Effects of Ottonia anisum plant extract on local anesthetic, analgesic, anti-inflammatory and HCl-induced acute lung injury activities: a study in animal models

Abstract

Ottonia anisum (O. anisum), belonging to the family Piperaceae, is renowned for its medicinal properties. The plant is rich in alkaloids, terpenoids and flavonoids with recorded bioactivities. The stems, roots, and leaves, of the O. anisum have been extensively used in the folk medicine. Therefore, the present study was conducted to examine the pharmacological activities of O. anisum root extract. Methanolic root extract of O. anisum was assessed for local anesthetic, analgesic, anti-inflammatory and HCl-induced acute lung injury activities in animal models. Local anesthetic activity assessed in frog and guinea pigs through foot withdrawal reflex and intradermal wheal method, respectively, revealed the dose-dependent onset time of anesthesia response. In the case of HCl-induced ALI, the mice group orally administered with O. anisum extract were assessed for bronchoalveolar lavage fluid (BLF) contents, oxidative stress, and proinflammatory molecules. The analysis revealed the reduction in inflammatory molecules, neutrophils, and oxidative stress in the extract treated mice group. In addition, the redox homeostasis, reduced GSH and the catalase activity was found to be restored in the treated groups. Intriguingly, the genes associated with the NFkB expression was found to be downregulated in O. anisum extract treated groups. Moreover, the extract unveiled the significant analgesic and anti-inflammatory activities. Overall, the findings emphasize the clinical applicability of O. anisum extract in the treatment of ALI as well as the potential usage in local anesthetic, analgesic, and anti-inflammatory agents during the treatments.

Keywords

Ottonia anisum / Local anesthetic agent / Acute lung injury / Proinflammatory molecules / Redox homeostasis / Analgesic

References

Aebi H. Catalase in vitro. Methods Enzymol, 1984, 105: 121-126.

Alawdi SH, Al-Zomor A, Shehab M. Evaluation of the local anesthetic activity and formulation of a topical local anesthetic gel from Chrysanthemum cinerarifolium extract. Saudi Med J, 2019, 4: 538-541.

Antony R, Raveendran J, Biju PG. Anti-inflammatory activity of Mollugo cerviana methanolic extract in LPS-induced acute inflammatory RAW 2647 macrophages. Comb Chem High Throughput Screen, 2022, 25: 1661-1671.

Batista D, Campos P, Silva VR, Santos LDS, Bezerra DP, Soares MB, . Piper anisum as a promising new source of bioactive metabolites. Chem Pap, 2020, 74: 1505-1515.

Butt Y, Kurdowska A, Allen TC. Acute lung injury: a clinical and molecular review. Arch Pathol Lab Med, 2016, 140: 345-350.

Chatterjee A, Sen B, Das S, Chatterjee TK. Anti-inflammatory and analgesic activity of methanolic extract of medicinal plant Rhodiola rosea rhizomes. Int J Pharmacol Res Rev, 2015, 4: 1-8.

Cunico MM, Trebien HA, Galetti FC, Miguel OG, Miguel MD, Auer CG, . Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae). Ann Acad Bras Cienc., 2015, 87: 1991-2000.

Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys, 1959, 82: 70-77.

Ema RS, Kabir Zihad SMN, Islam MN, Sifat N, Rouf R, Shilpi JA, Uddin SJ. Analgesic, anti-inflammatory activity and metabolite profiling of the methanolic extract of Callicarpa arborea Roxb. leaves. J Ethnopharmacol, 2023, 300: 115757.

Formagio ASN, de Oliveira PC, Volobuff CRF, Kassuya CAL, Ferreira DC, Cardoso CAL, Sarragiotto MH, Pereira ZV. Anti-inflammatory activity of methanolic extract and an alkaloid from Palicourea crocea (Sw.) roem and schult. Inflammation, 2019, 42: 1045-1055.

Galani VJ, Patel BG. Psychotropic activity of Argyreia speciosa roots in experimental animals. Ayu, 2011, 32: 380.

Ghauri MA, Iqbal L, Raza A, Hayat U, Atif N, Javeed A. In vivo anti-inflammatory, antipyretic, analgesic activity and in vitro anti-proliferative activity of aqueous methanolic extract of Euphorbia granulata Forssk. Fut J Pharmaceut Sci, 2021, 7(1): 1-10.

Johnson ER, Matthay MA. Acute lung injury: epidemiology, pathogenesis, and treatment. J Aerosol Med Pulm Drug Deliv, 2010, 23: 243-252.

Kanti PS, Mohan P, Barua CC, Sarkar BK, Lahon LC. Analgesic, anti-inflammatory and local anesthetic activity of methanol extract of Bryophyllum pinnatum leaves. J Entomol Zool Stud, 2020, 8: 07-11.

Kapoor K, Singla E, Sahu B, Naura AS. PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice. Mol Cell Biochem, 2015, 400: 153-162.

Kaur G, Jaswal P, Banga R, Dharwal V, Kumar A, Naura AS. Hydroalcoholic extract of Argyreia speciosa roots ameliorates HCl-mediated acute lung injury in mice. Pharmacogn Mag, 2018, 14: 8.

Kellner M, Noonepalle S, Lu Q, Srivastava A, Zemskov E, Black SM. ROS signaling in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Adv Exp Med Biol, 2017, 967: 105-137.

Kuete V, Viertel K, Efferth T. Antiproliferative potential of African medicinal plants. Medicinal plant research in Africa, 2013, Amsterdam: Elsevier, 711-724.

Kumar SR, Garg A, Shrimali K (2022) Botanical description, photochemistry, traditional uses, and pharmacology of the “wonder plant” Kalanchoe Pinnata (Linn.) Pers: an updated review. J Pharmaceut Med Chem 8

Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther, 2017, 2: 17023.

Lloyd CM, Marsland BJ. Lung homeostasis: influence of age, microbes, and the immune system. Immunity, 2017, 46: 549-561.

López KS, Marques AM, Moreira DDL, Velozo LS, Sudo RT, Zapata-Sudo G, . Local anesthetic activity from extracts, fractions and pure compounds from the roots of Ottonia anisum Spreng (Piperaceae). Ann Acad Bras Cienc., 2016, 88: 2229-2237.

Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem, 1951, 193: 265-275.

Malairajan P, Gopalakrishnan G, Narasimhan S, Veni KJK. Analgesic activity of some Indian medicinal plants. J Ethnopharmacol, 2006, 106: 425-428.

Malik A, Najda A, Bains A, Nurzyńska-Wierdak R, Chawla P. Characterization of citrusnobilis peel methanolic extract for antioxidant, antimicrobial, and anti-inflammatory activity. Molecules, 2021, 26: 4310.

Marques AM, Velozo LS, Carvalho MA, Serdeiro MT, Honório NA, Kaplan MAC, Maleck M. Larvicidal activity of Ottonia anisum metabolites against Aedes aegypti: a potential natural alternative source for mosquito vector control in Brazil. J Vector Borne Dis, 2017, 54: 61-68.

Muralikrishnan K, Asokan S, Priya PG, Ahmed KSZ, Ayyappadasan G. Comparative evaluation of the local anesthetic activity of root extract of Anacyclus pyrethrum and its interaction at the site of injection in guinea pigs. Anesth Essays Res, 2017, 11: 444.

Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 1979, 95: 351-358.

Olela B, Mbaria J, Wachira T, Moriasi G. Acute oral toxicity and anti-inflammatory and analgesic effects of aqueous and methanolic stem bark extracts of Piliostigma thonningii (Schumach.). Evid-Based Compl Alt Med, 2020, 5651390: 1-10.

Patel NB, Galani VJ, Patel BG. Antistress activity of Argyreia speciosa roots in experimental animals. J Ayurveda Integr Med, 2011, 2: 129.

Raghavendra HL, Kekuda TR. Ethnobotanical uses, phytochemistry and pharmacological activities of Peperomia pellucida (L.) Kunth (piperaceae)—a review. Int J Pharm Pharm Sci, 2018, 10: 1.

Ramanathan T, Gurudeeban S, Satyavani K. Local anesthetic effect of Citrullus colocynthis on Rana hexadactyla. Res J Med Plant, 2011, 5: 338-342.

Rates SMK, Chaves CG, Von Posser GL. Investigation of local anesthetic effect and toxicity of Ottonia propinqua (Piperaceae). Acta Farm Bonaerense, 1997, 16: 113-116.

Reza MS, Jashimuddin M, Ahmed J, Abeer M, Naznin NE, Jafrin S, . Pharmacological investigation of analgesic and antipyretic activities of methanol extract of the whole part of Aeginetia indica. J Ethnopharmacol, 2021, 271.

Tang X, Liu D, Shishodia S, Ozburn N, Behrens C, Lee JJ, . Nuclear factor-κB (nf-κB) is frequently expressed in lung cancer and preneoplastic lesions. Cancer, 2006, 107: 2637-2646.

Tsuchiya H. Anesthetic agents of plant origin: a review of phytochemicals with anesthetic activity. Molecules, 2017, 22: 1369.

Tsushima K, King LS, Aggarwal NR, De Gorordo A, D'Alessio FR, Kubo K. Acute lung injury review. Inter Med, 2009, 48: 621-630.

Udegbunam RI, Asuzu UI, Kene RO, Udegbunam SO, Nwaehujor CO. Local anesthetic and tissue effects of the leaf extract and fractions of Sterculia tragacantha Lindl. J Pharmacol Toxicol, 2012, 7: 192-196.

Wan L, Meng D, Wang H, Wan S, Jiang S, Huang S, . Preventive and therapeutic effects of thymol in a lipopolysaccharide-induced acute lung injury mice model. Inflammation, 2018, 41: 183-192.

Wang H, Joseph JA. Quantifying cellular oxidative stress by dichlorofluorescein assay using microplate reader. Free Radic Biol Med, 1999, 27: 612-616.

Woolfe G, MacDonald AD. The evaluation of the analgesic action of pethidine hydrochloride (Demerol). J Pharmacol Exp Ther, 1944, 80: 300-307.

Zahler WL, Cleland WW. A specific and sensitive assay for disulfides. J Biol Chem, 1968, 243: 716-719.

Zhu T, Wang DX, Zhang W, Liao XQ, Guan X, Bo H, . Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-κB. PLoS ONE, 2013, 8.