Three new compounds from the litters of Casuarina equisetifolia

Phytochemistry Letters 35 (2020) 58–62

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Three new compounds from the litters of Casuarina equisetifolia a

a,b

a

a

a

a

Pei Wang , Haisheng Wang , Caihong Cai , Hao Wang , Fandong Kong , Jingzhe Yuan , Haofu Daia, Lei Lib,*, Wenli Meia,*

T

a

Hainan Key Laboratory of Research and Development of Natural Product from Li Folk Medicine, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou, 571101, China College of Life Sciences, Hainan Normal University, Haikou, 570228, China

b

ARTICLE INFO

ABSTRACT

Keywords: Casuarina equisetifolia Litters α-glycosidase inhibition activity Acetyl cholinesterase (AChE) inhibition activity

Two new cyclic diarylheptanoids, casuaritriol A (1) and casuaritriol B (2), were isolated from the EtOAc extract of litters (including branches and leaves) of Casuarina equisetifolia, along with a new triterpene casuariene (3), and two known compounds diarylheptanoids adanin (4) and ostryopsitriol (5). Their structures were elucidated by spectroscopic analysis (including HRESIMS, 1D NMR and 2D NMR data), and the absolute configuration of 3 was determined by analysis of the ECD data according to the octant rule. Compound 1 exhibited inhibitory activity against α-glycosidase with inhibition rate of 45.1 ± 1.4 % at a concentration of 500 μg/mL. In addition, compound 4 showed weak inhibitory activity against acetyl cholinesterase (AChE) with inhibition rate of 14.9 ± 1.1 % at a concentration of 50 μg/mL.

1. Introduction Casuarina equisetifolia, one piece of Casuarina Adans (Casuarinaceae), indigenous to Australia and Pacific islands, which is planted as conifer-like angiosperm with resistance to typhoon, desertification, drought, stress tolerance, and salinity (Flora Editorial Board of Chinese Academy of Sciences, 2004, Ye et al., 2019). The genome of C. equisetifolia has been sequenced, and it will provide basis for related researches of this plant. (Ye et al., 2019). As early as 1897, C. equisetifolia was introduced to China from Australia and cultivated in tropical and sub-tropical zones (Yang et al., 1995; Zhong et al., 2010; Ye et al., 2019). In southern China, cultivated area of C. equisetifolia is more than 300,000 hm2 in total (Zhong and Bai, 1996; Zhong et al., 2005; Ye et al., 2019). Only in Hainan, the coastline Casuarina forest is 50,000 hm2 (Liu et al., 2013; Ye et al., 2019). C. equisetifolia was planted widely as an evergreen tree in China, and a mass of litters are produced each year. The main investigations of litters of C. equisetifolia were in ecology (Rajendran et al., 2004, Soumare et al., 2002). However, the allelopathy research of litters showed the chemical constituents of the litters may be the main reason for the degeneration of the Casuarina forest year by year (Rice, 1984; Hata et al., 2010). The branches and leaves of C.equisetifolia are used in folk medicine for the treatment of astringent, in diarrhea, cough, ulcers, toothache, lotion for swelling and diabetes (Gumgumjee and Hajar, 2012). The previous reports showed that the extracts of bark and wood

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exhibited significant anticancer (Aher et al., 2008) and anthelmintic activities (Aher et al., 2006), as well as the extracts of leaves exhibited antibacterial (Parekh et al., 2005), hypoglycemic (Han, 1998) and antifungal (Han, 1998) activities. It will turn waste into wealth and may be effectively alleviate the degradation of Casuarina forest at the same time if the litters can be used for people’s life. It is very important to investigate the chemical constituents from the litters of C. equisetifolia for using them. However, the report for the chemical constituents of litters of C. equisetifoliawas infrequent, and only the fresh leaves, wood or fruits were reported to produce coumaroyl triterpenes, aromatic compounds, and flavonoids. (Takahashi et al., 1999, El-Ansariet al., 1977, Madhulata et al., 1985). During our investigation on the litters ofC. equisetifolia (including branches and leaves), two triterpene derivatives, two cyclic diarylheptanoids and three flavonoids derivatives were isolated, and they exhibited inhibitory activities against α-glycosidase and acetyl cholinesterase (AChE) (Wang et al., 2018), which related to the treatment of diabetes and Alzheimer’s disease (AD), the most common metabolic andneurodegenerative diseases, respectively (Hakamata et al., 2009; Weinstock, 1999). Herein, the ongoing research on chemical investigations of the litters of C. equisetifolia led to the isolation of two new cyclic diarylheptanoids, casuaritriol A (1) and casuaritriol B (2), and one new triterpene casuariene (3), along with the previously reported cyclic diarylheptanoids adanin (4) (Yasue, 1968) and ostryopsitriol (5) (Zhang et al., 2013). Compounds 1–5 were tested for their inhibitory activities against α-glycosidase and AChE. Herein,

Corresponding authors. E-mail addresses: [email protected] (L. Li), [email protected] (W. Mei).

https://doi.org/10.1016/j.phytol.2019.10.011 Received 5 June 2019; Received in revised form 10 October 2019; Accepted 31 October 2019 1874-3900/ © 2019 Phytochemical Society of Europe. Published by Elsevier Ltd. All rights reserved.

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P. Wang, et al.

of five aromatic protons ascribable to two aromatic rings: the signals at δC/H 129.8/6.98 (1H, dd, J = 8.1, 2.3 Hz), δC/H 115.3/6.78 (1H, d, J =8.1 Hz), δC/H 134.0/6.53 (1H, d, J =2.3 Hz), δC/H 132.2/6.53 (1H, s) and δC/H 98.2/6.46 (1H, s), attributing to a 1,2,5-trisubstituted benzene unit and 1,2,4,5-tetrasubstituted benzene unit, respectively. In addition, the signals for two oxymethines at δC/H 76.9/4.40 (1H, dd, J = 6.6, 1.7 Hz) and δC/H 72.3/4.05 (1H, m), four methylenes, one methoxyl at δC/H 54.5/3.85 (3H, s) and a ketocarbonyl at δC 219.3 were also exhibited. By comparison, compound 2 has a similar cyclic diarylheptanoid skeleton to the previously reported casuarinondiol (Kaneda et al., 1990a, Kaneda et al., 1990,), as confirmed by 1H-1H COSY correlations from H-3 to H-4, from H-7 to H-8, and from H-10 to H-13 through H-12, together with the HMBC correlations (Figure 2) from H-3 to C-1 and C-5, from H-6 to C-2 and C-4, from H-19 to C-17, C15, C-13, and C-1, from H-16 to C-18 and C-14, from H-12 to C-14, from H-10 to C-9, from H-8 to C-5, and from H-7 to C-6 and C-9. The only difference between them was that H-15 in casuarinondiol was substituted by a methoxyl in 2, as evidenced by HMBC correlation from 15OCH3 to C-15. Thus, the planar structure of compound 2 was identified as that shown in Fig. 1 and named as casuaritriol B. The elemental composition of compound 3 was established as C30H48O4 by its HRESIMS data. Interpretation of the 1H NMR and 13C NMR data (Table 2) of 3 revealed eight tertiary methyls (δH/C 1.22/ 27.2, 1.00/21.9, 0.99/15.7, 0.97/10.5, 0.96/27.0, 0.85/29.8, 0.77/ 17.7 and 0.73/22.5), seven sp3 mehylenes, seven methines (including an olefinic methine and three oxymethines), seven quaternary carbons (including an olefinic one) and a carbonyl (δC 219.9). There were seven degrees of unsaturation in compound 3 indicated by valence bond calculations, which accounted for one carbonyl, a double bond and five rings. Comparison of above data with those of the previously reported 6β,16β-dihydroxy-olean-12-en-3-one (Wang et al., 2003) suggested that their basic skeletons were similar. However, one difference between them was the position of the hydroxyl substituent, which was linked at C-7 in 3 instead of at C-6 in the previously reported compound, as evidence by the sequential COSY correlations from H-5 to H-7 through H2-6, together with the HMBC correlations from H2-6 to C-7, C-8 and C10, as well as from H-7 to C-26. In addition, one proton of the CH2-21 in 6β,16β-dihydroxyolean-12-en-3-one was substituted by a hydroxyl group in 3, which was proved by the COSY correlations of H-18 to H219 and H-21 to H2-22, combined with the key HMBC correlations from H2-19 to H3-28 and H3-29, from H-21 to H3-28 and H3-29, from H-18 to C-20, as well as from H2-22 to C-18 and C-20. ROESY correlations from H-7 (δH 3.83) to H-5 (δH 1.40) and H-9 (δH 1.47), from H-6a (δH 1.56) to H3-25 (δH 0.99) and H3-26 (δH 0.97), from H3-27 (δH 1.22) to H-9, H-16 (δH 3.97) and H-15a (δH 1.86), from H3-30 to H-15b (δH 1.66), H-18 (δH 2.1) and H-21 (δH 3.42) suggested the relative configuration of 3 as shown in Fig. 3. The ECD curve (Fig. 4a) of 3 showed obvious negative cotton effect around 330 nm due to the n-π* transition of the 3-ketone functional group, which led to the assignment of the absolute configuration of 3 as 5S, 7R, 8S, 9S, 10S, 14S, 16R, 17R, 18R and 21S according to the octant rule (Jiao et al., 2013). Thus, the structure of compound 3 was established as shown in Fig. 1 and was named as casuariene.

Table 1 1 H and 13C NMR data for 1 and 2 in CD3OD-d4 (500 and 125 MHz, δ in ppm). Position

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 15-OCH3

1

2

δC

δH, mult.(J in Hz)

δC

δH, mult. (J in Hz)

145.7 145.9 116.0 124.6 132.1 117.6 28.9 35.4 65.7 48.0 65.3 34.1 21.5 127.7 150.8 115.5 116.5 151.1 116.6 –

– – 6.70, 6.65, – 6.51, 2.59, 1.77, 3.04, 1.55, 3.06, 1.75, 3.15, – – 6.68, 6.77, – 6.40, –

127.1 152.1 115.3 129.8 128.2 134.0 39.4 76.9 219.3 39.1 31.2 72.3 36.4 118.2 158.8 98.2 153.1 117.5 132.2 54.5

– – 6.78, d, (8.1) 6.98,dd, (8.1, 2.3) – 6.53, d, (2.3) 3.47, m; 2.85, m 4.40, dd, (6.6, 1.7) – 3.42, m; 3.06, m 1.86, m; 2.10, m 4.05, m 2.69, m; 2.88, m – – 6.46, s – – 6.53, s 3.85, s

d, (8.5) dd, (8.5, 2.0) d, (2.0) m m; 1.42, m m m m m; 1.43, m m; 2.21, m d, (8.6) dd, (8.6, 2.9) d, (2.9)

we describe the isolation, structural determination, and biological activities of compounds 1–5. 2. Results and discussion 2.1. Structural elucidation of 1-3 Compound 1 was obtained as yellow powder, which gave a pseudomolecular ion peak at m/z 353.1360 [M + Na]+ (calcd. for C19H22O5Na: 353.1359) in the HRESIMS spectrum, indicating a molecular formula C19H22O5. The 1H NMR data (Table 1) of 1 exhibited signals at δH 6.77 (1H, dd, J = 8.6, 2.9 Hz), 6.70 (1H, d, J = 8.5 Hz), 6.68 (1H, d, J =8.6 Hz), 6.65 (1H, dd, J = 8.5, 2.0 Hz), 6.51 (1H, d, J =2.0 Hz) and 6.40 (1H, d, J =2.9 Hz), which were assignable to six aromatic protons of two ABX systems. Analysis of 13C NMR and DEPT indicated the presence of six olefinic methines (δC 124.6, 117.6, 116.6, 116.5, 116.0, 115.5), two oxygenated methines (δC 65.7 and 65.3), five methylenes (δC48.0, 35.4, 34.1, 28.9 and 21.5), six nonprotonated carbons (δC151.1, 150.8, 145.9, 145.7, 132.1, and 127.7). The above data indicated a typical cyclic diarylheptanoid derivative (Masullo et al., 2015). The NMR data (Table 1) of 1 were very similar to the previously reported 4,12,16-trihydroxy-2-oxatricyclo[13.3.1.13,7]-nonadeca-1(18),3,5,7(20),8,15,17-heptaene (Singldinger et al., 2018), suggesting that they shared the same diaryl ether heptanoid skeleton. This is evidenced by the COSY correlations of H-3/H-4 and H2-7/H2-8/ H-9/H2-10/H-11/H2-12/H2-13, together with the HMBC correlations (Figure 2) of H-6 (δH6.51) with the 13C resonances at δC 145.9 (C-2), 124.6 (C-4) and 28.9 (C-7), H-19 (δH 6.40) with the 13C resonances at δC150.8 (C-15), 21.5 (C-13) and 116.5 (C-17), H-4 (δH6.65) with C-7, H-8 with the 13C resonances at δC132.1 (C-5), and H-12 with the 13C resonances at δC127.7 (C-14). The differences between them are that the olefinic functional groups (δC 131.1 and 131.2) and a methylenes (δC 27.6) in 4,12,16-trihydroxy-2-oxatricyclo[13.3.1.13,7]-nonadeca1(18),3,5,7(20),8,15,17-heptaene were replaced by two methylenes (δC 28.9 and 35.4) and a oxygenated methine (δC 65.7), respectively, as deduced by the sequential COSY correlations from H2-7 to H-9 through H2-8, together with the HMBC correlations from H2-7 to C-9, as well as from H2-8 to C-5. Thus, the planar structure of compound 1 was identified as that shown in Fig. 1, and named as casuaritriol A. Compound 2 was isolated as white powder, and its molecular formula was established as C20H22O6 on the basis of its HRESIMS data. Analysis of its 1H NMR, 13C NMR and HSQC data revealed the presence

2.2. The bioactivities of compounds 1–5 from Litters of Casuarina equisetifolia Compounds 1–5 were test for their inhibitory activities against αglycosidase and AChE. Among them, compound 1 showed weak inhibitory activity against α-glycosidase with inhibition rates of 45.1 ± 1.4 % at a concentration of 500 μg/mL. Compound 4 exhibited weak inhibitory activity against AChE with inhibition rates of 14.9 ± 1.1 % at a concentration of 50 μg/ mL.

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Fig. 1. Chemical structures of 1–5.

Fig. 3. The key 1H-1H ROESY correlations for 3.

Fig. 2. The key 2D NMR correlations for 1 and 2.

instrument as KBr discs. NMR spectra were recorded on a Bruker Avance III 500 MHz NMR spectrometer at 500 MHz for 1 H NMR spectrum and 125 MHz for 13C NMR spectrum. ESIMS and HRESIMS were recorded with amaZon SL (Bruker) or Compact QqTOF (Bruker). Semi-preparative HPLC was carried out using an ODS column (Cosmosil-pack, 10 × 250 mm, 5 μm, 4 mL/min). RP-18 gel (20–45 μm, Fuji SilysiSa Chemical Co., Ltd., Greenville, NC, UA), Silica gel (60–80, 200–300 mesh, Qingdao Marine Chemical Co., Ltd., Qingdao, China), Sephadex LH-20 (Merck, Kenilworth, NJ, USA) were used for column chromatograghy.

Table 2 1 H and 13C NMR Data for 3 in CD3OD-d4 (500 and 125 MHz, δ in ppm). 3 Position 1 2

δC 40.1 35.1

3

Position 16 17

δC 67.4 41.0

δH, mult.(J in Hz) 3.97, d, (11.9,4.9) –

219.9

δH, mult.(J in Hz) 1.81, m;1.33, m 2.46, ddd, (16.1, 10.6, 7.3,) 2.31, ddd, (16.1, 7.0, 4.0) –

18

50.8

4

48.3

–

19

40.1

5 6

53.7 31.3

1.40, dd, (12.4, 2.2) 1.56, m; 1.50, m

20 21

37.2 74.0

7 8 9 10 11 12 13 14 15

73.6 46.7 47.6 37.9 24.9 124.4 143.7 46.3 39.8

3.83, dd, (11.2, 4.9)

22 23 24 25 26 27 28 29 30

39.5 22.0 27.0 15.7 10.5 27.2 17.7 29.8 22.5

2.10, dd, (14.2, 4.5) 1.77, m; 1.05, dd, (14.2, 4.61) – 3.42, dd, (12.1, 4.4) 2.20, m; 0.98, m 1.00, s 0.96, s 0.99, s 0.97, s 1.22, s 0.77, s 0.85, s 0.73, s

1.47, dd, (12.2, 5.8) – 1.98, m; 1.83, m 5.26,t, (3.1) – – 1.86, m; 1.66, dd, (13.9, 4.7)

3.2. Plant material and extraction The litters of C. equisetifolia including branches and leaves was collected from the front of C.equisetifolia forest (N20° 01′ 02′', E110° 31′ 20′') in Guilin Ocean Development Zone in Hainan province. After shattering, located litters ofC. equisetifolia(14.5 kg) were extracted by 95 % ethyl alcohol (15 L) three times and for five days each time. The EtOH extract (180.0 g) was dissolved in H2O (2 L) and extracted three times by petroleum ether (2 L), ethyl acetate (2 L) and nbutyl alcohol (2 L) successively. 3.3. Isolation

3. Experimental

The EtOAc extract (61.6 g) was subjected to a silica gel VLC column (30 × 100 cm) eluting with a gradient of petroleum ether−CHCl3 (v/v, 100:0–0:100) and then with CHCl3-MeOH (v/v, 100:1-0:100), to give thirteen fractions (Fr.1–Fr.13). Fr.8 (10.3 g) was isolated via MIC column to get eight fractions (Fr.8.1–Fr.8.8). Fr.8.2 (700.4 mg) was separated to nine fractions (Fr.8.2.1–Fr.8.2.9) by CC over Sephadex LH-

3.1. General experimental procedures Optical rotations were measured on a Rudolph Autopol III automatic polarimeter. IR spectra were taken on a Nicolet 380 FT-IR 60

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P. Wang, et al.

Fig. 4. a) CD spectra for 3; b) Application of octant rule to 3.

20, eluting with MeOH/CHCl3 (v/v, 1:1). Fr.8.2.6 (49.7 mg) was subjected to Sephadex LH-20 column eluting with MeOH to give compound 1 (1.0 mg). Fr.8.2.5 (14.1 mg) was purified over RP-18 column to give compound 2 (1.0 mg). Compounds 4 (2.0 mg) and 5 (2.5 mg) were obtained from Fr.8.2.7 (53.5 mg) via RP-18 column eluting with 25 % MeOH in water (v/v). Fr.7 (14.6 g) was separated to sixteen fractions (Fr.7.1–Fr.7.16) via MIC column. Fr.7.11 (318.6 mg) was subjected to sephadex LH-20 column eluting with MeOH to give seven fractions (Fr.7.11.1–Fr.7.11.7). Fr.7.11.3 (13.4 mg) was purified on ODS column over semi-preparative HPLC eluting with 45 % C2H3N to yield compound 3 (3.0 mg).

were tested for AChE and α-glycosidase inhibitory activities in vitro, among them, compounds 1 and 4 exhibited the inhibitory activity against α-glycosidase and AChE with inhibition rates of 45.1 ± 1.4 % at a concentration of 500 μg/mL and 14.9 ± 1.1 % at a concentration of 50 μg/mL, respectively. About constituents of the plants of Casuarina genus, three species, C. equisetifolia (Takahashi et al., 1999, Ma et al., 1977, Madhulata et al., 1985), C. glauca (Jorgea et al., 2019), and C. junghuhniana (Kaneda et al., 1990a, Kaneda et al., 1990,) have been investigated, and triterpenes, aromatic compounds, and flavonoids were their mainly constituents. Cyclic diarylheptanoids were a kind of bioactive compounds, which exhibited several biological activities such as antitumor activity (Ishidaa et al., 2000; Lee et al., 2002), anti-inflammatory activity (Tao et al., 2002), antibacterial activity (Reddy et al., 2003), etc. In the previous report, from the root of another member of the genus, C. junghuhniana, two cyclic diarylheptanoids (Kaneda et al., 1990a, Kaneda et al., 1990c,) were obtained, but the various plant parts of C. equisetifolia have not afforded this kind of compounds. In our research on chemical investigations of the litters ofC. equisetifolia, a series of these compounds were found.

3.3.1. Casuaritriol A (1) Yellow powder; [α]25 D= - 29.8 (c 0.115, CH3OH); IR (KBr) νmax (cm-1): 3413, 2929, 1621, 1508 cm -1; 1H and 13C NMR data, see Table 1; HRESIMS m/z 353.1360 [M + Na]+ (calcd for C19H22O5 Na, 353.1359). 3.3.2. Casuaritriol B (2) White powder; [α]25 D= - 117.2 (c 0.106, CH3OH); IR (KBr) νmax (cm-1): 3414, 2930, 1699,1624,1507 cm-1; 1H and 13C NMR data, see Table 1; HRESIMS m/z 357. 1341 [M−H]- (calcd for C20H22O6, 357.1344).

Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

3.3.3. Casuariene (3) White powder; [α]25 D= + 17.5 (c 0.18, CH3OH); IR (KBr) νmax (cm-1): 3446, 1633, 1106 cm-1. 1H and 13C NMR data, see Table 2; HRESIMS m/z 495.3432 [M + Na]+ (calcd for C30H48O4Na, 495.3445).

Acknowledgment

The method optimized by Ellman et al. (Ellman et al., 1961) was performed in vitro to test the AChE inhibitory activity of compounds 1–5. Tacrine was used as positive control with inhibition rates of 54.3 ± 4.7 % at a concentration of 50 μg/mL.

This work was supported by the Innovative Research Team Grant of the Natural Science Foundation of Hainan Province (No. 2018CXTD337 and 2017CXTD020), Financial Fund of the Ministry of Agriculture and Rural Affairs, P. R of China (NFZX2018), Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences (No. 1630052016008).

3.5. Bioassay for α-glycosidase inhibitory activity

Appendix A. Supplementary data

The method optimized by Jong et al. (Jong-Anurakkun et al., 2007) was performed in vitro to test the α-glucosidase inhibitory activity of compounds 1–5. Acarbose was used as positive control with inhibition rates of 75.5 ± 0.9 % at a concentration of 0.5 mg/mL.

Supplementary material related to this article can be found, in the online version, at doi:https://doi.org/10.1016/j.phytol.2019.10.011.

4. Conclusion

Flora Editorial Board of Chinese Academy of Sciences, 2004. Flora Reipublicae Popularis Sinicae. Science Press, Beijing 1, 2-3. Ye, G.F., Zhang, H.X., Chen, B.H., Nie, S., Liu, H., Gao, W., Wang, H.Y., Gao, Y.B., Gu, L.F., 2019. De novo genome assembly of the stress tolerant forest species Casuarina equisetifolia provides insight into secondary growth. Plant J. 97 (4), 779–794. Kaneda, N., Kinghorn, A.D., Farnsorth, N.R., Tuchinda, P., Udchchon, J., Santisuk, T.,

3.4. Bioassay for AChE inhibitory activity

References

In conclusion, chemical investigation on EtOAc extract of the litters of C. equisetifolia led to the isolation and identification of two new cyclic diarylheptanoids and a new triterpenes. All the obtained compounds 61

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P. Wang, et al. Reutrakul, 1990a. Two diarylheptanoids and alignan from Casuarina junghuhniana. Phytochemlstry 29 (10), 3366–3368. Yang, J., Chang, T., Chen, T., Chen, Z., 1995. Provenance trial of Casuarina equisetifolia in Taiwan. 1. Seed weight and seedling growth. Bulle. Taiwan For. Res. Inst. 10, 195–207. Zhong, C.L., Zhang, Y., Chen, Y., Jiang, Q.B., Chen, Z., Liang, J.F., Pinyopusarerk, K., Franche, C., Bogusz, D., 2010. Casuarina research and applications in China. Symbiosis 50, 107–114. Zhong, C., Bai, J., 1996. Introduction trials of casuarinas in southern China. In recent Casuarina research and development. In: Proceedings of the Third International Casuarina Workshop. Danang, Vietnam. pp. 4–7. Zhong, C., Bai, J., Zhang, Y., 2005. Introduction and conservation of Casuarina trees in China. For. Res. 18, 345–350. Liu, C., Ran, Y., Tao, Y., Ning, X., Bai, L., Ye, H., Li, X., Li, L., 2013. The present situation investigation of Coastline casuarina forest in Hainan island. For. Resour. Manage. 4, 102–118. Rajendran, K., Devaraj, P., 2004. Biomass and nutrient distribution and their return of Casuarina equisetifolia inoculated with biofertilizers in farm land. Biomass Bioenerg. 26 (3), 235–249. Soumare, M.D., Mnkeni, P.N.S., Khouma, M., 2002. Effects of Casuarina equisetifolia composted litter and ramial-wood chips on tomato growth and soil properties in niayes, Senegal. Biol. Agric. Hortic. 20 (2), 111–113. Rice, E.L., 1984. Allelopathy. Academic Press, Orlando, pp. 309–315. Hata, K., Kato, H., Kachi, N., 2010. Litter of an alien tree, Casuarina equisetifolia, inhibits seed germination and initial growth of a native tree on the Ogasawara Islands (subtropical oceanic islands). J. For. Res.-Jpn. 5 (6), 384–390. Gumgumjee, N.M., Hajar, A.S., 2012. Antimicrobial efficacy of Casuarina equisetifolia extracts against some pathogenic microorganisms. J. Med. Plants Res. 6 5819-582. Aher, A.N., Pal, S.C., Patil, U.K., Yadav, S.K., 2008. Evaluation of preliminary anticancer activity of Casuarina equisetifolia Frost (Casuarinaceae). Planta Indica 4, 45–48. Aher, A.N., Pal, S.C., Patil, U.K., Yadav, S.K., 2006. Evaluation of anthelmintic activity of Casuarina equisetifolia frost (Casuarinaceae). Planta Indica 2, 35–37. Parekh, J., Jadeja, D., Chandra, S., 2005. Efficacy of aqueous and methanolic extracts of some medicinal plants for potential antibacterial activity. Turk. J. Biol. 29, 203–210. Han, S.T., 1998. Medicinal Plants in South Pacific. WHO Regional Publications, Geneva, Switzerland. Takahashi, H., Luchi, M., Fujita, Y., Minami, Hiroyuki, Fukuyama, Y., 1999. Coumaroyl triterpenes from Casuarina equisetifolia. Phytochemistry 51, 543–550 1999. Madhulata, W., Sundara Rao, V.S., Reddy, K.K., Sastry, K.N.S., 1985. Phenolic constituents present in Casuarina fruits and wood. Leather Sci. 32, 38–39. Wang, H.S., Dai, H.F., Wang, P., Cai, C.H., Zhou, L.M., Li, L., Mei, W.L., 2018. Chemical constituents from litters ofCasuarina equisetifolia and their biological activity. Nat. Prod. Res. Dev. 30, 390–395. Hakamata, W., Kurihara, M., Okuda, H., Nishio, T., Oku, T., 2009. Design and screening strategies for α-glucosidase inhibitors based on enzymological information. Curr. Top. Med. Chem. 9, 3–12. Weinstock, M., 1999. Selectivity of cholinesterase inhibition. CNS Drugs 12 (4), 307–323.

Yasue, M., 1968. Studies on wood extractives of ostrya japonica: chemical structures of asadanin and related compounds. Bull. Gov. For. Expt. Sta. 209, 77–168 (Mar.). Tokyo. Zhang, Y.X., Xia, B., Zhou, Y., Ding, L.S., Peng, S.L., 2013. Two new cyclic diarylheptanoids from the stems of Ostryopsis nobilis. Chin. Chem. Lett. 24, 512–514. Masullo, M., Cerulli, A., Olas, B., Pizzam, C., Piacente, S., 2015. Giffonins A-I, antioxidant cyclized diarylheptanoids from the leaves of the Hazelnut tree (Corylus avellana), source of the italian PGI product “Nocciola di Giffoni”. J. Nat. Prod. 78, 17–25. Singldinger, B., Dunkel, A., Bahmann, D., Bahmann, C., Kadow, D., Bisping, B., Hormann, T., 2018. New taste-active 3-(O-#- D- glucosyl)-2-oxoindole-3-acetic acids and diarylheptanoids in cimiciato-infected hazelnuts. J. Agric. Food Chem. 66, 4660–4673. Wang, W.S., Gao, K., Wang, C.M., Jia, Z.J., 2003. Cytotoxic triterpenes from Ligulariopsis shichuana. Pharmazie 58, 148–150. Jiao, R.H., Xu, H., Cui, J.T., Ge, H.M., Tan, R.X., 2013. Neuraminidase inhibitors from marine- derived actinomycete Streptomyces seoulensis. J. Appl. Microbiol. 114, 1046–1105. El-Ansari, M.A., Ishak, M.S., Ahmed, A.A., Saleh, N.A.M., 1977. Notizen: flavonol glycosides of Carya pecan and Casuarina equisetifolia. Z Naturforshch 32, 444–445. Ellman, G.L., Courtney, K.D., Andres, V., Featherstone, R.M., 1961. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 7, 88–90. Jong-Anurakkun, N., Bhandari, M.R., Kawabata, J., 2007. α-glucosidase inhibitors from Deviltree (Alstonia scholaris). Food Chem. 103, 1319–1323. Jorgea, T.F., Tohgeb, T., Wendenburgc, R., Ramalhod, J.C., Lidone, F.C., Ribeiro-Barrosa, A.I., Ferniec, A.R., António, C., 2019. Salt-stress secondary metabolite signatures involved in the ability of Casuarina glauca to mitigate oxidative stress. Environ. Exp. Bot. 166, 103808. Kaneda, N., Kinghorn, A.D., Farnsorth, N.R., Tuchinda, P., Udchchon, J., Santisuk, T., Reutrakul, 1990c. Two diarylheptanoids and alignan from Casuarina junghuhniana. Phytochemlstry 29 (10), 3366–3368. Ishidaa, J., Kozukaa, M., Wanga, H.K., Konoshimab, T., Tokudac, H., Okudac, M., Mouc, X.Y., Nishinoc, H., Sakuraid, N., Leea, K.H., Nagaid, M., 2000. Antitumor-promoting effects of cyclic diarylheptanoids on Epstein–Barr virus activation and two-stage mouse skin carcinogenesis. Cancer Lett. 159, 135–140. Kaneda, N., Kinghorn, A.D., Farnsworth, N.R., Udchachon, J., Santisuk, T., Reutrakul, V., 1990. Two diarylheptanids and a lignan from Casuarina junghuhniana. Phytochemlstry 29, 3366–3368. Lee, K.S., Li, G., Kim, S.H., Lee, C.S., Woo, M.H., Lee, S.H., Jhang, Y.D., Son, J.K., 2002. Cytotoxic diarylheptanoids from the roots of Juglans mandshurica. J. Nat. Prod. 65 (11), 1707–1708. Tao, J., Morikawa, T., Toguchida, I., Ando, S., Matsuda, H., Yoshikawa, M., 2002. Inhibitors of nitric oxide production from the bark of Myrica rubra: structures of new biphenyl type diarylheptanoid glycosides and taraxerane type triterpene. Biomed. Chem. Res. Methods 10, 4005–4012. Reddy, V.L.N., Ravinder, K., Srinivasulu, M., Goud, T.V., Reddy, S.M., Srujankumar, D., Rao, T.P., Murty, U.S., Venkateswarlu, Y., 2003. Two new macrocyclic diaryl ether heptanoids from Boswellia ovalifoliolata. Chem. Pharm. Bull. 51, 1081–1084.

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