The chemical constituents of Piper kadsura and their cytotoxic and anti-neuroinflammtaory activities

Figures & data

Table 1.  The ¹H and ¹³C NMR data for compound 1 (δ in ppm, 500 MHz for ¹H and 125 MHz for ¹³C, in CDCl₃)^a.

Position	δH	δC	HMBC (H→C)
1	2.22 (m)	53.4	C-3, C-5, C-6, C-10, C-14
2	1.82 (m)	26.3	C-4, C-5, C-10
3α 3β	2.18 (m) 2.38 (m)	30.1	C-1, C-5, C-15
4		154.2
5	2.62 (t, 10.5)	55.6	C-2, C-4, C-6, C-7, C-15
6	3.5 (t, 10.5)	69.3	C-4, C-5, C-7, C-8
7	1.58 (m)	48.7	C-5, C-6, C-9, C-12, C-13
8α 8β	1.31 (m) 1.77 (m)	19.7	C-6, C-10, C-11
9α 9β	1.65 (m) 1.8 (m)	37.2	C-7, C-14
10		73.3
11	2.23 (m)	27.9	C-8, C-12, C-13
12	0.93 (d, 7)	21.5	C-7, C-13
13	0.86 (d, 7)	16.5	C-7, C-12
14	1.18 (s)	29.7	C-1, C-9, C-10
15	5.01 (s)5.05 (s)	108.7	C-3, C-5

^aJ values are in parentheses and reported in Hz; the assignments were based on ¹H-¹H COSY, HMQC, HMBC and NOESY experiments.

Figure 1.  Chemical structures of 1–14.

Table 2.  The effects of compounds 1–14 and L-NMMA on LPS-induced NO production in BV-2 microglia cells.

Compound	Inhibition (%)^a5 μM	Inhibition (%) 20 μM	IC50 (μM)
1	na^b	na	-
2	47.5	83.8	5.62
3	na	na	-
4	na	na	-
5	na	na	-
6	24.2	54.7	17.4
7	na	na	-
8	na	na	-
9	na	na	-
10	na	na	-
11	46	71.4	6.71
12	21.9	75	9.14
13	46.3	82.5	6.32
14	27.5	57.3	16.5
L-NMMA	10	54.2	17.7

^aValues are the inhibition of NO production relative to the LPS control (n=3). ^bna, not active.

Figure 2.  The effects of compounds 2, 6, and 11–14 on PGE₂ production in LPS-stimulated BV-2 microglia cells. PGE₂ was assessed by using a competitive enzyme immunoassay kit after treatment with LPS (100 ng/mL) for 24 h in the presence or absence of compounds 2, 6, and 11–14 (5 and 20 μM). All data are presented as the mean ± SEM of three independent experiments. *p<0.05 indicates statistically significant differences compared to treatment with LPS alone.

Table 3.  Cytotoxicity of compounds 1–14 against four cultured human tumour cell lines using the SRB assay in vitro.

Compound	IC50 (μM)^a
	A549	SK-OV-3	SK-MEL-2	HCT-15
1	83.3	>100	80	95.4
2	>100	>100	58.2	>100
3	96.3	>100	85.5	>100
4	32.9	20.8	28.1	21.8
5	>100	>100	>100	>100
6	17.8	23.1	28.2	24
7	83.1	>100	97.6	>100
8	>100	>100	>100	>100
9	98.2	>100	>100	>100
10	96.6	>100	>100	>100
11	>100	52	37.5	64.2
12	20.5	54.5	58.2	>100
13	10.1	18.3	8.3	27.8
14	21.7	14.4	11.6	21.3
Doxorubicin^b	0.06	0.08	0.04	0.22

^aIC₅₀ values against cell lines, defined as the concentration (μM) that caused 50% inhibition of cell growth in vitro. ^bDoxorubicin as positive control.