Cases of liver disorders and hepatic disturbances are on the rise, including alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), hepatitis, cirrhosis, and liver cancer. From a standpoint of critical and complex management, these conditions pose a public health challenge, especially given the liver’s central role in maintaining whole-body homeostasis. Research is exploring integrated medicine approaches that can support traditional therapies, which are often accompanied by a range of side effects. Phytotherapy could offer a promising avenue, according to evidence from a recent Indian study published in Toxicology Reports.
The Liver’s Central Role
The liver holds a pivotal place in the body’s dynamics. It serves as a multifunctional organ supporting essential processes: regulating macronutrient metabolism, handling proteins and amino acids, bolstering immune defenses, maintaining blood volume, managing lipid balance and cholesterol, transmitting endocrine signals, and detoxifying xenobiotics, including a wide array of medications. It is also indispensable for nitrogen waste metabolism via the urea cycle, among other functions. Protecting its health and battling the rising burden of liver diseases that affect it and originate from it is essential.
Globally, deaths related to liver diseases are increasing significantly, now numbering around 2 million annually, with about one million attributable to cirrhosis complications and roughly half a million from liver cancer and viral hepatitis, to name the major causes. Unhealthy lifestyle choices and environmental factors, such as infections, alcohol use, obesity, and metabolic syndrome, toxins, and clinical aspects including metabolic disorders and insulin resistance, can contribute to the higher prevalence of hepatic conditions, including ALD, NAFLD, hepatitis, and cirrhosis, with nonalcoholic steatohepatitis (NASH) representing a more severe form of NAFLD, characterized by inflammation and damage to liver cells.
Traditional Medicine and Integrated Therapies
Traditional pharmacological approaches have long played a crucial role in managing liver diseases, for example by slowing disease progression. However, they are often associated with significant side effects, such as drug resistance with drug-induced damage, which in some cases may outweigh the benefits. Moreover, the high cost of therapies and the need for lifelong treatment pose additional barriers to care, particularly in low-income regions, and the lack of personalized strategies can reduce therapeutic effectiveness in certain patients.
In this context, certain natural compounds isolated from plants—alkaloids, flavonoids, and glycosides—have demonstrated hepatoprotective pharmacological effects or immunomodulatory actions that could be clinically meaningful, suggesting potential for the future development of modern medicines. Among plant-derived metabolites for mitigating and managing various hepatic disorders, particular attention is drawn to natural phytochemicals, including phenolic acids, flavonoids, catechins, tannins, lignans, stilbenes, and anthocyanidins, noted for their antioxidant, chemopreventive, and pharmacological activities; polyphenols, especially flavonoids, possess notable antioxidant properties that shield cells from ROS and oxidative stress (OS) and suppress pro-inflammatory signaling pathways.
Numerous in vivo, in vitro, and ex vivo studies have demonstrated that bioactive polyphenols possess a broad therapeutic spectrum, including immunomodulatory, antimicrobial, antioxidant, anti-mutagenic, lipid-lowering, hypoglycemic, gastroprotective, anti-inflammatory, anti-tumor, and chemopreventive effects. In short, they help mitigate the harmful effects of drugs, chemicals, and their metabolites by modulating intracellular signaling pathways.
They also activate the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway through extracellular signal-regulated kinase (ERK) and PI3K/Akt signaling routes, which in turn regulate various transcription factors. While some pathways, including SP/NR1 signaling, can be negatively affected, overall, these bioactive compounds appear to assist in countering the oxidative stress caused by drugs and chemicals, help normalize intracellular enzyme levels, protect cells from toxicity, and facilitate the detoxification of harmful compounds within the cell itself.
Role of Plant Metabolites in Mitigation of Hepatotoxicity
Latest studies and systematic reviews increasingly suggest that plants hold medicinal properties capable of preventing or treating hepatic disorders, with the added advantages of broad accessibility, enduring therapeutic effects, and minimal adverse effects. Herbal preparations may also support the regeneration of liver cells, potentially accelerating the healing process, which would position certain plants as viable options in managing various hepatic disturbances.
Particular attention is given to plant metabolites derived from silibinin (silymarin), resveratrol, glycyrrhizin, curcumin, berberine, hesperidin, diosgenin, quercetin, rutin, epigallocatechin gallate, apigenin, baicalin, catechin, rosmarinic acid, thymoquinone, kaempferol, Morinda, punicalagin, luteolin, betulinic acid, silibinin, schisandrin B, aucubin, chlorogenic acid, esculetin.
In Conclusion
Natural products are emerging as a promising alternative to conventional medications, particularly in the realm of liver protection. Their effectiveness, coupled with minimal side effects and the added benefit of being dietary components, positions them as preferred options over synthetic drugs, which are often tied to toxicity concerns. Plant-based hepatoprotective agents stand out for safety, efficacy, and cost-effectiveness, contributing significantly to maintaining liver health and function.
Source
Syed Sanober Qadri S, Javaid D, Reyaz A et al. Liver disorders and phytotherapy. Toxicology Reports, 2025, 10:14:102047. Doi: 10.1016/j.toxrep.2025.102047.
Subscribe to Integrated Medicine
