Abstract
A multi-herbal combination (MHC) of five herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced significant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na+/K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose significantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered acetaminophen (APAP) biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Furthermore, MHC significantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane fluidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroinflammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.
Highlights
At present time, a holistic therapeutic approach using botanicals is intensely required to underscore the complex cell biology coupled with multi-factorial pathogenesis
It was observed that multi-herbal combination (MHC) administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers, phase I reaction enzymes (NADPH-cytochrome P450 reductase and nicotinamide adenine dinucleotide hydride (NADH)-cytochrome b5 reductase), and oxidant biomarkers
It was observed that the highest amount of kaempferol (40.68 μg/mg) was detected in MHC followed by ellagic acid, gallic acid, quercetin, and epicatechin
Summary
A holistic therapeutic approach using botanicals is intensely required to underscore the complex cell biology coupled with multi-factorial pathogenesis. The notion of the pharmacological action of botanicals due to a single active principle or purified compound has been substituted by the concept of the cumulative effect of several phytoconstituents (Carmona and Pereira 2013). This perspective engrosses the interaction between different plant-derived bioactive constituents and forms the basis of phytotherapy. Based on the folklore uses and beneficial health effects five plants i.e. Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers, and Trigonella corniculata L. were scrutinized for the development of a multi-herbal combination (MHC) with biofunctional importance in antioxidative and antihepatoma studies, as discussed in our previous study (Kaur et al 2019). The present study is the auxiliary investigation of MHC for its in vivo hepatoprotective significance against acetaminophen (APAP)-induced acute toxicity or drug-induced liver injury (DILI) in Wistar rats
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