Anti-diabetic Molecules Research Articles

Insights into the Chemistry, Pharmacokinetics and Analytical Techniques of Lobeglitazone: A Novel Anti-diabetic Drug

Objective: This review article aims to provide crucial insights related to the chemistry, pharmacology and analytical techniques associated with Lobeglitazone, a promising anti-diabetic molecule. Diabetes is a chronic ailment which hinders the normal functioning of beta pancreatic cells due to which the pancreas becomes incapable of producing sufficient amount of insulin or the body is not able to utilize the insulin that is produced by the beta-pancreatic cells. Lobeglitazone is a novel thiazolidinedione class of drug approved for type-II diabetes management by regulatory agencies in South Korea and India. The molecule has the potential to replace pioglitazone for the treatment of type-II diabetes due to its lower effective dose (0.5 mg) and better safety profile. Method: A comprehensive literature review was conducted using sources like PubMed, ScienceDirect, and Google Scholar. The review focused on chemistry, pharmacology, efficacy, safety, and advancements in analytical techniques for Lobeglitazone estimation in biological samples, bulk, and dosage forms. Result: Lobeglitazone exhibits potent therapeutic efficacy in treating type-II diabetes with fewer adverse effects compared to previous thiazolidinedione drugs. It demonstrates a better safety profile, especially in terms of cardiovascular risk. However, current analytical methods for lobeglitazone rely on solvents that do not adhere to green chemistry principles, highlighting the need for eco-friendly alternatives. Conclusion: Lobeglitazone holds substantial potential to replace older thiazolidinedione drugs due to its lower effective dose and improved safety profile. Future research should focus on developing sustainable analytical methods that align with green chemistry principles, further reinforcing its role in diabetes management.

Assessing Cardiovascular Target Attainment in Type 2 Diabetes Mellitus Patients in Tertiary Diabetes Center in Romania.

Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) share a bidirectional link, and the innovative antidiabetic molecules GLP-1 Ras and SGLT-2is have proven cardiac and renal benefits, respectively. This study aimed to evaluate CV risk categories, along with lipid-lowering and antidiabetic treatments, in patients with T2DM from a real-life setting in Romania. A cross-sectional evaluation was conducted on 405 consecutively admitted patients with T2DM in an ambulatory setting, assessing them according to the 2019 ESC/EAS guidelines for moderate, high, and very high CV risk categories. The average age of the group was 58 ± 9.96 years, with 38.5% being female. The mean HbA1C level was 7.2 ± 1.7%. Comorbidities included HBP in 88.1% of patients, with a mean SBP and DBP of 133.2 ± 13.7 mm Hg and 79.9 ± 9 mm Hg, respectively, and obesity in 66.41%, with a mean BMI of 33 ± 6.33 kg/m2. The mean LDL-C levels varied by CV risk category: 90.1 ± 34.22 mg/dL in very high risk, 98.63 ± 33.26 mg/dL in high risk, and 105 ± 37.1 mg/dL in moderate risk. Prescribed treatments included metformin (100%), statins (77.5%), GLP-1 Ras (29.4%), and SGLT-2is (29.4%). In Romania, patients with T2DM often achieve glycemic control targets but fail to meet composite targets that include glycemic, BP, and lipid control. Additionally, few patients benefit from innovative glucose-lowering therapies with proven cardio-renal benefits or from statins.

A Comparative Study on the Antidiabetic Activity, Cytotoxicity and Lipid Profile of Trichilia emetica Oils.

The Trichilia emetica plant is traditionally used for medicinal and food purposes. However, there are limited studies on the bioactivity and cytotoxicity of its seed butter and aril oil. This study aimed to assess the antidiabetic activity and cytotoxicity of seed butter and aril oil, obtained via two different extraction methods, and compare their lipid profiles. The plant samples were collected from the Faifa mountains and extracted using a Soxhlet apparatus for hot extraction and a magnetic stirrer for cold maceration. The antidiabetic activity and cytotoxicity were evaluated using the α-amylase and MTT assays, respectively. The fatty acids were quantified utilizing gas chromatography-mass spectrometry. This study proves the impact of the extraction method on the yield, cytotoxicity, antidiabetic activity and lipid profile. The highest cytotoxicity was observed with the seed butter obtained via Soxhlet extraction. The α-amylase inhibition was observed at the highest levels with the seed butter and aril oil obtained via cold maceration. The palmitic acid (PA) and oleic acid (OA) were detected at their maximal concentrations in the seed butter obtained via Soxhlet extraction and aril oil obtained via cold maceration, respectively. This study represents an essential basis for understanding the importance of T. emetica as a valuable tree for food, cosmetic and medicinal purposes. Further experiments can lead to the development of green extraction techniques and isolation of the cytotoxic and antidiabetic molecules that can be developed into new pharmaceutical products or serve as lead molecules for new drugs.

Novel triterpenoid, Schidigeragenin B resourced from the mother tincture of Conium maculatum: A promising future Antidiabetic drug

Novel triterpenoid, Schidigeragenin B resourced from the mother tincture of Conium maculatum: A promising future Antidiabetic drug

Natural hypoglycaemic bioactives: Newer avenues and newer possibilities.

The incidences of endocrine and metabolic disorders like diabetes have increased worldwide. Several proposed molecular pathways mechanisms for the management of diabetes have been identified, but glycaemic control is still a challenging task in the drug discovery process. Most of the drug discovery processes lead to numerous scaffolds that are prominent in natural products. The review deals with the natural bioactives as an α-amylase inhibitors, α-glucosidase inhibitors, protein tyrosine phosphatase-1B inhibitors, dipeptidyl peptidase-IV inhibitors, G-protein coupled receptors-40 agonists, PPAR-γ agonists and the activators of 5'-adenosine monophosphate-activated protein kinase and glucokinase. So, in this review, we focused on the hypoglycaemic bioactives, which will assist scientific developers, traditional medicinal practitioners, and readers to discover some potent antidiabetic molecules. Strategies like chemometric approaches, scaffold hopping, and total synthesis of natural products by group modification or ring opening/closing mechanism could be useful for the development of novel hit/lead antidiabetic molecules. The study concludes that each phyto molecule inherits a potential to get explored by repurposing techniques for various antidiabetic targets and offer an alternative antidiabetic therapeutic medicinal potential.

Chemoinformatic-aided Antidiabetic Analysis of the Therapeutic Potential of Phytoconstituents in Eremomastax speciosa Extracts

This research attempts to establish the antihyperglycemic potential of Eremomastax speciosa, a medicinal plant utilized in traditional West African diabetes therapy, through virtual simulation. While numerous reports have validated its biological potency, studies on the drug-likeness and antidiabetic properties of its compounds are limited. The in silico pharmacological, and toxicological profile of aqueous, methanolic/methylene phytochemicals from previously reported work was analyzed using Swiss ADME and Protox II online server. The docking process was performed using PyRx-0.8, coupled with AutoDock Vina. Phytochemicals that aligned with Lipinski’s rules for drugs were then subjected to a virtual docking simulation. This simulation replicated the inhibitory effects of E. speciosa phytochemicals on sodium-glucose co-transporters (SGLT2) and α-amylase, similar to metformin, an FDA-approved antidiabetic medicine utilized as a control. Phytochemicals such as 8, 9,10-dimethyltricyclo[4.2.1.1(2,5)]decane-9,10-diol (-6.6 kcal/mol), 11-isopropylidenetricyclo[4.3.1.1(2,5)]undec-3-en-10-one (-7.9 kcal/mol), 4-(1,5-dihydroxy-2,6,6-trimethylcyclohex-2-enyl)but-3-en-2-one (-7.3 kcal/mol), and N-methyl-N-4-[2-acetoxymethyl-1-pyrrolidyl]-2-butynyl]-acetamide (-7.5 kcal/mol) exhibits superior binding affinities to the specific proteins targeted, compared to metformin, implying that E. speciosa is a source of druggable antidiabetic molecules that can be enhanced to achieve better efficacy.

Stability indicating for Quality Control Assessment of three antidiabetic molecules using HPLC technique: Stability Assessment of three antidiabetic molecules

Diabetes mellitus responds better to co-formulated tablet dosages of dapagliflozin (DFZN), metformin (MFMN), and vildagliptin (VDGN). For the purpose of studying stability and quantifying DFZN, VDGN, and MFMN in bulk forms and in dosage forms, an efficient and fast HPLC method of analysis is currently developed. The mobile phase featured 80:20 (v/v) 0.2 M, pH 3.0, ammonium acetate buffer and acetonitrile mixed together and Luna's HPLC C-18 column, named Phenyl hexyl, was utilised for DFZN, VDGN, and MFMN separation and its quantification. The PDA type detector operating at 235 nm wavelength was deployed. The “International Conference on Harmonisation” recommendations were strictly adhered throughout the validation process. A strong linear association between response and quantity in the range of 2.5–15 µg/ml (DFZN), 25–150 µg/ml (VDGN), and 125–750 µg/ml (MFMN) is supported by the regression information for the DFZN, VDGN, and MFMN calibration plots. The precision, selectivity, accuracy, sensitivity, ruggedness and robustness were satisfactory for the method. The tablet sample of DFZN, VDGN, and MFMN was subjected to acid, water, base, sodium bisulfite, light, dry heat and peroxide degradations. Significant differences in retention times were observed between the well-resolved peaks of the degradants and the primary peaks (DFZN, VDGN, and MFMN). Thus, the assay might be characterised as stability indicating. The contents of DFZN, VDGN, and MFMN in dosage forms were assessed precisely and accurately by currently developed HPLC technique. This technique may be applied to ensure the quality of formulation doses for DFZN, VDGN, and MFMN contents.

PLGA‐Based Drug Delivery Systems: A Promising Carrier for Antidiabetic Drug Delivery

AbstractPoly(lactic‐co‐glycolic acid) (PLGA) nanoparticles have emerged as a versatile platform for drug delivery due to their biodegradability, biocompatibility, and tunable release kinetics. One of the primary applications of PLGA nanoparticles in diabetes management is the encapsulation and controlled release of insulin, overcoming the limitations of frequent injections. Such systems provide sustained and stable glycemic control, reducing the risk of hypoglycemia. Different types of PLGAs and their derivatives are used for preparing varieties of micro/nanocarriers to deliver insulin as well as diverse antidiabetic molecules, including glucagon‐like peptide‐1 (GLP‐1) and its analog (exendin‐4), crocetin, metformin hydrochloride, gliclazide, ferulic acid (FA), etc., to reduce hyperglycemia. Here the current state of research and development in PLGA‐based drug delivery systems for diabetes management are summarized. Various strategies employed to enhance the targeting specificity of PLGA nanoparticles in diabetes therapy are explored. The outcome will provide an insight into the drug delivery potential and efficiency of PLGA in managing hyperglycemia and that will be useful in designing novel therapeutic to improve better control of diabetes mellitus. As research in this field continues to progress, PLGA‐based systems hold great potential for revolutionizing the treatment paradigm for diabetes mellitus.

Thiazolidine-2,4-dione hybrids as dual alpha-amylase and alpha-glucosidase inhibitors: design, synthesis, in vitro and in vivo anti-diabetic evaluation.

Twelve 3,5-disubstituted-thiazolidine-2,4-dione (TZD) hybrids were synthesized using solution phase chemistry. Continuing our previous work, nine O-modified ethyl vanillin (8a-i) derivatives were synthesized and reacted with the TZD core via Knoevenagel condensation under primary reaction conditions to obtain final derivatives 9a-i. Additionally, three isatin-TZD hybrids (11a-c) were synthesized. The intermediates and final derivatives were characterized using 1H and 13C NMR spectroscopy, and the observed chemical shifts agreed with the proposed structures. The in vitro alpha-amylase and alpha-glucosidase inhibitory evaluation of newly synthesized derivatives revealed compounds 9F and 9G as the best dual inhibitors, with IC50 values of 9.8 ± 0.047 μM for alpha-glucosidase (9F) and 5.15 ± 0.0017 μM for alpha-glucosidase (9G), 17.10 ± 0.015 μM for alpha-amylase (9F), and 9.2 ± 0.092 μM for alpha-amylase (9G). The docking analysis of synthesized compounds indicated that compounds have a higher binding affinity for alpha-glucosidase as compared to alpha-amylase, as seen from docking scores ranging from -1.202 to -5.467 (for alpha-amylase) and -4.373 to -7.300 (for alpha-glucosidase). Further, the molecules possess a high LD50 value, typically ranging from 1000 to 1600 mg kg-1 of body weight, and exhibit non-toxic properties. The in vitro cytotoxicity assay results on PANC-1 and INS-1 cells demonstrated that the compounds were devoid of significant toxicity against the tested cells. Compounds 9F and 9G showed high oral absorption, i.e., oral absorption >96%, and their molecular dynamics simulation yielded results closely aligned with the observed docking outcomes. Finally, compounds 9F and 9G were evaluated for in vivo antidiabetic assessment by the induction of diabetes in Wistar rats using streptozotocin. Molecule 9G has been identified as the most effective anti-diabetic molecule due to its ability to modulate several biochemical markers in blood plasma and tissue homogenates. The results were further confirmed by histology investigations conducted on isolated pancreas, liver, and kidney.

Novel gurmarin-like peptides from Gymnema sylvestre and their interactions with the sweet taste receptor T1R2/T1R3.

Gymnema sylvestre (GS) is a traditional medicinal plant known for its hypoglycemic and hypolipidemic effects. Gurmarin (hereafter Gur-1) is the only known active peptide in GS. Gur-1 has a suppressive sweet taste effect in rodents but no or only a very weak effect in humans. Here, 8 gurmarin-like peptides (Gur-2 to Gur-9) and their isoforms are reported in the GS transcriptome. The molecular mechanism of sweet taste suppression by Gur-1 is still largely unknown. Therefore, the complete architecture of human and mouse sweet taste receptors T1R2/T1R3 and their interaction with Gur-1 to Gur-9 were predicted by AlphaFold-Multimer (AF-M) and validated. Only Gur-1 and Gur-2 interact with the T1R2/T1R3 receptor. Indeed, Gur-1 and Gur-2 bind to the region of the cysteine-rich domain (CRD) and the transmembrane domain (TMD) of the mouse T1R2 subunit. In contrast, only Gur-2 binds to the TMD of the human T1R2 subunit. This result suggests that Gur-2 may have a suppressive sweet taste effect in humans. Furthermore, AF-M predicted that Gα-gustducin, a protein involved in sweet taste transduction, interacts with the intracellular domain of the T1R2 subunit. These results highlight an unexpected diversity of gurmarin-like peptides in GS and provide the complete predicted architecture of the human and mouse sweet taste receptor with the putative binding sites of Gur-1, Gur-2, and Gα-gustducin. In addition, gurmarin-like peptides may serve as promising drug scaffolds for the development of antidiabetic molecules.

Integrating In Silico and In vitro Approaches to Screen the Antidiabetic Properties from Trachyspermum ammi leaves

AIM: The purpose of this study was to explore the possible mechanisms through which Trachyspermum ammi may be beneficial in managing diabetes by in vitro methods and to predict the potential bioactive constituent/s responsible for its anti-diabetic activity through in silico docking study.
 Study Design: This study engaged in vitro and in silico studies to investigate the enzyme inhibition assay and molecular docking studies of phytochemical constituents when compare with standard treatment.
 Place and Duration of Study: Gokaraju Rangaraju college of pharmacy, Bachupally, Hyderabad, India. December 2021-2022.
 Methodology: Methanolic leaf extract of Trachyspermum ammi was prepared using maceration extraction. Plant extract was evaluated for its in vitro anti-diabetic activity. Further, docking screening was performed using Mcule software to predict potential moiety which may be responsible for its anti-diabetic activity.
 Results: Maceration extraction resulted in extractive yield of 16.15%. The presence of phenolic and flavonoid components in extract (135.59 ± 8.87 GAE/gm and 62.1 ± 4.17 quercetin/gm) dried extract respectively. In vitro anti-diabetic assays revealed that anti-hyperglycaemic activity of this plant can be attributed to its high efficiency to inhibit α-amylase (69.7%) and glucosidase (62.23%) enzymatic activity and protein glycation assay (95.23%), which are well established targets for the management of diabetes. Further, through docking studies we predicted that Apigenin, luteolin, Germacrene D and γ-Tocopherol present in this plant might be responsible for the anti-diabetic properties exhibited by this plant. These results provide a scientific justification for the traditional anti-diabetic use of this plant
 Conclusion: It may control diabetes through lowering dietary glucose uptake. Predicted anti-diabetic molecules need to be screened further for the management of hyperglycemia. It may conclude that Trachyspermum ammi is an important vegetable with a potent source of natural antioxidants and antidiabetic activity justifying its traditional use in green therapeutics.

STRUGGLE FOR. Italian-Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023 for better control of classical modifiable risk factors in clinical practice.

The progress in pharmacotherapy that has been made in recent years, including the introduction of very effective and safe lipid-lowering and antihypertensive drugs, has not yet translated into the expected universal control of blood pressure, lipid disorders and diabetes. In the STRUGGLE FOR Italian- -Polish-Spanish-Uzbek-Vietnamese Expert Forum Position Paper 2023, experts from five countries recounted several points about the paradigms of cardiological and cardiometabolic care for better control of classical modifiable risk factors in the year 2023. It is believed herein, that the need to intensify treatment, actively search for patients with cardiovascular risk factors, especially with arterial hypertension, hypercholesterolemia and diabetes, should go hand in hand with the implementation of the latest therapy, based on single pill combinations including proven, effective antihypertensive, lipid-lowering and antidiabetic molecules, many of which are listed in the present document. There is a need to use both new technological concepts, completely new drugs, as well as novel treatment concepts such as metabolic treatment in coronary artery disease, try to intensify the fight against smoking in every way, including the available range of drugs and procedures reducing the harm. This approach will provide substantially better control of the underlying cardiovascular risk factors in countries as varied as Italy, Poland, Spain, Uzbekistan and Vietnam.

In vitro anti-inflammatory, antidiabetic, antibacterial, and in silico studies of Ferruginan A isolated from Olea ferruginea Royle (Oleaceae)

Traditionally, Olea ferruginea Royle (Oleaceae) has been used as a painkiller and antidiabetic in various ailments. To provide a scientific background to this folklore the current study was designed to anti-inflammatory and antidiabetic effects of one of the isolated compound from this plant. Ferruginan A was isolated from the ethyl acetate extract of Olea ferruginea bark. This isolated molecule was subjected to in-vitro anti-inflammatory and antidiabetic effects using HRBCs and glucose uptake tests. The compound was also tested for molecular docking and ADMET study. Regarding the anti-inflammatory effect, the tested compound demonstrated a 69.82% inhibition at a concentration of 100µg/mL, while the Ferruginan A (100µl/mL) increased the uptake of glucose (3.79-71.86%) in the yeast cell. Similarly, the zone of inhibition values of Ferruginan A (24.98mm) against Escherichia coli were found to be comparable to standard (Imipenem: 31.09mm). The mechanism of antidiabetic and anti-inflammatory effects was explored by using docking simulations performed on four molecular targets related to diabetes and inflammation. The results showed that the isolated compound may act as an antidiabetic agent by inhibiting the 5' Adenosine monophosphate-activated protein kinase (AMPK). While it also showed inhibition of anti-inflammatory targets COX-1, COX-2, and Tumor necrosis factor alpha (TNF-α). The ADMET prediction study revealed that isolated compound possesses favorable ADMET profile. It was concluded that Ferruginan A might be a significant anti-inflammatory and antidiabetic molecule.

Exploring the potential of machine learning to design antidiabetic molecules: a comprehensive study with experimental validation

Recent advances in hardware and software algorithms have led to the rise of data-driven approaches for designing therapeutic modalities. One of the major causes of human mortality is diabetes. Thus, there is a tremendous opportunity for research into effective antidiabetic designs. Therefore, in this study, we used machine learning-based small molecule design. We used various chemoinformatic and binary fingerprint techniques on small molecules to construct multiple models for alpha-amylase inhibitors. Among these models, the top models were used for ensemble-based machine learning predictions on libraries of organic molecules supplemented with synthetic scaffolds that could be used as antidiabetic agents. Further, involved identifying 10 promising molecules from computational studies and determining their inhibitory effects on alpha-amylase. These molecules were synthesised and thoroughly analysed to assess their biological inhibitory properties. Then, thermodynamic simulations were conducted to determine the stability and affinity of experimentally active molecules. The research results showcased the top 10 ML models recorded impressive statistics with an average model score of 0.8216, Pearson-r value of 0.827 and external validation yielding a Q 2 value of 0.835, proving their reliability and accuracy. Ten derivatives of benzothiophene dioxolane was prime research focus due to computational predictions. The biological inhibitory assay of synthesised molecules showed that small molecules with ID ALC5 and ALC6 exhibited inhibitory efficiencies (IC50) of 2.1 ± 0.14 µM and 5.71 ± 0.02 µM against alpha-amylase enzyme, whereas other molecules showed moderate inhibition. In conclusion, the positive results of the experiment indicate that researchers should explore machine learning-driven design. Communicated by Ramaswamy H. Sarma

Pioglitazone Nanoparticle Deposited Biologically Active Substrate to Potentiate Antidiabetic Activity

Background:: Diabetes is one of the most escalating endocrine disorders around the global countries. Researchers are paying more attention towards herbal drugs for treating these chronic ailments. As per the statistics, the incidence of diabetes is increasing not only in adults but also in neonates. Herbal plants like Okra and Neem have been used in India since the ages to treat various kinds of ailments. Methods:: The methodology includes the preparation of granules from the okra gum and neem extract, which is compressed into tablets. The nanoparticle dispersion of Pioglitazone is prepared by using the 2% w/v polyvinyl pyrrolidone (PVP) and 1% sodium lauryl sulphate (SLS), which are then sprayed on the drug-free tablet substrate. This process enhances the area of the Pioglitazone particles and thereby increases the bioavailability of the drug. The spraying of the nanoparticles on the surface of the substrate reduces the aggregation of the particles, which is a drawback of nanoparticles. Results:: The results show that the release rate is increased 2.14 times compared with the pure drug by depositing Pioglitazone nanoparticles on a tablet substrate composed of the okra mucilage and alcoholic extract of Neem. It also shows that there is a remarkable reduction in the glucose levels in vivo when compared with the product formulated by employing the traditional wet granulation technique. Conclusion:: This study concluded that the addition of herbal antidiabetic molecules as excipients can improve the therapeutic effect significantly. Better antidiabetic activity may be obtained with the deposition of hydrophobic antidiabetic drugs on herbal antidiabetic components.

Mechanistic and Etiological Similarities in Diabetes Mellitus and Alzheimer's Disease: Antidiabetic Drugs as Optimistic Therapeutics in Alzheimer's Disease.

Diabetes mellitus and Alzheimer's disease are two common diseases that majorly affect the elderly population. Patients in both cases are increasing day by day. They are considered two independent diseases, but recent evidence suggests that they have a lot in common. In this review, we focused on the connection between Alzheimer's disease and diabetes and highlighted the importance of antidiabetic drugs against Alzheimer's disease. Common pathways such as obesity, vascular diseases, oxidative stress, mitochondrial dysfunction, mutation of the ApoE4 gene, and Sirtuin gene were found to manipulate both diseases. Antidiabetic drugs are found to have promising effects on Alzheimer's disease, acting by reducing insulin resistance, neuronal protection, and reducing amyloid-beta plaques. Some anti-diabetic drugs have shown promising results in vivo and in vitro studies. No review present focuses on the structural features of the antidiabetic molecules against Alzheimer's disease, their crosslinking pathophysiology, the role of natural bioactive molecules, in silico advancements followed by preclinical and clinical studies, and current advancements. Hence, we concentrated on the factors mentioned in the objectives. Alzheimer's disease can be considered a form of 'type-3 diabetes,' and repurposing the anti-diabetic drug will open up new paths of research in the field of Alzheimer's disease drug discovery.

PHYTOCHEMICAL STUDY AND ANTIOXIDANT, ANTIBACTERIAL AND ANTIDIABETIC ACTIVITIES OF FLACOURTIA INDICA LEAVES EXTRACTS FROM THE TOGOLESE FLORA

Objective: Faced with the devastating effect of diabetes, the search for new natural antidiabetic molecules is an exploratory avenue. Methods: In this study, the leaves of Flacourtia indica were collected from the Togolese flora, and their antioxidant activity was evaluated using DPPH and FRAP assays, following a phytochemical screening conducted through colorimetric and precipitation reactions. The content of total phenols was determined using Folin-Ciocalteu's reagent and flavonoids by aluminum trichloride. The antibacterial activity of the extracts was evaluated using the method of dilution in agar wells with Muller-Hinton® agar. Additionally, the extracts' antidiabetic effect was evaluated in rats made diabetic by alloxan at a dose of 120 mg/kg. b.w. Results: The results of our work showed the presence of flavonoids, tannins, anthocyanins, and saponins in the extracts. The best polyphenol and flavonoid contents were measured in the hydroethanolic extract and were 186.46±0.308 mg EqAG/g and 464.14±17.043 mgEqQ/g. ES respectively. The hydroethanolic extract has a higher antioxidant power with an IC50 = 110.22 µg/ml. The reducing powers of the ferric ions were 3706±12.124 and 3777±9.238 µmol/ml, respectively for the hydroethanolic and aqueous extracts. The extracts were active against Staphylococcus aureus and are bacteriostatic. The hydroethanolic extract of the leaves of Flacourtia indica significantly reduced (p = 0.0014) blood glucose levels in diabetic rats. Conclusion: This plant can therefore be a potential medicine in the treatment of diabetes.

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy-A Systematic Review and Meta-Analysis.

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles.

Biotechnological approaches for the production of gymnemic acid from Gymnema sylvestre R. Br.

Diabetes is a chronic disease that affects several organs and can be treated using phytochemicals found in medicinal plants. Gymnema sylvestre (Asclepiadaceae) is one such medicinal plant rich in anti-diabetic properties. The plant is commonly known as madhunashini in Sanskrit because of its ability to cure diabetes (sugar). Gymnemic acid(GA) is a phytochemical (a triterpenoid saponin) responsible for the herb's main pharmacological activity. This secondary metabolite has a lot of potential as a phytochemical with pharmacological properties including nephroprotection, hypoglycemia, antioxidant, antimicrobial, and anti-inflammatory. Gymnema has acquired a lot of popularity in recent years due to its low side effects and high efficacy in healing diabetes, which has led to overexploitation by pharmaceutical enterprises for its biomass in the wild for the purification of gymnemic acid. Modern biotechnological techniques involving the establishment of cell and organ cultures from G. sylvestre will assist us in fulfilling the need for gymnemic acid production. The present review provides insights on the establishment of cell and organ cultures for the production of a potent antidiabetic molecule gymnemic acid. Further, the review also delves into the intricacies of the different strategies for improved production of gymnemic acid using various elicitors. There is huge potential for sustainable production of gymnemic acid which could be met by establishment of bioreactor scale production. Understanding and engineering the biosynthetic pathway could also lead to improved GA production. KEY POINTS: • Gymnemic acid is one of the potential anti-diabetic molecules from madhunashini • Cell and organ culture offers potential approach for gymnemic acid production • Elicitation strategies have improved the gymnemic acid production.

Thymoquinone: A Promising Anti-diabetic Molecule!

Thymoquinone: A Promising Anti-diabetic Molecule!