down the onset of
seizures in the PTZ-induced seizure test, telling a potential involvement of
GABA A receptors. In addition, prolonged onset of seizures in picrotoxin and
strychnine-initiated piperine-treated seizure models, although deprived of upsetting
mortality, also indicates the involvement of GABAergic and glycinergic signaling
paths, possibly with a widely recognized downstream pathway. Certainly, piperine’s acute effect on cortical and hippocampal GABA estimate the prevalence that
piperine intervention has increased GABA levels in these areas and fits into the PTZ
experiment with its anticonvulsant influence. Earlier works indicate the involvement of GABA transmission in animal models with anticonvulsant responses of
piperine (Zaugg et al. 2010). In addition, da Cruz et al. study (2013) encourage our
results because it advocates that piperine enhances basal GABA and glycine
amounts in the brain (da Cruz et al. 2013). From the other hand, serotonergic
modulation in MES induced convulsions could be a potential mechanism for the
protective role (Browning et al. 1983). In fact, our acute study indicated that
piperine facilitated the release of serotonin in cortex and hippocampus (Li et al.
2007) which may result in increased seizure threshold and this facilitatory effect on
serotonin release (Pei 1983). Interestingly, piperine has provided effective protection in seizures provoked by BAYK-8644 (a glutamate receptor agonist dependent
on L-type voltage) (Gasior et al. 1995), in line with the PASS prediction that
piperine may affect L-type channels. Piperine modulatory impacts of the Ca
2+
channel have been reported earlier in in vitro studies utilizing rat hippocampal
neurons (Fu et al. 2010). In patch clamp tests, piperine merely poorly blocked
L-type channels. Piperine may reduce the inclination of BAYK-8644 to L-type
calcium channels allosterically, thus compensating for the difference between both
the in vitro and in vivo effects (Bukhari et al. 2013; D'Hooge et al. 1996; Mishra
et al. 2015). The dose-dependent anticonvulsant impact of piperine in the convulsions induced by MES mentioned the idea of piperine inhibiting sodium channel
22 Piperine: Sources, Properties, Applications …
767