Protective Effect of Pharmacological Preconditioning of Total Flavones of Abelmoschl Manihot on Cerebral Ischemic Reperfusion Injury in Rats

Wen, Jiyue; Chen, Zhiwu

doi:10.1142/s0192415x07005144

Cited by 39 publications

(25 citation statements)

References 17 publications

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“…Abelmoschus manihot flavonoids were also proved to be effective for protecting poststroke depression injury in mice (Liu et al, 2009) and cerebral ischemic reperfusion injury in rats (Wen & Chen, 2007).…”

Section: Discussionmentioning

confidence: 99%

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Guo

Shang

et al. 2015

Pharmaceutical Biology

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Objective: Flavonoids are main active components of A. manihot, which can be transformed into glucuronide/sulfate conjugates in vivo. Exploring the pharmacokinetic profile of these conjugates is necessary to further elucidate the mechanism of action. Material and method: Flavonoid fraction of A. manihot (FFA) was extracted from A. manihot flower with ethanol. FFA (400 mg/kg) was orally given to normal rats and chronic kidney disease (CKD) model rats. Blood samples were collected at 5, 15, 30, 45, 60, 90, 120, 240, 360, and 720 min after administration. The plasma concentrations of quercetin and isorhamnetin glucuronide/sulfate conjugates were analyzed by UPLC-MS/MS. Results: In normal rats, AUC of quercetin-glucuronide conjugates, isorhamnetin-glucuronide conjugates, quercetin-sulfate conjugates, and isorhamnetin-sulfate conjugates was 459. 45 ± 192.70, 1153.01 ± 697.04, 417.81 ± 220.31, and 2475.19 ± 1085.22 mmol h/L, respectively. While AUC of quercetin and isorhamnetin was 5.47 ± 2.54 and 30.73 ± 25.95 mmol h/L. AUC of the glucuronide-sulfate conjugates of quercetin and isorhamnetin is 125-times higher than that of aglycone (quercetin and isorhamnetin), showing that glucuronide/sulfate conjugates represent the major circulating forms of A. manihot flavonoid in vivo. AUC of isorhamnetinglucuronide conjugates and quercetin-sulfate conjugates was 719.65 ± 619.22 and 275.49 ± 1 60.95 mmol h/L, indicating that less conjugated metabolites were formed in CKD rats compared with normal rats. The ratio of AUC glucuronide/sulfate /AUC aglycone decreased from 125 to 104, which implied the impaired phase II metabolism ability in CKD rat. Discussion and conclusion: Glucuronide-sulfate conjugates provide an important clue for further elucidating the activity of conjugated metabolites and their relationship with the nephroprotective efficacy of A. manihot. It is necessary to take caution when extrapolating pharmacokinetics parameters from healthy animals in designing pharmacological studies.

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Section: Discussionmentioning

confidence: 99%

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Guo

Shang

et al. 2015

Pharmaceutical Biology

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“…15,22 TFA has been found to have therapeutic effect on cerebral ischemic reperfusion injury and poststroke depression in the corresponding animal models. 13,23 The chemical constituents of TFA have been isolated, and their structures have been identified by spectroscopic analysis. TFA contains seven flavone glycosides that were identified as quercetin-3-O-robinobioside, hyperoside, isoquercetin, hibifolin, myricetin, quercetin-3 0 -O-glucoside, and quercetin.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 As a well-known traditional Chinese medicine, Flos Abelmoschus manihot L. Medic has been used as the neuroprotective drug for cerebral ischemic reperfusion injury in recent studies. 13,14 Total flavone glycosides of Flos A. manihot (TFA) contain seven chemically identified flavone glycosides 15 and have therapeutic effects on cerebral ischemic reperfusion and postmenopausal osteoporosis.…”

Section: Introduction Dmentioning

confidence: 99%

Pretreatment with the Total Flavone Glycosides of FlosAbelmoschus manihotand Hyperoside Prevents Glomerular Podocyte Apoptosis in Streptozotocin-Induced Diabetic Nephropathy

Zhou

Teng

et al. 2012

Journal of Medicinal Food

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Diabetic nephropathy (DN) is an important diabetic complication, and podocyte apoptosis plays a critical role in the development of DN. In the present study, we examined the preventive effect of the total flavone glycosides of Flos Abelmoschus manihot (TFA) on urinary microalbumin and glomerular podocyte apoptosis in experimental DN rats. The preliminary oral administration of TFA (200 mg/kg/day) for 24 weeks significantly decreased the urinary microalbumin to creatinine ratio and 24-h urinary total protein in streptozotocin-induced DN rats. Terminal deoxynucleotidyl transferasemediated dUTP nick end-labeling assay indicated glomerular cell apoptosis in DN rats was significantly improved by pretreatment with TFA. Furthermore, fluorescence-activated cell sorting and Hoechst 33342 staining suggested preincubation with hyperoside (50 and 200 lg/mL), the major active constituent of TFA, could significantly mitigate cultured podocyte apoptosis induced by the advanced glycation end-products (AGEs). Western blot analysis showed that increased caspase-3 and caspase-8 expressions induced by AGEs were also inhibited by pretreatment with hyperoside at both doses. Our results demonstrate that TFA pretreatment can decrease urinary albumin excretion in early-stage DN, which might be accomplished by preventing renal damage and podocyte apoptosis.

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“…[6,7] The ethanol extract of flower was screened for antiviral activity, and it was observed that the hyperoside shown significant anti HBV activity. [8] The leaves were tested on bone loss in ovarectomised rats and it was observed that it was able to prevent the ovariectomyinduced femoral osteopenia. [9] The modulatory effect of total flavone of Abelmoschus manihot (TFA) on NMDAactivated current (I NMDA ) was investigated in cultured rat hippocampal neurons using the whole-cell patch-clamp technique.…”

Section: [45]mentioning

confidence: 99%

Isolation of Phytoconstituents and Evaluation of Anti-inflammatory Activity of the Leaves of Abelmoschus manihot

Jain¹,

Todarwal²,

Bari³

et al. 2011

Phcog Commn.

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Protective Effect of Pharmacological Preconditioning of Total Flavones of Abelmoschl Manihot on Cerebral Ischemic Reperfusion Injury in Rats

Cited by 39 publications

References 17 publications

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Conjugated metabolites represent the major circulating forms ofAbelmoschus manihot in vivoand show an altered pharmacokinetic profile in renal pathology

Pretreatment with the Total Flavone Glycosides of FlosAbelmoschus manihotand Hyperoside Prevents Glomerular Podocyte Apoptosis in Streptozotocin-Induced Diabetic Nephropathy

Isolation of Phytoconstituents and Evaluation of Anti-inflammatory Activity of the Leaves of Abelmoschus manihot

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