Abstract
Background
Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities.
Aim
Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model.
Methods
Male Wistar rats weighing 200–250 g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2 ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines.
Results
We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-β(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001–0.05), fibrosis (P < 0.001–0.05), and oxidative (P < 0.001–0.05) factors, while propagating the anti-oxidant marker (P < 0.001–0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300 µg/ml (P > 0.05).
Conclusion
G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.
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Data availability
The data used to support the findings of this study are available on reasonable requests.
Abbreviations
- BALF:
-
Broncho-alveolar lavage fluid
- CAT:
-
Catalase
- COPD:
-
Chronic obstructive pulmonary disease
- CFA:
-
Coal fly ash
- CXCL-1:
-
C-X-C motif chemokine ligand 1
- GSH:
-
Glutathione
- GSH-Px:
-
Glutathione peroxidase
- GR:
-
Glutathione reductase
- GST:
-
Glutathione S-transferase
- G. glabra:
-
Glycyrrhiza glabra
- ICAM-1:
-
Intercellular adhesion molecule 1
- IFN-γ:
-
Interferon-gamma
- IL-4:
-
Interleukin-4
- LTB4:
-
Leukotriene
- MDA:
-
Malondialdehyde
- MCP-1:
-
Monocyte chemoattractant protein-1
- NO:
-
Nitric oxide
- PAI:
-
Plasminogen activator inhibitors
- PGE2:
-
Prostaglandin E2
- SOD:
-
Superoxide dismutase
- TBARS:
-
Thiobarbituric acid reactive substances
- TXB2:
-
Thromboxane
- tPA:
-
Tissue-type plasminogen activators
- TGF-β:
-
Transforming growth factor-beta
- uPA:
-
Urokinase-type plasminogen activators
References
Arung W, Meurisse M, Detry O (2011) Pathophysiology and prevention of postoperative peritoneal adhesions. World J Gastroenterol 17(41):4545–4553. https://doi.org/10.3748/wjg.v17.i41.4545
Askari VR, Rezaee SA, Abnous K, Iranshahi M, Boskabady MH (2016) The influence of hydro-ethanolic extract of Portulaca oleracea L. on Th1/Th2 balance in isolated human lymphocytes. J Ethnopharmacol 194:1112–1121. https://doi.org/10.1016/j.jep.2016.10.082
Askari VR, Fereydouni N, Rahimi VB, Askari N, Sahebkar AH, Rahmanian-Devin P et al (2018a) β-Amyrin, the cannabinoid receptors agonist, abrogates mice brain microglial cells inflammation induced by lipopolysaccharide/interferon-γ and regulates Mφ1/Mφ2 balances. Biomed Pharmacother 101:438–446
Askari VR, Rahimi VB, Zamani P, Fereydouni N, Rahmanian-Devin P, Sahebkar AH et al (2018b) Evaluation of the effects of Iranian propolis on the severity of post operational-induced peritoneal adhesion in rats. Biomed Pharmacother 99:346–353. https://doi.org/10.1016/j.biopha.2018.01.068
Askari VR, Baradaran Rahimi V, Tabatabaee SA, Shafiee-Nick R (2019) Combination of Imipramine, a sphingomyelinase inhibitor, and β-caryophyllene improve their therapeutic effects on experimental autoimmune encephalomyelitis (EAE). Int Immunopharmacol 77:105923. https://doi.org/10.1016/j.intimp.2019.105923
Askari VR, Baradaran Rahimi V, Assaran A, Iranshahi M, Boskabady MH (2020a) Evaluation of the anti-oxidant and anti-inflammatory effects of the methanolic extract of Ferula szowitsiana root on PHA-induced inflammation in human lymphocytes. Drug Chem Toxicol 43:353–360. https://doi.org/10.1080/01480545.2019.1572182
Askari VR, Rahimi VB, Zargarani R, Ghodsi R, Boskabady M, Boskabady MH (2020b) Anti-oxidant and anti-inflammatory effects of auraptene on phytohemagglutinin (PHA)-induced inflammation in human lymphocytes. Pharmacol Rep. https://doi.org/10.1007/s43440-020-00083-5
Baradaran Rahimi V, Askari VR (2021) Promising anti-melanogenic impacts of Portulaca oleracea on B16F1 murine melanoma cell line: an in-vitro vision. S Afr J Bot 142:477–485. https://doi.org/10.1016/j.sajb.2021.07.033
Baradaran Rahimi V, Askari VR, Mousavi SH (2019b) Ellagic acid dose and time-dependently abrogates d-galactose-induced animal model of aging: Investigating the role of PPAR-γ. Life Sci 232:116595
Baradaran Rahimi V, Mousavi SH, Haghighi S, Soheili-Far S, Askari VR (2019c) Cytotoxicity and apoptogenic properties of the standardized extract of Portulaca oleracea on glioblastoma multiforme cancer cell line (U-87): a mechanistic study. EXCLI J 18:165–186. https://doi.org/10.17179/excli2019-1063
Baradaran Rahimi V, Rakhshandeh H, Raucci F, Buono B, Shirazinia R, Samzadeh Kermani A et al (2019d) Anti-inflammatory and anti-oxidant activity of portulaca oleracea extract on lps-induced rat lung injury. Molecules. https://doi.org/10.3390/molecules24010139
Baradaran Rahimi V, Rajabian A, Rajabi H, Mohammadi Vosough E, Mirkarimi HR, Hasanpour M et al (2020) The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies. J Ethnopharmacol 256:112706. https://doi.org/10.1016/j.jep.2020.112706
Baradaran Rahimi, V., Askari, V. R., Hosseini, M., Yousefsani, B. S., & Sadeghnia, H. R. (2019a). Anticonvulsant Activity of Viola tricolor against Seizures Induced by Pentylenetetrazol and Maximal Electroshock in Mice. Iranian journal of medical sciences, 44(3), 220–226. https://pubmed.ncbi.nlm.nih.gov/31182888
Boland GM, Weigel RJ (2006) Formation and prevention of postoperative abdominal adhesions. J Surg Res 132(1):3–12. https://doi.org/10.1016/j.jss.2005.12.002
Chandrasekaran CV, Deepak HB, Thiyagarajan P, Kathiresan S, Sangli GK, Deepak M et al (2011) Dual inhibitory effect of Glycyrrhiza glabra (GutGard™) on COX and LOX products. Phytomedicine 18(4):278–284. https://doi.org/10.1016/j.phymed.2010.08.001
Dinarvand P, Hassanian SM, Weiler H, Rezaie AR (2015) Intraperitoneal administration of activated protein C prevents post-surgical adhesion band formation. Blood 125(8):1339–1348. https://doi.org/10.1182/blood-2014-10-609339
Du XH, Liu JQ, Xin K, Liu GH (2015) Dexamethasone and sodium carboxymethyl cellulose prevent postoperative intraperitoneal adhesions in rats. Braz J Med Biol Res 48(4):344–348. https://doi.org/10.1590/1414-431x20144211
Duron JJ (2007) Postoperative intraperitoneal adhesion pathophysiology. Colorectal Dis 9(Suppl 2):14–24. https://doi.org/10.1111/j.1463-1318.2007.01343.x
Fiore C, Eisenhut M, Ragazzi E, Zanchin G, Armanini D (2005) A history of the therapeutic use of liquorice in Europe. J Ethnopharmacol 99(3):317–324. https://doi.org/10.1016/j.jep.2005.04.015
Flevaris P, Vaughan D (2017) The role of plasminogen activator inhibitor type-1 in fibrosis. Semin Thromb Hemost 43(2):169–177. https://doi.org/10.1055/s-0036-1586228
Ghadiri M, Baradaran Rahimi V, Moradi E, Hasanpour M, Clark CCT, Iranshahi M et al (2021) Standardised pomegranate peel extract lavage prevents postoperative peritoneal adhesion by regulating TGF-β and VEGF levels. Inflammopharmacology 29(3):855–868. https://doi.org/10.1007/s10787-021-00819-6
Huo HZ, Wang B, Liang YK, Bao YY, Gu Y (2011) Hepatoprotective and anti-oxidant effects of licorice extract against CCl-induced oxidative damage in rats. Int J Mol Sci 12(10):6529–6543. https://doi.org/10.3390/ijms12106529
Jaafari A, Baradaran Rahimi V, Vahdati-Mashhadian N, Yahyazadeh R, Ebrahimzadeh-Bideskan A, Hasanpour M et al (2021) Evaluation of the therapeutic effects of the hydroethanolic extract of portulaca oleracea on surgical-induced peritoneal adhesion. Mediators Inflamm 2021:8437753. https://doi.org/10.1155/2021/8437753
Kim KK, Sheppard D, Chapman HA (2018) TGF-β1 Signaling and tissue fibrosis. Cold Spring Harb Perspect Biol. https://doi.org/10.1101/cshperspect.a022293
Kim SH, Hong JH, Yang WK, Geum JH, Kim HR, Choi SY et al (2020) Herbal combinational medication of Glycyrrhiza glabra, Agastache rugosa Containing Glycyrrhizic Acid tilianin inhibits neutrophilic lung inflammation by affecting CXCL2 Interleukin-17/STAT3 signal pathways in a murine model of COPD. Nutrients. https://doi.org/10.3390/nu12040926
Kotian S, Bhat K, Pai S, Nayak J, Souza A, Gourisheti K et al (2018) The role of natural medicines on wound healing: a biomechanical, histological, biochemical and molecular study. Ethiop J Health Sci 28(6):759–770. https://doi.org/10.4314/ejhs.v28i6.11
Liang P, Shan W, Zuo Z (2018) Perioperative use of cefazolin ameliorates postoperative cognitive dysfunction but induces gut inflammation in mice. J Neuroinflammation 15(1):235. https://doi.org/10.1186/s12974-018-1274-6
Mohamed NE (2019) Effect of aqueous extract of Glycyrrhiza glabra on the biochemical changes induced by cadmium chloride in rats. Biol Trace Elem Res 190(1):87–94. https://doi.org/10.1007/s12011-018-1525-5
Moris D, Chakedis J, Rahnemai-Azar AA, Wilson A, Hennessy MM, Athanasiou A et al (2017) Postoperative abdominal adhesions: clinical significance and advances in prevention and management. J Gastrointest Surg 21(10):1713–1722. https://doi.org/10.1007/s11605-017-3488-9
Nair SK, Bhat IK, Aurora AL (1974a) Role of proteolytic enzyme in the prevention of postoperative intraperitoneal adhesions. Arch Surg 108(6):849–853
Nazari S, Rameshrad M, Hosseinzadeh H (2017) Toxicological Effects of Glycyrrhiza glabra (Licorice): a review. Phytother Res 31(11):1635–1650
Osma-Garcia IC, Punzon C, Fresno M, Diaz-Munoz MD (2016) Dose-dependent effects of prostaglandin E2 in macrophage adhesion and migration. Eur J Immunol 46(3):677–688. https://doi.org/10.1002/eji.201545629
Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP (2018a) Liquorice (Glycyrrhiza glabra): a phytochemical and pharmacological review. Phytotherapy Research : PTR 32(12):2323–2339. https://doi.org/10.1002/ptr.6178
Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP (2018b) Liquorice (Glycyrrhiza glabra): a phytochemical and pharmacological review. Phytother Res 32(12):2323–2339. https://doi.org/10.1002/ptr.6178
Rahimi VB, Shirazinia R, Fereydouni N, Zamani P, Darroudi S, Sahebkar AH et al (2017a) Comparison of honey and dextrose solution on post-operative peritoneal adhesion in rat model. Biomed Pharmacother 92:849–855. https://doi.org/10.1016/j.biopha.2017.05.114
Rahimi VB, Askari VR, Mousavi SH (2018) Ellagic acid reveals promising anti-aging effects against d-galactose-induced aging on human neuroblastoma cell line, SH-SY5Y: A mechanistic study. Biomed Pharmacother 108:1712–1724. https://doi.org/10.1016/j.biopha.2018.10.024
Rahmanian-Devin P, Rakhshandeh H, Baradaran Rahimi V, Sanei-Far Z, Hasanpour M, Memarzia A et al (2021) Intraperitoneal lavage with crocus sativus prevents postoperative-induced peritoneal adhesion in a rat model: evidence from animal and cellular studies. Oxid Med Cell Longev 2021:5945101. https://doi.org/10.1155/2021/5945101
Rasool M, Iqbal J, Malik A, Ramzan HS, Qureshi MS, Asif M et al (2014) Hepatoprotective effects of silybum marianum (Silymarin) and Glycyrrhiza glabra (Glycyrrhizin) in Combination: a possible synergy. Evid-Based Complement Alternative Med. https://doi.org/10.1155/2014/641597
Roohbakhsh Y, Baradaran Rahimi V, Silakhori S, Rajabi H, Rahmanian-Devin P, Samzadeh-Kermani A et al (2020a) Evaluation of the effects of peritoneal lavage with rosmarinus officinalis extract against the prevention of postsurgical-induced peritoneal adhesion. Planta Med 86(06):405–414. https://doi.org/10.1055/a-1118-3918
Roohbakhsh Y, Rahimi VB, Silakhori S, Rajabi H, Rahmanian-Devin P, Samzadeh-Kermani A et al (2020b) Evaluation of the effects of peritoneal lavage with Rosmarinus officinalis extract against the prevention of postsurgical-induced peritoneal adhesion. Planta Med 86(06):405–414
Sahbaz A, Isik H, Aynioglu O, Gungorduk K, Gun BD (2014) Effect of intraabdominal administration of Allium sativum (garlic) oil on postoperative peritoneal adhesion. Eur J Obstet Gynecol Reprod Biol 177:44–47. https://doi.org/10.1016/j.ejogrb.2014.03.018
Sarap MD, Scher KS, Jones CW (1986) Anaerobic coverage for wound prophylaxis. Comparison of cefazolin and cefoxitin. Am J Surg 151(2):213–215. https://doi.org/10.1016/0002-9610(86)90072-3
Schnüriger B, Barmparas G, Branco BC, Lustenberger T, Inaba K, Demetriades D (2011) Prevention of postoperative peritoneal adhesions: a review of the literature. Am J Surg 201(1):111–121. https://doi.org/10.1016/j.amjsurg.2010.02.008
Syahputra DA, Mashudy A, Dasrul, (2020) The effect of addition of dexamethasone into normal saline irrigation solution on prevention of intraperitoneal adhesion post laparotomy in wistar rats (Rattus norvegicus). Ann Med Surg (lond) 59:57–63. https://doi.org/10.1016/j.amsu.2020.08.053
Tian X, Liu Y, Liu X, Gao S, Sun X (2019) Glycyrrhizic acid ammonium salt alleviates Concanavalin A-induced immunological liver injury in mice through the regulation of the balance of immune cells and the inhibition of hepatocyte apoptosis. Biomed Pharmacother 120:109481. https://doi.org/10.1016/j.biopha.2019.109481
Ward BC, Panitch A (2011) Abdominal adhesions: current and novel therapies. J Surg Res 165(1):91–111. https://doi.org/10.1016/j.jss.2009.09.015
Wei G, Chen X, Wang G, Fan L, Wang K, Li X (2016) Effect of resveratrol on the prevention of intra-abdominal adhesion formation in a rat model. Cell Physiol Biochem 39(1):33–46. https://doi.org/10.1159/000445603
Wynn TA (2008) Cellular and molecular mechanisms of fibrosis. J Pathol 214(2):199–210. https://doi.org/10.1002/path.2277
Zhang H, Zhang R, Chen J, Shi M, Li W, Zhang X (2017) High mobility group box1 Inhibitor Glycyrrhizic acid attenuates kidney injury in streptozotocin-induced diabetic rats. Kidney Blood Press Res 42(5):894–904. https://doi.org/10.1159/000485045
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This study was financially supported by the research council of Mashhad University of Medical Sciences (950312).
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HR: conceptualization, methodology, software, supervision, visualization, investigation, writing—reviewing and editing; VBR, BD, PR, AJ, MHa, and MI: visualization, investigation, writing—reviewing and editing; VRA: conceptualization, methodology, software, supervision, visualization, investigation, writing—reviewing and editing.
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Rakhshandeh, H., Baradaran Rahimi, V., Dehghan-Naieri, B. et al. Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model. Inflammopharmacol 31, 899–914 (2023). https://doi.org/10.1007/s10787-023-01139-7
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DOI: https://doi.org/10.1007/s10787-023-01139-7