Table Info

Table 1.

The body weights and clinical observations of treated KM mice and SD rats were recorded for a period of 7 days

Groups			Body weight (g)				Death/treated individuals	Mortality latency	Clinical signs
Groups			Day 1	Day 2	Day 3	Day 4	Death/treated individuals	Mortality latency	Clinical signs
KM mice	Control	Male	16.20 ± 1.25	16.64 ± 1.13	17.14 ± 1.16	17.64 ± 1.06	0/5	None	None
	Control	Female	18.42 ± 1.75	18.90 ± 1.74	19.40 ± 1.64	19.92 ± 1.61	0/5	None	None
	160 mg/kg	Male	15.62 ± 1.15	16.16 ± 1.16	16.60 ± 1.11	17.24 ± 1.09	0/5	None	None
	160 mg/kg	Female	18.38 ± 0.84	18.08 ± 0.81	19.32 ± 0.87	19.86 ± 0.9	0/5	None	None
SD rats	Control	Male	107.06 ± 2.36	116.70 ± 2.02	126.14 ± 2.61	134.20 ± 2.53	0/5	None	None
	Control	Female	114.34 ± 2.08	123.68 ± 2.32	133.74 ± 2.08	141.84 ± 3.27	0/5	None	None
	160 mg/kg	Male	106.84 ± 0.91	116.44 ±1.66	127.18 ± 2.41	135.02 ± 1.05	0/5	None	None
	160 mg/kg	Female	116.20 ± 2.54	125.44 ± 3.24	134.80 ± 3.50	143.94 ± 2.30	0/5	None	None

Values are expressed as mean ± standard deviation, n = 5. The Dunnett t-test was used to determine the significance of data variability between the treated and control groups. Statistical significance was considered at ^*P < 0.05

Declarations

Author contributions

KY and KG equally contributed to: Conceptualization, Methodology, Validation, Investigation, Writing—original draft, Writing—review & editing. FG and CX: Methodology, Software, Validation, Formal analysis, Data curation. JC: Supervision, Project administration, Funding acquisition. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The research protocol received approval from the Ethics Committee of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (20220421).

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

This work was supported by the Midstream Research Programme for Universities from the Innovation and Technology Commission of Hong Kong [MRP/027/18X]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Xie YJ, Wang QL, Adu-Frimpong M, Liu J, Zhang KY, Xu XM, et al. Preparation and evaluation of isoliquiritigenin-loaded F127/P123 polymeric micelles. Drug Dev Ind Pharm. 2019;45:1224–32. [DOI] [PubMed]

Peng F, Xiong L, Xie X, Tang H, Huang R, Peng C. Isoliquiritigenin derivative regulates miR-374a/BAX axis to suppress triple-negative breast cancer tumorigenesis and development. Front Pharmacol. 2020;11:378. [DOI] [PubMed] [PMC]

He J, Deng Y, Ren L, Jin Z, Yang J, Yao F, et al. Isoliquiritigenin from licorice flavonoids attenuates NLRP3-mediated pyroptosis by SIRT6 in vascular endothelial cells. J Ethnopharmacol. 2023;303:115952. [DOI] [PubMed]

Liu N, Liu M, Jiang M, Li Z, Chen W, Wang W, et al. Isoliquiritigenin alleviates the development of alcoholic liver fibrosis by inhibiting ANXA2. Biomed Pharmacother. 2023;159:114173. [DOI] [PubMed]

Bai Y, Zhou J, Zhu H, Tao Y, Wang L, Yang L, et al. Isoliquiritigenin inhibits microglia-mediated neuroinflammation in models of Parkinson’s disease via JNK/AKT/NFκB signaling pathway. Phytother Res. 2023;37:848–59. [DOI] [PubMed]

Zhang Z, Yung KK, Ko JK. Therapeutic intervention in cancer by isoliquiritigenin from licorice: a natural antioxidant and redox regulator. Antioxidants (Basel). 2022;11:1349. [DOI] [PubMed] [PMC]

Wang KL, Yu YC, Hsia SM. Perspectives on the role of isoliquiritigenin in cancer. Cancers (Basel). 2021;13:115. [DOI] [PubMed] [PMC]

Zhang Z, Chen WQ, Zhang SQ, Bai JX, Liu B, Yung KK, et al. Isoliquiritigenin inhibits pancreatic cancer progression through blockade of p38 MAPK-regulated autophagy. Phytomedicine. 2022;106:154406. [DOI] [PubMed]

hen C, Huang S, Chen CL, Su SB, Fang DD. Isoliquiritigenin inhibits ovarian cancer metastasis by reversing epithelial-to-mesenchymal transition. Molecules. 2019;24:3725. [DOI] [PubMed] [PMC]

10.

Lee CH, Tsai HY, Chen CL, Chen JL, Lu CC, Fang YP, et al. Isoliquiritigenin inhibits gastric cancer stemness, modulates tumor microenvironment, and suppresses tumor growth through glucose-regulated protein 78 downregulation. Biomedicines. 2022;10:1350. [DOI] [PubMed] [PMC]

11.

Qiao F, Zhao Y, Mai Y, Guo J, Dong L, Zhang W, et al. Isoliquiritigenin nanosuspension enhances cytostatic effects in A549 lung cancer cells. Planta Med. 2020;86:538–47. [DOI] [PubMed]

12.

Wang Y, Zhang C, Xiao M, Ganesan K, Gao F, Liu Q, et al. A tumor-targeted delivery of oral isoliquiritigenin through encapsulated zein phosphatidylcholine hybrid nanoparticles prevents triple-negative breast cancer. J Drug Deliv Sci Technol. 2023;79:103922. [DOI]

13.

Zhang XY, Qiao H, Ni JM, Shi YB, Qiang Y. Preparation of isoliquiritigenin-loaded nanostructured lipid carrier and the in vivo evaluation in tumor-bearing mice. Eur J Pharm Sci. 2013;49:411–22. [DOI] [PubMed]

14.

Shi W, Cao X, Liu Q, Zhu Q, Liu K, Deng T, et al. Hybrid membrane-derived nanoparticles for isoliquiritin enhanced glioma therapy. Pharmaceuticals (Basel). 2022;15:1059. [DOI] [PubMed] [PMC]

15.

Cao M, Wang Y, Jing H, Wang Z, Meng Y, Geng Y, et al. Development of an oral isoliquiritigenin self-nano-emulsifying drug delivery system (ILQ-SNEDDS) for effective treatment of eosinophilic esophagitis induced by food allergy. Pharmaceuticals (Basel). 2022;15:1587. [DOI] [PubMed] [PMC]

16.

Xiao M, Wu S, Cheng Y, Ma J, Luo X, Chang L, et al. Colon-specific delivery of isoliquiritigenin by oral edible zein/caseate nanocomplex for ulcerative colitis treatment. Front Chem. 2022;10:981055. [DOI] [PubMed] [PMC]

17.

Zhang K, Wang Q, Yang Q, Wei Q, Man N, Adu-Frimpong M, et al. Enhancement of oral bioavailability and anti-hyperuricemic activity of isoliquiritigenin via self-microemulsifying drug delivery system. AAPS PharmSciTech. 2019;20:218. [DOI] [PubMed]

18.

Moustafa MA, El-Refaie WM, Elnaggar YSR, El-Mezayen NS, Awaad AK, Abdallah OY. Fucoidan/hyaluronic acid cross-linked zein nanoparticles loaded with fisetin as a novel targeted nanotherapy for oral cancer. Int J Biol Macromol. 2023;241:124528. [DOI] [PubMed]

19.

Yu X, Wu H, Hu H, Dong Z, Dang Y, Qi Q, et al. Zein nanoparticles as nontoxic delivery system for maytansine in the treatment of non-small cell lung cancer. Drug Deliv. 2020;27:100–9. [DOI] [PubMed] [PMC]

20.

Lee HS, Kang NW, Kim H, Kim DH, Chae JW, Lee W, et al. Chondroitin sulfate-hybridized zein nanoparticles for tumor-targeted delivery of docetaxel. Carbohydr Polym. 2021;253:117187. [DOI] [PubMed]

21.

Sun L, Yang Z, Zhang J, Wang J. Isoliquiritigenin attenuates acute renal injury through suppressing oxidative stress, fibrosis and JAK2/STAT3 pathway in streptozotocin-induced diabetic rats. Bioengineered. 2021;12:11188–200. [DOI] [PubMed] [PMC]

22.

Liu C, Xu B, McClements DJ, Xu X, Cui S, Gao L, et al. Properties of curcumin-loaded zein-tea saponin nanoparticles prepared by antisolvent co-precipitation and precipitation. Food Chem. 2022;391:133224. [DOI] [PubMed]

23.

Brotons-Canto A, González-Navarro CJ, Gil AG, Asin-Prieto E, Saiz MJ, Llabrés JM. Zein nanoparticles improve the oral bioavailability of curcumin in Wistar rats. Pharmaceutics. 2021;13:361. [DOI] [PubMed] [PMC]

24.

Tsai YH, Yang YN, Ho YC, Tsai ML, Mi FL. Drug release and antioxidant/antibacterial activities of silymarin-zein nanoparticle/bacterial cellulose nanofiber composite films. Carbohydr Polym. 2018;180:286–96. [DOI] [PubMed]

25.

Liu Q, Qin Y, Jiang B, Chen J, Zhang T. Development of self-assembled zein-fucoidan complex nanoparticles as a delivery system for resveratrol. Colloids Surf B Biointerfaces. 2022;216:112529. [DOI] [PubMed]

26.

Zhang Q, Li D, Guan S, Liu D, Wang J, Xing G, et al. Tumor-targeted delivery of honokiol via polysialic acid modified zein nanoparticles prevents breast cancer progression and metastasis. Int J Biol Macromol. 2022;203:280–91. [DOI] [PubMed]

27.

Liu L, Yang S, Chen F, Cheng KW. Polysaccharide-zein composite nanoparticles for enhancing cellular uptake and oral bioavailability of curcumin: characterization, anti-colorectal cancer effect, and pharmacokinetics. Front Nutr. 2022;9:846282. [DOI] [PubMed] [PMC]

28.

Zhang Q, Wang J, Liu D, Zhu W, Guan S, Fan L, et al. Targeted delivery of honokiol by zein/hyaluronic acid core-shell nanoparticles to suppress breast cancer growth and metastasis. Carbohydr Polym. 2020;240:116325. [DOI] [PubMed]

29.

van Ballegooie C, Wretham N, Ren T, Popescu IM, Yapp DT, Bally MB. PEG conjugated zein nanoparticles for in vivo use. Pharmaceutics. 2022;14:1831. [DOI] [PubMed] [PMC]

30.

Ganesan K, Wang Y, Gao F, Liu Q, Zhang C, Li P, et al. Targeting engineered nanoparticles for breast cancer therapy. Pharmaceutics. 2021;13:1829. [DOI] [PubMed] [PMC]

31.

Gagliardi A, Bonacci S, Paolino D, Celia C, Procopio A, Fresta M, et al. Paclitaxel-loaded sodium deoxycholate-stabilized zein nanoparticles: characterization and in vitro cytotoxicity. Heliyon. 2019;5:e02422. [DOI] [PubMed] [PMC]

32.

Kong B, Liu R, Guo J, Lu L, Zhou Q, Zhao Y. Tailoring micro/nano-fibers for biomedical applications. Bioact Mater. 2022;19:328–47. [DOI] [PubMed] [PMC]

33.

Ganesan K, Ramkumar KM, Xu B. Vitexin restores pancreatic β-cell function and insulin signaling through Nrf2 and NF-κB signaling pathways. Eur J Pharmacol. 2020;888:173606. [DOI] [PubMed]

34.

Zhu H, You J, Wen Y, Jia L, Gao F, Ganesan K, et al. Tumorigenic risk of Angelica sinensis on ER-positive breast cancer growth through ER-induced stemness in vitro and in vivo. J Ethnopharmacol. 2021;280:114415. [DOI] [PubMed]

35.

Zhang F, Ganesan K, Liu Q, Chen J. A review of the pharmacological potential of Spatholobus suberectus Dunn on cancer. Cells. 2022;11:2885. [DOI] [PubMed] [PMC]

36.

Gong G, Ganesan K, Xiong Q, Zheng Y. Antitumor effects of ononin by modulation of apoptosis in non-small-cell lung cancer through inhibiting PI3K/Akt/mTOR pathway. Oxid Med Cell Longev. 2022;2022:5122448. [DOI] [PubMed] [PMC]

37.

McAleer CW, Long CJ, Elbrecht D, Sasserath T, Bridges LR, Rumsey JW, et al. Multi-organ system for the evaluation of efficacy and off-target toxicity of anticancer therapeutics. Sci Transl Med. 2019;11:eaav1386. [DOI] [PubMed]

38.

Robinson K. Evaluations of organ system development in juvenile toxicology testing. Reprod Toxicol. 2008;26:51–3. [DOI] [PubMed]

39.

Yang Y, Qin Z, Zeng W, Yang T, Cao Y, Mei C, et al. Toxicity assessment of nanoparticles in various systems and organs. Nanotechnol Rev. 2017;6:279–89. [DOI]

40.

Kaufmann W, Jacobsen MC. Examination of organ toxicity. In: Reichl FX, Schwenk M, editors. Regulatory toxicology. Berlin: Springer Nature; 2014. pp. 89–98. [DOI]

41.

Ganesan K, Xu B. Telomerase inhibitors from natural products and their anticancer potential. Int J Mol Sci. 2018;19:13. [DOI] [PubMed] [PMC]

42.

Nagarajan S, Mohandas S, Ganesan K, Xu B, Ramkumar KM. New insights into dietary pterostilbene: sources, metabolism, and health promotion effects. Molecules. 2022;27:6316. [DOI] [PubMed] [PMC]

43.

Ganesan K, Xu B. Anti-obesity effects of medicinal and edible mushrooms. Molecules. 2018;23:2880. [DOI] [PubMed] [PMC]

44.

Al-Qahtani WH, Alshammari GM, Ajarem JS, Al-Zahrani AY, Alzuwaydi A, Eid R, et al. Isoliquiritigenin prevents doxorubicin-induced hepatic damage in rats by upregulating and activating SIRT1. Biomed Pharmacother. 2022;146:112594. [DOI] [PubMed]

45.

Han B, Zhang M, Tang T, Zheng Q, Wang K, Li L, et al. The long-term fate and toxicity of PEG-modified single-walled carbon nanotube isoliquiritigenin delivery vehicles in rats. J Nanomater. 2014;2014:257391. [DOI]

46.

Song Z, Zhang Y, Zhang H, Rajendran RS, Wang R, Hsiao CD, et al. Isoliquiritigenin triggers developmental toxicity and oxidative stress-mediated apoptosis in zebrafish embryos/larvae via Nrf2-HO1/JNK-ERK/mitochondrion pathway. Chemosphere. 2020;246:125727. [DOI] [PubMed]

47.

Ganesan K, Jayachandran M, Xu B. A critical review on hepatoprotective effects of bioactive food components. Crit Rev Food Sci Nutr. 2018;58:1165–229. [DOI] [PubMed]

48.

Ganesan K, Xu B. Molecular targets of vitexin and isovitexin in cancer therapy: a critical review. Ann N Y Acad Sci. 2017;1401:102–13. [DOI] [PubMed]

49.

Islam T, Ganesan K, Xu B. New insight into mycochemical profiles and antioxidant potential of edible and medicinal mushrooms: a review. Int J Med Mushrooms. 2019;21:237–51. [DOI] [PubMed]

50.

Jayasuriya R, Dhamodharan U, Ali D, Ganesan K, Xu B, Ramkumar KM. Targeting Nrf2/Keap1 signaling pathway by bioactive natural agents: possible therapeutic strategy to combat liver disease. Phytomedicine. 2021;92:153755. [DOI] [PubMed]

51.

Ganesan K, Sukalingam K, Xu B. Solanum trilobatum L. ameliorate thioacetamide-induced oxidative stress and hepatic damage in albino rats. Antioxidants (Basel). 2017;6:68. [DOI] [PubMed] [PMC]

52.

Jayachandran M, Wu Z, Ganesan K, Khalid S, Chung SM, Xu B. Isoquercetin upregulates antioxidant genes, suppresses inflammatory cytokines and regulates AMPK pathway in streptozotocin-induced diabetic rats. Chem Biol Interact. 2019;303:62–9. [DOI] [PubMed]

53.

Ganesan K, Xu B. A critical review on polyphenols and health benefits of black soybeans. Nutrients. 2017;9:455. [DOI] [PubMed] [PMC]

54.

Ganesan K, Xu B. Polyphenol-rich lentils and their health promoting effects. Int J Mol Sci. 2017;18:2390. [DOI] [PubMed] [PMC]