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Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1
Open accessAbstract
Introduction: Paracetamol is a potent hepatotoxin and may cause severe acute hepatocellular injury. The present study was intended to assess the hepatoprotective potential of Caralluma umbellata Haw. (Asclepiadaceae) (C. umbellata) against paracetamol-induced hepatotoxicity in vitro and in vivo experimental models. Methods: Preliminary analysis for antioxidant and hepatoprotective property was evaluated for methanolic (MCU), aqueous (ACU) and hydro methanolic (HCU) extracts of C. umbellata using in vitro cell-free antioxidant such as DPPH, ABTS, nitric oxide, lipid peroxidation models and cell-based hepatoprotective study using BRL3A cells. In vivo, hepatoprotective activity was studied in paracetamol treated male Wistar albino rats. Furthermore, molecular mechanism behind the protective effect of MCU was explored by RT PCR technique by utilizing cytochrome P450 (CYP) CYP2E1. Results: C. umbellata extracts especially, MCU showed a better antioxidant property. MCU offered significant dose-dependent protection against paracetamol-induced hepatic damage in both in vitro and in vivo assays by improving all the biochemical findings towards the normal range. In a mechanism-based study, MCU has offered significant down-regulation (p < 0.05) of CYP2E1. These findings were in line with the hepatoprotective activity findings where MCU showed significant protection. Conclusion: In conclusion, these findings suggest that MCU possess hepatoprotective activity. One of the possible mechanisms behind the protective effect of MCU is found to be inhibition of CYP2E1.
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TL;DR
Methanolic extract of *Caralluma umbellata* (MCU) showed the strongest antioxidant and hepatoprotective effects among the tested extracts against paracetamol-induced liver injury in BRL3A cells and male Wistar rats. The protection was associated with restored GSH/MDA and serum liver markers plus downregulation of CYP2E1 expression.
Key findings
- MCU had the highest flavonoid content (56.90 ± 1.57 mg gallic acid equivalent/g dry weight) and total phenolic content (12.74 ± 0.33 mg gallic acid equivalent/g dry weight) among extracts; HPLC detected lupeol, β-sitosterol, and quercetin.
- In BRL3A cells, paracetamol (2000 µg/mL) caused 49.74 ± 0.54% cytotoxicity; MCU co-treatment reduced cell death to 30.86 ± 1.86% and 24.61 ± 0.8% in the two MCU groups, and restored GSH and MDA toward normal.
- Paracetamol increased CYP2E1 expression, while MCU co-treatment decreased expression from 0.91 folds to 0.38 and 0.244 folds at 150 µg/mL and 350 µg/mL, respectively.
- In rats, paracetamol raised AST, ALT, ALP, and total bilirubin and lowered total protein; MCU (200 and 400 mg/kg) significantly improved these markers, and histopathology showed less necrosis/inflammation than paracetamol alone.
Methods
- In vitro: cell-free antioxidant assays (DPPH, ABTS, nitric oxide, superoxide, lipid peroxidation, total antioxidant capacity, reducing power) and BRL3A hepatocyte assays with paracetamol, MCU/ACU/HCU, and silymarin; GSH and MDA measured in cell lysates, with semi-quantitative RT-PCR for CYP2E1 normalized to GAPDH.
- In vivo: 30 male Wistar rats divided into 5 groups of 6; MCU (200 or 400 mg/kg) or silymarin (100 mg/kg) orally for 5 days, then paracetamol (2 g/kg p.o.) on day 6; serum AST, ALT, ALP, total bilirubin, and total protein measured, with liver histopathology.
- Analysis: one-way ANOVA followed by Dunnett or Tukey multiple comparison tests, with significance at P < 0.05.
Limitations
- The paper states no formal limitations section; it notes that detailed studies on phytochemical constituents are in progress.
- Evident from the text: only MCU was advanced to in vivo and CYP2E1 studies, while ACU and HCU were tested mainly in vitro; CYP2E1 effects are transcript-level only, and histopathology is qualitative.
- Evident from the text: the in vitro cytotoxicity text and Table 1 appear inconsistent in assigning the 150 and 350 µg/mL MCU groups to the reported cell-death values.
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8 of 41 cited sources checked · 3 supported · 0 flagged · accuracy not yet measured
- Findingcitation§ Discussion · p. 6
MCU also showed better antioxidant potential with other models tested, including nitric oxide and lipid peroxidation.
“MCU also showed better antioxidant potential with other models tested which are also considered for antioxidant potential as with nitric oxide and lipid peroxidation. 33,34”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [33] source
The review discusses nitric oxide and lipid peroxidation, including lipid peroxidation in an experimental stroke model (section B, page unavailable). Neither that passage nor searches for MCU and antioxidant-testing models found evidence that MCU was tested or showed better antioxidant potential. The available copy is truncated. (LLM, conf=0.73)
Experimental — accuracy not yet measured - cites [34] Badmus J, 2011, Lipid peroxidation inhibition and anti-radical activities of some leaf fractions of Mangifera indica, Acta Pol Pharm
- Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
MCU administered at 200 and 400 mg/kg body weight significantly blocked the elevation of serum AST, ALT, ALP, and total bilirubin levels compared to group 2 (P < 0.05 and P < 0.01).
“MCU administered groups (200 and 400 mg/kg body weight), significantly blocked the elevation of serum AST, ALT, ALP, total bilirubin levels significantly ( P < 0.05 and P < 0.01) as compared to group 2.”
Quote in the paperSubstantial claim - Findingown data§ Discussion · p. 6
Overall MCU showed better activity as compared to the rest of the other extracts.
“Overall MCU showed better activity as compared to rest of other extracts, similar kind of observations from other species were recorded from Caralluma diffusa (Wight.) and Caralluma. adscendens (Roxb.). 18,36”
Quote in the paperNot a substantial claim - Findingown data§ Cytoprotective effect of test extracts in BRL3A cells · p. 4
Paracetamol treatment induced 49.74 ± 0.54% cell death in BRL3A cells.
“Treatment with paracetamol-induced 49.74 ± 0.54% cell death, while treatment with 150 µg/mL and 350 µg/mL MCU significantly reduced paracetamol induced cell death to 30.86 ± 1.86% and 24.61 ± 0.8, respectively.”
Quote in the paperSubstantial claim - Findingown data§ Abstract · p. 1
MCU offered significant dose-dependent protection against paracetamol-induced hepatic damage in both in vitro and in vivo assays by improving all biochemical findings towards normal range.
“MCU offered significant dose dependent protection against paracetamol-induced hepatic damage in both in vitro and in vivo assays by improving all the biochemical findings towards the normal range.”
Quote in the paperSubstantial claim
- Findingown data§ CYP2E1 RT PCR · p. 5
MCU in the absence of paracetamol did not show significant fold expression compared to control.
“The treatment with MCU, in the absence of paracetamol, did not show significant fold expression as compared to control; indicating that MCU has a negligible effect on normal expression of CYP2E1 (Fig. 3).”
Quote in the paperNot a substantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
No abnormalities were detected in the necropsy examinations of rats administered MCU.
“No abnormalities were detected in the necropsy examinations.”
Quote in the paperSubstantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
Administration of paracetamol after 24 hours intoxication significantly increased AST, ALT, ALP, and total bilirubin in group 2 compared to group 1 (P < 0.001).
“Administration of paracetamol after 24 hours intoxication resulted in a significant increase ( P < 0.001) in AST, ALT, ALP, total bilirubin and decrease ( P < 0.01) in total protein in group 2 as compared to group 1.”
Quote in the paperSubstantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
Administration of paracetamol after 24 hours intoxication significantly decreased total protein in group 2 compared to group 1 (P < 0.01).
“Administration of paracetamol after 24 hours intoxication resulted in a significant increase ( P < 0.001) in AST, ALT, ALP, total bilirubin and decrease ( P < 0.01) in total protein in group 2 as compared to group 1.”
Quote in the paperSubstantial claim - Findingown data§ Phytochemical study · p. 3
The flavonoid content was highest in MCU (56.90 ± 1.57 mg gallic acid equivalent/g dry weight).
“The content of flavonoids was highest in MCU (56.90 ± 1.57 mg gallic acid equivalent/g dry weight), followed by HCU and ACU which showed 12.74 ± 0.33, 8.73 ± 0.34 and 2.87 ± 0.21 mg gallic acid equivalent/g dry weight, respectively.”
Quote in the paperNot a substantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
MCU significantly increased serum protein content.
“Furthermore MCU also significantly increased serum protein content.”
Quote in the paperNot a substantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
Silymarin showed better protection against liver damage (P < 0.001).
“Silymarin also showed better protection ( P < 0.001) against the liver damage (Table 2).”
Quote in the paperSubstantial claim - Findingown data§ Histopathology observations · p. 5
Normal animal liver tissue showed well-preserved architecture with intact parenchyma, central veins, and sinusoids; perivenular, periportal, and midzonal hepatocytes were normal.
“Histological observation of liver tissue in normal animal showed well-preserved architecture with intact parenchyma, central veins and sinusoids. The perivenular, periportal and midzonal hepatocytes were normal (Fig. 4A).”
Quote in the paperNot a substantial claim - Findingown data§ Cytoprotective effect of test extracts in BRL3A cells · p. 4
MCU at 150 and 350 μg/mL significantly reduced paracetamol-induced cell death to 30.86 ± 1.86% and 24.61 ± 0.8%, respectively.
“Treatment with paracetamol-induced 49.74 ± 0.54% cell death, while treatment with 150 µg/mL and 350 µg/mL MCU significantly reduced paracetamol induced cell death to 30.86 ± 1.86% and 24.61 ± 0.8, respectively.”
Quote in the paperSubstantial claim - Findingown data§ Effect of MCU on hepatic markers in rats · p. 5
MCU administered to female rats at doses up to 2000 mg/kg b.w did not produce any toxicity or mortality over a period of 14 days.
“MCU administered to female rats at doses up to 2000 mg/ kg b.w did not produce any toxicity or mortality over a period of 14 days.”
Quote in the paperSubstantial claim - Findingown data§ Discussion · p. 6
Similar observations were recorded from our antioxidant data, where methanolic extracts having higher reducing potential possessed better lipid peroxidation inhibition potential.
“Similar observations were recorded from our antioxidant data, where methanolic extracts having higher reducing potential possessed better lipid peroxidation inhibition potential. 35”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [35] source
- Findingreasoning§ Discussion · p. 6
Co-treatment with MCU showed restored levels of altered parameters by protecting cells from damage.
“The co-treatment with MCU showed restored levels of altered parameters by protecting cell from damage.”
Quote in the paperSubstantial claim - Findingown data§ Abstract · p. 1
C. umbellata extracts, especially MCU, showed better antioxidant property.
“C. umbellata extracts, especially MCU showed better antioxidant property.”
Quote in the paperNot a substantial claim - Findingown data§ Discussion · p. 6
In this study, phytoconstituents such as quercetin, lupeol and β-sitosterol were identified in C. umbellata.
“In this study, phytoconstituents such as quercetin, lupeol and β- sitosterol were identified in C. umbellata .”
Quote in the paperNot a substantial claim - Findingreasoning§ Discussion · p. 7
Pretreatment with MCU maintained the levels of AST and ALT towards normal levels.
“Pretreatment with MCU maintained the levels of AST, ALT towards normal levels suggesting an indication of stabilization plasma membrane and repair of cellular damage caused due to toxicity.”
Quote in the paperSubstantial claim - Findingown data§ Discussion · p. 7
The abnormalities caused in the liver architecture due to paracetamol treatment were mostly reversed following treatment with MCU.
“The abnormalities caused in the liver architecture due to the paracetamol treatment were mostly reversed following treatment with MCU.”
Quote in the paperSubstantial claim - Findingown data§ Discussion · p. 7
MCU pretreated groups were found to have ALP and TB levels equivalent to normal groups.
“MCU pretreated groups found to have ALP and TB levels equivalent to normal groups, suggesting the effective improvement in the secretary mechanism of hepatocytes.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion · p. 6
The cytochrome P450 (CYP450) system, especially CYP2E1, has been known to enhance the toxic damage caused by paracetamol by increasing the formation of NAPQI.
“On the other hand, cytochrome P450 (CYP450) system, especially CYP2E1 has been known to enhance the toxic damage caused by paracetamol by increasing the formation of NAPQI. 5”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [5] source
- Interpretationown data§ CYP2E1 RT PCR · p. 5
MCU has a negligible effect on normal expression of CYP2E1.
“The treatment with MCU, in the absence of paracetamol, did not show significant fold expression as compared to control; indicating that MCU has a negligible effect on normal expression of CYP2E1 (Fig. 3).”
Quote in the paperNot a substantial claim - Interpretationcitation§ Discussion · p. 6
The observed antioxidant activity of the extracts may be attributed to the presence of phytoconstituents such as phenols, flavonoids and other constituents such as quercetin, difenakum, ethyl iso-allocholate, and β-sitosterol.
“The observed antioxidant activity of the extracts may be attributed due to the presence of phytoconstituents such as phenols, flavonoids and other constituents such as quercetin, difenakum, ethyl iso-allocholate, and β-sitosterol as reported earlier. 29”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Jerome JJ, 2013, A study of phytochemical constituents in Caralluma umbellata by GC-Ms anaylsis, Int J Pharm Sci Invent
- Interpretationreasoning§ Discussion · p. 6
The restoration of altered GSH levels from MCU may be due to the presence of antioxidant phytoconstituents such as quercetin and β-sitosterol.
“The restoration of altered GSH levels from MCU may be due to the presence of antioxidant phytoconstituents such as quercetin, β-sitosterol.”
Quote in the paperNot a substantial claim - Interpretationown data§ Discussion · p. 6
Protection from cell damage from MCU may be due to its inhibitory potential against progression of lipid peroxidation as evident from the antioxidant studies.
“Also protection from cell damage from MCU may be due to its inhibitory potential against progression of lipid peroxidation as evident from the antioxidant studies.”
Quote in the paperSubstantial claim- Rests on an assumption: A compound with better reducing capacity will inhibit lipid peroxidation process significantly.
- Interpretationown data§ Abstract · p. 1
MCU possesses hepatoprotective activity.
“In conclusion these findings suggest that MCU possess hepatoprotective activity.”
- Also stated in: § Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 · p. 1 · plain
“Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1”
Quote in the paperSubstantial claim - Also stated in: § Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 · p. 1 · plain
- Interpretationown data§ Abstract · p. 1
One possible mechanism behind the protective effect of MCU is inhibition of CYP2E1 expression.
“One of the possible mechanisms behind the protective effect of MCU is found to be the inhibition of CYP2E1 expression.”
- Also stated in: § Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 · p. 1 · plain
“Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1”
Quote in the paperSubstantial claim - Also stated in: § Caralluma umbellata Haw. protects liver against paracetamol toxicity and inhibits CYP2E1 · p. 1 · plain
- Interpretationown data§ Effect of MCU on hepatic markers in rats · p. 5
MCU showed a comparable hepatoprotective activity to that of a marketed product.
“Thus MCU showed a comparable hepatoprotective activity to that of a marketed product.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion · p. 7
The maintenance of AST and ALT towards normal levels suggests stabilization of plasma membrane and repair of cellular damage caused due to toxicity.
“Pretreatment with MCU maintained the levels of AST, ALT towards normal levels suggesting an indication of stabilization plasma membrane and repair of cellular damage caused due to toxicity.”
Quote in the paperSubstantial claim - Interpretationreasoning§ What is new here? · p. 7
The study discusses the probable mechanism for the hepatoprotection, which states that the activity may be attributed to the combined effect of antioxidant property and inhibition of CYP2E1 expression from C. umbellata.
“The study discusses the probable mechanism for the hepatoprotection, which states that the activity may be attributed to the combined effect of antioxidant property and inhibits CYP2E1 expression from C. umbellata.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion · p. 7
TP level will be depressed in hepatic conditions leading to defective protein biosynthesis.
“MCU treatment also restored the protein synthesis, since TP level will be depressed in hepatic conditions leading to defective protein biosynthesis. 44”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [44] source
- Interpretationown data§ Discussion · p. 7
Histopathological examinations substantiate the hepatoprotective nature of MCU.
“Histopathological examinations substantiate the hepatoprotective nature of MCU.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Conclusion · p. 7
Hepatoprotective activities of MCU may be attributed to the combined effect of antioxidant property and reduced CYP2E1 expression.
“In conclusion, hepatoprotective activities of MCU may be attributed to the combined effect of antioxidant property and reduced CYP2E1 expression.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Conclusion · p. 7
These effects may be associated with the phytoconstituents present in the extract, especially flavonoids and phenolic compounds.
“These effects may be associated with the phytoconstituents present in the extract especially flavonoids and phenolic compounds.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion · p. 7
Hepatic necrosis leads to elevated levels of serum enzymes AST and ALT which are indicative of cellular leakage and loss of functional integrity of cell membrane in the liver.
“Hepatic necrosis leads to the elevated levels of serum enzymes AST and ALT which are indicative of cellular leakage and loss of functional integrity of cell membrane in the liver. 41”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] source
- Interpretationreasoning§ Discussion · p. 7
MCU treatment restored protein synthesis.
“MCU treatment also restored the protein synthesis, since TP level will be depressed in hepatic conditions leading to defective protein biosynthesis. 44”
Quote in the paperNot a substantial claim - Interpretationown data§ Discussion · p. 7
The equivalence of ALP and TB levels to normal groups suggests effective improvement in the secretory mechanism of hepatocytes.
“MCU pretreated groups found to have ALP and TB levels equivalent to normal groups, suggesting the effective improvement in the secretary mechanism of hepatocytes.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 25
- It may state two separate claims as one. 25
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Introduction · p. 1Paracetamol is a major cause of drug-induced acute liver failure and has been extensively studied for its liver damage.
“Paracetamol is considered as one of the major causes for drug-induced ALF, and has been extensively studied for its liver damage. 3,4”
Quote in the paperNot a substantial claim1 of 2 sources checkedIt may state two separate claims as one.
Findingcitation§ Discussion · p. 6The results of the present study are in agreement with previous studies; treatment of paracetamol caused depletion of GSH, cell damage (MDA levels) and mitochondrial dysfunction.
“The results of present study are in agreement with previous studies; we found that treatment of paracetamol caused depletion of GSH, cell damage (MDA levels) and mitochondrial dysfunction. 4,7,38”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [4] source
- cites [7] source
The Results section ('Effects on serum AST and ALT activities'; page not provided) reports increased liver-injury markers after acetaminophen administration in rats, supporting the general claim of liver damage. The paper does not report GSH depletion, MDA levels, or mitochondrial dysfunction; searches for those terms found no supporting passage. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [38] source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Abstract · p. 2Traditionally Caralluma umbellata has been used to relieve stomach disorders and abdominal pains.
“Traditionally this plant has been used to relieve stomach disorders and abdominal pains. 12”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [12] source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Discussion · p. 6Polyphenols from plants represent potential substances which are effective ROS scavengers and metal chelators.
“Polyphenols from plants represent potential substances which are effective ROS scavengers and metal chelators. 28”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [28] source
The Background says that plant-derived phytochemicals are largely antioxidants and that antioxidants can eliminate free radicals and reactive oxygen species. The paper also discusses phenolic compounds as antioxidants, but the passages do not establish the claim that plant polyphenols chelate metals. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Abstract · p. 1Earlier studies have illustrated Caralluma plants' antidiabetic, anti-inflammatory, anti-nociceptive, antiulcerogenic, anti-oxidant and hepatoprotective activities.
“Earlier studies have illustrated their antidiabetic, anti-inflammatory, anti-nociceptive, antiulcerogenic anti-oxidant and hepatoprotective activities. 12”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [12] source
Section 1.2 lists anti-inflammatory, antiulcer, antinociceptive, antioxidant, and antihyperglycemic properties of Caralluma, broadly supporting five of the six activities claimed. It does not mention hepatoprotective activity. No page number is available in our copy. (LLM, conf=0.89)
Experimental — accuracy not yet measured
It may state two separate claims as one.
Findingcitation§ Discussion · p. 6Treatment with paracetamol alone increased the expression of CYP2E1 by 0.6 folds followed with GSH depletion.
“Treatment with paracetamol alone increased the expression of CYP2E1 by 0.6 folds followed with GSH depletion. 39”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [39] source
The Results (page not provided) report that acetaminophen raised hepatic CYP2E1 activity and depleted GSH in mice; Table 2 shows lower GSH in the acetaminophen-only group than in controls. The paper reports activity, not a 0.6-fold increase in CYP2E1 expression, and does not establish the stated sequence between that increase and GSH depletion. (LLM, conf=0.88)
Experimental — accuracy not yet measured
It may state two separate claims as one.
Findingown data§ Histopathology observations · p. 5Treatment with silymarin and MCU decreased the abnormality of liver architecture induced by paracetamol and restored the altered histopathological changes.
“Treatment with silymarin and MCU decreased the abnormality of liver architecture induced by paracetamol (Fig. 4C, D and E) and restored the altered histopathological changes.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ Cytoprotective effect of test extracts in BRL3A cells · p. 4Paracetamol treatment significantly reduced GSH and MDA levels in cells, while MCU restored GSH and MDA to near normal levels.
“Similarly, paracetamol the treatment significantly reduced the GSH and MDA levels in cells, while treatment with MCU restored GSH and MDA to near normal levels.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ Abstract · p. 2Our preliminary studies with C. umbellata showed the presence of flavonoids and phenols in extracts and further in vitro antioxidant tests showed promising antioxidant potential.
“Our preliminary studies with C. umbellata showed the presence of flavonoids and phenols in extracts and further in vitro antioxidant tests showed promising antioxidant potential.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ ABTS radical scavenging assay · p. 4In ABTS assay, the extracts showed good scavenging activity with IC50 ranging from 11.53 ± 0.47 to 20.9 ± 0.4 μg/mL; HCU showed stronger activity with IC50 11.53 ± 0.47 μg/mL.
“The extracts were found to have good scavenging activity against ABTS radical, IC 50 value ranging from 11.53 ± 0.47 to 20.9 ± 0.4 µg/mL. HCU showed stronger activity with IC 50 of 11.53 ± 0.47 µg/mL (Fig. 2C).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Discussion · p. 6MCU had better scavenging capacity followed by HCU and ACU.
“MCU having better scavenging capacity which was followed to HCU and ACU.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Total antioxidant capacity · p. 4MCU possessed highest total antioxidant capacity (355.03 ± 5.68 mg equivalent to ascorbic acid per g extract), followed by HCU (284.56 ± 1.78) and ACU (107.04 ± 2.84 mg/g).
“MCU possessed highest total antioxidant capacity with 355.03 ± 5.68 mg equivalent to ascorbic acid content per g of extract, followed by HCU and ACU at 284.56 ± 1.78, 107.04 ± 2.84 mg/g respectively.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown data§ Phytochemical study · p. 3The preliminary phytochemical analysis indicates the presence of carbohydrates, sterols, triterpenoids, phenols, flavonoids, saponins and glycosides in all extracts.
“As mentioned in the supplementary Table 1, the preliminary phytochemical analysis indicates the presence of carbohydrates, sterols, triterpenoids, phenols, flavonoids, saponins and glycosides in all extracts, and in a quantitative study for flavonoids and total phenols.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Nitric oxide radical inhibition assay · p. 4In nitric oxide radical inhibition assay, ACU showed maximum activity with IC50 791.17 ± 4.71 μg/mL, followed by MCU at 873.3 ± 5.8 μg/mL and HCU at 1000 μg/mL.
“The extracts have moderate inhibition capacity against nitric oxide radical. Among them ACU showed maximum activity with IC 50 value at 791.17 ± 4.71 µg/mL followed by MCU at 873.3 ± 5.8 µg/mL and HCU at 1000 µg/mL (Fig. 2B).”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown data§ Reducing power assay · p. 4MCU was found to have high reducing potential.
“From reducing power data, MCU was found to have high reducing potential as depicted in Fig. 2F.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Phytochemical study · p. 3Total phenolic content was highest in MCU (12.74 ± 0.33 mg gallic acid equivalent/g dry weight), followed by HCU (8.73 ± 0.34) and ACU (2.87 ± 0.21).
“Total phenolic content also varied among the samples. MCU showed the highest levels (12.74 ± 0.33), followed by HCU (8.73 ± 0.34) and ACU (2.87 ± 0.21 mg gallic acid equivalent/g, dry weight respectively).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Discussion · p. 6Higher reducing potential was found for MCU, similarly with scavenging potential.
“Higher reducing potential was found for MCU as similarly with scavenging potential.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ HPLC analysis of MCU · p. 4HPLC chromatogram showed the presence of lupeol, β-sitosterol and quercetin in MCU at retention times 2.682, 3.290 and 4.315 respectively at 250 nm.
“HPLC chromatogram showed the presence of all three phytoconstituents at retention times 2.682 (lupeol), 3.290 (β-sitosterol) and 4.315 (quercetin) at 250 nm (Fig. 1).”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown data§ Effect of MCU on hepatic markers in rats · p. 5Body weights increased in the animals administered MCU compared to their initial weights.
“Body weights were increased in these animals compared to their initial weights.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown data§ Cytoprotective effect of test extracts in BRL3A cells · p. 4Silymarin as positive control exhibited similar trend in activity.
“Silymarin was used a positive control also exhibited the similar trend in the activity.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ Histopathology observations · p. 5The paracetamol-induced group showed focally distorted architecture, midzonal hepatocyte necrotic changes with moderate inflammatory infiltration, and focal aggregates of mononuclear inflammatory cells amidst liver parenchyma.
“In the paracetamol induced group, histological observation showed focally distorted architecture. Midzonal hepatocytes showed necrotic changes with moderate inflammatory infiltration. There were focal aggregates of mononuclear inflammatory cells amidst the liver parenchyma (Fig. 4B).”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown data§ Plant collection and extraction · p. 2The plant material was authenticated by a Botanist by comparing with housed authenticated specimens.
“The authentication was done by a Botanist, Dr. Madava Chetty, S. V University, Tirupati by comparing with the housed authenticated specimens.”
Quote in the paperNot a substantial claimProbably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
Premisenone given§ Discussion · p. 6In vitro assays such as cell-based models have gained importance in recent years due to their low cost, quick and reliability.
“In vitro assays such as cell-based models have gained importance in recent years due to their low cost, quick and reliability.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Abstract · p. 1The key phytochemical ingredients in Caralluma are pregnane glycosides, flavone glycosides, megastigmane glycosides, bitter principles, triterpenes and saponins.
“The key phytochemical ingredients in Caralluma are pregnane glycosides, flavone glycosides, megastigmane glycosides, bitter principles, triterpenes and saponins. 13-15”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 6Preliminary phytochemical analysis showed the presence of various phytoconstituents.
“Preliminary phytochemical analysis showed the presence of various phytoconstituents. 29”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [29] Jerome JJ, 2013, A study of phytochemical constituents in Caralluma umbellata by GC-Ms anaylsis, Int J Pharm Sci Invent
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 6For preliminary screening for hepatoprotection, liver cell lines such as BRL3A and HepG2 have been routinely used, since they resemble in vivo models.
“For preliminary screening for hepatoprotection, liver cell lines such as BRL3A and HepG2 have been routinely used, since they resemble to the in vivo models. 37”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [37] source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductcitation§ Gene expression study · p. 3Specific primers for CYP2E1 and GAPDH were selected as per Yao et al and Gene runner software.
“Specific primers for CYP2E1 and GAPDH primers were selected as per Yao et al , and Gene runner, ver 3.05, Hasting software Inc., respectively for amplification. 24”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Yao et al
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [24] Yao XM, 2011, Effects of bicyclol on the activity and expression of CYP450 enzymes of rats after partial hepatectomy, Yao Xue Xue Bao
Probably not a substantial claim.
Premisecitation§ Discussion · p. 6Supplementation of exogenous antioxidants may normalize redox status during oxidative stress.
“Therefore supplementation of exogenous antioxidants may normalize redox status during oxidative stress. 27”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Kunwar A, 2011, Free radicals, oxidative stress and importance of antioxidants in human health, J Hist Med Allied Sci
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 6High free radical scavenging ability is regarded as high antioxidant activity.
“High free radical scavenging ability is regarded as high antioxidant activity. 31”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31] source
It may state two separate claims as one.
Premisecitation§ Discussion · p. 6Total phenols and flavonoids were present in higher amounts in extracts correlating to their antioxidant capacity.
“Total phenols and flavonoids were present in higher amounts in extracts correlating to their antioxidant capacity. 30”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [30] source
It may state two separate claims as one.
Premisecitation§ Introduction · p. 1Paracetamol toxicity is mainly due to reduction of hepatocyte GSH and increased CYP2E1 activity.
“The mechanism behind paracetamol toxicity is mainly due to the reduction of hepatocyte GSH and increased CYP2E1 activity where paracetamol is metabolized to an extremely reactive toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) along with generation of reactive oxygen species in augmenting oxidative stress. 3,5,6”
Quote in the paperSubstantial claim0 of 3 sources checkedIt may state two separate claims as one.
Premisecitation§ Introduction · p. 1Paracetamol is metabolized to the reactive toxic metabolite NAPQI, with generation of reactive oxygen species that augment oxidative stress.
“The mechanism behind paracetamol toxicity is mainly due to the reduction of hepatocyte GSH and increased CYP2E1 activity where paracetamol is metabolized to an extremely reactive toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) along with generation of reactive oxygen species in augmenting oxidative stress. 3,5,6”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 6Similar kind of observations from other species were recorded from Caralluma diffusa (Wight.) and Caralluma adscendens (Roxb.).
“Overall MCU showed better activity as compared to rest of other extracts, similar kind of observations from other species were recorded from Caralluma diffusa (Wight.) and Caralluma. adscendens (Roxb.). 18,36”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Abstract · p. 1The genus Caralluma plants form the central part of the traditional medicine system and are used for the treatment of diabetes and stomach disorders.
“These plants form the central part of the traditional medicine system and are used for the treatment of diabetes and stomach disorders. 10,11”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [10] source
- cites [11] Ahmad MM, 1993, Anti-inflammatory activity of Caralluma tuberculata alcoholic extract, Fitoterapia
It may state two separate claims as one.
Interpretationreasoning§ Discussion · p. 6Cytoprotection offered from MCU may also be attributed to the partial inhibition of CYP2E1 expression which in turn maintained normal GSH levels, along with combined effect of lowered ROS formation as evident from the various in vitro antioxidant potential.
“Therefore, cytoprotection offered from MCU may also be attributed to the partial inhibition of CYP2E1 expression which in turn maintained normal GSH levels, along with combined effect of lowered ROS formation as evident from the various in vitro antioxidant potential.”
Quote in the paperSubstantial claim- Rests on an assumption: Oxidative stress plays a role in the deleterious effect attributed to paracetamol hepatotoxicity involving the CYP system.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
Interpretationreasoning§ Conclusion · p. 7The observed hepatoprotective activity might be attributed to the synergistic activity with these constituents because the mixtures of antioxidants were more active than the individual ones.
“The observed hepatoprotective activity might be attributed to the synergistic activity with these constituents because the mixtures of antioxidants were more active than the individual ones.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown data§ What is new here? · p. 7Our studies indicate that the C. umbellata extract counters against free radicals and CYP2E modulation at the cellular level.
“Furthermore, our studies indicate that the C. umbellata extract counters against the free radicals and CYP2E modulation at the cellular level.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper may give no reason why it holds.
Premisecitation§ What is current knowledge? · p. 7Previous published report suggests that C. umbellata has hepatoprotective activity.
“Previous published report suggests that C. umbellata has hepatoprotective activity.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone given§ Ethical approval · p. 7All studies conducted on animals were approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt Ltd, Bangalore, Karnataka (Approval No: RR/IAEC/05a-2015).
“All studies conducted on animals were approved by the Institutional Animal Ethical Committee (IAEC) of Radiant Research Services Pvt Ltd, Bangalore, Karnataka (Approval No: RR/IAEC/05a-2015).”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ Discussion · p. 7ALP is an indicator of pathological alteration in biliary flow, whereas serum albumin furnishes liver functioning and is used to assess chemical-induced hepatic damage.
“On the other hand, ALP is an indicator of pathological alteration in biliary flow, whereas serum albumin furnishes liver functioning and used to chemical-induced hepatic damage. 42,43”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [42] Hill RL, Everds NE. Principles of clinical pathology for toxicology studies. In: Wallace HA, editor. Principle and Methods of Toxicology. New York: Raven Press;1989.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- cites [43] Harper HA. The functions and tests of the liver. In: Review of Physiological Chemistry. Los Altos, California: Lange Medical Publishers; 1961.
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 7Similar observations have been made by Punniamurthy et al and Shanmugam et al for the hepatoprotective potential of C. umbellata.
“Similar observations have been made by Punniamurthy et al 45 and Shanmugam et al 46 for the hepatoprotective potential of C. umbellata.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [45] Punniamurthy N, 2014, Hepatoprotective Activity of Caralluma umbellata in Chicken, Indian Vet J
- cites [46] source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ Discussion · p. 7The study of hepatic markers such as AST, ALT, ALP, TB and TP have been found to be of great value in the assessment of clinical and experimental liver damage.
“The study of hepatic markers such as AST, ALT, ALP, TB and TP have been found to be of great value in the assessment of clinical and experimental liver damage. 40”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [40] source
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
Premisenone given§ What is current knowledge? · p. 7Paracetamol is known for causing liver damage and CYP2E1 is the main enzyme which produces highly reactive metabolite NAPQI causing hepatocellular damage.
“Paracetamol is known for causing liver damage and CYP2E1 is the main enzyme which produces highly reactive metabolite NAPQI causing hepatocellular damage.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Treatment of liver diseases with allopathic drugs is often associated with serious side effects.
“The treatment of liver diseases with allopathic drugs is often associated with serious side effects.”
The paper relies on this without support.
Plants which consist of several classes of phytoconstituents may offer protection at multiple targets.
“Hence plants which consist of several classes of phytoconstituents may offer protection at multiple targets.”
The paper relies on this without support.
Oxidative stress plays a role in the deleterious effect attributed to paracetamol hepatotoxicity involving the CYP system.
“Oxidative stress also plays a larger role in the deleterious effect attributed to paracetamol hepatotoxicity involving CYP system.”
The paper relies on this without support.
A compound with better reducing capacity will inhibit lipid peroxidation process significantly.
“A compound with better reducing capacity will inhibit lipid peroxidation process significantly.”
The paper relies on this without support.
Paracetamol at high dosage produces centrilobular hepatic necrosis which can be fatal.
“Paracetamol at high dosage produces centrilobular hepatic necrosis which can be fatal.”
The paper relies on this without support.
Paracetamol-induced hepatotoxicity is a conventional model to evaluate the efficacy of plant-based drugs for their liver-protecting activity.
“In higher models such as in rats, paracetamol-induced hepatotoxicity is one of the conventional model to evaluate the efficacy of plant based drugs for their liver protecting activity.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
MCU cytotoxicity results are assigned to the opposite doses
MajorThe text assigns 30.86% cell death to 150 μg/mL MCU and 24.61% to 350 μg/mL. Table 1 assigns those values to 350 and 150 μg/mL, respectively, reversing the reported dose response.
“treatment with 150 µg/mL and 350 µg/mL MCU significantly reduced paracetamol induced cell death to 30.86 ± 1.86% and 24.61 ± 0.8, respectively.”
“| 5 | MCU (350 µg/mL)+ Paracetamol | 30.86 ± 1.86 *** | 0.605 ± 0.015 ** | | 10.05 ± 0.69 ** | | 6 | MCU (150 µg/mL)+ Paracetamol | 24.61 ± 0.8 ***”
HPLC detection wavelength differs between methods and figure
MinorThe HPLC method and results specify detection at 250 nm, but the Figure 1 caption specifies 254 nm.
“detection by UV at 250 nm.”
“Fig. 1. HPLC UV chromatogram of MCU. Detection was recorded at 254 nm.”
Post hoc statistical test differs between methods and tables
MinorThe statistical-analysis section says Dunnett's test was used, whereas the captions for Tables 1 and 2 say Tukey's post test was used.
“followed by Dunnett multiple comparison test using GraphPad Prism 5.0 software”
“One-way ANOVA followed by Tukey post test.”
Significance claimed for both MCU doses is absent for some markers
MinorThe results say the 200 and 400 mg/kg MCU groups significantly lowered total bilirubin and increased total protein. In Table 2, neither result has a significance marker for the 200 mg/kg group.
“MCU administered groups (200 and 400 mg/kg body weight), significantly blocked the elevation of serum AST, ALT, ALP, total bilirubin levels significantly ( P < 0.05 and P < 0.01) as compared to group 2. Furthermore MCU also significantly increased serum protein content.”
“| Group V MCU (200 mg/kg, po) | 320.2 ± 7.5** | 237.2 ± 4.5* | 146.3 ± 5.7* | 18.1 ± 0.82 | 4.55 ± 0.95 |”
Paracetamol is said to reduce MDA despite a higher reported level
MinorThe results text says paracetamol reduced MDA. Table 1 instead reports MDA of 13.25 for paracetamol treatment, compared with 6.123 for normal control.
“paracetamol the treatment significantly reduced the GSH and MDA levels in cells”
“| 4 | Paracetamol (2000 µg/mL) | 49.74 ± 0.54 | 0.527 ± 0.025 ### | 13.25 ± | 1.13 ### |”
Total-bilirubin significance is overstated in the text
MinorThe text reports P < 0.001 for the paracetamol-induced increase in total bilirubin. Table 2 marks that result ##, defined as P < 0.01, rather than ###, defined as P < 0.001.
“a significant increase ( P < 0.001) in AST, ALT, ALP, total bilirubin”
“| Group II Paracetamol | 359.8 ± 12.6 ### | 266.4 ± 8.9 ### | 170.7 ± 5.5 ### | 21.6 ± 0.40 ## | 2.22 ± 0.39 ## |”
MCU ALP levels are described as equivalent to normal
MinorThe discussion calls ALP levels in MCU-pretreated groups equivalent to normal, but Table 2 reports 139.6 and 146.3 IU/L for those groups, versus 40.08 IU/L for normal controls.
“MCU pretreated groups found to have ALP and TB levels equivalent to normal groups”
“| Group I Normal control | 83.6 ± 6.5 | 43.6 ± 4.5 | 40.08 ± 5.2 | 18.8 ± 0.30 | 5.54 ± 0.37 |”
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Metadata
- Authors
- Bellamakondi, P. K., Godavarthi, A., & Ibrahim, M.
- Corresponding author
- Bellamakondi, Pavan Kumar
- Venue
- BioImpacts
- Publisher
- Maad Rayan Publishing Company
- Published
- 2017-10-30
- Volume
- 8
- Issue
- 1
- Pages
- 23-30
- ISSN
- 2228-5652 (ISSN-L)
- 2228-5660
- PMC
- PMC5915705
- OpenAlex
- W2794584041
- Semantic Scholar
- 9466f1c35d6d85c1878d7f8711ef6bdb0cee1736
- Cited by
- 15
- References
- 44
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 4
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc
- Locations
- Bioimpacts (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Plant Toxicity and Pharmacological Properties
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry Medicinal Plant Applications
- Keywords
- acetaminophen hepatotoxicity, hepatoprotection, CYP2E1 inhibition, antioxidant activity, methanol extract, lipid peroxidation, acute liver injury, medicinal plants
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-07, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-07 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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