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Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia and insulin resistance. 4-hydroxyisoleucine (4-HIL) is a non-proteinogenic amino acid isolated from the fenugreek seeds and has enormous pharmacological activities. The present study was undertaken to investigate the antihyperglycemic effect of 4-HIL in streptozotocin (STZ)-induced diabetic rats. Moreover, its toxicity was evaluated in vitro and in vivo employing human embryonic kidney cells (HEK-293) and healthy rats, respectively. In experiment 1, STZ-induced diabetic male rats were subjected to an oral treatment of 4-HIL (100 mg/kg), while experiment 2 deals with the effects of 4-HIL on healthy male and female rats following oral administration. The treatment (experiment 1) declined the elevated blood glucose level, feed intake, and increased body weight(s). Additionally, blood glucose impairment was improved as observed by OGTT and IPGT tests. Pancreatic histopathology revealed mild changes in the 4-HIL group. Moreover, experiment 2 showed increased body weight, normal blood glucose levels (male—106.06 ± 7.49 mg/dl and female—100.06 ± 14.69 mg/dL), hematological parameters, and histopathological profiles in the treatment group. 4-HIL did not affect the viability of HEK-293 cells, and no signs of toxicity were observed in healthy rats. Therefore, the study concludes that 4-HIL has potential antihyperglycemic activity without any toxic effects. [ABSTRACT FROM AUTHOR]

Background: Diethylene glycol monoethyl ether (DEGEE) is widely used as a solubilizer in cosmetics as well as in oral, topical, transdermal and injectable pharmaceutical formulations. Due to the unavailability of detailed toxicological studies on DEGEE, the Scientific Committee on Consumer Products (SCCP) found its toxicological reports to be unsatisfactory, comprising only summaries. Also, a few reports have raised concern on the use of DEGEE as it might cause damage to the kidneys. Objective: Safety assessment of DEGEE using in vitro and in vivo models. Methods: In vitro effects of DEGEE (0.5–25 mg/ml) were assessed in the HEK293 human embryonic kidney cells. In vivo effects were evaluated after single acute exposure of DEGEE via intraperitoneal route in Swiss albino mice and further, a 28 days subchronic exposure study was conducted where DEGEE was administered orally, once daily. Results: DEGEE was cytotoxic to HEK293 cells, and an IC50 of 15 mg/ml was established. An increase in the intracellular levels of ROS and alteration in the mitochondrial membrane potential led to nuclear fragmentation and induction of apoptosis in these cells. Survival rate of animals administered intraperitoneally with a single acute dose of 1000 mg/kg DEGEE was 100% with no significant changes in the behavioural and histological parameters. However, the dose of 3000 mg/kg and above led to total mortality within 14 days of acute exposure. Subchronic oral exposure of 500–2000 mg/kg DEGEE showed no significant changes in the hematological, biochemical and histopathological parameters. Conclusions: The in vitro findings indicate that the nephrotoxic potential of DEGEE cannot be ruled out. The results of the in vivo studies reveal that the degree of toxic effects shown by DEGEE varies, depending on the dose, duration of exposure and routes of administration. Therefore, the present findings are of relevance and thorough studies should be conducted before using this substance in clinical formulations. [ABSTRACT FROM AUTHOR]

Alternanthera brasiliana L. is a flowering plant belonging to the family Amaranthaceae and is popularly known as "penicillin". It is used in folk medicine to treat infections, coughs, wound healing, and inflammatory diseases. Aim of the study : We investigated the effect of Alternanthera brasiliana L. leaves hydroalcoholic extract (AB) against oxidative stress, inflammation, and fibrotic changes in an experimental model of carbon tetrachloride (CCl 4)-induced liver injury and fibrosis in mice. Thirty-six male Balb/C mice were randomized into five groups: normal control, AB control, CCl 4 control, CCl 4 + AB-200 mg/kg, and CCl 4 + AB-400 mg/kg. In mice, liver injury was induced by intraperitoneal injection of CCl 4 (20% in corn oil, 5 ml/kg body weight) thrice a week for six consecutive weeks. AB extract at two doses (200 mg/kg and 400 mg/kg body weight) was administered orally for six consecutive weeks. Liver injury-related serum markers (ALT, AST, ALP), antioxidants (GSH, GST, SOD, and vitamin C), pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-18, ultrasonographic and histological alterations, proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinase-1 (TIMP-1), nuclear factor-κB (p65) (NF-κB), nod-like receptor protein 3 (NLRP3), and TGF-β/Smad signaling were accessed. LC-Q-TOF-MS/MS analysis of AB was performed. AB treatment significantly decreased the CCl 4 -induced rise in serum ALT, AST, and ALP activities and improved the histological alterations. Compared with the CCl 4 -treated group, treatment with AB significantly restored the hepatic antioxidants and reduced the pro-inflammatory cytokines in the liver. The antioxidant activity of AB may be attributed to its terpenoid constituents, which was confirmed by LC-Q-TOF-MS/MS analysis. The CCl 4 -induced rise in expression of MMP-2 and MMP-9 and decrease in TIMP-1 were markedly restored in the AB-treated groups. Further findings revealed a significant reduction in the protein levels of phospho–NF–κB (p65), NLRP3, TGF-β, pSmad2/3, collagen I, and α-smooth muscle actin (α-SMA) in the AB treatment groups. The hepatoprotective effect of AB may be attributed to the high content of terpenoid compounds and alleviates liver injury and associated fibrotic changes through modulating MMPs, NF-κB (p65), and the TGF-β/Smad axis. [Display omitted] • Alternanthera brasiliana extract (AB) exhibits hepatoprotective effect in mice. • LC-Q-TOF-MS/MS analysis reveals terpenoids (38.7%) are major constituents in AB. • AB restores antioxidants and reduces pro-inflammatory cytokines in the liver. • AB treatment impedes the MMP2/MMP9/TIMP-1 and the TGF-β/Smad signaling axis. [ABSTRACT FROM AUTHOR]