@article {1527, title = {Natural Compounds in Hepatic Protection and Injury: A Dual-Spectrum Review of Medicinal Plants}, journal = {Pharmacognosy Research}, volume = {18}, year = {2026}, month = {November 2025}, pages = {1-6}, type = {Review Article}, chapter = {1}, abstract = {

Hepatotoxicity remains a persistent global clinical challenge, driven by exposure to a broad spectrum of xenobiotics prescription drugs, over-the-counter medications, industrial chemicals, and increasingly, herbal supplements that disrupt the intricate balance of hepatic homeostasis. Paradoxically, a growing body of evidence demonstrates that many of these same medicinal plants exhibit dose-dependent hepatoprotective activities, highlighting the critical importance of delineating their dual-spectrum effects. In this review, we systematically classify a selection of widely used species into hepatotoxic and hepatoprotective cohorts, detailing their principal bioactive phytochemicals (e.g., pyrrolizidine alkaloids, flavonoids, triterpenoids), key molecular targets (including Nrf2/ARE, NF-κB, caspase cascades, and major CYP450 isoforms), and dose-response safety margins. We further summarize contemporary extraction and standardization methodologies such as supercritical fluid extraction, green solvent systems, and HPLC fingerprinting that ensure reproducibility and quality control across studies. Advanced in vitro and in vivo platforms, including three-dimensional hepatic spheroids and microfluidic liver-on-chip models, are reviewed for their enhanced physiological relevance and predictive capacity. Integration of preclinical data with findings from clinical trials investigating compounds like silymarin, glycyrrhizin, and EGCG is critically examined, with special attention to safety considerations such as herb drug interactions, cumulative toxicity thresholds, and idiosyncratic reactions. Finally, we propose future research trajectories leveraging network pharmacology, nanocarrier delivery systems, and international regulatory harmonization to accelerate the safe translation of phytochemical-based interventions for liver protection.

}, keywords = {CYP450, Hepatoprotection, Hepatotoxicity, Nrf2, Phytochemicals, Systems Pharmacology.}, doi = {10.5530/pres.20260034}, author = {Dilsar Gohil and Rajesh Maheshwari} } @article {1336, title = {Ethanolic Extract of aerial parts of Achyranthes aspera Attenuates Hepatotoxicity and Nephrotoxicity Induced by Cisplatin in Rat}, journal = {Pharmacognosy Research}, volume = {17}, year = {2025}, month = {January 2025}, pages = {60-69}, type = {Original Article}, chapter = {60}, abstract = {

Background: The chemotherapeutic agents used to treat cancer are known to possess potent adverse effects like nephrotoxicity and hepatotoxicity among others. Objectives: The aim of this current study happened to be the isolation of phytoconstituent from Achyranthes aspera and assess the protective effect of the compound against cisplatin-induced hepato- and nephrotoxicity in rats. Materials and Methods: Toluene: Ethyl Acetate (9:1) was used as the solvent system to isolate the phenolic compound from ethanolic extract of the leaves and stem of A. aspera. The isolated compounds were studied using mass spectroscopy, 1H NMR, FT-IR and UV. The effect of the isolated phenolic was assessed by study of various factors like body weight, organ weight, serum biomarkers and histopathological studies. Results: The treatment of cisplatin led to a significant increase the weight of the organs, hepatic and kidney biomarkers in serum suggesting toxicity whereas the the isolated component reversed the elevated levels (p\<0.05 compared to positive control). Conclusion: It could be concluded from the results that pretreatment with isolated component (coumarin) was able to attenuate the hepato-and nephron-toxicity induced by anticancer drug cisplatin.

}, keywords = {Achyranthes aspera, Cisplatin, Hepatotoxicity, Isolation, Nephrotoxicity}, doi = {10.5530/pres.20251905}, author = {Arijit Chaudhuri and Udichi Kataria and Anurag Dubey} } @article {1189, title = {Hepatoprotective Assessment of Copper Calx against Anti-Tubercular Drug-induced Hepatotoxicity in Rats}, journal = {Pharmacognosy Research}, volume = {15}, year = {2023}, month = {October 2023}, pages = {806-812}, type = {Original Article}, chapter = {806}, abstract = {

Background: Anti-Tubercular Drugs (ATDs), while effective in treating tuberculosis, are associated with hepatotoxicity, leading to liver damage and complications. Calx of Copper, a traditional Ayurvedic preparation, has shown potential hepatoprotective properties. Objectives: To investigate the potential hepatoprotective role of Calx of Copper in mitigating ATD-induced hepatotoxicity and to examine its impact on liver function markers and histopathological changes in rats. Materials and Methods: Thirty male Wistar rats were randomly divided into five groups (n=6 per group): control, ATD, Calx of Copper, ATD+Calx of Copper, and silymarin (used as a standard hepatoprotective agent). Hepatotoxicity was induced in the ATD, ATD+Calx of Copper, and silymarin groups by administering a combination of isoniazid, rifampicin, and pyrazinamide for 25 days. Calx of Copper and silymarin were orally administered at doses of 6.17 mg/kg and 12.33 mg/kg, and 300 mg/kg b.w, respectively, in their respective groups. Liver function markers, including serum transaminase and alanine Aminotransferase (ALT), were measured at the end of the study. A histopathological examination of liver tissues was also performed. Results: ATDinduced hepatotoxicity was evident through elevated serum SGPT, SGOT, ALT, and ALP levels and histopathological alterations in liver tissue. Co-administration of Calx of Copper significantly reduced SGPT, SGOT, ALT, and ALP (p\<0.05) and improved liver histopathological changes compared to the ATD group. The hepatoprotective effect of Calx of Copper was comparable to that of silymarin. Conclusion: Copper calx demonstrated significant hepatoprotective activity against ATD-induced hepatotoxicity in rats, as evidenced by normalizing liver function markers and histopathological improvements. These findings suggest that Calx of Copper may be a promising adjuvant therapy for mitigating liver damage associated with anti-tubercular drug treatment.

}, keywords = {Anti-Tubercular, Antioxidant, Copper Calx, Hepatotoxicity, Rat}, doi = {10.5530/pres.15.4.085}, author = {Mohammad Sharique and Hariprasad M.G and Moqbel Ali Moqbel Redhwan and Ashish Jain and Shambhavi S and Mamatha A and Niranjana} } @article {337, title = {Attenuation of Methotrexate-induced Hepatorenal Damage by Terminalia bellerica Fruit Extract in Experimental Rats}, journal = {Pharmacognosy Research}, volume = {10}, year = {2018}, month = {July 2018}, pages = {301-308}, type = {Original Article}, chapter = {301}, abstract = {

Background: Methotrexate (MTX) is used for numerous malignancies and autoimmune disorders. With such widespread use, MTX-induced hepatorenal toxicity is an issue of concern that still needs to be addressed. Objective: The aim of the present study is to evaluate the role of Terminalia bellerica extract (TBE) in MTX-induced hepatorenal toxicity in Wistar albino rats. Materials and Methods: Rats were randomly divided into six groups (n = 6) {\textendash} received MTX 20 mg/kg intraperitoneally on the 4th day along with pretreatment with different doses of TBE (100 mg/kg, 200 mg/kg, and 400 mg/kg, p.o) given from 1st to 15th day. MTX-induced hepatorenal toxicity was evaluated by biochemical hepatic and renal parameters along with histopathology and immunohistochemistry. Results: Hepatorenal toxicity induced by MTX was attributed to increased oxidative stress, biochemical liver, and kidney parameters and upregulation of caspase-3 and nuclear factor kappa B (NFkB). MTX-treated group observed twofold to threefold rise in aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), and creatinine values{\textendash}138.49 IU/L, 125.81 IU/L, 63.09 mg/dl, and 1.895 mg/dl, respectively. Groups pretreated with TBE (400 mg/kg) observed a significant decrease (P \< 0.001) in oxidative stress and biochemical parameters {\textendash} AST (63.94 IU/L), ALT (55.98 IU/L), BUN (37.02 mg/dl), and creatinine (1.065 mg/dl). Pretreatment with TBE 400 mg/kg, histopathology of both liver and kidney tissues showed improved architectural damage and immunohistochemistry showed downregulation of increased antigens-caspase-3 and NFkB. Conclusion: T. bellerica fruit extract (400 mg/kg) showed significant hepatorenal protection by reducing oxidative stress, elevating serum enzymes, and downregulating the tissue expressions of caspase-3 and NFkB.

}, keywords = {caspase-3, Hepatotoxicity, Methotrexate, Nephrotoxicity, Nuclear factor kappa B, Terminalia bellerica}, doi = {10.4103/pr.pr_159_17}, author = {Prerna Chauhan and Himanshu Sharma and Surender Singh and Yogendra Kumar Gupta and Uma Kumar} } @article {267, title = {Effect of Pomegranate (Punica granatum) Seed Oil on Carbon Tetrachloride-Induced Acute and Chronic Hepatotoxicity in Rats}, journal = {Pharmacognosy Research}, volume = {10}, year = {2018}, month = {April 2018}, pages = {124-129}, type = {Original Article}, chapter = {124}, abstract = {

Background: Carbon tetrachloride (CCl4) is one of the most widely used Hepatotoxin that is known to induce oxidative stress and causes hepatic damage by the formation of reactive free radicals in laboratory animals. Objective: This study aims to investigate the hepatoprotective role of pomegranate seed oil (PSO) on histological structure, some biochemical parameters and lipid peroxidation on CCl4-induced acute and chronic liver injury induced rats. Materials and Methods: The study material comprised 80 male Wistar albino rats. They were divided into two study groups including 40 rats for acute and 40 rats for chronic hepatotoxicity induction by CCl4. Hematoxylin and eosin staining was used to evaluate degree of steatosis, inflammation, necrosis, and fibrosis semiquantitatively. Blood serum aspartate transaminase, alanine transaminase, and alkaline phosphatase enzyme activities and glucose, triglyceride, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, total protein, albumin and liver malondialdehyde, and nitric oxide levels were measured. Results: All control and only PSO given animals liver showed normal histological architecture, but in the acute CCl4-treated animals, an intensive macro and microvesicular steatosis, mononuclear inflammatory cell infiltrations in portal area and parenchyma, and necrotic alterations; in the chronic CCl4-treated group, additionally to acute findings mild-to-severe fibrosis with lobulation formation were observed. Conclusion: The results suggest that administration of PSO has partially ameliorative effects on biochemical and lipid peroxidation parameters in acute period, but it has no effect on the recovery of liver tissue damage or histopathological changes and biochemical parameters induced by CCl4 in chronic period.

}, keywords = {Carbon tetrachloride, Hepatotoxicity, Histopathology, Pomegranate seed oil, Rat}, doi = {10.4103/pr.pr_122_17}, author = {Duygu Yaman Gram and Ayhan Atasever and Meryem Eren} } @article {719, title = {Hepatoprotective activity of Ocimum sanctum alcoholic leaf extract against paracetamol-induced liver damage in Albino rats}, journal = {Pharmacognosy Research}, volume = {3}, year = {2011}, month = {April 2011}, pages = {13-18}, type = {Original Article}, chapter = {13}, abstract = {

Background:\ There is a lack of reliable hepatoprotective drugs in modern medicine to prevent and treat drug-induced liver damage. Leaves of Sacred/Holy Basil, i.e. Green Tulsi (Ocimum sanctum), belonging to family Lamiaceae are used traditionally for their hepatoprotective effect. We wanted to evaluate the hepatoprotective activity of\ Ocimum sanctum and observe whether synergistic hepatoprotection exists with silymarin.\ Materials andMethods:\ Albino rats (150-200 g) were divided into five groups. Groups A and B were normal and experimental controls, respectively. Groups C, D and E received the alcoholic extract of\ Ocimum Sanctum\ leaves (OSE) 200 mg/kg BW/day, silymarin 100 mg/kg BW/day and OSE 100 mg/kg BW/day + silymarin 50 mg/kg BW/day p.o., respectively, for 10 days. Hepatotoxicity was induced in Groups B, C, D and E on the eighth day with paracetamol 2 g/kg BW/day. The hepatoprotective effect was evaluated by performing an assay of the serum proteins, albumin globulin ratio, alkaline phosphatase, transaminases and liver histopathology. The assay results were presented as mean and standard error of mean (SEM) for each group. The study group was compared with the control group by one-way ANOVA, followed by Bonferoni{\textquoteright}s test. A\ P-value of \<0.01 was considered significant.\ Results:\ In groups C, D and E, liver enzymes and albumin globulin ratio were significantly (P\ \< 0.01) closer to normal than in group B. Reduction in sinusoidal congestion, cloudy swelling and fatty changes and regenerative areas of the liver were observed on histopathological examination in groups C, D and E, whereas group B showed only hepatic necrosis.\ Conclusion:\ The Ocimum sanctum alcoholic leaf extract shows significant hepatoprotective activity and synergism with silymarin.

}, keywords = {Hepatoprotective, Hepatotoxicity, Ocimum sanctum, Paracetamol, Silymarin}, doi = {10.4103/0974-8490.79110}, author = {Kingshuk Lahon and Swarnamoni Das} } @article {746, title = {Protective Effect of Stem Bark of Ceiba pentandra linn. against Paracetamol-induced Hepatotoxicity in Rats}, journal = {Pharmacognosy Research}, volume = {2}, year = {2010}, month = {March 2010}, pages = {26-30}, type = {Original Article}, chapter = {26}, abstract = {

The present study reports protective activity of ethyl acetate fraction of methanol extract of stem bark of Ceiba pentandra against paracetamol-induced liver damage in rats. The ethyl acetate fraction (400 mg/kg) was administered orally to the rats with hepatotoxicity induced by paracetamol (3 gm/kg). Silymarin (100 mg/kg) was used as positive control. High performance thin layer chromatography (HPTLC) fingerprinting of ethyl acetate fraction revealed presence of its major chemical constituents. A significant (P \< 0.05) reduction in serum enzymes GOT (ALT), aspartate aminotransferase (AST), GPT alkaline phosphatase (ALP), total bilirubin content and histopathological screening in the rats treated gave indication that ethyl acetate fraction of methanolic extract of Ceiba pentandra possesses hepatoprotective potential against paracetamol-induced hepatotoxicity in rats.

}, keywords = {Ceiba pentandra, Hepatoprotective, Hepatotoxicity, Paracetamol}, doi = {10.4103/0974-8490.60584}, author = {Nirmal K Bairwa and Neeraj K Sethiya and SH Mishra} }