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Cited by 37Alzheimer's disease research and treatmentsMedicinal Plants and NeuroprotectionDementia and Cognitive Impairment Research

Effects of the combination of high-intensity interval training and Ecdysterone on learning and memory abilities, antioxidant enzyme activities, and neuronal population in an Amyloid-beta-induced rat model of Alzheimer’s disease

Open access
Gholipour, Parsa, Komaki, Alireza, Ramezani, Mahdi, Parsa, Hesam·2022·Physiology & Behavior
DOI 10.1016/j.physbeh.2022.113817

Published version of a preprint

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Abstract

Aims Oxidative stress and neuronal death are the primary reasons for the progression of amyloid-beta (Aβ) deposition and cognitive deficits in Alzheimer's disease (AD). Ecdysterone (ecdy), a common derivative of ecdysteroids, possesses free radical scavenging and cognitive-improving effects. High-intensity interval training (HIIT) can be a therapeutic strategy for improving cognitive decline and oxidative stress. The present study was aimed to evaluate the effect of HIIT exercise and ecdy consumption synergistically on the changes in learning and memory functions, activities of hippocampal antioxidant enzymes, and neuronal population after AD induced by Aβ in male rats.Materials and methods Following ten days of Aβ injection, HIIT exercise and ecdy treatment (10 mg/kg/day; P.O.) were initiated and continued for eight consecutive weeks in rats. At the end of the treatment period, the rat's learning and memory functions were assessed using Morris water maze and passive avoidance tests. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRx), and changes in neuronal population were evaluated in rats' brains.Results The results indicated that Aβ injection disrupted spatial/passive avoidance learning and memory in both tests, accompanied by a decrease in the SOD and CAT (as endogenous antioxidants) in rats' hippocampus. Additionally, Aβ injection resulted in neuronal loss in the cerebral cortex and hippocampus. Although the consumption of ecdy separately improved spatial/passive avoidance learning and memory impairments, recovered hippocampal activity of SOD, CAT, GRx, and prevented the hippocampal neuronal loss, its combination along with HIIT resulted in a more powerful and effective amelioration in all the above-mentioned Aβ-neuropathological changes.Conclusion Our results confirm that a combination of HIIT and ecdy treatment could be a promising potential therapeutic option against AD-associated cognitive decline, owing to their free radical scavenging and neuroprotective properties.

AI snapshot

Written from the paper’s full text.

TL;DR

In an Aβ1-42-induced rat model of Alzheimer’s disease, eight weeks of Ecdysterone alone improved some learning/memory, antioxidant enzyme, and neuronal outcomes, while HIIT alone did not; combining HIIT with Ecdysterone produced the strongest amelioration. The authors conclude the combination may be a promising therapeutic approach against AD-associated cognitive decline.

Key findings

  • Aβ injection impaired spatial/passive avoidance learning and memory and reduced hippocampal antioxidant enzymes and neuronal populations: swimming distance increased on training days 2, 3, and 4 (P=0.0341, P<0.001, P=0.007), escape latency increased on days 3 and 4 (P=0.0033, P<0.001), STLr and TDC decreased (F8,63=37, P<0.001; F8,63=47.96, P<0.001), and intact neurons decreased in CA1, CA3, DG, and CC (F4,10=16.88, 49.25, 44.42, 6.308; P<0.001, <0.001, <0.001, =0.0072).
  • Ecdysterone alone improved several outcomes: decreased swimming distance on days 3 and 4 (P=0.0411, P=0.0232), decreased escape latency on day 4 (P=0.0253), increased STLr and TDC (P=0.0251, P=0.0132), increased intact neurons in CA1, CA3, and DG (P=0.0205, P=0.0171, P=0.0186), and improved SOD, CAT, and GRx, but not GPx.
  • Ecdysterone + HIIT was more effective: decreased swimming distance on days 3 and 4 (P<0.001, P=0.0034), decreased escape latency on days 3 and 4 (P=0.0019, P=0.0014), increased target-quadrant time (P=0.0026), increased STLr and TDC (P<0.001, P<0.001), increased intact neurons in CA1, CA3, DG, and CC (P=0.0022, P<0.001, P<0.001, P=0.0407), and improved GPx (P=0.0199) among other enzymes.
  • HIIT alone did not alter behavioral alterations in the Morris water maze or passive avoidance, antioxidant enzyme content, or neuronal population; body weights did not differ significantly between groups (F8,63=2.712; P=0.9860).

Methods

  • Seventy-two adult male Wistar rats (175–200 g) were assigned to nine groups (n=8): control, sham, Ecdy, HIIT, Ecdy+HIIT, Alzheimer’s, Alzheimer’s+Ecdy, Alzheimer’s+HIIT, and Alzheimer’s+Ecdy+HIIT. AD was induced by intrahippocampal Aβ1-42 injection; treatments lasted eight weeks: Ecdysterone 10 mg/kg/day by oral gavage and/or HIIT treadmill exercise 5 sessions/week, with 1-min intervals at 90%/50% maximal capacity, 30 min in week 1 increasing to 60 min by week 7, plus 5-min warm-up and cool-down.
  • Outcomes included Morris water maze and passive avoidance tests, Nissl staining for intact neurons in hippocampal CA1, CA3, DG, and cerebral cortex, and hippocampal SOD, CAT, GPx, and GRx. Data were analyzed with two-way and one-way ANOVA followed by Tukey’s post hoc test, with significance at P<0.05.

Limitations

  • The authors state that further and more fundamental research is required to investigate the involved mechanisms in detail.
  • Evident from the text: only male Wistar rats and an Aβ1-42 intrahippocampal model were used; sample sizes were small for histology (3 rats/group) and biochemistry (5 rats/group), and no female, other AD model, or dose-response comparisons were included.
  • Evident from the text: control, sham, and positive-control groups did not differ significantly, so sham and positive controls were ignored in analyses; HIIT alone was ineffective in this protocol, and some results text appears inconsistent (e.g., CAT/GRx paragraphs refer to SOD), which may affect interpretation.

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

Integrity signals

Registry

Crossref · 10.1016/j.physbeh.2022.113817

Cites

83 of 83 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 27 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Aβ injection decreased superoxide dismutase and catalase in rat hippocampus.

    “accompanied by a decrease in the superoxide dismutase and catalase (as endogenous antioxidants) in rat hippocampus.”
    Quote in the paperSubstantial claim
  • Findingown data

    Aβ injection resulted in neuronal loss in the cerebral cortex and hippocampus.

    “Additionally, Aβ injection resulted in neuronal loss in the cerebral cortex and hippocampus.”
    Quote in the paperSubstantial claim
  • Findingown data

    Combination of HIIT with Ecdysterone resulted in more powerful and effective amelioration in all above-mentioned Aβ-neuropathological changes than Ecdysterone alone.

    “its combination with HIIT resulted in a more powerful and effective amelioration in all the above-mentioned Aβ-neuropathological changes.”
    Quote in the paperSubstantial claim
  • Findingown data

    Ecdysterone alone recovered hippocampal activity of SOD, CAT, GRx, GRx.

    “recovered hippocampal activity of SOD, CAT, GRx, GRx”
    Quote in the paperSubstantial claim
  • Findingown data

    Ecdysterone alone prevented hippocampal neuronal loss.

    “and prevented the hippocampal neuronal loss”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim. 2
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 9

  • The quote only partly states this claim.

    Findingown data

    The Alzheimer group spent significantly less time in the target quadrant compared to the control group.

    “the time that rats in the Alzheimer group spent in the target quadrant dropped signi cantly (F 8, 63 = 5.008; P < 0.001)”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Ecdy+HIIT treatment group caused a noticeable increase in time spent in the target quadrant compared to the Alzheimer group.

    “although the Ecdy+HIIT treatment group caused an increase in it noticeably (P = 0.0026)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Aβ-induced experimental Alzheimer produced spatial memory impairments in the Morris water maze and decreased learning and memory in the passive avoidance task.

    “In the present survey, Aβ-induced experimental Alzheimer produced a wide array of disorders such as spatial memory impairments in MWM and decreased learning and memory in PAT.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

  • May combine two claims.

    Findingown data

    Ecdy decreased swimming distance and escape latency to the hidden platform in training days and improved total swimming distance in the probe day.

    “While Ecdy as a natural hormone decreased swimming distance and escape latency to the hidden platform in training days, it also caused an improvement in total swimming distance in the probe day.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

  • May combine two claims.

    Findingown data

    Consumption of Ecdy alone (except for GPx) and in combination with HIIT increased SOD, CAT, GPx, and GRx enzyme levels in the hippocampus tissue that were dropped because of Aβ injection.

    “biomechanical experiments revealed that consumption of Ecdy separate (except GPx) and in combination with HIIT exercise augmented to the Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx) and Glutathione Reductase (GRx) enzymes in the hippocampus tissue that were dropped because of Aβ injection.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.
    • Rests on an assumption: The measured antioxidant enzyme activities in the hippocampus reflect oxidative stress status in the brain.

  • May combine two claims.

    Findingown data

    Ecdysterone has antioxidant properties separately and could help alleviate neuronal loss and behavioral deficits a little bit.

    “The present survey results (Fig. 8) displayed that, although Ecdysterone has antioxidant properties separately and could help alleviate neuronal loss and behavioral de cits a little bit”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

  • May combine two claims.

    Findingown data

    Ecdy and HIIT+Ecdy increased the amount of SOD in the Alzheimer group (P = 0.0276 and P < 0.001 respectively).

    “In comparison, Ecdy and group of HIIT+Ecdy could promote the amount of SOD considerably in the Alzheimer group (P = 0.0276, P < 0.001 respectively) (Fig. 7B).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.
    • Rests on an assumption: The measured antioxidant enzyme activities in the hippocampus reflect oxidative stress status in the brain.

  • May combine two claims.

    Findingown data

    Eight weeks of HIIT accompanied by Ecdy decreased swimming distance and escape latency to the hidden platform in training days and improved total swimming distance and total time spent in the target quadrant in the probe day.

    “Additionally, eight weeks of HIIT accompanied by Ecdy could help decrease swimming distance and escape latency to the hidden platform in training days, and also, they caused an improvement in total swimming distance and total time spent in the target quadrant in the probe day.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

  • May combine two claims.

    Findingown data

    Ecdy and HIIT+Ecdy increased the amount of SOD in the Alzheimer group (P = 0.0019 and P = 0.0079 respectively).

    “In comparison, Ecdy and group of HIIT+Ecdy could promote the amount of SOD considerably in the Alzheimer group (P = 0.0019, P = 0.0079 respectively) (Fig. 7D).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.
    • Rests on an assumption: The measured antioxidant enzyme activities in the hippocampus reflect oxidative stress status in the brain.

  • May combine two claims.

    Findingown data

    Eight weeks of Ecdy and a combination of HIIT and Ecdy promoted latency time to the dark compartment (STLr) and time spent in the dark compartment (TDC).

    “Nevertheless, eight weeks of consumption of Ecdy and a combination of both HIIT and Ecdy could promote latency time to the dark compartment (STLr) and time spent in the dark compartment (TDC).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

  • May combine two claims.

    Findingown data

    Ecdy+HIIT treated group improved neuronal distraction in the hippocampal CA1, CA3, and DG areas and also in the cerebral cortex (CC) compared with the Alzheimer group (P = 0.0022, P < 0.001, P < 0.001, and P = 0.0407 respectively).

    “Meanwhile, Ecdy+HIIT treated group markedly culminated in improvement of neuronal distraction in the hippocampal CA1 (P = 0.0022), CA3 (P < 0.001), DG (P < 0.001) areas and also in CC (P = 0.0407) compared with the Alzheimer group (Fig.6).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.
    • Rests on an assumption: Nissl staining intact neurons accurately reflect neuronal population or survival.

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

    Premisecitation

    Supplementations with antioxidant properties are helpful, particularly in the early stages of disease.

    “It is reported that supplementations with antioxidant properties are helpful, particularly in the early stages of disease (10).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Arab, 2016, The effect of green tea consumption on oxidative stress markers and cognitive function in patients with Alzheimer’s disease: a prospective intervention study, Caspian J. Internal Med.

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Natural antioxidants from plants, including phytoestrogens, can alleviate oxidative stress.

    “At the same time, an array of natural antioxidants have been drawn from plants, including phytoestrogens, which can alleviate oxidative stress (11,12).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [11] Parveen, 2016, Recent investigations for discovery of natural antioxidants: a comprehensive review, Crit. Rev.™ Eukaryotic Gene Expression

      Not checked in the free run.

    • cites [12] A Sobenin, 2016, Phytoestrogen-rich dietary supplements in anti-atherosclerotic therapy in postmenopausal women, Curr. Pharm. Des. source

      Not checked in the free run.

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

    Premisecitation

    Previous studies suggested that Ecdy can promote learning, memory and orally treat cognitive dysfunctions of rats induced by beta-amyloid peptide fragment 25-35 and raise the expression of C-fos.

    “previous studies suggested that Ecdy can promote learning, memory and orally treat cognitive dysfunctions of rats induced by beta-amyloid peptide fragment 25-35 (Aβ [25][26][27][28][29][30][31][32][33][34][35] ) and raise the expression of C-fos.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Osinskaia, 1992, Antiradical properties and antioxidant activity of ecdysterone, Ukrainskii biokhimicheskii zhurnal (1978)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Earlier behavioral studies indicated that Ecdy caused shorter latency and searching distance in the Morris water maze test between Aβ-induced rats, meaning Ecdy could improve impaired spatial memory.

    “earlier studies in terms of behavioral investigations have indicated that Ecdy caused shorter latency and searching distance in Morris water maze test between Aβ-induced rats that means Ecdy could improve impaired spatial memory (22).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] Su-fen, 2005, Protective effect of ecdysterone on PC12 cells cytotoxicity induced by Beta-amyloid 25–35, Chinese J. Integrat. Med. source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Rats were randomly assigned into nine groups.

    “Then they were randomly assigned into nine groups(n=8 per group)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Exercise training increases hippocampal neurogenesis, synaptic plasticity, and neurotransmission in the hippocampus.

    “ET accomplishment increases hippocampal Neurogenesis, synaptic plasticity, as well, neurotransmission in the hippocampus”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [25] Liu, 2009, Differential effects of treadmill running and wheel running on spatial or aversive learning and memory: roles of amygdalar brain-derived neurotrophic factor and synaptotagmin I, J. Physiol. source

      Not checked in the free run.

    • cites [26] Dao, 2013, Treadmill exercise prevents learning and memory impairment in Alzheimer's disease-like pathology, Curr. Alzheimer Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HIIT regulates hippocampal oxidative stress, BDNF, and inflammatory mediators in laboratory animals.

    “Additionally, this training method regulates hippocampal oxidative stress, BDNF, and in ammatory mediators in laboratory animals.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Dao, 2014, Regular exercise prevents non-cognitive disturbances in a rat model of Alzheimer's disease, Int. J. Neuropsychopharmacol source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Incubation of Aβ 1-42 at 37°C for seven days leads to fibril formation, which has neurotoxic properties.

    “This action leads to bril formation, which has neurotoxic properties (36).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Lin, 2019, Steroid-ENRICHED FRAction of Achyranthes bidentata protects Amyloid β peptide 1–40-induced cognitive dysfunction and neuroinflammation in rats, Mol. Neurobiol. source

      Not checked in the free run.

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

    Premisecitation

    A particular dosage of Ecdy promoted spatial memory and learning in rats that faced memory impairment after Aβ injection.

    “a survey showed that a particular dosage of Ecdy promoted spatial memory and learning in the rats that faced a memory impairment after Aβ injection.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [54] Komaki, 2015, The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats, Pharmacol. Biochem. Behav. source

      Not checked in the free run.

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

    Premisecitation

    HIIT for eight minutes per day promotes memory and learning impairment in Aβ-induced rats, due to an increase in antioxidant enzymes SOD and CAT and decreased lipid peroxidation in the hippocampus.

    “A study indicated that HIIT for eight minutes per day promotes memory and learning impairment in Aβ-induced rats; it was due to an increase in antioxidant enzymes of Super Oxide Dismutase and Catalase and decreased Lipid peroxidation in the hippocampus.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [50] Ghazvini, 2016, Effects of treatment with estrogen and progesterone on the methamphetamine-induced cognitive impairment in ovariectomized rats, Neurosci. Lett. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    A combination of Ecdysterone and HIIT causes synaptic refinement and behavioral improvement.

    “Hence, a combination of both causes synaptic re nement and behavioral improvement concerning the prepared study.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.

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

    Premisecitation

    Treatment with Ecdy in three dosages (1, 10, 100 mg/kg/day), especially the higher dosage for 12 weeks, orally reversed conditions caused by type 1 diabetes in rats.

    “the treatment with Ecdy in three dosages (1,10,100 mg/kg/day), especially in higher dosage for 12 weeks, orally reversed the conditions mentioned above caused by diabetes (33).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Afzalpour, 2015, Comparing interval and continuous exercise training regimens on neurotrophic factors in rat brain, Physiol. Behav. source

      Not checked in the free run.

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

    Premisecitation

    Six weeks of HIIT exercise (6 sessions per week) caused a significant increase in SOD antioxidant enzyme and Total Antioxidant Capacity in the cerebellum but not in the cerebral cortex.

    “The other survey reported that six weeks of HIIT exercise (6 sessions per week) caused a signi cant increase in Super Oxide Dismutase antioxidant enzyme and Total Antioxidant Capacity in the cerebellum but not in the cerebral cortex.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [51] Zarrinkalam, 2016, Effects of endurance, resistance, and concurrent exercise on learning and memory after morphine withdrawal in rats, Life Sci. source

      Not checked in the free run.

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

    Premisecitation

    Peritoneal injection of Ecdy (16 mg/kg) for seven days resulted in significant decreases in neuronal death rate, brain water content, MDA content, and a noticeable increase in SOD enzymes in the hippocampus compared with the TBI group.

    “The study with Shihao et al. on traumatic brain injury (TBI) in rats reported that peritoneal injection of Ecdy (16 mg/kg) for seven days resulted in signi cant decreases in the neuronal death rate, brain water content, MDA content, and a noticeable increase in SOD enzymes in the hippocampus compared with TBI group”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Genet, 2002, Alterations in antioxidant enzymes and oxidative damage in experimental diabetic rat tissues: effect of vanadate and fenugreek (Trigonella foenum graecum), Mol. Cell. Biochem. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    The behavioral inadequacies in the Aβ-induced Alzheimer rats were related to the Aβ concentration in the hippocampus and cerebral cortex and to oxidative stress.

    “These behavioral inadequacies were related to the Aβ concentration in the hippocampus and cerebral cortex and oxidative stress that is one of the fundamental causes for Aβ-induced tissue damage.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The Aβ-induced rat model is a valid model of Alzheimer's disease.
    • Rests on an assumption: Oxidative stress is one of the fundamental causes for Aβ-induced tissue damage.
26 of 26

  • The authors state this as an assumption.

    No supporting evidence identifies which combination of time, frequency, intensity, and type of exercise has a more significant effect on cognitive niches.

    “However, never should it be forgotten that there is no supporting evidence to illustrate which combination of time, frequency, intensity, and generally type of exercise may have a more signi cant effect on cognitive niches.”

  • The paper relies on this without support.

    The Aβ-induced rat model is a valid model of Alzheimer's disease.

    “Aβ-induced experimental Alzheimer produced a wide array of disorders such as spatial memory impairments in MWM and decreased learning and memory in PAT.”

  • The paper relies on this without support.

    Oxidative stress is one of the fundamental causes for Aβ-induced tissue damage.

    “oxidative stress that is one of the fundamental causes for Aβ-induced tissue damage.”

  • The paper relies on this without support.

    Extra amounts of reactive oxygen species (ROS) lead to oxidative damage, including lipid peroxidation and protein oxidation, culminating in programmed cell death and neuronal loss in the hippocampus and cerebral cortex.

    “Under such a condition, extra amounts of reactive oxygen species (ROS) lead to oxidative damage, including lipid peroxidation and protein oxidation, culminating in programmed cell death and neuronal loss in the hippocampus and cerebral cortex.”

  • The paper relies on this without support.

    Nissl staining intact neurons accurately reflect neuronal population or survival.

    “Histological studies through Nissl staining demonstrated that eight weeks of Ecdy separately increased the number of intact neurons in the hippocampal DG, CA1, CA3 areas but not CC.”

  • The paper relies on this without support.

    The measured antioxidant enzyme activities in the hippocampus reflect oxidative stress status in the brain.

    “biomechanical experiments revealed that consumption of Ecdy separate (except GPx) and in combination with HIIT exercise augmented to the Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPx) and Glutathione Reductase (GRx) enzymes in the hippocampus tissue that were dropped because of Aβ injection.”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • HIIT alleviated learning and memory loss together with anti-oxidant potential; in combination with 20E, it was more effective for neuronal protection.

    “HIIT alleviated learning and memory loss together with the anti-oxidant potential in the animals; however, in combination with 20E, it was more effective for neuronal protection [54].”

    From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [54]

    The Discussion reports that HIIT alone did not alleviate learning and memory impairments in the Aβ-induced rats and did not restore hippocampal antioxidant-enzyme levels. It does report improved neuronal outcomes with the HIIT–ecdysterone combination, but that does not support the claim that HIIT alone produced the preceding benefits. (LLM, conf=0.89)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • In the Aβ-induced rat AD model, spatial avoidance learning and memory were deprived, and these functions declined parallel with anti-oxidant enzymes (SOD, CAT, and GTx).

    “In the Aβ-induced rat AD model, spatial avoidance learning and memory were deprived. These functions declined parallel with anti-oxidant enzymes (SOD, CAT, and GTx).”

    From Molecular Targets of 20-Hydroxyecdysone in Mammals, Mechanism of Action: Is It a Calorie Restriction Mimetic and Anti-Aging Compound? (2025) · cites this paper as [54]

  • Ecdysterone does not appear to possess any severe side effects.

    “Furthermore, ecdysterone does not appear to possess any severe side effects [19,47,49,50,51,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101].”

    From Ecdysterone and Turkesterone—Compounds with Prominent Potential in Sport and Healthy Nutrition (2024) · cites this paper as [76]

    The Methods section describes eight weeks of ecdysterone dosing in rats, and the reported outcomes concern learning, antioxidant activity, and neuronal populations. I searched our copy for severe side effects, adverse effects, toxicity, and safety, but found no passage assessing whether ecdysterone has severe side effects. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • Several published reports have written about the ROS-scavenger and antioxidant properties of 20E in several in vitro and in vivo systems.

    “Several published reports have written about the ROS-scavenger and antioxidant properties of 20E in several in vitro [30,31] and in vivo systems [32,33].”

    From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [32]

  • 20E increased the activity of SOD, CAT, GPx, and GRx in neurons of an amyloid-beta-induced rat model of Alzheimer's disease.

    “Gholipour et al. [32], who demonstrated a 20E-mediated increase in the activity of superoxide dismutase (SOD), catalase (CAT), Glutathione Peroxidase (GPx), and Glutathione Reductase (GRx) in neurons of an amyloid-beta-induced rat model of Alzheimer’s disease.”

    From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [32]

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.

  • GRx result switches to SOD in the same comparison

    Minor

    The paragraph presents the Figure 7D result as a measurement of GRx, then says the treatments increased SOD instead.

  • Treatment start is described as both ten days and one week after injection

    Minor

    The abstract says HIIT and Ecdysterone treatment began ten days after Aβ injection, whereas the methods say treatment began after one week of recovery following surgery.

  • CAT result switches to SOD in the same comparison

    Minor

    The paragraph identifies the measured enzyme as CAT and associates the comparison with Figure 7B, but describes the treatment effect as an increase in SOD.

3 of 3

Cites

Flagged first, then by citations

7 of the 90 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Yang, 2006, The effect of ECR on the learning and memory dysfunction of the rats induced by Aβ 25-35 involved in ChAT Activity, 遵義醫學院學報, 29, 106
  2. Shihao, 2012, Ecdysterone protects brain injury against free radical in rats, J. Third Military Med. Univ., 2012, 23

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Authors
Gholipour, P., Komaki, A., Ramezani, M., & Parsa, H.
Affiliations
  • Hamedan University of Medical Sciences (IR)
  • Bu-Ali Sina University (IR)
Corresponding author
  • Ramezani, Mahdi
  • Parsa, Hesam
ORCID
Venue
Physiology & Behavior
Publisher
Elsevier BV
Published
2022-07
Volume
251
Pages
113817
ISSN
0031-9384 (ISSN-L)
DOI
10.1016/j.physbeh.2022.113817
OpenAlex
W4224107092
Cited by
37
References
90
Citations by year
2026: 7 · 2025: 9 · 2024: 9 · 2023: 9 · 2022: 3
FWCI
4.67
Type
journal article
Language
en
Open access
Licence
Locations
  • Physiology & Behavior (publishedVersion)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Hamadan University of Medical Sciences
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, amyloid-beta, high-intensity interval training, 20-hydroxyecdysone, learning and memory, oxidative stress, antioxidant enzymes, superoxide dismutase, catalase, glutathione reductase, hippocampus, neuronal loss, neuroprotection, cognitive decline, exercise therapy
MeSH terms
High-Intensity Interval Training, Alzheimer Disease, Animals, Antioxidants, Avoidance Learning, Disease Models, Animal, Ecdysterone, Free Radicals, Hippocampus, Male, Peptide Fragments, Superoxide Dismutase, Amyloid beta-Peptides, Maze Learning, Rats

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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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