DOMINANCE OF HERBAL MEDICINES IN TREATING SICKEL CELL ANEMIA

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical problems. Several drugs are available for treating SCD, these medicines are insufficiently effective, toxic, or too expensive to be used. So there is a need to arise a safe, effective, and inexpensive therapeutic agent from indigenous plants used in ethnomedicines. SCD is affecting millions of people worldwide. Due to lack of progress in drug discovery and appropriate treatment methods, victims often turn to traditional Ayurvedic medicines that take advantage of the plant extracts. The use of complementary and alternative medicine (CAM) has been thought worldwide, most especially in patients with chronic diseases. SCD is one of such chronic diseases. Sickle cell anemia (SCA) has been treated for ages with natural products, especially herbs and Ayurvedic medicines worldwide. The proven medicines for sickle cell anemia includes, the use of hydroxyurea, folic acid and amino acids supplementation that manage the condition of blood transfusions and stabilize the patient’s hemoglobin level. But these clinical treatments are quite expensive and have attendant risk factors. As a research for medicinal plants into anti-sickling properties has been satisfy, so the alternative therapy of using phytomedicines has proven to reduce the crisis and reverse for sickling of RBC’s. As the use of medicinal plants and nutrition in managing SCD is gaining attention so the enormous benefits of phyto-medicine and nutraceuticals are discussed in this paper. Here in we have summarized the use of tradition Ayurvedic medicines in treating SCA

Mutant p53 Depletion by Novel Inhibitors for HSP40/J-Domain Proteins Derived from the Natural Compound Plumbagin

Accumulation of missense mutant p53 (mutp53) in cancers promotes malignant progression. DNAJA1, a member of HSP40 (also known as J-domain proteins: JDPs), is shown to prevent misfolded or conformational mutp53 from proteasomal degradation. Given frequent addiction of cancers to oncogenic mutp53, depleting mutp53 by DNAJA1 inhibition is a promising approach for cancer therapy. However, there is no clinically available inhibitor for DNAJA1. Our in silico molecular docking study with a natural compound-derived small molecule library identified a plumbagin derivative, PLIHZ (plumbagin–isoniazid analog), as a potential compound binding to the J domain of DNAJA1. PLIHZ efficiently reduced the levels of DNAJA1 and several conformational mutp53 with minimal impact on DNA contact mutp53 and wild-type p53 (wtp53). An analog, called PLTFBH, which showed a similar activity to PLIHZ in reducing DNAJA1 and mutp53 levels, inhibited migration of cancer cells specifically carrying conformational mutp53, but not DNA contact mutp53, p53 null, and wtp53, which was attenuated by depletion of DNAJA1 or mutp53. Moreover, PLTFBH reduced levels of multiple other HSP40/JDPs with tyrosine 7 (Y7) and/or tyrosine 8 (Y8) but failed to deplete DNAJA1 mutants with alanine substitution of these amino acids. Our study suggests PLTFBH as a potential inhibitor for multiple HSP40/JDPs