PMID: 

Biomed Pharmacother. 2019 Sep ;117:109162. Epub 2019 Jun 26. PMID: 31254739

Abstract Title: 

Flos Abelmoschus manihot extract attenuates DSS-induced colitis by regulating gut microbiota and Th17/Treg balance.

Abstract: 

Flos Abelmoschus manihot is widely used as traditional drug in China. Abelmoschus manihot (AM) extracted from Flos Abelmoschus manihot that has been applied for treating chronic inflammatory diseases. Here we showed that AM significantly alleviated DSS-induced colitis in mice. AM modified gut microbiota composition, increased microbial diversity, and in particularly, elevated the abundance of short chain fatty acids (SCFAs)-producing gut microbiota in colitic mice. Consequently, levels of SCFAs especially butyrate and acetate were increased upon AM treatment, which, primarily through peroxisome proliferator-activated receptor gamma (PPARγ) pathway, led to the enhanced Treg generation and the suppressed Th17 development. Together, we herein provide the first evidences to support that AM, a natural plant-derived complex, can potentially reset gut microbiome and metabolism, resume immune and tissue homeostasis, and hence prevent colitis, which may provide a new perspective on IBD pathogenesis and suggest a novel microbiota-targeting therapy for inflammatory gut diseases.

read more

PMID: 

Iran J Pharm Res. 2019 ;18(1):369-382. PMID: 31089371

Abstract Title: 

Effect ofPowder on Ovarian Histology, Expression of Apoptotic Genes and Oxidative Stress in Diabetic Rats Fed with High Fat Diet.

Abstract: 

Okra () is an antidiabetic plant whose beneficial effect on ovarian dysfunction in diabetes condition has not been clarified. The present study was designed to examine the effect of Okra powder on serum oxidant/antioxidant status, ovarian structure, and expression of apoptotic/antiapoptotic related genes in ovary of experimentally induced high fat diet diabetic rats. Diabetes was induced by 5 weeks feeding of Wistar rats with high fat diet (HFD) and subsequent i.p injection of STZ (35 mg/kg). Diabetic animals (serum glucose above 250 mg/dL) were treated with Okra powder (200mg/kg) supplemented in diet or metformin (200mg/kg) for 30days. After 30 days of treatment, animals were euthanized and insulin resistance markers (insulin and glucose levels and HOMA-IR), ovarian expression of apoptotic/antiapoptotic genes (Bax, caspase3 and Bcl2) and serum oxidant/antioxidant levels (SOD, GPX and CAT activities and MDA level) were determined. The ovaries were also processed for histological study. Hyperglycemia and reduced body weight of diabetic rats were improved after administration of Okra for 30days. This effect was relatively similar to metformin. Okra resulted in reduction of follicular atresia in concomitant with down regulation of apoptotic related genes (Bax and caspase3in ovary of diabetic rats. Okra could also diminished oxidative stress in diabetic rats by increasing of serum GPX and CAT activities and reducing the lipid peroxidation level. The results of the present study revealed that Okra powder could be useful intervention for improvement of ovaian dysfunction in diabetic rat by three probable mechanisms; attenuation of glucotoxicity, down regulation of ovarian apoptosis related genes and reduction of oxidative stress.

read more

PMID: 

World J Gastroenterol. 2018 Aug 14 ;24(30):3414-3425. PMID: 30122880

Abstract Title: 

Total flavone ofsuppresses epithelial-mesenchymal transitioninterfering transforming growth factor-β1 signaling in Crohn's disease intestinal fibrosis.

Abstract: 

AIM: To explore the role and mechanism of total flavone of(TFA) on epithelial-mesenchymal transition (EMT) progress of Crohn's disease (CD) intestinal fibrosis.METHODS: First, CCK-8 assay was performed to assess TFA on the viability of intestinal epithelial (IEC-6) cells and select the optimal concentrations of TFA for our further studies. Then cell morphology, wound healing and transwell assays were performed to examine the effect of TFA on morphology, migration and invasion of IEC-6 cells treated with TGF-β1. In addition, immunofluorescence, real-time PCR analysis (qRT-PCR) and western blotting assays were carried out to detect the impact of TFA on EMT progress. Moreover, western blotting assay was performed to evaluate the function of TFA on the Smad and MAPK signaling pathways. Further, the role of co-treatment of TFA and si-Smad or MAPK inhibitors has been examined by qRT-PCR, western blotting, morphology, wound healing and transwell assays.RESULTS: In this study, TFA promoted transforming growth factor-β1 (TGF-β1)-induced (IEC-6) morphological change, migration and invasion, and increased the expression of epithelial markers and reduced the levels of mesenchymal markers, along with the inactivation of Smad and MAPK signaling pathways. Moreover, we revealed that si-Smad and MAPK inhibitors effectively attenuated TGF-β1-induced EMT in IEC-6 cells. Importantly, co-treatment of TFA and si-Smad or MAPK inhibitors had better inhibitory effects on TGF-β1-induced EMT in IEC-6 cells than either one of them.CONCLUSION: These findings could provide new insight into the molecular mechanisms of TFA on TGF-β1-induced EMT in IEC-6 cells and TFA is expected to advance as a new therapy to treat CD intestinal fibrosis.

read more

PMID: 

Oxid Med Cell Longev. 2018 ;2018:8987173. Epub 2018 Aug 5. PMID: 30174782

Abstract Title: 

The Protective Effect of the Total Flavonoids ofL. Flowers on Transient Cerebral Ischemia-Reperfusion Injury Is due to Activation of the Nrf2-ARE Pathway.

Abstract: 

L. has favorable nutritional/medicinal features. We found the content of total flavonoids in flower extract to be the highest (788.56 mg/g) of all the different parts of; according to high-performance liquid chromatography, the quercetin-3-O-[-D-glu-(1 → 6)]–D-glucopyranoside content was 122.13 mg/g. Protective effects of an extract of the total flavonoids offlowers (AFF) on transient cerebral ischemia-reperfusion injury (TCI-RI) were investigated. Compared with the model group, mice treated with AFF (300 mg/kg) for 7 days showed significantly reduced neurologic deficits, infarct area, and histologic changes in brain tissue, accompanied by increased contents of superoxide dismutase, whereas contents of nitric oxide and malondialdehyde decreased. AFF upregulated the expression of Nrf2, HO-1, and NQO1. These data suggest that AFF protects against TCI-RI by scavenging free radicals and activating the Nrf2-ARE pathway.

read more

PMID: 

J Food Drug Anal. 2019 Jan ;27(1):135-144. Epub 2018 Aug 14. PMID: 30648566

Abstract Title: 

Abelmoschus esculentus subfractions improved nephropathy with regulating dipeptidyl peptidase-4 and type 1 glucagon-like peptide receptor in type 2 diabetic rats.

Abstract: 

Abelmoschus esculentus (AE) has been used in traditional medicine to ameliorate hyperglycemia, but its mucilage increased bioassay difficulties. We have obtained a series of AE subfractions. Among them F1 and F2 regulated dipeptidyl peptidase-4 (DPP-4) and type 1 glucagon-like peptide receptor (GLP-1R), the treatment targets for type 2 diabetes. F1, F2 and fraction residues (FR) showed advantage on different aspects, which attenuates insulin resistance and metabolic disorder in vivo, and prevents renal-tubular change in vitro. In the present study, using type 2 diabetes model induced by high fat diet (HFD) and streptozotocin (STZ), we aim to investigate whether AE prevent diabetic nephropathy by regulating the putative markers. The results showed that all the subfractions ameliorated albuminuria and renal hyperfiltration (measured by creatinine clearance rate; CCr) accompanied with diabetes, while F2 acted most promptly and consistently. Histologically AE reduced renal tubular change, fibrosis and fat deposition. F2 and FR exerted significant effects to decrease DPP-4 while increase GLP-1R. Although all the subfractions were effective to reduce oxidative stress, only F2 acted on kidneys specifically. In conclusion, we have demonstrated AE has benefits to regulate DPP-4 and GLP-1R, to reduce oxidative stress and renal fibrosis, with resultant to improve renalfunction and prevent diabetic renal damage. Taken together, F2 could be more promising to be developed as adjuvant for diabetic nephropathy.

read more

PMID: 

Molecules. 2019 May 17 ;24(10). Epub 2019 May 17. PMID: 31108940

Abstract Title: 

Polysaccharide from Okra ((L.) Moench) Improves Antioxidant Capacity via PI3K/AKT Pathways and Nrf2 Translocation in a Type 2 Diabetes Model.

Abstract: 

Polysaccharide extracted from okra ((L.) Moench), a traditional functional food, is a biologically active substance reported to possess hypoglycemic and anti-oxidative qualities. However, it is unknown which polysaccharides play a role and have the potential mechanism. This present study is to assess the possible impacts of a novel polysaccharide isolated from okra (OP) on mice fed with a high-fat diet (HFD) combined with an intraperitoneal injection () of 100 mg/kg streptozotocin (STZ) twice, to induce type 2 diabetes mellitus (T2DM). We found that an eight-week administration of OP at 200 or 400 mg/kg body weight significantly alleviated the symptoms, with elevations in blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), as well as reducing high-density lipoprotein cholesterol (HDL-C), body weight, food, and water consumption. The OP treatment increased the hepatic glycogen and decreased the mussy hepatic cords and liver fibrosis in the T2DM mice. The decreases of ROS and MDA and the increases of SOD, GSH-Px and CAT in liver were observed after administration of OP. OP alleviated the T2DM characteristics through the activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase 3 beta (GSK3β) pathway, and enhanced the nuclear factor erythroid-2 (Nrf2) expression and promoted Nrf2-medicated heme oxygenase-1(HO-1) and superoxide dismutase 2 (SOD2) expression. OP also relieved mitochondrial dysfunction by inhibiting NOX2 activation. Taken together, these findings suggest that a polysaccharide isolated from okra exerts anti-T2DM effects partly by modulating oxidative stress through PI3K/AKT/GSK3β pathway-medicated Nrf2 transport. We have determined that a polysaccharide possesses hypoglycemic activity, as well as its underlying mechanism.

read more

PMID: 

PLoS One. 2019 ;14(6):e0217400. Epub 2019 Jun 25. PMID: 31237881

Abstract Title: 

Abelmoschus esculentus subfractions attenuate beta amyloid-induced neuron apoptosis by regulating DPP-4 with improving insulin resistance signals.

Abstract: 

The association of Alzheimer disease (AD) and Diabetes (DM) is less clear. Accumulation of beta amyloid (Aβ) and presence of hyperphosphorylated tau (p-tau) are hallmarks of AD, spreading in the region where insulin receptors are also found. Aβ exerts neuron toxicity, and could disturb insulin signaling of phosphatidylinositol 3-kinase (PI3K), glycogen synthase kinase (GSK)-3β and AMP-activated protein kinase (AMPK), but increase IRS-1-Ser307 phosphorylation which is viewed as insulin resistance marker. Previously we reported dipeptidyl peptidase-4 (DPP-4) mediate insulin resistance signals, and Abelmoschus esculentus (AE) subfractions F1 (rich in quercetin glucosides and triterpene ester) andF2 (containing large amount of polysaccharides) attenuate DPP-4-mediated apoptosis. In the present study, we aim to investigate if Aβ induce neuron death by regulating DPP-4 and insulin resistance signals, and the putative effect of F1 and F2. By MTT, microscopy, and Western blotting, we demonstrate treatment of appropriate doses of AE subfractions prevent Aβ-induced neuron apoptosis. F1 attenuate Aβ-induced caspase 3 expression especially at 25 μg/mL, while F2 attenuate caspase 3 activation even at the low dose of 1 μg/mL. Both AE subfractions decrease Aβ-enhanced DPP-4, but increase Aβ-reduced p-AMPK and p-PI3K. The activity analysis reveals that F2 is more valid than F1 to reduce DPP-4 activity. The inhibition of DPP-4 demonstrates it plays the pivotal role in Aβ-induced neuron apoptosis. Moreover, although both F1 and F2 are effective to inhibit p-IRS-1-Ser307, F2 takes advantage to reduce p-Tau while F1 is superior to enhance p-GSK-3β. This implies AE subfractions act on different targets, and could be developed respectively. In conclusion, we demonstrate AE is potential to prevent Aβ-induced neuron damage by regulating DPP-4 and the insulin resistance cascades. AE could be an adjuvant to protect neuron degenerative disease related to Aβ and insulin resistance.

read more

PMID: 

Nat Prod Res. 2019 Jul 8:1-7. Epub 2019 Jul 8. PMID: 31282220

Abstract Title: 

Abscisic acid identification in Okra,L. (Moench): perspective nutraceutical use for the treatment of diabetes.

Abstract: 

Okra,L. (Moench), also known as Lady's Fingers, gombo, or bamje, is an annual plant belonging to thefamily. Traditional olistic medicine since centuries directly associates this plant and its parts to a beneficial health hypoglycemic effect. Since the abscisic acid (ABA) has been associated to an interesting hypoglycemic effect, this triggered us to verify and quantify the presence of the abscisic acid in the okra phytocomplex. In particular, ABA, a plant derived hormone, has been proven by recent studies to be effective on mammals. To determine and quantify the ABA content, different parts of the Okra plant extracts have been evaluated, and HPLC-DAD analysis has been used allowing us to report for the first time the presence of this isoprenoid compound. Bioaccessibility has been also investigated using a simulated gastro intestinal (GI) digestion protocol with the aim of explore the possibility of okra extract as nutraceutical.

read more

PMID: 

Int J Biol Macromol. 2019 Aug 20 ;140:568-576. Epub 2019 Aug 20. PMID: 31442509

Abstract Title: 

The anti-nephritic activity of a polysaccharide from okra (Abelmoschus esculentus (L.) Moench) via modulation of AMPK-Sirt1-PGC-1α signaling axis mediated anti-oxidative in type 2 diabetes model mice.

Abstract: 

Diabetic nephropathy (DN) with high morbidity and mortality is one of the most severe diabetes complications and affects nearly one-third of people with diabetes. Our present experiment was designed to assess the potential therapeutic of a polysaccharide purified from okra (OP) on DN in high-fat diet-fed and streptozotocin (STZ)-induced diabetic mice. We found that an 8-week treatment with OP could significantly decrease the 24-h urine protein (24-h UP), serum creatinine (Scr), serum urea nitrogen (SUN) and glycosylated hemoglobin (HbA1c) levels, which are regard as the biomarkers of renal injury. The results of immunohistochemical analysis and histopathological examination showed that the diabetic-induced microstructural changes and fibrosis in kidney can be alleviated by the administration of OP (400 mg/kg). Our immunofluorescences results demonstrated that OP (400 mg/kg) could greatly reduce the level of reactive oxygen species (ROS) in kidney. In addition, we also studied the level of SOD, GSH, CAT, HO-1, Nrf2, p-AMPK, PGC-1α, Sirt1, Bcl-2, cleaved caspase-3 and Bax in renal tissue by assay kit and western blot. Our results suggested that OP ameliorated DN in diabetic mice, which is possibly related to suppressing apoptosis and oxidative stress through activating AMPK-Sirt1-PGC-1α signaling axis.

read more

PMID: 

Pharmacogn Mag. 2018 Jan-Mar;14(53):116-123. Epub 2018 Feb 20. PMID: 29576711

Abstract Title: 

Fraction induces apoptosis and G2/M Arrest via c-Jun N-Terminal kinase signaling pathway in oral squamous carcinoma KB Cells.

Abstract: 

Background: fraction (CMF) has been shown to possessantitumor activity against human chronic myeloid leukemia K562 cells in our previous research.Materials and Methods: Theinhibitory activities of CMF on the growth of KB cells were evaluated by viability assay. The apoptotic and cell cycle influences of CMF were detected by 4',6-diamidino-2-phenylindole staining and flow cytometry assay. The expression of different apoptosis-associated proteins and cell cycle regulatory proteins was examined by Western blot assay. The nuclear localization of c-Jun was observed by fluorescence staining.Objective: The objective of this study was to investigate the antiproliferative effect of CMF as well as the mechanism underlying the apoptosis and cell cycle arrest it induces in KB cells.Results: CMF suppressed KB cells' proliferation in a dose- and time-dependent manner. Flow cytometric analysis indicated that CMF induced G2/M cell cycle arrest and apoptosis. Western blot analysis revealed that CMF induced caspase-3, caspase-9, and PARP cleavages, and increased the Bax/Bcl-2 ratio. CMF also led to increased expression of p21, decreased expression of cyclin B1, mitotic phosphatase cdc25c, and mitotic kinase cdc2, as well as unchanged expression of p53. In addition, CMF stimulated c-Jun N-terminal kinases (JNK) protein phosphorylations, resulting in upregulated expression of c-Jun and nuclear localization of c-Jun. Pretreatment with JNK inhibitor SP600125 suppressed CMF-induced apoptosis and G2/M arrest.Conclusions: CMF is capable of modulating c-Jun caspase and Bcl-2 family proteins through JNK-dependent apoptosis, which results in G2/M phase arrest in KB cells. CMF could be developed as a promising candidate for the new antitumor agents.SUMMARY: CMF exhibited strong anticancer activity against oral squamous carcinoma KB cellsCMF inhibited KB cells' proliferation via induction of apoptosis and G2/M cell cycle arrestCMF activated JNK signaling pathway and promoted the nuclear localization of c-JunCMF regulated the apoptosis- and cell cycle-related proteins in a manner dependent on JNK/c-Jun pathway.CMF:fraction; OSCC: Oral squamous cell carcinoma; JNK: c-Jun N-terminal kinase.

read more