scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory conditions induced by PTY-2 against STZ-induced stress in islets.

TL;DR: The results showed that PTY-2 favorably changed all the expressions via anti-oxidant, anti-apoptotic,Anti-hypoxic and anti-inflammatory pathways, making itself as a protective agent against streptozotocin induced islet stress in rats.
Abstract: The earlier assessment of Pueraria tuberosa (PT) has shown anti-diabetic effects through enhancing incretin action and DPP-IV (Dipeptidyl peptidase-IV) inhibition. The aim of this work was to further explore the protective role of aqueous extract of Pueraria tuberosa tuber (PTY-2) against streptozotocin (STZ) induced islet stress in rats. Diabetes was induced by STZ (65 mg/kg body weight) in charles foster male rats. After 60 days of STZ administration, animals with blood glucose levels > 200 g/dL were considered as diabetic. All the rats were later divided into three groups: Group-1 (STZ untreated normal rats), Group-2 (Diabetic control), and Group-3 (PTY-2 [50 mg/100 g bw treatment for next 10 days to diabetic rats). The rats were then sacrificed after the 10th day of treatment accordingly. STZ treatment led to an increase in expression of Matrix metalloproteinases-9 (MMP-9), Tumour necrosis factor-α (Tnf-α), Hypoxia inducible factor-α (HIF-1α), Vascular endothelial growth factor (VEGF), Interleukin-6 (IL-6), Protein kinase C-e (PKC-e), Nuclear factor kappa-light-chain-enhancer of activated B-cells (NFkB), and Caspase-3. Reverse Transcriptase-PCR (RT-PCR), Immunohistochemistry and Western-Blot analysis showed an increase in the expressions of Superoxide Dismutase (SOD) and Nephrin, and a decrease in the expressions of NFkB, PKC-e, TNF-α, MMP-9, HIF-1α, VEGF, Caspase-3 and IL-6 after 10 days of PTY-2 treatment. The results showed that PTY-2 favorably changed all the expressions via anti-oxidant, anti-apoptotic, anti-hypoxic and anti-inflammatory pathways, making itself as a protective agent against STZ induced islet stress. Further evaluation of PTY-2 might be helpful in establishing its role in the management of diabetes mellitus.
Citations
More filters
Journal ArticleDOI
TL;DR: Pueraria tuberosa (Roxb. ex Willd.) DC. as mentioned in this paper is a perennial herb distributed throughout India and other Asian countries, and its extracts have been reported for nutritional and medicinal properties in Ayurveda as well as in Chinese traditional practices.
Abstract: Pueraria tuberosa (Roxb. ex Willd.) DC. (Fabaceae), also known as Indian Kudzu (vidari kand), is a perennial herb distributed throughout India and other Asian countries. Traditionally, tuber and leaves of this plant have extensively been reported for nutritional and medicinal properties in Ayurveda as well as in Chinese traditional practices. The objective of the present review is to compile and update the published data on traditional uses, pharmacological potential, and phytochemistry of compounds isolated from the plant Pueraria tuberosa. P. tuberosa extracts and its purified compounds possess multiple activities such as anticancer, anticonvulsant, antidiabetic, antifertility, anti-inflammatory, antioxidant, anti-stress, antiulcerogenic, cardioprotective, hypolipidemic, hepatoprotective, immunomodulatory, nephroprotective, nootropic, neuroprotective, and wound healing. Tuber and leaf extracts of P. tuberosa contain several bioactive constituents such as puerarin, daidzein, genistein, quercetin, irisolidone, biochanin A, biochanin B, isoorientin, and mangiferin, which possess an extensive range of pharmacological activities. The extensive range of pharmacological properties of P. tuberosa provides opportunities for further investigation and presents a new approach for the treatment of ailments. Many phytochemicals have been identified and characterized from P. tuberosa; however, some of them are still unexplored, and there is no supporting data for their activities and exact mechanisms of action. Therefore, further investigations are warranted to unravel the mechanisms of action of individual constituents of this plant.

22 citations

Journal ArticleDOI
TL;DR: Wang et al. as mentioned in this paper found that purslane seed (MCXZ) treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice.
Abstract: Portulaca oleracea L., known as the "vegetable for long life," is an annual succulent herb that is widely distributed worldwide. Many clinical and experimental studies have demonstrated that purslane seed (MCXZ) can be used as an adjunctive and alternative therapy for the treatment of diabetes mellitus (DM). However, the underlying active constituents and pharmacological mechanisms through which MCXZ exerts effects in DM remain unclear. In the present study, we confirmed that MCXZ treatment resulted in hypoglycemic activity, lowering the fasting blood glucose and glycated hemoglobin levels in streptozotocin-induced diabetic mice. Then, ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry was used to systematically analyze the chemical profile of MCXZ, resulting in the identification of 84 constituents, including 31 organic acids and nine flavonoids. Finally, the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine was employed to analyze the key active components of MCXZ and the molecular mechanisms through which these components acted in DM. Ten key active compounds were identified based on the topological importance of their corresponding putative targets within the known DM-associated therapeutic target network of known MCXZ putative targets. Functionally, these candidate targets play critical anti-hyperlipidemia, anti-hyperglycemia, immunity regulation, and inflammatory roles involving DM-related pathways, such as the vascular endothelial growth factor (VEGF) signaling pathway and Fc gamma R-mediated phagocytosis, which indicated that MCXZ exhibited anti-diabetic activity through multi-faced actions.

4 citations

Journal ArticleDOI
TL;DR: In this paper, two new polysaccharides (PLB-1-1 and PLB- 1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9.1 × 103 Da and 3.8 × 103 da, respectively, and evaluated by monosaccharide composition, GC-MS and NMR spectroscopy.
Abstract: Diabetes seriously endangers public health and brings a heavy economic burden to the country. Inflammation is one of the main inducing factors of type-2 diabetes (T2D) and may cause some complications of diabetes, such as diabetic encephalopathy and peripheral neuropathy. In-depth research and development of drugs to cure diabetes and complications are of great significance. Pueraria lobate is a medicinal herb used in several countries to treat many diseases. Here, two new polysaccharides (PLB-1-1 and PLB-1-2) were isolated and purified from the root of Pueraria lobata with molecular weights of 9.1 × 103 Da and 3.8 × 103 Da, respectively. The structure was evaluated by monosaccharide composition, GC-MS and NMR spectroscopy. It was determined that PLB-1-1 comprised →4)-α-D-Glcp-(1→, α-D-Glcp-(1→, →6)-β-D-Galp-(1→, →3)-α-L-Araf-(1→, →3,6)-β-D-Manp-(1→ and →4,6)-β-D-Manp-(1→, and PLB-1-2 consisted of →4)-α-D-Glcp-(1→, β-D-Glcp-(1→, →4,6)-β-D-Glcp-(1→, →3,6)-β-D-Manp-(1→ and α-L-Fucp-(1→. Furthermore, both PLB-1-1 and PLB-1-2 showed anti-inflammatory and inhibitory activities of α-glucosidase and α-amylase in vitro. Therefore, the new polysaccharides, i.e., PLB-1-1 and PLB-1-2, may be considered candidates for the treatment of diabetes and its related complications.

4 citations

Posted ContentDOI
14 Jun 2019-bioRxiv
TL;DR: No adverse alterations in cardiac fibers of the heart, size and shapes in crypts and villi of intestine, seminiferous tubules and spermatozoa count in testis, three zones of adrenal gland, and spleen were seen in all treated groups of PTWE.
Abstract: Objective The present study was undertaken to investigate the safe doses of Pueraria tuberosa water extract (PTWE) on different organs. Methodology Haematoxylin and eosin staining was used to study the morphological alterations in heart, intestine, testis, adrenal gland and spleen. Followed the OECD guidelines 407 of repeated toxicity with respect to the selection of dose and days for different organs. The selected doses of PTWE were 250, 500, 1000 and 2000 mg/kg bw and the durations selected were 7, 14, 21 and 28 days. Result According to the obtained results, we have found no any types of adverse alteration in cardiac fibers of the heart, size and shapes in crypts and villi of intestine, semeniferous tubules and spermatozoa count were normal in testis, all three zones of adrenal gland were normally identified and no any adverse sign of pulps in spleen was seen in all treated groups of PTWE Conclusion There was no any types of adverse morphological alteration found in any organs. The drug PTWE are safe at 1000 mg/kg bw upto 28 days and 2000 mg/ kg bw upto 21 days respectively.

2 citations


Cites background from "Anti-oxidant, anti-apoptotic, anti-..."

  • ...However, for the first time we reported its action of GLP-1, GIP, TNF-alpha, IL-6 and HIF-1 which were inhibited by Pueraria Tuberosa in different experimental conditions such as diabetes and kidney damage (Srivastava et al 2019)....

    [...]

Journal ArticleDOI
TL;DR: The protective action of PTY-2 against STZ mediated intestinal damage is demonstrated and may be taken as a herbal remedy for diabetes-induced intestinal damages.
Abstract: BACKGROUND: Enhanced expression of PTY-2 dipeptidyl-peptidase-IV (DPP-IV) has been found to improve has been found in various intestinal diseases. Pueraria tuberosa tuber water extract-2 (PTY-2) is already known to have DPP-IV inhibitory potential. At the mRNA level, this inhibition has not yet been investigated. Increased incretin secretion due to inhibition of DPP-IV could lead to the suppression of stress and apoptosis of intestinal cells. AIM: In this research, we tried to study the antioxidant, anti-apoptotic, and DPP-IV inhibitory effect of PTY 2 against intestinal damage induced by STZ. METHODS: We found morphological damage to the intestine following streptozotocin (STZ) injection (65 mg/kg bw) in male Charles foster rats through histological examination. Superoxide dismutase (SOD) and DPP-IV mRNA expressions were analyzed by polymerase chain reaction and cell apoptosis was examined by tunnel assay and Bcl 2 immunoexpression. RESULTS: In STZ-induced diabetic control, the number and length of villi were decreased, but these damages were reversed by 10 days of PTY-2 treatment. SOD expression was found to be decreased whereas DPP-IV expression was enhanced with significant intestinal cell apoptosis in the diabetic control group. Treatment with PTY-2 decreases stress by upregulating SOD expression and by downregulating the expression of DPP-IV. These PTY-2 recoveries contribute to the suppression of apoptosis in the intestinal cells. CONCLUSION: The protective action of PTY-2 against STZ mediated intestinal damage is demonstrated by these short studies. Therefore, PTY-2 may be taken as a herbal remedy for diabetes-induced intestinal damages.

2 citations

References
More filters
Journal ArticleDOI
TL;DR: Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer.

1,513 citations

Journal ArticleDOI
TL;DR: Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours.
Abstract: Apoptosis can be induced in response to hypoxia. The severity of hypoxia determines whether cells become apoptotic or adapt to hypoxia and survive. A hypoxic environment devoid of nutrients prevents the cell undergoing energy dependent apoptosis and cells become necrotic. Apoptosis regulatory proteins are delicately balanced. In solid tumours, hypoxia is a common phenomenon. Cells adapt to this environmental stress, so that after repeated periods of hypoxia, selection for resistance to hypoxia induced apoptosis occurs. These resistant tumours probably have a more aggressive phenotype and may have decreased responsiveness to treatment. The key regulator of this process, hypoxia inducible factor 1 (HIF-1), can initiate apoptosis by inducing high concentrations of proapoptotic proteins, such as BNIP3, and can cause stabilisation of p53. However, during hypoxia, antiapoptotic proteins, such as IAP-2, can be induced, whereas the proapoptotic protein Bax can be downregulated. During hypoxia, an intricate balance exists between factors that induce or counteract apoptosis, or even stimulate proliferation. Understanding the regulation of apoptosis during hypoxia and the mechanisms of resistance to apoptosis might lead to more specific treatments for solid tumours.

697 citations

Journal ArticleDOI
David E. Moller1
TL;DR: Current evidence suggests that administration of exogenous TNF-alpha to animals can induce insulin resistance, whereas neutralization of T NF-alpha can improve insulin sensitivity, and it is still probable that TTF-alpha is a contributing factor in common metabolic disturbances such as insulin resistance and dyslipidemia.
Abstract: Tumor necrosis factor alpha (TNF-alpha) has well-described effects on lipid metabolism in the context of acute inflammation, as in sepsis. Recently, increased TNF-alpha production has been observed in adipose tissue derived from obese rodents or human subjects and TNF-alpha has been implicated as a causative factor in obesity-associated insulin resistance and the pathogenesis of type 2 diabetes. Thus, current evidence suggests that administration of exogenous TNF-alpha to animals can induce insulin resistance, whereas neutralization of TNF-alpha can improve insulin sensitivity. Importantly, results from knockout mice deficient in TNF-alpha or its receptors have suggested that TNF-alpha has a role in regulating in vivo insulin sensitivity. However, the absence of TNF-alpha action might only partially protect against obesity-induced insulin resistance in mice. Multiple mechanisms have been suggested to account for these metabolic effects of TNF-alpha. These include the downregulation of genes that are required for normal insulin action, direct effects on insulin signaling, induction of elevated free fatty acids via stimulation of lipolysis, and negative regulation of PPAR gamma, an important insulin-sensitizing nuclear receptor. Although current evidence suggests that neutralizing TNF-alpha in type 2 diabetic subjects is not sufficient to cause metabolic improvement, it is still probable that TNF-alpha is a contributing factor in common metabolic disturbances such as insulin resistance and dyslipidemia.

665 citations

Journal ArticleDOI
TL;DR: Evidence is provided that GLP-1 added to freshly isolated human islets preserves morphology and function and inhibits cell apoptosis, and better-preserved three-dimensional islet morphology in the GLp-1-treated islets, compared with controls.
Abstract: The peptide hormone, glucagon-like peptide 1 (GLP-1), has been shown to increase glucose-dependent insulin secretion, enhance insulin gene transcription, expand islet cell mass, and inhibit -cell apoptosis in animal models of diabetes. The aim of the present study was to evaluate whether GLP-1 could improve function and inhibit apoptosis in freshly isolated human islets. Human islets were cultured fo r5di n thepresence, or absence, of GLP-1 (10 nM, added every 12 h) and studied for viability and expression of proapoptotic (caspase-3) and antiapoptotic factors (bcl-2) as well as glucose-dependent insulin production. We observed better-preserved three-dimensional islet morphology in the GLP-1-treated islets, compared with controls. Nuclear condensation, a feature of cell apoptosis, was inhibited by GLP-1. The reduction in the number of apoptotic cells in GLP-1-treated islets was particularly evident at d 3 (6.1% apoptotic nuclei in treated cultures vs. 15.5% in controls; P < 0.01) and at d 5 (8.9 vs. 18.9%; P < 0.01). The antiapoptotic effect of GLP-1 was associated with the downregulation of active caspase-3 (P < 0.001) and the up-regulation of bcl-2 (P < 0.01). The effect of GLP-1 on the intracellular levels of bcl-2 and caspase-3 was observed at the mRNA and protein levels. Intracellular insulin content was markedly enhanced in islets cultured with GLP-1 vs. control (P < 0.001, at d 5), and there was a parallel GLP-1-dependent potentiation of glucose-dependent insulin secretion (P < 0.01 at d 3; P < 0.05 at d 5). Our findings provide evidence that GLP-1 added to freshly isolated human islets preserves morphology and function and inhibits cell apoptosis. (Endocrinology 144: 5149 –5158, 2003)

645 citations

Journal ArticleDOI
TL;DR: It is demonstrated that GLP-1 receptor signaling directly modifies the susceptibility to apoptotic injury, and provides a new potential mechanism linking GLP -1 receptor activation to preservation or enhancement of β cell mass in vivo.

582 citations