Drug discovery through ethnobotany in Nigeria: some results. Okogun, Joseph I. National Institute for Pharmaceutical Research and Development, Abuja, Nigeria. Advances in Phytomedicine (2002), 1(Ethnomedicine and Drug Discovery), 145-154. Publisher: Elsevier Science B.V., CODEN: APDHB8 Journal; General Review written in English. CAN 139:206817 AN 2003:104632 CAPLUS
Abstract
A review. Ethnobotany and ethnomedicine are as old as man's history. The combination of ethnobotany and ethnomedicine is a popular research field in Nigeria that, unfortunately, has not led to the prodn. of many market products. The plant Zanthoxylum zanthoxyloides (Lam). Zepernich & Timter (Rutaceae) is used in ethnomedicine for a no. of ailments. The exts. of the plant contain a wide variety of secondary metabolites assocd. with a no. of biol. activities. The active principles in its exts. responsible for its antisickling effect have been identified, and the synthetic conversion of one of its metabolites yielded the antisickling acid, DBA. With assistance from various organizations, NIPRISANR, a herbal drug of ethnomedicine source that is used for sickle cell anemia disorder, is in its third clin.-trial development phase at the National Institute for Pharmaceutical Research and Development, Abuja, Nigeria.
Indexing -- Section 1-0 (Pharmacology)
Biology
(botany, ethnobotany; drug discovery through ethnobotany in Nigeria)
Drugs
Human
Human groups
Sickle cell anemia
(drug discovery through ethnobotany in Nigeria)
Natural products, pharmaceutical
Role: PAC (Pharmacological activity); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(drug discovery through ethnobotany in Nigeria)
Medicine
(ethnomedicine; drug discovery through ethnobotany in Nigeria)
Supplementary Terms
review drug discovery ethnobotany
Citations
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Efficacy of niprisan in the prophylactic management of patients with sickle cell disease. Wambebe, Charles O.; Bamgboye, Elijah Afolabi; Badru, Bidemi O.; Khamofu, Hadiza; Momoh, Jafaru A.; Ekpeyong, Margaret; Audu, Benedict S.; Njoku, Simon O.; Nasipuri, Nathaniel R.; Kunle, Olubayo O.; Okogun, Joseph I.; Enwerem, Nkechi M.; Gamaniel, Shingu K.; Obodozie, Oby O.; Samuel, Babatunde; Fojule, Gloria; Ogunyale, Paul O. National Institute for Pharmaceutical Research and Development, Abuja, Nigeria. Current Therapeutic Research (2001), 62(1), 26-34. Publisher: Excerpta Medica, Inc., CODEN: CTCEA9 ISSN: 0011-393X. Journal written in English. CAN 135:162254 AN 2001:136276 CAPLUS
Abstract
Niprisan is a new drug extd. from indigenous herbs that has been developed by the Nigerian National Institute for Pharmaceutical Research and Development for the prophylactic management of patients with sickle cell disease. The objective of this study was to assess the efficacy and tolerability of niprisan in the management of patients with sickle cell disease. This was a randomized, double-blind, placebo-controlled, crossover trial. Patients who met the criteria for homozygous sickle cell disease and had 3 painful or vaso-occlusive crises per yr were randomized to 1 of 2 study groups. Group A took niprisan 12 mg/kg body wt. for 6 mo before crossing over to placebo for another 6 mo; group B took placebo for 6 mo before crossing over to niprisan for another 6 mo. There was a 1-mo washout period before the crossover. The main outcome measures were the incidence of crises; the occurrence of painful episodes; certain clin., hematol., and biochem. measures; and patients' daily self-assessment of health. Eighty-four patients met the inclusion criteria, but complete data were available for only 69 patients at the end of 12 mo, 33 in group A and 36 in group B. Loss to follow-up was related to social and logistic factors rather than study drug. One oral dose of 12 mg/kg niprisan daily significantly reduced the frequency of sickle cell crises, bone pain, and hospital admission (P < 0.05). The mean no. of crises per person per mo was 0.05 in patients who received niprisan initially, compared with 0.11 per person per mo after the crossover to placebo. Patients generally rated their health as better and reported less sickness and absenteeism with niprisan than with placebo. Apart from headache, which was reported by 9 patients while taking niprisan, there were no important adverse effects. Niprisan was efficacious in the prophylactic management of patients with sickle cell disease, although addnl. confirmatory studies in larger sample sizes are needed.
Indexing -- Section 1-8 (Pharmacology)
Sickle cell anemia
(efficacy of niprisan in prophylactic management of patients with sickle cell disease)
Natural products, pharmaceutical
Role: ADV (Adverse effect, including toxicity); BAC (Biological activity or effector, except adverse); BSU (Biological study, unclassified); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(niprisan; efficacy of niprisan in prophylactic management of patients with sickle cell disease)
Supplementary Terms
niprisan sickle cell disease management
Citations
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11) Murtaza, L; Br Med J 1981, 282, 1048
12) Charache, S; Medicine 1996, 75, 300
n vitro effects of NIPRISAN (Nix-0699): a naturally occurring, potent antisickling agent. Iyamu, Efemwonkiekie W.; Turner, Ernest A.; Asakura, Toshio. Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA. British Journal of Haematology (2002), 118(1), 337-343. Publisher: Blackwell Science Ltd., CODEN: BJHEAL ISSN: 0007-1048. Journal written in English. CAN 137:195307 AN 2002:631927 CAPLUS
Abstract
Among the various potential antisickling agents tested, hydroxyurea (HU) has been the most effective compd. used for the treatment of patients with sickle cell disease (SCD). Although HU is effective in many patients, not all patients respond to this drug. In addn., some patients reveal adverse effects, including myelosuppression. In an attempt to find other effective agents with less adverse effects, we investigated the antisickling effect of NIPRISAN (Nix-0699). We found that Nix-0699, an ethanol/water ext. from indigenous plants, has a strong antisickling effect. The concn. of Nix-0699 required to inhibit 50% of erythrocyte sickling was about 0.05 mg/mL. As for the kinetics of polymn., addn. of 0.05 g/mL Nix-0699 caused a sixfold prolongation of the delay time prior to deoxy-Hb S polymn. when compared with that of untreated Hb S samples. The soly. of deoxy-Hb S significantly increased upon treatment with Nix-0699. Anal. of the effect of Nix-0699 on the Hb S oxygen affinity indicated that the drug slightly shifted the oxygen-dissocn. curve of Hb S toward the left without any apparent change in the Hill coeff. These results suggest that the antisickling properties of Nix-0699 may involve direct interaction with Hb mols. Incubation of red blood cell (RBC) suspensions with various concns. of Nix-0699 did not dehydrate RBCs, cause hemolysis, increase the amt. of denatured Hb, nor form met-Hb. In view of the outcome of this study, Nix-0699 may be a promising option for the treatment of patients with SCD.
Indexing -- Section 1-8 (Pharmacology)
Hypoxia
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: effect of drug on sickle cell under hypoxic condition)
Blood analysis
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: effect of drug on soly. of deoxy-Hb S)
Erythrocyte
Hemolysis
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: rate of hemolysis, formation of met-Hb, size of RBC, and level of MADH)
Hemoglobins
Hemoglobins, methemoglobins
Role: BSU (Biological study, unclassified); BIOL (Biological study)
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: rate of hemolysis, formation of met-Hb, size of RBC, and level of MADH)
Human
Sickle cell anemia
(in vitro effects of NIPRISAN (Nix-0699): naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients)
Natural products, pharmaceutical
Role: DMA (Drug mechanism of action); PAC (Pharmacological activity); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(in vitro effects of NIPRISAN (Nix-0699): naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients)
Embryophyta
(medicinal plant; in vitro effects of NIPRISAN (Nix-0699): naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients)
376643-51-5, NIPRISAN
Role: DMA (Drug mechanism of action); PAC (Pharmacological activity); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(Nix 0699; in vitro effects of NIPRISAN (Nix-0699): naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients)
7782-44-7, Oxygen, biological studies
Role: BSU (Biological study, unclassified); BIOL (Biological study)
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: detn. whether antisickling property is attributed to left-shift of blood-oxygen dissocn. curve)
9035-22-7, Hemoglobin S
Role: BSU (Biological study, unclassified); BIOL (Biological study)
(in vitro effects of NIPRISAN (Nix-0699) naturally occurring, potent antisickling agent effect on blood of sickle cell anemia patients: effect of drug on soly. of deoxy-Hb S)
Supplementary Terms
herb natural product Nix0699 Hb soly sickle cell anemia
Citations
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Sunshine, H; Nature 1978, 275, 238
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Wambebe, C; Current Therapeutic Research 2001, 62, 26
nvestigational agents for sickle cell disease. Okpala, Iheanyi. St Thomas' Hospital, University of London, London, UK. Expert Opinion on Investigational Drugs (2006), 15(8), 833-842. Publisher: Informa Healthcare, CODEN: EOIDER ISSN: 1354-3784. Journal; General Review written in English. CAN 145:240787 AN 2006:722229 CAPLUS
Abstract
A review. Developments in the treatment of sickle cell disease (SCD) have not kept pace with advances in understanding the pathophysiol. of this haemoglobinopathy. Drugs undergoing preclin. and clin. assessment for the therapy of these globin gene disorders are discussed in this article. Beginning with investigational agents for treatment of SCD as a whole, the discussion proceeds to drugs being developed for specific manifestations or iatrogenic complications. Despite being licensed in the USA, the prototype antisickling agent, hydroxycarbamide, has not attained worldwide clin. use because of concerns about long-term toxicity. The less toxic decitabine, which (as with hydroxycarbamide) increases fetal Hb level, cannot be administered orally; therefore, the search continues for effective and safe antisickling drugs that can be taken orally. The naturally occurring benzaldehyde 5-hydroxymethyl-2-furfural has shown promising antisickling properties in vitro, and when administered to transgenic sickle mice. These effects are surpassed by the new synthetic pyridyl derivs. of benzaldehyde. Studies in humans with SCD are required to assess the clin. efficacy of these benzaldehydes. Niprisan, another antisickling agent with significant clin. efficacy and an attractive safety profile, is undergoing further development. The prospects of antiadhesion therapy in SCD are demonstrated by a recombinant protein contg. the Fc fragment of IgG fused to the natural ligand for selectins: the conjugate significantly inhibited blood vessel occlusion in transgenic sickle mice. Whereas the orally administrable iron-chelating agent deferasirox is likely to increasingly take the place of desferrioxamine (which can only be given parenterally), effective treatment of priapism in SCD remains a distressing challenge.
Indexing -- Section 1-0 (Pharmacology)
Human
Sickle cell anemia
(investigational agents for sickle cell disease)
127-07-1, Hydroxycarbamide
Role: ADV (Adverse effect, including toxicity); PAC (Pharmacological activity); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(investigational agents for sickle cell disease)
67-47-0, 5-Hydroxymethyl-2-furfural
2353-33-5, Decitabine
201530-41-8, Deferasirox
376643-51-5, Niprisan
Role: PAC (Pharmacological activity); THU (Therapeutic use); BIOL (Biological study); USES (Uses)
(investigational agents for sickle cell disease)
Supplementary Terms
review sickle cell disease therapy drug
Citations
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