Cheng-Ting Zi

Cytotoxic bibenzyl dimers from the stems of Dendrobium fimbriatum Hook

The bioassay-guided chemical investigation of the stems of Dendrobium fimbriatum Hook led to the isolation of seven first reported bibenzyl dimers with a linkage of a methylene moiety, fimbriadimerbibenzyls A-G (1-7), together with a new dihydrophenanthrene derivative (S)-2,4,5,9-tetrahydroxy-9,10-dihydrophenanthrene (8) and thirteen known compounds (9-21). The structure of the new compound was established by spectroscopic analysis. Biological evaluation of bibenzyl derivatives against five human cell lines indicated that seven of those compounds exhibited broad-spectrum and cytotoxic activities with IC50 values ranging from 2.2 to 21.2 μM. Those rare bibenzyl dimers exhibited cytotoxic activities in vitro and the cytotoxicity decreased as the number of oxygen-containing groups in the structure decreases.

Five new phenolic compounds from Dendrobium aphyllum.

One new phenanthrene, aphyllone A (1) and four new bibenzyl derivatives, aphyllone B (2) and aphyllals C-D (3-5), together with nine known compounds (6-14), were isolated from the stems of Dendrobium aphyllum (Roxb.) C. E. Fischer. The structures of these new compounds were elucidated by means of extensive spectroscopic analyses, and the absolute configuration of compound 1 was determined by single crystal X-ray diffraction and quantum calculations. Compounds 6, 8 and 14 inhibited NO production at the concentration of 25 μM in LPS-stimulated RAW264.7 cells with the inhibition (%) of 32.48, 35.68, and 38.50. Compound 2 possessed significant DPPH radical scavenging activity with scavenging percentage of 87.97% at the concentration of 100 μg/mL.

Synthesis and Biological Testing of Novel Glucosylated Epigallocatechin Gallate (EGCG) Derivatives

Epigallocatechin gallate (EGCG) is the most abundant component of green tea catechins and has strong physiological activities. In this study, two novel EGCG glycosides (EGCG-G1 and EGCG-G2) were chemoselectively synthesized by a chemical modification strategy. Each of these EGCG glycosides underwent structure identification, and the structures were assigned as follows: epigallocatechin gallate-4′′-O-β-d-glucopyranoside (EGCG-G1, 2) and epigallocatechin gallate-4′,4′′-O-β-d-gluco-pyranoside (EGCG-G2, 3). The EGCG glycosides were evaluated for their anticancer activity in vitro against two human breast cell lines (MCF-7 and MDA-MB-231) using MTT assays. The inhibition rate of EGCG glycosides (EGCG-G1 and EGCG-G2) is not obvious. The EGCG glycosides are more stable than EGCG in aqueous solutions, but exhibited decreasing antioxidant activity in the DPPH radical-scavenging assay (EGCG > EGCG-G2 > EGCG-G1). Additionally, the EGCG glycosides exhibited increased water solubility: EGCG-G2 and EGCG-G1 were 15 and 31 times as soluble EGCG, respectively. The EGCG glycosides appear to be useful, and further studies regarding their biological activity are in progress.

Four new glycosides from the stems of Dendrobium fimbriatum Hook

Abstract Four new glucosides, named as gigantol-5-O-β-d-glucopyranoside (1), 9,10-dihydro-aphyllone A-5-O-β-d-glucopyranoside (2), ficusal-4-O-β-d-glucopyranoside (3), botrydiol-15-O-β-d-glucopyranoside (4), together with eight known compounds (5–12) were isolated from the n-BuOH extract of the stems of Dendrobium fimbriatum Hook. Their structures were elucidated by the analyses of spectroscopic data.

Seco-Dendrobine-Type Alkaloids and Bioactive Phenolics from Dendrobium findlayanum

Investigation of the 95% EtOH extract of stems of Dendrobium findlayanum afforded four new seco-dendrobines, findlayines A-D (1-4); two known dendrobines, dendrobine (5) and 2-hydroxydendrobine (6); and four new phenolic compounds, dendrofindlaphenols A-C (7, 9, and 10) and 6″-de-O-methyldendrofindlaphenol A (8). Compounds 1 and 2 are the first seco-dendrobines possessing a seven-membered lactam moiety, with 3 and 4 derived from the oxidative cleavage of the C-2-C-3 bond of dendrobine. The structures were established using spectroscopic methods and by comparison with literature data. The absolute configurations of 1-4 were confirmed via single-crystal X-ray diffraction data. Cytotoxic activity assays against HL-60, SMMC-7721, A-549, MCF-7, and SW480 human cancer cell lines revealed IC50 values ranging from 2.3 to 5.3 μM for compound 7, from 19.4 to 34.4 μM for 8, and from 49.4 to 96.8 μg/mL for the EtOAc extract. An assay of the inhibition of NO production with RAW 264.7 cells indicated that 8 had an IC50 value of 21.4 μM, and the EtOAc extract, 10.5 μg/mL. The EtOAc extract possessed DPPH radical scavenging activity of 69.93% at 100 μg/mL.

Synthesis, antioxidant activity, and density functional theory study of catechin derivatives

Catechin derivatives were synthesized, and their structures were characterized by 1H-NMR, 13C-NMR, and mass spectrometry. The target compounds were evaluated for their antioxidant activities. Compound 2 showed the highest antioxidant activity, with an IC50 value of 136.637 μM, whereas methylated derivatives showed weak activity. Density functional theory (DFT) studies were carried out at the B3LYP/6-311++G (d, p) level of theory. According to the geometries, molecular electrostatic potential (MEP), bond dissociation enthalpy (EDE), the HOMO and LUMO, and reactivity indices (η, μ, ω, ω+, and ω−), we predicted the free radical scavenging capacity of catechins and their derivatives from their structures. We also found that the B-ring of catechins is a stronger electron donor than the A- or D-ring, and that there is a good relationship between the bond dissociation enthalpies (BDEs). These theoretical results will be helpful in the development of new or modified antioxidant compounds.

Protective effects of cycloartane triterpenoides from Passiflora edulis Sims against glutamate-induced neurotoxicity in PC12 cell

Four new cycloartane triterpenoids, 1α,3β-dihydroxy-16-keto-24(31)-en-cycloartane (1), 31-methoxyl-passifloic acid (2), cyclopassifloside XIV (3), and cyclopassifloside XV (4), together with six known compounds (5-10) were isolated from Passiflora edulis Sims. Their structures were elucidated on the basis of extensive spectroscopic analysis. All the compounds were evaluated for protective effects against damage of PC12 cell induced by glutamate according to traditional usage of the herbal medicine, and the results indicated that cycloartane triterpenoids maybe one of the active compositions of P. edulis Sims for the treatment of neurodegenerative disease.

Oleanane-type triterpene saponins from Hydrocotyle nepalensis.

Five new oleanane-type triterpene saponins including steganogenin 3-O-β-D-glucopyranoside (1), steganogenin 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (2), steganogenin 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (3), chichipegenin 3-O-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside (4) and chichipegenin 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside (5), along with four known oleanane-type triterpenes and triterpene saponins (6-9) were isolated from EtOH extract of the whole plant of Hydrocotyle nepalensis. To the best of our knowledge, oleanane-type triterpenes possessing skeleton with 17, 22-seco-backbone (1-3) are not common in natural products. Compound 8 was isolated as a new natural product. The structures of new compounds were elucidated by extensive spectroscopic methods and chemical evidence. Moreover, the cytotoxic activity of all the isolates against five selected human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480) was evaluated and the results indicated that compounds 6 and 7 show stronger cytotoxic activity.

Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists

The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as “Zhizhuxiang” in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Cav2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n-BuOH and H2O soluble parts (0.01 mg/ml, respectively) were tested herein on Cav2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Cav2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (1–17). All isolates were then sent for further bioactive verification (1 and 3 at concentration of 10 μM, others at 30 μM). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Cav2.2 with an EC50 of 3.3 and 4.8 μM, respectively, and had weaker or no effect on Cav1.2, Cav2.1 and Cav3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Cav2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Cav2.2 channel. Our work is the first demonstration of inhibition of Cav2.2 by iridoids, which may provide a fresh source for finding new analgesics.

Dendrobium officinale Orchid Extract Prevents Ovariectomy-Induced Osteoporosis in Vivo and Inhibits RANKL-Induced Osteoclast Differentiation in Vitro

Background: Dendrobium officinale, a traditional Chinese medical herb with high value that is widely used in Asia, possesses many positive effects on human health, including anti-chronic inflammation, anti-obesity, and immune modulation properties; however, whether D. officinale has inhibitory effects on postmenopausal osteoporosis remains unknown. Objective: We investigated the effects of D. officinale extract (DOE) on ovariectomy-induced bone loss in vivo and on osteoclastogenesis in vitro. Methods: In vivo, female rats were divided into a sham-operated (sham) group and five ovariectomized (OVX) subgroups: OVX with vehicle (OVX), OVX with Xian-Ling-Gu-Bao capsule (240 mg/kg body weight/day), and OVX with low-, medium-, and high-dose DOE (150, 300, and 600 mg/kg body weight/day, respectively). Animals in each group were administered their corresponding treatments for 13 weeks. Body weight, serum biochemical parameters, uterine and femoral physical parameters, bone mineral density (BMD), bone biomechanical properties, and bone microarchitecture were obtained. In vitro, the effects of DOE on osteoclastogenesis were examined using RAW264.7 cells. The effects of DOE on osteoclastogenesis and the expression of osteoclast-specific marker genes and proteins were determined. Results: DOE effectively ameliorated serum biochemical parameters, especially alleviated estradiol (E2) deficiency and maintained calcium and phosphorus homeostasis. DOE improved uterine and femoral physical parameters. In addition, DOE improved femoral BMD and biomechanical properties. DOE significantly ameliorated bone microarchitecture. Moreover, DOE inhibited osteoclastogenesis independent of its cytoxicity and suppressed the expression of osteoclast-specific marker genes and proteins. Conclusion: DOE can effectively prevent ovariectomy-induced bone loss in vivo and inhibit osteoclastogenesis in vitro.