Recent advances in immunotherapeutics have not yet changed the routine management of autoimmune type 1 diabetes. There is an opportunity to repurpose therapeutics used to treat other diseases to treat type 1 diabetes, especially when there is evidence for overlapping mechanisms. Janus kinase (JAK) 1/JAK2 inhibitors are in development or clinical use for indications including rheumatoid arthritis. There is good evidence for activation of the JAK1/JAK2 and signal transducer and activator of transcription (STAT) 1 pathway in human type 1 diabetes and in mouse models, especially in β-cells. We tested the hypothesis that using these drugs to block the JAK-STAT pathway would prevent autoimmune diabetes. The JAK1/JAK2 inhibitor AZD1480 blocked the effect of cytokines on mouse and human β-cells by inhibiting MHC class I upregulation. This prevented the direct interaction between CD8 T cells and β-cells, and reduced immune cell infiltration into islets. NOD mice treated with AZD1480 were protected from autoimmune diabetes, and diabetes was reversed in newly diagnosed NOD mice. This provides mechanistic groundwork for repurposing clinically approved JAK1/JAK2 inhibitors for type 1 diabetes.
The present study was designed to evaluate the antidiabetic potential of the aqueous leaves extract of Zanthoxylum armatum DC. leaves using in vivo and in vitro approaches. For in vivo studies, blood glucose level was monitored at different intervals after administration of varying doses of the extract for its hypoglycemic (100–6000 mg/kg b.w.) and antihyperglycemic (250 mg/kg b.w.) effect in normoglycemic and diabetic mice. In vitro enzymatic inhibition activity was tested against α-amylase, α- and β-glucosidase and lipase. Additionally hydroxyl radical, hydrogen peroxide scavenging assay and phytochemical screening were also performed. Element analysis of the plant was studied by Atomic Absorption Spectrometry (AAS) and Inductively Coupled Plasma Atomic Emission Spectrometer (ICP-AES). The plant extract showed significant hypoglycemic and antihyperglycemic effect in normoglycemic and diabetic mice. The IC50 values of extract for α-amylase, β-glucosidase, lipase, hydroxyl radical scavenging activity, hydrogen peroxide scavenging activity were 7.40 mg/ml, 0.30 mg/ml, 8.35 mg/ml, 3.25 mg/ml, 9.62 mg/ml respectively and the percentage of inhibition for α-glucosidase was 79.82% at 0.8 mg/ml. In vitro studies were compared with their respective standards. Elemental analysis revealed the presence of essential elements such as Mg, V, Fe, Cr, Zn, Cu, Mo, Mn, K, Ca, P and Sr which are all known to play a role in regulating blood glucose. The results demonstrate that Z. armatum aqueous leaves extract possess antidiabetic property in both in vivo and in vitro condition.
Uncontrolled inflammatory responses or cytokine storm associated with viral infections results in deleterious consequences such as vascular leakage, severe hemorrhage, shock, immune paralysis, multi‐organ failure, and even death. With the emerging new viral infections and lack of effective prophylactic vaccines, evidence‐based complementary strategies that limit viral infection‐mediated hyperinflammatory responses could be a promising approach to limit host tissue injury. The present review emphasizes the potentials of antiinflammatory phytochemicals in limiting hyperinflammatory injury caused by viral infections. The predominant phytochemicals along with their mechanism in limiting hyperimmune and pro‐inflammatory responses under viral infection have been reviewed comprehensively. How certain phytochemicals can be effective in limiting hyper‐inflammatory response indirectly by favorably modulating gut microbiota and maintaining a functional intestinal barrier has also been presented. Finally, we have discussed improved systemic bioavailability of phytochemicals, efficient delivery strategies, and safety measures for effective antiinflammatory phytotherapies, in addition to emphasizing the requirement of tightly controlled clinical studies to establish the antiinflammatory efficacy of the phytochemicals. Collectively, the review provides a scooping overview on the potentials of bioactive phytochemicals to mitigate pro‐inflammatory injury associated with viral infections.
The present study was investigated to identify the active fraction of P. fulgens with aldose reductase (AR) inhibitory potential. AR is the rate limiting step of polyol pathway implicated in the onset of chronic complications of diabetes. In this study, kidney homogenates of normoglycemic and diabetic mice were used as a source of AR enzyme preparation for in vitro analysis. The Terpenoid/Phenolic (TP) fraction of P. fulgens had the lowest IC50 value (0.152 mg/ml) for AR than the other fractions. TP fraction was separated using thin layer chromatography (TLC) and separated TLC fractions were tested for their AR inhibitory activity. Among the TLC fractions, F-V had the lowest IC50 value (0.156 mg/ml) and was characterized further using High Performance Liquid Chromatography (HPLC), Infra-Red (IR) Spectroscopy and Mass Spectroscopy (MS). F-V showed absorption maxima at λ230 nm and λ280 nm. HPLC profile of this fraction showed the presence of one prominent peak with a retention time of 1.621. IR spectra of the prominent peak indicated the presence of aromatic group which is phenolic in nature. MS of the prominent peak showed m/z ratio of 458.8. The active fraction isolated from P. fulgens has been shown to inhibit AR in normoglycemic and diabetic mice.
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