• The application of P. guineense seeds in sickle cell disorder probably relies on their content of piperine, capsaicin, cubebin, and caryophyllene, or closely related compounds.
• Piperine and capsaicin are vanilloids that interact with receptors/ion channels associated with pain; both possess aspirin-like effects such as allosteric binding to hemoglobin —
a property shared with several other by-products of shikimic acid.
• Cubebin, a tetrahydrodiperonyl-2-furanol, is also a vanilloid that contains furan — an allosteric regulator of hemoglobin possessing an antisickling effect.
• ß-Caryophyllene is an agonist of cannabinoid receptor type 2, which functions in endogenous pain control.
• Remarkably, vanillin, methyl salicylate, and ß-caryophyllene are also present in E. caryophyllata, which, like P. guineense, is one of the components of Niprisan antisickling drug developed in Nigeria.
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