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Neuroprotective effects of Tiliacora triandra (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation

  • Authors:
    • Napatr Sriraksa
    • Siwaporn Praman
    • Utcharaporn Kamsrijai
    • Arunothai Wanta
    • Shisanupong Anukanon
    • Prachak Inkaew
    • Thaneeya Hawiset
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand, Department of Physiology, School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand, Department of Anatomy, School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand, Integrative Natural Therapeutics and Health Innovation Research Unit (INTHI), Mae Fah Luang University, Chiang Rai 57100, Thailand, Department of Chemistry, School of Science, Mae Fah Luang University, Chiang Rai 57100, Thailand
    Copyright: © Sriraksa et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 75
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    Published online on: April 24, 2026
       https://doi.org/10.3892/br.2026.2148
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Abstract

Neurodegenerative diseases are characterized by progressive neuronal loss associated with neuroinflammation. Lipopolysaccharide (LPS) is used as a proinflammatory stimulus in neurodegenerative models, as it induces neuroinflammatory responses and activates microglia and astrocytes, leading to the release of cytokines [such as tumor necrosis factor‑α (TNF‑α), interleukin (IL)‑1β and IL‑6] that exacerbate neuronal damage. Tiliacora triandra, a medicinal plant native to Southeast Asia, has antioxidant and anti‑inflammatory properties. The present study investigated the neuroprotective effects of T. triandra leaf extract (TTE) against LPS‑induced memory impairment and neuroinflammation in rats. Animals were randomly divided into five treatment groups, namely a vehicle‑control, vehicle plus LPS, ibuprofen plus LPS (positive control) and TTE‑treated plus LPS groups receiving 200 or 400 mg/kg body weight (BW) TTE for 14 consecutive days. Starting on day 8, LPS (250 µg/kg BW) was administered intraperitoneally for 7 days to induce neuroinflammation. At the end of the treatment period, animals were sacrificed and hippocampal tissues were collected for histological and biochemical analyses. The results demonstrated that TTE significantly ameliorated LPS‑induced memory deficits and sickness‑like behavior. TTE treatment reduced neuroinflammatory responses, as evidenced by decreased levels of proinflammatory cytokines, such as TNF‑α and IL‑1β, compared with the vehicle plus LPS group. Additionally, compared with the vehicle plus LPS group, TTE treatment resulted in a reduced number of activated microglia and astrocytes, as indicated by a reduced number of positive cells of ionized calcium‑binding adapter molecule 1 and glial fibrillary acidic protein in the hippocampus, respectively. Furthermore, the results of the present study suggested that TTE treatment promoted neuronal survival in hippocampal regions affected by LPS administration. Overall, these findings suggested that TTE mitigated the LPS‑induced neuroinflammation and cognitive impairment, which indicates that it may have potential as a therapeutic agent for neuroinflammatory and memory‑related disorders.
View Figures

Figure 1

Schematic diagram of the present
experimental study. In the present study, animals were orally
administered a distilled water vehicle, 50 mg/kg BW ibuprofen or
TTE at doses of 200 or 400 mg/kg BW once daily for 14 days. Each
group consisted of six animals. From days 8-14, all animals, except
for those in the vehicle-control group (which received daily i.p.
injections of 0.9% sodium chloride), received daily i.p. injections
of 250 µg/kg BW LPS. Behavioral assessments were carried out on day
14 following the final treatment. BW, body weight; TTE, T.
triandra leaf extract; LPS, lipopolysaccharide; NORT, novel
object recognition test; OFT, open field test; YMT, Y-maze test;
i.p., intraperitoneal.

Figure 2

Effect of TTE on BW and locomotive
behavior. (A) Percentage of BW change (analyzed using two-way mixed
ANOVA). Number of times each animal (B) reared or (C) crossed
(analyzed using one-way ANOVA). The data is presented as the mean ±
SEM (n=6). ##P<0.01 and ###P<0.001 vs.
the V-CON group. *P<0.05 and **P<0.01
vs. the V plus LPS group. BW, body weight; TTE, T. triandra
leaf extract; LPS, lipopolysaccharide; V-CON, vehicle-control; V,
vehicle; IBU, ibuprofen.

Figure 3

Effect of TTE on cognitive
performance. (A) Discrimination index (%). (B) Spontaneous
alternation (%). One-way ANOVA was used to analyze the data, and
the data is presented as the mean ± SEM (n=6).
##P<0.01 vs. the V-CON group. *P<0.05
and **P<0.01 vs. the V plus LPS group. TTE, T.
triandra leaf extract; LPS, lipopolysaccharide; V-CON,
vehicle-control; V, vehicle; IBU, ibuprofen.

Figure 4

Effect of TTE on proinflammatory
cytokines. (A) TNF-α. (B) IL-1β. One-way ANOVA was used to analyze
the data, and the data is presented as the mean ± SEM (n=6).
###P<0.001 vs. the V-CON group. *P<0.05
and ***P<0.001 vs. the V plus LPS group. TTE, T.
triandra leaf extract; LPS, lipopolysaccharide; V-CON,
vehicle-control; V, vehicle; IBU, ibuprofen; TNF-α, tumor necrosis
factor-α; IL-1β, interleukin-1β.

Figure 5

Effect of TTE on the number of
surviving neurons in the hippocampus. (A) Nissl-stained section of
the rat hippocampus. Number of surviving neurons in the (B) CA1,
(C) CA3 and (D) DG. Micrographs of the (E) CA1, (F) CA3 and (G) DG
sections of the hippocampus at 20x magnification (scale bar, 20
µm). The red arrowheads indicate the dark, shrunken and damaged
neurons. The black arrows indicate the neurons that were still
alive. One-way ANOVA was used to analyze the data, and the data is
presented as the mean ± SEM (n=6). ###P<0.001 vs. the
V-CON group. *P<0.05, **P<0.01 and
***P<0.001 vs. the V plus LPS group. TTE, T.
triandra leaf extract; LPS, lipopolysaccharide; V-CON,
vehicle-control; V, vehicle; IBU, ibuprofen; CA1/3, cornu ammonis
1/3; DG, dentate gyrus.

Figure 6

Effect of TTE on the number of Iba1-
and GFAP-positive cells in the CA1. Number of (A) Iba1- and (B)
GFAP-positive cells. The immunofluorescence of (C) Iba1-positive
cells (green) and (D) GFAP-positive cells (red) in the CA1. Hoechst
33258 (blue) labels the nuclei of all cell types, including neurons
and glial cells. Hippocampal neurons are characterized by larger,
diffusely stained nuclei arranged in a dense and organized laminar
pattern. The glial cells (microglia and astrocytes) exhibit
smaller, intensely stained (punctate) nuclei that co-localize with
Iba1 or GFAP immunoreactivity (43,44).
The images were captured at 20x magnification (scale bar, 50 µm).
One-way ANOVA was used to analyze the data, and the data is
presented as the mean ± SEM (n=6). ###P<0.001 vs. the
V-CON group. *P<0.05 and **P<0.01 vs.
the V plus LPS group. TTE, T. triandra leaf extract; LPS,
lipopolysaccharide; V-CON, vehicle-control; V, vehicle; IBU,
ibuprofen; CA1, cornu ammonis 1; Iba1, ionized calcium-binding
adapter molecule 1; GFAP, glial fibrillary acidic protein.

Figure 7

Effect of TTE on the number of Iba1-
and GFAP-positive cells in the CA3. Number of (A) Iba1- and (B)
GFAP-positive cells. The immunofluorescence of (C) Iba1-positive
cells (green) and (D) GFAP-positive cells (red) in the CA3. Hoechst
33258 (blue) labels the nuclei of all cell types, including neurons
and glial cells. Hippocampal neurons are characterized by larger,
diffusely stained nuclei arranged in a dense and organized laminar
pattern. The glial cells (microglia and astrocytes) exhibit
smaller, intensely stained (punctate) nuclei that co-localize with
Iba1 or GFAP immunoreactivity (43,44).
The images were captured at 20x magnification (scale bar, 50 µm).
One-way ANOVA was used to analyze the data, and the data is
presented as the mean ± SEM (n=6). ###P<0.001 vs. the
V-CON group. *P<0.05 and **P<0.01 vs.
the V plus LPS group. TTE, T. triandra leaf extract; LPS,
lipopolysaccharide; V-CON, vehicle-control; V, vehicle; IBU,
ibuprofen; CA3, cornu ammonis 3; Iba1, ionized calcium-binding
adapter molecule 1; GFAP, glial fibrillary acidic protein.

Figure 8

Effect of TTE on the number of Iba1-
and GFAP-positive cells in the DG. Number of (A) Iba1- and (B)
GFAP-positive cells. The immunofluorescence of (C) Iba1-positive
cells (green) and (D) GFAP-positive cells (red) in the DG. Hoechst
33258 (blue) labels the nuclei of all cell types, including neurons
and glial cells. Hippocampal neurons are characterized by larger,
diffusely stained nuclei arranged in a dense and organized laminar
pattern. The glial cells (microglia and astrocytes) exhibit
smaller, intensely stained (punctate) nuclei that co-localize with
Iba1 or GFAP immunoreactivity (43,44).
The images were captured at 20x magnification (scale bar, 50 µm).
One-way ANOVA was used to analyze the data, and the data is
presented as the mean ± SEM (n=6). ###P<0.001 vs. the
V-CON group. *P<0.05, **P<0.01 and
***P<0.001 vs. the V plus LPS group. TTE, T.
triandra leaf extract; LPS, lipopolysaccharide; V-CON,
vehicle-control; V, vehicle; IBU, ibuprofen; DG, dentate gyrus;
Iba1, ionized calcium-binding adapter molecule 1; GFAP, glial
fibrillary acidic protein.

Figure 9

Proposed mechanisms of the possible
neuroprotective actions of TTE against neuroinflammation and
cognitive impairment. TTE may exert neuroprotective effects by
reducing neuroinflammation and supporting neuronal survival. It
lowers the levels of proinflammatory cytokines and suppresses
microglial and astrocyte activation, as evidenced by reduced Iba1-
and GFAP-positive cells in the hippocampus, which reduced
inflammation-induced damage. These effects potentially contribute
to improved cognitive function and reduced sickness-like behavior,
suggesting its therapeutic potential for neuroinflammatory and
memory-related disorders. LPS, lipopolysaccharide; GFAP, glial
fibrillary acidic protein; Iba1, ionized calcium-binding adapter
molecule 1; TNF-α, tumor necrosis factor-α; IL-1β, interleukin-1β;
BBB, blood-brain barrier; YMT, Y-maze test; NORT, novel object
recognition test; OFT, open field test; DI, discrimination index;
i.p., intraperitoneal injection.
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Copy and paste a formatted citation
Spandidos Publications style
Sriraksa N, Praman S, Kamsrijai U, Wanta A, Anukanon S, Inkaew P and Hawiset T: Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation. Biomed Rep 24: 75, 2026.
APA
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., & Hawiset, T. (2026). Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation. Biomedical Reports, 24, 75. https://doi.org/10.3892/br.2026.2148
MLA
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., Hawiset, T."Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation". Biomedical Reports 24.6 (2026): 75.
Chicago
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., Hawiset, T."Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation". Biomedical Reports 24, no. 6 (2026): 75. https://doi.org/10.3892/br.2026.2148
Copy and paste a formatted citation
x
Spandidos Publications style
Sriraksa N, Praman S, Kamsrijai U, Wanta A, Anukanon S, Inkaew P and Hawiset T: Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation. Biomed Rep 24: 75, 2026.
APA
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., & Hawiset, T. (2026). Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation. Biomedical Reports, 24, 75. https://doi.org/10.3892/br.2026.2148
MLA
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., Hawiset, T."Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation". Biomedical Reports 24.6 (2026): 75.
Chicago
Sriraksa, N., Praman, S., Kamsrijai, U., Wanta, A., Anukanon, S., Inkaew, P., Hawiset, T."Neuroprotective effects of <em>Tiliacora triandra</em> (Colebr.) Diels leaf extract against lipopolysaccharide‑induced memory impairment via anti‑neuroinflammation". Biomedical Reports 24, no. 6 (2026): 75. https://doi.org/10.3892/br.2026.2148
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