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Cited by 15Liver Disease Diagnosis and TreatmentDrug-Induced Hepatotoxicity and ProtectionMedicinal plant effects and applications

Intervention by picroside II on FFAs induced lipid accumulation and lipotoxicity in HepG2 cells

Open access
Dhami-Shah, Hiteshi, Vaidya, Rama, Talwadekar, Manasi, Shaw, Eisha, Udipi, Shobha, Kolthur-Seetharam, Ullas, Vaidya, Ashok D.B.·2021·Journal of Ayurveda and Integrative Medicine
DOI 10.1016/j.jaim.2021.04.007PMC PMC8377190
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Abstract

BACKGROUND: Accumulation of free fatty acids (FFAs) in hepatocytes is a hallmark of liver dysfunction and non-alcoholic fatty liver disease (NAFLD). Excessive deposition of FFAs alters lipid metabolism pathways increasing the oxidative stress and mitochondrial dysfunction. Attenuating hepatic lipid accumulation, oxidative stress, and improving mitochondrial function could provide potential targets in preventing progression of non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH). Earlier studies with Picrorhiza kurroa extract have shown reduction in hepatic damage and fatty acid infiltration in several experimental models and also clinically in viral hepatitis. Thus, the effect of P. kurroa's phytoactive, picroside II, needed mechanistic investigation in appropriate in vitro liver cell model. OBJECTIVE(S): To study the effect of picroside II on FFAs accumulation, oxidative stress and mitochondrial function with silibinin as a positive control in in vitro NAFLD model. MATERIALS AND METHODS: HepG2 cells were incubated with FFAs-1000μM in presence and absence of Picroside II-10 μM for 20 hours. RESULTS: HepG2 cells incubated with FFAs-1000μM lead to increased lipid accumulation. Picroside II-10μM attenuated FFAs-induced lipid accumulation (33%), loss of mitochondrial membrane potential (ΔΨm), ATP depletion, and production of reactive oxygen species (ROS). A concomitant increase in cytochrome C at transcription and protein levels was observed. An increase in expression of MnSOD, catalase, and higher levels of tGSH and GSH:GSSG ratios underlie the ROS salvaging activity of picroside II. CONCLUSION: Picroside II significantly attenuated FFAs-induced-lipotoxicity. The reduction in ROS, increased antioxidant enzymes, and improvement in mitochondrial function underlie the mechanisms of action of picroside II. These findings suggest a need to develop an investigational drug profile of picroside II for NAFLD as a therapeutic strategy. This could be evaluated through the fast-track path of reverse pharmacology.

AI snapshot

Written from the paper’s full text.

TL;DR

In an in vitro NAFLD model using FFAs-loaded HepG2 cells, picroside II (10 μM) attenuated lipid accumulation and lipotoxicity, including oxidative stress and mitochondrial dysfunction. The findings support further investigation of picroside II for NAFLD, though only in HepG2 cells and with mechanistic gaps noted by the authors.

Key findings

  • Picroside II reduced FFAs-induced lipid accumulation by 33% (p < 0.01); silibinin, the positive control, reduced it by 32% (p < 0.01).
  • FFAs (1000 μM) increased ROS production by 97.9% (p < 0.05); picroside II and silibinin decreased ROS formation by 38.3% and 37.8%, respectively. Picroside II also rescued glutathione depletion, increased tGSH and GSH:GSSG, and increased MnSOD and Catalase mRNA expression by 1.5-fold (p < 0.01).
  • FFAs caused a 48.84% decrease in ATP (p < 0.01) and loss of mitochondrial membrane potential (ΔΨm, p < 0.001); picroside II prevented ATP reduction and reversed ΔΨm loss (p < 0.05). Picroside II also increased cytochrome C mRNA and protein expression (p < 0.05).
  • Silibinin did not affect GSH:GSSG, MnSOD, or Catalase, whereas picroside II did.

Methods

  • HepG2 cells were incubated with FFAs at 1000 μM (oleic:palmitic acid 2:1) for 20 h, with or without picroside II at 10 μM; phytoactives were pre-treated for 2 h before FFAs. Silibinin (10 μM) was used as a positive control.
  • Assays included MTT cytotoxicity, Oil Red O lipid quantification, DCFH2-DA ROS measurement, total glutathione and GSH:GSSG estimation, ATP luciferase assay, TMRM flow cytometry for ΔΨm, qRT-PCR, and Western blot.
  • Statistical analysis used GraphPad Prism with one- and two-way ANOVA; 4–6 independent experiments were performed, with p < 0.05 considered significant.

Limitations

  • The paper states that HepG2 cells are not primary hepatocytes and that results should be followed up in other models such as hepatic spherules, dual cell cultures with Kupffer cells, or primary hepatocytes.
  • The authors note that other P. kurroa compounds (e.g., picroside I, apocynin) and other NAFLD pathways (insulin resistance, inflammation, apoptosis, fibrogenesis, etc.) were not explored, and that effects on mitochondrial complexes I and III remain to be studied.
  • Evident from the text: this is an in vitro study only, with no in vivo, preclinical toxicity, or clinical data; the mechanistic conclusions are therefore limited to the HepG2 cell model.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.jaim.2021.04.007

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

14 of 37 cited sources checked · 6 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Picroside II effectively attenuated fatty acid accumulation in HepG2 cells via decreasing FFAs uptake and lipogenesis.

    “Picroside II effectively attenuated the fatty acid accumulation in HepG2 cells via decreasing FFAs uptake and lipogenesis.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Dhami-Shah, 2018, Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis, Clin Mol Hepatol source
  • Premisecitation

    Picroside I did not show any effect on fatty acid accumulation in HepG2 cells.

    “Picroside I on the other hand, did not show any effect on fatty acid accumulation in HepG2 cells.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Dhami-Shah, 2018, Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis, Clin Mol Hepatol source
  • Premisecitation

    Impairment in mitochondrial function and ATP generation is observed in NAFLD.

    “Impairment in mitochondrial function and ATP generation is also observed.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [7] Cohen, 2011, Human fatty liver disease: old questions and new insights, Science source

      In “What Factors Contribute to NAFLD Progression?” (page not provided), the paper says saturated fats can inhibit mitochondrial function in model organisms. It does not report impaired ATP generation or establish that mitochondrial impairment was observed in people with NAFLD. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [8] Day, 1998, Steatohepatitis: a tale of two hits, Gastroenterology source
  • Premisecitation

    Picroside II attenuates fatty acid accumulation in HepG2 cells by decreasing FFAs uptake and synthesis.

    “Earlier, it was shown that picroside II significantly reduced fatty acid accumulation in HepG2 cells by decreasing the FFAs uptake and synthesis [18].”
    • Also stated in: § Discussion · plain
      “Picroside II attenuates FFAs accumulation, decreases the production of ROS, and increases the levels of antioxidants (glutathione, MnSOD and Catalase).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [18] Dhami-Shah, 2018, Picroside II attenuates fatty acid accumulation in HepG2 cells via modulation of fatty acid uptake and synthesis, Clin Mol Hepatol source
  • Premisecitation

    An increase in ROS formation is accompanied by decrease in the levels of glutathione, MnSOD and Catalase.

    “An increase in ROS formation was accompanied by decrease in the levels of glutathione, MnSOD and Catalase [31].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [31] Masarone, 2018, Role of oxidative stress in pathophysiology of nonalcoholic fatty liver disease, Oxid Med Cell Longev source

      Section 2.1 reports that, in a high-fat-diet mouse model, increased oxidative stress was associated with lower glutathione levels and reduced catalase and superoxide-dismutase activity. Section 2 separately links reduced MnSOD activity to increased ROS production. The paper supports the general association, but it does not report decreased MnSOD and catalase levels together with increased ROS; it discusses enzyme activity, and the findings come from different contexts. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Classified as probably not a substantial claim. 18
  • May combine two claims. 9
  • The quote only partly states this claim. 1

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The Ct value of each gene was normalized with β-actin.

    “The Ct value of each gene was normalized with β-actin [27].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [27] Zanoni, 2009, mRNA expression analysis by real-time PCR, Protocol Exchange source

      The Introduction specifies 18S RNA, not β-actin, as the endogenous control used to adjust target-gene expression for differences in template amount. The indexed copy provides no page number for this passage. (LLM, conf=0.90)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Oxidative stress contributes to the production of reactive oxygen species, lipid peroxidation products and decreases the levels of antioxidants such as superoxide dismutase, glutathione, and catalase.

    “Oxidative stress contributes to the production of reactive oxygen species, lipid peroxidation products and decreases the levels of antioxidants such as superoxide dismutase, glutathione, and catalase.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [7] Cohen, 2011, Human fatty liver disease: old questions and new insights, Science source

      The section “What Factors Contribute to NAFLD Progression?” mentions oxidative-stress pathways as implicated in progression to NASH, but does not describe the effects attributed to oxidative stress here. Searches for reactive oxygen species, lipid peroxidation, superoxide dismutase, glutathione, and catalase found no passage establishing their production or decreased levels. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
    • cites [8] Day, 1998, Steatohepatitis: a tale of two hits, Gastroenterology source

  • Classified as probably not a substantial claim.

    Premisecitation

    Complexes I and III are the major sites for superoxide formation.

    “since they are the major sites for superoxide formation [[36], [37], [38], [39], [40], [41]].”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [36] Escobar, 1996, Sod and catalase inactivation by singlet oxygen and peroxyl radicals, Free Radic Biol Med source
    • cites [37] Hüttemann, 2011, The multiple functions of cytochrome c and their regulation in life and death decisions of the mammalian cell: from respiration to apoptosis, Mitochondrion source
    • cites [38] Fromenty, 1995, Inhibition of mitochondrial beta-oxidation as a mechanism of hepatotoxicity, Pharmacol Ther source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Disruption in complexes I and III increases formation of ROS, diminishes tGSH, and depletes ATP generation.

    “Disruption in the complexes I and III has shown to increase formation of ROS, diminish tGSH, and deplete ATP generation [42].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [42] Simões, 2018, Mitochondria in non-alcoholic fatty liver disease, Int J Biochem Cell Biol source

      Section 2.2.2 identifies complexes I and III as major sites of superoxide production and reports diminished GSH-related antioxidant activity in NAFLD. Section 2.1.2 reports reduced ATP synthesis alongside ETC alterations. The paper does not establish that disruption of complexes I and III specifically causes all three effects, or that total glutathione (tGSH) is depleted. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Animal models of mitochondrial dysfunction in NASH have shown alteration in the ETC complexes I, III, and IV.

    “Animal models of mitochondrial dysfunction in NASH have shown alteration in the ETC complexes I, III, and IV [35].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [35] Rector, 2010, Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of nonalcoholic fatty liver disease in an obese rodent model, J Hepatol source

      The Results (page not provided) report mitochondrial dysfunction in OLETF rats, including reduced fatty acid oxidation and cytochrome c content. The Methods’ enzyme activity assays and Results do not identify alterations in ETC complexes I, III, and IV, so the source does not support that specific part of the claim. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductcitation

    The blot intensity was quantified using Image J software and the results were reported relative to tubulin band density used as a load control.

    “The blot intensity was quantified using Image J software and the results were reported relative to tubulin band density used as a load control [28].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [28] Mahmood, 2012, Western blot: technique, theory, and trouble shooting, N Am J Med Sci source

      The Theory > Quantification section says western blots provide relative comparisons of protein levels and that differences in loading and transfer need to be standardized (page not available). It does not mention ImageJ or reporting results relative to tubulin band density, so it supports only the general rationale for relative quantification. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Oxidative stress is a key pathogenetic mechanism in NAFLD contributing to hepatic injury.

    “Oxidative stress is a key pathologenetic mechanism in NAFLD contributing to hepatic injury [30].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [30] Ucar, 2013, The relationship between oxidative stress and nonalcoholic fatty liver disease: its effects on the development of nonalcoholic steatohepatitis, Redox Rep source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Pre-clinical and clinical studies have shown anti-oxidant properties of silibinin.

    “Pre–clinical and clinical studies have shown anti-oxidant properties of silibinin [45].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [45] Surai, 2015, Silymarin as a natural antioxidant: an overview of the current evidence and perspectives, Antioxidants source

      Section 4.1 reports antioxidant effects of silibinin in cell experiments, and section 4.4 reports protective effects in animal experiments. These support the pre-clinical part of the claim, but the cited passages do not establish that clinical studies showed antioxidant effects of silibinin; the study of monocytes from pre-eclamptic women was conducted in vitro. No page numbers are available in our copy. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    FFAs-loading at 1000 μM decreased total glutathione levels in HepG2 cells, suggesting glutathione depletion (p < 0.01).

    “In the present study, there was a decrease in total glutathione levels on FFAs-loading suggesting glutathione depletion, p < 0.01.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingnone given

    In FFAs-treated HepG2 cells, silibinin treatment increases ΔΨm and ATP generation compared to FFAs alone.

    “Similarly, silibinin pre-treated group showed an increase in ΔΨm and ATP generation compared to FFAs-treated group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    NAFLD is caused by the accumulation of fat within the hepatocytes (>5.5%) in the absence of significant alcohol intake.

    “Non-alcoholic fatty liver disease (NAFLD) is caused by the accumulation of fat within the hepatocytes (>5.5%) in the absence of significant alcohol intake [1].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Angulo, 2002, Nonalcoholic fatty liver disease, N Engl J Med source

  • May combine two claims.

    Premisecitation

    Picrorhiza kurroa extract has shown reduction in hepatic damage and fatty acid infiltration in several experimental models and clinically in viral hepatitis.

    “Picrorhiza kurroa is one of the medicinal plants known for its clinical and experimental hepatoprotective activity [10].”
    • Also stated in: § Introduction · plain
      “The extracts of P. kurroa significantly reduced hepatic fatty infiltration induced by CCl4, galactosamine, paracetamol, thioacetamide, and high-fat diet in rat models [[11], [12], [13], [14], [15], [16], [17]].”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [10] Tolman, 2007, Treatment of non-alcoholic fatty liver disease, Therapeut Clin Risk Manag
    • cites [11] Acharya, 2001

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites [12] Antarkar, 1978, A pilot phase II trial with Arogyawardhini and Punarnavadi kwath in viral hepatitis, Panminerva Med

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Interpretationown data

    The reduction in ROS, increased antioxidant enzymes, and improvement in mitochondrial function underlie the mechanisms of action of picroside II.

    “The reduction in ROS, increased antioxidant enzymes, and improvement in mitochondrial function underlie the mechanisms of action of picroside II.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: MnSOD and Catalase prevent oxidative damage by quenching ROS and decreasing the production of hydrogen peroxide.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The pathogenesis of NAFLD comprises several other dynamic pathways and cross-talks between two or more cell types in the liver.

    “The pathogenesis of NAFLD also comprises of several other dynamic pathways and cross-talks between two or more cell types in liver [47].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Garcia-Ruiz, 2010, Mitochondrial complex I subunits are decreased in murine nonalcoholic fatty liver disease: implication of peroxynitrite, J Proteome Res source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The experiments were repeated four times.

    “The experiments were repeated four times.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationcitation

    An increase in Cytochrome C expression implies activation of its function as a single electron carrier in the electron transport chain, catalyzing the reduction of oxygen to water and leading to more ATP.

    “An increase in expression of Cytochrome C implies activation of its function as a single electron carrier in the electron transport chain catalyzing the reduction of oxygen molecule to water, thus leading to more ATP [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Begriche, 2006, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Clinical studies have reported an increase in lipid peroxidation in patients with NASH.

    “Clinical studies have also reported an increase in lipid peroxidation in patients with NASH [33].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Chalasani, 2004, Systemic levels of lipid peroxidation and its metabolic and dietary correlates in patients with nonalcoholic steatohepatitis, Am J Gastroenterol source

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationcitation

    Given earlier clinical and in vitro activities of P. kurroa and picroside II, the results in HepG2 cells gain relevance.

    “But in view of the earlier clinical and in vitro activities shown by P. kurroa and picroside II, these results in HepG2 cells gain relevance [48].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Chavez-Tapia, 2011, In vitro models for the study of non-alcoholic fatty liver disease, Curr Med Chem source
    • Rests on an assumption: Primary hepatocytes are a standard model for studying mechanisms of molecular activity of a compound.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Silibinin inhibits formation of ROS by increasing tGSH, MnSOD, Catalase, and glutathione peroxidase levels in rat Kupffer cells, hepatocytes, HepG2 cells, and isolated rat hepatic mitochondria.

    “Silibinin has shown to inhibit the formation of ROS by increasing tGSH, MnSOD, Catalase, and glutathione peroxidase levels in rat Kupffer cells, hepatocytes, HepG2 cells, and isolated rat hepatic mitochondria [46].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Loguercio, 2011, Silybin and the liver: from basic research to clinical practice, World J Gastroenterol source

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    A minimum of four to six independent experiments were carried out and the standard error of the mean (SEM) was derived.

    “A minimum of four to six independent experiments were carried out and the standard error of the mean (SEM) was derived.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Besides picroside II, P. kurroa contains many other active compounds, including picroside I and apocynin, whose activities on other NAFLD targets have not been explored.

    “Besides picroside II, there are many other active compounds present in P. kurroa. These include picroside I and apocynin whose activities have not been explored on other targets involved in pathogenesis of NAFLD such as insulin resistance, altered lipid metabolism, lipotoxicity, oxidative stress and inflammation, activation of immune cells, apoptosis, necrosis, fibrogenesis, and collagen turnover”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Loguercio, 2011, Silybin and the liver: from basic research to clinical practice, World J Gastroenterol source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    An increase in ROS damages mitochondrial DNA.

    “Also, increase in the ROS is shown to damage mitochondrial DNA [43].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [43] Begriche, 2006, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In patients with NASH, an increase in ROS is associated with impaired mitochondrial electron transport chain (ETC) and loss in ΔΨm.

    “In patients with NASH, an increase in the ROS is associated with impaired mitochondrial electron transport chain (ETC) and loss in the ΔΨm [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Begriche, 2006, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion source
23 of 23

  • The paper relies on this without support.

    Findings in FFAs-loaded HepG2 cells are predictive of therapeutic effects in human NAFLD.

    “These findings suggest a need to develop an investigational drug profile of picroside II for NAFLD as a therapeutic strategy.”

  • The paper relies on this without support.

    Silibinin is an appropriate positive control for picroside II in this in vitro NAFLD model.

    “To study the effect of picroside II on FFAs accumulation, oxidative stress and mitochondrial function with silibinin as a positive control in in vitro NAFLD model.”

  • The paper relies on this without support.

    MnSOD and Catalase prevent oxidative damage by quenching ROS and decreasing the production of hydrogen peroxide.

    “The antioxidant enzymes (MnSOD and Catalase) prevent oxidative damage by quenching ROS and decreasing the production of hydrogen peroxide.”

  • The paper relies on this without support.

    Oxidative stress and mitochondrial dysfunction play a significant role in the progression of NAFL to NASH.

    “Oxidative stress and mitochondrial dysfunction play a significant role in the progression of NAFL to NASH.”

  • The paper relies on this without support.

    Primary hepatocytes are a standard model for studying mechanisms of molecular activity of a compound.

    “Primary hepatocytes have been proposed as a standard model for studying mechanisms of molecular activity of a compound.”
5 of 5

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.

  • Figure 5 reverses the reported effect on mitochondrial membrane potential

    Minor

    The Figure 5 caption says picroside II decreases ΔΨm, whereas the discussion says it increases ΔΨm. These are opposite directions for a reported effect central to the paper's conclusion about improved mitochondrial function.

1 of 1

Cites

Flagged first, then by citations

5 of the 54 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Begriche, 2006, Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it, Mitochondrion, 6, 1, 10.1016/j.mito.2005.10.004 · DOI · Paper page

Cited by

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Related

Authors
Dhami-Shah, H., Vaidya, R., Talwadekar, M., Shaw, E., Udipi, S., Kolthur-Seetharam, U., & Vaidya, A. D. B.
Affiliations
Tata Institute of Fundamental Research (IN)
Corresponding author
Dhami-Shah, Hiteshi
ORCID
Venue
Journal of Ayurveda and Integrative Medicine
Publisher
Elsevier BV
Published
2021-07
Volume
12
Issue
3
Pages
465-473
ISSN
0975-9476 (ISSN-L)
DOI
10.1016/j.jaim.2021.04.007
PMC
PMC8377190
OpenAlex
W3190193027
Semantic Scholar
0105e15e347145a8c89db056065e3cc2b0239c20
Cited by
15
References
54
Citations by year
2026: 3 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 4
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Ayurveda and Integrative Medicine (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Department of Science and Technology, Ministry of Science and Technology, India (SR/WOS-A/LS-1135/2014)
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal plant effects and applications
Keywords
picroside II, Picrorhiza kurroa, free fatty acids, hepatic lipid accumulation, lipotoxicity, non-alcoholic fatty liver disease, oxidative stress, mitochondrial dysfunction, reactive oxygen species, cytochrome c, antioxidant enzymes, glutathione, mitochondrial membrane potential, HepG2 cells

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