Therapeutic Potential of Plants and Plant Derived Phytochemicals against Acetaminophen-Induced Liver Injury

Abstract

Acetaminophen (APAP), which is also known as paracetamol or N-acetyl-p-aminophenol is a safe and potent drug for fever, pain and inflammation when used at its normal therapeutic doses. It is available as over-the-counter drug and used by all the age groups. The overdose results in acute liver failure that often requires liver transplantation. Current clinical therapy for APAP-induced liver toxicity is the administration of N-acetyl-cysteine (NAC), a sulphydryl compound an approved drug which acts by replenishing cellular glutathione (GSH) stores in the liver. Over the past five decades, several studies indicate that the safety and efficacy of herbal extracts or plant derived compounds that are used either as monotherapy or as an adjunct therapy along with conventional medicines for hepatotoxicity have shown favorable responses. Phytochemicals mitigate necrotic cell death and protect against APAP-induced liver toxicityby restoring cellular antioxidant defense system, limiting oxidative stress and subsequently protecting mitochondrial dysfunction and inflammation. Recent experimental evidences indicat that these phytochemicals also regulate differential gene expression to modulate various cellular pathways that are implicated in cellular protection. Therefore, in this review, we highlight the role of the phytochemicals, which are shown to be efficacious in clinically relevant APAP-induced hepatotoxicity experimental models. In this review, we have made comprehensive attempt to delineate the molecular mechanism and the cellular targets that are modulated by the phytochemicals to mediate the cytoprotective effect against APAP-induced hepatotoxicity. In this review, we have also defined the challenges and scope of phytochemicals to be developed as drugs to target APAP-induced hepatotoxicity.

Sterols and Triterpenes: Antiviral Potential Supported by In-Silico Analysis

“…Asiatic acid (20) is a naturally occurring aglycone of ursane-type pentacyclic triterpenoids. It has been previously reported from a wide range of plants e.g., Actinida argute roots, Centella Asiatica leaves, and Combretum laxum Stems [ 43 ]. It has poly-pharmacological properties like antioxidant, anti-inflammatory.…”

“…Numerous in vivo and in vitro studies reported that asiatic acid (20) influences many enzymes, receptors, growth, and transcription factors, in addition to several cell signaling cascades. Moreover, it inhibits both HIV-1 and enterovirus 71 (EV71) replications in acutely infected host cells with IC 50 equal to 9 and 20 µM, respectively [ 43 , 44 ].…”

“…It has been found that the addition of ureides or the C-28 amide group to betulinic acid increases its anti-HSV-1 activity [ 61 , 62 ]. Moreover, the 3-oxime derivatives of betulinic acid were more active than betulinic acid against the influenza A virus with EC 50 of 2.8 µM [ 43 ], whereas betulinic aldehyde showed antiviral activity against the H9N2 subtype of the avian influenza virus [ 48 ]. Another betulinic acid derivative called 3β,28-di-onicotinoylbetulin is active against human papillomavirus (HPV) type 11 with an IC 50 value of 12.4 µM type [ 49 ].…”

Cinnamon oil against acetaminophen-induced acute liver toxicity by attenuating inflammation, oxidative stress and apoptosis

“…When APAP is uses as the dose of a physician, it is effective and nontoxic analgesic and antipyretic. Nevertheless, long term administration or overdoses of APAP can cause a deleterious effect on the liver [ 6 ]. APAP-induced liver injury was well recognized by numerous studies- [ [7] , [8] , [9] ].…”

Auriculatone Sulfate Effectively Protects Mice Against Acetaminophen-Induced Liver Injury

“…Overdose of APAP may cause a wide range of adverse effects [40,41]. Although quite a number of compounds (e.g., silymarin, glycyrrhizic acid and oleanolic acid) were shown to possess hepatoprotective effect against APAP-induced hepatotoxicity [42], their hepatoprotective effects and mechanisms of action might not be satisfactory enough, and administration of NAC is still one of the best clinical therapies for APAP-induced liver toxicity. Our study demonstrated that AS almost completely prevented APAP-induced liver injury as NAC in every aspect, and the hepatoprotection is associated with its retaining expression of CYP enzymes and inhibition of the activities of CYP2E1 and CYP3A11 to decrease APAP bioactivation.…”