A Review on Bioengineering Approaches to Insulin Delivery: A Pharmaceutical and Engineering Perspective

Diabetes mellitus (DM) is the most prevalent non‐contagious disease, which has affected a large number of people all over the world. Among all treatments known to have a positive influence in the control of DM, insulin therapy is the most common and effective one. Nowadays, various methods of insulin delivery are under investigation, which are able to reach a plausible bioavailability with ignorable side effects instead of insulin injection. This article presents a comprehensive review of the insulin therapy approach with a focus on modified methods in insulin delivery strategies and current advances in engineered insulin delivery systems.     

Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H₂O₂) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.     

Protective Effects of Ferulic Acid on Metabolic Syndrome: A Comprehensive Review

Metabolic syndrome (MetS) is a complex disease in which protein, fat, carbohydrates and other substances are metabolized in a disorderly way. Ferulic acid (FA) is a phenolic acid found in many vegetables, fruits, cereals and Chinese herbs that has a strong effect on ameliorating MetS. However, no review has summarized the mechanisms of FA in treating MetS. This review collected articles related to the effects of FA on ameliorating the common symptoms of MetS, such as diabetes, hyperlipidemia, hypertension and obesity, from different sources involving Web of Science, PubMed and Google Scholar, etc. This review summarizes the potential mechanisms of FA in improving various metabolic disorders according to the collected articles. FA ameliorates diabetes via the inhibition of the expressions of PEPCK, G6Pase and GP, the upregulation of the expressions of GK and GS, and the activation of the PI3K/Akt/GLUT4 signaling pathway. The decrease of blood pressure is related to the endothelial function of the aortas and RAAS. The improvement of the lipid spectrum is mediated via the suppression of the HMG-Co A reductase, by promoting the ACSL1 expression and by the regulation of the factors associated with lipid metabolism. Furthermore, FA inhibits obesity by upregulating the MEK/ERK pathway, the MAPK pathway and the AMPK signaling pathway and by inhibiting SREBP-1 expression. This review can be helpful for the development of FA as an appreciable agent for MetS treatment.     

Potential Therapeutic Target Protein Tyrosine Phosphatase-1B for Modulation of Insulin Resistance with Polyphenols and Its Quantitative Structure–Activity Relationship

The increase in the number of cases of type 2 diabetes mellitus (T2DM) and the complications associated with the side effects of chemical/synthetic drugs have raised concerns about the safety of the drugs. Hence, there is an urgent need to explore and identify natural bioactive compounds as alternative drugs. Protein tyrosine phosphatase 1B (PTP1B) functions as a negative regulator and is therefore considered as one of the key protein targets modulating insulin signaling and insulin resistance. This article deals with the screening of a database of polyphenols against PTP1B activity for the identification of a potential inhibitor. The research plan had two clear objectives. Under first objective, we conducted a quantitative structure–activity relationship analysis of flavonoids with PTP1B that revealed the strongest correlation (R² = 93.25%) between the number of aromatic bonds (naro) and inhibitory concentrations (IC₅₀) of PTP1B. The second objective emphasized the binding potential of the selected polyphenols against the activity of PTP1B using molecular docking, molecular dynamic (MD) simulation and free energy estimation. Among all the polyphenols, silydianin, a flavonolignan, was identified as a lead compound that possesses drug-likeness properties, has a higher negative binding energy of −7.235 kcal/mol and a pKd value of 5.2. The free energy-based binding affinity (ΔG) was estimated to be −7.02 kcal/mol. MD simulation revealed the stability of interacting residues (Gly183, Arg221, Thr263 and Asp265). The results demonstrated that the identified polyphenol, silydianin, could act as a promising natural PTP1B inhibitor that can modulate the insulin resistance.     

The Multifunctional Role of Herbal Products in the Management of Diabetes and Obesity: A Comprehensive Review

Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues that have a big impact on people’s lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.     

Pharmacological and Therapeutic Potential of Myristicin: A Literature Review

Natural products have been used by humanity for many centuries to treat various illnesses and with the advancement of technology, it became possible to isolate the substances responsible for the beneficial effects of these products, as well as to understand their mechanisms. In this context, myristicin, a substance of natural origin, has shown several promising activities in a large number of in vitro and in vivo studies carried out. This molecule is found in plants such as nutmeg, parsley, carrots, peppers, and several species endemic to the Asian continent. The purpose of this review article is to discuss data published in the last 10 years at Pubmed, Lilacs and Scielo databases, reporting beneficial effects, toxicity and promising data of myristicin for its future use in medicine. From 94 articles found in the literature, 68 were included. Exclusion criteria took into account articles whose tested extracts did not have myristicin as one of the major compounds.     

NAFLD患者TE成像特点与其病情严重程度及胰岛素抵抗的关系研究

本研究旨在分析NAFLD(非酒精性脂肪性肝病)患者TE(瞬时弹性成像技术)成像特点与其病情严重程度及胰岛素抵抗的关系。通过选择我院NAFLD患者112例,健康体检的患者108例,对比两组患者基线资料,将NAFLD患者根据病情分组并对比相关资料。研究表明NAFLD组患者肝功能、血清胰岛素、HOMA-IR(胰岛素抵抗指数)显著高于对照组,差异显著(P<0.05)。随着脂肪肝严重程度增加,患者普遍年龄增高,男性多于女性,肝脏硬度、肝功能、胰岛素相关指标均明显上升,差异显著(P<0.05)。ROC曲线分析表明CAP(受控衰减参数)对轻度、中度和重度NAFLD均有较高的诊断价值,灵敏度分别为0.865、0.861、0.931,特异度分别为0.614、0.819、0.822。随着NAFLD病情严重程度的加重,CAP与HOMA-IR值均升高,呈显著正相关(r=0.536,r=0.479)。据此可推断NAFLD患者的TE成像特点与不同程度NAFLD密切相关,胰岛素抵抗可临床辅助诊断NAFLD。     

Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells

Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes.     

The Effect of Chrysin-Loaded Phytosomes on Insulin Resistance and Blood Sugar Control in Type 2 Diabetic db/db Mice

Although a variety of beneficial health effects of natural flavonoids, including chrysin, has been suggested, poor solubility and bioavailability limit their practical use. As a promising delivery system, chrysin-loaded phytosomes (CPs) were prepared using egg phospholipid (EPL) at a 1:3 molar ratio and its antidiabetic effects were assessed in db/db diabetic mice. Male C57BLKS/J-db/db mice were fed a normal diet (control), chrysin diet (100 mg chrysin/kg), CP diet (100 mg chrysin equivalent/kg), metformin diet (200 mg/kg) or EPL diet (vehicle, the same amount of EPL used for CP preparation) for 9 weeks. Administration of CP significantly decreased fasting blood glucose and insulin levels in db/db mice compared with the control. An oral glucose tolerance test and homeostatic model assessment for insulin resistance were significantly improved in the CP group (p < 0.05). CP treatment suppressed gluconeogenesis via downregulation of phosphoenolpyruvate carboxykinase while it promoted glucose uptake in the skeletal muscle and liver of db/db mice (p < 0.05). The CP-mediated improved glucose utilization in the muscle was confirmed by upregulation of glucose transporter type 4, hexokinase2 and peroxisome proliferator-activated receptor γ during treatment (p < 0.05). The CP-induced promotion of GLUT4 plasma translocation was confirmed in the skeletal muscle of db/db mice (p < 0.05). Based on the results, CP showed greater antidiabetic performance compared to the control by ameliorating insulin resistance in db/db mice and phytosome can be used as an effective antidiabetic agent.     

The Biological Activities and Therapeutic Potentials of Baicalein Extracted from Oroxylum indicum: A Systematic Review

In Southeast Asia, traditional medicine has a longestablished history and plays an important role in the health care system. Various traditional medicinal plants have been used to treat diseases since ancient times and much of this traditional knowledge remains preserved today. Oroxylum indicum (beko plant) is one of the medicinal herb plants that is widely distributed throughout Asia. It is a versatile plant and almost every part of the plant is reported to possess a wide range of pharmacological activities. Many of the important bioactivities of this medicinal plant is related to the most abundant bioactive constituent found in this plant—the baicalein. Nonetheless, there is still no systematic review to report and vindicate the biological activities and therapeutic potential of baicalein extracted from O. indicum to treat human diseases. In this review, we aimed to systematically present in vivo and in vitro studies searched from PubMed, ScienceDirect, Scopus and Google Scholar database up to 31 March 2020 based on keywords “Oroxylum indicum” and “baicalein”. After an initial screening of titles and abstracts, followed by a full-text analysis and validation, 20 articles that fulfilled all the inclusion and exclusion criteria were included in this systematic review. The searched data comprehensively reported the biological activities and therapeutic potential of baicalein originating from the O. indicum plant for anti-cancer, antibacterial, anti-hyperglycemia, neurogenesis, cardioprotective, anti-adipogenesis, anti-inflammatory and wound healing effects. Nonetheless, we noticed that there was a scarcity of evidence on the efficacy of this natural active compound in human clinical studies. In conclusion, this systematic review article provides new insight into O. indicum and its active constituent baicalein as a prospective complementary therapy from the perspective of modern and scientific aspect. We indicate the potential of this natural product to be developed into more conscientious and judicious evidencebased medicine in the future. However, we also recommend more clinical research to confirm the efficacy and safety of baicalein as therapeutic medicine for patients.     

Comparative G-Protein-Coupled Estrogen Receptor (GPER) Systems in Diabetic and Cancer Conditions: A Review

For many patients, diabetes Mellitus and Malignancy are frequently encountered comorbidities. Diabetes affects approximately 10.5% of the global population, while malignancy accounts for 29.4 million cases each year. These troubling statistics indicate that current treatment approaches for these diseases are insufficient. Alternative therapeutic strategies that consider unique signaling pathways in diabetic and malignancy patients could provide improved therapeutic outcomes. The G-protein-coupled estrogen receptor (GPER) is receiving attention for its role in disease pathogenesis and treatment outcomes. This review aims to critically examine GPER’ s comparative role in diabetes mellitus and malignancy, identify research gaps that need to be filled, and highlight GPER’s potential as a therapeutic target for diabetes and malignancy management. There is a scarcity of data on GPER expression patterns in diabetic models; however, for diabetes mellitus, altered expression of transport and signaling proteins has been linked to GPER signaling. In contrast, GPER expression in various malignancy types appears to be complex and debatable at the moment. Current data show inconclusive patterns of GPER expression in various malignancies, with some indicating upregulation and others demonstrating downregulation. Further research should be conducted to investigate GPER expression patterns and their relationship with signaling pathways in diabetes mellitus and various malignancies. We conclude that GPER has therapeutic potential for chronic diseases such as diabetes mellitus and malignancy.     

A Comprehensive Review with Updated Future Perspectives on the Ethnomedicinal and Pharmacological Aspects of Moringa oleifera

Moringa oleifera is an ancient remedy plant, known as the miraculous plant due to its many prominent uses and significant health benefits. It is a nutrient-rich plant, with exceptional bioactive compounds, such as polyphenols that possess several medicinal properties. Many significant studies have been carried out to evaluate the ethnomedicinal and pharmacological properties of M. oleifera in various applications. Therefore, this comprehensive review compiles and summarizes important findings from recent studies on the potential properties of different parts of M. oleifera. The pharmacological properties of M. oleifera have been studied for various potential biological properties, such as cardio-protective, anti-oxidative, antiviral, antibacterial, anti-diabetic and anti-carcinogenic effects. Therefore, the potential of this plant is even more anticipated. This review also highlights the safety and toxicity effects of M. oleifera treatment at various doses, including in vitro, in vivo and clinical trials from human studies.     

Recent Advances in Understanding the Mechanisms of Elemene in Reversing Drug Resistance in Tumor Cells: A Review

Malignant tumors are life-threatening, and chemotherapy is one of the common treatment methods. However, there are often many factors that contribute to the failure of chemotherapy. The multidrug resistance of cancer cells during chemotherapy has been reported, since tumor cells’ sensitivity decreases over time. To overcome these problems, extensive studies have been conducted to reverse drug resistance in tumor cells. Elemene, an extract of the natural drug Curcuma wenyujin, has been found to reverse drug resistance and sensitize cancer cells to chemotherapy. Mechanisms by which elemene reverses tumor resistance include inhibiting the efflux of ATP binding cassette subfamily B member 1(ABCB1) transporter, reducing the transmission of exosomes, inducing apoptosis and autophagy, regulating the expression of key genes and proteins in various signaling pathways, blocking the cell cycle, inhibiting stemness, epithelial–mesenchymal transition, and so on. In this paper, the mechanisms of elemene’s reversal of drug resistance are comprehensively reviewed.     

Annexin A6 is highly abundant in monocytes of obese and type 2 diabetic individuals and is downregulated by adiponectin in vitro

Adiponectin stimulates cholesterol efflux in macrophages and low adiponectin may in part contribute to disturbed reverse cholesterol transport in type 2 diabetes. Monocytes express high levels of annexin A6 that could inhibit cholesterol efflux and it was investigated whether the atheroprotective effects of adiponectin are accompanied by changes in annexin A6 levels. Adiponectin reduces annexin A6 protein whereas mRNA levels are not affected. Adiponectin-mediated activation of peroxisome proliferator-activated receptor α (PPARα) and AMP-activated protein kinase (AMPK) does not account for reduced annexin A6 expression. Further, fatty acids and lipopolysaccharide that are elevated in obesity do not influence annexin A6 protein levels. Annexin A6 in monocytes from overweight probands or type 2 diabetic patients is significantly elevated compared to monocytes of normal-weight controls. Monocytic annexin A6 positively correlates with body mass index and negatively with systemic adiponectin of the blood donors. Therefore, the current study demonstrates that adiponectin reduces annexin A6 in monocytes and thereby may enhance cholesterol efflux. In agreement with these in vitro finding an increase of monocytic annexin A6 in type 2 diabetes monocytes was observed.     

High Endogenously Synthesized N-3 Polyunsaturated Fatty Acids in Fat-1 Mice Attenuate High-Fat Diet-Induced Insulin Resistance by Inhibiting NLRP3 Inflammasome Activation via Akt/GSK-3β/TXNIP Pathway

High-fat (HF) diets and low-grade chronic inflammation contribute to the development of insulin resistance and type 2 diabetes (T2D), whereas n-3 polyunsaturated fatty acids (PUFAs), due to their anti-inflammatory effects, protect against insulin resistance. Interleukin (IL)-1β is implicated in insulin resistance, yet how n-3 PUFAs modulate IL-1β secretion and attenuate HF diet-induced insulin resistance remains elusive. In this study, a HF diet activated NLRP3 inflammasome via inducing reactive oxygen species (ROS) generation and promoted IL-1β production primarily from adipose tissue preadipocytes, but not from adipocytes and induced insulin resistance in wild type (WT) mice. Interestingly, endogenous synthesized n-3 polyunsaturated fatty acids (PUFAs) reversed this process in HF diet-fed fat-1 transgenic mice although the HF diet induced higher weight gain in fat-1 mice, compared with the control diet. Mechanistically, palmitic acid (PA), the main saturated fatty acid in an HF diet inactivated AMPK and led to decreased GSK-3β phosphorylation, at least partially through reducing Akt activity, which ultimately blocked the Nrf2/Trx1 antioxidant pathway and induced TXNIP cytoplasm translocation and NLRP3 inflammasome activation, whereas docosahexaenoic acid (DHA), the most abundant n-3 PUFA in fat-1 adipose tissue, reversed this process via inducing Akt activation. Our GSK-3β shRNA knockdown study further revealed that GSK-3β played a pivot role between the upstream AMPK/Akt pathway and downstream Nrf2/Trx1/TXNIP pathway. Given that NLRP3 inflammasome is implicated in the development of most inflammatory diseases, our results suggest the potential of n-3 PUFAs in the prevention or adjuvant treatment of NLRP3 inflammasome-driven diseases.     

The Potential Role of Polyphenols in Modulating Mitochondrial Bioenergetics within the Skeletal Muscle: A Systematic Review of Preclinical Models

Polyphenols are naturally derived compounds that are increasingly being explored for their various health benefits. In fact, foods that are rich in polyphenols have become an attractive source of nutrition and a potential therapeutic strategy to alleviate the untoward effects of metabolic disorders. The last decade has seen a rapid increase in studies reporting on the bioactive properties of polyphenols against metabolic complications, especially in preclinical models. Various experimental models involving cell cultures exposed to lipid overload and rodents on high fat diet have been used to investigate the ameliorative effects of various polyphenols against metabolic anomalies. Here, we systematically searched and included literature reporting on the impact of polyphenols against metabolic function, particularly through the modulation of mitochondrial bioenergetics within the skeletal muscle. This is of interest since the skeletal muscle is rich in mitochondria and remains one of the main sites of energy homeostasis. Notably, increased substrate availability is consistent with impaired mitochondrial function and enhanced oxidative stress in preclinical models of metabolic disease. This explains the general interest in exploring the antioxidant properties of polyphenols and their ability to improve mitochondrial function. The current review aimed at understanding how these compounds modulate mitochondrial bioenergetics to improve metabolic function in preclinical models on metabolic disease.     

Redox-mediated Negative Differential Resistance (NDR) Behavior in Perylenediimide Derivative: A Supramolecular Approach

Deaggregated perylenediimide (PDI) derivatives exhibit exceptionally high quantum yields, photostability and appropriate molecular features for organic electronics. This work demonstrates a metal–dye–metal framework with a large and stable negative differential resistance (NDR) at ambient conditions, built using a supramolecular strategy. The deaggregation achieved through the encapsulation of the bay-substituted phenyl groups of aggregated (l/d )-Phe-PDI dyes by the β-CD macrocyclic host is validated through detailed spectroscopic and imaging techniques. The host–guest interaction resulted in a dramatic enhancement in the emission yield from 0.28 to 0.90. In the thin film deposits, the β-CD/(l/d )-Phe-PDI complex displayed well-connected sheet-like morphology, whereas the uncomplexed (l/d )-Phe-PDI dye remained as scattered lumps. The large and reversible I–V characteristics displaying strong NDR behavior is attributed to the oxidation/reduction processes involving the rigid π-rich PDI core and is stable at least for about six months at ambient conditions, a promising system for organic electronics applications.     

Advancements in Perovskite-Based Cathode Materials for Solid Oxide Fuel Cells: A Comprehensive Review

The high-temperature solid oxide fuel cells (SOFCs) are the most efficient and green conversion technology for electricity generation from hydrogen-based fuel as compared to conventional thermal power plants. Many efforts have been made to reduce the high operating temperature (>800 °C) to intermediate/low operating temperature (400 °C<T<800 °C) in SOFCs in order to extend their life span, thermal compatibility, cost-effectiveness, and ease of fabrication. However, the major challenges in developing cathode materials for low/intermediate temperature SOFCs include structural stability, catalytic activity for oxygen adsorption and reduction, and tolerance against contaminants such as chromium, boron, and sulfur. This research aims to provide an updated review of the perovskite-based state-of-the-art cathode materials LaSrMnO₃ (LSM) and LaSrCOFeO₃ (LSCF), as well as the recent trending Ruddlesden-Popper phase (RP) and double perovskite-structured materials SOFCs technology. Our review highlights various strategies such as surface modification, codoping, infiltration/impregnation, and composites with fluorite phases to address the challenges related to LSM/LSCF-based electrode materials and improve their electrocatalytic activity. Moreover, this study also offers insight into the electrochemical performance of the double perovskite oxides and Ruddlesden-Popper phase materials as cathodes for SOFCs.     

β-Sitosterol Circumvents Obesity Induced Inflammation and Insulin Resistance by down-Regulating IKKβ/NF-κB and JNK Signaling Pathway in Adipocytes of Type 2 Diabetic Rats

β-sitosterol (SIT), the most abundant bioactive component of vegetable oil and other plants, is a highly potent antidiabetic drug. Our previous studies show that SIT controls hyperglycemia and insulin resistance by activating insulin receptor and glucose transporter 4 (GLUT-4) in the adipocytes of obesity induced type 2 diabetic rats. The current research was undertaken to investigate if SIT could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of SIT (20 mg/kg b.wt) was administered orally for 30 days to high fat diet and sucrose induced type-2 diabetic rats. Metformin, the conventionally used antidiabetic drug was used as a positive control. Interestingly, SIT treatment restores the elevated serum levels of proinflammatory cytokines including leptin, resistin, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) to normalcy and increases anti-inflammatory adipocytokines including adiponectin in type 2 diabetic rats. Furthermore, SIT decreases sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) gene expression in adipocytes of diabetic rats. The gene and protein expression of c-Jun-N-terminal kinase-1 (JNK1), inhibitor of nuclear factor kappa-B kinase subunit beta (IKKβ) and nuclear factor kappa B (NF-κB) were also significantly attenuated in SIT treated groups. More importantly, SIT acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that SIT inhibits obesity induced insulin resistance by ameliorating the inflammatory events in the adipose tissue through the downregulation of IKKβ/NF-κB and c-Jun-N-terminal kinase (JNK) signaling pathway.