Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology
Abstract
:1. Introduction
2. Results
2.1. Structure Elucidation
2.2. Bioactivity of the Compounds towards Autophagic Flux
3. Discussion
4. Materials and Methods
4.1. General Experimental
4.2. Plant Material
4.3. Extraction and Isolation
4.3.1. Euphjatrophane A (1)
4.3.2. Euphjatrophane B (2)
4.3.3. Euphpepluone G (3)
4.3.4. Euphjatrophane C (4)
4.3.5. Euphjatrophane D (5)
4.3.6. Euphjatrophane E (6)
4.3.7. Euphjatrophane F (7)
4.3.8. Euphjatrophane G (8)
4.3.9. Euphpepluone K (9)
4.3.10. Euphpepluone L (10)
4.4. Flow Cytometry Analysis
4.5. Tandem mCherry-GFP Fluorescence Microscopy
4.6. Construction of U251 Cells with Stable Expression of the Mutant MAPT (MAPT P301S) Gene
4.7. Western Blot
4.8. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Euphjatrophane A (1) | Euphjatrophane B (2) | |||
---|---|---|---|---|
Position | δH (J in Hz) | δC | δH (J in Hz) | δC |
1α | 2.41 dd (14.2, 8.4) | 46.8 | 2.99 dd (14.0, 7.6) | 46.4 |
1β | 1.93 dd (14.2, 12.2) | 1.65 dd (14.0, 12.4) | ||
2 | 2.32 m | 38.7 | 2.26 m | 38.3 |
3 | 5.84 t (3.6) | 78.0 | 5.42 t (3.0) | 76.6 |
4 | 2.76 dd (10.2, 3.6) | 50.5 | 2.78 br d (3.0) | 53.0 |
5 | 5.75 d (10.2) | 72.9 | 5.81 br s | 68.5 |
6 | 142.4 | 147.4 | ||
7α | 2.09 m | 25.0 | 4.78 br d (6.8) | 69.4 |
7β | 1.87 m | |||
8α | 2.57 m | 34.1 | 2.18 m | 33.5 |
8β | 2.23 m | 2.05 m | ||
9 | 211.6 | 5.04 m | 75.4 | |
10 | 5.63 d (16.2) | 50.4 | 40.7 | |
11 | 5.62 d (16.2) | 135.7 | 5.93 d (16.2) | 137.9 |
12 | 3.45 m | 130.9 | 5.70 dd (16.2, 9.0) | 129.9 |
13 | 44.2 | 3.52 m | 42.9 | |
14 | 212.2 | 212.7 | ||
15 | 4.28 s | 84.7 | 93.0 | |
16 | 1.05 d (6.4) | 14.0 | 0.88 d (6.6) | 13.4 |
17a | 5.18 s | 114.8 | 5.01 m | 109.6 |
17b | 4.84 s | |||
18 | 1.22 s | 23.5 | 1.13 s | 26.2 |
19 | 1.21 s | 23.7 | 1.07 s | 24.1 |
20 | 1.37 d (6.6) | 20.9 | 1.19 d (6.8) | 19.5 |
OAc-2 | ||||
C=O | ||||
OAc-3 | ||||
C=O | 169.8 | |||
2.11 s | 21.2 | |||
OAc-5 | ||||
C=O | 169.2 | 169.6 | ||
1.84 s | 20.7 | 2.13 s | 21.3 | |
OAc-7 | ||||
C=O | 170.2 | |||
1.37 s | 20.2 | |||
OAc-8 | ||||
C=O | ||||
OAc-9 | ||||
C=O | ||||
OAc-14 | ||||
C=O | ||||
OAc-15 | ||||
C=O | 170.5 | |||
2.13 s | 21.3 | |||
OBz-3 | ||||
C=O | 166.0 | |||
1′ | 129.7 | |||
2′,6′ | 8.11 d (7.8) | 129.9 | ||
3′,5′ | 7.45 t (7.6) | 128.5 | ||
4′ | 7.56 t (7.2) | 134.0 | ||
OBz-9 | ||||
C=O | 165.4 | |||
1′ | 129.8 | |||
2′,6′ | 7.99 d (7.8) | 129.6 | ||
3′,5′ | 7.46 t (7.8) | 128.7 | ||
4′ | 7.56 t (7.4) | 133.2 | ||
OPrp-7 | ||||
C=O | ||||
1″ | ||||
2″ | ||||
OiBu-7 | ||||
C=O | ||||
1″ | ||||
2″ | ||||
3″ | ||||
OH-15 | 4.31 s |
Euphpepluone G (3) | Euphjatrophane C (4) | |||
---|---|---|---|---|
Position | δH (J in Hz) | δC | δH (J in Hz) | δC |
1α | 2.67 d (15.0) | 50.2 | 2.24 d (15.0) | 53.3 |
1β | 2.15 d (15.0) | 2.14 d (15.0) | ||
2 | 88.4 | 78.5 | ||
3 | 5.87 d (5.8) | 80.4 | 5.48 d (3.8) | 82.4 |
4 | 3.36 dd (5.8, 3.6) | 44.6 | 3.37 t (3.6) | 44.1 |
5 | 5.75 d (3.6) | 71.8 | 5.83 d (3.2) | 71.2 |
6 | 144 | 144.1 | ||
7α | 5.24 s | 68.4 | 5.60 s | 67.9 |
7β | ||||
8α | 4.03 d (11.0) | 69.9 | 4.97 s | 80.5 |
8β | ||||
9 | 4.72 s | 86.0 | 5.23s | 70.5 |
10 | 40.0 | 40.7 | ||
11 | 5.92 d (16.0) | 133.9 | 5.83 d (16.0) | 133.9 |
12 | 5.58 dd (16.0, 9.6) | 131.0 | 5.70 dd (16.0, 9.6) | 131.6 |
13 | 2.68 m | 37.5 | 2.83 m | 36.6 |
14 | 5.10 s | 79.3 | 5.13 s | 79.7 |
15 | 84.0 | 83.5 | ||
16 | 1.51 s | 22.6 | 1.34 s | 24.3 |
17a | 4.87 s | 109.4 | 4.95 s | 110.2 |
17b | 4.50 s | 4.57 s | ||
18 | 1.01 s | 27.2 | 0.92 s | 26.3 |
19 | 1.28 s | 23.2 | 1.33 s | 23.8 |
20 | 1.14 d (7.2) | 23.6 | 1.15 d (7.0) | 23.4 |
OAc-2 | ||||
C=O | 170.7 | |||
2.15 s | 22.3 | |||
OAc-3 | ||||
C=O | ||||
OAc-5 | ||||
C=O | 168.5 | 168.3 | ||
2.00 s | 21.1 | 1.80 s | 20.6 | |
OAc-7 | ||||
C=O | ||||
OAc-8 | ||||
C=O | 169.7 | |||
2.04 s | 20.6 | |||
OAc-9 | ||||
C=O | 171.9 | 169.7, | ||
2.05 s | 20.6 | 2.02 s | 20.6 | |
OAc-14 | ||||
C=O | 170.4 | 171.0 | ||
2.08 s | 20.5 | 2.10 s | 20.8 | |
OAc-15 | ||||
C=O | ||||
OBz-3 | ||||
C=O | 164.9 | 165.2 | ||
1′ | 130.0 | 130.0 | ||
2′,6′ | 8.07 d (8.4) | 129.7 | 8.04 d (8.4) | 129.6 |
3′,5′ | 7.43 t (7.8) | 128.5 | 7.43 t (7.8) | 128.5 |
4′ | 7.57 t (7.4) | 133.2 | 7.56 t (7.4) | 133.3 |
OBz-9 | ||||
C=O | ||||
1′ | ||||
2′,6′ | ||||
3′,5′ | ||||
4′ | ||||
OPrp-7 | ||||
C=O | 171.9 | |||
1″ | 2.36 m | 27.5 | ||
2″ | 1.17 t (7.6) | 9.0 | ||
OiBu-7 | ||||
C=O | 176.3 | |||
1″ | 2.66 m | 34.1 | ||
2″ | 1.28 d (7.0) | 19.3 | ||
3″ | 1.24 d (7.0) | 18.5 |
Euphjatrophane D (5) | Euphjatrophane E (6) | Euphjatrophane F (7) | ||||
---|---|---|---|---|---|---|
Position | δH (J in Hz) | δC | δH (J in Hz) | δC | δH (J in Hz) | δC |
1α | 2.70 d (14.2) | 49.1 | 2.61 d (14.6) | 50.7 | 2.67 d (14.6) | 49.5 |
1β | 2.07 d (14.2) | 2.18 d (14.6) | 2.10 d (14.6) | |||
2 | 88.7 | 88.1 | 88.6 | |||
3 | 5.74 d (5.8) | 79.9 | 5.82 d (5.6) | 80.2 | 5.76 d (5.8) | 79.7 |
4 | 3.51 m | 44.3 | 3.29 dd (5.6, 3.8) | 44.6 | 3.40 m | 44.5 |
5 | 5.78, br d (1.8) | 72.1 | 5.73 br d (3.2) | 72.0 | 5.79 br d (3.2) | 71.9 |
6 | 146.4 | 144.7 | 145.3 | |||
7 | 4.33 s | 67.9 | 5.40 s | 67.8 | 4.48 br d (5.0) | 68.3 |
8 | 5.14 s | 71.7 | 3.96 br d (5.5) | 70.7 | 5.09 s | 72.3 |
9 | 4.84 s | 80.8 | 3.62 s | 84.0 | 3.61 s | 82.2 |
10 | 40.4 | 40.7 | 41.2 | |||
11 | 5.87 d (16.0) | 134.5 | 5.91 d (16.2) | 134.5 | 5.86 d (16.0) | 135.3 |
12 | 5.62 dd (16.0, 9.4) | 131.2 | 5.52 dd (16.2, 9.4) | 129.9 | 5.54 dd (16.0, 9.6) | 130.2 |
13 | 2.61 m | 37.7 | 2.62 m | 37.4 | 2.58 m | 37.6 |
14 | 5.08 s | 79.6 | 5.08 s | 79.6 | 5.06 s | 79.9 |
15 | 83.9 | 83.8 | 83.7 | |||
16 | 1.50 s | 23.3 | 1.53 s | 22.1 | 1.50 s | 22.6 |
17a | 4.93 s | 109.2 | 4.94 s | 109.1 | 5.05 s | 109.3 |
17b | 4.53 s | 4.52 s | 4.54 s | |||
18 | 1.01 s | 26.9 | 1.07 s | 26.9 | 1.12 s | 26.4 |
19 | 1.36 s | 23.8 | 1.19 s | 23.8 | 1.21 s | 24.0 |
20 | 1.13 d (6.8) | 23.3 | 1.12 d (7.2) | 23.6 | 1.14 d (6.2) | 23.5 |
OAc-2 | ||||||
C=O | 170.6, | 170.7 | 170.9 | |||
2.14 s | 22.3 | 2.14 s | 22.3 | 2.13 s | 22.3 | |
OAc-5 | ||||||
C=O | 168.0, | 168.7 | 168.0 | |||
1.93 s | 20.9 | 1.96 s | 20.0 | 1.93 s | 20.9 | |
OAc-9 | ||||||
C=O | 170.8, | |||||
2.11 s | 20.5 | |||||
OAc-14 | ||||||
C=O | 170.8, | 170.4 | 171.0 | |||
2.17 s | 21.0 | 2.07 s | 20.5 | 2.10 s | 20.6 | |
OBz-3 | ||||||
C=O | 165.3 | 164.8 | 165.5 | |||
1′ | 129.8 | 130.0 | 129.7 | |||
2′,6′ | 8.11 d (8.0) | 129.7 | 8.08 d (8.2) | 129.7 | 8.10 d (8.4) | 129.8 |
3′,5′ | 7.46 t (7.4) | 128.5 | 7.44 t (7.8) | 128.5 | 7.45 t (7.8) | 128.5 |
4′ | 7.59 t (7.4) | 133.4 | 7.57 t (7.4) | 133.2 | 7.59 t (7.4) | 133.5 |
OiBu-7 | ||||||
C=O | 174.8 | |||||
1″ | 2.63 m | 34.0 | ||||
2″ | 1.20 d (7.0) | 18.8 | ||||
3″ | 1.23 d (7.0) | 19.0 | ||||
OiBu-8 | ||||||
C=O | 174.8 | 175.3 | ||||
1″ | 2.50 m | 34.0 | 2.49 m | 34.0 | ||
2″ | 1.05 d (7.0) | 18.8 | 1.07 d (7.0) | 18.8 | ||
3″ | 1.12 d (7.0) | 19.2 | 1.03 d (7.0) | 19.4 |
Euphjatrophane G (8) | Euphpepluone K (9) | Euphpepluone L (10) | ||||
---|---|---|---|---|---|---|
Position | δH (J in Hz) | δC | δH (J in Hz) | δC | δH (J in Hz) | δC |
1a | 2.71 d (14.0) | 48.9 | 2.84 d (14.4) | 49.8 | 2.76 d (14.0) | 48.8 |
1b | 2.00 d (14.0) | 2.10 d (14.4) | 1.98 d (14.0) | |||
2 | 88.8 | 88.5 | 88.8 | |||
3 | 5.67 d (6.2) | 80.2 | 5.98 (6.0) | 80.9 | 5.70 d (6.6) | 80.0 |
4 | 3.70 m | 44.3 | 3.70 m | 44.9 | 3.94 m | 44.4 |
5 | 5.74 d (4.2) | 72.5 | 5.81 br d (3.4) | 72.0 | 5.81 br d (3.8) | 72.3 |
6 | 147.4 | 143.8 | 146.5 | |||
7 | 4.11 d (8.0) | 67.0 | 5.37 s | 68.8 | 4.52 d (8.8) | 67.4 |
8 | 3.94 d (8.0) | 70.5 | 4.20 d (10.8) | 70.3 | 5.21 s | 71.8 |
9 | 4.70 s | 84.8 | 5.06 s | 86.8 | 5.07 s | 82.2 |
10 | 40.1 | 40.3 | 40.8 | |||
11 | 5.94 d (16.0) | 134.6 | 6.15 d (16.0) | 133.7 | 6.14 d (16.0) | 134.6 |
12 | 5.52 dd (16.0, 9.8) | 130.5 | 5.67 dd (16.0, 9.8) | 131.6 | 5.67 dd (16.0, 9.8) | 131.4 |
13 | 2.62 m | 37.9 | 2.88 m | 37.4 | 2.73 m | 38.1 |
14 | 5.08 s | 69.6 | 5.15 s | 79.4 | 5.12 s | 79.6 |
15 | 84.1 | 84.3 | 84.2 | |||
16 | 1.47 s | 24.0 | 1.48 s | 23.4 | 1.46 s | 24.5 |
17a | 4.91 s | 108.2 | 4.78 s | 109.2 | 4.81 s | 108.5 |
17b | 4.70 s | 4.49 s | 4.41 s | |||
18 | 1.04 s | 27.2 | 1.09 s | 27.3 | 1.07s | 27.3 |
19 | 1.28 s | 23.3 | 1.38 s | 23.2 | 1.44 s | 23.6 |
20 | 1.12 d (7.2) | 23.3 | 1.18 d (7.2) | 23.6 | 1.14 d (7.0) | 23.3 |
OAc-2 | ||||||
C=O | 170.9, | 170.9 | 171.6 | |||
2.09 s | 22.2 | 2.17 s | 22.4 | 2.23 s | 22.5 | |
OAc-5 | ||||||
C=O | 168.6 | 168.6 | 167.9 | |||
2.08 s | 21.2 | 2.05 s | 21.1 | 2.07 s | 20.5 | |
OAc-14 | ||||||
C=O | 170.4, | 170.4 | 170.6 | |||
2.07 s | 20.5 | 2.11 s | 20.5 | 2.11 s | 21.0 | |
OBz-3 | ||||||
C=O | 165.6 | 165.0 | 165.5 | |||
1′ | 129.7 | 130.0 | 129.7 | |||
2′,6′ | 8.09 d (8.4) | 129.8 | 8.05 d (8.4) | 129.7 | 8.07 d (8.4) | 129.7 |
3′,5′ | 7.45 t (7.8) | 128.5 | 7.41 t (7.8) | 128.4 | 7.42 t (7.8) | 128.4 |
4′ | 7.59 t (7.4) | 133.4 | 7.55 t (7.4) | 133.2 | 7.56 t (7.4) | 133.4 |
OTig-8 | ||||||
C=O | 164.2 | |||||
1″ | 126.1 | |||||
2″ | 5.75 m | 141.7 | ||||
3″ | 1.68 d (7.2) | 15.8 | ||||
4″ | 1.52 m | 19.5 | ||||
OiBu-9/8 | OiBu-9 | OiBu-8 | ||||
C=O | 178.2 | 174.9 | ||||
1″ | 2.67 m | 34.4 | 2.53 m | 34.0 | ||
2″ | 1.27 d (7.0) | 18.7 | 1.05 d (7.0) | 18.8 | ||
3″ | 1.25 d (7.0) | 18.8 | 1.15 d (7.0) | 19.3 | ||
ONic-9 | ||||||
C=O | 166.0 | 164.9 | ||||
2″ | 9.23 s | 151.4 | 9.39 s | 151.3 | ||
3″ | 124.9 | 126.3 | ||||
4″ | 8.29 d (8.0) | 137.4 | 8.41 d (8.0) | 137.4 | ||
5″ | 7.34 dd (8.0, 4.8) | 123.1 | 7.39 dd (8.0, 4.8) | 123.3 | ||
6″ | 8.76 d (4.8) | 153.7 | 8.78 d (4.8) | 153.4 |
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Share and Cite
Yan, Y.; Zhou, Q.; Ran, X.; Lu, Q.; Zhang, C.; Peng, M.; Tang, L.; Luo, R.; Di, Y.; Hao, X. Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology. Int. J. Mol. Sci. 2023, 24, 1088. https://doi.org/10.3390/ijms24021088
Yan Y, Zhou Q, Ran X, Lu Q, Zhang C, Peng M, Tang L, Luo R, Di Y, Hao X. Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology. International Journal of Molecular Sciences. 2023; 24(2):1088. https://doi.org/10.3390/ijms24021088
Chicago/Turabian StyleYan, Ying, Qi Zhou, Xiaoqian Ran, Qingyun Lu, Cuishan Zhang, Mingyou Peng, Lei Tang, Rongcan Luo, Yingtong Di, and Xiaojiang Hao. 2023. "Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology" International Journal of Molecular Sciences 24, no. 2: 1088. https://doi.org/10.3390/ijms24021088