Review Article

Hepatoprotective activities of polyherbal formulations: A systematic review

Elizabeth B. Aladejana, Adebowale E. Aladejana

Received: 24 Apr. 2023; Accepted: 27 Aug. 2023; Published: 24 Oct. 2023

Copyright: © 2023. The Author(s). Licensee: AOSIS.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background: Liver diseases pose a substantial global public health challenge, encompassing conditions such as liver failure, hepatitis, cirrhosis and associated complications Safeguarding the liver becomes important as these conditions impact human health. Hepatoprotective agents play a pivotal role in mitigating liver damage caused by chemicals, drugs and toxins. Polyherbal formulations, combining botanical components from traditional medicine, offer a promising approach to addressing liver disorders. Their popularity arises from a multi-targeted strategy in treating complex diseases, marking a shift in focus toward these formulations.

Aim: The study aimed to conduct a thorough review of the existing literature on the hepatoprotective activity of polyherbal formulations and provide a comprehensive overview of their mechanisms of action. This review provides the overview of the use of polyherbal formulations in the management of liver disease.

Method: A systematic search of electronic databases, including : Scopus, Academia, Elsevier, Science Direct, Wiley, BioMed Central, PubMed, and Google Scholar, was conducted using a combination of keywords such as ‘polyherbal formulations’, ‘hepatoprotective’ and ‘liver diseases’. Studies published between January 2010 and April 2023 were included in the review.

Results: A total of 61 articles were reviewed, and the studies showed that polyherbal formulations possess significant hepatoprotective activity against various hepatotoxic agents. The mechanisms of action of these formulations include antioxidant, antiinflammatory, antifibrotic and antiapoptotic effects. Additionally, some polyherbal formulations were found to stimulate liver regeneration, enhance bile secretion and promote detoxification processes.

Conclusion: Polyherbal formulations have shown promising hepatoprotective activity, and their multitargeted approach to treating complex diseases makes them a potential alternative to conventional medicines. However, identifying the active compounds responsible for the hepatoprotective effects of these formulations and their pharmacokinetics and pharmacodynamics could provide insights into the development of new and effective drugs for liver disorders.

Contribution: This article contributes to the growing body of literature on the potential of polyherbal formulations as hepatoprotective agents.

Keywords: antioxidant; hepatoprotection; hepatotoxins; liver disease; polyherbal formulation.

Introduction

Hepatoprotective substances or drugs play a critical role in protecting the liver from damage and preventing injury. As a pivotal organ, the liver regulates many important metabolic functions such as detoxification, metabolism and nutrient storage, thereby maintaining homeostasis of the body. Liver impairment can be induced by various factors including pathogens like bacteria, viruses and parasites, autoimmune diseases like autoimmune hepatitis, primary biliary cirrhosis, as well as toxic compounds such as carbon tetrachloride (CCl₄), and excessive consumption of alcohol (Guan & He 2013; Kalra, Yetiskul & Wehrle 2022). In addition, several chemical agents and medications such as antibiotics, antitubercular drugs, paracetamol, aspirin and ibuprofen which are used on a routine basis contribute to cellular and metabolic liver damage, primarily driven by mechanisms such as lipid peroxidation and other oxidative damage (Mistry, Dutt & Jena 2013). According to Manfo, Nantia and Kuete (2014), xenobiotics such as drugs, food additives, alcohol, chlorinated solvents, peroxidized fatty acids, fungal toxins, radioactive isotopes, environmental toxicants and even some medicinal plants are the leading cause of liver injury or impairment of liver function. The liver disorder encompasses various conditions such as steatosis, fibrosis, hepatitis, cirrhosis and liver cancer which can ultimately result in liver failure and death (Patel, Shah & Tank 2013). In this context, liver disease poses a substantial challenge for both public health and the pharmaceutical industry.

While there are no dedicated allopathic medications that function solely as hepatoprotectants, certain drugs such as colestyramine, cetirizine, naltrexone, spironolactone, furosemide, propranolol, loratadine and vasopressin are employed to manage hepatotoxicity symptoms. Nonetheless, these drugs are not without their limitations, potentially causing adverse effects such as diarrhoea, constipation, flatulence, abdominal discomfort, variable responses and the possibility of exacerbating liver dysfunction (Bhardwaj et al. 2011). In addition, several natural and synthetic compounds like silymarin, curcumin, glycyrrhizin and ursodeoxycholic acid have demonstrated hepatoprotective potential through mechanisms like antioxidation, antiinflammation and antiapoptosis; however, they also have some limitations (Murray 2020; Vargas-Mendoza et al. 2014).

Herbal medicines have been used to cure different ailments since ancient times, and some plant extracts and natural compounds can either protect the liver or induce toxicity (Manfo et al. 2014). Amid this landscape, the efficacy of polyherbal formulations (PHFs) in hepatoprotection assumes increasing significance. Polyherbal medicine is the combination of several herbs and plants to treat various health conditions or to promote overall well-being. This type of traditional medicine has been practised for centuries in many cultures around the world and is still widely used today. The use of multiple herbs in a formula allows for a synergistic effect, where the different constituents work together to enhance the therapeutic effects and minimise potential side effects. Polyherbal medicines can be found in various forms, including teas, tinctures, capsules and topical preparations, and are often customised based on individual needs and symptoms. These formulations have been traditionally used in various cultures for the management of liver diseases, and recent studies have shown promising results in their hepatoprotective effects, with negligible side effects (Iroanya, Adebesin & Okpuzor 2014; Padmanabhan & Jangle 2014; Shetty et al. 2018, 2020). They have been found to contain a variety of bioactive compounds such as flavonoids, alkaloids and terpenoids, which exhibit various pharmacological activities such as antioxidant, antiinflammatory and hepatoprotective effects (Ghayas, Hannan & Rizwani 2022).

The rationale for the review and problem statement

Liver diseases are a significant public health concern globally, and their prevalence is increasing. Conventional drugs used to manage liver diseases can be expensive and with potential side effects, leading to an increased interest in herbal remedies. Herbal medicines, including PHFs, have been used for centuries to treat various ailments, including liver diseases. Polyherbal formulations are gaining popularity because of their potential synergistic effects, improved efficacy and safety compared to single herb formulations. Despite the increasing popularity of PHF, there is a need for a comprehensive review of their hepatoprotective potential against different hepatic dysfunctions. This review aims to discuss the hepatoprotective activities of PHFs based on the results obtained from several studies, assess its effectiveness against hepatic dysfunctions and their mechanisms of action, and provide insight into the potential use of PHF as a safe and effective alternative to conventional drugs for the management of liver diseases.

Methods

A thorough and careful systematic review was conducted using a variety of online databases to gain a complete understanding of the potential of PHFs to protect the liver. This methodical approach ensures that the findings are trustworthy and comprehensive.

The following databases were strategically chosen to ensure that they cover the entire body of literature: Scopus, Academia, Elsevier, ScienceDirect, Wiley, BioMed Central, PubMed and Google Scholar. These databases collectively cover a wide range of scientific disciplines, providing a comprehensive understanding of the hepatoprotective properties of PHFs.

The selection of specific search terms was methodically designed to maximise the retrieval of relevant studies that align with the primary research objective. Search terms used included, but were not limited to, ‘polyherbal formulations’, ‘liver diseases’, ‘hepatoprotective’, ‘herbal medicines’ and ‘liver damage’. These carefully chosen terms ensure the inclusivity of studies investigating various aspects of PHFs’ hepatoprotective properties.

To ensure a robust and current perspective, the review was limited to studies published on the hepatoprotective activities of polyherbal medicines between 2010 and 2023. This timeframe allows for the incorporation of the most recent advancements and insights while maintaining a contemporary context.

The final selection of studies was made using stringent criteria. Studies were carefully selected based on their relevance to the central research question, scientific rigour and methodological quality. This strict inclusion criterion ensures that the studies included contribute significantly to the advancement of knowledge in the field. A total of 61 studies were carefully selected for inclusion in this comprehensive review as a result of this meticulous selection process.

The studies chosen collectively investigate the hepatoprotective potential of PHFs, encompassing their effects against a variety of hepatotropic infections and hepatotoxic agents. By meticulously synthesising the findings of these studies, this review provides a cohesive understanding of the multifaceted hepatoprotective potentials of PHFs and paves the way for deeper insights into their therapeutic mechanisms.

Ethical considerations

Ethical clearance is not applicable to this article, as no survey, human or animal experiment was carried out. The authors make use of available materials from the Internet. All the unique materials used are readily available from the author.

Review findings and discussion

Various research studies have discovered that mixtures of various herbs are surprisingly effective at protecting the liver from harm. Scientists have been studying how these herbal mixtures can help keep the liver healthy, and as a result, numerous studies have been conducted that, when taken together, they provide a comprehensive understanding of how these plant-based interventions work. Experts created these mixtures by combining various natural remedies that act as protectors, shielding the liver from various harmful substances. As we began to look into these published research articles, we discovered a complex system of how these mixtures protect the liver. Researchers in the studies reviewed dedicated significant effort to exploring different combinations of herbs, aiming to find ways to support liver health and maintain its proper function. They have conducted a range of studies with the common goal of reducing liver damage using a mixture of compounds derived from plants. Table 1 displays the hepatoprotective efficacy of PHFs as demonstrated in articles published between 2010 and 2023. Figure 1 and Figure 2 illustrate the hepatotoxins utilised in the experiments to induce liver dysfunction in animal models, as well as the frequency with which each hepatotoxin was used. They include CCl₄ (Ahmad et al. 2020; Arsul, Wagh & Mayee 2011; Balkrishna, Lochab & Varshney 2022; Bera et al. 2012; Gurusamy et al. 2010; Nipanikar, Chitlange & Nagore 2017; Said et al. 2022; Sarhadynejad et al. 2016; Yogi & Mishra 2017), thioacetamide (Balkrishna et al. 2022), hydrogen peroxide (H₂O₂) (Ndefo et al. 2021), gentamicin (Aziz et al. 2017), methotrexate (MTX) (Anila et al. 2015), cadmium chloride (CdCl₂) (Singh et al. 2023), D-galactosamine (Khan et al. 2015; Sachdeva, Bajpai & Razdan 2013; Shetty et al. 2020), alcohol (Dey et al. 2020; Kanchana & Jayapriya 2013; Nipanikar et al. 2017; Rafi Reshi et al. 2022; Shetty et al. 2018), cisplatin (Abuzinadah & Ahmad 2020), isoniazid (INH) (Sankar, Rajkumar & Sridhar 2015), acetaminophen (Ali et al. 2014; Fiaz et al. 2017; Gupta et al. 2013; Mayuren et al. 2010; Nipanikar et al. 2017; Patel et al. 2013; Ray, Taraphdar & Gupta 2022; Saroj, Mani & Mishra 2012; Sen et al. 2015; Shakya 2011; Shrivastava & Garg 2015; Singh et al. 2015; Sivakumar et al. 2014; Srivastava, Kaushik & Lal 2018), aceclofenac (Darbar et al. 2010) and ascorbic acid (Fiaz et al. 2017).

FIGURE 1: List of substances recognised as inducers of hepatic damage in animal models, as discussed in the reviewed research articles. These substances include CCl4, thioacetamide, H2O2, gentamicin, MTX, CdCl2, D-galactosamine, alcohol, cisplatin, INH and acetaminophen.

FIGURE 2: Frequency of use of each hepatotoxin in all the reviewed articles.

Briefly, CCl₄ is one of the most extensively used hepatotoxicants in animal studies; in fact, it was used in 36% of the studies reviewed (Figure 2). It undergoes metabolic activation by cytochrome P450 enzymes to produce highly reactive free radicals, leading to lipid peroxidation, oxidative stress and ultimately hepatocyte damage. This results in the development of liver fibrosis, cirrhosis, necrosis and even hepatocellular carcinoma (Kenjale, Shaikh & Sathaye 2011; Rasheed et al. 2014). Paracetamol (C₈H₉NO₂), also known as acetaminophen, is a widely used analgesic and antipyretic medication that is commonly metabolised by the two pathways, glucuronidation and sulfation, which yield non-toxic metabolites that are easily eliminated from the body. However, excessive and chronic consumption of acetaminophen results in the glucuronidation and sulfation pathways being overwhelmed, and acetaminophen being metabolised through a third pathway called cytochrome P450-mediated oxidation. This third pathway results in the production of the toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is quickly neutralised by the antioxidant glutathione (GSH). Excessive consumption of acetaminophen, however, results in the depletion of GSH and the intrahepatic accumulation of free NAPQI which can further bind to the hepatocellular proteins, causing oxidative stress, mitochondrial dysfunction and hepatic damage (Patel et al. 2013; Ray et al. 2022; Srivastava et al. 2018). Thioacetamide is another hepatotoxin widely used to induce liver damage in animal models. Thioacetamide is metabolised by cytochrome P450 enzymes to form toxic intermediates that bind to cellular proteins, induce oxidative stress and cause cell death. The resulting liver injury is characterised by centrilobular necrosis, inflammation and fibrosis. Studies have shown that thioacetamide-induced liver injury in rats is associated with increased expression of proinflammatory cytokines, such as TNF-α and IL-1β, and decreased expression of antiinflammatory cytokines, such as IL-10 (Kumar et al. 2013). Hydrogen peroxide (H₂O₂) is a powerful oxidant that can cause hepatotoxicity through oxidative stress. When H₂O₂ enters the hepatocytes, it can produce reactive oxygen species (ROS), which are highly reactive oxygen-containing molecules. Reactive oxygen species can harm hepatocellular components such as proteins, lipids and deoxyribonucleic acid (DNA). This oxidative stress can impair normal hepatocellular functions, resulting in inflammation, hepatocellular death and, eventually, hepatic damage. The liver’s ability to detoxify harmful substances may be jeopardised as a result of the oxidative stress caused by H₂O₂. Reactive oxygen species can also activate signalling pathways that promote inflammation and apoptosis (programmed cell death), exacerbating liver damage (Ndefo et al. 2021).

Furthermore, gentamicin is an aminoglycoside antibiotic that can cause nephrotoxicity and hepatotoxicity. The hepatotoxicity is thought to be caused by the accumulation of the drug in the liver, leading to oxidative stress and cell death. It has been shown to cause liver injury by increasing the levels of liver enzymes, such as alanine transaminase (ALT) and aspartate transaminase (AST), and causing histopathological changes in the liver. Gentamicin-induced liver injury is characterised by increased lipid peroxidation, decreased antioxidant levels and impaired mitochondrial function. This results in liver damage and dysfunction (Aziz et al. 2017). Methotrexate is a chemotherapy agent that can cause liver injury by inducing apoptosis and oxidative stress. Methotrexate-induced liver injury is characterised by inflammation, fibrosis and necrosis. Methotrexate induces hepatotoxicity by inhibiting dihydrofolate reductase, affecting folate metabolism and causing hazardous compounds to accumulate in rapidly developing liver cells. This buildup causes oxidative stress, inflammation and poor cellular function, eventually resulting in liver damage. Methotrexate can also stimulate an immunological response in the liver and disrupt normal metabolic processes, all of which contribute to its hepatotoxic effects (Anila et al. 2015). CdCl₂ is a toxic heavy metal that can cause hepatotoxicity. Its hepatotoxic effects are primarily attributed to its ability to cause oxidative stress and inflammation. Cadmium can disrupt the balance of antioxidants and ROS in liver cells, resulting in an excess of ROS. This oxidative stress can harm cellular components such as lipids, proteins and DNA, impairing cell function and promoting inflammation. Cadmium is also known to disrupt various cellular processes and signalling pathways in the liver. It can disrupt calcium homeostasis, mitochondrial function and energy production, all of which contribute to cellular dysfunction and damage. Furthermore, cadmium has been linked to the activation of specific genes and pathways that promote cell proliferation, potentially increasing the risk of liver cancer over time. The liver is essential in detoxifying harmful substances, such as heavy metals like cadmium. Chronic cadmium exposure, on the other hand, overwhelms the liver’s detoxification mechanisms, resulting in cumulative damage and hepatotoxicity, and increased levels of liver marker enzymes, such as ALT and AST (Singh et al. 2023). D-galactosamine causes hepatotoxicity primarily by interfering with protein and ribonucleic acid (RNA) synthesis in hepatocytes. It is taken up by hepatocytes and metabolised to UDP-galactosamine, causing uridine triphosphate (UTP) depletion. The lack of UTP impairs RNA and protein biosynthesis, which is essential for cell function and regeneration. Disruption of these critical cellular processes causes hepatocellular damage, inflammation and apoptosis, ultimately resulting in hepatotoxicity (Khan et al. 2015; Shetty et al. 2020). Alcohol abuse is a common cause of liver disease. Chronic alcohol consumption causes hepatotoxicity, which causes liver damage via a variety of mechanisms. Initially, alcohol is metabolised in the liver by alcohol dehydrogenase and cytochrome P450 enzymes, producing acetaldehyde, a toxic compound that can form adducts with proteins and DNA, causing cellular dysfunction and DNA damage. This causes oxidative stress, mitochondrial dysfunction and inflammation, disrupting hepatocyte function and promoting fibrosis. Furthermore, alcohol impairs fat metabolism, resulting in triglyceride accumulation in hepatocytes (fatty liver), exacerbating liver damage. These processes can progress over time to more severe conditions such as alcoholic hepatitis, cirrhosis and an increased risk of hepatocellular carcinoma (Tatiya et al. 2012). Cisplatin is a chemotherapeutic agent used to treat cancer. It can cause hepatotoxicity by inducing oxidative stress and mitochondrial dysfunction. The damage caused by cisplatin can be mitigated by antioxidants, such as N-acetylcysteine and vitamin E (Abuzinadah & Ahmad 2020). Isoniazid, an essential component of tuberculosis treatment, can cause hepatotoxicity via a variety of mechanisms. Hepatic enzymes metabolise the drug, with slow acetylators being more vulnerable due to higher drug levels. Metabolic processing can generate reactive metabolites, resulting in oxidative stress, mitochondrial dysfunction and lipid peroxidation. This disrupts cellular integrity, resulting in inflammation, hepatocyte damage and apoptosis. Furthermore, INH-induced immune responses and immune cell activation in the liver contribute to the overall hepatotoxic effect (Anusha et al. 2018; Sankar et al. 2015; Sharma et al. 2015).

Hepatic enzyme assessments, as demonstrated in the reviewed studies, are critical in evaluating liver injury caused by hepatotoxins (Said et al. 2022). Serum glutamyl pyruvate transaminase (SGPT), serum glutamyl oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), alanine ALT, AST, gamma-glutamyl transferase (GGT), serum albumin and lactate dehydrogenase (LDH) are the primary markers used to diagnose liver damage. These markers are especially sensitive because their serum levels rise after hepatocellular damage (Mistry et al. 2013). The researchers discovered that exposing animals to different hepatotoxins caused significant changes in liver morphology, biochemistry and histology.

Hepatoprotective activity of polyherbal formulations

The hepatoprotective PHF helps the liver clear away the toxins, regenerates the liver cells and prevents liver failure (Vadivu, Vidhya & Jayshree 2013). The review article investigated the hepatoprotective effects of various PHFs against liver damage induced by chemical toxins and drugs in animal models and cell lines. The formulations including DRHM^®, hydroalcoholic polyherbal formulation (HAF), Livshis, polyherbal tablet formulations (PTF-1, PTF-2), RVSPHF567, polyherbal syrup, Livomyn, Icturn, J-deenar, Gongronema latifolia, Ocimum gratissimum and Vernonia amygdalina (GOV), Habb-e-Asgand, DRDC/AY/8060, and a polyherbal preparation containing Phyllanthus amarus, Boerhavia diffusa and Tephrosia purpurea were found to exhibit significant hepatoprotective effects against H₂O₂, acetaminophen, CCl₄ and paracetamol-induced liver damage in animal models (Ali et al. 2014; Begum et al. 2022; Harshitha, Rodda & Rao 2013; Khan et al. 2015; Ndefo et al. 2021).

Among these, a formulation known as RVSPHF567 drew attention. It was made from a variety of herbs, including ajowan, cardamom, clove, mace and nutmeg. A dose of 1 mL/kg of the blend, given orally three times a day for 3 days, showed promising results in protecting the liver in a real-life study involving adult Wistar albino rats. It was discovered to affect serum levels of total bilirubin and liver enzymes such as SGOT, SGPT and ALP, all of which are indicators of liver health. Furthermore, RVSPHF567 increased the presence of essential proteins such as total proteins and albumin, indicating improved liver function. Microscopic examination also revealed that the formulation restored the liver’s structural integrity and prevented tissue damage (Kandasamy et al. 2010).

In a separate study, Livina, a concoction made up of various plant-based components, was tested for its hepatoprotective potential in people undergoing antituberculosis therapy (ATT). The oral administration of 1000 mg of Livina twice a day for 8 weeks successfully reversed the ATT-induced serum increases in liver function enzymes (AST, ALT and ALP). Furthermore, the treatment not only promotes treatment adherence but also aids in the prevention of the emergence of drug-resistant tuberculosis. This suggests that it has the potential to improve drug efficacy and maintain liver health during tuberculosis treatment (Gulati, Ray & Vijayan 2010). Livina’s efficacy was further demonstrated in a study involving Sprague-Dawley rats with aceclofenac-induced hepatic dysfunction. Doses of 0.25 mL, 0.5 mL and 1 mL of Livina, given orally every day for 60 days, demonstrated significant hepatoprotection, such as serum hepatic marker homeostasis, reduction of oxidative damage and positive changes in hepatic histopathology. Surprisingly, Livina’s efficacy was comparable to that of the well-known hepatoprotective drug silymarin, highlighting its potential as a valuable hepatoprotective agent (Darbar et al. 2010).

Another formulation made up of Terminalia chebula, Asteracantha longifolia, Cyprus rotundus and Bryophyllum pinnatum demonstrated impressive hepatoprotective properties. A dose of 250 mg/kg of the PHF given orally every day for 30 days significantly reduced serum levels of liver function enzymes and bilirubin in adult male albino Wistar rats. The efficacy of this formulation was attributed to its ability to stimulate healthy hepatocellular growth and inhibit specific enzymes, all of which contributed to overall hepatic efficiency (Gurusamy, Kokilavani & Arumuasamy 2010). The Hepjaun syrup formulation, which is available in various alcoholic and water-based extracts, demonstrated significant in vivo hepatoprotective effects against CCl₄-induced hepatic dysfunction in male Wistar rats when given orally every day for 14 days. Among these extracts, one labelled HA-II stood out for its potent hepatoprotective activity, implying potential benefits for jaundice and hepatitis prevention (Patel et al. 2010). Livactine, another formulation containing ingredients such as B. diffusa, Tinospora cordifolia, Andrographis paniculata and Emblica officinalis demonstrated in vivo dose-dependent hepatoprotective effects in albino Wistar rats. This was observed in the presence of CCl₄ and paracetamol-induced hepatic damage. Livactine (1 mL/kg and 2 mL/kg given orally for 10 days) effectively reversed elevated serum levels of liver function enzymes, demonstrating efficacy comparable to the well-known hepatoprotective drug Liv-52 (Mayuren et al. 2010).

Hepax, a plant blend made up of Plumbago zeylanica and Picrorrhiza kurroa, stood out as an exceptional defender against hepatic dysfunction caused by a variety of harmful substances. This formulation (100 mg/kg and 200 mg/kg given orally for 7 days) not only maintained hepatic weight in the male Wistar albino rats but also restored the liver biochemical parameters to normal levels, and prevented abnormalities in hepatic tissue structure. Its efficacy was comparable to that of the positive control silymarin (100 mg/kg), a well-known hepatoprotector (Devaraj et al. 2011). Also, Livergen, a combination of the herbs Andrographis paniculata and Phyllanthus niruri, demonstrated significant hepatoprotective effects in Wistar rats against ethanol, CCl₄ and D-galactosamine. A dose of 2.6 mL/kg of this formulation given orally every day for 5 days demonstrated its ability to maintain liver health by modulating SGOT, SGPT and ALP activities, as well as serum levels of cholesterol, bilirubin and total protein, and controlling lipid peroxidation (Kenjale et al. 2011).

In another study, researchers discovered that 250 mg/kg, 500 mg/kg and 1000 mg/kg of the Unani PHF Majoon-e-Dabeed-ul-ward (MD) given once only were effective in protecting female albino Sprague-Dawley rats from acetaminophen-induced hepatic damage. Majoon-e-Dabeed-ul-ward reversed the negative changes in serum liver function enzyme levels, restored oxidative stress parameters to normal and produced results similar to silymarin, highlighting its hepatoprotective potential (Shakya 2011). Punarnavashtak kwath (PNK), another polyherbal blend, demonstrated significant hepatoprotective effects in rats. The PNK doses of 100 mg/kg and 150 mg/kg given orally three times at 12-h intervals were able to lower serum liver function enzyme levels, improve protein levels and even shorten the duration of thiopentone-induced sleep. Punarnavashtak kwath also showed promise in promoting the viability of HepG2 hepatocytes, implying potential hepatoprotective properties (Shah, Shah & Bhatt 2011). The hepatoprotective PHF, which contained Coccinia indica, Sida cordata and Scoparia dulcis, demonstrated its mettle in defending against CCl₄ and paracetamol-induced hepatic damage in Wistar rats. The PHF doses of 100 mg/kg and 200 mg/kg given orally every day for 7 days maintained normal hepatic parameters in terms of structure and biochemistry while also preventing any abnormalities in the liver’s tissue structure, highlighting its potential as a hepatoprotective agent (Mistry et al. 2012). Saroj et al. (2012) further confirmed PHF’s hepatoprotective abilities in tests on female mice. The PHF doses of 300 mg/kg, 400 mg/kg and 500 mg/kg given orally every day for 7 days demonstrated the blend’s potential by providing significant defence against paracetamol-induced hepatic injury. The PHF effectively reduced the paracetamol-induced increases in serum liver function enzymes and bilirubin levels. Histology of the hepatic tissue revealed improved health, highlighting the formulation’s all-around liver protection potential.

A powerful defender against CCl₄-induced liver toxicity has also emerged in the form of a polyherbal formulation known as ‘Livshis’. This botanical blend at a dose of 5 mg/0.5 mL/100 g given through gavage for 14 days demonstrated its efficacy in male albino rats by reducing oxidative stress, restoring antioxidant enzymes and restoring serum liver marker enzymes (SGOT, SGPT, ALP) to normal levels. It not only repaired the liver on a cellular level but also reversed the negative structural and haematological changes caused by CCl₄ (Bera et al. 2012). A polyherbal blend of Andrographis paniculata, Phyllanthus niruri and Phyllanthus emblica demonstrated resistance to paracetamol, CCl₄ and ethanol-induced hepatic damage. The PHF doses of 100 mg/kg, 200 mg/kg and 400 mg/kg given orally to albino Wistar rats for 5 days demonstrated dose-dependent hepatoprotective effects and the ability to protect the liver against various toxins by significantly lowering serum elevated levels of liver function enzymes (Tatiya et al. 2012). In male Wistar rats, PTF-1 and PTF-2 containing Butea monosperma, Bauhinia variegata and Ocimum gratissimum demonstrated significant hepatoprotective activity. When used to treat paracetamol-induced hepatic damage, 50 mg/kg and 100 mg/kg of each of these formulations given orally once a day for 7 days effectively normalise serum levels of liver enzymes (SGPT, SGOT, ALP) and total bilirubin. PTF-2 was found to be more effective than PTF-1, highlighting the enhanced protection provided by this formulation (Gupta et al. 2013).

A polyherbal syrup containing Allium sativum, Curcuma longa, Ocimum sanctum and Aloe barbadensis demonstrated promising hepatoprotective effects. When combined with paracetamol, 100 mg/kg, 300 mg/kg and 500 mg/kg of the syrup given orally every day for 14 days reduced serum levels of liver function enzymes in adult male Wistar rats, indicating its potential as a hepatoprotective agent (Patel et al. 2013). A combination of Curcuma longa, Occimum sanctum, Murraya koenigii and Nyctanthes arbor-tristis also demonstrated its ability to protect against D-galactosamine-induced hepatotoxicity in rats. In vivo, 50 mg/kg, 100 mg/kg and 250 mg/kg of this PHF significantly reduced serum levels of liver function enzymes and bilirubin to normal levels, while restoring hepatic antioxidant levels, demonstrating its beneficial effect on hepatic health (Sachdeva et al. 2013). The hepatoprotective power of PHFs was further confirmed by Sivakumar et al. (2014), who focused on paracetamol-induced liver damage in rats. The administered (at 200 mg/kg/day orally for 8 days) polyherbal blends F-I, F-II and F-III which were constituted by the different concentrations of Tinospora cordifolia, Boerhavia diffuse, Phyllanthus amaraus, Euphorbia hirta and Wedelia chinensis displayed significant hepatoprotective effects, resulting in reduced serum levels of liver function enzymes. Assessments of liver structure and histopathology revealed improvements, suggesting positive effects on hepatic tissue. Enhanced liver functional parameters further underscored the potential of these formulations to restore liver homeostasis.

Rasheed et al. (2014) engaged in an in vivo study involving male Wistar rats to elucidate the effects of an herbal syrup comprising Aegle marmelos, Eclipta alba and P. amarus. Their research included a thorough evaluation of the syrup’s therapeutic capabilities against CCl₄-induced hepatotoxicity. Rasheed et al.’s findings were compelling, demonstrating the syrup’s significant ability to alleviate CCl₄-induced hepatotoxicity in rats. Notably, plasma concentrations of critical liver marker enzymes such as ALT, AST, SGOT, SGPT, ALP and total bilirubin were reduced significantly upon oral administration of 500 mg/kg of the syrup every day for 5 days. This decrease highlighted the syrup’s potent hepatoprotective properties. Furthermore, histopathological evaluations revealed positive results, indicating that the syrup is effective in reducing fatty degeneration and vacuole formation induced by CCl₄. The similarity of these histopathological improvements to those achieved by the established hepatoprotective agent, silymarin, confirms the efficacy of the herbal formulation.

Iroanya et al. (2014) investigated the hepatoprotective potential of a PHF-labelled GOV in a Wistar albino rat model. Their research focused on the formulation’s significant ability to counteract elevated levels of liver function enzymes upon daily oral doses of 2 g/kg, 4 g/kg and 8 g/kg (for 14 days), while simultaneously improving lipid profiles. This dual effect supported its protective role against acetaminophen-induced hepatotoxicity. In a similar vein, Padmanabhan and Jangle (2014) investigated the effect of a natural herbal combination, HP4, on liver protection. The combination when given orally to live mice at 250 mg/kg and 500 mg/kg every day for 7 days showed promise in preventing the escalation of specific liver function enzymes, owing to the synergistic effects of various constituent natural components working together to protect the liver from CCl₄-induced hepatic damage. Similarly, Ali et al. (2014) investigated the hepatoprotective potential of Habb-e-Asgand in male mice. Their research highlighted the significant protective effects of 250 mg/kg of this mixture, given orally every day for 14 days, against paracetamol-induced hepatic injury. This was accomplished by inhibiting the activities of harmful liver enzymes and cytochrome P450 and reducing oxidative damage while enhancing the activities of protective hepatic enzymes.

Ingawale, Shah and Patel (2015) investigated the hepatoprotective effects of Virgoliv Syrup (VLS) in Sprague-Dawley rats. They discovered that 1 mL/kg/day VLS taken orally for 7 days significantly reduced serum levels of liver function enzymes, implying that it can protect the liver similarly to silymarin. The PHF VLS also increases antioxidant enzyme levels, which aids in the reduction of oxidative damage to the liver. Similarly, Sharma et al. (2015) investigated the hepatoprotective effects of Amlycure DS in albino rats. They discovered that Amlycure DS in solid form (95 mg/kg/day and 285 mg/kg/day for 40 days) and liquid form (1402 mg/kg/day and 5608 mg/kg/day for 40 days) protected the liver from damage caused by INH, a hepatotoxic drug. The protective effects of Amlycure DS were attributed to the presence of various natural compounds with hepatoprotective properties.

Maheshwari et al. (2015) investigated the hepatoprotective potential of Livplus-A in a rat-based study in which Wistar albino rats were given 100 mg/kg, 200 mg/kg and 400 mg/kg of the PHF orally for 14 days. Their findings highlighted Livplus-A’s remarkable ability to correct serum elevated levels of liver function enzymes while also improving lipid profiles. These findings emphasised its potential as a hepatoprotective agent. Shrivastava and Garg (2015) examined 50 mg/kg/day and 100 mg/kg/day of a PHF blend in Wistar rats for 5 days and found similar results. This formulation provided dose-dependent liver protection similar to silymarin, as well as visible improvements in hepatic tissue health. This convergence of findings suggests that the PHFs may be useful in preventing hepatic damage.

Anila et al. (2015) conducted a thorough investigation of Ambrex’s hepatoprotective potential. Using both cell cultures and mice, they discovered that 250 mg/kg and 500 mg/kg of Ambrex given orally every day for 7 days could restore antioxidant equilibrium, reduce elevated serum levels of liver function enzymes and inhibit malondialdehyde – a harmful substance caused by MTX exposure. Singh et al. (2015) investigated the hepatoprotective properties of a PHF composite in a murine model, adding to the growing body of knowledge. Their research discovered that 300 mg/kg and 500 mg/kg of the PHF given daily for 7 days had the potential to significantly reduce deleterious hepatic enzyme levels, indicating its promise in counteracting paracetamol-induced hepatic damage. Khan et al. (2015) broadened the scope of investigation by studying the effects of DRDC/AY/8060 on hepatic health in Wistar rats. The administration of 120 mg/kg and 240 mg/kg of this mixture per day for 10 days demonstrated significant potential in lowering serum levels of liver function enzymes, reducing oxidative damage and increasing antioxidant levels. These findings suggested that it could protect the liver from the ravages of substances such as paracetamol and D-galactosamine.

Ghosh et al. (2015) followed a similar path, focusing on a natural ingredient composite (PHF) and its potential to strengthen liver protection, using albino rats as their experimental model. The formulation at 100 mg/kg, 200 mg/kg and 400 mg/kg doses given orally every day for 7 days demonstrated a significant ability to reduce increases in liver function enzymes, oxidative stress markers and oxidative damage provoked by CCl₄, suggesting its promising role in safeguarding liver integrity.

Sen et al. (2015) conducted a study that revealed the hepatoprotective properties of the Karisalai Karpam tablet. In rats, doses of 50 mg/kg, 100 mg/kg and 200 mg/kg of the tablet taken orally every day for 3 days reduced acetaminophen-induced hepatic oxidative damage. The tablet caused a dose-dependent decrease in hepatic markers, demonstrating its efficacy in reducing hepatic injury. Furthermore, the tablet’s ability to maintain GSH levels demonstrated its potential for reducing oxidative stress. Notably, the hepatoprotection conferred by Karisalai Karpam was comparable to that of the established standard drug silymarin, confirming its importance in promoting hepatic health. The formulation’s augmentation of antioxidant defences further bolstered its hepatoprotective attributes. Sankar et al. (2015) investigated the hepatoprotective potential of heptoplus, a blend of P. amarus, E. alba, T. purpurea, Curcuma longa, Picrrohiza kurooa, Withania somnifera, Pinius succinescens, Pistacia lentiscus, Orchis mascula and Cycas circinalis. Their study focused on its effectiveness in alleviating hepatic damage caused by INH and rifampicin. The study demonstrated the ability of 50 mg/kg and 100 mg/kg of the formulation, given orally every day for 30 days, to significantly decrease harmful hepatic markers, thereby preserving the structural integrity of the liver as evidenced by histopathological analysis in the Sprague-Dawley rats. These findings imply that heptoplus can counteract oxidative stress and restore hepatic function, particularly in cases of drug-induced hepatic dysfunction.

Similarly, Sarhadynejad et al. (2016) investigated the hepatoprotective effects of Zereshk-e-Saghir (ZES) against CCl4-induced hepatic damage in rats. Their investigation revealed that 250 mg/kg, 500 mg/kg, 750 mg/kg and 1500 mg/kg of ZES given orally every day for 15 days effectively reduced elevated levels of hepatic damage markers, highlighting its potential to mitigate hepatic injury. Notably, ZES demonstrated comparable efficacy to the established hepatoprotective agent silymarin, highlighting its significant impact. This study established ZES as a viable contender in strategies for liver protection against chemical hepatotoxins. Yogi and Mishra (2016, 2017) conducted a thorough investigation into a natural ingredient blend containing Calotropis procera, Gymnema sylvestre and Lawsonia inermis. Their study revealed that 200 mg/kg of the formulation administered orally every day for 5 days protected albino Wistar rats from acute hepatic damage caused by CCl₄. The formulation’s hepatoprotection was attributed to the antiinflammatory properties of its natural constituents as well as their ability to scavenge free radicals. The study also highlighted the synergistic potential of the combined formulation, emphasising the value of these plant extracts when used together.

In another study, Fiaz et al. (2017) investigated the hepatoprotective effects of a PHF in female rabbits with paracetamol-induced hepatic dysfunction. The administration of 500 mg/kg of the PHF orally every day for 9 days resulted in significant reductions in elevated serum levels of liver function enzymes and total bilirubin, indicating its potential for mitigating hepatocyte injury. Interestingly, when the PHF was combined with ascorbic acid, its protective effects were negated, highlighting the importance of considering potential interactions between herbal formulations and other medications. Nipanikar et al. (2017) investigated AHPL/AYTAB/0613’s hepatoprotective efficacy against CCl4, ethanol and paracetamol-induced hepatic damage. Administering 110 mg/kg, 220 mg/kg and 440 mg/kg formulation orally every day for 14 days resulted in lower serum levels of hepatic enzymes and total bilirubin, ultimately preserving the integrity and architecture of hepatocytes. This comprehensive study confirmed the formulation’s ability to protect the liver in a variety of hepatotoxicity models.

Medhekar et al. (2017) conducted a thorough investigation into the hepatoprotective effects of Tritone (Livosone) against various hepatotoxic agents. Dosages of 40.1 mg/kg, 81 mg/kg and 162 mg/kg of the formulation given orally every day for 14 days resulted in significant reductions in serum liver function enzyme levels while improving total protein levels and cholinesterase activities. These changes indicated hepatoprotection at both the microscopic and molecular levels. Surprisingly, Tritone’s efficacy at 81 mg/kg and 162 mg/kg was comparable to that of the standard drug silymarin at 100 mg/kg, highlighting its potential as a potent hepatoprotective agent. Aziz et al. (2017) demonstrated the dose-dependent restorative effects of Qurs-e-afsanteen^® on hepatic function. Doses of 50 mg/kg and 100 mg/kg of Qurs-e-afsanteen^® given orally to rats every day for 14 days in conjunction with 80 mg/kg of gentamicin prevented gentamicin-induced hepatocytic damage, which was confirmed by microscopic examination. This study emphasised the formulation’s potential for reducing drug-induced hepatic dysfunction.

Shetty et al. (2018) investigated the potential of kadukkai maathirai (KM) in protecting the liver from ethanol-induced damage. The study found that 72 mg/kg and 400 mg/kg of KM given orally every day for 8 weeks significantly reduced elevated serum levels of liver function enzymes in adult female Sprague-Dawley rats while preserving liver structure at therapeutic doses. Intriguingly, a higher dose of KM did not yield the same benefits, suggesting a potential dose-dependent response. Concurrently, Khan et al. (2018) reported hepatoprotective effects of a PHF like silymarin. The oral administration of 100 mg/kg, 250 mg/kg and 500 mg/kg of the PHF every day for 14 days resulted in improved serum levels of liver function enzymes and improved hepatic histopathological architecture in Swiss albino mice, highlighting its efficacy against hepatic dysfunction. Srivastava et al. (2018) demonstrated the significant efficacy of HAF in preventing acetaminophen-induced hepatic damage in rats. HAF treatment (200 mg/kg/day and 400 mg/kg/day orally for 7 days) was associated with improved liver function tests and reduced histopathological changes, highlighting its potential as a hepatoprotective agent. Ahmad et al. (2020) extensively detailed the dose-dependent protective effects of Boerhavia diffusa, Solidago virgaurea, Vitex negundo and thymoquinone (BSVT) formulation against liver damage in rats. BSVT administration (at 25 mg/kg, 50 mg/kg and 100 mg/kg/day orally for 28 days) resulted in lower serum levels of liver enzymes, indicating hepatocellular membrane stabilisation. This study demonstrated BSVT’s potential as a potent hepatoprotective agent, significantly improving hepatic health. Shetty et al. (2020) investigated the hepatoprotective potential of KM, a polyherbal preparation containing T. chebula, Piper nigrum, Eclipta alba, Citrus limon and ferrous sulfate. Their rat experiment revealed that 144 mg/kg of KM provided significant hepatoprotection. Significant reductions in liver damage markers were observed, as were improvements in histopathological parameters. Furthermore, KM effectively counteracted the increase in serum levels of liver function enzymes caused by D-galactosamine. While silymarin was slightly more effective in lowering serum alanine aminotransferase (ALT), KM’s potential in hepatoprotection remains promising.

The CFCT PHF, which contains Costus speciosus, Fumaria indica and Cichorium intybus, has emerged as a potential antidote to cisplatin-induced hepatorenal toxicity. Abuzinadah and Ahmad (2020) investigated the efficacy of 25 mg/kg, 50 mg/kg and 100 mg/kg CFCTs given daily in male Wistar rats, revealing its ability to mitigate cisplatin-induced hepatic biomarker elevation and cholesterol imbalance. The mechanisms of CFCT were linked to its enhancement of antioxidant defences, which reduced oxidative stress and demonstrated hepatoprotective effects comparable to the established standard, Cystone^®. According to Saleem et al. (2020), the hepatoprotective effects of two PHFs, PH-1 and PH-2, highlighted the importance of formulation composition and plant interactions in hepatoprotection. It was discovered that 50 mg/kg and 100 mg/kg of PH2 (a blend of Piper longum, Glycyrrhiza glabra, Acacia arabica, Papaver somniferum and Viola odorata) given orally to albino healthy rats every day for three days significantly reduced ALP levels while increasing superoxide dismutase (SOD) and GSH levels. In contrast, PH-1 did not cause significant changes in ALT and AST levels. These findings highlighted the intricate interplay between botanical components and the importance of composition optimisation in designing effective hepatoprotective formulations.

According to Dey et al. (2020), BV-7310, a combination of Phyllanthus niruri, T. purpurea, B. diffusa and Andrographis paniculata, demonstrated promising hepatoprotective properties against alcohol-induced liver damage. The efficacy of 15 µg/mL, 50 µg/mL and 100 µg/mL of BV-7310 given for 48 h in preventing ethanol-induced cell death in HepG2 cells, as well as the efficacy of 250 mg/kg and 500 mg/kg of the blend given every day for 21 days in protecting against alcohol-induced liver damage in Sprague-Dawley rats, was demonstrated. The therapeutic implications went beyond alcoholic liver disease to include a broader range of liver toxicity-related conditions.

Ndefo et al. (2021) demonstrated that DRHM^® was an ameliorator in the context of oxidative stress-induced hepatic injury. The study demonstrated the efficacy of 1 mL/kg, 2 mL/kg and 3 mL/kg DRHM^® given orally to healthy male Wistar albino rats every day for 14 days in mitigating H₂O₂-induced hepatic damage, as evidenced by decreases in AST, ALT and total bilirubin levels. The similar efficacy of DRHM^® to silymarin highlighted its potential in alleviating oxidative stress-mediated liver impairment.

Furthermore, Icturn and J-deenar formulations given orally to mice at 2.6 mL/kg and 5.2 mL/kg daily for 7 days effectively counteracted CCl₄-induced hepatotoxicity in mice (Begum et al. 2022). Elevated serum levels of liver function enzymes were found to improve after treatment with these formulations, which was supported by improved liver histopathology. Similarly, Amalakyadi Gana (500 mg/kg and 700 mg/kg) given orally to Swiss albino mice every day for 7 days demonstrated dose-dependent efficacy against paracetamol-induced hepatotoxicity, comparable to silymarin, highlighting its potential in hepatoprotection (Ray et al. 2022).

Amir et al. (2022) detailed the Aab-e-Murawaqain formulation, offering a robust strategy against CCl₄-induced hepatotoxicity. A significant reduction in serum enzyme levels upon oral treatment of Wistar albino rats with 4.5 mL/kg of the medication twice a week for 28 days signified restored liver health and cellular integrity, affirming the formulation’s hepatoprotective potential. Furthermore, Livogrit (6 µg/kg, 28 µg/kg and 142 µg/kg for 14 days) emerged as an effective countermeasure to thioacetamide-induced hepatotoxicity in a zebrafish model (Balkrishna et al. 2022). The restoration of serum biochemical parameters and liver function highlighted Livogrit’s potential in reversing liver health aberrations.

In a recent study, Rafi Reshi et al. (2022) investigated the hepatoprotective effects of Dawa-ul-Kurkum and its hydroalcoholic extract using an in vivo rat model. For 6 weeks, rats were given oral doses of 250 mg/kg and 500 mg/kg. Dawa-ul-Kurkum and its extract exhibited significant hepatoprotective properties, effectively mitigating the negative effects of ethanol-induced liver damage. Notably, administration of these substances resulted in a decrease in serum levels of liver injury markers such as SGOT, SGPT, ALP, total bilirubin and direct bilirubin, while simultaneously increasing serum total protein levels. Dawa-ul-Kurkum and its hydroalcoholic extract alleviated ethanol-induced oxidative stress, as evidenced by elevated levels of malondialdehyde, nitrates and nitrites, as well as decreased levels of reduced GSH. Furthermore, the treatment was associated with an increase in body weight, which could be linked to an improved appetite, emphasising Dawa-ul-Kurkum’s hepatoprotective potential. These findings highlight the hepatoprotective potential of Dawa-ul-Kurkum and its hydroalcoholic extract against ethanol-induced liver damage. The observed reduction in liver injury markers and oxidative stress indicators, as well as the improvement in appetite and body weight, suggest a multifaceted protective effect. The study suggests that these herbal interventions could be used to treat liver dysfunction, anorexia, ascites and abdominal pain.

Another investigation by Singh et al. (2023) explored the hepatoprotective effects of Majoon-Najah (MN) and Majoon-Najah hydroalcoholic extract (MNHE) using a Guinea pig model. The study involved intragastric administration of MN and MNHE for 15 days. The experiment focused on countering hepatotoxicity induced by CdCl₂. The results demonstrated that CdCl₂ exposure led to hepatotoxicity characterised by altered liver function markers, serum biochemical indicators, lipid peroxidation, antioxidant enzyme activities, proinflammatory cytokine levels and liver cytoarchitecture. However, treatment with MN and MNHE effectively mitigated these adverse effects by normalising the altered parameters and enhancing enzymatic antioxidants. The hepatoprotective mechanisms involved the scavenging of free radicals, reduction in malondialdehyde levels, activation of antioxidant enzymes and downregulation of proinflammatory indicators. By enhancing antioxidant defences, reducing lipid peroxidation and suppressing proinflammatory responses, MN and MNHE exhibit a comprehensive defence against hepatotoxic insults.

Mechanism of action of polyherbal formulations

The hepatoprotective effects of PHFs encompass a multifaceted array of interactions that collectively shield hepatocytes from the damaging consequences of diverse hepatotoxins. These formulations demonstrate remarkable efficacy in reducing injuries caused by agents such as CCl₄, alcohol, pharmaceuticals and environmental toxins, allowing for the restoration of normal liver function.

Antioxidant effects

The cornerstone PHFs’ efficacy lies in their robust antioxidant properties, attributed to an assortment of phytoconstituents present within these formulations. Flavonoids, alkaloids, terpenoids, phenolic acids and tannins contribute significantly to these antioxidative actions by neutralising free radicals and reducing the burden of oxidative stress on hepatocytes. This role is pivotal, given that oxidative stress is a pivotal driver of hepatic pathogenesis. Through the inhibition of lipid peroxidation and the diminution of ROS, these formulations play a crucial role in protecting hepatocytes from apoptosis and injury (Amir et al. 2022; Ghosh et al. 2011; Singh et al. 2015; Sivakumar et al. 2014; Tatiya et al. 2012). Studies have demonstrated noteworthy antioxidant activities in specific formulations such as PNK, Tritone, ZES and Livactine, underscoring their potential to counteract oxidative stress-induced liver injury (Mayuren et al. 2010; Medhekar et al. 2017; Sarhadynejad et al. 2016; Shah et al. 2011).

Antiinflammatory and antifibrotic effects

Another critical aspect of these formulations is their antiinflammatory and antifibrotic properties. Chronic inflammation and fibrosis are important factors in the progression of hepatic dysfunction (Sharma & Nagalli 2022). These formulations act as potent antiinflammatory agents by modulating proinflammatory cytokines like TNF-α and IL-1β, as well as inhibiting central signalling pathways like NF-κB and MAPK (Padmanabhan & Jangle 2014). Furthermore, they inhibit the accumulation of extracellular matrix proteins such as collagen, reducing fibrosis (Sivakumar et al. 2014). Notable examples of such antiinflammatory prowess can be found in formulations such as KM and Livshis, which have demonstrated the ability to reduce proinflammatory cytokine levels and thus prevent inflammation-induced hepatic damage (Bera et al. 2011; Shetty et al. 2020).

Immunomodulatory effects

Immunomodulatory effects also feature prominently in the mechanisms by which these PHFs exert hepatoprotection (Belapurkar, Goyal & Tiwari-Barua 2014; Hamid et al. 2021). The presence of immunomodulating herbs like Andrographis paniculata and Tinospora cordifolia within formulations like Livina, PNK, Hepjaun Syrup, Livactine, Livergen, Livshis, DRDC/AY/8060, VLS, Clearliv, BV-7310, Amlycure DS and Livomyn orchestrates regulation of immune cell activity and cytokine production. These effects bolster immune responses against toxin-induced damage, thereby preserving immune homeostasis and mitigating immune-mediated hepatic injury (Rajanna et al. 2021; Saha & Ghosh 2012; Yadav, Yadav & Kharya 2016).

Liver regeneration and cellular function

The facilitation of liver regeneration and cellular function is a significant factor in these formulations’ hepatoprotective effects. The stimulation of hepatocyte proliferation and the synthesis of liver-specific proteins ensure not only the restoration of normal hepatic function but also the recovery from damage. Furthermore, the modulation of enzymes governing carbohydrate and lipid metabolism, such as glucose-6-phosphatase and fatty acid synthase, plays a critical role in preventing hepatic steatosis, contributing to the overall rejuvenation of hepatic health (Amir et al. 2022; Tatiya et al. 2012).

Detoxification capacity enhancement

Furthermore, an important aspect of the mechanism of action of PHFs is the enhancement of the liver’s detoxification capacity. These formulations improve the liver’s ability to neutralise and eliminate toxins by increasing the activity of phase I and phase II detoxification enzymes such as cytochrome P450, GSH S-transferase and uridine diphosphate glucuronosyltransferases. This, in turn, reduces the burden on the liver, lowering the risk of liver damage caused by toxic agents (Ghosh et al. 2011).

To summarise, the hepatoprotective effects of PHFs are due to the complex interplay of antioxidant, antiinflammatory, antifibrotic, immunomodulatory, regenerative and detoxification-enhancing properties. These formulations have a lot of potential as therapeutic interventions for preventing liver damage and maintaining overall hepatic health. However, a thorough understanding of the molecular pathways and interactions mediating these effects necessitates additional research. Such insights are critical in propelling the development of effective hepatoprotective interventions.

Conclusion

In conclusion, the reviewed studies indicated that polyherbal formulations possess significant hepatoprotective activity against various hepatotoxic agents, through multiple mechanisms of action such as antioxidant, antiinflammatory, immunomodulatory activities and hepatocyte regeneration. These formulations contain bioactive compounds such as alkaloids, flavonoids and polyphenols that exhibit diverse biological activities, which help reduce oxidative stress, inflammation and immune dysregulation that contribute to liver damage. The hepatoprotective effects were evident by the reduction in the levels of serum liver marker enzymes such as ALT, AST, ALP, and GGT, lipid peroxidation as well as restoration of the levels of serum bilirubin protein and enzymes. The herbal remedies also showed a dose-dependent reduction in lipid peroxidation, an increase in GSH and an improvement in liver histopathology. The observed hepatoprotective effects of some of the polyherbal formulations are comparable to those of standard drugs such as silymarin and Liv-52. Overall, these studies provide evidence for the hepatoprotective effects of various polyherbal formulations, which may have the potential for use as alternative treatments for liver diseases. These findings suggest that polyherbal formulations may be a promising alternative to conventional drugs for the prevention and treatment of liver diseases. However, further research is required to identify the bioactive compounds and fully understand the mechanisms of action of these polyherbal formulations. The development of new and effective drugs based on the knowledge gained from these formulations could offer new hope for patients suffering from liver disorders.

Acknowledgements

The authors acknowledge the Govan Mbeki Research and Development Center, University of Fort Hare for paying the publication fee.

The authors declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.

E.B.A. and A.E.A. conceptualised, gathered the materials, wrote and edited the article.

The author conceptualised, gathered the materials, wrote and edited the article.

Data sharing is not applicable to this article, as no new data were created or analysed in this study.

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of any affiliated agency of the authors.

References