Treadmill Exercise Attenuates Aß-Induced Mitochondrial Dysfunction and Enhances Mitophagy Activity in APP/PS1 Transgenic Mice.

Mitochondrial dysfunction is a hallmark of Alzheimer's disease (AD), which may be related to mitophagy failure. Previous reports suggest that treadmill exercise protects against mitochondrial dysfunction in AD. However, few studies have investigated the relationship between mitophagy and mitochondrial adaptation caused by treadmill exercise in AD. The current study aimed to investigate whether exercise-ameliorated AD is associated with changes in mitophagy activity. Both Wild-type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 9 for each group). WTE and ADE mice were subjected to treadmill exercise for 12 weeks, followed by evaluating the effect of treadmill exercise on learning and memory ability, Aß plaques, mitochondrial Aß peptide level, synaptic activity and mitochondrial function. Meanwhile, mitophagy-related proteins PINK1, Parkin, LC3II and P62 were measured in the hippocampal mitochondrial fractions. The results indicated that exercise not only restored learning and memory ability, but also reduced Aß plaque area, mitochondrial Aß peptide level, and increased levels of synaptic markers SYN and GAP43, as well as reversed mitochondrial dysfunction (defective mitochondrial ultrastructure, decreased PGC-1α, TFAM and ATP levels) in APP/PS1 transgenic mice. Moreover, exercise increased mitophagy activity as evidenced by a significant decrease in levels of P62 and PINK1 as well as an increase in levels of LC3II and Parkin in ADE mice. These findings suggest that treadmill exercise can enhance mitophagy activity in the hippocampus, which is efficient in ameliorating pathological phenotypes of APP/PS1 transgenic mice.

Effects of treadmill exercise on mitochondrial fusion and fission in the hippocampus of APP/PS1 mice.

Mitochondrial dysfunction is widely recognized as an early event in the pathogenesis of Alzheimer's disease (AD). Defects in mitochondrial fusion and fission have been proposed to lead to learning and memory impairments in AD. The current study aimed to investigate whether exercise-improved learning and memory were associated with improves in mitochondrial function by increased mitochondrial fusion and decreased mitochondrial fission. APP/PS1 transgenic mice were divided into transgenic sedentary (ADC, n = 15) and transgenic exercise (ADE, n = 15) groups. Wild-type mice were also separated into sedentary (WTC, n = 15) and exercise (WTE, n = 15) groups. The WTE and ADE mice were subjected to treadmill exercise for 12 weeks. In this study, learning and memory were significantly decreased in ADC mice compared with those in WTC mice, whereas exercise improved learning and memory in APP/PS1 transgenic mice. Meanwhile, ADC mice displayed defective mitochondrial function as evidenced by a significant increase in swollen mitochondria and vacuoles, loss of mitochondrial cristae, and decreased ATP levels, as well as an imbalance in mitochondrial fusion and fission as evidenced by significantly increased Drp1 and Mff and decreased Mfn1, Mfn2, and Opa1 in the hippocampus. Interestingly, exercise mitigated mitochondrial dysfunction as evidenced by a significant reduction in swollen mitochondria and vacuoles and increased mitochondrial cristae and ATP levels in ADE mice. Coincidentally, exercise promoted the balance of mitochondrial fusion and fission as evidenced by a significantly decreased Drp1 and Mff and increased Mfn1, Mfn2, and Opa1 in the hippocampus. These findings suggest that treadmill exercise efficiently enhances learning and memory in AD by improving mitochondrial dysfunction in APP/PS1 transgenic mice.

Cytotoxic triterpenoid saponins from the defatted seeds of Camellia oleifera Abel.

Five new oleanane-type triterpenoid saponins, oleiferasaponins D1-D5 (1-5), were isolated from the defatted seeds of Camellia oleifera Abel. Their structures were elucidated by spectroscopic and chemical methods. The cytotoxic activities of compounds 1-5 were evaluated against five human tumor cell lines (HCT-116, HepG2, BGC-823, NCI-H1650, and A2780). Compounds 1-2 exhibited cytotoxic activity against five human cancer cell lines, with IC50 values ranging from 3.31 to 10.23 µM. Compounds 3-5 showed moderate cytotoxic activities toward the tested cell lines.

Two new triterpenoid glycosides from the stems of Camellia oleifera Abel.

Two new oleanane-type triterpenoid glycosides, 3-O-ß-D-xylopyranosyl-(1→2)-α-L-arabinopyranosyl-(1→3)-[ß-D-glucuronopyranosyl-(1→2)]-ß-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol(1) and 3-O-ß-D-xylopyranosyl-(1→2)-α-L-arabinopyranosyl-(1→3)-[ß-D-glucuronopyranosyl-(1→2)]-ß-D-glucuronopyranosyl-21ß-acetyl-22α-angeloyloxyolean-12-ene-16α,28-diol (2) were isolated from the stems of Camellia oleifera Abel. Their structures were elucidated by means of spectroscopic methods and chemical evidence. The cytotoxic activities of compounds 1-2 were evaluated against five human tumour cell lines (HCT-8, BGC-823, A5049, and A2780). Compounds 1-2 showed cytotoxic activity against five human cancer cell lines, with IC50 values ranging from 3.15 to 7.32 µM.

[n-Butyl Alcohol-soluble Chemical Constituents of Psidium guajava Leaves].

OBJECTIVE: To study the chemical constituents of the leaves of Psidium guajava. METHODS: The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20 and MPLC. Their chemical structures were elucidated on the basis of special analysis. RESULTS: Seven compounds were isolated from n-butyl alcohol fraction, whose structures were elucidated as morin-3-O-α-L-arabopyranoside (1), morin-3-O-α-L-iyxopyranoside (2), 2,6-dihydroxy-4-O-ß-D-glucopyranosyl-benzophenone (3), casuarictin (4),2,6-dihydroxy-3,5-dimethyl-4-O-(6"-O-galloyl-ß-D-glucopyranosyl)-benzophenone(5), globulusin A(6), and kaempferol-3-O-ß-D-(6"-galloyl) galactopyranoside (7). CONCLUSION: Compounds 3 and 5 ~ 7 are isolated from this plant for the first time.

[Chemical Constituents from Camellia oleifera Stem].

OBJECTIVE: To study the chemical constituents of stem of Camellia oleifera. METHODS: The chemical constituents were isolated and purified by column chromatography on silica gel, ODS, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Seven compounds were isolated from the stem of Camellia oleifera, whose structures were elucidated as (-) -pinoresinol (1), (-) -medioresinol (2), skullcapflavone II (3), betulinic acid (4), ursolic acid (5), 3-O-ß-D-glucopyranosyl- (1 --> 2) -ß-D-xylopyransoyl-(1 --> 3) -[ß-D-glucopyranosyl- (1 --> 2)] -ß-D-glucuronopyranosyl-22α-angeloyloxyolean-12-ene-15α,16α,28-triol (6) and oleanolic acid (7). CONCLUSION: Compounds 1 - 6 are isolated from this plant for the first time, and compounds 1 - 3 are isolated from this genus for the first time.

Two new triterpenoids from Callicarpa kwangtungensis.

Two new triterpenoids, 2α,3ß,16α,19α,23-pentahydroxyolean-12-en-28-oic acid (1) and 2α,3α,11α,21α,23-pentahydroxyurs-12-en-28-oic acid (2), were isolated from the aerial parts of Callicarpa kwangtungensis. Their structures were elucidated by 1D and 2D analyses, as well as MS and IR spectra.

[Ethyl acetate-soluble chemical constituents from Callicarpa kwangtungensis].

OBJECTIVE: To study the ethyl acetate-soluble chemical constituents of Callicarpa kwangtungensis. METHODS: The chemical constituents were isolated by column chromatography on silica gel, Sephadex LH-20 and MPLC. Their chemical structures were elucidated on the basis of special analysis. RESULTS: Seven compounds were isolated from ethyl acetate part, whose structures were elucidated as caffeic acid(1),2α,3α, 19α-trihyhydroxy-urs-12-en-28-O-ß-D-glucopyranoside (2),2α,3, 19α-trihyhydroxy-olean-12-en-28-O-ß-D-glucopyranoside (3), 2α, 3α, 19α-trihyhydroxy-olean-12-en-28-O-ß-D-glucopyranoside (4), ferulic acid (5), 2α, 3ß, 19α-trihyhydroxy-urs-12-en-28-O-ß-D-glucopyranoside(6), and ( + )-isolariciresinol-9-O-ß-D-glucopyranoside(7). CONCLUSION: All these compounds are isolated from this plant for the first time.

[Chemical Constituents from Leaves of Liquidambar formosana].

OBJECTIVE: To study the chemical constituents of the leaves of Liquidambarformosana. METHODS: The chemical constituents were isolated and purified by column chromatography on silicagel, Sephadex LH-20 and MPLC. Their structures were elucidated on the basis of physicochemical properties and special analysis. RESULTS: Eight compounds were isolated from the leaves of Liquidambar formosana, whose structures were elucidated as gallic acid (1), p-hydroxy-benzoic acid (2), 3-methoxy-4-hydroxy-benzoic acid (3), 3,5-dihydroxy-4-methoxy-benzoic acid (4) kaempferol (5), 3,4-dihydroxy-benzoic acid (6), 3,4-dihydroxy-5-methoxy-benzoic acid (7) and 3ß,23,29-trihydroxy-olean-12-en-28-oic acid-ß-D-glucopyranosyl ester (8). CONCLUSION: Compounds 1-8 are isolated from the leaves of Liquidambar formosana for the first time.