The Role and Mechanism of Hyperoside against Depression-like Behavior in Mice via the NLRP1 Inflammasome
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials and Chemicals
2.2. Animals
2.3. Drug Administration in SD Rats
2.4. Plasma Collection
2.5. UPLC-Q-TOF/MS Analysis
2.6. Network Pharmacology Data Preparation and Network Construction
2.7. Chronic Stress Process
2.8. Sucrose Preference Test (SPT)
2.9. Tail-Suspension Test (TST)
2.10. Forced Swim Test (FST)
2.11. RT-PCR
2.12. Statistical Analysis
3. Results
3.1. Screening Hyp from HP by UPLC-Q-TOF/MS
3.2. Network Pharmacology Analysis
3.3. Hyp, Isoquercetin, and Quercetin Are the Main Active Components of HP
3.4. The Intersections of HP Active Component Targets and Depression Targets Were Analyzed by Network Pharmacology
3.5. Hyp Ameliorates Depressive-Like Behaviors in Chronic-Stress-Induced Mice
3.6. Hyp Decreases NLRP1 Inflammasome Expression in CUMS-Treated Mice
3.7. Hyp Downregulated Expression of CXCL1/CXCR2 and Upregulated BDNF e = Expression in CUMS-Treated Mice
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Hao, Y.; Ge, H.; Sun, M.; Gao, M.S. Selecting an Appropriate Animal Model of Depression. Int. J. Mol. Sci. 2019, 20, 4827. [Google Scholar] [CrossRef] [Green Version]
- Beurel, E.; Toups, M.; Nemeroff, C.B. The Bidirectional Relationship of Depression and Inflammation: Double Trouble. Neuron 2020, 107, 234–256. [Google Scholar] [CrossRef] [PubMed]
- Oliva, V.; Lippi, M.; Paci, R.; Del Fabro, L.; Delvecchio, G.; Brambilla, P.; De Ronchi, D.; Fanelli, G.; Serretti, A. Gastrointestinal side effects associated with antidepressant treatments in patients with major depressive disorder: A systematic review and meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021, 109, 110266. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Long, Y.; Yu, S.; Li, D.; Yang, M.; Guan, Y.; Zhang, D.; Wan, J.; Liu, S.; Shi, A.; et al. Natural volatile oils derived from herbal medicines: A promising therapy way for treating depressive disorder. Pharmacol. Res. 2021, 164, 105376. [Google Scholar] [CrossRef]
- Isacchi, B.; Bergonzi, M.C.; Carnevali, F.; van der Esch, S.A.; Vincieri, F.F.; Bilia, A.R. Analysis and stability of the constituents of St. John’s wort oils prepared with different methods. J. Pharm. Biomed. Anal. 2007, 45, 756–761. [Google Scholar] [CrossRef] [PubMed]
- Nobakht, S.Z.; Akaberi, M.; Mohammadpour, A.H.; Tafazoli Moghadam, A.; Emami, S.A. Hypericum perforatum: Traditional uses, clinical trials, and drug interactions. Iran. J. Basic Med. Sci. 2022, 25, 1045–1058. [Google Scholar] [PubMed]
- Kong, F.X.; Guo, Z.K. Research Progress of Anti—Depression Application of St John’s Wort. In Proceedings of the 10th Academic Conference of Mental Diseases Professional Committee of the Chinese Association of Integrated Traditional and Western Medicine, Xiamen, China, 18 November 2010; pp. 139–146. [Google Scholar]
- Xu, S.; Chen, S.; Xia, W.; Sui, H.; Fu, X. Hyperoside: A Review of Its Structure, Synthesis, Pharmacology, Pharmacokinetics and Toxicity. Molecules 2022, 27, 3009. [Google Scholar] [CrossRef]
- Stojanović, N.M.; Radulović, N.S.; Randjelović, P.J.; Laketić, D. Antinociceptive Properties of St. John’s Wort (Hypericum perforatum) and Other Hypericum Species. Nat. Prod. Commun. 2016, 11, 1741–1747. [Google Scholar] [CrossRef] [Green Version]
- Wang, Q.; Wei, H.C.; Zhou, S.J.; Li, Y.; Zheng, T.T.; Zhou, C.Z.; Wan, X.H. Hyperoside: A review on its sources, biological activities, and molecular mechanisms. Phytother. Res. PTR 2022, 36, 2779–2802. [Google Scholar] [CrossRef]
- Li, Q.; Song, F.; Zhu, M.; Wang, Q.; Han, Y.; Ling, Y.; Qiao, L.; Zhong, N.; Zhang, L. Hyperoside: A review of pharmacological effects. F1000Research 2022, 11, 635. [Google Scholar] [CrossRef]
- Doi, K.; Leelahavanichkul, A.; Yuen, P.S.T.; Star, R.A. Animal models of sepsis and sepsis-induced kidney injury. J. Clin. Investig. 2009, 119, 2868–2878. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chunzhi, G.; Zunfeng, L.; Chengwei, Q.; Xiangmei, B.; Jingui, Y. Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways. Oncotarget 2016, 7, 82602–82608. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, K.; Lu, C.; Wang, T.; Qiao, C.; Lu, L.; Wu, D.; Lu, M.; Chen, R.; Fan, L.; Tang, J. Hyperoside suppresses NLRP3 inflammasome in Parkinson’s disease via Pituitary Adenylate Cyclase-Activating Polypeptide. Neurochem. Int. 2022, 152, 105254. [Google Scholar] [CrossRef] [PubMed]
- Orzelska-Gorka, J.; Szewczyk, K.; Gawronska-Grzywacz, M.; Kedzierska, E.; Glowacka, E.; Herbet, M.; Dudka, J.; Biala, G. Monoaminergic system is implicated in the antidepressant-like effect of hyperoside and protocatechuic acid isolated from Impatiens glandulifera Royle in mice. Neurochem. Int. 2019, 128, 206–214. [Google Scholar] [CrossRef] [PubMed]
- Gong, Y.; Yang, Y.; Chen, X.; Yang, M.; Huang, D.; Yang, R.; Zhou, L.; Li, C.; Xiong, Q.; Xiong, Z. Hyperoside protects against chronic mild stress-induced learning and memory deficits. Biomed. Pharmacother. = Biomed. Pharmacother. 2017, 91, 831–840. [Google Scholar] [CrossRef]
- Fan, H.H.; Zhu, L.B.; Li, T.; Zhu, H.; Wang, Y.N.; Ren, X.L.; Hu, B.L.; Huang, C.P.; Zhu, J.H.; Zhang, X. Hyperoside inhibits lipopolysaccharide-induced inflammatory responses in microglial cells via p38 and NFkappaB pathways. Int. Immunopharmacol. 2017, 50, 14–21. [Google Scholar] [CrossRef]
- Ahn, H.; Lee, G.S. Isorhamnetin and hyperoside derived from water dropwort inhibits inflammasome activation. Phytomed. Int. J. Phytother. Phytopharm. 2017, 24, 77–86. [Google Scholar] [CrossRef]
- Yang, Y.; Li, J.; Rao, T.; Fang, Z.; Zhang, J. The role and mechanism of hyperoside against myocardial infarction in mice by regulating autophagy via NLRP1 inflammation pathway. J. Ethnopharmacol. 2021, 276, 114187. [Google Scholar] [CrossRef]
- Cao, Z.; Wang, F.; Xiu, C.; Zhang, J.; Li, Y. Hypericum perforatum extract attenuates behavioral, biochemical, and neurochemical abnormalities in Aluminum chloride-induced Alzheimer’s disease rats. Biomed. Pharmacother. = Biomed. Pharmacother. 2017, 91, 931–937. [Google Scholar] [CrossRef]
- Antoniuk, S.; Bijata, M.; Ponimaskin, E.; Wlodarczyk, J. Chronic unpredictable mild stress for modeling depression in rodents: Meta-analysis of model reliability. Neurosci. Biobehav. Rev. 2019, 99, 101–116. [Google Scholar] [CrossRef]
- Song, A.Q.; Gao, B.; Fan, J.J.; Zhu, Y.J.; Zhou, J.; Wang, Y.L.; Xu, L.Z.; Wu, W.N. NLRP1 inflammasome contributes to chronic stress-induced depressive-like behaviors in mice. J. Neuroinflamm. 2020, 17, 178. [Google Scholar] [CrossRef] [PubMed]
- Liu, S.; Xu, S.; Wang, Z.; Guo, Y.; Pan, W.; Shen, Z. Anti-Depressant-Like Effect of Sinomenine on Chronic Unpredictable Mild Stress-Induced Depression in a Mouse Model. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2018, 24, 7646–7653. [Google Scholar] [CrossRef] [PubMed]
- Wang, M.; Yang, L.; Chen, Z.; Dai, L.; Xi, C.; Wu, X.; Wu, G.; Wang, Y.; Hu, J. Geniposide ameliorates chronic unpredictable mild stress induced depression-like behavior through inhibition of ceramide-PP2A signaling via the PI3K/Akt/GSK3beta axis. Psychopharmacology 2021, 238, 2789–2800. [Google Scholar] [CrossRef] [PubMed]
- Sun, J.; Wang, F.; Hu, X.; Yang, C.; Xu, H.; Yao, Y.; Liu, J. Clostridium butyricum Attenuates Chronic Unpredictable Mild Stress-Induced Depressive-Like Behavior in Mice via the Gut-Brain Axis. J. Agric. Food Chem. 2018, 66, 8415–8421. [Google Scholar] [CrossRef]
- Kong, X.; Liu, C.; Lu, P.; Guo, Y.; Zhao, C.; Yang, Y.; Bo, Z.; Wang, F.; Peng, Y.; Meng, J. Combination of UPLC-Q-TOF/MS and Network Pharmacology to Reveal the Mechanism of Qizhen Decoction in the Treatment of Colon Cancer. ACS Omega 2021, 6, 14341–14360. [Google Scholar] [CrossRef]
- Zhou, M.; Huo, J.; Wang, C.; Wang, W. UPLC/Q-TOF MS Screening and Identification of Antibacterial Compounds in Forsythia suspensa (Thunb.) Vahl Leaves. Front. Pharmacol. 2021, 12, 704260. [Google Scholar] [CrossRef]
- Ersoy, E.; Eroglu Ozkan, E.; Boga, M.; Yilmaz, M.A.; Mat, A. Anti-aging potential and anti-tyrosinase activity of three Hypericum species with focus on phytochemical composition by LC–MS/MS. Ind. Crops Prod. 2019, 141, 111735. [Google Scholar] [CrossRef]
- Pradeep, M.; Kachlicki, P.; Franklin, G. Simultaneous determination of naphtodianthrones, emodin, skyrin and new bisanthrones in Hypericum perforatum L. in vitro shoot cultures. Ind. Crops Prod. 2020, 144, 112003. [Google Scholar] [CrossRef]
- Tusevski, O.; Krstikj, M.; Stanoeva, J.P.; Stefova, M.; Gadzovska Simic, S. Phenolic profile and biological activity of Hypericum perforatum L.: Can roots be considered as a new source of natural compounds? S. Afr. J. Bot. 2018, 117, 301–310. [Google Scholar] [CrossRef]
- Novelli, M.; Masiello, P.; Beffy, P.; Menegazzi, M. Protective Role of St. John’s Wort and Its Components Hyperforin and Hypericin against Diabetes through Inhibition of Inflammatory Signaling: Evidence from In Vitro and In Vivo Studies. Int. J. Mol. Sci. 2020, 21, 8108. [Google Scholar] [CrossRef]
- Kovacik, J.; Dresler, S.; Peterkova, V.; Babula, P. Nitrogen nutrition modulates oxidative stress and metabolite production in Hypericum perforatum. Protoplasma 2020, 257, 439–447. [Google Scholar] [CrossRef] [PubMed]
- Menegazzi, M.; Masiello, P.; Novelli, M. Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics. Antioxidants 2020, 10, 18. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Shao, B.; Yu, H.; Xu, F.; Wang, P.; Yu, K.; Han, Y.; Song, M.; Li, Y.; Cao, Z. Neuroprotective role of hyperforin on aluminum maltolate-induced oxidative damage and apoptosis in PC12 cells and SH-SY5Y cells. Chem.-Biol. Interact. 2019, 299, 15–26. [Google Scholar] [CrossRef] [PubMed]
- Nawrot, J.; Gornowicz-Porowska, J.; Budzianowski, J.; Nowak, G.; Schroeder, G.; Kurczewska, J. Medicinal Herbs in the Relief of Neurological, Cardiovascular, and Respiratory Symptoms after COVID-19 Infection A Literature Review. Cells 2022, 11, 1897. [Google Scholar] [CrossRef] [PubMed]
- Knauthe, A.; Mittag, S.; Bloch, L.; Albring, K.F.; Schmidt, M.; Werz, O.; Huber, O. Hyperforin and Myrtucommulone Derivatives Act as Natural Modulators of Wnt/beta-Catenin Signaling in HCT116 Colon Cancer Cells. Int. J. Mol. Sci. 2022, 23, 2984. [Google Scholar] [CrossRef]
- Cristina de Brito Toscano, E.; Leandro Marciano Vieira, E.; Boni Rocha Dias, B.; Vidigal Caliari, M.; Paula Goncalves, A.; Varela Giannetti, A.; Mauricio Siqueira, J.; Kimie Suemoto, C.; Elaine Paraizo Leite, R.; Nitrini, R.; et al. NLRP3 and NLRP1 inflammasomes are up-regulated in patients with mesial temporal lobe epilepsy and may contribute to overexpression of caspase-1 and IL-beta in sclerotic hippocampi. Brain Res. 2021, 1752, 147230. [Google Scholar] [CrossRef] [PubMed]
- Arioz, B.I.; Tastan, B.; Tarakcioglu, E.; Tufekci, K.U.; Olcum, M.; Ersoy, N.; Bagriyanik, A.; Genc, K.; Genc, S. Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway. Front. Immunol. 2019, 10, 1511. [Google Scholar] [CrossRef]
- Jing, G.; Wang, H.; Nan, F.; Liu, Y.; Zhang, M. Naofucong Ameliorates High Glucose Induced Hippocampal Neuron Injury Through Suppressing P2X7/NLRP1/Caspase-1 Pathway. Front. Pharmacol. 2021, 12, 647116. [Google Scholar] [CrossRef]
- Zhu, Y.J.; Fan, J.J.; Wu, F.Y.; Zhang, M.; Song, A.Q.; Li, Y.; Li, Y.K.; Wu, W.N. Aging Promotes Chronic Stress-Induced Depressive-Like Behavior by Activating NLRP1 Inflammasome-Driven Inflammatory Signaling in Mice. Inflammation 2022, 45, 2172–2185. [Google Scholar] [CrossRef]
- Oliveira, A.I.; Pinho, C.; Sarmento, B.; Dias, A.C. Neuroprotective Activity of Hypericum perforatum and Its Major Components. Front. Plant Sci. 2016, 7, 1004. [Google Scholar] [CrossRef]
- Radulovic, N.S.; Gencic, M.S.; Stojanovic, N.M.; Randjelovic, P.J.; Baldovini, N.; Kurteva, V. Prenylated beta-diketones, two new additions to the family of biologically active Hypericum perforatum L. (Hypericaceae) secondary metabolites. Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc. 2018, 118, 505–513. [Google Scholar] [CrossRef] [PubMed]
- Tian, J.; Zhang, F.; Cheng, J.; Guo, S.; Liu, P.; Wang, H. Antidepressant-like activity of adhyperforin, a novel constituent of Hypericum perforatum L. Sci. Rep. 2014, 4, 5632. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wurglics, M.; Schubert-Zsilavecz, M. Hypericum perforatum: A modern herbal antidepressant. Clin. Pharmacokinet. 2006, 45, 449–468. [Google Scholar] [CrossRef] [PubMed]
- Xie, W.; Jiang, Z.; Wang, J.; Zhang, X.; Melzig, M.F. Protective effect of hyperoside against acetaminophen (APAP) induced liver injury through enhancement of APAP clearance. Chem.-Biol. Interact. 2016, 246, 11–19. [Google Scholar] [CrossRef] [PubMed]
- Zhu, X.; Ji, M.; Han, Y.; Guo, Y.; Zhu, W.; Gao, F.; Yang, X.; Zhang, C. PGRMC1-dependent autophagy by hyperoside induces apoptosis and sensitizes ovarian cancer cells to cisplatin treatment. Int. J. Oncol. 2017, 50, 835–846. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bighelli, I.; Castellazzi, M.; Cipriani, A.; Girlanda, F.; Guaiana, G.; Koesters, M.; Turrini, G.; Furukawa, T.A.; Barbui, C. Antidepressants versus placebo for panic disorder in adults. Cochrane Database Syst. Rev. 2018, 4, CD010676. [Google Scholar] [CrossRef]
- Fathinezhad, Z.; Sewell, R.D.E.; Lorigooini, Z.; Rafieian-Kopaei, M. Depression and Treatment with Effective Herbs. Curr. Pharm. Des. 2019, 25, 738–745. [Google Scholar] [CrossRef]
- Zheng, M.; Liu, C.; Pan, F.; Shi, D.; Zhang, Y. Antidepressant-like effect of hyperoside isolated from Apocynum venetum leaves: Possible cellular mechanisms. Phytomed. Int. J. Phytother. Phytopharm. 2012, 19, 145–149. [Google Scholar] [CrossRef]
- V Butterweck, G.J.; Nahrstedt, A.; Winterhoff, H. Flavonoids from Hypericum perforatum show antidepressant activity in the forced swimming test. Planta Med. 2000, 66, 3–6. [Google Scholar] [CrossRef]
- Colucci-D’Amato, L.; Speranza, L.; Volpicelli, F. Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer. Int. J. Mol. Sci. 2020, 21, 7777. [Google Scholar] [CrossRef]
- Gelle, T.; Samey, R.A.; Plansont, B.; Bessette, B.; Jauberteau-Marchan, M.O.; Lalloue, F.; Girard, M. BDNF and pro-BDNF in serum and exosomes in major depression: Evolution after antidepressant treatment. Prog. Neuropsychopharmacol. Biol. Psychiatry 2021, 109, 110229. [Google Scholar] [CrossRef] [PubMed]
- Silva, R.L.; Lopes, A.H.; Guimaraes, R.M.; Cunha, T.M. CXCL1/CXCR2 signaling in pathological pain: Role in peripheral and central sensitization. Neurobiol. Dis. 2017, 105, 109–116. [Google Scholar] [CrossRef] [PubMed]
- Chai, H.H.; Fu, X.C.; Ma, L.; Sun, H.T.; Chen, G.Z.; Song, M.Y.; Chen, W.X.; Chen, Y.S.; Tan, M.X.; Guo, Y.W.; et al. The chemokine CXCL1 and its receptor CXCR2 contribute to chronic stress-induced depression in mice. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 2019, 33, 8853–8864. [Google Scholar] [CrossRef] [PubMed]
Gene | Forward Primer, 5′–3′ | Reverse Primer, 5′–3′ |
---|---|---|
NLRP1 | 5-GCTGAATGACCTGGGTGATGGT-3 | 5-CTTGGTCACTGAGAGATGCCTG-3 |
ASC | 5-CTTGTCAGGGGATGAACTCAAAA-3 | 5-GCCATACGACTCCAGATAGTAGC-3 |
Caspase-1 | 5-TCCGCGGTTGAATCCTTTTC-3 | 5-CCTTTCCAACAGGGCGTGAA-3 |
CXCR2 | 5-CTCTATTCTGCCAGATGCTGTCC-3 | 5-ACAAGGCTCAGCAGAGTCACCA-3 |
CXCL1 | 5-ACTGCACCCAAACCGAAGTC-3 | 5-TGGGGACACCTTTTAGCATCTT-3 |
BDNF | 5-TCATACTTCGGTTGCATGAAGG-3 | 5-AGACCTCTCGAACCTGCCC-3 |
ACTIN | 5-TTCCTTCCTGGGTATGGAAT-3 | 5-GAGGAGCAATGATCTTGATC-3 |
IL-6 | 5-CTGCAAGAGACTTCCATCCAG-3 | 5-AGTGGTATAGACAGGTCTGTTGG-3 |
IL-18 | 5-TATCGACCGAACAGCCAACG-3 | 5-GATAGGGTCACAGCCAGTCC-3 |
IL-1β | 5-GAAATGCCACCTTTTGACAGTG-3 | 5-TGGATGCTCTCATCAGGACAG-3 |
TNF-α | 5-CCTGTAGCCCACGTCGTAG-3 | 5-GGGAGTAGACAAGGTACAACCC-3 |
NO. | Name | Formula | RT/Min | Cal [M-H]- | [M-H]- | Diff (ppm) | Fragment Ions |
---|---|---|---|---|---|---|---|
C1 | Quinic acid | C7H12O6 | 1.18 | 191.0560 | 191.0561 | 0.52 | 173.0452,127.0396,111.0083 |
C2 | Pyrocatechol | C6H6O2 | 2.42 | 109.0294 | 109.0292 | −1.83 | 90.0111,80.0262,79.0184 |
C3 | Chlorogenic acid | C16H18O9 | 3.28 | 353.0878 | 353.0875 | −0.79 | 191.0562,173.0454,135.0447 |
C4 | Caffeic acid | C9H8O4 | 4.17 | 179.0350 | 179.0349 | −0.34 | 135.0450,134.0372,111.0079 |
C5 | Catechin | C15H14O6 | 4.77 | 289.0717 | 289.0712 | −1.87 | 245.0811,123.0448,125.074 |
C6 | Rutin | C27H30O16 | 8.78 | 609.1461 | 609.1464 | 0.53 | 343.0466,300.0278.301.0347 |
C7 | Hyperoside | C21H20O12 | 8.83 | 463.0882 | 463.0883 | 0.26 | 300.0279,.0346,271.0247 |
C8 | Isoquercetin | C21H20O12 | 9.28 | 463.0882 | 463.0883 | 0.26 | 300.0275,301.0342,271.0239 |
C9 | Kaempferol 3-O-glucoside | C21H20O11 | 10.65 | 447.0933 | 447.0933 | 0.09 | 300.0281,301.0350,271.0246 |
C10 | Guaijaverin | C20H18O11 | 11.05 | 433.0776 | 433.0781 | 1.13 | 300.0278,301.0348,271.0247 |
C11 | Quercetin | C21H20O11 | 11.72 | 447.0933 | 447.0941 | 1.88 | 300.0283,301.0342,271.0247 |
C12 | Protohypericin | C30H18O8 | 14.72 | 505.0971 | 505.0980 | 1.78 | 300.0268,301.0345,271.0243 |
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Song, A.; Wu, Z.; Zhao, W.; Shi, W.; Cheng, R.; Jiang, J.; Ni, Z.; Qu, H.; Qiaolongbatu, X.; Fan, G.; et al. The Role and Mechanism of Hyperoside against Depression-like Behavior in Mice via the NLRP1 Inflammasome. Medicina 2022, 58, 1749. https://doi.org/10.3390/medicina58121749
Song A, Wu Z, Zhao W, Shi W, Cheng R, Jiang J, Ni Z, Qu H, Qiaolongbatu X, Fan G, et al. The Role and Mechanism of Hyperoside against Depression-like Behavior in Mice via the NLRP1 Inflammasome. Medicina. 2022; 58(12):1749. https://doi.org/10.3390/medicina58121749
Chicago/Turabian StyleSong, Aoqi, Zhenghua Wu, Wenjuan Zhao, Wenqing Shi, Ru Cheng, Jingjing Jiang, Zhuojun Ni, Han Qu, Xijier Qiaolongbatu, Guorong Fan, and et al. 2022. "The Role and Mechanism of Hyperoside against Depression-like Behavior in Mice via the NLRP1 Inflammasome" Medicina 58, no. 12: 1749. https://doi.org/10.3390/medicina58121749