The Bronchodilator Potential of Astragalus sarcocolla: An in vitro Experiment.

OBJECTIVE: To evaluate the bronchodilatory mechanism of Astragalus sarcocolla (ASE) extract on tracheal smooth muscles of rabbits. STUDY DESIGN: In-vitro experimental study. Place and Duration of the Study: The animal house of CMH Lahore Medical College, Lahore, and Institute of Dentistry, NUMS, from October 2022 to May 2023. METHODOLOGY: Six rabbits were randomly divided into four groups. After euthanising the rabbit, the trachea was carefully dissected out and stabilised in Kreb's Henseleit solution for 30 minutes and then, stimulated by acetylcholine (Ach) 1µm, under mimicked physiological conditions. Group I served as the control group with tracheal smooth muscles stabilised with 1g tension. In Group II (positive control), tracheal smooth muscles were stimulated by potassium chloride (KCl) (80 mM and 25 mM, respectively) to get maximum tracheal smooth muscle contractions. Later, the tissue was exposed to theophylline with three molar concentrations 0.2, 0.4, 0.6, and 0.8 mM, and cumulative dose response curves were formed. In Group III (ASE group), tracheal smooth muscles were stimulated by KCl (80 mM and 25 mM) and was exposed to increasing concentration of ASE. In group IV, tissue was stimulated by KCl (25 mM) and glibenclamide (3 µM), later exposed to increasing concentration of ASE to confirm the bronchodilatory mechanism. The change in isometric contraction of the tissue was recorded using the force displacement transducer connected to a PowerLab data acquisition system. Concentration response curves were drawn, and median effective concentrations (EC50 values) and percentage inhibition were calculated. Non-linear regression was applied for the analysis of the concentration-response curves. RESULTS: ASE inhibited the KCl-induced low potassium (25 mM) contractions (EC50 = 0.38 mg/ml, 95% CI: 0.04 - 0.38, n = 6). It only partially inhibited the high potassium-induced contractions in tracheal smooth muscles. Pretreatment with glibenclamide showed a rightward shift of the dose-response curve. Theophylline and ASE significantly reduced the low K+ induced smooth muscle contractions in comparison to the control group (p <0.001, each). CONCLUSION: Astragalus sarcocolla extract produced bronchodilator effects through the activation of ATP sensitive potassium channels in isolated rabbit trachea. KEY WORDS: Astragalus sarcocolla, Bronchodilators, ATP-sensitive potassium channels, Effective concentration 50, Concentration response curves.

Pharmacological Basis for the Antidiarrheal and Antispasmodic Effects of Cuminaldehyde in Experimental Animals: In Silico, Ex Vivo and In Vivo Studies.

BACKGROUND: Medicinal herbs are frequently used for the management of gastrointestinal disorders because they contain various compounds that can potentially amplify the intended therapeutic effects. Cuminaldehyde is a plant-based constituent found in oils derived from botanicals such as cumin, eucalyptus, myrrh, and cassia and is responsible for its health benefits. Despite the utilization of cuminaldehyde for several medicinal properties, there is currently insufficient scientific evidence to support its effectiveness in treating diarrhea. Hence, the present investigation was carried out to evaluate the antidiarrheal and antispasmodic efficacy of cuminaldehyde, with detailed pharmacodynamics explored. METHODS: An in vivo antidiarrheal test was conducted in mice following the castor oil-induced diarrhea model, while an isolated small intestine obtained from rats was used to evaluate the detailed mechanism(s) of antispasmodic effects. RESULTS: Cuminaldehyde, at 10 and 20 mg/kg, exhibited 60 and 80% protection in mice from episodic diarrhea compared to the saline control group, whereas this inhibitory effect was significantly reversed in the pretreated mice with glibenclamide, similar to cromakalim, an ATP-dependent K+ channel opener. In the ex vivo experiments conducted in isolated rat tissues, cuminaldehyde reversed the glibenclamide-sensitive low K+ (25 mM)-mediated contractions at significantly higher potency compared to its inhibitory effect against high K+ (80 mM), thus showing predominant involvement of ATP-dependent K+ activation followed by Ca++ channel inhibition. Cromakalim, a standard drug, selectively suppressed the glibenclamide-sensitive low K+-induced contractions, whereas no relaxation was observed against high K+, as expected. Verapamil, a Ca++ channel inhibitor, effectively suppressed both low and high K+-induced contractions with similar potency, as anticipated. At higher concentrations, the inhibitory effect of cuminaldehyde against Ca++ channels was further confirmed when the preincubated ileum tissues with cuminaldehyde (3 and 10 mM) in Ca++ free medium shifted CaCl2-mediated concentration-response curves (CRCs) towards the right with suppression of the maximum peaks, similar to verapamil, a standard Ca++ ion inhibitor. CONCLUSIONS: Present findings support the antidiarrheal and antispasmodic potential of cuminaldehyde, possibly by the predominant activation of ATP-dependent K+ channels followed by voltage-gated Ca++ inhibition. However, further in-depth assays are recommended to know the precise mechanism and to elucidate additional unexplored mechanism(s) if involved.

Ameliorative effects of Scutellaria Pinnatifida subsp. pichleri (Stapf) Rech.f. Extract in streptozotocin-induced diabetic rats: chemical composition, biochemical and histopathological evaluation.

BACKGROUNDS: Scutellaria Pinnatifida subsp. pichleri (Stapf) Rech.f. (SP) is used in folk medicine for the treatment of diabetes. The aim of the study was to determine the phenolic profile of SP extract (SPE) by LC-MS/MS and to investigate the antidiabetic, hepatoprotective and nephroprotective effects of SPE in streptozotosin (STZ)-induced diabetic rat model. METHODS: Forty-two rats were randomly divided into six groups (n = 7): Control (nondiabetic), diabetes mellitus (DM), DM + SP-100 (diabetic rats treated with SPE, 100 mg/kg/day), DM + SP-200 (diabetic rats treated with SPE, 200 mg/kg/day), DM + SP-400 (diabetic rats treated with SPE, 400 mg/kg/day) and DM + Gly-3 (diabetic rats treated with glibenclamide, 3 mg/kg/day). Live body weight, fasting blood glucose (FBG) level, antidiabetic, serum biochemical and lipid profile parameters, antioxidant defense system, malondyaldehyde (MDA) and histopathological examinations in liver, kidney and pancreas were evaluated. RESULTS: Apigenin, luteolin, quinic acid, cosmosiin and epigallocatechin were determined to be the major phenolic compounds in the SPE. Administration of the highest dose of SP extract (400 mg/kg) resulted in a significant reduction in FBG levels and glycosylated hemoglobin levels in STZ-induced diabetic rats, indicating an antihyperglycemic effect. SPE (200 and 400 mg/kg) and glibenclamide significantly improved MDA in liver and kidney tissues. In addition, SPE contributed to the struggle against STZ-induced oxidative stress by stimulating antioxidant defense systems. STZ induction negatively affected liver, kidney and pancreas tissues according to histopathological findings. Treatment with 400 mg/kg and glibenclamide attenuated these negative effects. CONCLUSIONS: In conclusion, the extract of the aerial part of Scutellaria pinnatifida subsp. pichleri has hepatoprotective, nephroprotective and insulin secretion stimulating effects against STZ-induced diabetes and its complications due to its antidiabetic and antioxidant phytochemicals such as apigenin, luteolin, quinic acid, cosmosiin and epigallocatechin.

Investigation of the effect of addition of Momordica charantia to glibenclamide on amelioration of endothelial dysfunction in diabetic rats by activating Takeda G protein-coupled receptor 5.

Endothelial dysfunction (ED) is a significant risk factor of blood vessel related diseases of diabetes and this study evaluate the effect of adding Momordica charantia (Mc) to glibenclamide (GLB) on ED markers in diabetic rats. Streptozotocin (STZ-40mg/kg b. w.) induced diabetic rats were randomly put into 3 groups with 10 rats/group; diabetic control [DC] group, glibenclamide treated group (GLB -2.5mg/kg) and GLB-Mc treated group (2.5mg/kg + 400mg/kg). Serum glucose was measured weekly for eight weeks whereas insulin, sVCAM-1, vWF-Ag and interleukin-6 [IL-6] were measured at week 0 and week 8. Luciferase assay was performed to determine luminescence. At week 8, GLB and GLB-Mc groups revealed improvements in blood glucose and insulin concentrations (P≤0.05) when compared to corresponding baseline values with GLB-Mc group showing slightly greater improvements. GLB-M c group also revealed improvement (P≤0.05) in vWF-Ag, sVCAM-1 and IL-6 concentrations but was non-significant in GLB group when compared to corresponding baseline values. Comparison between GLB and GLB-Mc group showed significantly high concentration of sVCAM-1 in GLB group (P≤0.05) due to its minimal effect on TGR5 activation. We conclude that adding M. charantia to GLB may be a useful choice for modulating diabetes induced ED due to its stimulatory effect on TGR5 receptors.

Single versus Double Coffee-Ring Effect Patterns in Thin-Layer Chromatography Coupled with Surface-Enhanced Raman Spectroscopic Analysis of Anti-Diabetic Drugs Adulterated in Herbal Products.

In thin-layer chromatography coupled with surface-enhanced Raman spectroscopy (TLC-SERS), the coffee ring effect (CRE) describes the formation of a ring-shape spot (blank in the middle and darker on the edge) caused by the aggregation of silver nanoparticles (Ag NPs), alone (single CRE) or with the analytes (double CRE). In this work, the SCRE and DCRE were investigated in two anti-diabetic drugs, hydrophobic glibenclamide (GLB) and more hydrophilic metformin (MET). The SCRE occurred in GLB analysis, as opposed to the DCRE that occurred in MET. It was proven that for optimization of the TLC-SERS analytical procedure, it is necessary to distinguish the CRE patterns of analytes. Additionally, MET and GLB were analyzed with the developed TLC-SERS method and confirmed by another validated method using high-performance liquid chromatography. Four herbal products collected on the market were found to be adulterated with GLB or/and MET; among those, one product was adulterated with both MET and GLB, and two products were adulterated with GLB at a higher concentration than the usual GLB prescription dose. The TLC-SERS method provided a useful tool for the simultaneous detection of adulterated anti-diabetic herbal products, and the comparison of the SCRE and DCRE provided more evidence to predict CRE patterns in TLC-SERS.

Evaluation of acute oral toxicity, anti-diabetic and antioxidant effects of Aloe vera flowers extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Aloe vera (L.) Burm.f. is widely used in various traditional systems of medicine worldwide. Since over 5000 years ago, several cultures have used A. vera extract medicinally for conditions ranging from diabetes to eczema. It has been shown to reduce the symptoms of diabetes by enhancing insulin secretion and protecting pancreatic islets. AIM OF THE WORK: This research study aimed to investigate the in-vitro antioxidant effect, the acute oral toxicity, and the possible pharmacological in-vivo anti-diabetic activity with histological examination of the pancreas of the standardized deep red A. vera flowers methanolic extracts (AVFME). MATERIALS AND METHODS: The liquid-liquid extraction procedure and TLC technique were used to investigate chemical composition. Total phenolics and flavonoids in AVFME were quantified by Folin-Ciocalteu and AlCl3 colorimetric methods, respectively. The present study involved evaluating the in-vitro antioxidant effect of AVFME using ascorbic acid as the reference standard, an acute oral toxicity study by using thirty-six albino rats and different concentrations of AVFME (200 mg/kg, 2, 4, 8 and 10 g/kg b.w.). Furthermore, the in-vivo anti-diabetic study was performed on alloxan-induced diabetes in rats (120 mg/kg, I.P.) and two doses of AVFME (200 and 500 mg/kg b.w., orally) were used as compared to glibenclamide (5 mg/kg, orally) as a standard hypoglycemic sulfonylurea medication. A histological examination of the pancreas was performed. RESULTS: AVFME resulted in the highest phenolic content of 150.44 ± 4.62 mg gallic acid equivalent per gram (GAE/g) along with flavonoid content of 70.38 ± 0.97 mg of quercetin equivalent per gram (QE/g). An in-vitro study revealed that the antioxidant effect of AVFME was strong as ascorbic acid. The results of the in-vivo studies showed that the AVFME didn't cause any apparent toxicity signs or death in all groups at different doses which proves the safety of this extract with a wide therapeutic index. The antidiabetic activity of AVFME demonstrated a considerable drop in blood glucose levels as glibenclamide, without severe hypoglycemia or significant weight gain which is considered an advantage of AVFME over glibenclamide use. The histopathological study of pancreatic tissues confirmed the protective effect of AVFME on the pancreatic beta-cells. The extract is proposed to have antidiabetic activity through inhibition of α-amylase, α-glucosidase, and dipeptidyl peptidase IV (DPP-IV). Molecular docking studies were conducted to understand possible molecular interactions with these enzymes. CONCLUSION: AVFME represents a promising alternative source of active constituents against diabetes mellitus (DM) based on its oral safety, antioxidant, anti-hyperglycemic activities, and pancreatic protective effects. These data revealed the antihyperglycemic activity of AVFME is mediated by pancreatic protective effects while significantly enhancing insulin secretion through increasing functioning beta cells. This suggests that AVFME has the potential as a novel antidiabetic therapy or a dietary supplement for the treatment of type 2 diabetes (T2DM).

Carbohydrate digestive enzyme inhibition, hepatoprotective, antioxidant and antidiabetic benefits of Persea americana.

The medicinal use of Persea americana in the treatment of some diseases like hypertension, diabetes, is often with dearth of supporting scientific proof. Thus, we evaluated its ethnomedicinal benefits for possible scientific justification. Thirty healthy Wistar rats were randomly grouped in fives. Alloxan was used to induce diabetes in the rats in groups II to VI. The diabetic rats in group II were treated with glibenclamide, while those in group III were not treated. Also, the diabetic rats in groups IV to VI were treated with the ethanol extracts of the stem bark, leaf, and root of P. americana respectively. The parts of P. americana comparatively possess highest amounts of phenols (250.50 ± 0.68-bark), saponin (436.80 ± 3.76-leaf), flavonoid (382.80 ± 0.67-leaf) and tannins (58.34 ± 0.09-root). The extracts exhibited high reducing property (FRAP and total reducing), as well as high ABTS and DPPH free radical scavenging ability. The enzyme (alpha-glycosidase and alpha-amylase) inhibitory activity of P. americana increases with increasing concentration of the extracts. Administration of methanol extracts of P. americana bark, leaf and root to alloxan-induced diabetic rats resulted in significant (P < 0.05) decreases in AST, ALP, ALT, Total bilirubin, LPO, plasma glucose and significant (P < 0.05) increases in GSH, CAT and SOD. These effects were like that of glibenclamide. The enzyme inhibitory, hepatoprotective, antioxidant and antidiabetic properties of P. americana are some of the benefits derived from its consumption and ethnomedicinal use.

Crude extract from Euphorbia prostrata extended curative period of glibenclemide in alloxan-induced diabetic rats.

OBJECTIVES: Euphorbia prostrata is traditionally used alongside antidiabetic agents to manage diabetes. Bioactive ingredients of medicinal herbs may alter the overall pharmacokinetics of antidiabetic agents. METHODS: We assessed hypoglycemic activities of ethanolic plant extract (EPE) singly and its effects on antidiabetic properties of gliclazide, glibenclemide and metformin in allaxonized rats. Varying concentrations of EPE (250 and 500 mg/kg) with or without metformin (10 mg/kg), glibenclemide (2 mg/kg) and gliclazide (5 mg/kg) were orally administered to evaluate herb-drug interaction. RESULTS: The levels of blood glucose declined significantly after treatment with metformin, glibenclemide and gliclazide singly (p<0.01) or concomitantly with EPE (p<0.001). Concentration dependent mild to moderate reduction (5.2 and 10.0%) was registered in blood glucose for 250 and 500 mg/kg of EPE respectively. The overall reduction in blood glucose due to combined treatment with EPE and standard agents was additive. On the other hand, synergistic herb-drug interaction was registered for insulin levels in rats that received glibenclamide and gliclazide alongside EPE. Extract with metformin had antagonistic insulin outcome. Regarding the duration of hypoglycemic activities, periodical changes were similar in case of glibenclamide and gliclazide separately or in combination with EPE. However, in case of metformin with extract, the blood glucose continued to decline for 14 h and retained at 15.0% below the baseline values even after 24 h of treatment. CONCLUSIONS: In conclusion, the extract itself had weak hypoglycemic effects but prolonged the therapeutic duration of metformin to more than 24 h when administered combinedly.

The protective effect of green tea on diabetes-induced hepato-renal pathological changes: a histological and biochemical study.

We investigated the protective effect of green tea on diabetic hepato-renal complications. Thirty male Wistar rats were randomly divided into five equal groups: normal control, diabetic control, glibenclamide-treated, green tea-treated, and combined therapy-treated groups; ethical approval number "BERC-014-01-20." After eight weeks, animals were sacrificed by CO2 euthanasia method, liver and kidney tissues were processed and stained for pathological changes, and blood samples were collected for biochemical analysis. Diabetic rats showed multiple hepato-renal morphological and apoptotic changes associated with significantly increased some biochemical parameters, while serum albumin and HDL decreased significantly compared to normal control (p < .05). Monotherapy can induce significant improvements in pathological and biochemical changes but has not been able to achieve normal patterns. In conclusion, green tea alone has a poor hypoglycaemic effect but can reduce diabetic complications, whereas glibenclamide cannot prevent diabetic complications. The addition of green tea to oral hypoglycaemic therapy has shown a potent synergistic effect.

Stink bean (Parkia speciosa) empty pod: a potent natural antidiabetic agent for the prevention of pancreatic and hepatorenal dysfunction in high fat diet/streptozotocin-induced type 2 diabetes in rats.

The present study investigated the effect of polyphenol-rich extract of Parkia speciosa (PPS) against pancreatic and hepatorenal dysfunction in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetes. Diabetic rats were treated with PPS (100 and 400 mg/kg) and glibenclamide. The results revealed that diabetic rats displayed marked hyperglycaemia, hyperlipidaemia, hypoinsulinemia as well as alterations in serum renal and kidney function markers. Furthermore, diabetic rats showed significant increase in hepatorenal level of malonaldehyde as well as suppression of antioxidant enzyme activities. Whereas, diabetic rats that received PPS displayed marked attenuation in most of the aforementioned parameters compared to the untreated diabetic rats. Additionally, histological examination revealed restoration of histopathological alterations of the pancreas, liver, and kidney of PPS treated diabetic rats. In conclusion, the results demonstrated that PPS could decrease serum lipids and blood glucose level, enhance insulin level and hepatorenal antioxidant capacity, as well as ameliorate hepatorenal dysfunction in rats.

The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes.

This study was conducted to evaluate the anti-diabetic and antioxidant effects of hydroalcoholic pomegranate peel extract (APE) in alloxan-induced diabetes rat models. We divided 60 rats into the following six equal groups (n = 10): Healthy control; diabetic control (100 mg/kg alloxan); sham + glibenclamide (10 mg/kg); diabetic + glibenclamide (10 mg/kg); sham + APE (200 mg/kg) and diabetic + APE (200 mg/kg). After 8 weeks, kidneys were taken out for biochemical and molecular studies. Following APE treatment, biochemical parameters including malondialdehyde (MDA), and glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) significantly induced in the treated group as compared with the control group (p < 0.05). Also, gene expression of GPx (3-fold), CAT (2.6-fold), and SOD (1.5-fold) were increased as compared to controls (p < 0.05). Overall, our results indicated that pomegranate can be used as an antioxidant agent to reduce complications from diseases associated with oxidative stress.

Chitosan-Encapsulated Nano-selenium Targeting TCF7L2, PPARγ, and CAPN10 Genes in Diabetic Rats.

This study investigates the antidiabetic and antioxidant potential of chitosan-encapsulated selenium nanoparticles in streptozotocin-induced diabetic model. Glibenclamide was used as a reference antidiabetic drug. Forty-eight adult male Wistar rats were used along the study and divided equally into 6 groups of (I) normal control, (II) chitosan-encapsulated selenium nanoparticles (CTS-SeNPs), (III) glibenclamide, (IV) streptozotocin (STZ), (V) STZ + CTS-SeNPs, and (VI) STZ + Glib. The animals were sacrificed on the 35th day of the experiment. Serum glucose, insulin, IGF-1, ALT, AST, CK-MB, oxidative stress, lipid profile, and inflammatory parameters were subsequently assessed. Also, the expression level of TCF7L2, CAPN10, and PPAR-γ genes were evaluated using qPCR. In addition, histopathological studies on pancreatic tissue were carried out. The results revealed that STZ induced both diabetes and oxidative stress in normal rats, manifested by the significant changes in the studied parameters and in the physical structure of pancreatic tissue. Oral administration of CTS-SeNPs or Glib results in a significant amelioration of the levels of serum fasting blood glucose, insulin, IGF-1, AST, ATL, and CK-MB as compared with STZ-induced diabetic rats. CTS-SeNPs and Glib diminished the level of lipid peroxidation, increased total antioxidant capacity level, as well as possessed strong inhibition against serum α-amylase and α-glucosidase activities. Diabetic animals received CTS-SeNPs, or Glib demonstrated a significant (p < 0.05) decrease in the expression level of TCF7L2 and CAPN10 genes with a significant increase in the expression level of PPAR-γ gene, compared to STZ group. The above findings clarify the promising antidiabetic and antioxidant effect of CTS-SeNPs, recommending its inclusion in the currently used protocols for the treatment of diabetes and in the prevention of its related complications.

Bio-guided study of the antinociceptive, anti-inflammatory, and free-radical scavenging capacity of the leaves of Rhus virens Lindh. ex A. Gray and its possible mechanism of antinociception.

ETHNOPHARMACOLOGICAL RELEVANCE: Rhus genus is commonly known as sumac and widely used in the folk medicine. Rhus virens is a plant commonly used to treat diabetes or pain in the northern territory of Mexico. Even though R. virens is used in the folk medicine there is still a lack of evidence about the pharmacological effect of this species. AIM OF THE STUDY: The aim of this study was to determine the antinociceptive, anti-inflammatory and antioxidant effect of R. virens through a bio-guided chemical separation. MATERIALS AND METHODS: The aqueous, methanolic, and hexane extract of R. virens were obtained and tested in the formalin test, TPA-induced ear edema, and DPPH, ABTS, and FRAP assay. Also, possible interaction of pain pathways was studied using naloxone, bicuculline, L-NAME, ODQ, and glibenclamide in the formalin test in mice. RESULTS: Rhus virens methanolic extract (30 mg/kg, p.o.) produced higher antinociceptive activity in both the early and late phases of the formalin test (35.0 and 52.9%, respectively). Also, pre-administration with naloxone, bicuculline, L-NAME, ODQ and glibenclamide prevented the antinociceptive effect of R. virens in the early phase of the formalin test. Meanwhile, only naloxone and bicuculline prevented the antinociceptive effect on the late phase of the formalin test. Chemical separation of methanolic extract allowed to isolate 1,2,3,4,6-penta-O-galloyl-glucopyranose (PGG), it was tested in the formalin test, producing an antinociceptive effect on the late phase of the formalin test. On the other hand, topical application of the derivatives of R. virens methanolic extract produced an anti-inflammatory effect in the TPA-induced ear edema, being PGG an anti-inflammatory molecule. Lastly, radical scavenging activity was higher in the extracts of higher polarity, comparable to the standard used Camellia sinensis. CONCLUSIONS: In conclusion, R. virens produce an antinociceptive, anti-inflammatory and free-radical scavenging activity. The antinociceptive effect could be related to the opioidergic, GABAergic, and NO-GMPc-K + ATP channels pathways. These effects could be partially produced by the presence of PGG.

Vulgarin, a Sesquiterpene Lactone from Artemisia judaica, Improves the Antidiabetic Effectiveness of Glibenclamide in Streptozotocin-Induced Diabetic Rats via Modulation of PEPCK and G6Pase Genes Expression.

The current investigation assessed the effect of the eudesmanolid, Vulgarin (VGN), obtained from Artemisia judaica (A. judaica), on the antidiabetic potential of glibenclamide (GLB) using streptozotocin (STZ) to induce diabetes. Seven groups of rats were used in the study; the first group received the vehicle and served as normal control. The diabetic rats of the second to the fifth groups were treated with the vehicle (negative control), GLB at 5 mg/kg (positive control), VGN at 10 mg/kg (VGN-10) and VGN at 20 mg/kg (VGN-20), respectively. The diabetic rats of the sixth and seventh groups were administered combinations of GLB plus VGN-10 and GLB plus VGN-20, respectively. The diabetic rats treated with GLB plus VGN-20 combination showed marked improvement in the fasting blood glucose (FBG), insulin and glycated hemoglobin (HbA1c), as well as the lipid profile, compared with those treated with GLB alone. Further, the pancreatic tissues of the diabetic rats that received the GLB+VGN-20 combination showed superior improvements in lipid peroxidation and antioxidant parameters than those of GLB monotherapy. The insulin content of the ß-cells was restored in all treatments, while the levels of glucagon and somatostatin of the α- and δ-endocrine cells were reduced in the pancreatic islets. In addition, the concurrent administration of GLB+VGN-20 was the most effective in restoring PEPCK and G6Pase mRNA expression in the liver. In conclusion, the results demonstrated that the GLB+VGN-20 combination led to greater glycemic improvement in diabetic rats compared with GLB monotherapy through its antioxidant effect and capability to modulate PEPCK and G6Pase gene expression in their livers.

Co-administration of Pterocarpus marsupium Extract and Glibenclamide Exhibits Better Effects in Regulating Hyperglycemia and Associated Changes in Alloxan-induced Diabetic Mice.

BACKGROUND: Diabetes mellitus (DM) is a well-known global metabolic disorder. For its treatment, glibenclamide (GLB) is very often prescribed. However, herbal drugs are considered effective and better alternatives due to their low risk of side effects. This study was conducted to determine the combined effects of GLB and Pterocarpus marsupium (PM, a commonly available Indian herb) extract for the effective and safe treatment of hyperglycemia in the mouse model. METHODS: Healthy adult male mice were distributed into five groups (n=7 in each group). Group I acted as the control, whereas groups II, III, IV, and V were considered experimental groups which received a single dosage (150 mg/kg body weight) of alloxan (ALX) intraperitoneally (i.p.). In addition, groups III, IV, and V received a pre-standardized dose of GLB (500 µg/kg body weight), PM extract (150 mg/kg body weight), and GLB+PM, respectively, at the same doses as used in individual treatment, after the seventh day of ALX administration for 15 days and the alterations in different DM related parameters were evaluated. RESULTS: ALX-induced hyperglycemia and other adverse effects were nearly normalized by GLB and PM co-treatment as evidenced by marked suppression in glucose, triglyceride, total-cholesterol, lipid-peroxidation, and lipid-hydroperoxides with an increase in antioxidants status and liver glycogen content. The positive effects were more pronounced when both GLB and PM were given, as compared to that of either of the drugs, administered alone. Liver ultra-structure, analyzed through histology and transmission electron microscopy revealed normalization of the ALX-induced damaged hepatocytes. The presence of epicatechin, the major phytoconstituent of the PM extract, as confirmed by high-performance liquid chromatography (HPLC), is responsible for its antioxidative and glucose-lowering activities. CONCLUSION: These findings reveal that PM, along with GLB, exhibits synergistic and better effects than the individual drug in regulating hyperglycemia and associated changes in alloxan-induced mice.

Investigation of the Chemical Composition, Antihyperglycemic and Antilipidemic Effects of Bassia eriophora and Its Derived Constituent, Umbelliferone on High-Fat Diet and Streptozotocin-Induced Diabetic Rats.

This study was designed to investigate the chemical profile, antihyperglycemic and antilipidemic effect of total methanolic extract (TME) of Bassia eriophora and isolated pure compound umbelliferone (UFN) in high-fat diet (HFD)- and streptozotocin (STZ)- induced diabetic rats. TME was subjected to various techniques of chromatography to yield UFN. Diabetes was induced after eight weeks of HFD by administration of STZ (40 mg/kg) intraperitoneally, and experimental subjects were divided into five groups. The diabetic control showed an increase in levels of blood glucose throughout the experiment. Treatments were initiated in the other four groups with glibenclamide (GLB) (6 mg/kg), TME (200 mg/kg and 400 mg/kg) and isolated UFN (50 mg/kg) orally. The effect on blood glucose, lipid profile and histology of the pancreatic and adipose tissues was assessed. Both 200 and 400 mg/kg of TME produced a comparably significant decrease in blood glucose levels and an increase in insulin levels with GLB. UFN began to show a better blood sugar-lowering effect after 14 days of treatment, comparatively. However, both 400 mg/kg TME and UFN significantly returned blood glucose levels in diabetic rats compared to normal rats. Analysis of the lipid profile showed that while HFD + STZ increased all lipid profile parameters, TME administration produced a significant decrease in their levels. Histopathological examinations showed that treatment with TME and UFN revealed an improved cellular architecture, with the healthy islets of Langerhans and compact glandular cells for pancreatic cells distinct from damaged cells in non-treated groups. Conversely, the adipose tissue displayed apparently normal polygonal fat cells. Therefore, these results suggest that TME has the potential to ameliorate hyperglycemia conditions and control lipid profiles in HFD + STZ-induced diabetic rats.

Phytochemical Analysis and hypoglycemic potential of Filago hurdwarica (Wall. ex DC.) Wagenitz in alloxan induced diabetic mice.

Plants have profound therapeutic benefits, more economical treatments, fewer side effects, and a relatively cheap cost, making them a source of drugs for protective, preventative, curative, or conducive purposes and creating novel phytomedicines. Plant derived medicines are relatively safe compared to synthetic medicines. Many plants have proved to successfully aid in the treatment of diabetes including Filago hurdwarica (Wall. ex DC.) Wagenitz. The current investigations were therefore designed to assess the phytochemical, antioxidant, antidiabetic, and antihyperlipidemic activities of F. hurdwarica. The phytochemical investigations and antioxidant activities of different extracts were carried out using standard chemical tests, DPPH, and H2O2 scavenging assays. F. hurdwarica plant extract in Hydromethanolic solution were prepared by Soxhletation method and stored in refrigerator at 4°C for two days before use. Swiss Albino mice were made diabetic by a single dose of alloxan (150 mg/kg). Hydromethanolic plant extract and fractions of F. hurdwarica were screened for antidiabetic activity and given to the alloxan-induced diabetic mice at a concentration of 150-250 mg/kg of body weight in different groups of 6 diabetic mice each orally once a day for 15 days. Glibenclamide is also given to another group to as a standard drug to support the result at a dose of 10 mg/kg of body weight orally once a day for 15 days. Blood glucose levels and body weights of mice were measured on 0, 4, 7, 11 and 15th days. The study found that the extract was safe up to the dose level of 2000 mg/kg and the dose response effect of chloroform extract (150-250 mg/kg) of F. hurdwarica showed expressive antihyperglycemic effects and also improved other altered biochemical parameters associated with diabetes. The FTIR and XRD spectra demonstrated the occurrence of phenols, alcohols, alkenes, alkyl halides, ketones, and aromatic compounds and confirmed the amorphous nature of the extract. GC-MS spectral analysis showed the tentative presence of 31 phytochemical constituents in the chloroform extract of F. hurdwarica with different retention time. To conclude, the chloroform extract (250 mg/kg) of F. hurdwarica revealed considerable antioxidant, antihyperglycemic, and antihyperlipidemic potential and is safe for treating diabetes and related complications.

Vitamin D Supplementation Could Enhance the Effectiveness of Glibenclamide in Treating Diabetes and Preventing Diabetic Nephropathy: A Biochemical, Histological and Immunohistochemical Study.

Diabetes mellitus is an oxidative stress-related disease characterized by hyperglycemia and a variety of complications, including nephropathy. Vitamin D has variable functions extending beyond the calcium metabolism to prevent oxidative tissue damage. We aimed to investigate whether vitamin D supplements could enhance Glibenclamide's effectiveness in treating diabetes and minimize the risk of associated pathology. Wistar rats were divided into normal control (n = 10) and diabetic (n = 30), where animals received two low doses of Streptozotocin 30 mg/kg/BW intraperitoneally to develop diabetes. The diabetic rats were then randomly divided into three equal groups: untreated, treated with Glibenclamide (0.6 mg/kg), and treated with Glibenclamide and Vitamin D3 (500 IU/kg). After eight weeks, the animals were sacrificed, and blood samples and kidney tissues were collected to evaluate biochemical, anti-oxidant, and pro-inflammatory cytokine levels and histological and immunohistochemical changes. Diabetic animals had significantly increased fasting blood glucose, lipid profile, blood urea, serum creatinine, and Malondialdehyde levels, whereas serum insulin, albumin, and the anti-oxidant enzymes superoxide dismutase and catalase were significantly decreased compared to normal control (p < 0.01). Furthermore, some renal histological changes were observed together with significantly increased immunoreactivity of anti-p53, anti-TNF-α, and anti-IL-6 antibodies when compared to the normal control. All abnormal parameters improved significantly with Glibenclamide therapy (p < 0.01), but combination therapy with vitamin D produced a much better result. In conclusion, vitamin D supplementation along with anti-diabetic medication can help prevent or reduce the severity of diabetic nephropathy due to its potent antioxidant, anti-inflammatory, and anti-apoptotic properties.

Ameliorative role of Cyanus depressus (M.Bieb.) Soják plant extract against diabetes-associated oxidative-stress-induced liver, kidney, and pancreas damage in rats.

In this original article, we aimed to assess the ameliorative role of Cyanus depressus (CD) plant ethanolic extract treatment of streptozotocin (STZ)-induced liver, kidney, and pancreas damage in rats. The rats were divided into five groups (n = 7): control, CD, Diabetes mellitus (DM), DM + CD, and DM + glibenclamide (Gly). The DM groups were injected with a single dose of 50 mg/kg STZ intraperitoneally (i.p.). While the CD and DM + CD groups received 400 mg/kg/day intragastrically for 21 days, the DM + Gly group received 3 mg/kg/day of Gly intragastrically throughout the experiment. Statistically significance was accepted as p < .05. According to our liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) data, quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid were the major compounds, in descending order. Weekly blood glucose, serum glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and urea, malondialdehyde (MDA) (liver and pancreas), and blood glycosylated hemoglobin % (HbA1c %) were significantly decreased, whereas finally live body weights (LBWs), reduced glutathione (GSH), glutathione S-transferase (GST) and catalase (CAT) (pancreas), and pancreatic islet diameter and area were increased significantly in the CD-treated diabetic group. Moreover, CD administration was found to be effective in the protection of the histology of the liver, kidneys, and pancreatic islets in the STZ-induced rats. Consequently, we concluded that CD administration reduces hyperglycemia, oxidative stress, and histopathology in STZ-induced experimental rats by improving antioxidant defenses. PRACTICAL APPLICATIONS: Today, the prevalence of diabetes is increasing rapidly throughout the world and it causes complications such as kidney damage, blindness, amputations, and cardiovascular diseases. Despite medical technological advances, people's interest in medicinal herbal products is gradually increasing. Biochemical and histopathological findings showed that the use of the plant CD at the determined dose (400 mg/kg/day) in rats with DM by STZ had strong antioxidant and antidiabetic effects. CD may have a drug potential in preventing DM and its complications because of its phytochemical content including some phenolic acids such as quinic acid, cosmosiin, nicotiflorin, apigenin, and protocatechuic acid. Isolation of bioactive compounds from CD and investigation of their therapeutic effects could be planned as further studies.

Phytochemical Analysis, Acute Toxicity, as well as Antihyperglycemic and Antidiabetic Activities of Corchorus olitorius L. Leaf Extracts.

Backgroundand Aim. Diabetes mellitus is a metabolic disorder that has no known cure with continuous endeavors to find a therapy for the condition. According to some studies, traditional leafy vegetables could prevent and manage diabetes by modifying the carbohydrate and lipid metabolism. In this study, a phytochemical analysis, acute toxicity, as well as antihyperglycemic and antidiabetic activity testing of the methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. was performed. Materials and Methods. Methanolic, diethyl ether, and aqueous leaf extracts of Corchorus olitorius L. were prepared by serial extraction. Phytochemical analysis was performed following standard methods. 52 mice were separated into 13 groups (A-M) of 4 and received extracts' doses ranging from 1000 mg/kg to 5000 mg/kg for the acute toxicity testing. For the antihyperglycemic and antidiabetic activities testing, 48 rats were divided into 8 groups of 6 and received 500 mg/kg of each extract. 10 mg/kg of glibenclamide and distilled water were used as controls. Data were analyzed using Prism GraphPad version 8.0.2 (263). Results. Phytochemical analysis revealed the presence of alkaloids, reducing sugars, saponins, and terpenoids. There were no acute toxicity signs observed in this study. Corchorus olitorius L. extracts demonstrated moderate antihyperglycemic and antidiabetic activities. The methanolic extract exhibited the highest degree of antihyperglycemic activity. However, there was no statistically significant difference between the extracts and the negative control (p > 0.05), but with glibenclamide (p < 0.01). Conclusion. Corchorus olitorius L. is a safe and potential postprandial antidiabetic vegetable that could minimize the rise in blood glucose after a meal. We therefore recommend further investigations into the antidiabetic properties of the vegetable using purified extracts.