Regulatory Effects of Chromium Picolinate and Phytochemicals on Blood Glucose via AMPK Pathway Activation
Abstract
The study examines the scientific work and clinical reports to emphasise the roles of Brassica juncea in glucose metabolism and glycogen synthesis, Gymnema sylvestre in insulin secretion and beta-cell regeneration and chromium picolinate in chromodulin synthesis and insulin receptor activation. Additionally, focus was placed on their combined ability to aggregate AMP-activated protein kinase (AMPK) signalling pathway, which play major role in insulin sensitivity and cellular energy homeostasis. By promoting glucose metabolism, chromium picolinate improves insulin sensitivity. By boosting insulin release and decreasing glucose absorption, Gymnema sylvestre helps manage diabetes. Glycogen production and enzyme activation are two ways that Brassica juncea aids in blood sugar management. When combined, these compounds enhance glucose absorption and decrease gluconeogenesis by activating the AMPK pathway. These synthetic and natural substances present encouraging diabetic treatment approaches. When combined with dietary changes, they can improve the effectiveness of treatment. Clarifying their mechanisms and improving their therapeutic uses should be the main goals of future studies.
References
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009 Jan;32 Suppl 1(Suppl 1):S62-7. doi: 10.2337/dc09-S062.
Fazakerley DJ, Krycer JR, Kearney AL, Hocking SL, James DE. Muscle and adipose tissue insulin resistance: malady without mechanism? J Lipid Res. 2019;6010:1720–32. doi: 10.1194/jlr.R087510.
Skarbez K, Priestley Y, Hoepf M, Koevary SB. Comprehensive review of the effects of diabetes on ocular health. Expert Rev Ophthalmol. 2010;54:557–77. doi: 10.1586/eop.10.44.
Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus—atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus: mechanisms, management and clinical considerations. Circulation. 2016;13324:2459–502. doi: 10.1161/CIRCULATIONAHA.116.022194.
Antar SA, Ashour NA, Sharaky M, Khattab M, Ashour NA, Zaid RT, et al. Diabetes mellitus: Classification, mediators and complications; a gate to identify potential targets for the development of new effective treatments. Biomed Pharmacother. 2023;168:115734. doi: 10.1016/j.biopha.2023.115734.
Tomic D, Shaw JE, Magliano DJ. The burden and risks of emerging complications of diabetes mellitus. Nat Rev Endocrinol. 2022;189:525–39. doi: 10.1038/s41574-022-00690-7
Ong KL, Stafford LK, McLaughlin SA, Boyko EJ, Vollset SE, Smith AE, et al. Global, regional and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;40210397:203–234. doi: 10.1016/S0140-67362301301-6.
Siam NH, Snigdha NN, Tabasumma N, Parvin I. Diabetes mellitus and cardiovascular disease: exploring epidemiology, pathophysiology and treatment strategies. Rev Cardiovasc Med. 2024;2512:436. doi: 10.31083/j.rcm2512436.
Murtaza G, Riaz S, Zafar M, Ahsan Raza M, Kaleem I, Imran H, et al. Examining the growing challenge: Prevalence of diabetes in young adults (Review). Med Int (Lond). 2025;51:2. doi: 10.3892/mi.2024.201.
Ling S, Zaccardi F, Issa E, Davies MJ, Khunti K, Brown K. Inequalities in cancer mortality trends in people with type 2 diabetes: 20-year population-based study in England. Diabetologia. 2023;664:657–73. doi: 10.1007/s00125-022-05854-8.
Iheagwam FN, Iheagwam OT. Diabetes mellitus: The pathophysiology as a canvas for management elucidation and strategies. Medicine in Novel Technology and Devices. 2025;25:100351. doi: 10.1016/j.medntd.2025.100351.
Koskinen MK, Helminen O, Matomäki J, Aspholm S, Mykkänen J, Mäkinen M, et al. Reduced β-cell function in early preclinical type 1 diabetes. Eur J Endocrinol. 2016;1743:251–9. doi: 10.1530/EJE-15-0674.
Di Giuseppe G, Ciccarelli G, Soldovieri L, Capece U, Cefalo CMA, Moffa S, et al. First-phase insulin secretion: can its evaluation direct therapeutic approaches? Trends Endocrinol Metab. 2023;344:216–30. doi: 10.1016/j.tem.2023.02.001.
Kahn BB. Type 2 diabetes: When insulin secretion fails to compensate for insulin resistance. Cell. 1998;925:593–6. doi: 10.1016/S0092-8674(0081125-3.
Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020 Aug 30;21(17):6275. doi: 10.3390/ijms21176275.
Ye W, Luo C, Huang J, Li C, Liu Z, Liu F. Gestational diabetes mellitus and adverse pregnancy outcomes: systematic review and meta-analysis. BMJ. 2022;377:e067946. doi: 10.1136/bmj-2021-067946.
Choudhury AA, Devi Rajeswari V. Gestational diabetes mellitus – A metabolic and reproductive disorder. Biomed Pharmacother. 2021;143:112183. doi: 10.1016/j.biopha.2021.112183.
Zhou Z, Xu M, Xiong P, Yuan J, Zheng D, Piao S. Prognosis and outcome of latent autoimmune diabetes in adults: T1DM or T2DM? Diabetol Metab Syndr. 2024 Oct 7;16(1):242. doi: 10.1186/s13098-024-01479-6.
Makahleh L, Othman A, Vedantam V, Vedantam N. Ketosis-prone type 2 diabetes mellitus: an unusual presentation. Cureus. 2022;1410:e30031. doi: 10.7759/cureus.30031.
Serbis A, Kantza E, Siomou E, Galli-Tsinopoulou A, Kanaka-Gantenbein C, Tigas S. Monogenic defects of beta cell function: From clinical suspicion to genetic diagnosis and management of rare types of diabetes. Int J Mol Sci. 2024;2519:10501. doi: 10.3390/ijms251910501.
Parker VE, Semple RK. Genetics in endocrinology: genetic forms of severe insulin resistance: what endocrinologists should know. Eur J Endocrinol. 2013;1694:R71–R80. doi: 10.1530/EJE-13-0327.
Popoviciu MS, Paduraru L, Nutas RM, Ujoc AM, Yahya G, Metwally K, et al. Diabetes mellitus secondary to endocrine diseases: an update of diagnostic and treatment particularities. Int J Mol Sci. 2023;2416. doi: 10.3390/ijms241612676.
Fathallah N, Slim R, Larif S, Hmouda H, Ben Salem C. Drug-induced hyperglycaemia and diabetes. Drug Saf. 2015;3812:1153–68. doi: 10.1007/s40264-015-0339-z.
Mine K, Yoshikai Y, Takahashi H, Mori H, Anzai K, Nagafuchi S. Genetic susceptibility of the host in virus-induced diabetes. Microorganisms. 2020;88:1133. doi: 10.3390/microorganisms8081133.
Padhi S, Nayak AK, Behera A. Type II diabetes mellitus: a review on recent drug based therapeutics. Biomed Pharmacother. 2020;131:110708. doi: 10.1016/j.biopha.2020.110708.
Lorenzati B, Zucco C, Miglietta S, Lamberti F, Bruno G. Oral hypoglycemic drugs: pathophysiological basis of their mechanism of action. Pharmaceuticals (Basel). 2010;39:3005–20. doi: 10.3390/ph3093005.
LeRoy JM, Stellpflug SJ. Antidiabetic agents. In: Brent J, Burkhart K, Dargan P, Hatten B, Mégarbane B, Palmer R, Editors. Critical care toxicology. Cham: Springer International Publishing; 2016. p. 1–25.
The DCCT Research Group. Diabetes Control and Complications Trial (DCCT): results of feasibility study. Diabetes Care. 1987;101:1–19. doi: 10.2337/diacare.10.1.1.
Tamborlane WV, Ahern J. Implications and results of the Diabetes Control and Complications Trial. Pediatr Clin North Am. 1997;442:285–300. doi: 10.1016/S0031-3955(0570477-6.
Havel PJ. A scientific review: the role of chromium in insulin resistance. Diabetes Educ. 2004;Suppl:2-14. PMID: 15208835.
Wiernsperger N, Rapin J. Trace elements in glucometabolic disorders: an update. Diabetol Metab Syndr. 2010;21:70. doi: 10.1186/1758-5996-2-70.
Talab AT, Abdollahzad H, Nachvak SM, Pasdar Y, Eghtesadi S, Izadi A, et al. Effects of chromium picolinate supplementation on cardiometabolic biomarkers in patients with type 2 diabetes mellitus: a randomized clinical trial. Clin Nutr Res. 2020;92:97–106. doi: 10.7762/cnr.2020.9.2.97.
Wang ZQ, Yu Y, Zhang XH, Komorowski J. Chromium-insulin reduces insulin clearance and enhances insulin signaling by suppressing hepatic insulin-degrading enzyme and proteasome protein expression in KKAy mice. Front Endocrinol (Lausanne). 2014;5:99. doi: 10.3389/fendo.2014.00099.
Tiwari P, Mishra BN, Sangwan NS. Phytochemical and pharmacological properties of Gymnema sylvestre: an important medicinal plant. Biomed Res Int. 2014;2014:830285. doi: 10.1155/2014/830285.
Kanetkar P, Singhal R, Kamat M. Gymnema sylvestre: A memoir. J Clin Biochem Nutr. 2007;412:77–81. doi: 10.3164/jcbn.2007010.
Kannan P, Raghunathan M, Mohan T, Palanivelu S, Periandavan K. Gymnemic acid ameliorates pancreatic β-cell dysfunction by modulating Pdx1 expression: a possible strategy for β-cell regeneration. Tissue Eng Regen Med. 2022;193:603–16. doi: 10.1007/s13770-022-00435-7.
Ayadi J, Debouba M, Rahmani R, Bouajila J. Brassica genus seeds: A review on phytochemical screening and pharmacological properties. Molecules. 2022;2718:6008. doi: 10.3390/molecules27186008.
Rahman M, Khatun A, Liu L, Barkla BJ. Brassicaceae mustards: phytochemical constituents, pharmacological effects and mechanisms of action against human disease. Int J Mol Sci. 2024;2516:9039. doi: 10.3390/ijms25169039.
Ko DY, Seo SM, Lee YH, Gil CS, Lee H, Ku KM. Turning glucosinolate into allelopathic fate: investigating allyl isothiocyanate variability and nitrile formation in eco-friendly Brassica juncea from South Korea. Sci Rep. 2024;141:15423. doi: 10.1038/s41598-024-65938-w.
Coughlan KA, Valentine RJ, Ruderman NB, Saha AK. AMPK activation: a therapeutic target for type 2 diabetes? Diabetes Metab Syndr Obes. 2014;7:241–53. doi: 10.2147/DMSO.S43731.
Kakoti BB, Alom S, Deka K, Halder RK. AMPK pathway: an emerging target to control diabetes mellitus and its related complications. J Diabetes Metab Disord. 2024;231:441–59. doi: 10.1007/s40200-024-01420-8.
Li M, Ding L, Cao L, Zhang Z, Li X, Li Z, et al. Natural products targeting AMPK signaling pathway therapy, diabetes mellitus and its complications. Front Pharmacol. 2025;16:1534634. doi: 10.3389/fphar.2025.1534634.
Yuan X, Chen Z, Luo S, Xu X, Guo Y, Lin Y, et al. Photoinduced oxidation of chromium picolinate to hexavalent chromium in the presence of ferric ions. J Hazard Mater. 2024;477:135416. doi: 10.1016/j.jhazmat.2024.135416.
Sawicka E, Jurkowska K, Piwowar A. Chromium (III) and chromium (VI) as important players in the induction of genotoxicity—current view. Ann Agric Environ Med. 2021;281:1–7. doi: 10.26444/aaem/118228.
DesMarais TL, Costa M. Mechanisms of chromium-induced toxicity. Curr Opin Toxicol. 2019;14:1–7. doi: 10.1016/j.cotox.2019.05.003.
Ali A, Ma Y, Reynolds J, Wise JP Sr, Inzucchi SE, Katz DL. Chromium effects on glucose tolerance and insulin sensitivity in persons at risk for diabetes mellitus. Endocr Pract. 2011;171:16–25. doi: 10.4158/EP10131.OR.
Maleki V, Izadi A, Farsad-Naeimi A, Alizadeh M. Chromium supplementation does not improve weight loss or metabolic and hormonal variables in patients with polycystic ovary syndrome: a systematic review. Nutr Res. 2018;56:1–10. doi: 10.1016/j.nutres.2018.04.003.
Basiri R, Seidu B, Cheskin LJ. Key nutrients for optimal blood glucose control and mental health in individuals with diabetes: a review of the evidence. Nutrients. 2023;1518:3929. doi: 10.3390/nu15183929.
Jach ME, Serefko A, Ziaja M, Kieliszek M. Yeast protein as an easily accessible food source. Metabolites. 2022;121:63. doi: 10.3390/metabo12010063.
Vajdi M, Khajeh M, Safaei E, Moeinolsadat S, Mousavi S, Seyedhosseini-Ghaheh H, et al. Effects of chromium supplementation on body composition in patients with type 2 diabetes: A dose-response systematic review and meta-analysis of randomized controlled trials. J Trace Elem Med Biol. 2024;81:127338. doi: 10.1016/j.jtemb.2023.127338.
Henriksen C, Bügel S. Chromium – a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2023;67. doi: 10.29219/fnr.v67.10325.
Chromium supplementation and the essentiality of chromium to human nutrition: a narrative review. arXiv preprint arXiv:2309.10820. 2023. doi: 10.48550/arXiv.2309.10820.
Hua Y, Clark S, Ren J, Sreejayan N. Molecular mechanisms of chromium in alleviating insulin resistance. J Nutr Biochem. 2012;234:313–9. doi: 10.1016/j.jnutbio.2011.11.001.
Zhang W, Chen H, Ding Y, Xiang Q, Zhao J, Feng W, et al. Effect of chromium citrate on the mechanism of glucose transport and insulin resistance in Buffalo rat liver cells. Indian J Pharmacol. 2020;521:31–8. doi: 10.4103/ijp.IJP_608_18.
Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther. 2022;71:216. doi: 10.1038/s41392-022-01073-0.
Clodfelder BJ, Emamaullee J, Hepburn DD, Chakov NE, Nettles HS, Vincent JB. The trail of chromium(III) in vivo from the blood to the urine: the roles of transferrin and chromodulin. J Biol Inorg Chem. 2001;65-6:608-17. doi: 10.1007/s007750100238.
Monga A, Fulke AB, Dasgupta D. Recent developments in essentiality of trivalent chromium and toxicity of hexavalent chromium: Implications on human health and remediation strategies. J Hazard Mater Adv. 2022;7:100113. doi: 10.1016/j.hazadv.2022.100113.
Kumpulainen JT. Chromium content of foods and diets. Biol Trace Elem Res. 1992;32:9–18. doi: 10.1007/BF02784582.
Masironi R, Wolf W, Mertz W. Chromium in refined and unrefined sugars: possible nutritional implications in the etiology of cardiovascular diseases. Bull World Health Organ. 1973;493:322–4. PMC2481154.
Hambidge KM. Chromium nutrition in man. Am J Clin Nutr. 1974;275:505–14. doi: 10.1093/ajcn/27.5.505.
Carlsen MH, Halvorsen BL, Holte K, Bøhn SK, Dragland S, Sampson L, et al. The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J. 2010 Jan 22;9:3. doi: 10.1186/1475-2891-9-3.
Wang H, Hu L, Li H, Lai YT, Wei X, Xu X, et al. Mitochondrial ATP synthase as a direct molecular target of chromium(III) to ameliorate hyperglycaemia stress. Nat Commun. 2023;141:1738. doi: 10.1038/s41467-023-37351-w.
Genchi G, Lauria G, Catalano A, Carocci A, Sinicropi MS. The double face of metals: the intriguing case of chromium. Appl Sci. 2021;112:638. doi: 10.3390/app11020638.
Song G, Tan H, Cheng C, Li P, Sun X, Zhou Y, et al. Development of a fast method using inductively coupled plasma mass spectrometry coupled with high-performance liquid chromatography and exploration of the reduction mechanism of Cr(VI) in foods. Toxics. 2024;125:325. doi: 10.3390/toxics12050325.
Zhitkovich A. Chromium in drinking water: Sources, metabolism and cancer risks. Chem Res Toxicol. 2011;2410:1617–29. doi: 10.1021/tx200251t.
Baghirov H. Mechanisms of receptor-mediated transcytosis at the blood-brain barrier. J Control Release. 2025;381:113595. doi: 10.1016/j.jconrel.2025.113595.
Thomsen MS, Johnsen KB, Kucharz K, Lauritzen M, Moos T. Blood-brain barrier transport of transferrin receptor-targeted nanoparticles. Pharmaceutics. 2022;1410:2237. doi: 10.3390/pharmaceutics14102237.
Devangan S, Varghese B, Johny E, Gurram S, Adela R. The effect of Gymnema sylvestre supplementation on glycemic control in type 2 diabetes patients: A systematic review and meta-analysis. Phytother Res. 2021;3512:6802–12. doi: 10.1002/ptr.7265.
Zamani M, Ashtary-Larky D, Nosratabadi S, Bagheri R, Wong A, Rafiei MM, et al. The effects of Gymnema sylvestre supplementation on lipid profile, glycemic control, blood pressure and anthropometric indices in adults: a systematic review and meta-analysis. Phytother Res. 2023;373:949–64. doi: 10.1002/ptr.7585.
Muzaffar H, Qamar I, Bashir M, Jabeen F, Irfan S, Anwar H. Gymnema sylvestre supplementation restores normoglycemia, corrects dyslipidemia and transcriptionally modulates pancreatic and hepatic gene expression in alloxan-induced hyperglycemic rats. Metabolites. 2023;134:516. doi: 10.3390/metabo13040516.
Kashif M, Nasir A, Gulzaman, Rafique MK, Abbas M, Ur Rehman A, et al. Unlocking the anti-diabetic potential of Gymnema sylvestre, Trigonella foenum-graecum and their combination thereof: an in-vivo evaluation. Food Sci Nutr. 2023;1112:7664–72. doi: 10.1002/fsn3.3685.
Bandala C, Carro-Rodríguez J, Cárdenas-Rodríguez N, Peña-Montero I, Gómez-López M, Hernández-Roldán AP, et al. Comparative effects of Gymnema sylvestre and berberine on adipokines, body composition and metabolic parameters in obese patients: a randomized study. Nutrients. 2024;1614:2284. doi: 10.3390/nu16142284.
Miranda DG, Tomé FM, Miguel MMV, Liberato S, Marcucci MC, Vigerelli H, et al. Gymnema sylvestre as a potential anti-inflammatory and anti-biofilm agent against anaerobic infections: an in vitro study. Plants (Basel). 2025;144. doi: 10.3390/plants14040497.
Mayyas A, Al-Samydai A, Oraibi AI, Debbabi N, Hassan SS, Al-Hussainy HA, et al. Deciphering the anti-diabetic potential of Gymnema sylvestre using integrated computer-aided drug design and network pharmacology. J Cell Mol Med. 2025 Jan;29(1):e70349. doi: 10.1111/jcmm.70349.
Nani A, Bertuzzi F, Meneghini E, Mion E, Pintaudi B. Combined inositols, α-lactalbumin, Gymnema sylvestre and zinc improve the lipid metabolic profile of patients with type 2 diabetes mellitus: a randomized clinical trial. J Clin Med. 2023;1224:7650. doi: 10.3390/jcm12247650.
Hechtman L. Polycystic ovary syndrome (PCOS). In: Pizzorno JE, Murray MT, editors. Textbook of natural medicine. 5th ed. St. Louis (MO): Churchill Livingstone; 2020. p. 1694–1706.e7.
Shivakumara KT, Chinapolaiah A, Keerthi MC, Ramya RS, Gotyal BS. Identification and characterization of novel resistant genotypes of Gymnema sylvestre (Retz.) R. Br. ex Sm. against invasive mealybug species, Phenacoccus solenopsis Tinsley and Paracoccus marginatus Williams and Granara de Willink for sustainable pest management. J Appl Res Med Aromat Plants. 2024;39:100534. doi: 10.1016/j.jarmap.2024.100534.
Pham HTT, Hoang MC, Ha TKQ, Dang LH, Tran VO, Nguyen TBT, et al. Discrimination of different geographic varieties of Gymnema sylvestre, an anti-sweet plant used for the treatment of type 2 diabetes. Phytochemistry. 2018;150:12–22. doi: 10.1016/j.phytochem.2018.02.013.
Sinsheimer JE, McIlhenny HM. Constituents from Gymnema sylvestre leaves. II. Nitrogenous compounds. J Pharm Sci. 1967;566:732–6. doi: 10.1002/jps.2600560615.
Shanmugasundaram ER, Gopinath KL, Shanmugasundaram KR, Rajendran VM. Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given Gymnema sylvestre leaf extracts. J Ethnopharmacol. 1990;303:265–79. doi: 10.1016/0378-87419090106-4.
Neel S, Mandal A, Saha S, Das A, Kundu A, Singh A. Gymnema sylvestre saponins for potential antifungal action: in vitro and in silico perspectives. Front Plant Sci. 2025;16:1508454. doi: 10.3389/fpls.2025.1508454.
Sathya S, Kokilavani R, Gurusamy K. Hypoglycemic effect of Gymnema sylvestre (retz.,) R.Br leaf in normal and alloxan induced diabetic rats. Anc Sci Life. 2008 Oct;28(2):12-4. PMID: 22557305.
Turner S, Diako C, Kruger R, Wong M, Wood W, Rutherfurd-Markwick K, et al. Consuming Gymnema sylvestre reduces the desire for high-sugar sweet foods. Nutrients. 2020;124:1046. doi: 10.3390/nu12041046.
Jangam A, Tirunavalli SK, Adimoolam BM, Kasireddy B, Patnaik SS, Erukkambattu J, et al. Anti-inflammatory and antioxidant activities of Gymnema sylvestre extract rescue acute respiratory distress syndrome in rats via modulating the NF-κB/MAPK pathway. Inflammopharmacol. 2023;312:823–44. doi: 10.1007/s10787-022-01133-5.
Al-Romaiyan A, Liu B, Persaud SJ, Jones PM. A novel Gymnema sylvestre extract protects pancreatic beta-cells from cytokine-induced apoptosis. Phytother Res. 2020;341:161–72. doi: 10.1002/ptr.6512.
Liu M, Zhou T, Zhang J, Liao G, Lu R, Yang X. Identification of C21 steroidal glycosides from Gymnema sylvestre (Retz.) and evaluation of their glucose uptake activities. Molecules. 2021;2621:6549. doi: 10.3390/molecules26216549.
Netala VR, Hou T, Devarapogu R, Bethu MS, Zhang Z, Vijaya T. Exploring the therapeutic potential of triterpenoid saponins from Gymnema sylvestre: Mechanistic insights into hepatoprotection, immunomodulation, anticancer activities, molecular docking and pharmacokinetics. Heliyon. 2024;1023:e40850. doi: 10.1016/j.heliyon.2024.e40850.
Aditi SL, More P, Ghangale G, Tare H. Effect of Gymnema sylvestre in the control of diabetes: A review. Int J Pharm Qual Assur. 2023;141:214–9. doi: 10.25258/ijpqa.14.1.37.
Persaud SJ, Al-Majed H, Raman A, Jones PM. Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability. J Endocrinol. 1999;1632:207–12. doi: 10.1677/joe.0.1630207.
Abiola JO, Oluyemi AA, Idowu OT, Oyinloye OM, Ubah CS, Owolabi OV, et al. Potential role of phytochemicals as glucagon-like peptide 1 receptor (GLP-1R) agonists in the treatment of diabetes mellitus. Pharmaceuticals. 2024;176:736. doi: 10.3390/ph17060736.
Rahman MM, Dhar PS, Sumaia, Anika F, Ahmed L, Islam MR, et al. Exploring the plant-derived bioactive substances as antidiabetic agent: An extensive review. Biomed Pharmacother. 2022;152:113217. doi: 10.1016/j.biopha.2022.113217.
Di Fabio G, Romanucci V, Di Marino C, Pisanti A, Zarrelli A. Gymnema sylvestre R. Br., an Indian medicinal herb: traditional uses, chemical composition and biological activity. Curr Pharm Biotechnol. 2015;166:506–16. doi: 10.2174/138920101606150407112903.
Muddapur UM, Manjunath S, Alqahtani YS, Shaikh IA, Khan AA, Mannasaheb BA, et al. Exploring bioactive phytochemicals in Gymnema sylvestre: biomedical uses and computational investigations. Separations. 2024;112:50. doi: 10.3390/separations11020050.
Wen SY, Gao RR, Chen YY, Wang YJ, Wang XT, Liu HX. Brassinin from Brassica campestris L. inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis. Anim Model Exp Med. 2025. doi: 10.1002/ame2.12521.
Rizwan D, Masoodi FA. Brassica-derived isothiocyanates as anticancer therapeutic agents and their nanodelivery. Phytother Res. 2024 Jan;38(1):331-48. doi: 10.1002/ptr.8042.
Mandrich L, Caputo E. Brassicaceae-derived anticancer agents: Towards a green approach to beat cancer. Nutrients. 2020;123:868. doi: 10.3390/nu12030868.
Kim JS, Han S, Kim H, Won SY, Park HW, Choi H, et al. Anticancer effects of high glucosinolate synthesis lines of Brassica rapa on colorectal cancer cells. Antioxidants (Basel). 2022;1112:2463. doi: 10.3390/antiox11122463.
Kwak Y, Lee J, Ju J. Anti-cancer activities of Brassica juncea leaves in vitro. EXCLI J. 2016;15:699–710. doi: 10.17179/excli2016-586.
Batool U, Nawaz R, Ahmad S, Irshad MA, Irfan A, Gaafar ARZ, et al. Physico- and phytochemical properties of Brassica juncea as affected by agroclimatic conditions. Sci Rep. 2024;141:797. doi: 10.1038/s41598-023-48808-9.
Szőllősi R. Indian mustard (Brassica juncea L.) seeds in health. In: Preedy VR, Watson RR, editors. Nuts and seeds in health and disease prevention. 2nd ed. London: Academic Press; 2020. p. 357–64. doi: 10.1016/B978-0-12-818553-7.00025-5.
Das G, Tantengco OAG, Tundis R, Robles JAH, Loizzo MR, Shin HS, et al. Glucosinolates and omega-3 fatty acids from mustard seeds: Phytochemistry and pharmacology. Plants (Basel). 2022;1117. doi: 10.3390/plants11172290.
Sicard A, Thamm A, Marona C, Lee YW, Wahl V, Stinchcombe JR, et al. Repeated evolutionary changes of leaf morphology caused by mutations to a homeobox gene. Curr Biol. 2014;2416:1880–6. doi: 10.1016/j.cub.2014.06.061.
Retta MA, Van Doorselaer L, Driever SM, Yin X, de Ruijter NCA, Verboven P, et al. High photosynthesis rates in Brassiceae species are mediated by leaf anatomy enabling high biochemical capacity, rapid CO₂ diffusion and efficient light use. New Phytol. 2024;2445:1824–36. doi: 10.1111/nph.20136.
Baker RL, Yarkhunova Y, Vidal K, Ewers BE, Weinig C. Polyploidy and the relationship between leaf structure and function: implications for correlated evolution of anatomy, morphology and physiology in Brassica. BMC Plant Biol. 2017;171:3. doi: 10.1186/s12870-016-0957-3.
Tian Y, Deng F. Phytochemistry and biological activity of mustard (Brassica juncea): a review. CyTA J Food. 2020;181:704–18. doi: 10.1080/19476337.2020.1833988.
Torrijos R, Righetti L, Cirlini M, Calani L, Mañes J, Meca G, et al. Phytochemical profiling of volatile and bioactive compounds in yellow mustard (Sinapis alba) and oriental mustard (Brassica juncea) seed flour and bran. LWT. 2023;173:114221. doi: 10.1016/j.lwt.2022.114221.
Sheu MJ, Yeh MC, Tsai MC, Wang CC, Chang YL, Wang CJ, et al. Glucosinolates extracts from Brassica juncea ameliorate HFD-induced non-alcoholic steatohepatitis. Nutrients. 2023;1516:3497. doi: 10.3390/nu15163497.
Thirumalai T, Therasa SV, Elumalai EK, David E. Hypoglycemic effect of Brassica juncea (seeds) on streptozotocin-induced diabetic male albino rats. Asian Pac J Trop Biomed. 2011;14:323–5. doi: 10.1016/S2221-16911160052-X.
Farag MA, Goyal V, Baky MH. Comparative metabolome variation in Brassica juncea different organs from two varieties as analyzed using SPME and GC-MS techniques coupled to chemometrics. Sci Rep. 2024;141:19900. doi: 10.1038/s41598-024-69865-8.
Zhang B, Johnson MM, Yuan T, Nguyen TN, Okada J, Yang F, et al. Hepatic glycogen directly regulates gluconeogenesis through an AMPK/CRTC2 axis in mice. J Clin Invest. 2025;13511. doi: 10.1172/jci188363.
Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019;99:430. doi: 10.3390/biom9090430.
Vaou N, Voidarou C, Rozos G, Saldari C, Stavropoulou E, Vrioni G, et al. Unraveling nature’s pharmacy: transforming medicinal plants into modern therapeutic agents. Pharmaceutics. 2025;176:754. doi: 10.3390/pharmaceutics17060754.
Jadhav R, Das J, Rajyaguru S, Kyada S, Kale V, Teja PK, et al. Regulations, current development and future prospects of phytopharmaceuticals, a new class of herbal medicines in India. Discov Pharm Sci. 2025;11:6. doi: 10.1007/s44395-025-00006-4.
Aydin S, Tekinalp SG, Tuzcu B, Cam F, Sevik MO, Tatar E, et al. The role of AMP-activated protein kinase activators on energy balance and cellular metabolism in type 2 diabetes mellitus. Obes Med. 2025;53:100577. doi: 10.1016/j.obmed.2024.100577.
Safaie N, Masoumi S, Alizadeh S, Mirzajanzadeh P, Nejabati HR, Hajiabbasi M, et al. SGLT2 inhibitors and AMPK: The road to cellular housekeeping? Cell Biochem Funct. 2024;421:e3922. doi: 10.1002/cbf.3922.
Hawley SA, Russell FM, Ross FA, Hardie DG. BAY-3827 and SBI-0206965: potent AMPK inhibitors that paradoxically increase Thr172 phosphorylation. Int J Mol Sci. 2023;251. doi: 10.3390/ijms25010453.
Steinberg GR, Hardie DG. New insights into activation and function of the AMPK. Nat Rev Mol Cell Biol. 2023;244:255–72. doi: 10.1038/s41580-022-00547-x.
Fogarty S, Ross FA, Vara Ciruelos D, Gray A, Gowans GJ, Hardie DG. AMPK causes cell cycle arrest in LKB1-deficient cells via activation of CAMKK2. Mol Cancer Res. 2016;148:683–95. doi: 10.1158/1541-7786.MCR-15-0479.
Derosa G, D’Angelo A, Angelini F, Belli L, Cicero AFG, Da Ros R, et al. Nutraceuticals and supplements in management of prediabetes and diabetes. Nutrients. 2025;171:14. doi: 10.3390/nu17010014.
Wang YQ, Dong Y, Yao MH. Chromium picolinate inhibits resistin secretion in insulin-resistant 3T3-L1 adipocytes via activation of AMP-activated protein kinase. Clin Exp Pharmacol Physiol. 2009;368:843–9. doi: 10.1111/j.1440-1681.2009.05164.x.
Hoffman NJ, Penque BA, Habegger KM, Sealls W, Tackett L, Elmendorf JS. Chromium enhances insulin responsiveness via AMPK. J Nutr Biochem. 2014;255:565–72. doi: 10.1016/j.jnutbio.2014.01.007.
Viollet B. The energy sensor AMPK: adaptations to exercise, nutritional and hormonal signals. 2018 Mar 8. In: Spiegelman B, editor. Hormones, Metabolism and the benefits of exercise [Internet]. Cham (CH): Springer; 2017. PMID: 31314464.
Srivastava RA, Pinkosky SL, Filippov S, Hanselman JC, Cramer CT, Newton RS. AMP-activated protein kinase: an emerging drug target to regulate imbalances in lipid and carbohydrate metabolism to treat cardio-metabolic diseases. J Lipid Res. 2012;5312:2490–514. doi: 10.1194/jlr.R025882.
Garcia D, Shaw RJ. AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell. 2017;666:789–800. doi: 10.1016/j.molcel.2017.05.032.
Ke R, Xu Q, Li C, Luo L, Huang D. Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol Int. 2018;424:384–92. doi: 10.1002/cbin.10915.
Göransson O, McBride A, Hawley SA, Ross FA, Shpiro N, Foretz M, et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem. 2007;28245:32549–60. doi: 10.1074/jbc.M706536200.
Buccato DG, Ullah H, De Lellis LF, Morone MV, Larsen DS, Di Minno A, et al. Efficacy and tolerability of a food supplement based on Zea mays L., Gymnema sylvestre (Retz.) R.Br. ex Sm, zinc and chromium for the maintenance of normal carbohydrate metabolism: a monocentric, randomized, double-blind, placebo-controlled clinical trial. Nutrients. 2024;1615:2459. doi: 10.3390/nu16152459.
Li R, Zhang P, Barker LE, Chowdhury FM, Zhang X. Cost-effectiveness of interventions to prevent and control diabetes mellitus: a systematic review. Diabetes Care. 2010;338:1872–94. doi: 10.2337/dc10-0843.
Choudhury H, Pandey M, Hua CK, Mun CS, Jing JK, Kong L, et al. An update on natural compounds in the remedy of diabetes mellitus: a systematic review. J Tradit Complement Med. 2018;83:361–76. doi: 10.1016/j.jtcme.2017.08.012.
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).