Alpinumisoflavone Research Articles

Alpinumisoflavone ameliorates H2O2-induced intracellular damages through SIRT1 activation in pre-eclampsia cell models

Pre-eclampsia (PE) is classified as pregnancy-specific hypertensive disease and responsible for severe fetal and maternal morbidity and mortality, which influenced an approximate 3 ∼ 8 % of all pregnancies in both developed and developing countries. However, the exact pathological mechanism underlying PE has not been elucidated and it is urgent to find innovate pharmacotherapeutic agents for PE. Recent studies have reported that a crucial part of the etiology of PE is played by placental oxidative stress. Therefore, to treat PE, a possible treatment approach is to mitigate the placental oxidative stress. Alpinumisoflavone (AIF) is a prenylated isoflavonoid originated in mandarin melon berry called Cudrania tricuspidate, and is well known for its versatile pharmacotherapeutic properties, including anti-fibrotic, anti-inflammatory, anti-tumor, and antioxidant activity. However, protective property of AIF on extravillous trophoblast (EVT) under placental oxidative stress has not been elucidated yet. Therefore, we assessed stimulatory effects of AIF on the viability, invasion, migration, mitochondria function in the representative EVT cell line, HTR-8/SVneo cell. Moreover, protective activities of AIF from H2O2 were confirmed, in terms of reduction in apoptosis, ROS production, and depolarization of mitochondrial membrane. Furthermore, we confirmed the direct interaction of AIF with sirtuin1 (SIRT1) using molecular docking analysis and SIRT1-mediated signaling pathways associated with the protective effects of AIF on HTR-8/SVneo cells under oxidative stress. Finally, beneficial efficacy of AIF against oxidative stress was further confirmed using BeWo cells, syncytiotrophoblast cell lines. These results suggest that AIF may ameliorate H2O2-induced intracellular damages through SIRT1 activation in human trophoblast cells.

The beneficial effects of the active components from Maclura tricuspidata fruits in the treatment of diabetes mellitus

Five active compounds, daidzein, luteolin, alpinumisoflavone (AI), 6,8-diprenylgenistein (DG), and warangalone (WA), were identified from the fruits of Maclura tricuspidata via LC-Q/TOF-MS. WA and DG were shown to reverse the high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVECs), indicating their potential protective effects in alleviating diabetic symptoms. Network pharmacology was conducted to reveal the potential mechanisms of action of the compounds, and Hsp90α (degree: 47), Src (degree: 49), Akt (degree: 69) and p53 (degree: 60) were shown as the core targets related to antidiabetic properties. Further experimental verification suggested that the compounds could enhance phosphorylation of Src and Akt, increase p53 expression act as Hsp90 inhibitors, and protect against HG induced endothelial dysfunction. Our findings will provide a comprehensive understanding of the active substances of M. tricuspidata, which will be helpful for their utilisation.

Alpinumisoflavone Exhibits the Therapeutic Effect on Prostate Cancer Cells by Repressing AR and Co-Targeting FASN- and HMGCR-Mediated Lipid and Cholesterol Biosynthesis.

Prostate cancer (PCa) is the most common cancer in men, and this has been mainly noticed in Western and Asian countries. The aggregations of PCa and castration-resistant PCa (CRPC) progression are the crucial causes in the mortality of patients without the effective treatment. To seek new remedies for the lethal PCa diseases is currently an urgent need. In this study, we endeavored to investigate the therapeutic efficacy of alpinumisoflavone (AIF), a natural product, in PCa. LNCaP (androgen- sensitive) and C4-2 (CRPC) PCa cells were used. An MTT-based method, soft agar colony forming assay, biological progression approaches were applied to determine cell viability, migration, and invasion. A fatty acid quantification kit, a cholesterol detection kit and oil red O staining were conducted to analyze the intracellular levels of lipids and cholesterols. Apoptosis assays were also performed. AIF reduced cell viability, migration, and invasion in PCa cells. The expression of androgen receptor (AR), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was substantially inhibited by AIF treatment in PCa cells. Furthermore, by inhibiting FASN and HMGCR expression, AIF decreased the amounts of intracellular fatty acids, cholesterols, and lipid droplets in PCa cells. Significantly, through coordinated targeting FASN- and HMGCR-regulated biosynthesis and the AR axis, AIF activated the caspase-associated apoptosis in PCa cells. These results collectively demonstrated for the first time the potential of AIF as a novel and attractive remedy and provided an alternative opportunity to cure PCa malignancy.

Alpinumisoflavone ameliorates choroidal neovascularisation and fibrosis in age-related macular degeneration in in vitro and in vivo models

Age-related macular degeneration (AMD) is a major cause of vision loss in the elderly population. Anti-vascular endothelial growth factor (VEGF) antibody therapy is applicable to neovascularisation of AMD; however, the prevention of fibrosis after anti-VEGF monotherapy is an unmet medical need. Subretinal fibrosis causes vision loss in neovascular age-related macular degeneration (nAMD) even with anti-VEGF therapy. We report the anti-fibrotic and anti-neovascularisation effects of alpinumisoflavone (AIF), an isoflavonoid derived from unripe Maclura tricuspidata fruit, in in vitro and in vivo models. For in vitro study, we treated H2O2 or THP-1 conditioned media (TCM) following activation with phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) in a human retinal pigment epithelial cell line (ARPE-19). Choroidal neovascularisation (CNV) was induced by laser photocoagulation in mice, immediately followed by intravitreal administration of 25 μg AIF. CNV area and fibrosis were measured 7 days after laser photocoagulation. AIF showed anti-fibrosis and anti-neovascularisation effects in both the models. The laser induced CNV area was reduced upon AIF administration in nAMD mouse model. Additionally, AIF decreased the levels of the cleaved form of crystallin alpha B (CRYAB), a chaperone associated with VEGF stabilisation and fibrosis. Our results demonstrate a novel therapeutic application of AIF against neovascularisation and fibrosis in nAMD.

Efficacy of Alpinumisoflavone Isolated from Maclura tricuspidata Fruit in Tumor Necrosis Factor-α-Induced Damage of Human Dermal Fibroblasts.

The skin is an important organ in the human body that protects the body from environmentally hazardous substances. Reactive oxygen species (ROS) cause inflammatory reactions and degradation of the extracellular matrix leading to skin aging and various cutaneous lesions. This study evaluated the potential of isoflavones isolated from Maclura tricuspidata fruit to prevent TNF-α-induced skin inflammation in normal human dermal fibroblasts (HDFs). It focused on alpinumisoflavone (AIF) that suppressed the accumulation of ROS and nitric oxide (NO) in tumor necrosis factor-alpha (TNF-α)-treated HDFs. AIF inhibited the TNF-α-induced increase in matrix metalloproteinase-1, decreased procollagen I α1, and suppressed pro-inflammatory mediators and pro-inflammatory cytokines, including NO synthase, cyclooxygenase-2, interleukin (IL)-1β, IL-6, and IL-8 that trigger inflammatory responses. AIF inhibited nuclear factor-κB and activating protein 1 mitogen-activated protein kinases that were increased by TNF-α stimulation. These results suggest that AIF may protect skin from aging and various cutaneous lesions.

Alpinumisoflavone triggers GSDME-dependent pyroptosis in esophageal squamous cell carcinomas.

Esophageal squamous cell carcinoma (ESCC) presents a common human malignancy in the digestive system. We aimed to explore the critical effects of alpinumisoflavone (AIF) on ESCC in vitro and in vivo. The cell counting kit-8 assay was used to determine cell viability. Colony formation assay was employed to examine the effect of AIF on the long-term growth of ESCC cells. Cell apoptosis was determined by flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Cell morphologies were observed by light microscopy. The enzyme-linked immunosorbent assay was performed to examine the lactate dehydrogenase release from AIF-treated cells. Immunofluorescent labeling was utilized to examine AIF-induced GSDME expression. Western blot was employed to determine the expression levels of the associated proteins. Immunohistochemistry was performed to determine the localization and expression of the associated proteins in mice tumor tissues. AIF inhibited ESCC cell viability and suppressed cell growth in a dose- and time-dependent fashion. Results showed that AIF promoted apoptosis in ESCC cells. Meanwhile, our results also showed that AIF triggered pyroptotic cell death in ESCC, which was mediated by gasdermin E (GSDME) cleavage. In addition, our experiments provided experimental evidence that AIF-induced GSDME cleavage was dependent on caspase-3 activation. Moreover, the inhibition of GSDSE by knockdown was able to switch the form of cell death from pyroptosis to apoptosis. Furthermore, the results from the xenograft animal model also supported our findings in vitro that AIF was able to promote GSDME-mediated pyroptotic cell death in ESCC. AIF inhibited ESCC growth in vitro and in vivo by triggering GSDME-mediated pyroptotic cell death, which is dependent on caspase-3 activation.

Antiangiogenesis Potential of Alpinumisoflavone as an Inhibitor of Matrix Metalloproteinase-9 (MMP-9) and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2)

Background: Cancer is a very serious public health problem ranking as the second leading cause of death worldwide. Angiogenesis plays a vital role as a prerequisite for tumor growth and metastasis, and is indispensable in the further stage advancement of cancer. Objective: Targeting several enzymes and receptors in angiogenesis’ signal transduction pathway will likely offer many more prospects for successful and superior therapeutic intervention. Method: Thus, druggable targets in the angiogenesis pathway such as pro-MMP9, MMP-9, EGFR, VEGF-A, VEGFR-1, VEGFR-2, c-MET kinase, KIT kinase, CSF1R, TIE-2, and RET tyrosine kinase were the subject of this molecular docking study involving Alpinumisoflavone (AIF), a multi-targeted natural product with known anticancer activities. Results: The results showed that AIF exhibited good binding affinity with all the selected key angiogenesis promoting proteins with greatest in silico activity in MMP-9 and VEGFR-2. Moreover, in silico ADMET studies showed that AIF has good intestinal absorption property and solubility, and very low probability of being carcinogenic, mutagenic, and toxic to embryo or fetus. Conclusion: Molecular docking study revealed that Alpinumisoflavone (AIF) could serve as a promising lead in the development of angiogenesis (multikinase) inhibitor based on its predicted binding affinity with vital angiogenesis targets.

Alpinumisoflavone suppresses hepatocellular carcinoma cell growth and metastasis via NLRP3 inflammasome-mediated pyroptosis.

This research aims to explore the effect of alpinumisoflavone (AIF) as an anti-cancer drug for the treatment of patients with hepatocellular carcinoma (HCC). Cell counting kit-8 (CCK-8) and colony formation assay were used to evaluate the viability of the cells and their clonogenic ability. Cellular migration and their invasion capabilities were detected using the wound-healing and transwell assay, respectively. The release of lactate dehydrogenase (LDH) was detected using the LDH kit. The expression levels of genes in the cells and tumor tissues were examined by qRT-PCR, western blotting, and immunohistochemical techniques. The cells transfected with mRFP-GFP-LC3 adenoviruses were stained to determine their autophagy status. MCC950 (NLRP3 inflammasome inhibitor) and NLRP3 shRNA were used to block NLRP3-mediated pyroptosis. Chloroquine and Atg 5 siRNA were used to inhibit the autophagy of the cells. AIF suppressed cell proliferation, migration, and invasion capacity of SMMC 7721 and Huh7 cells. The incorporation of AIF induced the formation of NLRP3 inflammasome assembly, pyroptosis, and autophagy of the cells. However, the anti-proliferative and anti-metastatic effects of AIF on the HCC cells were attenuated by NLRP3 inhibitor and knockdown. Furthermore, Atg 5 knockdown inhibited autophagy and enhanced the rate of AIF-induced pyroptosis of the cells. AIF also suppressed tumor growth and increased the levels of pyroptosis-related genes in tumor tissues, which were consistent with in vitro observations. AIF inhibited HCC cell growth and metastasis by inducing NLRP3 inflammasome-mediated pyroptosis. Furthermore, AIF-induced autophagy augmented pyroptosis in HCC.

Alpinumisoflavone suppresses human Glioblastoma cell growth and induces cell cycle arrest through activating peroxisome proliferator-activated receptor-γ.

As a common subtype of malignant gliomas, glioblastoma multiforme (GBM) is associated with poor prognosis. This study is aimed to examine the anticancer activities of alpinumisoflavone (AIF) and its underlying mechanisms. Our results demonstrated that AIF inhibited the proliferation of GBM cells (U373 and T98G) in a time and dose-dependent manner. In addition, flow cytometry analysis not only confirmed AIF arrested cell cycle at the G0/G1 phase but also the induced apoptosis of U373 and T98G cells. Western blotting also confirmed that AIF altered the expression levels of cell cycle-related proteins. Further mechanism studies revealed that AIF inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis of U373 and T98G cells through activating PPARγ, as evidenced by the fact that GW9662 (PPARγ inhibitor) could effectively reverse the effects of AIF on U373 and T98G cells. Furthermore, the in vivo study also revealed that AIF suppressed tumor growth and caused cell cycle arrest. Collectively, these results highlighted the potential use of AIF in the treatment of GBM.

Alpinumisoflavone Inhibits Tumor Growth and Metastasis in Papillary Thyroid Cancer via Upregulating miR-141-3p.

Alpinumisoflavone (AIF) as a principal active ingredient of traditional Chinese herb Derris eriocarpa exerts a broad spectrum of anticancer activities against solid tumors. However, little is known about the effect of AIF on papillary thyroid cancer (PTC). Objectives of this study are to investigate the effect of AIF on cell growth, apoptosis, and metastasis of PTC cells and uncover its underlying mechanisms. Results showed that AIF treatment notably suppressed cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) process, as well as induced apoptotic cell death. In addition, microarray analysis results revealed that miR-141-3p level was dramatically elevated upon AIF insulation, suggesting that miR-141-3p may mediate the suppressive role of AIF against PTC. Moreover, miR-141-3p knockdown effectively reversed the effects of AIF on cell growth, migration, invasion, and EMT, while promoted PTC cell apoptosis escape. Furthermore, in vivo findings also confirmed that the antigrowth and antimetastasis activities of AIF were, at least partly, mediated by upregulation of miR-141-3p. Overall, AIF could serve as a potential anticancer compound for PTC treatment. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1842-1850, 2020. © 2019 American Association for Anatomy.

Alpinumisoflavone Exhibits Anticancer Activities in Glioblastoma Multiforme by Suppressing Glycolysis.

Glioblastoma multiforme (GBM, WHO grade IV astrocytoma) has become a public health burden worldwide. Alpinumisoflavone (AIF) is a flavonoid compound isolated from Derris eriocarpa. This study aims to examine the role of AIF in GBM. Our results showed that AIF could decrease the cell viability of both T98G and U373 GBM cell lines. AIF treatment also caused cell cycle arrest at G1/G0 phase along with upregulation of p27 and downregulation of cyclin D1. AIF could significantly induce apoptosis in GBM cells. Activation of caspase-9, disruption of mitochondrial membrane potential and loss of mitochondrial cytochrome C were also observed following AIF treatment. Inhibition of glycolysis by AIF was demonstrated by reducing glucose consumption and lactate output in GBM cells. Moreover, HK2 was identified as the molecular target responsible for the anticancer activities of AIF against GBM cells. The results showed that HK2 knockdown enhanced the anticancer activities of AIF whereas ectopic HK2 expression compromised its effect. Furthermore, the antineoplastic activities of AIF in vivo were also validated in xenograft murine model. Our results showed that AIF can exhibit anticancer activities in GBM by promoting apoptosis and inhibiting glycolysis via targeting HK2.

A Pharmacological Overview of Alpinumisoflavone, a Natural Prenylated Isoflavonoid.

Over the last decade, several studies demonstrated that prenylation of flavonoids enhances various biological activities as compared to the respective nonprenylated compounds. In line with this, the natural prenylated isoflavonoid alpinumisoflavone (AIF) has been explored for a number of biological and pharmacological effects (therapeutic potential). In this review, we summarize the current information on health-promoting properties of AIF. Reported data evidenced that AIF has a multitherapeutic potential with antiosteoporotic, antioxidant and anti-inflammatory, antimicrobial, anticancer, estrogenic and antiestrogenic, antidiabetic, and neuroprotective properties. However, research on these aspects of AIF is not sufficient and needs to be reevaluated using more appropriate methods and methodology. Further series of studies are needed to confirm these pharmacological effects, and this review should lay the basis for the design of respective investigations. Overall, despite the drawbacks of studies recorded, AIF exhibits a potential as drug candidate.

Isolation and Characterization of Secondary Metabilites and Evaluation of Antimicrobial, Antioxidant and Thrombolytic Potentials of Erythrina variegata L. Bark

Six compounds, sitosta-4-en-3-one (1), 3β,28-dihydroxyolean-12-en (2), scandenone (3), alpinum isoflavone (4), stigmasterol (5) and lupeol (6) were isolated from the methanol soluble extract of the stem bark of Erythrina variegata. The structure of the compounds was established by extensive NMR studies as well as co-TLC with authentic sample. The petroleum ether, carbon tetrachloride, chloroform and aqueous soluble fractions of the methanolic extract of Erythrina variegata were evaluated for antimicrobial, antioxidant and thrombolytic properties. In the antimicrobial study, most of the fractions of the extract exhibited mild to moderate antimicrobial activity where the zone of inhibition were ranging from 7.69 to 19.51 mm. The chloroform soluble fraction showed significant antioxidant activity with IC50 value 66.28 μg/mL as compared to standard BHT (IC50 value 23.09 μg/mL). The thrombolytic property of different extracts of E. variegata exhibited moderate activity ranging from 31.25 to 57.78 %.

RETRACTED: Alpinumisoflavone protects against glucocorticoid-induced osteoporosis through suppressing the apoptosis of osteoblastic and osteocytic cells

The long-term use of glucocorticoids is found to cause osteoporosis. This study is designed to evaluate the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone(Dex)-induced osteoporosis. We use a rat model to investigate the apoptosis of osteoblastic and osteocytic cells. The results indicate that AIF effectively protects against dexamethasone-induced osteoporosis. Moreover, AIF effectively reversed dexamethasone-induced apoptosis in osteoblastic and osteocytic cells through inhibiting ROS overproduction and regulating the Nrf2 pathway. In conclusion, the AIF activated Nrf2 signaling pathway was observed to suppress Dex-induced ROS production in osteoblastic and osteocytic cells, which may explain its anti-osteoporotic effects against dexamethasone-induced osteoporosis.

Alpinumisoflavone rescues glucocorticoid-induced apoptosis of osteocytes via suppressing Nox2-dependent ROS generation.

Long term use of glucocorticoids is one of the most common causes of secondary osteoporosis. Osteocyte, the most abundant cell type in bone, coordinates the function of osteoblast and osteoclast. This study evaluates the protective effect of alpinumisoflavone (AIF), a naturally occurring flavonoid compound, on dexamethasone (Dex)-induced apoptosis of osteocytes. MLO-Y4 cell was used as a cell model. The effect of AIF on the cell viability was assessed by MTT assay. Apoptosis of MYL-Y4 cells was determined by DNA fragment detection ELISA kit and flow cytometry. Intracellular ROS level was determined by DCFH-DA staining. mRNA and protein expression of target genes were determined by qRT-PCR and western blot, respectively. AIF effectively protected MLO-Y4 cells against Dex-induced apoptosis, which was associated with attenuation of Dex-induced ROS generation in MLO-Y4 cells. Furthermore, our data indicated that the expression of NAD(P)H oxidase 2 (Nox2) was suppressed by AIF, which in turn mediated the attenuating effect on Dex-induced ROS generation and apoptosis in MLO-Y4 cells. Moreover, our results showed that AIF modulated the expression of Nox2 by activating AMPK signaling. AIF activated AMPK-dependent Nox2 signaling pathway to suppress Dex-induced ROS production in cultured osteocytes, which might explain its anti-apoptotic effect. These results indicate that activation of AMPK pathway by AIF could have beneficial effects on bone damage induced by excessive oxidative stress and osteocyte apoptosis.

RETRACTED: Alpinumisoflavone radiosensitizes esophageal squamous cell carcinoma through inducing apoptosis and cell cycle arrest

Radiotherapy remains a mainstream treatment for patients with unresectable and locally advanced esophageal squamous cell carcinoma (ESCC). However, intrinsic radioresistance of ESCC tumors has largely compromised the efficacy of radiotherapy. The following study investigates the potential radiosensitizing effect of alpinumisoflavone (AIF) and explores its underlying mechanisms in ESCC. Briefly, our results showed that AIF could significantly increase radiosensitivity of ESCC cells both in vitro and in vivo, by increasing the effect of AIF on irradiation-induced DNA damage, apoptosis and cell cycle arrest. Mechanically, AIF aggravated irradiation-induced ROS generation in ESCC cells, which occurred via suppressing the expression of nuclear transcription factor Nrf2 and Nrf2-driven antioxidant molecule NQO-1 and HO-1. Collectively, we concluded that AIF functions as a potent radiosensitizer in human ESCC

Alpinumisoflavone inhibits osteoclast differentiation and exerts anti-osteoporotic effect in ovariectomized mice

Alpinumisoflavone (AIF), a naturally occurring flavonoid compound exacted from Derris eriocarpa, has been found to have a number of pharmacological activities. However, its role in bone disorder has not been investigated. The aim of this study is to evaluate the osteoprotective effect of AIF on ovariectomy-induced bone loss in mice model and related underlying mechanisms. Our study provides experimental evidence that AIF could regulate the remodeling process of bone and exert osteoprotective effect against ovariectomy-induced bone loss. Moreover, our results show that AIF suppresses osteoclast differentiation by attenuating RANKL-induced activation of p38, ERK and JNK pathways and consequently represses the expression of c-Fos and NFATc1.

Antimicrobial and antioxidant activity and chemical characterisation of Erythrina stricta Roxb. (Fabaceae)

Ethnopharmacological relevanceThe bark of Erythrina stricta Roxb. (Fabaceae) has been used in Indian indigenous systems as a remedy for rheumatism, stomach-ache, asthma, dysentery, contact dermatitis, eczema and skin infections. However, there have been limited phytochemical or biological studies on the bark of E. stricta and there are no studies that align with its traditional medicinal uses. Aim of the studyThe aim of this study was to assess the antimicrobial and antioxidant activity of the stem bark of E. stricta to support its topical use in the treatment of contact dermatitis, eczema and skin infections and to isolate and identify any bioactive compounds. Materials and methodsMTT microdilution and disc diffusion assays were used to determine the antimicrobial activities of n-hexane, dichloromethane, ethyl acetate, methanol and water extracts of the bark of E. stricta. Column and preparative thin layer chromatography were used for the purification of the dichloromethane extract. The structures of the compounds isolated were elucidated by extensive 1D and 2D NMR spectroscopic techniques and comparison with published data. The antioxidant activities of the extracts were determined by DPPH free radical scavenging and FRAP assays and the antioxidant activity of the pure compounds by dot-blot and DPPH staining methods. ResultsThe dichloromethane, ethyl acetate, and n-hexane extracts showed the most significant activity with MIC values of 7.8µg/mL, 125µg/mL, and 125µg/mL against a sensitive strain of Staphylococcus aureus. The dichloromethane and ethyl acetate extracts also showed significant activity against Candida albicans with MIC values of 125µg/mL and 1mg/mL respectively. GC-MS analysis of the n-hexane extract showed the presence of the antibacterial and antifungal compounds β-caryophyllene, caryophyllene oxide, α-selinene, β-selinene, selin-11-en-4-α-ol, α-copaene and δ-cadenine. Phytochemical studies of the dichloromethane extract led to the isolation of the novel compound erynone (1), together with six known compounds; wighteone (2), alpinum isoflavone (3), luteone (4), obovatin (5), erythrinassinate B (6) and isovanillin (7). Luteone (4) exhibited the most significant antibacterial activity with minimum inhibitory quantity (MIQ) values of 1.88µg, 1.88µg and 3.75µg, respectively, against sensitive (MSSA) and resistant strains (MRSA and MDRSA) of S. aureus using a TLC bioautography assay. Erynone (1) exhibited the greatest DPPH free radical scavenging activity. ConclusionsSeven compounds, including a new chromanone, were isolated from the antimicrobial dichloromethane extract of the stem bark of E. stricta. Six of the seven compounds showed antibacterial and/or antioxidant activities. These findings provide support for the customary (traditional and contemporary) use of E. stricta bark for the treatment of skin and wound infections.

Alpinumisoflavone and abyssinone V 4'-methylether derived from Erythrina lysistemon (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats.

Erythrina lysistemon was found to improve lipid profile in ovariectomized rats. Alpinumisoflavone (AIF) and abyssinone V 4'-methylether (AME) derived from this plant induced analogous effects on lipid profile and decreased atherogenic risks. To highlight the molecular mechanism of action of these natural products, we evaluated their effects on the expression of some estrogen-sensitive genes associated with cholesterol synthesis (Esr1 and Apoa1) and cholesterol clearance (Ldlr, Scarb1 and Cyp7a1). Ovariectomized rats were subcutaneously treated for three consecutive days with either compound at the daily dose of 0.1, 1 and 10 mg/kg body weight (BW). Animals were sacrificed thereafter and their liver was collected. The mRNA of genes of interest was analysed by quantitative real-time polymerase chain reaction. Both compounds downregulated the mRNA expression of Esr1, a gene associated with cholesterogenesis and cholesterol gallstone formation. AME leaned the Apoa1/Scarb1 balance in favour of Apoa1, an effect promoting high-density lipoprotein (HDL)-cholesterol formation. It also upregulated the mRNA expression of Ldlr at 1 mg/kg/BW per day (25%) and 10 mg/kg/BW per day (133.17%), an effect favouring the clearance of low-density lipoprotein (LDL)-cholesterol. Both compounds may also promote the conversion of cholesterol into bile acids as they upregulated Cyp7a1 mRNA expression. AIF and AME atheroprotective effects may result from their ability to upregulate mechanisms promoting HDL-cholesterol and bile acid formation.

Erythrina lysistemon – derived flavonoids account only in part for the plant's specific effects on rat uterus and vagina

BACKGROUND The stem bark ethyl acetate extract of Erythrina lysistemon was found to induce vaginal proliferation in ovariectomized rats orally treated. Alpinumisoflavone (AIF) and abyssinone V-4'-methyl-ether (AME), isolated as its major constituents, were reported to separately provoke uterine growth and/or vaginal proliferation. The present study aimed at evaluating the effects of the mixture of AIF and AME (51 mg/kg [AIF]+153 mg/kg [AME]) following their relative abundance in the extract, in order to compare these effects to those of E. lysistemon. METHODS The study was performed in ovariectomized rats treated intraperitoneally for 3 days. Estradiol valerate (E2 V) and AME were used for positive controls. Morphological and histological changes of animals' uterus and vagina were used as the hallmark of estrogenicity. RESULTS E. lysistemon extract induced estrogen-like effects only on the uterus and significantly increased uterine wet weight (p<0.01) and uterine epithelial height (p<0.01). These results suggest a tissue-selective action of E. lysistemon extract depending on the route of administration. The mixture of AIF and AME induced E. lysistemon-like effects only at a dose of 1 mg/kg BW/d (0.25 mg/kg+0.75 mg/kg), although these effects were lower in magnitude (p<0.05) compared to those induced by E. lysistemon extract. CONCLUSIONS Effects induced by the mixture of AIF and AME are analogous to those of E. lysistemon, but the low magnitude of these effects suggests that there are minor metabolites that interact with AIF and AME to provoke the specific effects of E. lysistemon.