Abstract:

Diabetes mellitus is a widespread and debilitating metabolic disorder marked by sustained elevated blood glucose levels, which can culminate in a range of severe complications if unmanaged. Flavonoids, polyphenolic chemicals originating from plants, have attracted a great deal of attention in the field of diabetes research because of their antidiabetic properties. These naturally occurring substances, which are 15 carbons in structure, are widely distributed in fruits, vegetables, and other plant-based diets, have been shown to offer a number of positive benefits, including the capacity to regulate many facets of insulin and glucose homeostasis. These compounds are classified into six major subclasses based on their structural differences. Numerous in vivo and in vitro studies have looked at the antidiabetic potential of flavonoids. Flavonoids have been found to modulate enzymes such as ά-glucosidase and ά-amylase, which are the key enzymes for the reduction of blood glucose levels. Emerging evidence suggests that flavonoids may exert their antidiabetic effects through their ability to modulate various cell signaling pathways involved in glucose metabolism, insulin sensitivity, and inflammation. It has been demonstrated that flavonoids contain anti-inflammatory and antioxidant qualities. These qualities are vital for reducing inflammation and oxidative stress, which are crucial factors to the onset of diabetes. This review aims providing comprehensive elucidation of the cellular and molecular mechanisms underlying the antidiabetic effects of flavonoids, considering their potential impact on various metabolic pathways involved in diabetes.

References:

[1] Choudhury, H., Pandey, M., Hua, C. K., Mun, C. S., Jing, J. K., Kong, L., Ern, L. Y., Ashraf, N. A., Kit, S. W., Yee, T. S., Pichika, M. R., Gorain, B., & Kesharwani, P., 2018, An update on natural compounds in the remedy of diabetes mellitus: A systematic review. Journal of Traditional and Complementary Medicine, 8(3): 361–376. https://doi.org/10.1016/j.jtcme.2017.08.012

[2] Kharroubi, A. T., 2015, Diabetes mellitus: The epidemic of the century. World Journal of Diabetes, 6(6): 850. https://doi.org/10.4239/wjd.v6.i6.850

[3] International Diabetes Federation, 2021, IDF Diabetes Atlas, 10th edition. https://idf.org/about-diabetes/diabetes-facts-figures/

[4] Missoun, F., 2018, Antidiabetic bioactive compounds from plants. Medical Technologies Journal, 2(2): 199–214. https://doi.org/10.26415/2572-004x-vol2iss2p199-214

[5] Caro-Ordieres, T., Marín-Royo, G., Opazo-Ríos, L., Jiménez-Castilla, L., Moreno, J. A., Gómez-Guerrero, C., & Egido, J., 2020, The coming age of flavonoids in the treatment of diabetic complications. Journal of Clinical Medicine, 9(2): 346. https://doi.org/10.3390/jcm9020346

[6] AL-Ishaq, Abotaleb, Kubatka, Kajo, & Büsselberg, 2019, Flavonoids and their anti-diabetic effects: Cellular mechanisms and effects to improve blood sugar levels. Biomolecules, 9(9): 430. https://doi.org/10.3390/biom9090430

[7] Venugopala, K. N., Chaudhary, J., Sharma, V., Jain, A., Kumar, M., Sharma, D., & et al., 2022, Exploring the potential of flavonoids as efflorescing antidiabetic: An updated SAR and mechanistic based approach. Pharmacognosy Magazine, 18(80): 791-807. http://www.phcog.com/text.asp?2022/18/80/791/357236

[8] Bai, L., Li, X., He, L., Zheng, Y., Lu, H., Li, J., Zhong, L., Tong, R., Jiang, Z., Shi, J., & Li, J., 2019, Antidiabetic potential of flavonoids from traditional Chinese medicine: A review. The American Journal of Chinese Medicine, 47(05): 933–957. https://doi.org/10.1142/s0192415x19500496

[9] Sohretoglu, D., & Sari, S., 2019, Flavonoids as alpha-glucosidase inhibitors: Mechanistic approaches merged with enzyme kinetics and molecular modelling. Phytochemistry Reviews, 19(5): 1081–1092. https://doi.org/10.1007/s11101-019-09610-6

[10] Ke, R. Q., Wang, Y., Hong, S. H., & Xiao, L. X., 2023, Anti-diabetic effect of quercetin in type 2 diabetes mellitus by regulating the microRNA-92b-3p/EGR1 axis. Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society, 74(2). https://doi.org/10.26402/jpp.2023.2.03

[11] Ansari, P., Choudhury, S. T., Seidel, V., Rahman, A. B., Aziz, Md. A., Richi, A. E., Rahman, A., Jafrin, U. H., Hannan, J. M. A., & Abdel-Wahab, Y. H. A., 2022, Therapeutic potential of quercetin in the management of type-2 diabetes mellitus. Life, 12(8): 1146. https://doi.org/10.3390/life12081146

[12] Yang, Y., Chen, Z., Zhao, X., Xie, H., Du, L., Gao, H., & Xie, C., 2022, Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review. Frontiers in Endocrinology, 13. https://doi.org/10.3389/fendo.2022.990299

[13] Kumari, G., Nigam, V. K., & Pandey, D. M., 2022, The molecular docking and molecular dynamics study of flavonol synthase and flavonoid 3’-monooxygenase enzymes involved for the enrichment of kaempferol. Journal of Biomolecular Structure and Dynamics, 41(6): 2478–2491. https://doi.org/10.1080/07391102.2022.2033324

[14] Qaddoori, M. H., & Al-Shmgani, H. S., 2023, Galangin-Loaded gold nanoparticles: Molecular mechanisms of antiangiogenesis properties in breast cancer. International Journal of Breast Cancer, 2023: 1–14. https://doi.org/10.1155/2023/3251211

[15] Al Duhaidahawi, D., Hasan, S. A., & Al Zubaidy, H. F. S., 2021, Flavonoids in the treatment of diabetes: Clinical outcomes and mechanism to ameliorate blood glucose levels. Current Diabetes Reviews, 17(6). https://doi.org/10.2174/1573399817666201207200346

[16] Mathew, M. G., Jeevanandan, G., Vishwanathaiah, S., Hamzi, K. A., Depsh, M. A. N., & Maganur, P. C., 2022, Parental and Child Outlook on the Impact of ECC on Oral Health-related Quality of Life: A Prospective Interventional Study. The Journal of Contemporary Dental Practice, 23(9), 877–882. https://doi.org/10.5005/jp-journals-10024-3397

[17] Jayaraman, S., Natarajan, S. R., Veeraraghavan, V. P., & Jasmine, S., 2023, Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). Journal of oral biology and craniofacial research, 13(6), 704–713. https://doi.org/10.1016/j.jobcr.2023.09.002

[18] Liao, Y., Hu, X., Pan, J., & Zhang, G., 2022, Inhibitory mechanism of baicalein on acetylcholinesterase: Inhibitory interaction, conformational change, and computational simulation. Foods, 11(2): 168. https://doi.org/10.3390/foods11020168

[19] Chan, S.-H., Hung, C.-H., Shih, J.-Y., Chu, P.-M., Cheng, Y.-H., Tsai, Y.-J., Lin, H.-C., & Tsai, K.-L., 2016, Baicalein is an available anti-atherosclerotic compound through modulation of nitric oxide-related mechanism under oxLDL exposure. Oncotarget, 7(28): 42881–42891. https://doi.org/10.18632/oncotarget.10263

[20] Cazarolli, L., Zanatta, L., Alberton, E., Bonorino Figueiredo, M. S., Folador, P., Damazio, R., Pizzolatti, M., & Barreto Silva, F. R., 2008, Flavonoids: Prospective drug candidates. Mini-Reviews in Medicinal Chemistry, 8(13): 1429–1440. https://doi.org/10.2174/138955708786369564

[21] Vishwanathaiah, S., Maganur, P. C., Manoharan, V., Jeevanandan, G., Hakami, Z., Jafer, M. A., Khanagar, S., & Patil, S., 2022, Does Social Media have any Influence during the COVID-19 Pandemic? An Update. The Journal of Contemporary Dental Practice, 23(3), 327–330

[22] Hanchang, W., Wongmanee, N., Yoopum, S., & Rojanaverawong, W., 2022, Protective role of hesperidin against diabetes induced spleen damage: Mechanism associated with oxidative stress and inflammation. Journal of Food Biochemistry, 46(12). https://doi.org/10.1111/jfbc.14444

[23] He, W., Wang, Y., Yang, R., Ma, H., Qin, X., Yan, M., Rong, Y., Xie, Y., Li, L., Si, J., Li, X., & Ma, K., 2022, Molecular mechanism of naringenin against high-glucose-induced vascular smooth muscle cells proliferation and migration based on network pharmacology and transcriptomic analyses. Frontiers in Pharmacology, 13. https://doi.org/10.3389/fphar.2022.862709

[24] Prasad, B.S., & Srinivasan, K.K., 2023, α-Glucosidase Inhibition and Upregulation of PPARγ by Flavonoid Naringenin from Tinospora sinensis Stem, a Possible Mechanism of Antidiabetic Activity. In: Arunachalam, K., Yang, X., Puthanpura Sasidharan, S. (eds) Natural Product Experiments in Drug Discovery. Springer Protocols Handbooks. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2683-2_18

[25] Martín, M. Á., & Ramos, S., 2021, Impact of dietary flavanols on microbiota, immunity and inflammation in metabolic diseases. Nutrients, 13(3): 850. https://doi.org/10.3390/nu13030850

[26] Ahangarpour, A., Sayahi, M., & Sayahi, M., 2019, The antidiabetic and antioxidant properties of some phenolic phytochemicals: A review study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 13(1): 854-857. https://doi.org/10.1016/j.dsx.2018.11.051

[27] Xu, Z., Ma, G., Zhang, Q., Chen, C., He, Y., Xu, L., Zhou, G., Li, Z., Yang, H., & Zhou, P., 2017, Inhibitory mechanism of epigallocatechin gallate on fibrillation and aggregation of amidated human islet amyloid polypeptide. ChemPhysChem, 18(12): 1611-1619. https://doi.org/10.1002/cphc.201700057

[28] Wang, W., Zhang, Y., Jin, W., Xing, Y., & Yang, A., 2018, Catechin weakens diabetic retinopathy by inhibiting the expression of NF-κB signaling pathway-mediated inflammatory factors. Annals of Clinical and Laboratory Science, 48(5): 594-600.

[29] Wen, L., Wu, D., Tan, X., Zhong, M., Xing, J., Li, W., Li, D., & Cao, F., 2022, The Role of Catechins in regulating diabetes: An update review. Nutrients, 14(21): 4681. https://doi.org/10.3390/nu14214681

[30] Jayaraman, S., Raj Natarajan, S., Ponnusamy, B., Veeraraghavan, V. P., & Jasmine, S., 2023, Unlocking the potential of beta sitosterol: Augmenting the suppression of oral cancer cells through extrinsic and intrinsic signalling mechanisms. The Saudi Dental Journal, 35(8), 1007–1013. https://doi.org/10.1016/j.sdentj.2023.08.003

[31] Kuryłowicz, A., 2020, The role of isoflavones in type 2 diabetes prevention and treatment—a narrative review. International Journal of Molecular Sciences, 22(1): 218. https://doi.org/10.3390/ijms22010218

[32] Hussain, H., & Green, I. R., 2017, A patent review of the therapeutic potential of isoflavones (2012-2016). Expert Opinion on Therapeutic Patents, 27(10): 1135-1146. https://doi.org/10.1080/13543776.2017.1339791

[33] S, D. P. A., Solete, P., Jeevanandan, G., Syed, A. A., Almahdi, S., Alzhrani, M., Maganur, P. C., & Vishwanathaiah, S., 2023, Effect of Various Irrigant Activation Methods and Its Penetration in the Apical Third of Root Canal-In Vitro Study. European Journal of dentistry, 17(1), 57–61. https://doi.org/10.1055/s-0041-1742122.

[34] Abbasi, E., & Khodadadi, I., 2023, Antidiabetic effects of genistein: Mechanism of action. Endocrine, Metabolic & Immune Disorders - Drug Targets, 23(13): 1599-1610. https://doi.org/10.2174/1871530323666230516103420

[35] Zhang, N., Zhang, W., Guo, X., Liu, J., Li, S., Zhang, H., & Fan, B., 2022, Genistein protects against hyperglycemia and fatty liver disease in diet-induced prediabetes mice via activating hepatic insulin signaling pathway. Frontiers in Nutrition, 9. https://doi.org/10.3389/fnut.2022.1072044

[36] Liu, Y., Wang, Q., Wu, K., Sun, Z., Tang, Z., Li, X., & Zhang, B., 2022, Anthocyanins’ effects on diabetes mellitus and islet transplantation. Critical Reviews in Food Science and Nutrition, 63(33): 12102-12125. https://doi.org/10.1080/10408398.2022.2098464

[37] Pazhani, J., Jayaraman, S., Veeraraghavan, V. P., & Jasmine, S., 2024, Endothelin-1 axis as a therapeutic target in oral squamous cell carcinoma: Molecular insights. Journal of stomatology, oral and maxillofacial surgery, 125(6), 101792. Advance online publication. https://doi.org/10.1016/j.jormas.2024.101792

[38] Yang, L., Qiu, Y., Ling, W., Liu, Z., Yang, L., Wang, C., Peng, X., Wang, L., & Chen, J., 2020, Anthocyanins regulate serum adipsin and visfatin in patients with prediabetes or newly diagnosed diabetes: A randomized controlled trial. European Journal of Nutrition, 60(4): 1935-1944. https://doi.org/10.1007/s00394-020-02379-x

[39] Lai, D., Huang, M., Zhao, L., Tian, Y., Li, Y., Liu, D., Wu, Y., & Deng, F., 2019, Delphinidin-induced autophagy protects pancreatic β cells against apoptosis resulting from high-glucose stress via AMPK signaling pathway. Acta Biochimica et Biophysica Sinica, 51(12): 1242-1249. https://doi.org/10.1093/abbs/gmz126

[40] Ahmed, Q. U., Ali, A. H. M., Mukhtar, S., Alsharif, M. A., Parveen, H., Sabere, A. S. M., Nawi, M. S. Mohd., Khatib, A., Siddiqui, M. J., Umar, A., & Alhassan, A. M., 2020, Medicinal potential of isoflavonoids: Polyphenols that may cure diabetes. Molecules, 25(23): 5491. https://doi.org/10.3390/molecules25235491

Abstract:

This study presents a comprehensive molecular docking analysis aimed at elucidating the potential antidiabetic activity of allin, a compound isolated from Allium sativum (garlic). Through computational modelling, we investigated the binding interactions between allin and Rheb, revealing that allin exhibited the lowest binding affinities with a binding energy of -3.24 kcal/mol. The docking results unveiled a significant role of the P13K/AKT signalling pathway in mediating the antidiabetic effects of allin. The interaction between allin and Rheb was characterized by the establishment of a single hydrogen bond involving SER-16 and GDP-201. This interaction contributed to the formation of a binding pocket encompassing key residues such as PRO-37, ARG-15, SER-16, THR-88, LEU-123, GLU-126, and GDP-201. The molecular docking analysis sheds light on the intricate molecular mechanisms underlying the antidiabetic potential of allin, providing insights into its specific interactions with key signalling components. Furthermore, our findings suggest a potential modulation of the P13K/AKT signalling pathway by the allin, emphasizing its significance in the context of antidiabetic activity. The results of this study suggest contributes valuable information to the understanding of the molecular basis of allin's therapeutic potential and provides a foundation for further experimental validations and exploration of its application in diabetes management.

References:

Abstract:

Diabetes mellitus is a chronic metabolic disorder that affects millions of people worldwide. The management of diabetes is a significant for new and effective therapeutic agents. Ajoene, a compound found in garlic, has been shown to have anti-diabetic properties. The Nrf2/Keap-1 signaling pathway has been identified as a potential target for the treatment of diabetes. The aim of this study is to investigate the role of ajoene from Aegle Marmelos Correa in the activation of the Nrf2/Keap-1 signaling pathway and its potential as an anti-diabetic agent. In silico analysis was performed using molecular docking and molecular dynamics simulations to investigate the interaction between ajoene and the Nrf2/Keap-1 signaling pathway. The molecular docking studies revealed that ajoene binds to the Nrf2/Keap-1 complex with high affinity, indicating a potential interaction between ajoene and Cul3 was establishment of a single hydrogen bond involving ILE258. This interaction contributed to the formation of a binding pocket encompassing key residues such as LEU-253, ILE-258, VAL-260, LEU-266, LEU-292. These findings suggest that ajoene may activate the Nrf2/Keap-1 signaling pathway, leading to the upregulation of antioxidant genes and the inhibition of oxidative stress, which are known to contribute to the development of diabetes. The results of this study suggest that ajoene from Aegle Marmelos Correa may have potential as anti-diabetic agent through its activation of the Nrf2/Keap-1 signaling pathway. The specific interaction between ajoene and Cul3, characterized by the establishment of a single hydrogen bond involving ILE258, contributes to the formation of a binding pocket encompassing key residues.

References:

[1] Gupta, R. K., Kesari, A. N., Watal, G., Murthy, P. S., Chandra, R., & Tandon, V., 2005, Hypoglycemic and antidiabetic effect of aqueous extract of leaves of Annona squamosa (L.) in experimental animals. Current Science, 1246-1254

[2] Bhatti, R., Sharma, S., Kumar, A., & Singh, A., 2013, Anti adipogenic activity of Aegle marmelos Correa. Pharmacognosy Magazine, 9(34), 132

[3] Hattori, A., Yamada, N., Nishikawa, T., Fukuda, H., & Fujino, T., 2005, Antidiabetic effects of ajoene in genetically diabetic KK-Ay mice. Journal of Nutritional Science and Vitaminology, 51(5), 382-384

[4] Kesari, A. N., Gupta, R. K., Singh, S. K., Diwakar, S., & Watal, G., 2006, Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats. Journal of Ethnopharmacology, 107(3), 374-379

[5] Tebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D., 2015, Mechanisms of activation of the transcription factor Nrf2 by redox

[6] Kensler, T. W., Wakabayashi, N., & Biswal, S., 2007, Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol., 47, 89-116

[7] Narendhirakannan, R. T., Subramanian, S., & Kandaswamy, M., 2006, Biochemical evaluation of antidiabetogenic properties of some commonly used Indian plants on streptozotocin-induced diabetes in experimental rats. Clinical and Experimental Pharmacology and Physiology, 33(12), 1150-1157

[8] International Diabetes Federation., 2019, IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation

[9] Kamalakkann, N., Rajadurai, M., & Prince, P. S., 2003, Effect of Aegle marmelos fruits on normal and streptozotocin-diabetic Wistar rats. Journal of Medicinal Food, 6(2), 93-98

[10] Hattori, A., Yamada, N., Nishikawa, T., Fukuda, H., & Fujino, T., 2005, Antidiabetic effects of ajoene in genetically diabetic KK-Ay mice. Journal of Nutritional Science and Vitaminology, 51(5), 382-384

[11] Zheng, H., Whitman, S. A., Wu, W., Wondrak, G. T., Wong, P. K., Fang, D., & Zhang, D. D., 2011, Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes, 60(11), 3055-3066

[12] Mathew, M. G., Jeevanandan, G., Vishwanathaiah, S., Hamzi, K. A., Depsh, M. A. N., & Maganur, P. C., (2022). Parental and Child Outlook on the Impact of ECC on Oral Health-related Quality of Life: A Prospective Interventional Study. The journal of Contemporary Dental Practice, 23(9), 877–882. https://doi.org/10.5005/jp-journals-10024-3397

[13] Itoh, K., Tong, K. I., & Yamamoto, M., 2004, Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radical Biology and Medicine, 36(10), 1208-1213

[14] Tan, Y., Ichikawa, T., Li, J., Si, Q., Yang, H., Chen, X., & Cui, T., 2011, Diabetic downregulation of Nrf2 activity via ERK contributes to oxidative stress-induced insulin resistance in cardiac cells in vitro and in vivo. Diabetes, 60(2), 625-633

[15] Paulose, C. S., Dakshinamurti, K., Packer, S., & Stephens, N. L., 1988, Sympathetic stimulation and hypertension in the Nrf2-knockout mouse. Hypertension, 53(4), 659-665

[16] Krishnan, R. P., Pandiar, D., & Ramani, P., 2023, Sclerosing Variant of Adenoid Cystic Carcinoma - A Case Report on the Role of Sclerosis in the Prognostic Outcome. Annals of Maxillofacial Surgery, 13(2), 248–251. https://doi.org/10.4103/ams.ams_116_23

[17] Kesari, A. N., Gupta, R. K., Singh, S. K., Diwakar, S., & Watal, G., 2006, Hypoglycemic and antihyperglycemic activity of Aegle marmelos seed extract in normal and diabetic rats. Journal of Ethnopharmacology, 107(3), 374-379

[18] https://pubchem.ncbi.nlm.nih.gov/compound/5386591

[19] Gopalakrishnan, U., Felicita, A. S., Qureshi, T., Muruganandhan, J., Hassan, A. A. A., El-Shamy, F. M., Osman, H. A., Medabesh, A. A., & Patil, S., 2022, Effect of Fluoridated Mouthwashes on Corrosion Property of Orthodontic Appliances: A Narrative Review. The Journal of Contemporary Dental Practice, 23(4), 460–466.

[20] Ulasov, A. V., Rosenkranz, A. A., Georgiev, G. P., & Soboleva, A. S., 2022, Nrf2/Keap1/ARE signaling: Towards specific regulation doi: 10.1016/j.lfs.2021.120111

[21] Furukawa, M., He, Y.J., Borchers, C., & Xiong, Y., 2003, Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases DOI: 10.1038/ncb1056

[22] Jayaraman, S., Natarajan, S. R., Veeraraghavan, V. P., & Jasmine, S., 2023, Unveiling the anti-cancer mechanisms of calotropin: Insights into cell growth inhibition, cell cycle arrest, and metabolic regulation in human oral squamous carcinoma cells (HSC-3). Journal of oral biology and craniofacial research, 13(6), 704–713. https://doi.org/10.1016/j.jobcr.2023.09.002

[23] Tiwari, R., Mishra, S., Danaboina, G., Pratap Singh Jadaun, G.,  Kalaivani, M., Kalaiselvan, V.,  Dhobi, M., & Raghuvanshi, R.S., 2023, Comprehensive chemo-profiling of coumarins enriched extract derived from Aegle marmelos (L.) Correa fruit pulp, as an anti-diabetic and anti-inflammatory agent Doi: 10.1016/j.jsps.2023.101708.

[24] Sharma, P., Joshi , T., Mathpal , S., Chandra, S., & Tamta, S., 2021, In silico identification of antidiabetic target for phytochemicals of A. marmelos and mechanistic insights by molecular dynamics simulations. Doi:10.1080/07391102.2021.1944910

Abstract:

Diabetes mellitus, a chronic metabolic disorder, has been a global health concern with rising prevalence. The search for novel therapeutic agents, especially from natural sources, remains a priority. Acacetin, a flavonoid found in various plants, has shown potential in various biological activities. However, its role in diabetes management, particularly its interaction with glycolytic enzymes, has been less explored. This study aimed to investigate the interaction of acacetin with glycolytic enzymes and its potential as a therapeutic agent for diabetes management. A comprehensive molecular docking analysis was employed to explore the binding affinity of acacetin to glycolytic enzymes, including hexokinase, phosphofructokinase, and pyruvate kinase. The study utilized advanced computational tools and techniques to simulate the interaction dynamics. The binding energy, interaction sites, and stability of the acacetin-enzyme complex were evaluated. Acacetin exhibited significant binding affinity towards all three glycolytic enzymes, with notable stability in the enzyme active sites. The binding energies indicated a strong interaction, suggesting potential inhibitory effects on the enzymes. The interaction was characterized by both hydrogen bonding and hydrophobic interactions, contributing to the stability of the complexes. The molecular docking analysis suggests that acacetin interacts effectively with key glycolytic enzymes, potentially inhibiting their activity. This interaction could impede the glycolytic pathway, which is crucial in diabetes pathophysiology. Therefore, acacetin emerges as a promising candidate for diabetes management, warranting further in-vitro and in-vivo studies to explore its therapeutic potential and mechanism of action.

References:

Abstract:

Colchicine, a naturally occurring alkaloid, has garnered attention for its potential anti-diabetic properties. This study delves into the molecular interactions between colchicine and antioxidant signaling molecules, aiming to uncover its therapeutic potential in managing diabetes. The primary aim of this research is to investigate the intricate molecular interactions between colchicine and key antioxidant signaling molecules. Additionally, through in-silico analysis, the study seeks to identify the antidiabetic activity of colchine. In this study, molecular docking simulations were employed to explore the binding affinities and interactions of colchicine with antioxidant signaling molecules like superoxide dismutase, catalase, glutathione peroxidase, Peroxiredoxin and Hemeoxygenase. The computational analysis was carried out using state-of-the-art software tools, allowing for a comprehensive assessment of potential binding energies. Furthermore, an in-silico analysis was conducted to predict colchicine’s ability to modulate key pathways related to diabetes. The findings reveal that colchicine exhibits strong binding affinities with antioxidant enzymes, suggesting its potential as an antioxidant agent. This study provides valuable insight into the molecular interactions between colchicine and antioxidant signaling molecules. The promising binding affinities and potential antidiabetic activity identified through in-silico analysis highlight colchicine as a candidate for further investigation as a therapeutic agent for diabetes. Further in vitro and in vivo experiments are warranted to validate these in-silico finding and unlock the full potential of colchicine in diabetes management.

References:

Abstract:

β-Sitosterol is a phytosterol which is universally present in most of the plant seeds and nuts. Its anti-inflammatory property has been studied in vitro in cell line studies and some in vivo studies have also been conducted but few studies have been done to establish its antioxidant property. In this study, we have attempted to explore the antioxidant property through the NRF2-KEAP pathway in the IMR 32 neuronal cell line. Initially, cell viability was checked for varying concentrations of sitosterol using an MTT assay. There was a decline in viability for increased concentration and time factors. Reactive oxygen species (ROS) assay revealed the tendency of sitosterol to inhibit lipid peroxides and hydrogen peroxides. An antioxidant activity assay depicted activating antioxidant enzymes, superoxide dismutase, and nonenzymatic antioxidants, such as reduced glutathione. In the gene expression analysis using Real Time-PCR NRF2 and KEAP expression was found to be observed maximum for concentration ranges of 10 µM concentration of β-Sitosterol. Current studies have substantiated the antioxidant property of β-Sitosterol through the NRF2- KEAP signalling pathway.

References:

Abstract:

Neurodegenerative disorders are on the rise globally. β-Sitosterol shows potential therapeutic benefits, but its neuroprotective mechanisms remain largely unexplored. This study aimed to assess the neuroprotective effects of β-Sitosterol on pro-inflammatory (NFκB) and antioxidant (NRF-2/KEAP-1) pathways in an in vivo in LPS-induced neurodegeneration model in albino rats. The rats were divided into four groups: normal control, LPS-induced, LPS-induced treated with β-Sitosterol (20 mg/kg/day for 4 weeks), and normal treated with β-Sitosterol. Neurotransmitters (dopamine and serotonin) and antioxidant enzymes (GSH and CAT) were measured by ELISA, and gene expression of NFκB, NRF-2, KEAP-1, IL-6, and IL-18 was assessed by Real-Time RT-PCR. Histopathology of brain tissues was performed. LPS induction significantly decreased neurotransmitters and antioxidant enzymes and upregulated NFκB while downregulating NRF-2 and KEAP-1 mRNA expression. β-Sitosterol treatment normalized these levels (p<0.05) and reduced hyperchromatic pyknotic changes in neuronal nuclei observed in LPS-induced rats. Normal rats treated with β-Sitosterol showed no significant alterations, indicating its safety. These findings suggest β-Sitosterol can reduce neuroinflammation by modulating antioxidant signaling, providing a potential therapeutic approach for neurodegenerative diseases.

References:

[1].   Uttara, B., Singh, A. V., Zamboni, P., & Mahajan, R. T., 2009, Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options. Current Neuropharmacology, 7(1), 65–74. https://doi.org/10.2174/157015909787602823.

[2].   S, D. P. A., Solete, P., Jeevanandan, G., Syed, A. A., Almahdi, S., Alzhrani, M., Maganur, P. C., & Vishwanathaiah, S., 2023, Effect of Various Irrigant Activation Methods and Its Penetration in the Apical Third of Root Canal-In Vitro Study. European Journal of dentistry, 17(1), 57–61. https://doi.org/10.1055/s-0041-1742122.

[3].   Prathipa S., Shanmuga, S., Geetha Rani, K.S., Krithika, Chandrasekar., Ramajayam Govindan., Mahesh Kumar, P., Jaideep Mahendra & Ponnulakshmi, R., 2023, Phytosterols and its Neuroprotective Effect – An Updated Review. European Chemical Bulletin.j. DOI:10.48047/ecb/2023.12.si4.701.

[4].   Kaspar, J. W., Niture, S. K., & Jaiswal, A. K., 2009, Nrf2:INrf2 (Keap1) Signaling in Oxidative Stress. Free Radical Biology & Medicine, 47(9), 1304–1309. https://doi.org/10.1016/j.freeradbiomed.2009.07.035.

[5].   Zhao, J., Bi, W., Xiao, S., Lan, X., Cheng, X., Zhang, J., Lu, D., Wei, W., Wang, Y., Li, H., Fu, Y., & Zhu, L., 2019, Neuroinflammation Induced by Lipopolysaccharide Causes Cognitive Impairment in Mice. Scientific Reports, 9(1), 5790. https://doi.org/10.1038/s41598-019-42286-8.

[6].   Gao, W., Guo, L., Yang, Y., Wang, Y., Xia, S., Gong, H., Zhang, B. K., & Yan, M. , 2022,  Dissecting the Crosstalk Between Nrf2 and NF-κB Response Pathways in Drug-Induced Toxicity. Frontiers in Cell and Developmental Biology, 9, 809952. https://doi.org/10.3389/fcell.2021.809952.

[7].   Juárez Olguín, H., Calderón Guzmán, D., Hernández García, E., & Barragán Mejía, G. , 2016, The Role of Dopamine and its Dysfunction as a Consequence of Oxidative Stress. Oxidative Medicine and Cellular Longevity, 2016, 9730467. https://doi.org/10.1155/2016/9730467

[8].   Yin, Y., Liu, X., Liu, J., Cai, E., Zhao, Y., Li, H., Zhang, L., Li, P., & Gao, Y., 2018, The Effect of Beta-Sitosterol and its Derivatives on Depression by the Modification of 5-HT, DA and GABA-Ergic Systems in Mice. RSC Advances, 8(2), 671–680. https://doi.org/10.1039/c7ra11364a

[9].   Sedlak, J., & Lindsay, R.H., 1968, Analytical Biochemistry,25, 192-205.

[10].  Takahara, S., Hamilton, H.B., Neel, J.V., Kobara,T.Y., Ogura, Y.,  & Nishimura, E.T., 1960, Journal of Clinical Investigation, 39, 610-619.

[11].  Vishwanathaiah, S., Maganur, P. C., Manoharan, V., Jeevanandan, G., Hakami, Z., Jafer, M. A., Khanagar, S., & Patil, S., 2022, Does Social Media have any Influence during the COVID-19 Pandemic? An Update. The Journal of Contemporary Dental Practice, 23(3), 327–330.

[12].  Lee, D. Y., Song, M. Y., & Kim, E. H., 2021, Role of Oxidative Stress and Nrf2/KEAP1 Signaling in Colorectal Cancer: Mechanisms and Therapeutic Perspectives with Phytochemicals. Antioxidants (Basel, Switzerland), 10(5), 743. https://doi.org/10.3390/antiox10050743

[13].  Babu, S., Krishnan, M., Rajagopal, P., Periyasamy, V., Veeraraghavan, V., Govindan, R., & Jayaraman, S., 2020, Beta-sitosterol Attenuates Insulin Resistance in Adipose Tissue via IRS-1/Akt Mediated Insulin Signaling in High Fat Diet and Sucrose Induced Type-2 Diabetic Rats. European Journal of Pharmacology, 873, 173004. https://doi.org/10.1016/j.ejphar.2020.173004

[14].  Saha, S., Buttari, B., Panieri, E., Profumo, E., & Saso, L., 2020, An Overview of Nrf2 Signaling Pathway and its Role in Inflammation. Molecules (Basel, Switzerland), 25(22), 5474. https://doi.org/10.3390/molecules25225474.

[15].  Sun, Y., Gao, L., Hou, W., & Wu, J., 2020, β-Sitosterol Alleviates Inflammatory Response via Inhibiting the Activation of ERK/p38 and NF-κB Pathways in LPS-Exposed BV2 Cells. BioMed Research International, 2020, 7532306. https://doi.org/10.1155/2020/7532306

[16].  Francois, A., Terro, F, Janet, T., Rioux Bilan, A., Paccalin, M., & Page, G.,2013, Involvement of Interleukin-1Beta in the Autophagic Process of Microglia: Relevance to Alzheimer’s Disease, Journal of Neuroinflammation,10,151.

[17].  Mathew, M. G., Jeevanandan, G., Vishwanathaiah, S., Hamzi, K. A., Depsh, M. A. N., & Maganur, P. C., 2022, Parental and Child Outlook on the Impact of ECC on Oral Health-related Quality of Life: A Prospective Interventional Study. The Journal of Contemporary Dental Practice, 23(9), 877–882. https://doi.org/10.5005/jp-journals-10024-3397.

[18].  Teleanu, R. I., Niculescu, A. G., Roza, E., Vladâcenco, O., Grumezescu, A. M., & Teleanu, D. M., 2022, Neurotransmitters-Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. International Journal of Molecular Sciences, 23(11), 5954. https://doi.org/10.3390/ijms23115954

[19].  Tagliamonte, A., Biggio, G., Vargiu, L., & Gessa, G. L., 1973, Free Tryptophan in Serum Controls Brain Tryptophan Level and Serotonin Synthesis. Life sciences. Pt. 2: Biochemistry, General and Molecular Biology, 12(6), 277–287. https://doi.org/10.1016/0024-3205(73)90361-5.

[20].  Babu, S., & Jayaraman, S., 2020, An Update on β-sitosterol: A Potential Herbal Nutraceutical for Diabetic Management. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 131, 110702. https://doi.org/10.1016/j.biopha.2020.110702.

[21].  Jayaraman, S., Devarajan, N., Rajagopal, P., Babu, S., Ganesan, S. K., Veeraraghavan, V. P., Palanisamy, C. P., Cui, B., Periyasamy, V., & Chandrasekar, K. (2021). 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. Molecules (Basel, Switzerland), 26(7), 2101. https://doi.org/10.3390/molecules26072101

Abstract:

Cancer is the rapid proliferation that causes abnormal cells which metastasize to distant tissues. This aberrant signalling mechanism disrupts the regulation of cell proliferation and persistence, ultimately becoming the primary cause of mortality worldwide. The need for novel medications for the treatment and prevention of this deadly disease is constantly rising. Herbal therapies have significance for both preventing and treating a variety of malignancies. Anticancer medications have been discovered and developed from many herbal medicines by the presence of their bioactive phytochemicals such as phenolics, alkaloids, flavonoids, carotenoids, and other secondary metabolites. These herbal products are said to have less toxic side effects when compared to modern treatment strategies. Therapeutic medicinal herbs suppress the progression of cancerous cells by influencing the action of particular enzymes and hormones. The bioactive phytochemicals obstruct cancerous cell multiplication, promote apoptosis of malignant cells, enforce the necrosis of tumors, and inhibit their translocation. They also exert their action by enhancing the number of leukocytes and platelets, promoting the reverse transformation from tumor cells back to usual cells, and they similarly prevent carcinogenesis of regular cells. This review paper enlightens the significance of herbal medicines as anticancer agents and explains, in brief, the mechanism of action and the effects of the herbal bioactive compound. This review helps to explore the potential therapeutic plants as a basis for the discovery of chemotherapy medications.

References:

Abstract:

Diabetic mellitus is an endocrine disorder characterized by hyperglycemia, polyphagia, polyuria, and polydipsia. In this condition, the cells and tissues are unable to utilize glucose for energy due to inadequate insulin secretion. The complications of the disease include diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy that affect the eyes, nerves, kidneys and stroke, renal failure, and heart attacks are other serious consequences of diabetes. The conventional modern medicines for treatment are oral hypoglycemic drugs, sulfonylureas and glinides, metformin and thiazolidinedione, dipeptidyl peptidase-4 (DPP4) inhibitors, and injections such as GLP-1 agonists. Due to the presence of a lot of side effects, the modern world is now turning to bioactive chemical components synthesized from plants. Today, drugs derived from herbs or plants are widely used because of the exploitation of specific compounds and their therapeutic actions. Various phytochemicals have notable and significant mechanisms for reducing the blood glucose level. These natural agents can have a protective and therapeutic effect on diabetes mellitus through cellular mechanisms such as the regeneration of pancreatic β cells, antioxidative stress, and intracellular signalling transduction pathways. The present study aims to review the mechanisms of various phytochemicals that play a role in antidiabetic activity. The possible mechanisms by which the antidiabetic herbs act are α-glucosidase inhibitors, PPAR activators, free radical scavengers, HMG Co suppressors, regenerators of beta cells, and cause an increase in insulin secretion and glycogen synthesis in glycemic control.

References:

[1]    American Diabetes Association, 2012, Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 36(Supplement_1), S67–S74. https://doi.org/10.2337/dc13-S067

[2]    International Diabetes Federation, 2021, IDF Diabetes Atlas, 10th edition. Brussels, Belgium: https://www.diabetesatlas.org/.

[3]    Kakkar, R., 2016, Rising burden of Diabetes-Public Health Challenges & way out. Nepal Journal of Epidemiology, 6(2), 557–559. https://doi.org/10.3126/nje.v6i2.15160

[4]    Ali, M. K., Narayan, K. M., & Tandon, N. 2010, Diabetes & coronary heart disease: current perspectives. The Indian journal of medical research, 132(5), 584–597.

[5]    Singh, N., Armstrong, D. G., & Lipsky, B. A., 2005, Preventing foot ulcers in patients with diabetes. JAMA, 293(2), 217. https://doi.org/10.1001/jama.293.2.217

[6]    Levetan, C., 2007, Oral antidiabetic agents in type 2 diabetes. Current Medical Research and Opinion, 23(4), 945–952. https://doi.org/10.1185/030079907x178766

[7]    Inzucchi, S. E., 2002, Oral antihyperglycemic therapy for type 2 diabetes. JAMA, 287(3), 360. https://doi.org/10.1001/jama.287.3.360

[8]    Mendoza, N., & Silva, E. M. E., 2018,  Introduction to phytochemicals: Secondary metabolites from plants with active principles for pharmacological importance. In Phytochemicals - Source of Antioxidants and Role in Disease Prevention. InTech.http://dx.doi.org/10.5772/intechopen.78226

[9]    Vinayagam, R., Xiao, J., & Xu, B., 2017, An insight into anti-diabetic properties of dietary phytochemicals. Phytochemistry Reviews, 16(3), 535–553. https://doi.org/10.1007/s11101-017-9496-2

[10]    Singh, V. K., Umar, S., Ansari, S. A., & Iqbal, M., 2008, Gymnema sylvestre for Diabetics. Journal of Herbs, Spices & Medicinal Plants, 14(1–2), 88–106. https://doi.org/10.1080/10496470802341508

[11]    Gulab S. Thakur., 2012, Gymnema sylvestre: An Alternative Therapeutic Agent for Management of Diabetes. Journal of Applied Pharmaceutical Science, 2(12), 001-006. https://doi.org/10.7324/japs.2012.21201

[12]    Persaud, S., Al-Majed, H., Raman, A., & Jones, P., 1999, Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. Journal of Endocrinology, 163(2), 207-212. https://doi.org/10.1677/joe.0.1630207

[13]    AlAttas, S. A., Zahran, F. M., & Turkistany, S. A., 2016, Nigella sativa and its active constituent thymoquinone in oral health. Saudi Medical Journal, 37(3), 235–244. https://doi.org/10.15537/smj.2016.3.13006

[14]    Varghese, R. M., Kumar, S. A., & Selvaraj, Y., 2023, Assessment of Soft Tissue, Airway Dimension and Hyoid Bone Position in Class II Patients Treated by PowerScope Class 2 Corrector. The Journal of Contemporary Dental Practice, 24(5), 308–313. https://doi.org/10.5005/jp-journals-10024-3485

[15]    Atangwho, I. J., Ebong, P. E., Eyong, E. U., Williams, I. O., Eteng, M. U., & Egbung, G. E., 2009, Comparative chemical composition of leaves of some antidiabetic medicinal plants: Azadirachta indica, Vernonia amygdalina and Gongronema latifolium. African Journal of Biotechnology, 8(18), 4685-4689.

[16]    Djeujo, F. M., Stablum, V., Pangrazzi, E., Ragazzi, E., & Froldi, G., 2023, Luteolin and Vernodalol as Bioactive Compounds of Leaf and Root Vernonia amygdalina Extracts: Effects on α-Glucosidase, Glycation, ROS, Cell Viability, and In Silico ADMET Parameters. Pharmaceutics, 15(5), 1541. https://doi.org/10.3390/pharmaceutics15051541

[17]    Baquer, N. Z., Kumar, P., Taha, A., Kale, R., Cowsik, S., & McLean, P., 2011, Metabolic and molecular action of Trigonella foenum-graecum (fenugreek) and trace metals in experimental diabetic tissues. Journal of Biosciences, 36(2), 383–396. https://doi.org/10.1007/s12038-011-9042-0

[18]    Sowmithra Devi, S., Sundari, S.,2023, Occlusal Contact Changes With Traumatic Occlusion After Orthodontic Treatment: A Prospective Study. Journal of Advanced Oral Research. 14(2):134-142. doi:10.1177/23202068231190202

[19]    Kahramanoğlu, İ., Chen, C., Chen, J., & Wan, C., 2019, Chemical Constituents, Antimicrobial Activity, and Food Preservative Characteristics of Aloe vera Gel. Agronomy, 9(12), 831. https://doi.org/10.3390/agronomy9120831

[20]    Tanaka, M., Misawa, E., Ito, Y., Habara, N., Nomaguchi, K., Yamada, M., … Higuchi, R., 2006, Identification of five phytosterols from aloe vera gel as anti-diabetic compounds. Biological and Pharmaceutical Bulletin, 29(7), 1418–1422. https://doi.org/10.1248/bpb.29.1418

[21]    Kumar, D., Mitra, A., & M, M., 2011, Azadirachtolide: An anti-diabetic and hypolipidemic effects from Azadirachta indica leaves. Pharmacognosy Communications, 1(1), 78–84. https://doi.org/10.5530/pc.2011.1.5

[22]    Ponnusamy, S., Haldar, S., Mulani, F., Zinjarde, S., Thulasiram, H., & RaviKumar, A., 2015. Gedunin and Azadiradione: Human Pancreatic Alpha-Amylase Inhibiting Limonoids from Neem (Azadirachta indica) as Anti-Diabetic Agents. PLOS ONE, 10(10), e0140113. https://doi.org/10.1371/journal.pone.0140113

[23]    Aabideen, Z. U., Mumtaz, M. W., Akhtar, M. T., Raza, M. A., Mukhtar, H., Irfan, A., Saari, N., 2021, Cassia fistula Leaves; UHPLC-QTOF-MS/MS Based Metabolite Profiling and Molecular Docking Insights to Explore Bioactives Role towards Inhibition of Pancreatic Lipase. Plants, 10(7), 1334. https://doi.org/10.3390/plants10071334

[24]    Adisakwattana, S., 2017, Cinnamic acid and its derivatives: Mechanisms for prevention and management of diabetes and its complications. Nutrients, 9(2), 163. https://doi.org/10.3390/nu9020163

[25]    Roy, J. R., Janaki, C. S., Jayaraman, S., Periyasamy, V., Balaji, T., Vijayamalathi, M., & Veeraraghavan, V. P., 2022, Carica papaya Reduces Muscle Insulin Resistance via IR/GLUT4 Mediated Signaling Mechanisms in High Fat Diet and Streptozotocin-Induced Type-2 Diabetic Rats. Antioxidants, 11(10), 2081. https://doi.org/10.3390/antiox11102081

[26]    Ansari, P., Flatt, P. R., Harriott, P., Hannan, J. M. A., & Abdel-Wahab, Y. H. A., 2021, Identification of Multiple Pancreatic and Extra-Pancreatic Pathways Underlying the Glucose-Lowering Actions of Acacia arabica Bark in Type-2 Diabetes and Isolation of Active Phytoconstituents. Plants, 10(6), 1190. https://doi.org/10.3390/plants10061190

[27]    Srinivasan, S., Sathish, G., Jayanthi, M., Muthukumaran, J., Muruganathan, U., & Ramachandran, V., 2013, Ameliorating effect of eugenol on hyperglycemia by attenuating the key enzymes of glucose metabolism in streptozotocin-induced diabetic rats. Molecular and Cellular Biochemistry, 385(1–2), 159–168. https://doi.org/10.1007/s11010-013-1824-2

[28]    Adebanke, O., Babatunde, A., Franklyn, I., Keleeko, A., Joseph, O., & Olubanke, O., 2023, Free radical scavenging activity, pancreatic lipase and a-amylase inhibitory assessment of ethanolic leaf extract of Phyllanthus amarus. Plant Science Today, 10(2), 20–26. https://doi.org/10.14719/pst.1809

[29]    Ahmad, N., Hasan, N., Ahmad, Z., Zishan, M., & Zohrameena, S., 2016,  MOMORDICA CHARANTIA: FOR TRADITIONAL USES AND PHARMACOLOGICAL ACTIONS. Journal of Drug Delivery and Therapeutics, 6(2), 40-44. https://doi.org/10.22270/jddt.v6i2.1202

[30]    Yan, L., Vaghari-Tabari, M., Malakoti, F., Moein, S., Qujeq, D., Yousefi, B., & Asemi, Z., 2022, Quercetin: An effective polyphenol in alleviating diabetes and diabetic complications. Critical Reviews in Food Science and Nutrition, 63(28), 9163–9186. https://doi.org/10.1080/10408398.2022.2067825

[31]    Varghese, R.M., Subramanian, A.K., Maliael, M.T., 2023, PowerScope™ for Class II Malocclusions: A Systematic Review and Meta-analysis. World Journal of Dentistry,14(7):639–647

[32]    Bozkurt, O., Kocaadam-Bozkurt, B., & Yildiran, H., 2022, Effects of curcumin, a bioactive component of turmeric, on type 2 diabetes mellitus and its complications: An updated review. Food & Function, 13(23), 11999–12010. https://doi.org/10.1039/d2fo02625b

[33]    Majeed, M., Mundkur, L., Paulose, S., & Nagabhushanam, K., 2022, Novel Emblica officinalis extract containing β-glucogallin vs. metformin: A randomized, open-label, comparative efficacy study in newly diagnosed type 2 diabetes mellitus patients with dyslipidemia. Food & Function, 13(18),9523–9531. https://doi.org/10.1039/d2fo01862d

[34]    Mathiyazhagan, J., & Kodiveri Muthukaliannan, G., 2020, The role of mTOR and oral intervention of combined Zingiberofficinale Terminalia chebula  extract in type 2 diabetes rat models. Journal of Food Biochemistry, 44(7). https://doi.org/10.1111/jfbc.13250

[35]    Mahindrakar, K. V., & Rathod, V. K., 2020, Antidiabetic potential evaluation of aqueous extract of wasteSyzygium cuminiseed kernel’s byin vitroα-amylase and α-glucosidase inhibition. Preparative Biochemistry & Biotechnology, 51(6), 589–598. https://doi.org/10.1080/10826068.2020.1839908

[36]    Rasool, S., Al Meslmani, B., & Alajlani, M., 2023, Determination of hypoglycemic, hypolipidemic and nephroprotective effects of berberis calliobotrys in alloxan-induced diabetic rats. Molecules, 28(8), 3533. https://doi.org/10.3390/molecules2808353

[37]    Etsassala, N. G. E. R., Badmus, J. A., Marnewick, J. L., Egieyeh, S., Iwuoha, Emmanuel. I., Nchu, F., & Hussein, A. A., 2022, Alpha-Glucosidase and Alpha-Amylase Inhibitory Activities, Molecular Docking, and Antioxidant Capacities of Plectranthus ecklonii Constituents. Antioxidants, 11(2), 378. https://doi.org/10.3390/antiox11020378

[38]    Maher, S., Choudhary, M. I., Saleem, F., Rasheed, S., Waheed, I., Halim, S. A., … Ahmad, S., 2020, Isolation of Antidiabetic Withanolides from Withania coagulans Dunal and Their In Vitro and In Silico Validation. Biology, 9(8), 197. https://doi.org/10.3390/biology9080197

[39]    Hsu, J.-H., Yang, C.-S., & Chen, J.-J., 2022, Antioxidant, Anti-α-Glucosidase, Antityrosinase, and Anti-Inflammatory Activities of Bioactive Components from Morus alba. Antioxidants, 11(11), 2222. https://doi.org/10.3390/antiox11112222

[40]    Kumar, R., Sood, P., Rana, Dr. V., & Prajapati, A. K., 2023, Combine therapy of gallic acid and allicin in management of diabetes. Journal for Research in Applied Sciences and Biotechnology, 2(3), 91–99. https://doi.org/10.55544/jrasb.2.3.12

Abstract:

Impaired wound healing is one of the serious problems among the diabetic patients. To prevent complications and damage to the skin tissue and promote fibroblastic growth, many biological dressing materials and skin grafting have been employed. The present study fabricated a novel wound healing gel/film (CH-CL) using chitosan (CH) and methanolic peel extract of Citrus limetta (CL) and investigated the potential towards the wound healing process. During this investigation, the peel extract of CL was subjected to GC-MS to reveal the bioactive compounds responsible for various activities of the extract. Moreover, the CL extract was analyzed for its anti-microbial, anti-oxidant and anti-inflammatory properties. The CH-CL film was also subjected to water absorption capacity and folding endurance. The extract was also investigated for its viability using normal keratinocytes cell lines. The physico chemical characterization of the gel was done to reveal the chemical composition using FTIR, XRD and SEM. The GC-MS analysis results clearly indicated that the gel is biocompatible, possessing anti-microbial, anti-oxidant and anti-inflammatory properties due to its bioactive compounds. Furthermore, the CH-CL film acts as a good water absorbing material with optimum folding endurance which are the key physical properties of a normal wound healing material. Thus, the study concluded that CH-CL gel has been proven as an efficient, cost-economic wound healing gel and can be applied for various types of wounds and other biomedical applications.

References:

Abstract:

Allogeneic bone grafts are considered to be an integral part of implant dentistry. These grafts have rich osteoconductivity, osteoinductivity and osteogencity and can act as a substrate material to fill the defects on bone surfaces and can augment bone fracture and tooth fracture healing. Based on such principles, this current study fabricated a novel graft composite for bone using egg shell powder (ESP), Hydroxyapatite (HA), Chitosan (CH) and Aqueous extract of fruits of Terminalia chebula (TC). The prepared new bone graft (ESP-HA-CH-Tc) was analyzed using various physico-chemical characterization techniques like FT-IR, XRD, TGA, and SEM to understand the chemical composition, evaluate its surface morphology and stability standard. The aqueous fruit extract of Terminalia chebula (Tc) was analysed for its phytochemical composition by GCMS and invitro pharmacological properties like antioxidant, anti-inflammatory, antimicrobial and the biocompatibility of the graft were assessed by cell culture studies in Breast cancer (MCF-7) cell lines. The incorporation of fruit extract of Terminalia chebula strengthens and augments the ossification property of the graft material and can extend its use in the treatment of fractures and further biomedical applications.

References:

Abstract:

Cancer, a multifaceted disease with increasing prevalence, remains a significant global health concern. Lung cancer, in particular, presents a formidable challenge due to its high mortality rates. Tomentin, a phytochemical extracted from Sphaeralcea angustifolia, has garnered interest for its potential anti-cancer properties. This study employs both in vitro and in silico methods to elucidate tomentin's efficacy against lung cancer, focusing on the A549 cell line, a model for lung adenocarcinoma. The study begins by exploring the cytotoxic effects of tomentin on A549 cells through viability assays, apoptosis induction, and molecular pathway modulation. Results indicate dose-dependent inhibition of cell proliferation and activation of apoptotic pathways by tomentin treatment. Further analysis reveals tomentin's ability to scavenge DPPH radicals and inhibit protein denaturation, suggesting potent antioxidant and anti-inflammatory properties. Moreover, mRNA expression analysis demonstrates tomentin's regulatory effects on key genes involved in inflammation and apoptosis. Molecular docking studies reveal strong binding affinity between tomentin and critical proteins implicated in cancer progression, including MCL1, p53, Bcl-2, and Caspases.

References:

Abstract:

Insulin function and sensitivity are compromised in type 2 diabetes (T2DM) due to various factors causing cellular stress and inflammation. With the increasing recognition of inflammation's role in both T1DM and T2DM, anti-inflammatory strategies are gaining importance in disease management. This study investigates the relationship between andrographolide and the enzymes α-glucosidase and α-amylase to elucidate its antidiabetic benefits. The study also evaluates andrographolide's ability to inhibit protein denaturation and examines its effects on the liver of T2DM rats through histological analysis. Methods included in vitro antidiabetic and anti-inflammatory activity assessments using α-glucosidase, α-amylase, and protein denaturation inhibition methods. Histopathological analysis of liver tissue from streptozotocin (STZ) and high-fat diet (HFD)-induced type-2 diabetic rats was conducted. In silico docking analysis was performed to confirm the binding affinity of andrographolide with pro-inflammatory signaling molecules. Data were analyzed using one-way ANOVA. Results indicated that molecular docking showed a good binding affinity with selected protein targets, attesting to andrographolide's powerful anti-inflammatory and antidiabetic effects. Histological analysis demonstrated that andrographolide could restore the hepatic architecture of diabetic livers. The in silico study further demonstrated high binding affinity against protein targets related to inflammatory and insulin signaling pathways. In conclusion, andrographolide may provide a promising basis for developing novel treatments and identifying critically needed pharmaceutical targets to address inflammation-related clinical problems in diabetes.

References:

Abstract:

In the field of Biomedicine, allogeneic grafts that possess excellent biocompatibility and immuno-compatibility play a major role in the treatment of untreated dental bone defects.  Filling these defects with bone substitute material prevents resorption of bone, preserves the alveolar ridge, and provides sufficient bone for immediate or subsequent implant placement. In this regard, the present study focused on the fabrication of a novel herbal bone graft material rich in biopolymers and phytochemicals was used as bone graft. The bone graft material was synthesized using biphasic calcium phosphate, casein, chitosan and ethanolic leaf extracts of Cassia Occidentalis. The prepared bone graft was subjected to various characterizations like FTIR, X-ray diffraction, thermos-gravimetric analysis, scanning electron microscopy to show its chemical composition, surface morphology, stability, mechanical strength to show its chemical composition, stability and porosity and GCMS analysis, anti-microbial, anti-oxidant, anti-inflammatory activity to reveal its bioactive components. Results revealed that the prepared bone graft of Cassia Occidentalis showed excellent osteogenic and can be well suggested for various biomedical applications like orthopedics, dental fillings, bone tissue engineering and in the treatment of rheumatoid arthritis. It also replaces the use of autogenous graft with high biocompatibility and osteogenesis.

References:

Abstract:

Ethyl iso-allocholate (EIA) has emerged as a compound of interest due to its potential antioxidant and antidiabetic properties. This study aimed to evaluate the antidiabetic and antioxidant potential of EIA through a combination of in vitro assays and in silico analysis. The antioxidant activity of EIA was assessed using the DPPH radical scavenging assay. EIA demonstrated significant antioxidant activity with inhibition percentages of 29% at 100μg, increasing to 88% at 500μg, compared to Vitamin C, the standard antioxidant, which showed 41% and 95% inhibition, respectively. In terms of antidiabetic potential, EIA’s efficacy was evaluated through alpha-amylase and alpha-glucosidase inhibition assays. EIA exhibited dose-dependent inhibition of alpha-amylase, with a maximum inhibition of 71.3% at 50μg, compared to 96% by acarbose, a standard antidiabetic agent. Similarly, in the alpha-glucosidase assay, EIA showed up to 70.25% inhibition at 50μg, while acarbose achieved 95.7%. The cytotoxicity of EIA was assessed in 3T3-L1 cells over 48 hours, indicating a favorable safety profile. Additionally, Real-time PCR analysis revealed that EIA positively modulated the expression of key insulin signaling components (IR, IRS1, Akt, PI3K, and GLUT4) in 3T3-L1 cells. In silico molecular docking studies further supported these findings, showing strong binding affinities of EIA with insulin receptor (IR), IRS1, Akt, GLUT4, and PI3K, with the highest binding affinity observed with GLUT4 (-8.5 kcal/mol) and PI3K (-8.8 kcal/mol). These results suggest that EIA could be a promising candidate for further research into its therapeutic potential for diabetes and oxidative stress management.

References:

Abstract:

Diabetes mellitus is a significant global health issue, affecting 425 million people worldwide, with projections estimating an increase to 629 million by 2045. The need for potent pharmacological agents is urgent, as current oral hypoglycemic drugs have adverse side effects. Hesperidin, a bioflavonoid with anti-hyperglycemic and anti-hyperlipidemic properties, offers promise as a natural therapeutic option. This study aimed to evaluate hesperidin's molecular and epigenetic effects on insulin signal transduction in the gastrocnemius muscle of STZ-induced type 2 diabetic rats. Methods involved dividing fully-grown male Wistar rats into five groups: Healthy control, STZ-induced diabetic, Diabetes+Hesperidin (100mg/kg), Diabetes+Metformin (50mg/kg), and Control+Hesperidin. At the experiment's conclusion, blood samples and gastrocnemius muscle tissues were collected to measure fasting blood glucose, serum insulin, antioxidant enzymes, oxidative stress markers, and histopathological and mRNA expression of insulin signalling molecules. Data were analyzed using one-way ANOVA, with significance set at p<0.05. Results indicated that STZ-induced diabetic rats exhibited significant increases in hyperglycemia, hyperinsulinemia, dyslipidemia, and oxidative stress markers, along with reduced superoxide dismutase (SOD) activity. Histopathological analysis revealed reduced muscle fibres and disrupted skeletal fibres. Additionally, mRNA expression of IRS-1, Akt, and GLUT 4 was significantly reduced. Remarkably, hesperidin treatment normalized these altered parameters. In conclusion, hesperidin effectively regulates insulin signalling in skeletal muscle, reducing diabetic risk. Thus, hesperidin shows potential as a therapeutic candidate for treating type 2 diabetes and its associated complications.

References:

[1] Manna, P., & Jain, S. K., 2015, Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metabolic Syndrome and Related Disorders, 13(10), 423–444. https://doi.org/10.1089/met.2015.0095.

[2] Bindu Jacob, & Narendhirakannan, R.T., 2019, Role of medicinal plants in the management of diabetes mellitus: a review. 3 Biotech, 9(1), 4. https://doi.org/10.1007/s13205-018-1528-0.

[3] Kim, J., Wie, M. B., Ahn, M., Tanaka, A., Matsuda, H., & Shin, T., 2019, Benefits of hesperidin in central nervous system disorders: a review. Anatomy & cell biology, 52(4), 369–377. https://doi.org/10.5115/acb.19.119.

[4] Giannini, I., Amato, A., Basso, L., Tricomi, N., Marranci, M., Pecorella, G., Tafuri, S., Pennisi, D., & Altomare, D. F., 2015, Flavonoids mixture (diosmin, troxerutin, hesperidin) in the treatment of acute hemorrhoidal disease: a prospective, randomized, triple-blind, controlled trial. Techniques in Coloproctology, 19(6), 339–345. https://doi.org/10.1007/s10151-015-1302-9.

[5] Prasad, M., Rajagopal, P., Devarajan, N., Veeraraghavan, V. P., Palanisamy, C. P., Cui, B., Patil, S., & Jayaraman, S., 2022, A comprehensive review on high -fat diet-induced diabetes mellitus: an epigenetic view. The Journal of Nutritional Biochemistry, 107, 109037. https://doi.org/10.1016/j.jnutbio.2022.109037.

[6] Georgel, P. T., & Georgel, P. (2021). Where Epigenetics Meets Food Intake: Their Interaction in the Development/Severity of Gout and Therapeutic Perspectives. Frontiers in Immunology, 12, 752359. https://doi.org/10.3389/fimmu.2021.752359.

[7] Drabkin, D.L., Austin, J.H., 1932, Spectrophotometric Studies: I. Spectrophotometric Constants for Common Hemoglobin Derivatives in Human, Dog, and Rabbit Blood. Journal of Biological Chemistry, 1932, 98, 719-733. 10.4236/oalib.1100648.

[8] Bannon P., 1982, Effect of pH on the elimination of the labile fraction of glycosylated hemoglobin. Clinical Chemistry, 28(10), 2183.

[9] Slaoui, M., & Fiette, L., 2011, Histopathology procedures: from tissue sampling to histopathological evaluation. Methods in molecular biology (Clifton, N.J.), 691, 69–82. https://doi.org/10.1007/978-1-60761-849-2_4.

[10] Gabe, M., 1968, Techniques Histologiques, 6th ed.; Massie e Cie: Paris, France, 1113p.

[11] Slaoui, M., & Fiette, L., 2011, Histopathology procedures: from tissue sampling to histopathological evaluation. Methods in Molecular Biology (Clifton, N.J.), 691, 69–82. https://doi.org/10.1007/978-1-60761-849-2_4.

[12] Gancedo, J. M., & Gancedo, C., 1971, Fructose-1,6-diphosphatase, phosphofructokinase and glucose-6-phosphate dehydrogenase from fermenting and non fermenting yeasts. Archiv fur Mikrobiologie, 76(2), 132–138. https://doi.org/10.1007/BF00411787.

[13] Galicia-Garcia, U., Benito-Vicente, A., Jebari, S., Larrea-Sebal, A., Siddiqi, H., Uribe, K. B., Ostolaza, H., & Martín, C., 2020, Pathophysiology of Type 2 Diabetes Mellitus. International Journal of Molecular Sciences, 21(17), 6275. https://doi.org/10.3390/ijms21176275.

[14] Merz, K. E., & Thurmond, D. C., 2020, Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Comprehensive Physiology, 10(3), 785–809. https://doi.org/10.1002/cphy.c190029.

[15] Thomas, D. D., Corkey, B. E., Istfan, N. W., & Apovian, C. M., 2019,  Hyperinsulinemia: An Early Indicator of Metabolic Dysfunction. Journal of the Endocrine Society, 3(9), 1727–1747. https://doi.org/10.1210/js.2019-00065.

[16] Wilcox G., 2005, Insulin and insulin resistance. The Clinical Biochemist. Reviews, 26(2), 19–39.

[17] Zhao, C., Yang, C., Wai, S. T. C., Zhang, Y., P Portillo, M., Paoli, P., Wu, Y., San Cheang, W., Liu, B., Carpéné, C., Xiao, J., & Cao, H., 2019, Regulation of glucose metabolism by bioactive phytochemicals for the management of type 2 diabetes mellitus. Critical Reviews in Food Science and Nutrition, 59(6), 830–847. https://doi.org/10.1080/10408398.2018.1501658.

[18] Stanley Mainzen Prince, P., & Kamalakkannan, N., 2006, Rutin improves glucose homeostasis in streptozotocin diabetic tissues by altering glycolytic and gluconeogenic enzymes. Journal of Biochemical and Molecular Toxicology, 20(2), 96–102. https://doi.org/10.1002/jbt.20117.

[19] Latha, M., & Pari, L., 2003, Antihyperglycaemic effect of Cassia auriculata in experimental diabetes and its effects on key metabolic enzymes involved in carbohydrate metabolism. Clinical and Experimental Pharmacology & Physiology, 30(1-2), 38–43. https://doi.org/10.1046/j.1440-1681.2003.03785.x.

[20] Peng, P., Jin, J., Zou, G., Sui, Y., Han, Y., Zhao, D., & Liu, L., 2021, Hesperidin prevents hyperglycemia in diabetic rats by activating the insulin receptor pathway. Experimental and Therapeutic Medicine, 21(1), 53. https://doi.org/10.3892/etm.2020.9485.

[21] Pari, L., & Rajarajeswari, N., 2009, Efficacy of coumarin on hepatic key enzymes of glucose metabolism in chemical induced type 2 diabetic rats. Chemico-biological Interactions, 181(3), 292–296. https://doi.org/10.1016/j.cbi.2009.07.018.

[22] Gothandam, K., Ganesan, V. S., Ayyasamy, T., & Ramalingam, S., 2019, Antioxidant potential of theaflavin ameliorates the activities of key enzymes of glucose metabolism in high fat diet and streptozotocin - induced diabetic rats. Redox report : Communications in free radical research, 24(1), 41–50. https://doi.org/10.1080/13510002.2019.1624085.

[23] Boucher, J., Kleinridders, A., & Kahn, C. R., 2014, Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harbor Perspectives in Biology, 6(1), a009191. https://doi.org/10.1101/cshperspect.a009191.

[24] Zhang Y, Xu W, Huang X et al., 2018, Fucoxanthin ameliorates hyperglycemia, hyperlipidemia and insulin resistance in diabetic mice partially through IRS-1/PI3K/Akt and AMPK pathways. Journal of Functional Foods, 48:515–524. 10.1016/j.jff.2018.07.048.

[25] Cai, S., Sun, W., Fan, Y., Guo, X., Xu, G., Xu, T., Hou, Y., Zhao, B., Feng, X., & Liu, T., 2016, Effect of mulberry leaf (Folium Mori) on insulin resistance via IRS-1/PI3K/Glut-4 signalling pathway in type 2 diabetes mellitus rats. Pharmaceutical Biology, 54(11), 2685–2691. https://doi.org/10.1080/13880209.2016.1178779.

[26] Wang, Y., Nishina, P. M., & Naggert, J. K., 2009, Degradation of IRS1 leads to impaired glucose uptake in adipose tissue of the type 2 diabetes mouse model TALLYHO/Jng. The Journal of Endocrinology, 203(1), 65–74. https://doi.org/10.1677/JOE-09-0026.

[27] Li, H., Yu, L., & Zhao, C., 2019, Dioscin attenuates high‑fat diet‑induced insulin resistance of adipose tissue through the IRS‑1/PI3K/Akt signaling pathway. Molecular Medicine Reports, 19(2), 1230–1237. https://doi.org/10.3892/mmr.2018.9700.

[28] Ramalingam, K., Yadalam, P. K., Ramani, P., Krishna, M., Hafedh, S., Badnjević, A., Cervino, G., & Minervini, G., 2024, Light gradient boosting-based prediction of quality of life among oral cancer-treated patients. BMC Oral Health, 24(1), 349. https://doi.org/10.1186/s12903-024-04050-x.

[29] Neralla, M., M, H., Preethi, A., Selvakumar, S. C., & Sekar, D., 2024, Expression levels of microRNA-7110 in oral squamous cell carcinoma. Minerva Dental and Oral Science, 73(3), 155–160. https://doi.org/10.23736/S2724-6329.23.04801-5.

[30] Ramsundar, K., Jain, R. K., Balakrishnan, N., & Vikramsimha, B., 2023, Comparative evaluation of bracket bond failure rates of a novel non-primer adhesive with a conventional primer-based orthodontic adhesive - a pilot study. Journal of Dental Research, Dental Clinics, Dental Prospects, 17(1), 35–39. https://doi.org/10.34172/joddd.2023.36953.