Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer

Boya Wang; Xinrui Guo; Lanhui Qin; Liheng He; Jingnan Li; Xudong Jin; Dapeng Chen; Guangbo Ge

doi:10.1016/j.jpha.2024.101074

Volume 15 Issue 4

May 2025

Turn off MathJax

Article Contents

Article Navigation > Journal of Pharmaceutical Analysis > 2025 > 15(4): 101074

Boya Wang, Xinrui Guo, Lanhui Qin, Liheng He, Jingnan Li, Xudong Jin, Dapeng Chen, Guangbo Ge. Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101074. doi: 10.1016/j.jpha.2024.101074

Citation:

Boya Wang, Xinrui Guo, Lanhui Qin, Liheng He, Jingnan Li, Xudong Jin, Dapeng Chen, Guangbo Ge. Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101074. doi: 10.1016/j.jpha.2024.101074

Citation:

Boya Wang, Xinrui Guo, Lanhui Qin, Liheng He, Jingnan Li, Xudong Jin, Dapeng Chen, Guangbo Ge. Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer[J]. Journal of Pharmaceutical Analysis, 2025, 15(4): 101074. doi: 10.1016/j.jpha.2024.101074

PDF( 1806 KB)

Pharmacological modulation of mitochondrial function as novel strategies for treating intestinal inflammatory diseases and colorectal cancer

doi: 10.1016/j.jpha.2024.101074

a. Department of Comparative Medicine, Dalian Medical University, Dalian, Liaoning, 116044, China;
b. Department of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China;
c. St. Hilda's College, Oxford University, Oxford, OX4 1DY, UK

Funds:

This work was financially supported by the National Science Foundation of China (Grant Nos.: U23A20516, 82273897, and 82141203), the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine, China (Grant No.: 2023YZZ02), Shanghai Municipal Health Commission's Traditional Chinese Medicine Research Project, China (Grant No.: 2022CX005), the Shanghai Science and Technology Innovation Action Plans of the Shanghai Science and Technology Committee, China (Grant No.: 21S21900600), the Three-year Action Plan of the Shanghai Traditional Chinese Medicine Development and Inheritance Program, China (Program No.: ZY (2021-2023)-0401), and the Basic Scientific Research Project of Liaoning Province Education Department, China (Project No.: LJKZ0832).

Received Date: May 08, 2024
Accepted Date: Aug. 16, 2024
Rev Recd Date: Aug. 01, 2024
Publish Date: Aug. 18, 2024

Abstract

Abstract

Inflammatory bowel disease (IBD) is a chronic and recurrent intestinal disease, and has become a major global health issue. Individuals with IBD face an elevated risk of developing colorectal cancer (CRC), and recent studies have indicated that mitochondrial dysfunction plays a pivotal role in the pathogenesis of both IBD and CRC. This review covers the pathogenesis of IBD and CRC, focusing on mitochondrial dysfunction, and explores pharmacological targets and strategies for addressing both conditions by modulating mitochondrial function. Additionally, recent advancements in the pharmacological modulation of mitochondrial dysfunction for treating IBD and CRC, encompassing mitochondrial damage, release of mitochondrial DNA (mtDNA), and impairment of mitophagy, are thoroughly summarized. The review also provides a systematic overview of natural compounds (such as flavonoids, alkaloids, and diterpenoids), Chinese medicines, and intestinal microbiota, which can alleviate IBD and attenuate the progression of CRC by modulating mitochondrial function. In the future, it will be imperative to develop more practical methodologies for real-time monitoring and accurate detection of mitochondrial function, which will greatly aid scientists in identifying more effective agents for treating IBD and CRC through modulation of mitochondrial function.
- Mitochondria,
- Inflammatory bowel disease,
- Colorectal cancer,
- Pharmacology,
- Mitochondrial DNA

FullText(HTML)

References(153)

References

[1]	A.B. Pithadia, S. Jain, Treatment of inflammatory bowel disease (IBD), Pharmacol. Rep. 63 (2011) 629-642.
[2]	J.D. Feuerstein, A.S. Cheifetz, Crohn disease: Epidemiology, diagnosis, and management, Mayo Clin. Proc. 92 (2017) 1088-1103.
[3]	M.C. Fantini, I. Guadagni, From inflammation to colitis-associated colorectal cancer in inflammatory bowel disease: Pathogenesis and impact of current therapies, Dig. Liver Dis. 53 (2021) 558-565.
[4]	S.K. Park, C.S. Song, H.J. Yang, et al., Field cancerization in sporadic colon cancer, Gut Liver 10 (2016) 773-780.
[5]	C.L. Alston, M.C. Rocha, N.Z. Lax, et al., The genetics and pathology of mitochondrial disease, J. Pathol. 241 (2017) 236-250.
[6]	T. Udhayabanu, A. Manole, M. Rajeshwari, et al., Riboflavin responsive mitochondrial dysfunction in neurodegenerative diseases, J. Clin. Med. 6 (2017), 52.
[7]	M. Monne, D.V. Miniero, V. Iacobazzi, et al., The mitochondrial oxoglutarate carrier: From identification to mechanism, J. Bioenerg. Biomembr. 45 (2013) 1-13.
[8]	F. Zhang, M. Pirooznia, H. Xu, Mitochondria regulate intestinal stem cell proliferation and epithelial homeostasis through FOXO, Mol. Biol. Cell 31 (2020) 1538-1549.
[9]	S. Marchi, S. Patergnani, S. Missiroli, et al., Mitochondrial and endoplasmic reticulum calcium homeostasis and cell death, Cell Calcium 69 (2018) 62-72.
[10]	P. Andrieux, C. Chevillard, E. Cunha-Neto, et al., Mitochondria as a cellular hub in infection and inflammation, Int. J. Mol. Sci. 22 (2021), 11338.
[11]	B. Banoth, S.L. Cassel, Mitochondria in innate immune signaling, Transl. Res. 202 (2018) 52-68.
[12]	A. Wang, A.V. Keita, V. Phan, et al., Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis, Am. J. Pathol. 184 (2014) 2516-2527.
[13]	J. Shi, W. Wang, S. Sun, et al., Advanced oxidation protein products induce Paneth cells defects by endoplasmic reticulum stress in Crohn’s disease, iScience 26 (2023), 107312.
[14]	M.M. Faas, P. de Vos, Mitochondrial function in immune cells in health and disease, Biochim. Biophys. Acta Mol. Basis Dis. 1866 (2020), 165845.
[15]	G.T. Ho, A.L. Theiss, Mitochondria and inflammatory bowel diseases: Toward a stratified therapeutic intervention, Annu. Rev. Physiol. 84 (2022) 435-459.
[16]	M.U. Mirkov, B. Verstockt, I. Cleynen, Genetics of inflammatory bowel disease: Beyond NOD2, Lancet Gastroenterol. Hepatol. 2 (2017) 224-234.
[17]	Y. Haberman, R. Karns, P.J. Dexheimer, et al., Ulcerative colitis mucosal transcriptomes reveal mitochondriopathy and personalized mechanisms underlying disease severity and treatment response, Nat. Commun. 10 (2019), 38.
[18]	K.E. Sosnovski, T. Braun, A. Amir, et al., GATA6-AS1 regulates intestinal epithelial mitochondrial functions, and its reduced expression is linked to intestinal inflammation and less favourable disease course in ulcerative colitis, J. Crohns Colitis 17 (2023) 960-971.
[19]	T. Dankowski, T. Schroder, S. Moller, et al., Male-specific association between MT-ND4 11719 A/G polymorphism and ulcerative colitis: A mitochondria-wide genetic association study, BMC Gastroenterol. 16 (2016), 118.
[20]	Y. Xu, J. Shen, Z. Ran, Emerging views of mitophagy in immunity and autoimmune diseases, Autophagy 16 (2020) 3-17.
[21]	G. Vincent, E.A. Novak, V.S. Siow, et al., Nix-mediated mitophagy modulates mitochondrial damage during intestinal inflammation, Antioxid. Redox Signal. 33 (2020) 1-19.
[22]	Z. Chen, Y. He, F. Hu, et al., Genkwanin alleviates mitochondrial dysfunction and oxidative stress in a murine model of experimental colitis: The participation of Sirt1, Ann. Clin. Lab. Sci. 52 (2022) 301-313.
[23]	R.K. Boyapati, D.A. Dorward, A. Tamborska, et al., Mitochondrial DNA is a pro-inflammatory damage-associated molecular pattern released during active IBD, Inflamm. Bowel Dis. 24 (2018) 2113-2122.
[24]	K.M. Alula, D.N. Jackson, A.D. Smith, et al., Targeting mitochondrial damage as a therapeutic for ileal Crohn’s disease, Cells 10 (2021), 1349.
[25]	M.C. Ludikhuize, M. Meerlo, M.P. Gallego, et al., Mitochondria define intestinal stem cell differentiation downstream of a FOXO/Notch axis, Cell Metab. 32 (2020) 889-900.e7.
[26]	E.L. Mills, B. Kelly, A. Logan, et al., Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages, Cell 167 (2016) 457-470.e13.
[27]	C. Vanpouille-Box, J.A. Hoffmann, L. Galluzzi, Pharmacological modulation of nucleic acid sensors — Therapeutic potential and persisting obstacles, Nat. Rev. Drug Discov. 18 (2019) 845-867.
[28]	G. Kroemer, C. Galassi, L. Zitvogel, et al., Immunogenic cell stress and death, Nat. Immunol. 23 (2022) 487-500.
[29]	D.S. Leslie, C.C. Dascher, K. Cembrola, et al., Serum lipids regulate dendritic cell CD1 expression and function, Immunology 125 (2008) 289-301.
[30]	Q. Zhang, M. Raoof, Y. Chen, et al., Circulating mitochondrial DAMPs cause inflammatory responses to injury, Nature 464 (2010) 104-107.
[31]	F. Bar, W. Bochmann, A. Widok, et al., Mitochondrial gene polymorphisms that protect mice from colitis, Gastroenterology 145 (2013) 1055-1063.e3.
[32]	S. Liao, J. Luo, T. Kadier, et al., Mitochondrial DNA release contributes to intestinal ischemia/reperfusion injury, Front. Pharmacol. 13 (2022), 854994.
[33]	S. Marchi, E. Guilbaud, S.W.G. Tait, et al., Mitochondrial control of inflammation, Nat. Rev. Immunol. 23 (2023) 159-173.
[34]	J. Zhou, M. Li, Q. Chen, et al., Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery, Nat. Commun. 13 (2022), 3432.
[35]	D. Babu, G. Leclercq, V. Goossens, et al., Mitochondria and NADPH oxidases are the major sources of TNF-α/cycloheximide-induced oxidative stress in murine intestinal epithelial MODE-K cells, Cell. Signal. 27 (2015) 1141-1158.
[36]	Y. Chen, J. Li, S. Li, et al., Uncovering the novel role of NR1D1 in regulating BNIP3-mediated mitophagy in ulcerative colitis, Int. J. Mol. Sci. 24 (2023), 14222.
[37]	V. Amash, K. Paithankar, S.P. Dharaskar, et al., Development of nanocarrier-based mitochondrial chaperone, TRAP-1 inhibitor to combat cancer metabolism, ACS Appl. Bio Mater. 3 (2020) 4188-4197.
[38]	P. Klos, S.A. Dabravolski, The role of mitochondria dysfunction in inflammatory bowel diseases and colorectal cancer, Int. J. Mol. Sci. 22 (2021), 11673.
[39]	L. Ren, L. Meng, J. Gao, et al., PHB2 promotes colorectal cancer cell proliferation and tumorigenesis through NDUFS1-mediated oxidative phosphorylation, Cell Death Dis. 14 (2023), 44.
[40]	Y. Wang, X. Sun, K. Ji, et al., Sirt3-mediated mitochondrial fission regulates the colorectal cancer stress response by modulating the Akt/PTEN signalling pathway, Biomed. Pharmacother. 105 (2018) 1172-1182.
[41]	T. Pan, J. Liu, S. Xu, et al., ANKRD22, a novel tumor microenvironment-induced mitochondrial protein promotes metabolic reprogramming of colorectal cancer cells, Theranostics 10 (2020) 516-536.
[42]	J. Han, D. Jackson, J. Holm, et al., Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer, Proc. Natl. Acad. Sci. U S A 115 (2018) 1057-1062.
[43]	Y. Liu, M. Jin, Y. Wang, et al., MCU-induced mitochondrial calcium uptake promotes mitochondrial biogenesis and colorectal cancer growth, Signal Transduct. Target. Ther. 5 (2020), 59.
[44]	J.Y. Kim, J.K. Kim, H. Kim, ABCB7 simultaneously regulates apoptotic and non-apoptotic cell death by modulating mitochondrial ROS and HIF1α-driven NFκB signaling, Oncogene 39 (2020) 1969-1982.
[45]	J. Tang, W. Peng, J. Ji, et al., GPR176 promotes cancer progression by interacting with G protein GNAS to restrain cell mitophagy in colorectal cancer, Adv. Sci. (Weinh) 10 (2023), e2205627.
[46]	L. Ding, H. Gu, Z. Lan, et al., Downregulation of cyclooxygenase-1 stimulates mitochondrial apoptosis through the NF-κB signaling pathway in colorectal cancer cells, Oncol. Rep. 41 (2019) 559-569.
[47]	J.J. Lemasters, Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging, Rejuvenation Res. 8 (2005) 3-5.
[48]	Y. Lu, Z. Li, S. Zhang, et al., Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation, Theranostics 13 (2023) 736-766.
[49]	W. Guo, Y. Sun, W. Liu, et al., Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer, Autophagy 10 (2014) 972-985.
[50]	H. Zhang, S. Li, Y. Si, et al., Andrographolide and its derivatives: Current achievements and future perspectives, Eur. J. Med. Chem. 224 (2021), 113710.
[51]	C. Mai, M. Wu, C. Wang, et al., Palmatine attenuated dextran sulfate sodium (DSS)-induced colitis via promoting mitophagy-mediated NLRP3 inflammasome inactivation, Mol. Immunol. 105 (2019) 76-85.
[52]	Z. Zhou, N. Xu, N. Matei, et al., Sodium butyrate attenuated neuronal apoptosis via GPR41/Gβγ/PI3K/Akt pathway after MCAO in rats, J. Cereb. Blood Flow Metab. 41 (2021) 267-281.
[53]	Z. Bian, Q. Zhang, Y. Qin, et al., Sodium butyrate inhibits oxidative stress and NF-κB/NLRP3 activation in dextran sulfate sodium salt-induced colitis in mice with involvement of the Nrf2 signaling pathway and mitophagy, Dig. Dis. Sci. 68 (2023) 2981-2996.
[54]	C. Liu, J. Wang, Y. Yang, et al., Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice, Biochem. Pharmacol. 155 (2018) 366-379.
[55]	L. Liang, W. Sun, X. Wei, et al., Oxymatrine suppresses colorectal cancer progression by inhibiting NLRP3 inflammasome activation through mitophagy induction in vitro and in vivo, Phytother. Res. 37 (2023) 3342-3362.
[56]	L. Tilokani, S. Nagashima, V. Paupe, et al., Mitochondrial dynamics: Overview of molecular mechanisms, Essays Biochem. 62 (2018) 341-360.
[57]	D. Wang, Y. Kuang, Z. Wan, et al., Aspartate alleviates colonic epithelial damage by regulating intestinal stem cell proliferation and differentiation via mitochondrial dynamics, Mol. Nutr. Food Res. 66 (2022), e2200168.
[58]	Y. Zhang, M. Wang, X. Xu, et al., Matrine promotes apoptosis in SW480 colorectal cancer cells via elevating MIEF1-related mitochondrial division in a manner dependent on LATS2-Hippo pathway, J. Cell. Physiol. 234 (2019) 22731-22741.
[59]	H.F. Hu, W.W. Xu, Y.J. Li, et al., Anti-allergic drug azelastine suppresses colon tumorigenesis by directly targeting ARF1 to inhibit IQGAP1-ERK-Drp1-mediated mitochondrial fission, Theranostics 11 (2021) 1828-1844.
[60]	H.-F. Hu, G.-B. Gao, X. He, et al., Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance, J. Adv. Res. 51 (2023) 135-147.
[61]	S.J. Annesley, P.R. Fisher, Mitochondria in health and disease, Cells 8 (2019), 680.
[62]	S.L. Kim, S. Shin, S.J. Yang, Iron homeostasis and energy metabolism in obesity, Clin. Nutr. Res. 11 (2022) 316-330.
[63]	P.H. Willems, R. Rossignol, C.E. Dieteren, et al., Redox homeostasis and mitochondrial dynamics, Cell Metab. 22 (2015) 207-218.
[64]	J. Zheng, Q. Wang, J. Chen, et al., Tumor mitochondrial oxidative phosphorylation stimulated by the nuclear receptor RORγ represents an effective therapeutic opportunity in osteosarcoma, Cell Rep. Med. 5 (2024), 101519.
[65]	W. Gao, T. Zhang, H. Wu, Emerging pathological engagement of ferroptosis in gut diseases, Oxid. Med. Cell. Longev. 2021 (2021), 4246255.
[66]	T. Miyazaki, Y. Shirakami, T. Mizutani, et al., Novel FXR agonist nelumal A suppresses colitis and inflammation-related colorectal carcinogenesis, Sci. Rep. 11 (2021), 492.
[67]	K. Wang, Q. Lv, Y. Miao, et al., Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway, Biochem. Pharmacol. 155 (2018) 494-509.
[68]	W. Zhang, W. Wang, C. Shen, et al., Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome, Aging (Albany NY) 13 (2021) 23193-23209.
[69]	B. Tang, J. Zhu, B. Zhang, et al., Therapeutic potential of triptolide as an anti-inflammatory agent in dextran sulfate sodium-induced murine experimental colitis, Front. Immunol. 11 (2020), 592084.
[70]	S. Mouzaoui, S. Banerjee, B. Djerdjouri, Low-dose curcumin reduced TNBS-associated mucin depleted foci in mice by scavenging superoxide anion and lipid peroxides, rebalancing matrix NO synthase and aconitase activities, and recoupling mitochondria, Inflammopharmacology 28 (2020) 949-965.
[71]	T. Gao, T. Wang, Z. Wang, et al., Melatonin-mediated MT2 attenuates colitis induced by dextran sodium sulfate via PI3K/AKT/Nrf2/SIRT1/RORα/NF-κB signaling pathways, Int. Immunopharmacol. 96 (2021), 107779.
[72]	Z. Huang, S. Gan, X. Zhuang, et al., Artesunate inhibits the cell growth in colorectal cancer by promoting ROS-dependent cell senescence and autophagy, Cells 11 (2022), 2472.
[73]	Y. Fu, Y. Ye, G. Zhu, et al., Resveratrol induces human colorectal cancer cell apoptosis by activating the mitochondrial pathway via increasing reactive oxygen species, Mol. Med. Rep. 23 (2021), 170.
[74]	C. Yan, X. Duanmu, L. Zeng, et al., Mitochondrial DNA: Distribution, mutations, and elimination, Cells 8 (2019), 379.
[75]	Y. Zheng, C. Liang, Z. Li, et al., Study on the mechanism of Huangqin Decoction on rats with ulcerative colitis of damp-heat type base on mtDNA, TLR4, p-PI3K, p-Akt protein expression and microbiota, J. Ethnopharmacol. 295 (2022), 115356.
[76]	K. Mosallanejad, J.C. Kagan, Control of innate immunity by the cGAS-STING pathway, Immunol. Cell Biol. 100 (2022) 409-423.
[77]	X. Liu, W. Zhou, X. Zhang, et al., Dimethyl fumarate ameliorates dextran sulfate sodium-induced murine experimental colitis by activating Nrf2 and suppressing NLRP3 inflammasome activation, Biochem. Pharmacol. 112 (2016) 37-49.
[78]	]A. Vanduchova, P. Anzenbacher, E. Anzenbacherova, Isothiocyanate from broccoli, sulforaphane, and its properties, J. Med. Food 22 (2019) 121-126.
[79]	Y. Zhao, P. Liu, Y. Zhang, et al., Demethyleneberberine blocked the maturation of IL-1β in inflammation by inhibiting TLR4-mitochondria signaling, Int. Immunopharmacol. 113 (2022), 109319.
[80]	A. Verma, S. Pittala, B. Alhozeel, et al., The role of the mitochondrial protein VDAC1 in inflammatory bowel disease: A potential therapeutic target, Mol. Ther. 30 (2022) 726-744.
[81]	R. Reifen, E. Levy, Z. Berkovich, et al., Vitamin A exerts its antiinflammatory activities in colitis through preservation of mitochondrial activity, Nutrition 31 (2015) 1402-1407.
[82]	S.P.M. Sok, D. Ori, A. Wada, et al., 1’-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression, Int. Immunol. 33 (2021) 373-386.
[83]	S. Mathur, P. Srivastava, A. Srivastava, et al., Regulation of metastatic potential by drug repurposing and mitochondrial targeting in colorectal cancer cells, BMC Cancer 24 (2024), 323.
[84]	M. Surti, M. Patel, A. Redhwan, et al., Ilimaquinone (marine sponge metabolite) induces apoptosis in HCT-116 human colorectal carcinoma cells via mitochondrial-mediated apoptosis pathway, Mar. Drugs 20 (2022), 582.
[85]	B. Somuncu, A. Ekmekcioglu, F.M. Antmen, et al., Targeting mitochondrial DNA polymerase gamma for selective inhibition of MLH1 deficient colon cancer growth, PLoS One 17 (2022), e0268391.
[86]	V. Ruiz-Torres, C. Rodriguez-Perez, M. Herranz-Lopez, et al., Marine invertebrate extracts induce colon cancer cell death via ROS-mediated DNA oxidative damage and mitochondrial impairment, Biomolecules 9 (2019), 771.
[87]	K. Shukla, H. Sonowal, A. Saxena, et al., Aldose reductase inhibitor, fidarestat regulates mitochondrial biogenesis via Nrf2/HO-1/AMPK pathway in colon cancer cells, Cancer Lett. 411 (2017) 57-63.
[88]	C. Qiao, N. Lu, Y. Zhou, et al., Oroxylin A modulates mitochondrial function and apoptosis in human colon cancer cells by inducing mitochondrial translocation of wild-type p53, Oncotarget 7 (2016) 17009-17020.
[89]	C. Herold, M. Ocker, M. Ganslmayer, et al., Ciprofloxacin induces apoptosis and inhibits proliferation of human colorectal carcinoma cells, Br. J. Cancer 86 (2002) 443-448.
[90]	A. Mortha, A. Chudnovskiy, D. Hashimoto, et al., Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis, Science 343 (2014), 1249288.
[91]	C. Danne, J. Skerniskyte, B. Marteyn, et al., Neutrophils: From IBD to the gut microbiota, Nat. Rev. Gastroenterol. Hepatol. 21 (2024) 184-197.
[92]	B.O. Schroeder, F. Backhed, Signals from the gut microbiota to distant organs in physiology and disease, Nat. Med. 22 (2016) 1079-1089.
[93]	Y. Yang, Y. Wang, L. Zhao, et al., Chinese herbal medicines for treating ulcerative colitis via regulating gut microbiota-intestinal immunity axis, Chin. Herb. Med. 15 (2023) 181-200.
[94]	D.N. Jackson, A.L. Theiss, Gut bacteria signaling to mitochondria in intestinal inflammation and cancer, Gut Microbes 11 (2020) 285-304.
[95]	E.E. Blaak, E.E. Canfora, S. Theis, et al., Short chain fatty acids in human gut and metabolic health, Benef. Microbes 11 (2020) 411-455.
[96]	C.A. Lopez, B.M. Miller, F. Rivera-Chavez, et al., Virulence factors enhance Citrobacter rodentium expansion through aerobic respiration, Science 353 (2016) 1249-1253.
[97]	Y. Zhang, J. Zhang, L. Duan, The role of microbiota-mitochondria crosstalk in pathogenesis and therapy of intestinal diseases, Pharmacol. Res. 186 (2022), 106530.
[98]	A.F. Perna, M.G. Luciano, D. Ingrosso, et al., Hydrogen sulfide, the third gaseous signaling molecule with cardiovascular properties, is decreased in hemodialysis patients, J. Ren. Nutr. 20 (2010) S11-S14.
[99]	G. Cirino, C. Szabo, A. Papapetropoulos, Physiological roles of hydrogen sulfide in mammalian cells, tissues, and organs, Physiol. Rev. 103 (2023) 31-276.
[100]	J.C. Mathai, A. Missner, P. Kugler, et al., No facilitator required for membrane transport of hydrogen sulfide, Proc. Natl. Acad. Sci. U S A 106 (2009) 16633-16638.
[101]	S.D. Hemelrijk, M.C. Dirkes, M.H.N. van Velzen, et al., Exogenous hydrogen sulfide gas does not induce hypothermia in normoxic mice, Sci. Rep. 8 (2018), 3855.
[102]	N. Stummer, R.G. Feichtinger, D. Weghuber, et al., Role of hydrogen sulfide in inflammatory bowel disease, Antioxidants 12 (2023), 1570.
[103]	H.B. Suliman, C.A. Piantadosi, Mitochondrial biogenesis: Regulation by endogenous gases during inflammation and organ stress, Curr. Pharm. Des. 20 (2014) 5653-5662.
[104]	C. Szabo, Hydrogen sulfide, an endogenous stimulator of mitochondrial function in cancer cells, Cells 10 (2021), 220.
[105]	H. Lin, Y. Yu, L. Zhu, et al., Implications of hydrogen sulfide in colorectal cancer: Mechanistic insights and diagnostic and therapeutic strategies, Redox Biol. 59 (2023), 102601.
[106]	A. Ma, F. Zou, R. Zhang, et al., The effects and underlying mechanisms of medicine and food homologous flowers on the prevention and treatment of related diseases, J. Food Biochem. 46 (2022), e14430.
[107]	]J. Chen, Essential role of medicine and food homology in health and wellness, Chin. Herb. Med. 15 (2023) 347-348.
[108]	Y. Zhou, L. Zhou, Z. Ruan, et al., Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes, Biosci. Biotechnol. Biochem. 80 (2016) 962-971.
[109]	J. Kong, Q. Xiang, G. Shi, et al., Licorice protects against ulcerative colitis via the Nrf2/PINK1-mediated mitochondrial autophagy, Immun. Inflamm. Dis. 11 (2023), e757.
[110]	A. Dermane, A.K.G. Kporvie, K.P. Kindji, et al., Immunomodulatory and anti-inflammatory activities of hydro-ethanolic extract of Securidaca longipedunculata Fresen leaves, J. Herbmed Pharmacol. 13 (2024) 280-288.
[111]	T.K. Ha, M.E. Kim, J.H. Yoon, et al., Galangin induces human colon cancer cell death via the mitochondrial dysfunction and caspase-dependent pathway, Exp. Biol. Med. (Maywood) 238 (2013) 1047-1054.
[112]	Y.J. Tang, J.S. Yang, C.F. Lin, et al., Houttuynia cordata Thunb extract induces apoptosis through mitochondrial-dependent pathway in HT-29 human colon adenocarcinoma cells, Oncol. Rep. 22 (2009) 1051-1056.
[113]	K. Zhang, X. Zhou, J. Wang, et al., Dendrobium officinale polysaccharide triggers mitochondrial disorder to induce colon cancer cell death via ROS-AMPK-autophagy pathway, Carbohydr. Polym. 264 (2021), 118018.
[114]	C.-Z. Wang, T.D. Calway, X.-D. Wen, et al., Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway, Int. J. Oncol. 42 (2013) 1018-1026.
[115]	K.-C. Lai, Y.J. Chiu, Y.J. Tang, et al., Houttuynia cordata Thunb extract inhibits cell growth and induces apoptosis in human primary colorectal cancer cells, Anticancer Res. 30 (2010) 3549-3556.
[116]	P.B. Yaffe, M.R. Power Coombs, C.D. Doucette, et al., Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress, Mol. Carcinog. 54 (2015) 1070-1085.
[117]	C.-M. Su, Y.S. Weng, L.-Y. Kuan, et al., Suppression of PKCδ/NF-κB signaling and apoptosis induction through extrinsic/intrinsic pathways are associated magnolol-inhibited tumor progression in colorectal cancer in vitro and in vivo, Int. J. Mol. Sci. 21 (2020), 3527.
[118]	L. Gao, H. Li, B. Li, et al., Traditional uses, phytochemistry, transformation of ingredients and pharmacology of the dried seeds of Raphanus sativus L. (Raphani Semen), A comprehensive review, J. Ethnopharmacol. 294 (2022), 115387.
[119]	J. Hu, Z. Lin, L. Li, et al., Oral administration of lotus-seed resistant starch protects against food allergy, Foods 12 (2023), 737.
[120]	K.H. Wong, G.Q. Li, K.M. Li, et al., Kudzu root: Traditional uses and potential medicinal benefits in diabetes and cardiovascular diseases, J. Ethnopharmacol. 134 (2011) 584-607.
[121]	M.H. Mehmood, A.H. Gilani, Pharmacological basis for the medicinal use of black pepper and piperine in gastrointestinal disorders, J. Med. Food 13 (2010) 1086-1096.
[122]	X. Yang, Y. Dai, Z. Ji, et al., Allium macrostemon Bunge. exerts analgesic activity by inhibiting NaV1.7 channel, J. Ethnopharmacol. 281 (2021), 114495.
[123]	A.V. Patel, J. Rojas-Vera, C.G. Dacke, Therapeutic constituents and actions of Rubus species, Curr. Med. Chem. 11 (2004) 1501-1512.
[124]	Y. Gan, G. Ai, J. Wu, et al., Patchouli oil ameliorates 5-fluorouracil-induced intestinal mucositis in rats via protecting intestinal barrier and regulating water transport, J. Ethnopharmacol. 250 (2020), 112519.
[125]	Y. Zhu, Y. Chai, G. Xiao, et al., Astragalus and its formulas as a therapeutic option for fibrotic diseases: Pharmacology and mechanisms, Front. Pharmacol. 13 (2022), 1040350.
[126]	T.T. Sham, A.C. Yuen, Y.F. Ng, et al., A review of the phytochemistry and pharmacological activities of Raphani Semen, Evid. Based Complement. Alternat. Med. 2013 (2013), 636194.
[127]	H. Su, J. Chen, S. Miao, et al., Lotus seed oligosaccharides at various dosages with prebiotic activity regulate gut microbiota and relieve constipation in mice, Food Chem. Toxicol. 134 (2019), 110838.
[128]	J. Wang, Q. Liang, Q. Zhao, et al., The effect of microbial composition and proteomic on improvement of functional constipation by Chrysanthemum morifolium polysaccharide, Food Chem. Toxicol. 153 (2021), 112305.
[129]	F. Arrari, M.A. Jabri, I. Hammami, et al., Extraction of pectin from orange peel and study of its protective effect against loperamide-induced impaired gastrointestinal motor functions and oxidative stress in rats, J. Med. Food 25 (2022) 892-901.
[130]	Y. Luan, D. Mao, A. Guo, et al., The effect of Codonopis bulleynana Forest ex Diels on chronically constipated mice, Saudi J. Biol. Sci. 26 (2019) 402-412.
[131]	Y. Li, Y. Peng, M. Wang, et al., Rapid screening and identification of the differences between metabolites of Cistanche deserticola and C. tubulosa water extract in rats by UPLC-Q-TOF-MS combined pattern recognition analysis, J. Pharm. Biomed. Anal. 131 (2016) 364-372.
[132]	X. Liu, M. Li, C. Jian, et al., Astragalus polysaccharide alleviates constipation in the elderly via modification of gut microbiota and fecal metabolism, Rejuvenation Res. 25 (2022) 275-290.
[133]	M. Gao, Z. Zhang, K. Lai, et al., Puerarin: A protective drug against ischemia-reperfusion injury, Front. Pharmacol. 13 (2022), 927611.
[134]	M.F. Tolba, H.A. Omar, S.S. Azab, et al., Caffeic acid phenethyl ester: A review of its antioxidant activity, protective effects against ischemia-reperfusion injury and drug adverse reactions, Crit. Rev. Food Sci. Nutr. 56 (2016) 2183-2190.
[135]	D. Lin, Y. Zhang, S. Wang, et al., Ganoderma lucidum polysaccharide peptides GL-PPSQ2 alleviate intestinal ischemia-reperfusion injury via inhibiting cytotoxic neutrophil extracellular traps, Int. J. Biol. Macromol. 244 (2023), 125370.
[136]	C. Guo, D. Guo, L. Fang, et al., Ganoderma lucidum polysaccharide modulates gut microbiota and immune cell function to inhibit inflammation and tumorigenesis in colon, Carbohydr. Polym. 267 (2021), 118231.
[137]	J. Gao, J. Cui, H. Zhong, et al., Andrographolide sulfonate ameliorates chronic colitis induced by TNBS in mice via decreasing inflammation and fibrosis, Int. Immunopharmacol. 83 (2020), 106426.
[138]	Y. Sheng, T. Wu, Y. Dai, et al., The effect of 6-gingerol on inflammatory response and Th17/Treg balance in DSS-induced ulcerative colitis mice, Ann. Transl. Med. 8 (2020), 442.
[139]	Z. Kang, Y. Zhonga, T. Wu, et al., Ginsenoside from ginseng: A promising treatment for inflammatory bowel disease, Pharmacol. Rep. 73 (2021) 700-711.
[140]	F. Wang, Y. Chen, K. Itagaki, et al., Wheat germ-derived peptide alleviates dextran sulfate sodium-induced colitis in mice, J. Agric. Food Chem. 71 (2023) 15593-15603.
[141]	X. Zhuge, X. Jin, T. Ji, et al., Geniposide ameliorates dextran sulfate sodium-induced ulcerative colitis via KEAP1-Nrf2 signaling pathway, J. Ethnopharmacol. 314 (2023), 116626.
[142]	J. Mo, J. Ni, M. Zhang, et al., Mulberry anthocyanins ameliorate DSS-induced ulcerative colitis by improving intestinal barrier function and modulating gut microbiota, Antioxidants (Basel) 11 (2022), 1674.
[143]	X. Min, Y. Guo, Y. Zhou, et al., Protection against dextran sulfate sodium-induced ulcerative colitis in mice by neferine, A natural product from Nelumbo nucifera Gaertn, Cell J. 22 (2021) 523-531.
[144]	Z. Lin, T. Gan, Y. Huang, et al., Anti-inflammatory activity of mulberry leaf flavonoids in vitro and in vivo, Int. J. Mol. Sci. 23 (2022), 7694.
[145]	H. Urushima, J. Nishimura, T. Mizushima, et al., Perilla frutescens extract ameliorates DSS-induced colitis by suppressing proinflammatory cytokines and inducing anti-inflammatory cytokines, Am. J. Physiol. Gastroint. Liver Physiol. 308 (2015) G32-G41.
[146]	Y.D. Jeon, J.H. Lee, Y.M. Lee, et al., Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model, Biomed. Pharmacother. 124 (2020), 109847.
[147]	S. Tang, W. Liu, Q. Zhao, et al., Combination of polysaccharides from Astragalus membranaceus and Codonopsis pilosula ameliorated mice colitis and underlying mechanisms, J. Ethnopharmacol. 264 (2021), 113280.
[148]	X. Zheng, T.-X. Xiong, K. Zhang, et al., Benefit effect of dendrobium officinale ultrafine powder on DSS-induced ulcerative colitis rats by improving colon mucosal barrier, Evid. Based Complement Alternat. Med. 2021 (2021), 9658638.
[149]	J. Kong, Q. Xiang, W. Ge, et al., Network pharmacology mechanisms and experimental verification of licorice in the treatment of ulcerative colitis, J. Ethnopharmacol. 324 (2024), 117691.
[150]	Z. Zang, L. Li, M. Yang, et al., Study on the ameliorative effect of honeysuckle on DSS-induced ulcerative colitis in mice, J. Ethnopharmacol. 325 (2024), 117776.
[151]	Y. Li, J. Wu, S. Jiang, et al., Exploring the immunological mechanism of Houttuynia cordata in the treatment of colorectal cancer through combined network pharmacology and experimental validation, Naunyn Schmiedebergs Arch. Pharmacol. 397 (2024) 9095-9110.
[152]	S.J. Chen, Y.C. Chung, H.L. Chang, et al., Synergistic effect of combined treatment with longan flower extract and 5-fluorouracil on colorectal cancer cells, Nutr. Cancer 72 (2020) 209-217.
[153]	J.Y. Jang, E. Im, N.D. Kim, Therapeutic potential of bioactive components from scutellaria baicalensis Georgi in inflammatory bowel disease and colorectal cancer: A review, Int. J. Mol. Sci. 24 (2023), 1954.