Standard Drug Metformin Research Articles

Synthesis and molecular docking studies of new aryl imeglimin derivatives as a potent antidiabetic agent in a diabetic zebrafish model

Diabetes mellitus (DM) is a persistent, progressive, and multifaceted disease characterized by elevated blood glucose levels. Type 2 diabetes mellitus is associated with a relative deficit in insulin mainly due to beta cell dysfunction and peripheral insulin resistance. Metformin has been widely prescribed as a primary treatment option to address this condition. On the other hand, an emerging glucose-reducing agent known as imeglimin has garnered attention due to its similarity to metformin in terms of chemical structure. In this study, an innovative series of imeglimin derivatives, labeled 3(a–j), were synthesized through a one-step reaction involving an aldehyde and metformin. The chemical structures of these derivatives were thoroughly characterized using ESI–MS, 1H, and 13C NMR spectroscopy. In vivo tests on a zebrafish diabetic model were used to evaluate the efficacy of the synthesized compounds. All compounds 3(a–j) showed significant antidiabetic effects. It is worth mentioning that compounds 3b (FBS = 72.3 ± 7.2 mg/dL) and 3g (FBS = 72.7 ± 4.3 mg/dL) have antidiabetic effects comparable to those of the standard drugs metformin (FBS = 74.0 ± 5.1 mg/dL) and imeglimin (82.3 ± 5.2 mg/dL). In addition, a docking study was performed to predict the possible interactions between the synthesized compounds and both SIRT1 and GSK-3β targets. The docking results were in good agreement with the experimental assay results.

<i>In Silico</i> Screening of a Phytochemical Naringin, Isolated from <i>Citrus decumana</i> var. <i>paradisi</i> Against the Genes of Polycystic Ovary Syndromenes of Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is a complex hormonal and metabolic disorder. The overproduction of androgens is the primary feature of PCOS. The currently available pharmacological agents recommended for the treatment of PCOS are linked with several adverse effects. Therefore, herbal-based drugs with lesser side effects, have become a favourable trend among people. A flavonoid glycoside, naringin isolated from different fruit parts of Citrus decumana var. paradisi (Macfad.) H.H.A. Nicholls exhibits a wide range of therapeutic properties. In the traditional system of medicine, it is used to improve ovarian health. To set down scientific evidence, molecular docking analysis was performed to find out the binding affinity of compound naringin with the protein CYP 17-cytochrome P 450, attributing to hyperandrogenism due to its overexpression, leading to PCOS. The docking score values were compared with the standard drug metformin to interpret the effectiveness of flavonoid naringin in the treatment of PCOS.

Antidiabetic action of the Chinese formula Shouhuitongbian and the underlying mechanism associated with alteration of gut microbiota

BackgroundThe prevalence and incidence of type 2 diabetes mellitus (T2DM) have dramatically increased. The intestinal flora and its derived metabolites are demonstrated to play vital roles in the etiology and onset of T2DM. Shouhuitongbian (SHTB) is a traditional Chinese formula to treat constipation. SHTB is composed of seven herbs and components of Colla corii asini (CCA) that are obtained from the hide of Equus asinus L.. Some of herbs in SHTB such as Aloe vera (L.) Burm.f., Cassia obtusifolia L., fruits of Lycium barbarum L., and Citrus aurantium L. have shown to improve insulin resistance (IR) and T2DM in early reports. We hypothesized that SHTB composed of these herbs has antidiabetic effects. The antidiabetic efficacy and mechanism of action of SHTB have not been previously reported. Hypothesis/PurposeTo demonstrate the antidiabetic effect and elucidate the underlying mechanisms of SHTB from the perspective of gut microbiota. Study designThe main compounds were identified and quantified by high-performance liquid chromatography (HPLC)-mass spectrometry analysis. High fat diet (HFD)-fed mice and db/db mice were used to assess the antidiabetic effects and the mechanism of SHTB. The underlying mechanisms were evaluated by enzyme-linked immunosorbent assay (ELISA), western blot analysis, quantitative real time polymerase chain reaction (qPCR) analysis, 16S rRNA high-throughput sequencing, and targeted metabolome analysis. MethodsHFD-fed mice and db/db mice were orally treated with the standard positive drug metformin (100 mg/kg/d) and with SHTB (200 and 100 mg/kg/d), which was chemically characterized according to the European Medicine Agency (EMA) guidelines. The beneficial effects of SHTB were studied by homeostasis model assessment of insulin resistance (HOMA-IR) index, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), total cholesterol (T-CHO), triglyceride (TG), and inflammation. Subsequently, 16S rDNA-based high-throughput pyrosequencing and GC-MS-based targeted metabolomics profiling were performed to analyze the gut microbiota composition and metabolites profile in the gut, respectively. Moreover, the mammalian target of rapamycin complex 1 (mTORC1) / insulin receptor substrate 1 (IRS-1) / phosphoinositide 3-kinase (PI3K) / protein kinase B (AKT) pathway was evaluated via qPCR and western blot. ResultsChemically characterized SHTB, in which six markers were quantified, effectively alleviated glucose intolerance and IR, ameliorated lipid metabolism dysfunction, and reduced inflammation. In addition, 16S rDNA sequencing found that SHTB reshaped the composition of intestinal flora, as indicated by the enrichment of Akkermansia and Parabacteroides in both HFD-fed and db/db mice. Moreover, SHTB enhanced the intestinal production of short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BSCFAs), and reduced the levels of the fecal and circulating branched-chain amino acids (BCAAs). The IRS-1/PI3K/AKT signaling pathway was upregulated after treatment with SHTB. ConclusionOrally administration of SHTB effectively improved IR and reduced hyperglycemia in mice. Treatment with SHTB regulated the gut BCAAs-mTORC1/IRS-1/PI3K/AKT axis by enhancing the BCAAs catabolism in the gut, which attenuated the deleterious effect of BCAAs on the IRS-1 signaling pathway.

Evaluation of the Neuroprotective Action of <i>Azadirachta indica</i> Leaves Extract in Streptozotocin-induced Diabetic Rodent Model

Among the most common and painful consequences of diabetes mellitus, Diabetic Peripheral Neuropathy (DPN) is one of the most common. For DPN management, a variety of techniques have been used, ranging from traditional medicines to alternative approaches. Natural compounds are also the focus of research to explore the possible treatment by replacing or combining with the existing therapies. Different neurological changes in diabetic neuropathy and the effect of the Azadirachta indica (neem) extract were assessed with nerve conduction velocity, and biochemical and histological analysis in Streptozotocin-induced diabetic mellitus. The therapeutic effect of the extract was evaluated with doses 100, 200 and 500mg/kg body weight for 4 weeks after induction of diabetes. The protective effect was evaluated by treating the animals with hydroalcoholic extract of neem leaves in 500mg/kg dose before the induction of diabetes and post-treatment with the standard drug Metformin (500mg/kg). Both resulted in a significant reduction in blood glucose, additionally, 500mg/kg body weight dose revealed the signs of neuroprotection in diabetic rats. Neem leaf extract appears to be promising for future investigations, which might contribute to the emergence of new drugs for diabetes treatment and diabetic neuropathy either alone or in combination with conventional therapies.

Modulation of Oxidative Stress and Glycemic Control in Diabetic Wistar Rats: The Therapeutic Potential of Theobroma cacao and Camellia sinensis Diets.

Background Diabetes mellitus is a complex metabolic disorder characterized by oxidative stress and impaired glycemic control. This study investigates the therapeutic potential of Theobroma cacao and Camellia sinensis diets in diabetic Wistar rats and assesses their impact on oxidative stress markers and blood glucose levels. Methods In this experiment, eight groups of six male Wistar rats (n = 12.5%), aged 8 to 12 weeks, were carefully set up to see how different treatments for diabetes and oxidative stress affected the two conditions. The random selection process was implemented to minimize any potential bias and ensure that the results of the study would be representative of the general population of Wistar rats. The groups were as follows: a nondiabetic control group (NDC) served as the baseline, while diabetes was induced in the alloxan monohydrate group (150 mg/kg). Another group was given the standard drug metformin (M, 100 mg/kg), and two control groups that did not have diabetes were given extracts of Theobroma cacao (TC, 340 mg/kg) and Camellia sinensis (CS, 200 mg/kg). Three groups of diabetic rats were given a mix of these treatments. Theobroma cacao and Camellia sinensis extracts were given at set doses (TC, 340 mg/kg; CS, 200 mg/kg), along with 150 mg/kg of a drug that causes diabetes.Over a 21-day period, oxidative stress parameters such as glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione reductase (GSHrd) levels, and blood glucose were carefully measured to check for signs of oxidative stress and diabetes progression Results Considerable differences in GSH levels were noted across the groups, with the highest GSH concentration found in the group treated with the inducing drug, while the lowest GSH levels were observed in the diabetic group that was administered both Theobroma cacao and Camellia sinensis (p < 0.001). MDA levels also varied, with the diabetic group treated with Theobroma cacao having the highest MDA concentration (3.54 ± 0.29 μmol/L) and the nondiabetic control group treated with Camellia sinensis exhibiting the lowest MDA levels (1.66 ± 0.08 μmol/L; p < 0.001). SOD activity was highest in the standard drug group and lowest in the diabetic group treated with Theobroma cacao. GSH activity was notably higher in the diabetic groups that received dietary interventions (p < 0.001). Blood glucose levels showed diverse responses, with the standard drug group experiencing a substantial reduction, while the inducing drug group exhibited a consistent increase. Conclusion The study highlights the significant impact of dietary interventions with Theobroma cacao and Camellia sinensis on oxidative stress markers and blood glucose regulation in diabetic Wistar rats. These findings suggest a potential role for these dietary components in mitigating oxidative stress and improving glycemic control in diabetes, although further research is warranted to elucidate the underlying mechanisms and clinical implications.

Studies on the Effect of Piperine on Hepatocyte Nuclear Factor 1 Alpha (HNF-1α) and Sterol Regulatory Element-Binding Protein 1c (SREBP-1c) Levels in High-Fat-Diet and Sucrose-Induced Type 2 Diabetes Mellitus Rats.

Piperine, a naturally occurring compound in black pepper (Piper nigrum), is known for its potential health benefits, including its reported enhancement of insulin sensitivity. However, the precise impact of piperine on hepatocyte nuclear factor 1 alpha (HNF-1α) and sterol regulatory element-binding protein 1c (SREBP-1c), transcription factors for insulin signaling and glucose metabolism in hepatocytes, remains unclear. This study aims to investigate the effect of piperine, compared to metformin, on blood glucose and insulin levels by modifying the expression of hepatic HNF-1α and SREBP-1c in high-fat-diet (HFD) and sucrose-induced type 2 diabetes mellitus (T2DM) rats and in human Chang liver cells. Adult male albino rats were categorized into four groups: group 1 as the control, group 2 as T2DM, group 3 as T2DM rats treated with piperine (40 mg), and group 4 as T2DM rats treated with metformin (50 mg). Fasting blood glucose (FBG) and serum insulin levels were measured using enzyme-linked immunosorbent assay (ELISA), while real-time polymerase chain reaction (RT-PCR) analysis was conducted to assess the mRNA expression of HNF-1α and SREBP-1c. Further, piperine was treated with normal and high glucose-induced Chang liver cells, and gene expression was analysed.Data analysis was performed using one-way analysis of variance (ANOVA), with a significance set at p<0.05. Treatment with piperine led to a notable decrease in blood glucose levels and circulating insulin when compared with T2DM rats (group 2). Additionally, piperine administration resulted in the upregulation of HNF-1α mRNA expression and downregulation of SREBP-1c mRNA levels whose effects were found to be near that of the control and standard drug metformin's effects. In vitro study also confirmed that piperine improved the HNF-1αexpression and reduced the expression of SREBP-1c in Chang liver cells. Our findings suggest that piperine treatment effectively regulates hyperglycemic and hyperinsulinemic insulin resistance in the liver by modulating the expression of HNF-1α and SREBP-1c. Consequently, piperine emerges as a promising candidate for therapeutic intervention in managing T2DM.

Antioxidant and Antidiabetic Potential of Ormocarpum cochinchinense (Lour.) Merr. Leaf: An Integrated In vitro and In silico Approach.

Diabetes is a prevalent metabolic disorder associated with various complications. Inhibition of α-glucosidase and α-amylase enzymes is an effective strategy for managing non-insulin-dependent diabetes mellitus. This study aimed to investigate the antioxidant and antidiabetic potential of Ormocarpum cochinchinense leaf through in vitro and in silico approaches. The methanol extract exhibited the highest phenolic and flavonoid content over solvent extracts aqueous, acetone, hexane, and chloroform, the same has been correlating with strong antioxidant activity. Furthermore, the methanol extract demonstrated significant inhibitory effects on α-amylase and α-glucosidase enzymes, indicating its potential as an antidiabetic agent. Molecular docking analysis identified compounds, including myo-inositol, with favorable binding energies comparable to the standard drug metformin. The selected compounds displayed strong binding affinity towards α-amylase and α-glucosidase enzymes. Structural dynamics analysis revealed that myo-inositol formed a more stable complex with the enzymes. These findings suggest that O. cochinchinense leaf possesses antioxidant and antidiabetic properties, making it a potential source for developing therapeutic agents.

Formulation and evaluation of new herbal nutraceutical tablet for the treatment of diabetes mellitus

Abstract BACKGROUND: Herbal nutraceutical dosage forms a dietary supplement that improves various chronic diseases. This study aimed to formulate and evaluate new herbal nutraceutical tablets and assess antihyperglycemic and antihyperlipidemia effects in ob/ob mice. METHODS: A herbal nutraceutical tablet was prepared by the wet granulation method. Proximate composition was determined by the Association of Official Analytical Chemists methods. The high-performance liquid chromatography method was used for the estimation of water-soluble vitamins and fat-soluble vitamins. An atomic absorption spectrophotometer was used for analyzing trace elements. Oral glucose tolerance tests and biochemicals were analyzed to assess antihyperglycemic and antihyperlipidemia effects in ob/ob mice. RESULTS: Herbal nutraceutical tablet contains a good amount of energy. Iron, sodium, potassium, phosphorus, magnesium, iodine, copper, zinc, and calcium were present in the newly formulated herbal tablets. A reasonable amount of water-soluble and fat-soluble vitamins were also present. Administration of newly developed herbal nutraceutical tablets (200 mg/kg) in ob/ob mice significantly improved the antihyperglycemic and antihyperlipidemia effects compared to the standard drug metformin (200 mg/kg). CONCLUSIONS: Based on these findings, a newly formulated herbal nutraceutical tablet may be recommended as a dietary supplement and can be utilized as an active type 2 diabetes drug.

A clinical study on the effect of Lodhradi Kashaya on Madhumeha with special reference to Diabetes Mellitus (Type-2)

Introduction: Ayurveda describes Prameha as a disease entity which involves a number of diseases with various physical and chemical changes in urine. Madhumeha is included under Vatik Prameha where astringency is associated with sweetness in urine. The manifestation of metabolic abnormality as well as urinary tract pathology are included in two symptoms: Prabhuta Mutrata (excessive urination) and Avila Mutrata (urine turbidity). Sedentary life style, indulgence of Kapha-meda Vardhaka Ahara, avoidance of regular exercise, day sleep indicate Santarpanajanya origin of the disease. Methods: Lodhradi Kashaya with Lodhra, Musta, Katphal and Haritaki as described in Vasavarajeeyam is taken for this clinical study on 60 patients and its efficacy was compared with a standard drug metformin. Results: During the study it was found that both Lodhradi Kashaya and Metformin provided significant result in improving Signs and Symptoms like polyuria, turbid urination, Polydipsia, polyphagia, burning sensation, numbness, weakness, lassitude, pruritus, muscle cramps, and increased sweating. The test of significance shows that both the trial drug and control drug were highly significant at 0.1% level with p-value &lt;0.001 to improve glycosuria, FBS, PPBS and HbA1c in patients. Comparative analysis of the effectiveness of Lodhradi Kashaya and metformin w.r.t. objective sign and symptoms showed that both the treatments are almost equally effective to improve glycosuria, FBS, PPBS and HbA1c while Lodhradi Kashaya gives better clinical improvement than metformin in long term use in Diabetes. Lodhradi Kashaya is an efficient anti diabetic drug.

Gymnema sylvestre extract improves PCOS by altering the YAP1 protein in the mouse ovary via mitochondrial changes

BackgroundGymnema sylvestre (Retz.) R.Br. ex Sm. is a medicinal herb used in Ayurvedic medicine to treat diabetes. Through promoting obesity and lowering insulin resistance, anti-diabetic herbs may be more effective in treating polycystic ovarian syndrome (PCOS). Recently, YES‐associated protein-1 gene (YAP1) has been reported to be a new susceptibility gene for PCOS in clinical studies. Hence, we evaluated the effects of hydroalcoholic G. sylvestre extract on regulating the YAP1 protein in PCOS mice injected with dehydroepiandrosterone (DHEA) by examining mitochondrial alterations in the ovary. Materials and methodsThe DHEA-induced PCOS female C57BL6/J mice were treated with three doses of G. sylvestre and standard drug metformin. Study parameters include body weight gain, estrus cyclicity, glucose tolerance testing, serum hormone levels, lipid profiles, liver enzymes, and inflammatory cytokines. Electron microscopy, histological, and immuno-histochemical (IHC) analyses were used to determine the morphological changes of the ovary. IHC analysis was used to assess the expression of the YAP1 protein. ResultsAs compared with the control group, the G. sylvestre-treated groups showed decreased obesity, estrus irregularity, improved glucose metabolism, reduced AST and ALT values, hormonal abnormalities, and inflammatory cytokines (IL-6, IL-17, IL-23, TNF-α). Interestingly, metformin and G. sylvestre therapy reduced YAP1-positive cells in the ovary of DHEA-induced PCOS mice. ConclusionThese findings suggest that a higher concentration of G. sylvestre extract at 500 mg/kg improved mitochondrial architecture in the PCOS ovary via modulating the key pathogenic protein of PCOS, YAP1.

Evaluation of the Antidiabetic Potentials of Musa acuminata Leaves Crude Extract in Alloxan-Induced Wistar Rats

Context: Musa acuminata is a plant of the tropical and subtropical regions. Over the past few decades, the health benefits of Musa acuminata have received much attention. All parts of the plant, including fruits, peel, pseudo stem, corm, flowers, leaves, sap, and roots, have found their use in treating many diseases in traditional medicine.&#x0D; Aim: This study was conducted to appraise the protective effect of Musa acuminata extract on alloxan-induced Diabetics Mellitus in wistar rats.&#x0D; Settings and Design: This investigation was carried out using 24 Wistar rats, both males and females. The experimental models were divided into six groups; 4 rats per group.&#x0D; Materials and Methods: The experimental models were divided into six groups; 4 rats per group. Alloxan was intraperitonially injected at a dose of 150 mg/kg body weight for day 1 across all groups except the positive control which is Group A together with oral administration of the aqueous extract of Musa acuminata (100 mg/kg, 200mg/kg and 300mg/kg body weight for the treatment group) and Group F was administered a standard drug. The animals were sacrificed on the 11th day under deep anesthesia with chloroform. The blood was collected by cardiac puncture and kidneys were collected for the histological profile.&#x0D; Statistical Analysis: Kidney oxidative stress marker Malondialdehyde (MDA) and antioxidant enzyme activities Creatinine and Urea, were determined.&#x0D; Results: The alloxan injection indicated an increase in Malondialdehyde (MDA), with a decrease in Urea and Creatinine when compared with the control. A remarkable decrease in antioxidant enzymes was also observed. Oxidant/antioxidant imbalance, alloxan-induced diabetic mellitus, and histological changes in the kidneys were reduced almost to normal by the administration of Musa acuminata.&#x0D; Conclusion: Based on the current findings, Musa acuminata leaves at low dose (100 mg/kg body weight) in the alloxan Induced Wistar rat has some anti diabetics potential than at 200 mg/kg body weight, 300 mg/kg body weight and standard drug (Metformin).

In-Silico Prediction of Phytoconstituents from Manilkara Hexandra for Antidiabetic Activity Targeting GKRP (Glucokinase Regulatory Protein)

Objective: A complex metabolic condition known as diabetes mellitus is caused by either inadequate or dysfunctional insulin. Once more, medicinal plants are being researched for the treatment of diabetes. Prototypical compounds found in medicinal plants have been the source of many conventional medications. The part of our investigation was to test the phytoconstituents of Manilkara hexandra for antidiabetic efficacy, in-silico. Methods: The pattern of interaction between the phytoconstituents from the Manilkara hexandra (Roxb.) Dubard, plant and the crystal structure of the antidiabetic proteins is evaluated using molecular docking in Discovery Studio (PDB ID: 4LY9). Later, SwissADME and pkCSM were used to screen for toxicity as well as the pharmacokinetic profile. Results: The docked results suggest that quercetin (-9.3 kcal/mol), kaempferol (-9.1 kcal/mol), p-coumaric acid (-6.4 kcal/mol) and cinnamic acid (-6.3 kcal/mol) for 4LY9 macromolecule has best binding towards antidiabetic activity as compared to the standard drug metformin (-5.0 kcal/mol). According to ADMET tests, pharmacokinetics and toxicity characteristics were also within acceptable bounds. Conclusion: Results from the binding potential of phytoconstituents aimed at antidiabetic activity were encouraging. It promotes the usage of Manilkara hexandra and offers crucial details on pharmaceutical research and clinical care.

Investigation of Antidiabetic Activities of Cu(II) Complex of Anacardium occidentale Leaves Crude Extract

Many synthetic chemical drugs have been widely used for the treatment of diabetes. However, many of these drugs are not locally available, are less effective, and are unaffordable for many diabetic patients in developing and underdeveloped countries. Therefore, in order to search for a locally available, effective, and cost-effective antidiabetic agent, this study synthesized the Cu(II) complex of crude leaf extract of Anacardium occidentale and investigated its antidiabetic activity in alloxan induced albino rats. The leaf crude extract and its metal complex were characterized using atomic absorption spectroscopy (AAS) and infrared (IR) spectroscopy. Experimental diabetic animals were induced by a single intraperitoneal injection of alloxan monohydrate at a single dose of 140 mg/kg body weight (b.wt.), and animals with fasting blood glucose levels (BGL) &gt; 200 mg/dl were considered diabetic. Metformin was used as a standard drug. Fasting blood glucose level (BGL) and body weight were examined in assessing the antidiabetic activities of the crude extract and its complex in the rats. One-way ANOVA was used to determine the antidiabetic activity at a statistical significance level of p &lt; 0.05. The hypsochromic shifts of C=O and O-H bands in the Cu(II) complex and the high concentration of the metal ion in the metal complex established the coordination of the crude extract with the metal ion. A more significant reduction in the blood glucose level and increase in body weight in alloxan-induced diabetic albino rats was observed when treated with the leaves crude extract and its Cu(II) complex than when treated with the standard drug metformin. It can be concluded that the Cu(II) complex of Anacardium occidentale leaf extract at a dose of 400 mg/kg wt is more effective without abnormal weight gain and could be considered as a potential antidiabetic drug to replace some of the less effective and expensive conventional antidiabetic drugs.

Determination of Phytochemicals, Minerals, and Evaluation of Antioxidant, Antidiabetic Activities of Young Fronds of &lt;i&gt;Diplazium esculent&lt;/i&gt;um: A Vegetable of Tripura, India

Diplazium esculentum belongs to the family Athyriaceae, an edible fern rich in micronutrients, beta-carotene, folic acid, and minerals like calcium, iron, and phosphorus. The present study aims to determine secondary metabolites and minerals content and evaluate the antioxidant and antidiabetic activities of young fronds of Diplazium esculentum. The plant extract was prepared by the Soxhlet apparatus method. Total alkaloids and total tannin content were determined by the titrimetric method. Folin and Ciocalteu's colorimetric method used gallic acid as a standard drug to determine total phenols. The antioxidant activity of plant extract was evaluated by DPPH free radical scavenging and hydrogen peroxide scavenging assay. α-amylase inhibition assay was performed for evaluation of the antidiabetic activity of plant extract. Fronds of Diplazium esculentum contain a significant number of total alkaloids (145.54±1.49), phenols (174.2±0.95), and tannins (263.96±1.32) mg/g of dry extract. Fronds of Diplazium esculentum also contain a significant amount of minerals. Diplazium esculentum shows significant antioxidant activity compared to the standard drug ascorbic acid and antidiabetic activity compared to the standard drug metformin. Based on these findings, young fronds of Diplazium esculentum can be recommended as a good source of phytochemicals and minerals. It also shows significant antioxidant and antidiabetic activities.

Identification of starvation-mimetic bioactive phytocomponent from Withania somnifera using in-silico molecular modelling and flow cytometry-based analysis for the management of malaria

Multidrug resistance episodes in malaria increased from 3.9% to 20% from 2015 to 2019. Synchronizing the clinical manifestation in chronological sequence led to a unique impression on glucose demand (increased up to 100-fold) by the parasite-infected RBCs. Hence, restriction in the glucose uptake to parasite-infected RBCs could be an alternative approach to conquer the global burden of malaria to a greater extent. A C28 steroidal lactone Withaferin A (WS-3) isolated from Withania somnifera leave extract shows better thermodynamically stable interactions with the glucose transporters (GLUT-1 and PfHT) to standard drugs metformin and lopinavir. MD simulations for a trajectory period of 100 ns reflect stable interactions with the interactive amino acid residues such as Pro141, Gln161, Gln282, Gln283, Trp388, Phe389, and Phe40, Asn48, Phe85, His168, Gln169, Asn311 which potentiating inhibitory activity of WS-3 against GLUT-1 and PfHT respectively. WS-3 was non-hemotoxic (%hemolysis <5%) for a high concentration of up to 1 mg/ml in the physiological milieu. However, the %hemolysis significantly increased up to 30.55 ± 0.929% in a parasitophorous simulated environment (pH 5.0). Increased hemolysis of WS-3 could be due to the production of ROS in an acidic environment. Further, the inhibitory activity of WS-3 against both glucose transporters was supported with flow cytometry-based analysis of parasite-infected RBCs. Results show that WS-3 has low mean fluorescence intensities for both target proteins compared to conventional drugs, suggesting a potential sugar transporter inhibitor against GLUT-1 and PfHT for managing malaria. Communicated by Ramaswamy H. Sarma

Anti-diabetic activity of Mimosa pigra Linn (Fabaceae) methanol leaf extract on alloxan-induced diabetic rats

The leaves of Mimosa pigra have been reported in ethnobotany to be used for the management of the symptoms of diabetes. This study is to investigate the anti-diabetic activity of the methanol extract of the leaves of this plant. The leaves were dried, pulverized and macerated successively in n-hexane, acetone and methanol. The methanol extract (1 g/kg body weight) was evaluated in vivo for anti-diabetic activity using adult male Wistar albino rats. Alloxan (150 mg/kg b.wt.) was used for induction of hyperglycemia, and Metformin (2.5 mg/kg) was used as the standard oral hypoglycemic agent. Blood glucose levels were monitored with a glucometer. The data is presented as Standard deviation (±) of the mean of blood glucose levels (mg/dl), and analyzed using one way analysis of variance (ANOVA) at (p&lt;0.05). The methanol extract of the leaves showed significant percent decrease (p&lt;0.05) in blood glucose levels of 3.80, 7.15 and 10.35 %, at 60, 120 and 180 min, respectively, on Day 1. And from Day 2 to Day 7 there was a continued decrease of 10.75, 16.36, 22.09, 29.06, 33.4 and 36.67 %, respectively, compared to the control. For the same period, the standard drug Metformin demonstrated greater decreases of 24.45, 30.38, 37.37, 40.93, 46.18 and 52.30 %, respectively. Phytochemical screening revealed the presence of flavonoids and tannins in the methanol and acetone extracts, while saponins and triterpenes were present in both the hexane and methanol extracts. The presence of these metabolites could be responsible for the observed anti-diabetic activity of this plant.

Orally Administered Aqueous Extract of Pleurotus ostreatus Ameliorates Hyperglycemia in Streptozotocin-Induced Diabetic Rats

Pleurotus ostreatus (Jacq.) P. Kumm. (Family: Pleurotaceae), commonly known as oyster mushroom, has been widely used to treat various ailments from simple headache to serious ones like diabetes. The mushroom has been shown to exert anti-inflammatory and antioxidant activities. In the present study, aqueous extract of P. ostreatus (AEPO) was examined for its antidiabetic activity in streptozotocin (STZ)-induced diabetic rats. STZ was administered to rats at 50 mg/kg body weight (i.p.), AEPO was orally administered at 100 and 200 mg/kg body weight, and metformin (500 mg/kg) was administered as positive control. The hypoglycemic effects of the AEPO were analyzed by assessing the blood glucose levels (oral glucose tolerance test, acute and postprandial antihyperglycemic activity), lipid parameters, and other hematological studies in comparison to standard drug (metformin). Results showed that AEPO caused a 26% reduction in blood glucose during fasting while 45% reduction in blood glucose during postprandial antihyperglycemic test in STZ-diabetic rats. It also helped in the normalizations of various complications associated with diabetes mellitus in rats. Observations from the current experiments indicate that P. ostreatus help in reduction of blood glucose level, thus confirming its antidiabetic activity in STZ-induced diabetes in rats. This study further advocates that supplementation of edible mushroom P. ostreatus could be a preventive approach in diabetes as well as in obesity management.

Antidiabetic and Anticancer Potentials of Mangifera indica L. from Different Geographical Origins.

Mango fruit is well known for its nutritional and health benefits due to the presence of a plethora of phytochemical classes. The quality of mango fruit and its biological activities may change depending upon the variation in geographical factors. For the first time, this study comprehensively screened the biological activities of all four parts of the mango fruit from twelve different origins. Various cell lines (MCF7, HCT116, HepG2, MRC5) were used to screen the extracts for their cytotoxicity, glucose uptake, glutathione peroxidase activity, and α-amylase inhibition. MTT assays were carried out to calculate the IC50 values for the most effective extracts. The seed part from Kenya and Sri Lanka origins exhibited an IC50 value of 14.44 ± 3.61 (HCT116) and 17.19 ± 1.60 (MCF7). The seed part for Yemen Badami (119 ± 0.08) and epicarp part of Thailand (119 ± 0.11) mango fruit showed a significant increase in glucose utilization (50 μg/mL) as compared to the standard drug metformin (123 ± 0.07). The seed extracts of Yemen Taimoor seed (0.46 ± 0.05) and Yemen Badami (0.62 ± 0.13) produced a significant reduction in GPx activity (50 μg/mL) compared to the control cells (100 μg/mL). For α-amylase inhibition, the lowest IC50 value was observed for the endocarp part of Yemen Kalabathoor (108.8 ± 0.70 μg/mL). PCA, ANOVA, and Pearson's statistical models revealed a significant correlation for the fruit part vs. biological activities, and seed part vs. cytotoxicity and α-amylase activity (p = 0.05). The seed of mango fruit exhibited significant biological activities; hence, further in-depth metabolomic and in vivo studies are essential to effectively utilize the seed part for the treatment of various diseases.

Antidiabetes study of Spondias mombin (Linn) stem bark fractions in high-sucrose diet-induced diabetes in Drosophilamelanogaster

ObjectiveThe onset of insulin resistant diabetes has been associated with a high-sucrose diet in vertebrates and invertebrates. However, various parts of Spondias mombin reportedly possess antidiabetic potential. However, the antidiabetic efficacy of S. mombin stem bark in high-sucrose diet-induced Drosophila melanogaster model has not been explored. In this study, the antidiabetic and antioxidant effects of the solvent fractions of S. mombin stem bark were evaluated using in vitro, in vivo, and in silico methods. MethodsSuccessive fractionation of S. mombin stem bark ethanol extract was performed; the resulting fractions were subjected to in vitro antioxidant and antidiabetic assays using standard protocols. The active compounds identified from the high-performance liquid chromatography (HPLC) study of the n-butanol fraction were docked against the active site of Drosophila α-amylase using AutoDoc Vina. The n-butanol and ethyl acetate fractions of the plant were incorporated into the diet of diabetic and nondiabetic flies to study the in vivo antidiabetic and antioxidant properties. ResultsThe results obtained revealed that n-butanol and ethyl acetate fractions had the highest in vitro anti-oxidant capacity by inhibiting 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power, and hydroxyl radical followed by significant inhibition of α-amylase. HPLC analysis revealed the identification of eight compounds with quercetin having the highest peak followed by rutin, rhamnetin, chlorogenic acid, zeinoxanthin, lutin, isoquercetin, and rutinose showing the lowest peak. The fractions restored the glucose and antioxidant imbalance in diabetic flies, which is comparable with the standard drug (metformin). The fractions were also able to upregulate the mRNA expression of insulin-like peptide 2, insulin receptor, and ecdysone-inducible gene 2 in diabetic flies. The in silico studies revealed the inhibitory potential of active compounds against α-amylase with isoquercetin, rhamnetin, rutin, quercetin, and chlorogenic acid having higher binding affinity than the standard drug (acarbose). ConclusionOverall, the butanol and ethyl acetate fractions of S. mombin stem bark ameliorate type 2 diabetes in Drosophila. However, further studies are needed in other animal models to confirm the antidiabetes effect of the plant.

In vivo studies on anti hyperglycemic activity of sericin using rat model

Silk protein, sericin was isolated from raw silk fabrication in reeling industry and subsequent process of silk throwing. The majority of it is thrown in the waste water from silk manufacturing. Sericin was used in antibacterial, antioxidant, wound healing, moisturising, and antiaging medications and cosmetics. Limited reports on the use of sericin in the treatment of diabetes prompted the current study on the use of sericin in the control of diabetes in rats. Thus, the present study was aimed to investigate the antihyperglycemic activity of sericin protein using rat model. The results indicated that sericin treated groups showed a noteworthy augment in body weight than the standard drug (Metformin) treatment with diabetic control. Sericin @ 400mg/kg showed 152.6 mg/dl and 141.2 mg/dl on 7th and 21st day of treatment. Similarly, Sericin @ 800mg/kg showed 126.0 mg/dl and 114.0 mg/dl on 7th and 21st day of treatment when compared to control (206.0 mg/dl and 203.6 mg/dl). SGOT of 68.4 and 50.0 units per litre of serum was observed in sericin @ 400 mg/kg and 800mg/kg treated rats when compared to control 138.6 units. SGPT 0f 26.0 and 21.6 units per litre of serum was observed in sericin @ 400 mg/kg and 800mg/kg treated rats when compared to control (75.0 units). Triglycerides of 96.4 and 81. 4 units were observed in sericin @ 400 mg/kg and 800mg/kg treated rats when compared to control (152.8 units).