Exploring the Comprehensive Neuroprotective and Anticancer Potential of Afzelin.

Neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, Huntington's disease, and others) and cancer, seemingly disparate in their etiology and manifestation, exhibit intriguing associations in certain cellular and molecular processes. Both cancer and neurodegenerative diseases involve the deregulation of cellular processes such as apoptosis, proliferation, and DNA repair and pose a significant global health challenge. Afzelin (kaempferol 3-O-rhamnoside) is a flavonoid compound abundant in various plant sources. Afzelin exhibits a diverse range of biological activities, offering promising prospects for the treatment of diseases hallmarked by oxidative stress and deregulation of cell death pathways. Its protective potential against oxidative stress is also promising for alleviating the side effects of chemotherapy. This review explores the potential therapeutic implications of afzelin, including its capacity to mitigate oxidative stress, modulate inflammation, and promote cellular regeneration in neurodegenerative and cancer diseases.

Arbutin's Potential in Neuroprotection: A Promising Role in Mitigating Neurodegenerative Diseases.

Naturally occurring glycosylated hydroquinone Arbutin, has drawn interest due to its possible function in reducing the risk of neurodegenerative diseases such as Huntington's disease, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease. Arbutin is well-known for its anti-inflammatory and antioxidant properties, which are essential in preventing oxidative stress and neuroinflammation. Research has shown that arbutin might alter important physiological pathways connected to protein misfolding, synapse function, and neuronal survival processes linked to the development of neurodegenerative diseases. Arbutin can also penetrate the blood- -brain barrier, which increases its therapeutic potential. Arbutin's neuroprotective properties and promise as a therapeutic agent for neurodegenerative illnesses are summarized in this review, which also emphasizes the need for further study into the molecular processes behind these effects.

Cross Talks between CNS and CVS Diseases: An Alliance to Annihilate.

Cardiovascular and neurological diseases cause substantial morbidity and mortality globally. Moreover, cardiovascular diseases are the leading cause of death globally. About 17.9 million people are affected by cardiovascular diseases and 6.8 million people die every year due to neurological diseases. The common neurologic manifestations of cardiovascular illness include stroke syndrome which is responsible for unconsciousness and several other morbidities significantly diminished the quality of life of patients. Therefore, it is prudent need to explore the mechanistic and molecular connection between cardiovascular disorders and neurological disorders. The present review emphasizes the association between cardiovascular and neurological diseases specifically Parkinson's disease, Alzheimer's disease, and Huntington's disease.

Boosting the photocatalytic activity of g-C3N4 via loading bio-synthesized Ag0 nanoparticles and imidazole modification for the degradation and mineralization of fluconazole.

The emergence of fluorinated organic compounds in the pharmaceutical, agrochemical, and textile industries has led to a potential increase in the environmental issues and health problems. Herein, a modified heterojunction of bio-synthesized Ag nanoparticles (Ag0 NPs) immobilized on imidazole-modified graphite carbon nitride (Im/g-C3N4) as a suitable support (Ag0/Im/g-C3N4) was hydrothermally synthesized and studied for the photocatalytic removal of the most widely used antifungal organo-fluorine compound-fluconazole (FCZ). The optical properties were thoroughly investigated in the present study, and it was observed that the proposed modification to g-C3N4 has led to the shifting of conduction and valance band edge position (for g-C3N4, -0.73 and 1.54 eV and for ICA, -1.14 and 1.28 eV), narrowing of band gap energies, i.e., 2.01 eV, and reduced charge recombination rate. The external and internal surface morphologies were scrutinized through FE-SEM and HR-TEM analyses. Functionalities and potential crystallinity were investigated using FTIR and XRD techniques. The elemental state and composition of the composite were analyzed via XPS. The obtained results substantiate the intended modifications in the ICA composite. The photocatalyst Ag0/Im/g-C3N4 (ICA) was able to degrade 95.74% of FCZ with a high degradation rate (k1) of 0.0289 min-1 within 2-h of the solar illumination experiment. The overall degradation process was observed to be governed by a pseudo-first-order kinetic model. Detailed parameters such as effects of ions, pH (optimized pH 4, highest degradation rate k1 =0.039 min-1), dissolved organic matter (DOM), and optimization of catalysts dosage were studied. The major reactive oxygen species (ROS) was identified as super-oxide radicals (O2●-). The HR-MS and COD-TOC analysis were used to evaluate the degradation and mineralization of FCZ forced by ICA catalysts. The ICA catalyst was found to be stable and reusable for up to five cycles suggesting towards its potential towards the mitigation of environmental pollutants.

Targeting cardiovascular risk factors with eugenol: an anti-inflammatory perspective.

Inflammation is a multifaceted biological reaction to a wide range of stimuli, and it has been linked to the onset and progression of chronic diseases such as heart disease, cancer, and diabetes. Inflammatory markers found in the blood, including C-reactive protein, serum amyloid A, fibrinogen, plasma viscosity, erythrocyte sedimentation rate, interleukin-6, and soluble adhesion molecules (like intercellular adhesion molecule-1 and vascular cell adhesion molecule-1), are risk factors for cardiovascular diseases such as coronary heart disease, stroke, and peripheral arterial disease. These markers play a crucial role in understanding and assessing cardiovascular health. Due to this complicated relationship between inflammation and cardiovascular disease, anti-inflammatory agents of natural origin have been the subject of many preclinical and clinical studies in recent years. Eugenol is a natural phenolic compound found in clove oil, nutmeg oil, cinnamon oil, and bay leaf oil, as well as other essential oils. Eugenol has been shown to have anti-inflammatory properties in many forms of experimental inflammation. It may scavenge free radicals, which contribute to inflammation and tissue damage. Various studies also suggest that eugenol can limit the production of inflammatory mediators such as prostaglandins, cytokines, and chemokines. Animal models of arthritis, colitis, and lung damage, as well as human clinical studies, have shown that eugenol has phenomenal anti-inflammatory properties. These properties suggest that eugenol may be able to reduce the risk of cardiovascular diseases.

Effects of Tiliroside and Lisuride Co-Treatment on the PI3K/Akt Signal Pathway: Modulating Neuroinflammation and Apoptosis in Parkinson's Disease.

Researchers are actively exploring potential bioactive compounds to enhance the effectiveness of Lisuride (Lis) in treating Parkinson's disease (PD) over the long term, aiming to mitigate the serious side effects associated with its extended use. A recent study found that combining the dietary flavonoid Tiliroside (Til) with Lis has potential anti-Parkinson's benefits. The study showed significant improvements in PD symptoms induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) when Til and Lis were given together, based on various behavioral tests. This combined treatment significantly improved motor function and protected dopaminergic neurons in rats with PD induced by MPTP. It also activated important molecular pathways related to cell survival and apoptosis control, as indicated by the increased pAkt/Akt ratio. Til and Lis together increased B-cell lymphoma 2 (Bcl-2), decreased caspase 3 activity, and prevented brain cell decay. Co-administration also reduced tumor necrosis factor alpha (TNF-α) and Interleukin-1 (IL-1). Antioxidant markers such as superoxide dismutase (SOD), catalase, and reduced glutathione significantly improved compared to the MPTP-induced control group. This study shows that using Til and Lis together effectively treats MPTP-induced PD in rats, yielding results comparable to an 8 mg/kg dose of levodopa, highlighting their potential as promising Parkinson's treatments.

Ameliorative Effects of Isoeugenol and Eugenol against Impaired Nerve Function and Inflammatory and Oxidative Mediators in Diabetic Neuropathic Rats.

Diabetic polyneuropathy is characterized by structural abnormalities, oxidative stress, and neuroinflammation. The current study aimed to determine the antinociceptive effects of isoeugenol and eugenol and their combinations in neuropathic pain resulting from streptozotocin (STZ)-induced diabetes and neuroinflammation. Female SD rats were categorized into normal control, diabetic control, and treatment groups. On the 28th day and 45th day, behavioral studies (allodynia and hyperalgesia) were performed to analyze the development and protection of diabetic polyneuropathy. The levels of inflammatory and oxidative mediators, such as superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), catalase, reduced glutathione, and thiobarbituric acid reactive substances (TBARS), were estimated. In addition, the level of nerve growth factor (NGF) was estimated at the end of the study in different groups. The anti-NGF treatment decreased its upregulation in the dorsal root ganglion significantly. The results showed that isoeugenol, eugenol, and their combination have therapeutic potential against neuronal and oxidative damage induced by diabetes. In particular, both compounds significantly affected behavioral function in treated rats and showed neuroprotection against diabetic neuropathy, and their combination had synergistic effects.

Effects of Taraxerol on Oxidative and Inflammatory Mediators in Isoproterenol-Induced Cardiotoxicity in an Animal Model.

Myocardial infarction (MI) continues to be an important issue in healthcare systems worldwide, leading to high rates of morbidity and mortality. Despite ongoing efforts towards the development of preventive measures and treatments, addressing the challenges posed by MI remains difficult both in developed and developing countries. However, researchers recently investigated the potential cardioprotective effects of taraxerol utilizing an isoproterenol (ISO)-induced cardiotoxicity model among Sprague Dawley rats. Specifically, subcutaneous tissue injections consisting of 5.25 mg/kg or 8.5 mg/kg ISO were administered over two consecutive days as stimuli to induce cardiac injury. To investigate the possibility of preventing damage caused by ISO-induced cardiotoxicity by taraxerol treatment, five groups were formed: a normal control group (1% Tween 80), an ISO control group, an amlodipine group administered 5 mg/kg/day, and various doses of taraxerol. The study results showed that treatment significantly reduced cardiac marker enzymes. Additionally, pretreatment with taraxerol increased myocardial activity in SOD and GPx, leading to significant reductions in serum CK-MB levels along with MDA, TNF-α, and IL-6. Further histopathological analysis supported these observations, as treated animals had less cellular infiltration compared to untreated ones. These multifaceted findings suggest that oral administration of taraxerol could potentially protect hearts from ISO-caused damage by increasing endogenous antioxidant concentrations while decreasing pro-inflammatory cytokines.

Recent Advances in Research and Management of Human Monkeypox Virus: An Emerging Global Health Threat.

In 2003, the United States saw an epidemic of monkeypox that was later traced back to rodents of West Africa infected with the monkeypox virus (MPXV). Disease in the United States seemed less severe than the smallpox-like disease in the Democratic Republic of the Congo (DRC). In this study, researchers analyzed data from Central Africa: two distinct MPXV clades were confirmed by sequencing the genomes of MPXV isolates from Western Africa, the United States, and Central Africa. By comparing open reading frames across MPXV clades, scientists can infer which virus proteins might account for the observed variation in pathogenicity in humans. Monkeypox can be prevented and controlled with a better understanding of MPXV's molecular etiology and epidemiological and clinical features. In light of the current outbreaks worldwide, we provide updated information on monkeypox for medical professionals in this review.

The Cardioprotective Effect of Corosolic Acid in the Diabetic Rats: A Possible Mechanism of the PPAR-γ Pathway.

The study was conducted to determine whether corosolic acid could protect the myocardium of diabetic rats from damage caused by isoproterenol (ISO) and, if so, how peroxisome proliferator-activated receptor gamma (PPAR-γ) activation might contribute into this protection. Diabetes in the rats was induced by streptozotocin (STZ), and it was divided into four groups: the diabetic control group, diabetic rats treated with corosolic acid, diabetic rats treated with GW9662, and diabetic rats treated with corosolic acid plus GW9662. The study was carried out for 28 days. The diabetic control and ISO control groups showed a decrease in mean arterial pressure (MAP) and diastolic arterial pressure (DAP) and an increase in systolic arterial pressure (SAP). The rat myocardium was activated by corosolic acid treatment, which elevated PPAR-γ expression. A histopathological analysis showed a significant reduction in myocardial damage by reducing myonecrosis and edema. It was found that myocardial levels of CK-MB and LDH levels were significantly increased after treatment with corosolic acid. By decreasing lipid peroxidation and increasing endogenous antioxidant levels, corosolic acid therapy showed a significant improvement over the ISO diabetic group. In conclusion, our results prove that corosolic acid can ameliorate ISO-induced acute myocardial injury in rats. Based on these results, corosolic acid seems to be a viable new target for the treatment of cardiovascular diseases and other diseases of a similar nature.

Anticholinergic effect of resveratrol with vitamin E on scopolamine-induced Alzheimer's disease in rats: Mechanistic approach to prevent inflammation.

The most common form of dementia, Alzheimer's disease (AD), is characterized by gradual declines in cognitive abilities and behavior. It is caused by a combination of factors, including amyloid-ß (Aß) accumulation, acetylcholine (ACh) loss, oxidative stress, and inflammation. Phenolic compounds have a variety of health benefits, including antioxidant activities. Thus, the purpose of this study was to investigate how resveratrol (RES) alone and in combination with vitamin E affected rats with AD using scopolamine (SCO). Animals are categorized into groups; (i) control, (ii) SCO (1 mg/kg i.p.), (iii) SCO + donepezil, (iv) SCO + RES (50 mg/kg, p.o.), (v) SCO + RES (75 mg/kg, p.o.), (vi) SCO + RES (50 mg/kg + vitamin E 1 mg/kg, p.o.) for 17 days. In rats, studied behavioural (NOR and EPM) and biochemical characteristics. In addition, brain histopathology was examined to investigate any damage to the hippocampus and neuroprotection. SCO-induced changes in acetylcholinesterase, protein carbonyl, and TNF-α improved after resveratrol treatment. RES increased antioxidant levels, decreased SCO-induced lipid peroxidation, and reversed SCO-mediated changes compared with the drug donepezil. The results indicated that RES and vitamin E had nootropic action in the NOR and EPM tests, measured by the recognition index and the inflection ratio. This study supports the efficacy of RES as a preventive and treatment agent for AD. Vitamin E showed a synergistic effect on RES, which helps in managing cognitive impairment AD.

Quercetin Attenuates Nitroglycerin-Induced Migraine Headaches by Inhibiting Oxidative Stress and Inflammatory Mediators.

This study aimed to investigate the antimigraine potential of quercetin in migraine pain induced by nitroglycerin (NTG), 10 mg/kg, intraperitoneal injection in rats. Quercetin was administered orally for 1 week, and behavioral parameters associated with pain were assessed 30 min after NTG injection. At the end of the study, the rats were killed so that immunohistochemical examination of their brains could be performed. The time and frequency of rearing and sniffing in the category of exploratory behavior, walking in the category of locomotor behavior, and total time spent in the light chamber were reduced in the disease control group compared with the normal group during the assessment of behavioral parameters. Pathologic migraine criteria, such as increased levels of calcitonin gene-related peptide and increased release of c-fos cells, were more prominent in the caudal nucleus triceminalis of the NTG control group. In the treatment groups, behavioral and pathological measures were less severe after pretreatment with quercetin at doses of 250 and 500 mg/kg. Therefore, it was concluded that quercetin improved the pain behavior of migraine patients in the NTG-induced migraine rat model. Quercetin is thought to have antimigraine effects due to its antioxidant and anti-inflammatory potential. Quercetin may therefore be a novel agent that can treat or prevent migraine pain and associated avoidance behaviors.

Rutin Improves Anxiety and Reserpine-Induced Depression in Rats.

Mental disorders have a poor clinical prognosis and account for approximately 8% of the global burden of disease. Some examples of mental disorders are anxiety and depression. Conventional antidepressants have limited efficacy in patients because their pharmacological effects wear off, and side effects increase with prolonged use. It is claimed that herbal medicine's antioxidant capacity helps regulate people's mood and provide a more substantial pharmacological effect. With this background, the purpose of this study is to investigate the effect of rutin on reserpine-induced anxiety and depression in rats. The animals were divided into groups of six rats each: normal control (water), a depression model, a rutin-treated rat model, and an amitriptyline-treated rat model. According to the results, 14 days of treatment with rutin, once daily, showed a modest antidepressant effect. This effect was mediated by increased serotonin, norepinephrine, and dopamine levels in cortical and hippocampal regions. The antioxidant and vasodilator properties of rutin may contribute to its antidepressant properties. According to this study, rutin has shown antidepressant effects by reducing antioxidant activity and acetylcholinesterase.

Analgesic Action of Catechin on Chronic Constriction Injury-Induced Neuropathic Pain in Sprague-Dawley Rats.

Chronic neuropathy is a common and debilitating problem that poses a significant challenge to health care worldwide. Natural compounds have received considerable attention as potential sources of new drugs for the treatment of neuropsychiatric pain. Catechin is a well-known novel flavonoid with several therapeutic properties, notably in neurodegenerative diseases. The current study is designed to investigate the role of catechin in neuroprotective activity in the chronic constriction injury (CCI) model. Apparently, healthy adult male Sprague-Dawley rats weighing 160-190 g (8 weeks old) were selected and grouped into the following: sham (distilled water), CCI group (CCI), standard [CCI + pregabalin (10 mg/kg, p.o.)], and test catechin [CCI + catechin (50 and 100 µg/kg p.o.)] for 28 days. Behavioral, thermal, and mechanical changes were evaluated. The results showed that mechanical allodynia and thermal hyperalgesia were reduced in the catechin-treated group when compared with the CCI group. In addition, the relationship between the analgesic effect of catechin and the expressions of TNF-α, IL-6, and IL-ß was established. The results showed that catechin reversed the signs of neuropathic pain. It also decreased the levels of TNF-α, IL-6, and IL-ß in the rat brain. Therefore, the results suggested that catechin has promising potential in the treatment and management of neuropathic pain by decreasing the levels of NF-κß-regulated inflammatory cytokines in the chronic constriction injury model.

Nanotechnology-based approaches applied to nutraceuticals.

Nutraceuticals and food industries are opening to a tremendously upcoming technology in the field of "Nano science". A new prospect has been defined by nanotechnology by conferring modified properties of nanomaterials and its application in the development of nanoformulations, nutritional supplements and food industry. Nanomaterials reveal exclusive properties because of their small size and high surface/volume ratio; thus, they have a complete application in nutraceuticals and food sector. In the existent review article, we obligate to present a comprehensive outline of the application of nanomaterials in development of advanced nano-based nutraceuticals with enhanced bioavailability, solubility, improved encapsulation efficiency, increased stability, sustained and targeted drug delivery, protection against degradation and microbial contamination and with improved pharmacological activity. It also highlights the importance of nanomaterials as nanosensors/nano-bio sensors for encapsulating peptides, antibodies, enzymes, etc. and in the food packaging industry and its future application. Thus, the review aims to focus on the benefits and new dimensions provided by nanomaterials and nanotechnology in health sectors by improving treatment strategies and quality of life.

Neuroprotective effects of arbutin against oxygen and glucose deprivation-induced oxidative stress and neuroinflammation in rat cortical neurons.

In this study, the neuroprotective potential of arbutin (100 µmol L-1) pre-treatment and post-treatment against oxygen/ glucose deprivation (OGD) and reoxygenation (R) induced ischemic injury in cultured rat cortical neurons was explored. The OGD (60 min) and reoxygenation (24 h) treatment significantly (p < 0.001) compromised the antioxidant defence in cultured neurons. Subsequently, an increase (p < 0.001) in lipid peroxidation and inflammatory cytokines (tumour necrosis factor-α and nuclear factor kappa-B) declined neuron survival. In pre- and post-condition experiments, treatment with arbutin enhanced both survival (p < 0.01) and integrity (p < 0.05) of cultured neurons. Results showed that arbutin protects (p < 0.05) against peroxidative changes, inflammation, and enhanced the antioxidant activity (e.g., glutathione, superoxide dismutase and catalase) in cultured neurons subjected to OGD/R. It can be inferred that arbutin could protect against ischemic injuries and stroke. The anti-ischemic activity of arbutin can arrest post-stroke damage to the brain.

The Mechanisms of Cucurbitacin E as a Neuroprotective and Memory-Enhancing Agent in a Cerebral Hypoperfusion Rat Model: Attenuation of Oxidative Stress, Inflammation, and Excitotoxicity.

Impaired cerebral hemodynamic autoregulation, vasoconstriction, and cardiovascular and metabolic dysfunctions cause cerebral hypoperfusion (CH) that triggers pro-oxidative and inflammatory events. The sequences linked to ion-channelopathies and calcium and glutamatergic excitotoxicity mechanisms resulting in widespread brain damage and neurobehavioral deficits, including memory, neurological, and sensorimotor functions. The vasodilatory, anti-inflammatory, and antioxidant activities of cucurbitacin E (CuE) can alleviate CH-induced neurobehavioral impairments. In the present study, the neuroprotective effects of CuE were explored in a rat model of CH. Wistar rats were subjected to permanent bilateral common carotid artery occlusion to induce CH on day 1 and administered CuE (0.25, 0.5 mg/kg) and/or Bay-K8644 (calcium agonist, 0.5 mg/kg) for 28 days. CH caused impairment of neurological, sensorimotor, and memory functions that were ameliorated by CuE. CuE attenuated CH-triggered lipid peroxidation, 8-hydroxy-2'-deoxyguanosine, protein carbonyls, tumor necrosis factor-α, nuclear factor-kappaB, myeloperoxidase activity, inducible nitric oxide synthase, and matrix metalloproteinase-9 levels in brain resulting in a decrease in cell death biomarkers (lactate dehydrogenase and caspase-3). CuE decreased acetylcholinesterase activity, glutamate, and increased γ-aminobutyric acid levels in the brain. An increase in brain antioxidants was observed in CuE-treated rats subjected to CH. CuE has the potential to alleviate pathogenesis of CH and protect neurological, sensorimotor, and memory functions against CH.

Anti-atherogenic effect of Nepitrin-7-O-glucoside: A flavonoid isolated from Nepeta hindostana via acting on PPAR - α receptor.

Atherogenic dyslipidemia is a condition and responsible for the induction of major cardiovascular diseases. Traditionally, Nepeta hindostana a medicinal plant commonly used as cardioprotective in Indo-Pak regions has gained importance because of its therapeutic active flavonoid Nepitrin-7-O-glucoside. Flavonoid-glycosides are steroids having the ability to exert specific, decisive action on the cardiac muscle. In the present research work flavonoid, Nepitrin-7-O-glucoside was isolated from methanolic extract via chromatographic techniques. The structure was elucidated and confirmed by different spectral techniques like Mass and 1H NMR spectrometry. Various preclinical atherosclerosis parameters such as lipid levels, SGOT/SGPT, body weight, histology of aorta and heart were estimated and beneficial effect of Nepitrin in high-fat diet (HFD) induced atherosclerosis for six weeks were observed. Outcomes of the preclinical results showed and proved that Nepitrin significantly improved dyslipidemia at an effective dose of 50 mg/kg as compared with HFD control and Simvastatin. Molecular docking showed significant binding affinity towards the target PPAR-α receptor (PDB: 2P54). Further the docked ligands with PDB: 2P54 were exposed to molecular dynamics studies to confirm the dynamic behaviour of PPAR-α receptor. Outcomes of the results of the in-vivo study and molecular dynamics study were in correlation with each-others. Further, it can be concluded that Nepitrin has a potent antiatherogenic agent and act by reducing the lipid levels via acting on PPAR-α receptor and regenerating the damaged cells.

Corrigendum: The Mechanisms of Cucurbitacin E as a Neuroprotective and Memory-Enhancing Agent in a Cerebral Hypoperfusion Rat Model: Attenuation of Oxidative Stress, Inflammation, and Excitotoxicity.

[This corrects the article DOI: 10.3389/fphar.2021.794933.].

Evaluation of Gamma Amino Butyric Acid (GABA) and Glibenclamide Combination Therapy in Streptozotocin Induced Diabetes.

BACKGROUND: Type 1-diabetes (T1D) is characterized by autoimmune destruction of ß-cells and loss of endogenous insulin. A lifelong dependency on exogenous supply of insulin presents a great challenge in the pharmacotherapy of T1D that elicits a quest for alternative therapies, which can protect ß-cells and revive their insulinogenic functions. GABA (γ-aminobutyric acid) has immunoprotective and ß-cell regenerative capabilities. Co-administration of an insulin secretagogue, such as glibenclamide (Glib), along with GABA may enhance the pancreatic insulin output in T1D. OBJECTIVE: The present study evaluated the possible mechanism of GABA in the improvement of glucose tolerance and its effects in streptozotocin (STZ) induced T1D along with Glib. METHODS: Wistar rats (180-220 g) were administered a single dose of STZ (55 mg/kg, i.p.). GABA (100 mg/kg, i.p.) and Glib (5 or 10 mg/kg, i.p.) alone or in combination were administered for 28 days. Body weight (b.w.), water consumption, fasting blood glucose (FBG), oral glucose tolerance, plasma lipids, insulin, and muscle GLUT-4 (glucose transporters) protein level were assessed. RESULTS: T1D significantly decreased b.w. and increased water-intake in rats. An increase in FBG and a decrease in plasma insulin and muscle GLUT-4 indicated STZ-triggered destruction of ß-cells in diabetic rats accompanied with dyslipidemia. GABA or Glib (10 mg/kg) significantly improved b.w., plasma insulin and GLUT-4 levels, and ameliorated FBG and blood lipid profile in diabetic rats. GABA and Glib (5 mg/kg) combination therapy achieved far better control over hyperglycemia and related pathogenic conditions (b.w., water-intake, insulin, GLUT-4, lipids). The anti-diabetic effect of combination therapy was significantly more pronounced in comparison to individual drug treatments. Histopathological analysis revealed an increase in the number of functional pancreatic-islets by combination therapy. CONCLUSION: GABA revitalized ß-cells against STZ-toxicity. GABA and Glib synergistically augmented insulin secretion that can be used to manage T1D and its complications. GABA has the potential to remarkably enhance the therapeutic outcome in diabetic patients and reduce the dose of existing anti-diabetic drugs such as Glib.