Abstract
By using a feedback system control scheme, the best combination of formononetin, ononin, calycosin, and calycosin‐7‐O‐β‐d‐glucoside derived from Astragali Radix was shown to activate a hypoxia response element, a regulator for erythropoietin (EPO) transcription, in kidney fibroblast. In cyclophosphamide‐induced anemic rats, the treatment of combined flavonoids, or EPO, improved the levels of red blood cells, white blood cells, hemoglobin, and hematocrit. In addition, the altered levels of antioxidant capacity, super oxidase dismutase, and malondialdehyde, triggered in anemic rats, were restored to control levels by the treatment of flavonoids. Here, we proposed a possible therapy by using the common flavonoids in treating anemia.
Highlights
Anemia is a blood disorder associated with a series of health problems, for example, chronic kidney disease, congestive heart failure, chronic renal failure, diabetic, and nondiabetic renal disease [1]
Erythropoiesis-stimulating agents (ESA), that is, recombinant human epoein-a and darbepoetin-a, have been utilized for over two decades for the treatment of anemia associated with various diseases, in particular, cancer therapy-induced anemia [7,8]
An engineering approach, namely feedback system control (FSC) scheme, has been developed to search potent drug combinations in tens of iterations out of a hundred thousand possible trials [21,22]. By using this novel FSC screening method, we found the best combination of formononetin, ononin, calycosin, and calycosin-7-O-b-D-glucoside in activating the transcriptional activity of EPO gene [20]
Summary
Anemia is a blood disorder associated with a series of health problems, for example, chronic kidney disease, congestive heart failure, chronic renal failure, diabetic, and nondiabetic renal disease [1]. The treatment of cancer in combining radiotherapy, chemotherapy, and noncardiac or nonvascular surgery could lead to anemia [2,3]. Erythropoiesis-stimulating agents (ESA), that is, recombinant human epoein-a and darbepoetin-a, have been utilized for over two decades for the treatment of anemia associated with various diseases, in particular, cancer therapy-induced anemia [7,8]. Abbreviations CF, combined flavonoids; CYP, cyclophosphamide; DE, differential evolution; EPO, erythropoietin; ESA, erythropoiesis-stimulating agents; FSC, feedback system control; HIF, hypoxia-induced factor; HRE, hypoxia responsive element; MDA, malondialdehyde; SOD, super oxidase dismutase; T-AOC, total antioxidant capacity; TCM, traditional Chinese medicine. Cyclophosphamide (CYP), a nitrogen mustard alkylating agent, is used in the treatment of cancer chemotherapy and autoimmune disorders [11,12]. CYP exhibits many side effects, including bone marrow suppression and cytotoxicity leading to progressive anemia, oxidative stress, and immunological suppression [13,14]
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