Biological activities and potential functional optimization strategies of corosolic acid: a review

Abstract

Corosolic acid, a naturally occurring pentacyclic triterpenic acid, is widely recognized for its broad spectrum of biological activities, particularly its anti-diabetic properties, making it a popular ingredient in dietary supplements for regulating blood sugar levels. Beyond its anti-diabetic effects, recent studies have revealed its therapeutic potential in areas such as anti-cancer, anti-inflammatory, and antibacterial activities. However, its clinical application is hindered by poor water solubility and low bioavailability due to its molecular structure. This review systematically examines the pharmacological activities of corosolic acid, emphasizing its mechanisms of action in disease intervention. Emerging strategies to overcome its inherent limitations, including chemical modifications, microbial transformations, and advanced delivery systems, are also discussed. Notably, some chemical derivatives exhibit α-glucosidase inhibition with IC₅₀ values half that of corosolic acid. Microbial transformations have been shown to enhance its bioavailability while reducing cancer cell toxicity. Additionally, corosolic acid-based delivery systems have demonstrated significant improvements in solubility, stability, and biological activity. By consolidating current insights into its functional properties and biological activity enhancement methods, this review aims to emphasize the practical application values in food and medicine and the future development of corosolic acid as a versatile bioactive compound.

Keywords

Corosolic acid / Natural bioactive compound / Anti-diabetic properties / Anti-cancer activity / Biological activity

Author contributions

The authors confirm contribution to the paper as follows: formal analysis, writing - original draft: Shi B; investigation: Shi B, Sun H; supervision: Jia Q, Luo Z; validation: Mao Y; conceptualization; funding acquisition: Luo Z; writing - review and editing: Sun Z, Zhang H, Luo Z. All authors reviewed the results and approved the final version of the manuscript.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Acknowledgments

This research is funded by the National Key Research and Development Program of China (No. 2023YFD2201300), and the Key Research and Development Program of Zhejiang Province (2023C02042), China.

Conflict of interest

The authors declare that they have no conflict of interest.

References

[1] Samananda Singh L, Singh WS. 2024. Multifaceted therapeutic potential of corosolic acid: a novel bioactive compound. Obesity Medicine 49:100548

[2] Jin M, Li J, Zheng L, Huang M, Wu Y, et al. 2024. Corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis. International Immunopharmacology 132:111939

[3] Phakeovilay C, Bourgeade-Delmas S, Perio P, Valentin A, Chassagne F, et al. 2019. Antileishmanial compounds isolated from Psidium guajava L. using a metabolomic approach. Molecules 24(24):4536

[4] Sharma Y, Velamuri R, Fagan J, Schaefer J. 2020. Full-spectrum analysis of bioactive compounds in rosemary (Rosmarinus officinalis L.) as influenced by different extraction methods. Molecules 25(20):4599

[5] Ladurner A, Zehl M, Grienke U, Hofstadler C, Faur N, et al. 2017. Allspice and clove as source of triterpene acids activating the g ProteinCoupled bile acid receptor TGR5. Frontiers in Pharmacology 8:468

[6] Xue L, Carreiro B, Mia MS, Paetau-Robinson I, Khoo C, et al. 2024. Pentacyclic triterpenoid content in cranberry raw materials and products. Foods 13(19):3136

[7] Hu F, Liao X, Guo Y, Yamaki S, Li X, et al. 2020. Fast determination of isomeric triterpenic acids in Osmanthus fragrans (Thunb.) Lour. fruits by UHPLC coupled with triple quadrupole mass spectrometry. Food Chemistry 322:126781

[8] Olszewska M. 2008. Optimization and validation of an HPLC-UV method for analysis of corosolic, oleanolic, and ursolic acids in plant material: Application to Prunus serotina Ehrh. Acta Chromatographica 20(4):643-59

[9] Qian XP, Zhang XH, Sun LN, Xing WF, Wang Y, et al. 2021. Corosolic acid and its structural analogs: a systematic review of their biological activities and underlying mechanism of action. Phytomedicine 91:153696

[10] Mioc M, Milan A, Malița D, Mioc A, Prodea A, et al. 2022. Recent advances regarding the molecular mechanisms of triterpenic acids: a review (Part I). International Journal of Molecular Sciences 23( 14):7740

[11] Mioc M, Prodea A, Racoviceanu R, Mioc A, Ghiulai R, et al.2022.Recent advances regarding the molecular mechanisms of triterpenic acids: a review (Part II). International Journal of Molecular Sciences 23(16):8896

[12] Ni M, Pan J, Hu X, Gong D, Zhang G. 2019. Inhibitory effect of corosolic acid on α-glucosidase: kinetics, interaction mechanism, and molecular simulation. Journal of the Science of Food and Agriculture 99(13):5881-89

[13] Zhang BW, Xing Y, Wen C, Yu XX, Sun WL, et al. 2017. Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: structure-activity relationships and the synergism with acarbose. Bioorganic & Medicinal Chemistry Letters 27(22):5065-70

[14] Shi L, Zhang W, Zhou YY, Zhang YN, Li JY, et al. 2008. Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation. European Journal of Pharmacology 584( 1):21-29

[15] Yang J, Leng J, Li JJ, Tang JF, Li Y, et al. 2016. Corosolic acid inhibits adipose tissue inflammation and ameliorates insulin resistance via AMPK activation in high-fat fed mice. Phytomedicine 23(2):181-90

[16] Zhang C, Gao L, Zhang Y, Jin X, Wang M, et al. 2024. Corosolic acid inhibits EMT in lung cancer cells by promoting YAP-mediated ferroptosis. Phytomedicine 135:156110

[17] Peng Y, Li N, Tang F, Qian C, Jia T, et al. 2022. Corosolic acid sensitizes ferroptosis by upregulating HERPUD 1 in liver cancer cells. Cell Death Discovery 8( 1):376

[18] Lee MS, Cha EY, Thuong PT, Kim JY, Ahn MS, et al. 2010. Down-Regulation of human epidermal growth factor receptor 2/neu oncogene by corosolic acid induces cell cycle arrest and apoptosis in NCI-N87 human gastric cancer cells. Biological & Pharmaceutical Bulletin 33( 6):931-37

[19] Tang F, Peng Y, Liu J, Gao W, Xu Y. 2023. Integrating network pharmacology and experimental models to examine the mechanisms of corosolic acid in preventing hepatocellular carcinoma progression through activation PERK-elF2a-ATF 4 signaling. Naunyn-Schmiedeberg's Archives of Pharmacology 396( 12):3671-82

[20] Wu TK, Hung TW, Chen YS, Pan YR, Hsieh YH, et al. 2024. Corosolic acid inhibits metastatic response of human renal cell carcinoma cells by modulating ERK/MMP2 signaling. Environmental Toxicology 39(2):857-68

[21] Pundalik S, Hanumappa KR, Giresha AS, Urs D, Rajashekarappa S, et al. 2022. Corosolic acid inhibits secretory phospholipase A₂ lla as an AntiInflammatory function and exhibits anti-tumor activity in ehrlich ascites carcinoma bearing mice. Journal of Inflammation Research 15:6905-21

[22] Aguirre MC, Delporte C, Backhouse N, Erazo S, Letelier ME, et al. 2006. Topical anti-inflammatory activity of 2α-hydroxy pentacyclic triterpene acids from the leaves of Ugni molinae. Bioorganic & Medicinal Chemistry 14( 16):5673-77

[23] Garo E, Eldridge GR, Goering MG, DeLancey Pulcini E, Hamilton MA, et al. 2007. Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin. Antimicrobial Agents and Chemotherapy 51( 5):1813-17

[24] Zhou Y, Lv X, Chen M, Guo Y, Ding R, et al. 2020. Characterization of corosolic acid as a KPC-2 inhibitor that increases the susceptibility of KPC-2-positive bacteria to carbapenems. Frontiers in Pharmacology 11:1047

[25] Romsuk J, Srisawat P, Robertlee J, Yasumoto S, Miura K, et al. 2024. Heterologous production of corosolic acid, a phyto-insulin, in agroinfiltrated Nicotiana benthamiana leaves. Plant Biotechnology 41(3):277-88

[26] Furtado NJC, Pirson L, Edelberg H, Miranda LM, Loira-Pastoriza C, et al. 2017. Pentacyclic triterpene bioavailability: an overview of in vitro and in vivo studies. Molecules 22(3):400

[27] Spivak AY, Kuzmina US, Nedopekina DA, Dubinin MV, Khalitova RR, et al. 2024. Synthesis and comparative analysis of the cytotoxicity and mitochondrial effects of triphenylphosphonium and F16 maslinic and corosolic acid hybrid derivatives. Steroids 209:109471

[28] Feng X, Lu YH, Liu Z, Li DP, Zou YX, et al. 2017. Microbial transformation of the anti-diabetic agent corosolic acid by Cunninghamella echinulata. Journal of Asian Natural Products Research 19(7):645-50

[29] Li X, Widjaya AS, Liu J, Liu X, Long Z, et al. 2020. Cell-penetrating corosolic acid liposome as a functional carrier for delivering chemotherapeutic drugs. Acta Biomaterialia 106:301-13

[30] Li H, Tan X, Qin L, Gatasheh MK, Zhang L, et al. 2024. Preparation, process optimisation, stability and bacteriostatic assessment of composite nanoemulsion containing corosolic acid. Heliyon 10(19):e38283

[31] Zhao J, Zhou H, An Y, Shen K, Yu L. 2021. Biological effects of corosolic acid as an anti-inflammatory, anti-metabolic syndrome and antineoplasic natural compound. Oncology Letters 21(2):84

[32] Sivakumar G, Vail DR, Nair V, Medina Bolivar F, Lay JO. 2009. Plantbased corosolic acid: Future anti-diabetic drug? Biotechnology Journal 4(12):1704-11

[33] Rangel-Galván M, Pacheco-Hernández Y, Lozoya-Gloria E, Villa-Ruano N. 2024. Dietary natural products as inhibitors of α-amylase and α glucosidase: an updated review of ligand-receptor correlations validated by docking studies. Food Bioscience 62:105456

[34] Khalid H, Butt MH, Ur Rehman Aziz A, Ahmad I, Iqbal F, et al. 2024. Phytobioinformatics screening of ayurvedic plants for potential α glucosidase inhibitors in diabetes management. Current Plant Biology 40:100404

[35] Aydin S, Tekinalp SG, Tuzcu B, Cam F, Sevik MO, et al. 2025. The role of AMP-activated protein kinase activators on energy balance and cellular metabolism in type 2 diabetes mellitus. Obesity Medicine 53:100577

[36] Kwon EB, Kang MJ, Ryu HW, Lee S, Lee JW, et al. 2020. Acacetin enhances glucose uptake through insulin-independent GLUT4 translocation in L6 myotubes. Phytomedicine 68:153178

[37] XuS,Yu W, Zhang X, Wang W, Wang X. 2022. The regulatory role of Gnao 1 protein in diabetic encephalopathy in KK-Ay mice and strepto-zotocin-induced diabetic rats. Brain Research 1792:148012

[38] Miura T, Ueda N, Yamada K, Fukushima M, Ishida T, et al. 2006. Antidiabetic effects of corosolic acid in KK-Ay diabetic mice. Biological & Pharmaceutical Bulletin 29( 3):585-87

[39] Hibi M, Matsui Y, Niwa S, Oishi S, Yanagimoto A, et al. 2022. Corosolic acid improves glucose and insulin responses in middle-aged men with impaired fasting glucose: A randomized, double-blinded, placebocontrolled crossover trial. Journal of Functional Foods 97:105256

[40] Zhang W, Men X, Lei P. 2014. Review on anti-tumor effect of triterpene acid compounds. Journal of Cancer Research and Therapeutics 10:14-19

[41] Bahadori MB, Vandghanooni S, Dinparast L, Eskandani M, Ayatollahi SA, et al. 2019. Triterpenoid corosolic acid attenuates HIF-1 stabilization upon cobalt (II) chloride-induced hypoxia in A549 human lung epithelial cancer cells. Fitoterapia 134:493-500

[42] Woo SM, Seo SU, Min KJ, Im SS, Nam JO, et al. 2018. Corosolic acid induces Non-Apoptotic cell death through generation of lipid reactive oxygen species production in human renal carcinoma caki cells. International Journal of Molecular Sciences 19( 5):1309

[43] Tu S, Zou Y, Yang M, Zhou X, Zheng X, et al. 2025. Ferroptosis in hepatocellular carcinoma: mechanisms and therapeutic implications. Biomedicine & Pharmacotherapy 182:117769

[44] Li B, Li Y, Wang Q, Li F, Li F. 2019. Corosolic acid impairs human lung adenocarcinoma A549 cells proliferation by inhibiting cell migration. Oncology Letters 17( 6):5747-53

[45] Ku CY, Wang YR, Lin HY, Lu SC, Lin JY. 2015. Corosolic acid inhibits hepatocellular carcinoma cell migration by targeting the VEGFR2/ Src/FAK pathway. PLoS One 10(5):e126725

[46] Zhang C, Niu Y, Wang Z, Xu X, Li Y, et al. 2021. Corosolic acid inhibits cancer progression by decreasing the level of CDK19-mediated OGIcNAcylation in liver cancer cells. Cell Death & Disease 12( 10):811-89

[47] Park JB, Lee JS, Lee MS, Cha EY, Kim S, et al. 2018. Corosolic acid reduces 5-FU chemoresistance in human gastric cancer cells by activating AMPK. Molecular Medicine Reports 18( 3):2880-88

[48] Chen J, Kang J, Yuan S, O Connell P, Zhang Z, et al. 2024. Exploring the mechanisms of traditional chinese herbal therapy in gastric cancer: A comprehensive network pharmacology study of the Tiao-Yuan-TongWei decoction. Pharmaceuticals 17(4):414

[49] Kim JH, Kim YH, Song GY, Kim DE, Jeong YJ, et al. 2014. Ursolic acid and its natural derivative corosolic acid suppress the proliferation of APCmutated colon cancer cells through promotion of β-catenin degradation. Food and Chemical Toxicology 67:87-95

[50] Han S, Lim SL, Kim H, Choi H, Lee MY, et al. 2024. Ethyl acetate fraction of Osmanthus fragrans var. Aurantiacus and its triterpenoids suppress proliferation and survival of colorectal cancer cells by inhibiting NF- κB and COX2. Journal of Ethnopharmacology 319:117362

[51] Yoo KH, Park JH, Lee DY, Hwang-Bo J, Baek NI, et al. 2015. Corosolic acid exhibits anti-angiogenic and anti-lymphangiogenic effects on in vitro endothelial cells and on an in vivo CT-26 colon carcinoma animal model. Phytotherapy Research 29(5):714-23

[52] Luo X, Ye Z, Xu C, Chen H, Dai S, et al. 2024. Corosolic acid enhances oxidative stress-induced apoptosis and senescence in pancreatic cancer cells by inhibiting the JAK2/STAT3 pathway. Molecular Biology Reports 51( 1):176

[53] Jasim SA, Khalaf OZ, Alshahrani SH, Hachem K, Ziyadullaev S, et al. 2023. An in vitro investigation of the apoptosis-inducing activity of corosolic acid in breast cancer cells. Iranian Journal of Basic Medical Sciences 26(4):453-60

[54] Cui A, Li X, Ma X, Song Z, Wang X, et al. 2023. Quantitative transcriptomic and proteomic analysis reveals corosolic acid inhibiting bladder cancer via suppressing cell cycle and inducing mitophagy in vitro and in vivo. Toxicology and Applied Pharmacology 480:116749

[55] Fujiwara Y, Takaishi K, Nakao J, Ikeda T, Katabuchi H, et al. 2013. Corosolic acid enhances the antitumor effects of chemotherapy on epithelial ovarian cancer by inhibiting signal transducer and activator of transcription 3 signaling. Oncology Letters 6(6):1619-23

[56] Chen JL, Lai CY, Ying TH, Lin CW, Wang PH, et al. 2021. Modulating the ERK1/2-MMP1 axis through corosolic acid inhibits metastasis of human oral squamous cell carcinoma cells. International Journal of Molecular Sciences 22(16):8641

[57] Cai X, Zhang H, Tong D, Tan Z, Han D, et al. 2011. Corosolic acid triggers mitochondria and caspase-dependent apoptotic cell death in osteosarcoma MG-63 cells. Phytotherapy Research 25(9):1354-61

[58] Tang FF, Liu L, Tian XT, Li N, Peng YX, et al. 2023. Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression. BMC Complementary Medicine and Therapies 23:171

[59] Lee MS, Lee CM, Cha EY, Thuong PT, Bae K, et al. 2010. Activation of AMP-activated protein kinase on human gastric cancer cells by apoptosis induced by corosolic acid isolated from Weigela subsessilis. Phytotherapy Research 24(12):1857-61

[60] Lee HS, Park JB, Lee MS, Cha EY, Kim JY, et al. 2015. Corosolic acid enhances 5 -fluorouracil-induced apoptosis against SNU-620 human gastric carcinoma cells by inhibition of mammalian target of rapamycin. Molecular Medicine Reports 12( 3):4782-88

[61] Chan EWC, Soon CY, Tan JBL, Wong SK, Hui YW. 2019. Ursolic acid: an overview on its cytotoxic activities against breast and colorectal cancer cells. Journal of Integrative Medicine 17( 3):155-60

[62] Hudlikar RR, Sargsyan D, Wu R, Su S, Zheng M, et al. 2020. Triterpenoid corosolic acid modulates global CpG methylation and transcriptome of tumor promotor TPA induced mouse epidermal JB6 P+ cells. Chemico-Biological Interactions 321:109025

[63] Ooi KX, Poo CL, Subramaniam M, Cordell GA, Lim YM. 2023. Maslinic acid exerts anticancer effects by targeting cancer hallmarks. Phytomedicine 110:154631

[64] Xu YQ, Zhang JH, Yang XS. 2016. Corosolic acid induces potent anticancer effects in CaSki cervical cancer cells through the induction of apoptosis, cell cycle arrest and PI3K/Akt signalling pathway. Bangladesh Journal of Pharmacology 11( 2):453

[65] Li XQ, Tian W, Liu XX, Zhang K, Huo JC, et al. 2016. Corosolic acid inhibits the proliferation of glomerular mesangial cells and protects against diabetic renal damage. Scientific Reports 6:26854

[66] Zhang J, Zhao Y, Yan L, Tan M, Jin Y, et al. 2024. Corosolic acid attenuates cardiac ischemia/reperfusion injury through the PHB2/PINK1/parkin/mitophagy pathway. iScience 27(8):110448

[67] Alkholifi FK, Devi S, Yusufoglu HS, Alam A. 2023. The cardioprotective effect of corosolic acid in the diabetic rats: A possible mechanism of the PPAR- γ pathway. Molecules 28(3):929

[68] Wang ZP, Che Y, Zhou H, Meng YY, Wu HM, et al. 2020. Corosolic acid attenuates cardiac fibrosis following myocardial infarction in mice. International Journal of Molecular Medicine 45( 5):1425-35

[69] Che Y, Wang Z, Yuan Y, Zhou H, Wu H, et al. 2022. By restoring autophagic flux and improving mitochondrial function, corosolic acid protects against Dox-induced cardiotoxicity. Cell Biology and Toxicology 38( 3):451-67

[70] Luna-Vázquez FJ, Ibarra-Alvarado C, Del Rayo Camacho-Corona M, Rojas-Molina A, Rojas-Molina JI, et al. 2018. Vasodilator activity of compounds isolated from plants used in mexican traditional medicine. Molecules 23(6):1474

[71] Yamamura A, Fujiwara M, Kawade A, Amano T, Hossain A, et al. 2024. Corosolic acid attenuates platelet-derived growth factor signaling in macrophages and smooth muscle cells of pulmonary arterial hypertension. European Journal of Pharmacology 973:176564

[72] Sun Q, He M, Zhang M, Zeng S, Chen L, et al. 2020. Ursolic acid: A systematic review of its pharmacology, toxicity and rethink on its pharmacokinetics based on PK-PD model. Fitoterapia 147:104735

[73] Han H, Chen M, Li Z, Zhou S, Wu Y, et al. 2022. Corosolic acid protects rat chondrocytes against IL-1 β-Induced ECM degradation by activating autophagy via PI3K/AKT/mTOR pathway and ameliorates rat osteoarthritis. Drug Design, Development and Therapy 16:2627-37

[74] Peng M, Qiang L, Xu Y, Li C, Li T, et al. 2019. Inhibition of JNK and activation of the AMPK-Nrf2 axis by corosolic acid suppress osteolysis and oxidative stress. Nitric Oxide 82:12-24

[75] Hong G, Zhou L, Han X, Sun P, Chen Z, et al. 2020. Asiatic acid inhibits OVX-induced osteoporosis and osteoclastogenesis via regulating RANKL-mediated NF- κb and Nfatc1 signaling pathways. Frontiers in Pharmacology 11:331

[76] Shen H, Wang J, Ao J, Ye L, Shi Y, et al. 2023. The inhibitory mechanism of pentacyclic triterpenoid acids on pancreatic lipase and cholesterol esterase. Food Bioscience 51:102341

[77] Yamaguchi Y, Yamada K, Yoshikawa N, Nakamura K, Haginaka J, et al. 2006. Corosolic acid prevents oxidative stress, inflammation and hypertension in SHR/NDmcr-cp rats, a model of metabolic syndrome. Life Sciences 79(26):2474-79

[78] Zong W, Zhao G. 2007. Corosolic acid isolation from the leaves of Eriobotrta ja- ponica showing the effects on carbohydrate metabolism and differentiation of 3T3-L1 adipocytes. Asia Pacific Journal of Clinical Nutrition 6(Suppl1):346-52

[79] Guo X, Cui R, Zhao J, Mo R, Peng L, et al. 2016. Corosolic acid protects hepatocytes against ethanol-induced damage by modulating mito-gen-activated protein kinases and activating autophagy. European Journal of Pharmacology 791:578-88

[80] Fontanay S, Grare M, Mayer J, Finance C, Duval RE. 2008. Ursolic, oleanolic and betulinic acids: antibacterial spectra and selectivity indexes. Journal of Ethnopharmacology 120( 2):272-76

[81] Sycz Z, Tichaczek-Goska D, Wojnicz D. 2022. Anti-planktonic and antibiofilm properties of pentacyclic triterpenes-asiatic acid and ursolic acid as promising antibacterial future pharmaceuticals. Biomolecules 12(1):98

[82] Yum SJ, Kim SM, Yu YC, Jeong HG. 2017. Inhibition of growth and biofilm formation of Staphylococcus aureus by corosolic acid. Korean Society of Food Science and Technology 49(2):146-50

[83] Sinelius S, Lady J, Yunardy M, Tjoa E, Nurcahyanti ADR. 2023. Antibacterial activity of Lagerstreomia speciosa and its active compound, corosolic acid, enhances cefotaxime inhibitory activity against Staphylococcus aureus. Journal of Applied Microbiology 134( 8):d171

[84] Kurek A, Grudniak AM, Szwed M, Klicka A, Samluk L, et al. 2010. Oleanolic acid and ursolic acid affect peptidoglycan metabolism in Listeria monocytogenes. Antonie van Leeuwenhoek 97( 1):61-68

[85] Kim J, Park S, Shin YK, Kang H, Kim KY. 2018. In vitro antibacterial activity of macelignan and corosolic acid against the bacterial bee pathogens Paenibacillus larvae and Melissococcus plutonius. Acta Veterinaria Brno 87( 3):277-84

[86] Shin YK, Kim KY. 2016. Macelignan inhibits bee pathogenic fungi Ascophaera apis growth through HOG1 pathway. Brazilian Journal of Medical and Biological Research [Revista Brasileira de Pesquisas Medicas e Biologicas] 49( 7):e5313

[87] Zhao WB, Zhao ZM, Ma Y, Li AP, Zhang ZJ, et al. 2022. Antifungal activity and preliminary mechanism of pristimerin against Sclerotinia sclerotiorum. Industrial Crops and Products 185:115124

[88] Zhao HY, Zhu HY, Tang Q, Lin Q, Hao YK, et al. 2024. Anti-inflammatory and antiviral activities of compounds from the fruit of Pouteria caimito. Cogent Food & Agriculture 10:1

[89] Zhou JF, Zhang MR, Wang Q, Li MZ, Bai JS, et al. 2024. Two novel compounds inhibit Flavivirus infection in vitro and in vivo by targeting lipid metabolism. Journal of Virology 98( 9):e0063524

[90] Yang YH, Dai SY, Deng FH, Peng LH, Li C, et al. 2022. Recent advances in medicinal chemistry of oleanolic acid derivatives. Phytochemistry 203:113397

[91] Chen L, Gong J, Yong X, Li Y, Wang S. 2024. A review of typical biological activities of glycyrrhetinic acid and its derivatives. RSC Advances 14(1):6557-97

[92] Farina C, Pinza M, Pifferi G. 1998. Synthesis and anti-ulcer activity of new derivatives of glycyrrhetic, oleanolic and ursolic acids. II Farmaco 53(1):22-32

[93] Yan R, Liu L, Huang X, Quan ZS, Shen QK, et al. 2024. Bioactivities and structure-activity relationships of maslinic acid derivatives: a review. Chemistry & Biodiversity 21( 2):e202301327

[94] Hussain H, Ali I, Wang D, Hakkim FL, Westermann B, et al. 2021. Glycyrrhetinic acid: a promising scaffold for the discovery of anticancer agents. Expert Opinion on Drug Discovery 16( 12):1497-516

[95] Lv J, Sharma A, Zhang T, Wu Y, Ding X. 2018. Pharmacological review on asiatic acid and its derivatives: A potential compound. SLAS Technology 23(2):111-27

[96] Zhao ZX, Zou QY, Ma YH, Morris-Natschke SL, Li XY, et a. 2025. Recent progress on triterpenoid derivatives and their anticancer potential. Phytochemistry 229:114257

[97] Yang H, Deng M, Jia H, Zhang K, Liu Y, et al. 2024. A review of structural modification and biological activities of oleanolic acid. Chinese Journal of Natural Medicines 22( 1):15-30

[98] Huang J, Zang X, Yang W, Yin X, Huang J, et al. 2021. Pentacyclic triterpene carboxylic acids derivatives integrated piperazine-amino acid complexes for α-glucosidase inhibition in vitro. Bioorganic Chemistry 115:105212

[99] Liu X, Zang X, Yin X, Yang W, Huang J, et al. 2020. Semi-synthesis of C28-modified triterpene acid derivatives from maslinic acid or corosolic acid as potential α-glucosidase inhibitors. Bioorganic Chemistry 97:103694

[100] Heise NV, Csuk R, Mueller T. 2024. (Iso)quinoline amides derived from corosolic acid exhibit high cytotoxicity, and the potential for overcoming drug resistance in human cancer cells. European Journal of Medicinal Chemistry Reports 12:100198

[101] Xu J, Nie X, Hong Y, Jiang Y, Wu G, et al. 2016. Synthesis of water soluble glycosides of pentacyclic dihydroxytriterpene carboxylic acids as inhibitors of α-glucosidase. Carbohydrate Research 424:42-53

[102] Kumari H, Ganjoo A, Shafeeq H, Ayoub N, Babu V, et al. 2024. Microbial transformation of some phytochemicals into value-added products: A review. Fitoterapia 178:106149

[103] Abdel Bar FM, Elekhnawy E, Salkini AA, Soliman AF. 2024. Enhancement of antibacterial and antibiofilm properties of proximadiol through microbial transformation by Rhizopus oryzae. South African Journal of Botany 172:236-41

[104] Li DP, Feng X, Chu ZY, Guo FF, Zhang ZS. 2013. Microbial transformation of corosolic acid by Fusarium equiseti and Gliocladium catenulatum. Journal of Asian Natural Products Research 15(7):789-808

[105] Xu SH, Zhang C, Wang WW, Yu BY, Zhang J.2017. Site-selective biotransformation of ursane triterpenes by Streptomyces griseus ATCC 13273. RSC Advances 7(34):20754-59

[106] Kumar P, Bhadauria AS, Singh AK, Saha S. 2018. Betulinic acid as apoptosis activator: Molecular mechanisms, mathematical modeling and chemical modifications. Life Sciences 209:24-33

[107] Cui N, Li MJ, Wang YW, Meng Q, Shi YJ, et al. 2024. Boswellic acids: a review on its pharmacological properties, molecular mechanism and bioavailability. Traditional Medicine Research 9( 10):60

[108] Fernandes S, Vieira M, Prudêncio C, Ferraz R. 2024. Betulinic acid for glioblastoma treatment: Reality, challenges and perspectives. International Journal of Molecular Sciences 25( 4):2108

[109] Rehman Sheikh A, Wu-Chen RA, Matloob A, Mahmood MH, Javed M. 2024. Nanoencapsulation of volatile plant essential oils: a paradigm shift in food industry practices. Food Innovation and Advances 3( 3):305-19

[110] Malík M, Velechovský J, Tlustoš P. 2021. Natural pentacyclic triterpenoid acids potentially useful as biocompatible nanocarriers. Fitoterapia 151:104845

[111] Bildziukevich U, Özdemir Z, Wimmer Z. 2019. Recent achievements in medicinal and supramolecular chemistry of betulinic acid and its derivatives. Molecules 24(19):3546

[112] Bag BG, Garai C, Ghorai S. 2019. Vesicular self-assembly of a natural ursane-type dihydroxy-triterpenoid corosolic acid. RSC Advances 9(27):15190-95

[113] Bao H, Sun W, Sun H, Jin Y, Gong X, et al. 2022. Liquid chromatographic study of two structural isomeric pentacyclic triterpenes on reversed-phase stationary phase with hydroxypropyl- β-cyclodextrin as mobile phase additive. Journal of Pharmaceutical and Biomedical Analysis 207:114420

[114] Liu S, Liu Y, Li Q, Song Y, Zhang L, et al. 2024. Oleanolic acid nanoparti-cles-stabilized W/O pickering emulsions: fabrication, characterization, and delivery application. Food Chemistry 444:138598

[115] Liu Y, Xia H, Guo S, Lu X, Zeng C. 2022. Development and characterization of a novel naturally occurring pentacyclic triterpene self-stabilized pickering emulsion. Colloids and Surfaces A: Physicochemical and Engineering Aspects 634:127908

[116] Liu Y, Zhang R, Yang Y, Liu X, Jiang Y. 2025. Corosolic acid derivativebased lipid nanoparticles for efficient RNA delivery. Journal of Controlled Release 378:1-17

[117] Widjaya AS, Liu Y, Yang Y, Yin W, Liang J, et al. 2022. Tumor-permeable smart liposomes by modulating the tumor microenvironment to improve the chemotherapy. Journal of Controlled Release 344:62-79