Hence, the use of natural products for the abovementioned pharmacological aspects can be a suitable alternative. Lglutamine is an amino acid precursor for nicotinamide adenine dinucleotide. It is needed for the generation of reduced NAD in sickle cell erythrocytes.In the patient with SCA, glutathione and glutamine levels are low in spite of increasing availability of glutamine.These events possibly lead to an increase of oxidative stress and episodes of pain crisis.Though NAD production is adequate, but glutathione and glutamine levels in the erythrocyte are signicantly exhausted.Several plant extracts as well as pure molecules have been explored under the wide range of pharmacological treatment perspectives to manage SCA patients.Here, we are focused on the inhibition of hemoglobin polymerization activity by the characterized components in plant extracts or pure natural candidates.These two components as individual as well as in combination at same concentration level exhibit signicant protection against sickling of blood with respect to time. Larginine is an amino acid that helps for the production of nitric oxide.In SCA, nitric oxide level depletes that link to the complication of pain crisis.Further investigation of this compound reveals that it can protect the erythrocyte membrane from damage by transient oxidative species. Vanillin is a phenolic aldehyde mainly used as a avoring agentfood additive.This dual mechanism of vanillin may be responsible for antisickling activity. As vanillin is rapidly reasch Ospemifene degraded in the upper gastrointestinal tract of oral administration, a prodrug of vanillin, namely, MX, was explored in transgenic sickle mice that can develop pulmonary sequestrations under hypoxic condition.Treatment of MX signicantly reduced the percentage of sickle cell in blood as well as prolonged the survival time after oral as well as intraperitoneal administration in severe hypoxic condition. It is reported that INN and INN, pyridyl derivatives of vanillin, increased antisickling activity by fold as compared to vanillin.Research on antisickling activity by naturally occurring vemembered heterocyclic aldehydes evolve that hydroxymethylfurfural inhibit sickling of homozygous sickle red blood cells up to at the concentration of mM.Results illustrated that this molecule increased the oxygen afnity of hemoglobin and displayed strong antisickling activity. Nix decreased the percentage of sickle cell to at. A clinical trial to access the safety and efcacy of NIPRISAN was carried out.This phytomedicine is found to be safe in terms of liver and kidney function test.Moreover, it signicantly lowered the frequency of pain crisis. It showed antisickling activities where burkinabins C is the most active component. It is reported that these have the ability to induce differentiation and globin gene expression in human erythroid cells. Further research by the same research group illustrated that ursolic acid is present in the same plant part.These showed dosedependent and timedependent inhibition of in vitro sodium metabisulfateinduced polymerization of hemoglobin using SCA patient blood samples.SCA is a botanical drug that exhibits both in vitro and in vivo antisickling activities.Clinical investigation depicts that it can able to reduce chronic pain, but limited data is available on its mechanism. Anthocyanin is a avonoid class of compounds present in several plants.Dosedependent activity on inhibition of sickling was attributed to anthocyanin also showed in vitro antisickling activity in sodium metabisulfateinduced blood sample.