Deciphering the therapeutic actions of Brenania brieyi (Rubiaceae) fractions on oxidoinflammatory anomalies

Abstract

A decline in the antioxidant network during the inflammatory response plays a critical role in the pathogenesis of numerous diseases. We designed this study to decipher the therapeutic efficacy of Brenania brieyi in reducing oxidative stress caused by the inflammatory response to cotton pellets. Graded doses of methanol and chloroform fractions of B. brieyi (MFBB and CFBB) and indomethacin were administered to Wistar rats for seven days after implanting sterilised cotton pellets (20 mg). Thereafter, biochemical indices of oxidative stress were determined using blood samples taken through cardiac puncture. Furthermore, molecular interactions, drug-likeness, and toxicity features of B. brieyi phytochemicals were also assessed. Compared with the untreated group, the groups treated with MFBB and CFBB had a significant (p < 0.05) decrease in granuloma tissue weight and MDA levels while increasing glutathione levels, SOD, and CAT activities. In addition, a substantial increase in inflammatory-induced changes in antioxidant nutrients, together with a decline in liver enzymes, was obtained in the treated groups. The docking tests revealed that the top-scoring phytoconstituents of B. brieyi, n-hexadecanoic acid, and 9-octadecanoic acid interacted well with catalase, having docking scores of -6.19 and -7.58 kcal/mol, respectively. Moreover, the hits had good oral drug-likeness features and a safe toxicity profile. The findings of the study provide evidence that B. brieyi has antioxidant and anti-inflammatory properties, suggesting that it could be used as an alternative therapy to regulate oxidative stress-related diseases.

Keywords

• Inflammation
• Brenania brieyi
• Antioxidants
• Oxidative stress
• Lipid peroxidation

Supporting Institution

UNIVERSITY OF NIGERIA, NIGERIA

Project Number

UNN/FBS/EC/1049

Ethical Statement

UNN/FBS/EC/1049

References

1. Aebi, H.E. (1983). Catalase In Vitro Methods of Enzymatic Analysis (3rd editio). Bergmeyer, H.U., Ed.; Verlag Chemie: Weinhem.
2. Alothaid, H. (2022). Evaluation of cytotoxicity , oxidative stress and organ-specific effects of activated carbon from Al-Baha date palm kernels. Saudi Journal of Biological Sciences, 29(9), 103387. https://doi.org/10.1016/j.sjbs.2022.103387
3. Apeh, V.O., Chukwuma, F.I., Nwora, F.N., Njoku, O.U., & Nwodo, F.O. (2021). Significance of crude and degummed citrullus lanatus seed oil on inflammatory cytokines in experimental infection induced by candida albicans. Acta Pharmaceutica Sciencia, 59(3), 363–383. https://doi.org/10.23893/1307-2080.APS.05922
4. Apeh, V.O., Adegboyega, A.E., Chukwuma, I.F., Ugwah-Oguejiofor, C.J., Aja, P.M., Ofeimun, J.O., Ale, B.A., Johnson, G.I., Ebenyi, L.N., Iwaloye, O., Ejembi, S.A., Ezugworie, F.N., & Johnson, T.O. (2023). An in silico study of bioactive compounds of Annona muricata in the design of ani-prostate cancer agent: MM/GBSA, pharmacophore modeling and ADMET parameters. Informatics in Medicine Unlocked, 43, 101377. https://doi.org/10.1016/j.imu.2023.101377
5. Ashenafi, E., Abula, T., Abay, S. M., Arayaselassie, M., & Sori, M. (2023). Evaluation of the Antioxidant and Wound Healing Properties of 80% Methanol Extract and Solvent Fractions of the Leaves of Vernonia auriculifera Hiern. (Asteraceae). Journal of Experimental Pharmacology, 15, 29–40. https://doi.org/10.2147/CCID.S393379
6. Awan, S.S., Khan, T.R., Mehmood, A., Hafeez, M., Abass, Rizwan, S., Nazir, M., & Raffi, M. (2023). Ailanthus altissima leaf extract mediated green production of zinc oxide ( ZnO ) nanoparticles for antibacterial and antioxidant activity. Saudi Journal of Biological Sciences, 30(1), 103487. https://doi.org/10.1016/j.sjbs.2022.103487
7. Belahcene, S., Kebsa, W., Akingbade, T.V., Umar, H.I., Alex, D., Alshihri, A.A., Mansour, A.A., & Alhasaniah, A.H. (2024). Chemical Composition and Antioxidant and Anti- Inflammatory Activities of Myrtus communis L. Leaf Extract : Forecasting Absorption , Distribution , Metabolism , and Toxicity Profiling and Anti- Inflammatory Targets Using Molecular Docking Tools. Molecules, 29, 849–881.
8. Beutler, E., Duron, O., & Kelly, B.M. (1963). Improved method for determination of blood glutathione. J. Lab. Clin. Med., 61, 882–888.

9. Chukwuma, I.F., Apeh, V.O., Ezeanyika, L.U., & Ogugua, V.N. (2021). Brenania brieyi root bark extracts ameliorate chronic inflammation-mediated oxidative stress in Wistar rats. 1st International Electronic Conference on Antioxidants in Health and Disease, 1–7. https://doi.org/10.3390/cahd2020-08556
10. Chukwuma, I.F., Apeh, V.O., Nworah, F.N., Nkwocha, C.C., Emaimo, J., Ezeanyika, L.U., Sunday, & Ogugua, V.N. (2022). Inhibition of phospholipase A2 and prostaglandin synthase activities as possible mechanistic insight into the anti-inflammatory activity of Brenania brieyi methanol and chloroform fractions. Thai Journal of Pharmaceutical Sciences, 46(1), 75–84.
11. Chukwuma, I.F., Ezeorba, T.P.C., Nworah, F.N., Apeh, V.O., Khalid, M., & Sweilam, S.H. (2023). Bioassay-guided identification of potential Alzheimer ’ s disease therapeutic agent s from Kaempferol-Enriched fraction of Aframomum melegueta seeds using in vitro and chemoinformatics approaches. Arabian Journal of Chemistry, 16(9), 105089. https://doi.org/10.1016/j.arabjc.2023.105089
12. Doumas, B.T., Watson, W.A., & Biggs, H.G. (1971). Albumin standards and the measurement of serum albumin with bromocresol green. Clin Chim Acta, 31, 87–96.
13. Ezeala, I.C., Uzor, P.F., Obiora, C.U., Maryann, C., Anyadiegwu, C.I., & Nwodo, N.J. (2023). Antimicrobial and Antitrypanosomal Activities of Methanol Root Extract and Fractions of Brenania brieyi (De Wild) Petit (Rubiaceae). African Journal of Pharmaceutical Research and Deelopment, 15(3), 43–52. https://doi.org/10.59493/ajopred/2023.3.6
14. Ezeorba, Chidike Prince, T., Ezeugwu, L.A., Chukwuma, I.F., Anaduaka, G.E., & Udenigwe, C.C. (2024). Health-promoting properties of bioactive proteins and peptides of garlic (Allium sativum ). Food Chemistry, 435, 137632.
15. Fridovich, I. (1989). Superoxide dismutase: An adaptation to a paramagnetic gas. Journal of Biological Chemistry, 264, 7761–7764.
16. Gashaye, M.B., & Birhan, Y.S. (2023). Phytochemical constituents, antioxidant and antibacterial activities of Plectocephalus varians (A. Rich.) C. Jeffrey ex Cufod root extracts. BMC Complementary Medicine and Therapies, 23(1), 135 144. https://doi.org/10.1186/s12906-023-03919-8
17. Goodhart, R.S., & Shils, M.E. (1973). Modern Nutrition in Health and Disease: Dietotherapy. Lea & Febiger.
18. Hussen, E.M., & Endalew, S.A. (2023). In vitro antioxidant and free-radical scavenging activities of polar leaf extracts of Vernonia amygdalina. BMC Complementary Medicine and Therapies, 23(1), 146–157. https://doi.org/10.1186/s12906-023-03923-y
19. Jendrassik, L., & Grof, P. (1938). In vitro determination of total and direct bilirubin in serum. Biochem. J., 297, 81–83.
20. Johnsen, O., & Eliasson, R. (1987). Evaluation of a commercially available kit for the colorimetric determination of zinc. International Journal of Andrology, 10(2), 435–440.
21. Kaufmanova, J., Stikarova, J., Hlavackova, A., Chrastinova, L., Maly, M., Suttnar, J., & Dyr, J.E. (2021). Fibrin clot formation under oxidative stress conditions. Antioxidants, 10(6), 1–13. https://doi.org/10.3390/antiox10060923
22. Krishnaiah, L., Kumar, K.S., & Suvardhan, K. Chiranjeevi, P. (2003). Simple spectrophotometric determination of traces of selenium in environmental samples. Proceedings of the Third International Conference onEnvironment and Health. Proceedings of the Third International Conference OnEnvironment and Health, Chennai, 217-225.
23. Mosquera, D.M., Ortega, Y.H., Kilonda, A., Dehaen, W., Pieters, L., & Apers, S. (2011). Evaluation of the in vivo anti-inflammatory activity of a flavonoid glycoside from Boldoa purpurascens. Phytochemistry Letters, 4, 231-234.
24. Nkwocha, C.C., Ogugofor, M.O., Chukwuma, I.F., & Njoku, O.U. (2022). Identification and characterization of phytochemicals and constituents in Desmodium velutinum stem using high-performance liquid chromatography ( HPLC ). Pharmacological Research - Modern Chinese Medicine, 3(January), 100090. https://doi.org/10.1016/j.prmcm.2022.100090
25. Odo, I.F., Ezeanyika, L.U.S., Ogugua, V.N., Joshua, P.E., & Okagu, I.U. (2017). FTIR and GC-MS Spectroscopic Analysis of Methanol and Chloroform Extracts of Brenania brieyi Root Bark. American Journal of Research Communication, 5(3), 44–54. www.usa-journals.com
26. Onyesife, O.C., Chukwuma, I.F., Okagu, I.U., Ndefo, C.J., Amujiri, A.N., & Ogugua, V.N. (2023). Nephroprotective effects of Piper nigrum extracts against monosodium glutamate-induced renal toxicity in rats. Scientific African, 19, e01453. https://doi.org/10.1016/j.sciaf.2022.e01453
27. Paglia, P.E., & Valentine, W.N. (1967). Studies on the quantitation and qualitative characterization of erythrocytes glutathione peroxidase. Journal of Laboratory and Clinical Medicine, 70, 158–169.
28. Pearson, D. (1976). The chemical analysis of food (17th edit.). Churchill Livingston.
29. Pisoschi, A.M., Pop, A., Iordache, F., Stanca, L., Predoi, G., & Serban, A.I. (2021). Oxidative stress mitigation by antioxidants - An overview on their chemistry and influences on health status. European Journal of Medicinal Chemistry, 209, 112891. https://doi.org/10.1016/J.EJMECH.2020.112891
30. Radi, F.Z., Bencheikh, N., Bouhrim, M., Elbouzidi, A., Bnouham, M., & Zair, T. (2023). Phytochemical Analysis , Antioxidant , and Antihyperglycemic Activities of Crataegus monogyna Jacq Aqueous Extract. Natural Product Communications, 18, 1–15. https://doi.org/10.1177/1934578X231195157
31. Reitman, S., & Frankel, S.A. (1957). A colorimetric method for determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. American Journal of Clinical Pathology, 28, 56–63. https://doi.org/10.1093/ajcp/28.1.56
32. Rodrigues, S., Oliveira, V.D.C., Rodrigues, S.D.O., Souto, S.M.T., & Geraldo, A. (2024). Chemical profile and evaluation of the pharmacological activity of the dry extract and fraction of ethyl acetate obtained from the leaves of Mimosa caesalpiniifolia Chemical profile and evaluation of the pharmacological activity of the dry extract and fra. Journal of Ethnopharmacology, 323(January), 117716. https://doi.org/10.1016/j.jep.2024.117716
33. Ryter, S.W. (2022). Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular , Lung , and Related Metabolic Disorders. Antioxidants, 11, 555–580.
34. Sierra‐campos, E., Valdez‐solana, M., Avitia‐domínguez, C., Campos‐almazán, M., Flores‐molina, I., García‐arenas, G., & Téllez‐valencia, A. (2020). Effects of Moringa oleifera leaf extract on diabetes‐ induced alterations in paraoxonase 1 and catalase in rats analyzed through progress kinetic and blind docking. Antioxidants, 9(9), 1 19. https://doi.org/10.3390/antiox9090840
35. Tietz, N.W. (1995). Clinical Guide to Laboratory Test (3rd Editio). W. B.Saunders, Philadelphia,.
36. Wallin, B., Rosengren, B., Shertzer, H.G., & Camejo, G. (1993). Lipoprotein oxidation and measurement of TBARS formation in a single microtiter plate: Its use for evaluation of antioxidants. Analytical Biochemistry, 208, 10–15.
37. Yusuf, A.J., Adegboyega, A.E., Yakubu, A.H., Johnson, G.I., Asomadu, R.O., Adeduro, M. N., Chukwuma, I.F., Ugwah-oguejiofor, C.J., Okoh, O.S., & Johnson, T.O. (2023). Exploring Scutellaria baicalensis bioactives as EGFR tyrosine kinase inhibitors : Cheminformatics and molecular docking studies. Informatics in Medicine Unlocked, 43, 101406. https://doi.org/10.1016/j.imu.2023.101406