Ethnopharmacological impact of Melaleuca rugulosa (Link) Craven leaves extract on liver inflammation. (28th June 2022)

• Record Type: Journal Article
• Authors: Elsayed, Heba E.; Ebrahim, Hassan Y.; Mady, Mohamed S.; Khattab, Mohamed A.; El-Sayed, Elsayed K.; Moharram, Fatma A.
• Is Part Of: Journal of ethnopharmacology. Volume 292(2022)
• Publication Date: 2022-06-28
• Subjects: Antiapoptotic -- Anti-inflammatory -- Antioxidant -- Flavonoids -- Hepatoprotective -- Melaleuca rugulosa; Ethnopharmacology -- Periodicals; Pharmacognosy -- Periodicals; Herbs -- Periodicals; Herbs -- Periodicals; Pharmacognosy -- Periodicals; Pharmacognosie -- Périodiques; Herbes -- Périodiques; 615.1
• DOI: 10.1016/j.jep.2022.115215
• Languages: English
• ISSNs: 0378-8741

Abstract

Abstract: Ethnopharmacological relevance: Melaleuca species have been used by many ethnic communities for the management and treatment of several ailments as hemorrhoids, cough, skin infections, rheumatism, sore throat, pain, inflammation, and digestive system malfunctions. However, the detailed mechanistic pharmacological effect of Melaleuca rugulosa (Link) Craven leaves in the management of liver inflammation has not been yet addressed. Aim of the study: The present study aimed to evaluate the anti-inflammatory, antioxidant, and antiapoptotic capacities of the aqueous methanol extract of M. rugulosa leaves in relevance to their flavonoid content using an appropriate in vivo model. Materials and methods: The aqueous methanol extract of M. rugulosa leaves was administered to the rats at three non-toxic doses (250, 500, and 1000 mg/kg) for seven days prior to the initiation of liver-injury induced by paracetamol (3 g/kg). Liver enzymes including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were evaluated in serum samples. The oxidative stress markers including reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels as well as the inflammatory markers such as tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB), were assessed in liver homogenate. The results were supported by histopathological and immuno-histochemical studies. The phytochemical investigation of the flavonoid-rich fraction of the aqueous methanol extract was accomplished using different chromatographic and spectroscopic techniques. Results: The aqueous methanol extract of M. rugulosa leaves showed a powerful hepatoprotective activity evidenced by the significant reduction of MDA and NO levels, as well as increasing GSH and catalase activity. Moreover, the extract exhibited anti-inflammatory and antiapoptotic activities witnessed by decreasing TNF-α, NF-κB, iNOS, p-JNK, caspase-3, BAX, and increasing Bcl-2 levels. Moreover, the pretreatment of rats with all doses of M. rugulosa leaves extract showed a significant decrease in liver weight/body weight (LW/BW) ratio, and total bilirubin induced by paracetamol. On the other hand, the chromatographic separation of the flavonoid-rich fraction afforded twenty known flavonoids namely; iso-orientin (1 ), orientin (2 ), isovitexin (3), vitexin (4), quercetin-3- O - β- D-glucuronid methyl ether (5 ), quercetin-3- O - β -D-mannuronpyranoside (6), isoquercetin (7), quercitrin (8), kaempferol-3- O - β -D-mannuronopyranoside (9 ), kaempferol-7- O -methyl ether-3- O - β -D-glucopyranoside (10 ), guaijaverin (11), avicularin (12), kaempferide-3- O-β -D-glucopyranoside (13 ), astragalin (14 ), afzelin (15), luteolin (16 ), apigenin (17 ), quercetin (18), kaempferol (19 ), and catechin (20 ). Conclusion: The aqueous methanol extract of M. rugulosa leaves showed potential hepatoprotective, antioxidant, and anti-inflammatory activities against paracetamol-induced liver inflammation which is correlated at least in part to its considerable phenolic content. Graphical abstract: Image 1 Highlights: Ethnomedicinal value of Melaleuca rugulosa (Link) Craven leaves have been reported in several studies due to the therapeutic values of some indigenous phytochemicals just as phenolics. The present study provides evidence about the potent antioxidant, anti-inflammatory, and hepatoprotective potential of M. rugulosa (Link) Craven aqueous methanol extract on paracetamol induced liver injury. These remarkable effects are dedicated in part to its phenolic contents as tannins, phenolic acids, and flavonoids which mostly act in synergistic mode. M. rugulosa aqueous methanol extract could protect against liver diseases and xenobiotic-induced hepatotoxicity.